BACKGROUND OF THE INVENTION The ecteinascidins such as Et-743 are exceedingly potent antitumor agents isolated from the marine tunicate Ecteinascidia turbinata. Several ecteinascidins have been reported previously in the patent and scientific literature. See, for example: U. S. Patent N° 5, 256,663, which describes pharmaceutical compositions comprising matter extracted from the tropical marine invertebrate, Ecteinascidia turbinata, and designated therein as ecteinascidins, and the use of such compositions as antibacterial, anti-viral, and/or antitumor agents in mammals.

U. S. Patent N° 5, 089,273, which describes novel compositions of matter extracted from the tropical marine invertebrate, Ecteinascidia turbinata, and designated therein as ecteinascidins 729,743, 745,759A, 759B and 770. These compounds are useful as antibacterial and/or antitumor agents in mammals.

U. S. Patent N° 5, 478,932, which describes ecteinascidins isolated from the Caribbean tunicate Ecteinascidia turbinata, which provide in vivo protection against P388 lymphoma, B 16 melanoma, M5076 ovarian sarcoma, Lewis lung carcinoma, and the LX-1 human lung and MX-1 human mammary carcinoma xenografts.

U. S. Patent N° 5, 654,426, which describes several ecteinascidins isolated from the Caribbean tunicate Ecteinascidia turbinata, which provide in vivo protection against P388 lymphoma, B16 melanoma, M5076 ovarian sarcoma, Lewis lung carcinoma, and the LX-1 human lung and MX-1 human mammary carcinoma xenografts.

U. S. Patent N°. 5,721, 362, which describes a synthetic process for the formation of ecteinascidin compounds and related structures.

U. S. Patent N°. 6,124, 293, which relates to semisynthetic ecteinascidins.

WO 9846080, which provides nucleophile substituted and N-oxide ecteinascidins.

WO 9958125, relating to an ecteinascidin metabolite.

WO 0069862, which describes the synthesis of ecteinascidin compounds from cyanosafracin B.

WO 0177115, WO 0187894 and WO 0187895, which describe new synthetic compounds of the ecteinascidin series, their synthesis and biological properties.

See also: Corey, E. J. , J. Am. Chem. Soc. 1996, 118, 9202-9203; Rinehart, et al., Journal of National Products 1990,"Bioactive Compounds from Aquatic and Terrestrial Sources", 53,771-792 ; Rinehart et al., Pure and <BR> <BR> Appl. Chem. 1990, "Biologically active natural products", 62,1277-1280 ;<BR> Rinehart, et al., J. Org. Chem. 1990, "Ecteinascidins 729,743, 745,759A, 759B, and 770: Potent Antitumor Agents from the Caribbean Tunicate Ecteinascidia turbinata", 55,4512-4515 ; Wright et al., J. Org. Chem. 1990, "Antitumor Tetrahydroisoquinoline Alkaloids from the Colonial Ascidian Ecteinascidia turbinata", 55,4508-4512 ; Sakai et al., Proc. Natl. Acad. Sci.

USA 1992,"Additional antitumor ecteinascidins from a Caribbean tunicate: Crystal structures and activities in vivo", 89,11456-11460 ; Science 1994, "Chemical Prospectors Scour the Seas for Promising Drugs", 266,1324 ; <BR> <BR> Koenig, K. E. ,"Asymmetric Synthesis", ed. Morrison, Academic Press, Inc., Orlando, FL, vol. 5, 1985, pp. 71; Barton, et al., J. Chem Soc. Perkin Trans. I <BR> <BR> 1982, "Synthesis and Properties of a Series of Sterically Hindered Guandidine Bases", 2085; Fukuyama et al., J. Am Chem. Soc. 1982, "Stereocontrolled Total Synthesis of (+)-Saframycin B", 104, 4957; <BR> Fukuyama et al., J. Am Chem Soc. 1990, "Total Synthesis of (+)-Saframycin A", 112, 3712; Saito, et al., J. Org. Chem. 1989, "Synthesis of Saframycins.

Preparation of a Key Tricyclic Lactam Intermediate to Saframycin A", 54, 5391; Still, et al., J. Org. Chem. 1978, "Rapid Chromatographic Technique for Preparative Separations with Moderate Resolution", 43,2923 ; Kofron, W. G.; Baclawski, L. M. , J. Org. Chem. 1976, 41, 1879; Guan et al., J.

Biomolec. Struc. & Dynam.. 1993, 10, 793-817; Shamma et al.,"Carbon-13 NMR Shift Assignments of Amines and Alkaloids", p. 206, 1979 ; Lown et al., Biochemistry 1982, 21, 419-428; Zmijewski et al., Chem. Biol. Interactions 1985,52, 361-375; Ito, CRC CRIT. Rev. Anal. Chem. 1986,17, 65-143; Rinehart et al.,"Topics in Pharmaceutical Sciences 1989"pp. 613-626, D. D.

Breimer, D. J. A. Cromwelin, K. K. Midha, Eds. , Amsterdam Medical Press<BR> B. V. , Noordwijk, The Netherlands (1989); Rinehart et al.,"Biological Mass<BR> Spectrometry, "233-258 eds. Burlingame et al. , Elsevier Amsterdam (1990); Guan et al., Jour. Biomolec. Struct. & Dynam. 1993, 10, 793-817; Nakagawa et al., J. Amer. Chem. Soc. 1989, 111 : 2721-2722; Lichter et al.,"Food and Drugs from the Sea Proceedings" (1972), Marine Technology Society, Washington, D. C. 1973,117-127 ; Sakai et al., J. Amer. Chem. Soc. 1996, 118, 9017; Garcia-Rocha et al., Brit. J. Cancer 1996,73 : 875-883; Pommier et al., Biochemistry 1996,35 : 13303-13309; Rinehart, K. L. Med. Res. Rev.

2000,20, 1-27 and Manzanares I. et al. Org. Lett. 2000,2 (16), 2545-2548; Corey et al., Proc. Natl. Acad. Sci. USA 1999,96, 3496-3501.

SUMMARY OF THE INVENTION The present invention is directed to compounds of the general formula Ia.. la wherein the substituent groups defined by Ri, R2, R4, Rs are each independently selected of H, C (=O) R, C (=O) OR' substituted or unsubstituted Cl-Cls alkyl, substituted or unsubstituted C2-Cl8 alkenyl, substituted or unsubstituted C2-Cls alkynyl, substituted or unsubstituted aryl; wherein R6 and R7 are both =O and the dotted lines indicate a quinone ring, or R6 is-ORs, where R3 is H, C (=O) R', C (=O) OR' substituted or unsubstituted C 1-C is alkyl, substituted or unsubstituted C2-C l8 alkenyl, substituted or unsubstituted Ca-C is alkynyl, substituted or unsubstituted aryl, R7 is H, and the dotted lines indicate a phenyl ring; wherein each of the R groups is independently selected from the group consisting of H, OH, N02, NH2, SH, CN, halogen, =O, C (=O) H, C (=O) CH3, C02H, substituted or unsubstituted Ci-Cis alkyl, substituted or unsubstituted C2-Ci8 alkenyl, substituted or unsubstituted C2-Ci8 alkynyl, substituted or unsubstituted aryl; wherein the substituent groups for X2, X3, X4, Xs, X6 are independently selected of H, OH, OR', SH, SR', SOR', S02R', C (=O) R', C (=O) OR', N02, NH2, NHR', N (R') 2, NHC (O) R', CN, halogen, =0,', substituted or unsubstituted C-C24 alkyl, substituted or unsubstituted C2-Ci8 alkenyl, substituted or unsubstituted C2-Cl8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaromatic; wherein Xi is independently selected of ORs, CN, (=O), or H; wherein substituent groups for Ri, R2, R3, R4, and Rs are each independently selected from the group consisting of H, OH, OR, SH, SR', SOR', SOaR', C (=O) R', C (=O) OR', NO2, NH2, NHR', N (R') 2, NHC (O) R', CN, halogen, =O, substituted or unsubstituted Ci-Cls alkyl, substituted or unsubstituted C2- Ci8 alkenyl, substituted or unsubstituted C2-Ci8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclic.

More particularly, the invention provides compounds of formula (I) : I wherein the substituent groups defined by Ri, R2, R4, Rs are each independently selected of H, C (=O) R', C (=O) OR' substituted or unsubstituted Ci-Cis alkyl, substituted or unsubstituted C2-Ci8 alkenyl, substituted or unsubstituted C2-Cis alkynyl, substituted or unsubstituted aryl, or P=O (OR') 2 ; where R3 is H, C (=O) R', C (=O) OR' substituted or unsubstituted Ci-Cis alkyl, substituted or unsubstituted C2-Ci8 alkenyl, substituted or unsubstituted C2-Ci8 alkynyl, substituted or unsubstituted aryl, R7 is H, and the dotted lines indicate a phenyl ring; wherein each of the R groups is independently selected from the group consisting of H, OH, N02, NH2, SH, CN, halogen, =O, C (=O) H, C (=O) CH3, alkyloxycarbonyl, C02H, substituted or unsubstituted Ci-Cis alkyl, substituted or unsubstituted C2-Cl8 alkenyl, substituted or unsubstituted C2-Cl8 alkynyl, substituted or unsubstituted aryl; wherein the substituent groups for X2, X3, X4, X5 are independently selected of H, OH, OR, SH, SR', SOR', S02R', C (=O) R', C (=O) OR', N02, NH2, NHR', N (R') 2, NHC (O) R', CN, halogen, =O, substituted or unsubstituted Ci-Cls alkyl, substituted or unsubstituted C2-Ci8 alkenyl, substituted or unsubstituted C2-Cls alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaromatic ; wherein Xi is independently selected of ORi, CN, (=O), or H; wherein substituent groups for Ri, R2, R3, R4, and Rs are each independently selected from the group consisting of H, OH, OR, SH, SR', SOR', S02R', C (=O) R', C (=O) OR', N02, NH2, NHR', N (R') 2, NHC (O) R', CN, halogen, =O, substituted or unsubstituted Cl-Cis alkyl, substituted or unsubstituted C2- Cls alkenyl, substituted or unsubstituted C2-Cl8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaromatic.

In one aspect, the invention provides compounds of formula (I), wherein: Ri, R3 and R4 are independently selected from hydrogen, R', C=OR', or COOR', where R'is optionally substituted alkyl or alkenyl, the optional substituents being chosen from halo, amino including amino derived from amino acid, aryl or heterocyclic; R2 is hydrogen, alkyl or C (=O) OR', where R'is alkyl ; Rs is hydrogen, alkyl or C (=O) OR', where R'is alkylene.

Xi is hydrogen, hydroxy, or cyano; X2, X4 and X5 are hydrogen; X3 is OR', where R'is alkyl ; and X6 is hydrogen or alkyl.

Suitable halogen substituents in the compounds of the present invention include F, Cl, Br and I.

Alkyl groups preferably have from 1 to 24 carbon atoms. One more preferred class of alkyl groups has 1 to about 12 carbon atoms, yet more preferably 1 to about 8 carbon atoms, still more preferably 1 to about 6 carbon atoms, and most preferably 1,2, 3 or 4 carbon atoms. Another more preferred class of alkyl groups has 12 to about 24 carbon atoms, yet more preferably 12 to about 18 carbon atoms, and most preferably 13,15 or 17 carbon atoms. Methyl, ethyl and propyl including isopropyl are particularly preferred alkyl groups in the compounds of the present invention. As used herein, the term alkyl, unless otherwise modified, refers to both cyclic and noncyclic groups, although cyclic groups will comprise at least three carbon ring members.

Preferred alkenyl and alkynyl groups in the compounds of the present invention have one or more unsaturated linkages and from 2 to about 12 carbon atoms, more preferably 2 to about 8 carbon atoms, still more preferably 2 to about 6 carbon atoms, even more preferably 1, 2,3 or 4 carbon atoms. The terms alkenyl and alkynyl as used herein refer to both cyclic and noncyclic groups, although straight or branched noncyclic groups are generally more preferred.

Preferred alkoxy groups in the compounds of the present invention include groups having one or more oxygen linkages and from 1 to about 12 carbon atoms, more preferably from 1 to about 8 carbon atoms, and still more preferably 1 to about 6 carbon atoms, and most preferably 1,2, 3 or 4 carbon atoms.

Preferred alkylthio groups in the compounds of the present invention have one or more thioether linkages and from 1 to about 12 carbon atoms, more preferably from 1 to about 8 carbon atoms, and still more preferably 1 to about 6 carbon atoms. Alkylthio groups having 1,2, 3 or 4 carbon atoms are particularly preferred.

Preferred alkylsulfinyl groups in the compounds of the present invention include those groups having one or more sulfoxide (SO) groups and from 1 to about 12 carbon atoms, more preferably from 1 to about 8 carbon atoms, and still more preferebly 1 to about 6 carbon atoms.

Alkylsulfinyl groups having 1,2, 3 or 4 carbon atoms are particularly preferred.

Preferred alkylsulfonyl groups in the compounds of the present invention include those groups having one or more sulfonyl (S02) groups and from 1 to about 12 carbon atoms, more preferably from 1 to about 8 carbon atoms, and still more preferably 1 to about 6 carbon atoms. Alkylsulfonyl groups having 1,2, 3 or 4 carbon atoms are particularly preferred.

Preferred aminoalkyl groups include those groups having one or more primary, secondary and/or tertiary amine groups, and from 1 to about 12 carbon atoms, more preferably 1 to about 8 carbon atoms, still more preferably 1 to about 6 carbon atoms, even more preferably 1,2, 3 or 4 carbon atoms. Secondary and tertiary amine groups are generally more preferred than primary amine moieties.

Suitable heterocyclic groups include heteroaromatic and heteroalicyclic groups. Suitable heteroaromatic groups in the compounds of the present invention contain one, two or three heteroatoms selected from N, O or S atoms and include, e. g. , coumarinyl including 8-coumarinyl, quinolinyl including 8-quinolinyl, pyridyl, pyrazinyl, pyrimidyl, furyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, indolyl, benzofuranyl and benzothiazol. Suitable heteroalicyclic groups in the compounds of the present invention contain one, two or three heteroatoms selected from N, O or S atoms and include, e. g. , tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, morpholino and pyrrolindinyl groups.

Suitable carbocyclic aryl groups in the compounds of the present invention include single and multiple ring compounds, including multiple ring compounds that contain separate and/or fused aryl groups. Typical carbocyclic aryl groups contain 1 to 3 separate or fused rings and from 6 to about 18 carbon ring atoms. Specifically preferred carbocyclic aryl groups include phenyl including substituted phenyl such as 2-substituted phenyl, 3-substituted phenyl, 2.3-substituted phenyl, 2.5-substituted phenyl, 2.3. 5- substituted and 2.4. 5-substituted phenyl, including where one or more of the phenyl substituents is an electron-withdrawing group such as halogen, cyano, nitro, alkanoyl, sulfinyl, sulfonyl and the like; naphthyl including 1- naphthyl and 2-naphthyl; biphenyl; phenanthryl; and anthracyl.

References herein to substituted R'groups in the compounds of the present invention refer to the specified moiety, typically alkyl or alkenyl, that may be substituted at one or more available positions by one or more suitable groups, e. g. , halogen such as fluoro, chloro, bromo and iodo; cyano; hydroxyl; nitro; azido; alkanoyl such as a Cl-6 alkanoyl group such as acyl and the like; carboxamido; alkyl groups including those groups having 1 to about 12 carbon atoms or from 1 to about 6 carbon atoms and more preferably 1-3 carbon atoms; alkenyl and alkynyl groups including groups having one or more unsaturated linkages and from 2 to about 12 carbon or from 2 to about 6 carbon atoms; alkoxy groups having those having one or more oxygen linkages and from 1 to about 12 carbon atoms or 1 to about 6 carbon atoms; aryloxy such as phenoxy; alkylthio groups including those moieties having one or more thioether linkages and from 1 to about 12 carbon atoms or from 1 to about 6 carbon atoms; alkylsulfinyl groups including those moieties having one or more sulfinyl linkages and from 1 to about 12 carbon atoms or from 1 to about 6 carbon atoms; alkylsulfonyl groups including those moieties having one or more sulfonyl linkages and from 1 to about 12 carbon atoms or from 1 to about 6 carbon atoms; aminoalkyl groups such as groups having one or more N atoms and from 1 to about 12 carbon atoms or from 1 to about 6 carbon atoms; carbocylic aryl having 6 or more carbons, particularly phenyl (e. g. , R being a substituted or unsubstituted biphenyl moiety); and aralkyl such as benzyl; heterocyclic groups including heteroalicyclic and heteroaromatic groups, especially with 5 to 10 ring atoms of which 1 to 4 are heteroatoms, more preferably heterocyclic groups with 5 or 6 ring atoms and 1 or 2 heteratoms or with 10 ring atoms and 1 to 3 heteroatoms.

Preferred R'groups are present in groups of formula R', COR'or OCOR' and include alkyl or alkenyl, that may be substituted at one or more available positions by one or more suitable groups, e. g. , halogen such as fluoro, chloro, bromo and iodo, especially m-chloro or perfluoro; aminoalkyl groups such as groups having one or more N atoms and from 1 to about 12 carbon atoms or from 1 to about 6 carbon atoms, and especially including amino acid, notably glycine, alanine, arginine, asparagine, asparaginic acid, cystein, glutamine, glutamic acid, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine or valine, especially protected forms of such amino acids; carbocylic aryl having 6 or more carbons, particularly phenyl; and aralkyl such as benzyl; heterocyclic groups including heteroalicyclic and heteroaromatic groups, especially with 5 to 10 ring atoms of which 1 to 4 are heteroatoms, more preferably heterocyclic groups with 5 or 6 ring atoms and 1 or 2 heteratoms or with 10 ring atoms and 1 to 3 heteroatoms, the heterocyclic groups optionally being substituted with one or more of the subsitituents permitted for R'and especially amino such as dimethylamino or with keto.

DESCRIPTION OF PREFERRED EMBODIMENTS One class of preferred compounds of this invention includes compounds of this invention which have one or more of the following substituents: Ri is hydrogen; alkyl, more preferably alkyl of 1 to 6 carbon atoms; C (=O) R', where R'is alkyl, more preferably alkyl of 1 to 24 carbon atoms, especially 1 to 8 or 12 to 18 carbon atoms; haloalkyl, more preferably co- chloro-or perfluoro-alkyl of 1 to 4 carbon atoms, especially w-chloroethyl or perfluoromethyl, ethyl or propyl ; heterocylicalkyl, more preferably an aylkyl of 1 to 6 carbon atoms with an m-heterocyclic substituent suitably having 5 to 10 ring atoms and 1 to 4 heteroatoms, including fused heteroalicyclic with 3 hetero atoms, such as biotin; aminoalkyl, more preferably alkyl of 1 to 6 carbon atoms, especially 2 carbon atoms, with an m-amino group optionally protected for example with alkoxycarbonyl such as (CH3) 3C-O-C=O-or other protecting group; arylalkylene, especially cinnamoyl; alkylene, especially vinyl or allyl; aralkyl, such as benzyl; or C (=O) OR', where R'is alkyl, more preferably alkyl of 1 to 6 carbon atoms, especially branched alkyl ; alkenyl, more preferably allyl; R2 is hydrogen, methyl, or a protecting group including alkoxycarbonyl such as (CH3) 3C-O-C=O-.

R3 is hydrogen; alkyl, more preferably alkyl of 1 to 6 carbon atoms; (C=O) R', where R'is alkoxy, especially with an alkyl group of 1 to 6 carbon atoms; alkyl, more preferably alkyl of 1 to 24 carbon atoms, preferably 1 to 8 or 12 to 18 carbon atoms; haloalkyl, more preferably perfluoroalkyl of 1 to 4 carbon atoms, especially perfluoromethyl, ethyl or propyl ; arylalkylene, especially cinnamoyl; heterocylicalkyl, more preferably an alkyl of 1 to 6 carbon atoms with an m heterocyclic substituent suitably having 5 to 12 ring atoms and 1 to 4 heteroatoms, including fused heterocyclic with 3 ring atoms, such as biotin; heterocyclicalkyl, with preferably 1 carbon atom in the alkyl group, and more preferably heteroalicylicmethyl with 5 to 10 ring atoms and 1 to 4 ring atoms, especially fused heterocylic with 1 to 4 heteroatoms, such as dimethylaminocoumarin or coumarin; alkylene, especially allyl; aralkyl, such as benzyl; (C=O) OR', where R'is alkyl, more preferably alkyl of 1 to 6 carbon atoms; alkylene, especially vinyl or allyl; aralkyl, such as benzyl.

R4 is C (=O) R', where R'is alkyl, more preferably alkyl of 1 to 24 carbon atoms, preferably 1 to 8 or 12 to 18 carbon atoms; haloalkyl, more preferably co-chloro-or perfluoro-alkyl of 1 to 4 carbon atoms, especially co-chloroethyl or perfluoromethyl, ethyl or propyl ; aralkyl, such as benzyl or phenethyl ; arylalkylene, especially cinnamoyl; aminoalkyl, especially amino acid, more especially protected amino acid, including protected cysteinine, notably Fm- S CH2CH (NHAlloc) -cys or protected alanine, notably (CH3) 3C-O-C=O-ala ; heterocyclicalkyl, more preferably an alkyl of 1 to 6 carbon atoms with an o-heterocyclic substituent suitably having 5 to 12 ring atoms and 1 to 4 heteroatoms, including fused heterocyclic with 3 ring atoms, such as biotin; heterocyclicalkyl, with preferably 1 carbon atom in the alkyl group, and more preferably heteroalicyclicmethyl with 5 to 10 ring atoms and 1 to 4 ring atoms, especially fused heterocylic with 1 to 4 heteroatoms, such as coumarin or dimethylaminocoumarin; (C=O) OR', where R'is alkyl, more preferably alkyl of 1 to 6 carbon atoms; alkylene, especially vinyl or allyl; aralkyl, such as benzyl; P=O (OR') 2, where R'is benzyl.

Rs is hydrogen; alkyl, more preferably alkyl of 1 to 6 carbon atoms; (C=O) OR', where R'is alkylene, especially vinyl.

Xi is hydrogen, hydroxy, or cyano.

X2 is hydrogen.

X3 is OR', where R'is alkyl having 1 to 6 carbon atoms, especially methyl.

X4 is hydrogen.

X5 is hydrogen.

X6 is hydrogen or alkyl, especially hydrogen or alkyl of 1 to 6 carbon atoms, more especially hydrogen.

Compounds where R3 is not hydrogen are one class of preferred compounds. In the article by Corey et al. , Proc. Natl. Acad. Sci. USA 1999, 96,3496-3501, a structure-activity relationship is shown for ecteinascidin- type compounds, indicating that a hydrogen is essential. It is stated on page 3498 that"the protection of the other phenolic hydroxyl group on the E subunit resulted in diminished activity". We find the hydrogen is not essential, see compounds 96,97 and 98, among many others.

Compounds wherein R4 is an ester or an ether are among the preferred compounds, for example compounds 57,60, 61,63, 65,68 and 76. In general they have improved toxicology properties and thus give a wider therapeutic window.

In particular, compounds wherein both R3 and R4 are not hydrogen are preferred. Of those, compounds with an ester or ether at these positions are most preferred, and in particular esters and carbonates. See compounds 78,82, 83,84, 86,88, 92. Esters with bulky groups (long aliphatic or aromatic residues) give better results. Examples of particularly preferred substituents include octanoic, palmitic, cinnamoyl, hydrocinnamoyl. See compounds 86,92. Among the carbonates, terButyloxycarbonyl (tBOC) and vinyloxycarbonyl (VOC) are the most preferred substituents for these positions. See ompounds 86 and 92, which are among the best in activity and toxicology. For the ether substituents at these positions, ethyl or a bulky group is preferred.

Compounds with ethyl at Rs, N 2'are preferred, since there is activity at lower concentrations than those at which the compound begins to be toxic.

Compounds with changes at Ri are part of this invention, especially ester groups, Ri = R'CO-, with R'a long aliphatic or aromatic group.. See compounds 161,162, 164,165, 168,169, 170,171, 172,174, 175. Some of these compounds have substituents at both Ri and R3. They have good activity/toxicity properties. For example 170 is active and in heart and myelo non toxic. Compund 174 is very active (E-10) and toxic at higher concentrations (E-8).

There are compounds that have good ADME properties (absorption- distribution-metabolism-excretion) which are good indicative of pharmacokinetics.

As mentioned above, compounds of the present invention, preferably those with bulky substituted groups, have a good therapeutic window and the estherification of the phenols with different acids and carbonates, results in a general enhancement of the pharmaceutical properties: there is a significant decrease in hepatocyte toxicity, and also a good profile on drug- drug interactions since these derivatives do not show cytochrome inhibition having moreover higher metabolic stability.

In a related aspect of this invention, the compounds have one or more of the following features: Ri is not acetyl. Preferably it has at least 4,5 or 6 carbon atoms, for example up to 18 or 24 carbon atoms. Suitable substituents include esters COR', where R'is alkyl, alkenyl, often with one or more substituents. Alkyl, substituted alkyl, alkenyl and arylalkenyl are preferred, with suitable substituents including aryl, heterocyclic. Other defintions for RI include esters of formula COR'derived from an amino acid, optionally a protected amino acid.

R3 is not hydrogen. Preferably it is R', COR'or COOR'where R'is a substituent with some bulk. Such bulky substituents include those with branched chain groups, unsaturated groups or cyclic groups including aromatic groups. Thus, branched alkyl, cycloalkyl, branched alkenyl, aryl, heteroaromatic and related groups are preferred for inclusion within the structure of the substituent R3. Preferably the total number of carbon atoms in R3 is 2 to 24, more preferably 6 to 18 carbon atoms. Typically R3 is an ester, ether or carbonate, being of formula COR', R'or COOR'.

R4 is not hydrogen. Preferably it is R', COR'or COOR'where R'is a substituent with some bulk. Such bulky substituents include those with branched chain groups, unsaturated groups or cyclic groups including aromatic groups. Thus, branched alkyl, cycloalkyl, branched alkenyl, aryl, heteroaromatic and related groups are preferred for inclusion within the structure of the substituent R4. Preferably the total number of carbon atoms in R4 is 2 to 24, more preferably 6 to 18 carbon atoms. Typically R4 is an ester, ether or carbonate, being of formula COR', R'or COOR'.

Examples of protecting groups for amino and other substituents are given in WO 0069862, and we expressly incorporate that disclosure.

Without being exhaustive, another class of preferred compounds of this invention have one or more of the following definitions: Xi is H, -CN or-OH, most especially-OH or-CN.

X2 is hydrogen.

X3 is methoxy.

X4 and X5 are hydrogen.

Ri is preferably H or acetyl; arylalkyl, especially benzyl; alkyl-CO- (alkyl being up to 25 carbon atoms, such as up to 17,19 or 21 carbon atoms and preferably an odd number of carbon atoms corresponding to a fatty acid carboxylic acid of even number of carbon atoms or else a low number of carbon atoms such as 1 to 6) especially CH3- (CH2) n-CO- where n is for example 1.2. 4.6. 12.14 or 16; haloalkyl-CO-, especially trifluoromethylcarbonyl; arylalkyl-CO-, especially benzyl-CO- ; arylalkenyl- CO-, especially cinnamoyl-CO- ; most especially Ri is H, acetyl or cinnamoyl.

R2 is H; alkyl, especially methyl; alkyl-O-CO-, especially t-butyl-O-CO-or alkenyl-O-CO-, especially allyl-O-CO-.

R3 is preferably H or acetyl; alkyl (alkyl being 1 to 6 carbon atoms), especially Cl to C3 alkyl ; alkenyl, especially allyl; arylalkyl, especially benzyl; alkyl-CO- (alkyl being up to 25 carbon atoms, such as up to 17,19 or 21 carbon atoms and preferably an odd number of carbon atoms corresponding to a fatty acid carboxylic acid of even number of carbon atoms or else a low number of carbon atoms such as 1 to 6) especially CH3- (CH2) n-CO- where n is for example 1.2. 4.6. 12.14 or 16 and derivatives thereof, as in Biotin- (CH2) 4-CO- ; arylalkenyl-CO-, especially cinnamoyl-CO-; alkyl-O-CO-, especially t-butyl- O-CO- ; arylalkyl-O-CO-, especially benzyl-O-CO- ; alkenyl-O-CO, especially allyl-O-CO-.

R4 is preferably H, acetyl, alkyl (alkyl being 1 to 6 carbon atoms) especially Cl to C3 alkyl ; alkenyl, especially allyl; arylalkyl, especialy benzyl; alkyl-CO- (alkyl being up to 25 carbon atoms, such as up to 17,19 or 21 carbon atoms and preferably an odd number of carbon atoms corresponding to a fatty acid carboxylic acid of even number of carbon atoms or else a low number of carbon atoms such as 1 to 6) especially CH3- (CH2) n-CO- where n is for example 1.2. 4.6. 12.14 or 16 and derivatives thereof, as in Biotin- (CH2) 4-CO- ; haloalkyl-CO-, especially trifluoromethylcarbonyl ; amino acid acyl or a derivative thereof, as in FmSCH2CH (NHAlloc) CO- ; arylalkenyl-CO-, especially cinnamoyl-CO- ; alkyl-O-CO-, especially tert-butyl-O-CO- ; alkenyl-O-CO-, especially allyl-O-CO ; arylalkyl-O-CO-, especially benzyl-O-CO- ; protecting group as in PO (OBn) 2; most especially R4 is H, acyl y cinnamoyl.

Rs is H or alkyl (alkyl being 1 to 6 carbon atoms) and Rs is most especially H or Cl to C3 alkyl.

This application claims priority of a British patent application. We expressly incorporate by reference any disclosure which is in the specification of that British priority application and which is not in the present application.

Furthermore, we expressly incorporate by reference each of WO 0069862, WO 0177115, WO 0187894 and WO 0187895 for their discussion of substituents which correspond to the substituents of the present invention. Any definitions given in any of these earlier applications for a particular substituent can be adopted for a substituent of a compound of this invention.

Furthermore, we do not claim any of the compounds disclosed in the earlier applications, and we expressly disclaim any such compounds. We expressly incorporate by reference each of the earlier applications for the wording of any disclaimer which might be necessary.

In one aspect, this invention is concerend with a derivative of Et-743 or Et-770 or Et-729 which differs in one or more of the following aspects: Ri is not acetyl, and in particular is a group which is not COR'where R'is hydrogen, methyl or ethyl, or which is not COR'where R'is hydrogen, methyl, ethyl or propyl.

Ri is not R'where R'is methyl or ethyl, or where R'is methyl, ethyl or propyl or where R'is methyl, ethyl, propyl or butyl.

R2 is not methyl.

R6 is R3 and is not hydrogen.

R4 is not hydrogen.

Rs is not hydrogen.

R6 and R7 are =O.

Xi is not hydroxy or cyano.

In one aspect, this invention provides a derivative wherein: Ri is not acetyl, and in particular is a group which is not COR'where R'is hydrogen, methyl or ethyl, or which is not COR'where R'is hydrogen, methyl, ethyl or propyl ; Ri is not R'where R'is methyl or ethyl, or where R' is methyl, ethyl or propyl or where R'is methyl, ethyl, propyl or butyl; and R6 is R3 and is not hydrogen.

In a further aspect, this invention provides a derivative wherein: Ri is not acetyl, and in particular is a group which is not COR'where R'is hydrogen, methyl or ethyl, or which is not COR'where R'is hydrogen, methyl, ethyl or propyl ; Ri is not R'where R'is methyl or ethyl, or where R' is methyl, ethyl or propyl or where R'is methyl, ethyl, propyl or butyl; and R4 is not hydrogen.

In a related aspect, this invention provides a derivative wherein: R6 is R3 and is not hydrogen; and R4 is not hydrogen.

In yet another aspect, this invention provides a derivative wherein: Ri is not acetyl, and in particular is a group which is not COR'where R'is hydrogen, methyl or ethyl, or which is not COR'where R'is hydrogen, methyl, ethyl or propyl ; Ri is not R'where R'is methyl or ethyl, or where R' is methyl, ethyl or propyl or where R'is methyl, ethyl, propyl or butyl; R6 is R3 and is not hydrogen; R4 is not hydrogen.

The compounds of the present invention can be prepared synthetically from the intermediate compound 15 described in the U. S. Patent No 5.721. 362, ET-770 and ET-729. Numerous active antitumoral compounds have been prepared from this compound and it is believed that many more compounds can be formed in accordance with the teachings of the present disclosure.

ET-770 (1) ET-729 (19) 15 (34) Antitumoral activities of these compounds include leukaemias, lung cancer, colon cancer, kidney cancer, prostate cancer, ovarian cancer, breast cancer, sarcomas and melanomas.

Another especially preferred embodiment of the present invention is pharmaceutical compositions useful as antitumor agents which contain as active ingredient a compound or compounds of the invention, as well as the processes for their preparation.

Examples of pharmaceutical compositions include any solid (tablets, pills, capsules, granules etc. ) or liquid (solutions, suspensions or emulsions) with suitable composition or oral, topical or parenteral administration.

Administration of the compounds or compositions of the present invention may be any suitable method, such as intravenous infusion, oral preparation, intraperitoneal and intravenous preparation.

Administration of the compounds or compositions of the present invention may be by any suitable method, such as intravenous infusion, oral preparations, intraperitoneal and intravenous administration. We prefer that infusion times of up to 24 hours are used, more preferably 2-12 hours, with 2-6 hours most preferred. Short infusion times which allow treatment to be carried out without an overnight stay in hospital are especially desirable. However, infusion may be 12 to 24 hours or even longer if required. Infusion may be carried out at suitable intervals of say 2 to 4 weeks. Pharmaceutical compositions containing compounds of the invention may be delivered by liposome or nanosphere encapsulation, in sustained release formulations or by other standard delivery means.

The correct dosage of the compounds will vary according to the particular formulation, the mode of application, and the particular situs, host and tumour being treated. Other factors like age, body weight, sex, diet, time of administration, rate of excretion, condition of the host, drug combinations, reaction sensitivities and severity of the disease shall be taken into account. Administration can be carried out continuously or periodically within the maximum tolerated dose.

The compounds and compositions of this invention may be used with other drugs to provide a combination therapy. The other drugs may form part of the same composition, or be provided as a separate composition for administration at the same time or a different time. The identity of the other drug is not particularly limited, and suitable candidates include: a) drugs with antimitotic effects, especially those which target cytoskeletal elements, including microtubule modulators such as taxane drugs (such as taxol, paclitaxel, taxotere, docetaxel), podophylotoxins or vinca alkaloids (vincristine, vinblastine); b) antimetabolite drugs such as 5-fluorouracil, cytarabine, gemcitabine, purine analogues such as pentostatin, methotrexate); c) alkylating agents such as nitrogen mustards (such as cyclophosphamide or ifosphamide); d) drugs which target DNA such as the antracycline drugs adriamycin, doxorubicin, pharmorubicin or epirubicin; e) drugs which target topoisomerases such as etoposide; hormones and hormone agonists or antagonists such as estrogens, antiestrogens (tamoxifen and related compounds) and androgens, flutamide, leuprorelin, goserelin, cyprotrone or octreotide; g) drugs which target signal transduction in tumour cells including antibody derivatives such as herceptin; h) alkylating drugs such as platinum drugs (cis-platin, carbonplatin, oxaliplatin, paraplatin) or nitrosoureas; i) drugs potentially affecting metastasis of tumours such as matrix metalloproteinase inhibitors; j) gene therapy and antisense agents; k) antibody therapeutics; 1) other bioactive compounds of marine origin, notably the didemnins such as aplidine; m) steroid analogues, in particular dexamethasone; n) anti-inflammatory drugs, in particular dexamethasone; and o) anti-emetic drugs, in particular dexamethasone.

Examples of biological activities of the compounds of the present invention are included in tables I, II and III at the end of the document.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The preferred methods of producing the compounds are described below in schemes I-VI. R, O R10 NH OMe NH OMe MeC 0 : Ho Me MeO 0-.""R20 Me AcO s I Acus I 0 Me N--Me Me N--Me N /N O : O. \-O CN \-O CN Structure of Structure of formula I A or B or C or D A or B formula 11 HO HO Me0 NH OMe Me HO Me Ac0\ s j ! J Ace s AcgOT Me O t O CN /Et-770 c OX compound 1 R10 R10 R10 I I I I I I NH OMe Me0 NH OMe MQ i NR3 OMe MeO oz Ho Me MeO.""I R20 Me meo R20 Me ACO g I ACO g ACO $ I O + O O Me N--Me Me N--Me Me10 N--Me /N/N/N 0 CN CN Structure of Structure of Compounds 29, 30, formula I formula 11 31, 32 and 33 o Ho I o I Typ o<' VY 0 0 Me 0 0Me Acq-' Me N--Me Me N--Me /non \-O CN \-O CN 47 49 -00 -00 Me0 H OMe I NH0OMe MeO'MeO Mue (HO Me 0 0 Me Me I N--Me Me I N--Me /non O > O. t O CN tO CN 25 26 SCHEME I Scheme I includes acylation reactions through the different procedures described in the experimental part. Compound 1 corresponds to Et-770.

Starting from this compound it is possible to obtain target compounds following acylation methods: A ( (RCO) 20/base), B (RCOCl/base), C (RCOOH/DMAP/EDC. HCI) and D (ROCOCl/base). Other acylation reactions have been performed from compound 25 which belongs to the family of the structures of formula I and compound 47 whose structure is described further.

Compounds 29,30, 31,32 and 33 are compounds wherein Ri, R2 and R3 is a vinyl radical or an hydrogen atom. R10 R, O 1 p N H OMe NH OMe OHOL, Me OOJMe Ac0 O S I AcO g Ho Ay, /N i N O O tO CN tO CN Structure of Structure of formula I formula 11 E BnOp BnO-pÆO I i NH OMe I i NH OMe Me0 I NR3 OMe Me0, O' HO Me 0 I HO Me Me0 I HO Me AcO s AcO S G AcO s I Me) Me Me4>fMe oXNS N--Me N--Me i N i N tO tN tO tN tO-CN 53 Et-770 Structure of compound 1 formula III E (Mel) i MeO MeO HO ON H Met OMe Met OMe Me0 NH OMe 0''HO. Me 0''MeOJ. Me O'MeO-. Me + I Ac s + AcO s O i N O i N O i N tO CN tO tN tO CN 34 35 36 SCHEME II In Scheme II method E involves reactions of alkylation (RBr/Cs2CO3) and method G (RCHO/NaBCNBH3/AcOH) is the reductive alkylation at N-2'.

Compounds 34,35 and 36 are obtained when the alkylation reaction is performed with MeI. With these methodologies we generate N and 0-alkyl derivatives starting from compound 1. In compound 53 a phosphate group is introduced at position C-6'using dibenzyl phosphite. compound 1 SCHEME III Scheme III includes hydrolysis of tert-butylcarbonate in C-6'through method F (TFA/H20/CH2C12) and hydrolysis of acetyl groups in C-5 from compound 42 with KOH/H20/THF and in C-6'from compound 6 with TEA/MeOH/THF. Also is described the formation of compound 52 starting from compound 1 through an oxidation reaction of the right aromatic ring. R10 R10) I NH OMe NH OMe 0' HOkMe °"t HOk. Me AcO s I AcO s I Me N--Me H or I Me N--Me /N I/N t O CN \-O OH Structure of Final compound of the formula I structure of formula I RO RO I I/NH OMe Me0 I NH OMe MeO 0 *"'R20 OMe Me MeO 0 1 R20 Me Me s I H AcO s I e /N O tO CN t-O OH °-J 5N -0 OH Structure of Final compound of the formula 11 structure of formula 11 HO HO I Me0 NR3 OMe Me0 NR3 OMe O g"\ HO < Me O g"'HO < M Ho Me I N--Me Me I N--Me /non O : O : \-O CN \-O OH Structure of Final compound of the formula III structure of formula III SCHEME The different analogs of Et-743 wherein Rl, R2 and R3 are acyl, carbonate, carbamate or alkyl groups are prepared following method H (AgN03/CH3CN/H20) or I (CuBr/THF/H20) from the derivatives of Et-770 (Scheme IV). In both cases the reaction involves the transformation of the nitrile group in C-21 into the hydroxyl group. Other specific derivatives as compounds 96,97, 98,99, 100,101 and 102 are synthetised from their corresponding analogs of Et-770, compounds 51, 47,36, 31,32, 52 and 48 following the same methodology. o SoCo MeO 9\ HO Me 0 Ho Me AcO s I Mu N-mye I/N 0 -ozon 4 So4 o M e 01- MeO HO Me H S I Me 0 N--mye ION t O CN 106 A, B, C, or E o I MeO 4 NH OMe . I'I R20 Me 6 Mye 0 Razz RIO s O' _ t O CN HO F or J Structure of formula IV \ H OMe Me s. L Me OO RG 1 S Mu N mye I i NH OMe \-0 CN ° R20Me Ru S Structure of formula V Me W N--Me JHJorK AL/N J nu oye HO = -O OH I Me0 O..) NH OMe Structure of formula Vil Me 0 S Mu zu O t O OH Structure of formula Vl SCHEME V In Scheme V the starting material is compound 106 obtained from compound 4 by hydrolysis of the acetyl group in C-5 with KOH/THF/H20.

From compound 106 and by esterification and alkylation reactions can be prepared derivatives with structures of formula I. The next step includes the hydrolysis of the tert-butylcarbonate group (method F: TFA/H20/CH2C12 or method J: TMSC1, NaI ; CH3CN/H20) to afford derivatives of structures of formula III which are transformed into the final compounds (structure of formula IV) by conversion of the nitrile group in C-21 into the hydroxyl group. This last step is achieved following method H (AgNOs/CH3CN/H20), method I (CuBr/THF/H20) or method K (CuCl/THF/H20). In the case of derivatives of structure of formula I wherein Ri and R2 are Boc, Ri are Boc, AlaBoc and Voc radicals the hydrolysis of the tert-butylcarbonyl involves also the hydrolysis of these ester functionalities. These compounds are transformed into the final analogs through method H. HO N HOMe MeO HO Me ho S Mu N--H CN, Me 0 N -O CN HO 184 HO >NH OMe I MeO 0..", I N-Me OMe 0 AcOH Me p i N I N--Me Ace 0 po Zozo Et-729 0 185 KCN, II AcOH, OO MeOH I NH OMe Me0 y MeOH A 9 I NH OMe AllocCl AcO \ s MeO HO HO Me f DMAP me 0 NN 0 S : Dv. DMAP Me ßqn N--H \-O CN 187 0 \-O CN BoC20. D ! PEA RiO 186 < A RXO w I Boc20 Me0 I NH OMe ß O A"'HO < M PO PO mye N-ruz 1 NH OMe I NN-R2 MeO < NH OMe o < N > Ac0\ s j) J Ace me Compound Ri R2 188 H Boc wN 9^ O 189 Boc H O t0 CN 190 Boc Boc 188 0 0 "° I Me0 I NH OMe Me0 I NH OMe Me0 I NH OMe 0 oz HO Me 0 0 Me Ac0 g (Ac0 g Me 0 AllylBr me Me O N o N 0 N tO CN 0 CN \-0 CN 190 199 201 190 199 201 Ri0 O R, O) R 0- Me0 I NH OMe Me0 I NH OMe Me0 I NH OMe ) "'R Me) f"'R Me Ac0 g I Ac0 g I Ac0 g I Me N O F-Me I N H Me I A, 6 or 0 N N HO tO CN tO CN zu OH HO i NH OMe Structure of formula Vill Structure of formula IX Structure of forrnula X 0 mye AcO S I me N-o< 1 0 0 W° CN sCH3CN, CHO 188 NaBH3CN, HO HO HO I I AcOH N-Me OMe i N-Me OMe i N-Me OMe Me0 HO, Me 0''' ! HOkMe °''t HOkMe Ac0 g I Ac0 g I Ac0 g I me N-0-f\ ___ Me I N me 1 4 N i N O i N i N tO tN tO CN tO OH 200 209 217 SCHEME VI From Et-729 it is possible to obtain target compounds through different experimental conditions. In the attempts to prepare compound 186, other two compounds (184 and 185) were isolated as it is described in the scheme VI. Treatment of compound 186 with Alloc chloroformiate, pyridine and DMAP affords compound 187. With Boc anhydride with o whithout DIPEA we are able to obtain Boc derivatives (compounds 188,189 and 190). From compound 190 through an alkylation reaction (Cs2C03, allyl bromide) is prepared compound 199 which is transformed into compound 201 by hydrolysis of tert-butyl carbonate groups following method F.

From the key compound 188 through esterification reactions it is possible to generate compounds of structure of formula I mono or di sustitued. Hydrolisis of tert-butyl carbonate group (method F) and transformation of the nitrile group in C-21 into the hydroxyl group (method H) lead to the compounds of structure of fromula III. Also from compound 188 by a reductive methylation it is obtained compound 200 with a methyl group in position N-2'. Hydrolisis of the amide bond (method F) and conversion of the nitrile group into the hydroxyl group (method H) affords compound 217.

222 223 224 SCHEME VII In this scheme compound 221 can be obtained from compound 218, described in the Patent WO 0 1/77115 A 1 as compound 24, following a transamination reaction to afford 219 and a Pictect-Spengler cyclization to give compound 220. Final step is the conversion of nitrile group into OH in C-21 with the usual methodology (method K) using AgNOs. Also compound 224 can be obtained from compound 222, described in the WO 00/69862 as compound 36, following a Pictect-Splenger cyclization to give compound 223.

Final step is the conversion of nitrile group into OH in C-21 with the usual methodology (method K) EXPERIMENTAL PART Method A: To a solution of 1 equiv. of ET-770 (1) in CH2Cl2 (0.032M) under Argon were added 2 equiv. of the anhydride and 2 equiv. of pyridine. The reaction was followed by TLC and quenched with NaHCOs, extracted with CH2Cl2 and the organic layers dried over Na2SO4. Flash chromatography gives pure compounds.

Example 1.

1 2 2. lH-RMN (300 MHz, CDCIs) : 8 6.60 (s, 1H); 6.59 (s, 1H); 6.56 (s, 1H); 6.00 (dd, 2H); 5.73 (s, 1H) ; 5.01 (d, 1H) ; 4.55 (s, 1H) ; 4.32 (s, 1H) ; 4.27 (d, 1H) ; 4.17 (d, 1H) ; 4.11 (dd, 1H) ; 3.78 (s, 3H); 3.55 (s, 3H); 3.51 (d, 1H) ; 3.42 (s, 1H); 3.16-3. 06 (m, 1H); 2.94-2. 92 (m, 2H); 2.81-2. 75 (m, 1H); 2.64-2. 58 (m, 1H); 2.51-2. 44 (m, 1H) ; 2.35-2. 12 (m, 2H); 2.31 (s, 3H); 2.26 (s, 3H); 2.23 (s, 3H); 2.19 (s, 3H); 2.03 (s, 3H).

13C-RMN (75 MHz, CDC13) : 8 172.1, 168.9, 168.1, 148.4, 147.8, 145.3, 143.0, 141.3, 140.1, 138.5, 132.5, 130.8, 129.3, 128.7, 122.4, 121.0, 120. 7, 118.1, 118.0, 114.0, 111.8, 102.0, 101.8, 64.8, 61.1, 60.3, 60.1, 59.5, 55.1, 54.7, 53.3, 42.3, 41.9, 41.6, 39.5, 29.6, 28.6, 24.1, 20.5, 20.3, 15.7, 9.6.

ESI-MS m/z: Calcd for C42H44N4OloS : 812.3 Found (M+H+) : 813.3 Example 2 3. lH-RMN (300 MHz, CDCIs) : 8 6.48 (s, 1H); 6.47 (s, 1H); 6.44 (s, 1H); 6.01 (dd, 2H); 5.70 (s, 1H); 5.50 (s, 1H); 4.70-4. 78 (m, 2H); 4.39 (s, 1H); 4.24 (dd, 1H) ; 4.12-4. 08 (m, 2H); 3.80 (s, 3H); 3.59 (s, 3H); 3.55 (d, 1H) ; 3.42-3. 39 (m, 1H) ; 3.22 (d, 1H) ; 2.90 (d, 2H); 2.65 (t, 2H); 2.51 (d, 1H) ; 2.32 (s, 3H); 2.27- 2.03 (m, 2H); 2.40 (s, 3H); 2.12 (s, 3H); 2.03 (s, 3H).

13C-RMN (75 MHz, CDCIs) : 8 168.5, 167.6, 147.3, 145.4, 145.2, 143.1, 141.8, 140.7, 130.8, 129.7, 127.0, 126.3, 125.3, 122.5, 121.4, 118.5, 117.8, 114.3, 114.0, 113.8, 109.5, 102.1, 71.4, 62.2, 61.0, 60.3, 60.2, 60.1, 55.3, 55.1, 54.9, 42.6, 41.9, 39.0, 31.7, 29.3, 24.8, 22.8, 20.5, 15.7, 14.2, 9.9.

ESI-MS m/z: Calcd for C42H41F3N4011S : 867.2 Found (M+H+) : 866.2 Example 3 4. lH-RMN (300 MHz, CDCIs) : 56. 68 (s. lH) ; 6.58 (s, 1H) ; 6.57 (s, 1H) ; 6.00 (dd, 2H); 5.74 (s, 1H) ; 5.00 (d, 1H) ; 4.54 (s, 1H) ; 4.31 (s, 1H) ; 4.26 (dd, 1H) ; 4.17 (d 1H) ; 4.11 (dd, 1H) ; 3.78 (s, 3H); 3.58 (s, 3H); 3.51 (d, 1H) ; 3.42-3. 40 (m, 1H) ; 3.14-3. 06 (m, 1H) ; 2.94-2. 92 (m, 2H); 2.81-2. 75 (m, 1H) ; 2.64-2. 58 (m, 1H) ; 2.51-2. 44 (m, 1H); 2.35-2. 21 (m, 2H); 2.31 (s, 3H); 2.26 (s, 3H); 2.19 (s, 3H); 2.03 (s, 3H); 1.50 (s, 9H).

13C-RMN (75 MHz, CDCIs) : 8 172. 0,168. 0,151. 5,148. 5,147. 8,145. 3, 143.0, 141.2, 140.0, 138.8, 132.4, 130.7, 129.2, 128.6, 122.1, 122.0, 120.6, 118.1, 118.0, 113.9, 111.9, 101.8, 83.3, 64.7, 61.0, 60.2, 60.0, 59.6, 59.5, 55.2, 54.6, 54.5, 42.2, 41.8, 41.5, 39.5, 28.6, 27.5, 24.1, 20.3, 15.7, 9.6.

ESI-MS m/z: Calcd for C45HsoN4012S : 870.3 Found (M+H+) : 871.3 5 : lH-RMN (300 MHz, CDCIs) : 5 6. 92 (s, 1H); 6.69 (s, 1H); 6.55 (s, 1H); 6.00 (dd, 2H); 5.73 (s, 1H) ; 5.00 (d, 1H) ; 4.44 (s, 1H) ; 4.32 (s, 1H) ; 4.18 (d, 1H) ; 4.09 (dd, 1H) ; 3.93 (d, 1H) ; 3.79 (s, 3H); 3.58 (s, 3H); 3.53 (d, 1H) ; 3.46-3. 44 (m, 1H) ; 3.12-3. 04 (m, 1H) ; 2.97 (d, 2H); 2.83-2. 77 (m, 1H) ; 2.65-2. 58 (m, 1H) ; 2.51-2. 46 (m, 1H) ; 2.32-2. 03 (m, 2H); 2.32 (s, 3H); 2.31 (s, 3H); 2.17 (s, 3H); 2.04 (s, 3H); 1.53 (s, 9H); 1.50 (s, 9H).

13C-RMN (75 MHz, CDC1s) : 8 172. 0,168. 4,151. 5,151. 2,148. 5,148. 1, 145.6, 144.0, 141.3, 140.1, 138.9, 132.3, 131.3, 130.3, 128.7, 126.9, 124.3, 122.2, 121.0, 117.8, 113.8, 111.8, 101.9, 83.4, 83.2, 64.9, 61.1, 60.0, 59.9, 59.6, 59.1, 55.6, 55.2, 54.4, 42.2, 41.9, 41.5, 39.5, 28.6, 27.6, 27.5, 23.9, 20.1, 15.7, 9.6.

ESI-MS m/z: Calcd for CsoH58N40i4S : 970.1 Found (M+H+) : 971.3 Example 4 1 6 Compound 6 is obtained with 45 equiv of Ac20 and 113 equiv. of pyridine and catalytic amount of DMAP.

6. 1H-NMR (300 MHz, CDC13) : 8 6.95 (s, 1H), 6.62 (s, 1H), 6.54 (s, 1H), 6.02 (dd, 2H), 5.01 (d, 1H), 4.44 (bs, 1H), 4.32 (s, 1H), 4.19 (d, 1H), 4.12 (dd, 1H), 3.82 (d, 1H), 3.77 (s, 3H), 3.65 (s, 3H), 3.53 (bd, 1H), 3.47-3. 43 (m, 1H), 3.14-3. 05 (m, 1H), 3.00-2. 97 (m, 2H), 2.86-2. 78 (m, 1H), 2.69-2. 58 (m, 1H), 2.52-2. 44 (m, 1H), 2.38-2. 15 (m, 2H), 2.38 (s, 3H), 2.32 (s, 3H), 2.30 (s, 3H), 2.24 (s, 3H), 2.15 (s, 3H), 2.04 (s, 3H).

ESI-MS m/z: Calcd for C44H46N4012S : 854.3 Found (M+H+) : 855.3 Example 5.

Method B: To a solution of 1 equiv. of Et-770 (1) in CH2C12 (0.032M) under Argon at room temperature were added 2 equiv. of base and 2 equiv. of the acid chloride. The reaction was followed by TLC and quenched with NaHCOs, extracted with CH2C12 and the organic layers dried with Na2SO4.

Flash chromatography gives pure compounds.

1 7 After chromatographic purification 25% of starting material was recuperated.

7. lH-NMR (300 MHz, CDC13) : 5 6.59 (s, 2H); 6.56 (s, 1H); 6.00 (dd, 2H); 5.74 (s, 1H) ; 5.01 (d, 1H) ; 4.55 (s, 1H) ; 4.32 (s, 1H) ; 4.27 (dd, 1H) ; 4.17 (d, 1H); 4.11 (dd, 1H); 3.78 (s, 3H); 3.54 (s, 3H); 3.51 (d, 1H); 3.42 (s, 1H); 3.16- 3.05 (m, 1H); 2.94-2. 93 (m, 2H); 2.81-2. 75 (m, 1H); 2.64-2. 58 (m, 1H); 2.51- 2.44 (m, 1H) ; 2.48 (t, 2H); 2.35-2. 11 (m, 2H); 2.31 (s, 3H); 2.26 (s, 3H); 2.19 (s, 3H); 2.03 (s, 3H); 1.73 (m, 2H); 1.00 (t, 3H).

13C-NMR (75 MHz, CDC13) : 8 172.1, 168.9, 168.1, 148.4, 147.8, 145.3, 143.0, 141.3, 140.1, 132.4, 130.8, 129.3, 128.6, 122.4, 121.0, 120.7, 118.1, 114.0, 111.7, 107.2, 101.8, 64.8, 61.0, 60.3, 60.0, 59.6, 59. 5, 55.1, 54. 7, 54.6, 42.3, 41.9, 41.6, 39.5, 35.8, 33.7, 29.6, 28.6, 24.1, 20.3, 18.5, 15.7, 14.0, 9.6.

ESI-MS m/z: Calcd. for C44H48N4O11S : 840.3 Found (M+H+) : 841.3.

Example 6 1 8 After chromatographic purification 28% of starting material was recuperated.

8. lH-NMR (300 MHz, CDCIs) : 8 7.80 (d, 1H); 7.56-7. 54 (m, 2H); 7.41-7. 39 (m, 3H); 6.69 (s, 1H) ; 6.60 (s, 2H); 6.59 (d, 1H) ; 6.00 (dd, 2H); 5.74 (s, 1H) ; 5.03 (d, 1H) ; 4.56 (s, 1H) ; 4.33 (s, 1H) ; 4.28 (dd, 1H) ; 4.17 (d, 1H) ; 4.11 (dd, 1H); 3.79 (s, 3H); 3.58 (s, 3H); 3.52 (d, 1H); 3.42-3. 40 (m, 1H); 3.16-3. 06 (m, 1H) ; 2.96-2. 93 (m, 2H); 2.82-2. 75 (m, 1H) ; 2.64-2. 59 (m, 1H) ; 2.54-2. 46 (m, 1H); 2.38-2. 12 (m, 2H); 2.32 (s, 3H); 2.28 (s, 3H); 2.20 (s, 3H); 2.04 (s, 3H).

13C-NMR (75 MHz, CDC13) : 8 172.1, 169.0, 148.4, 147.8, 145.3, 143.0, 141.3, 140.1, 138.5, 132.5, 130.8, 129.3, 128.9, 128.6, 127.4, 127.3, 122.4, 121.0, 120.7, 118.1, 114.0, 111.7, 101.8, 64.8, 61.1, 60.3, 60.1, 59.6, 59.5, 55.1 54.7, 54.6, 42.3, 41.9, 41.6, 39.5, 29.7, 28.6, 24.1, 20.6, 20.4, 15.8, 9.7.

ESI-MS m/z: Calcd. for C49H48N4011S : 900.3 Found (M+H+) : 901.3 Example 7 9 was obtained using 10 equiv. of butyryl chloride and 10 equiv. of TEA.

1H-NMR (300 MHz, CDCIs) : 8 6.95 (s, 1H); 6.60 (s, 1H); 6.54 (s, 1H); 6.01 (dd, 2H); 5.01 (d, 1H) ; 4.45 (s, 1H) ; 4.32 (s, 1H) ; 4.17 (d, 1H) ; 4.09 (dd, 1H) ; 3.80 (d, 1H) ; 3.75 (s, 3H); 3.54 (s, 3H); 3.51 (d, 1H) ; 3.44 (s, 1H) ; 3.16-3. 05 (m, 1H) ; 2.99-2. 97 (m, 2H); 2.85-2. 79 (m, 1H) ; 2.64-2. 58 (m, 1H) ; 2.61 (t, 2H); 2.51-2. 44 (m, 1H); 2.48 (t, 2H); 2.33-2. 02 (m, 2H); 2.32 (s, 3H); 2.29 (s, 3H); 2.15 (s, 3H); 2.04 (s, 3H); 1.86 (m, 2H); 1.73 (m, 2H); 1.09 (t, 3H); 1.00 (t, 3H).

ESI-MS m/z: Calcd. for C48H54N4012S : 910.3 Found (M+ H+) : 911.3.

Example 8 1 10 10. lH-N M R (300 MHz, CDCIs) : 8 7. 94 (d, 1H) ; 7.81 (d, 1H) ; 7.63-7. 54 (m, 4H) ; 7.46-7. 39 (m, 6H) ; 6.99 (s, 1 H) ; 6.70 (s, 1 H) ; 6.66 (d, 1H) ; 6.60 (d, 1H) ; 6.59 (s, 1 H) ; 6.02 (dd, 2H) ; 5.04 (d, 1H) ; 4.55 (s, 1 H) ; 4.35 (s, 1 H) ; 4.21 (d, 1 H) ; 4.13 (dd, 1 H) ; 3.92 (d, 1 H) ; 3.79 (s, 3H) ; 3.57 (s, 3H) ; 3.54 (d, 1H) ; 3.48- 3.45 (m, 1H) ; 3.20-3. 10 (m, 1H) ; 3.01-2. 99 (m, 2H) ; 2.88-2. 80 (m, 1H) ; 2.74. 2.62 (m, 1H) ; 2.56-2. 50 (m, 1H) ; 2.41-2. 15 (m, 2H) ; 2.35 (s, 3H) ; 2.34 (s, 3H) ; 2.19 (s, 3H) ; 2.06 (s, 3H).

ESI-MS m/z: Calcd. for C58H54N4012S : 1030.3 Found (M+H+) : 1031.3.

Example 9 1 11 The reaction was performed using 4 equiv. of hydrocynamoyl chloride and 2 equiv. of pyridine. After chromatographic purification 25% of starting material was recuperated.

11. lH-NMR (300 MHz, CDCIs) : 5 7.31-7. 20 (m, 5H); 6.59 (s, 1H) ; 6.55 (s, 1H) ; 6.53 (s, 1H) ; 6.03 (s, 1H) ; 5.97 (s, 1H) ; 5.76 (s, 1H) ; 5.01 (d, 1H) ; 4.56 (s, 1H) ; 4.32 (s, 1H) ; 4.28 (d, 1H) ; 4.17 (d, 1H) ; 4.11 (dd, 1H) ; 3.78 (s, 3H); 3.56- 3.50 (m, 1H) ; 3.51 (s, 3H); 3.42 (s, 1H) ; 3.14-2. 92 (m, 3H); 3.02 (t, 2H); 2.87- 2.78 (m, 1H); 2.83 (t, 2H); 2.67-2. 43 (m, 4H); 2.3. 2.25 (m, 1H); 2.31 (s, 3H); 2.27 (s, 3H); 2.19 (s, 3H); 2.03 (s, 3H).

3C-RMN (75 MHz, CDCIs) : 8 172.2, 171.2, 148.6, 148.0, 145.5, 143.2, 141.5, 140.4, 140.3, 138.7, 132.6, 131.0, 129.6, 128.8, 128.7, 128.6, 128.5, 126.5, 122.6, 121. 2,120. 9, 118. 3, 118. 2, 114. 2, 111. 9,102. 1,65. 0, 61. 3, 60.5, 60.3, 59.8, 59.7, 55.3, 54.8, 54.7, 42.3, 42.1, 41.8, 39.6, 35.6, 35.5, 31.4, 30.9, 29.9, 28.6, 24.3, 20.6, 16.0, 9.9.

ESI-MS m/z: Calcd. for C49HsoN4O11S : 902.3 Found (M+H+): 903.2.

Example 10 12. lH-NMR (300 MHz, CDC13) : 8 6.68 (s, 1H) ; 6.58 (s, 1H) ; 6.47 (s, 1H) ; 6.06 (d, 1H) ; 5.97 (d, 1H) ; 5.02 (d, 1H) ; 4.59 (s, 1H) ; 4.37 (s, 1H) ; 4.29 (d, 1H) ; 4.19-4. 16 (m, 2H); 3.85 (s, 2H); 3.75 (s, 3H); 3.55 (s, 3H); 3.53 (s, 1H) ; 3.43 (d, 1H); 3.07-2. 80 (m, 5H); 3.00 (t, 2H); 2.83 (t, 2H); 2.61-2. 57 (m, 1H); 2.44-2. 33 (m, 1H); 2.37 (m, 3H); 2.29 (s, 3H); 2.21 (s, 3H); 2.03 (s; 3H).

ESI-MS m/z: Calcd. for C43H45ClN4011S : 860.2 Found (M+H+) : 861.3.

Example 11 13. lH-NMR (300 MHz, CDCIs) : 86. 69 (s, 1H); 6.63 (s, 1H); 6.59 (s, 1H); 6.04 (s, 1H) ; 5.96 (s, 1H) ; 5.74 (s, 1H) ; 5.02 (d, 1H) ; 4.58 (s, 1H) ; 4.33 (s, 1H) ; 4.28 (d, 1H) ; 4.18 (d, 1H) ; 4.13 (dd, 1H) ; 3.78 (s, 3H); 3.57 (s, 3H); 3.51 (d, 1H) ; 3.42 (s, 1H) ; 3.14-3. 06 (m, 1H) ; 2.94 (d, 2H); 2.82-2. 76 (m, 1H) ; 2.69- 2.59 (m, 1H); 2.54-2. 48 (m, 1H); 2.36-2. 14 (m, 1H); 2.32 (s, 3H); 2.26 (s, 3H); 2.19 (s, 3H); 2.03 (s, 3H).

ESI-MS m/z: Calcd. for C44H41F7N4011S : 966.2 Found (M+H+) : 967.3.

Example 12 Method C: To a solution of 1 equiv. of ET-770 (1) in CH2CI2 (0.032M) under Argon were added 2 equiv. of acid, 2 equiv. of DMAP and 2 equiv. of EDC. HC1. The reaction was stirred at room temperature for 2 h. After this time was diluted with CH2Cl2, washed with brine and the organic layer dried with Na2SO4. Flash chromatography gives pure compounds.

14. 1H-NMR (300 MHz, CDCIs) : 8 6.59 (s, 2H); 6.56 (s, 1H); 6.00 (dd, 2H); 5.72 (s, 1H) ; 5.01 (d, 1H) ; 4.55 (s, 1H) ; 4.32 (s, 1H) ; 4.27 (dd, 1H) ; 4.17 (d 1H) ; 4.10 (dd, 1H) ; 3.79 (s, 3H); 3.54 (s, 3H); 3.51 (d, 1H) ; 3.42 (s, 1H) ; 3.16- 3.05 (m, 1H); 2.94-2. 93 (m, 2H); 2.81-2. 75 (m, 1H); 2.64-2. 58 (m, 1H); 2.51- 2.44 (m, 1H); 2.49 (t, 2H); 2.35-2. 11 (m, 2H); 2.32 (s, 3H); 2.27 (s, 3H); 2.19 (s, 3H); 2.03 (s, 3H); 1.73-1. 68 (m, 2H); 1.25-1. 15 (m, 8H); 1.02 (t, 3H).

3C-NMR (75 MHz, CDCIs) : 8 172.1, 171.8, 148.4, 147.8, 145.3, 143.0, 141.3, 140.1, 138.6, 132.4, 130.8, 129.3, 128.6, 122.9, 122.4, 121.0, 120.7, 120.6, 118.1, 114.0, 111.7, 101.8, 64.8, 61.0, 60.3, 60.0, 59.6, 59.5, 55.1, 54.7, 54.6, 42.3, 41.8, 41.5, 39.5, 33.9, 33.7, 31.9, 31.6, 30.1, 29.3, 28.9, 28.8, 28.6, 26.9, 24.9, 24.1, 22.6, 22.5, 20.3, 15.7, 14.0, 9.6.

ESI-MS m/z: Calcd. for C48H56N4O11S : 896.3 Found (M+H+): 897.3.

Example 13 Compound 15 is obtained following method C, using 10 equiv. of octanoic acid and 10 equiv. Of EDC HC1 and 10 equiv. of DMAP) : 15. 1H-NMR (300 MHz, CDC13) : 8 6.94 (s, 1H); 6.59 (s, 1H); 6. 53 (s, 1H); 6.01 (dd, 2H); 5.01 (d, 1H) ; 4.45 (s, 1H) ; 4.32 (s, 1H) ; 4.18 (d, 1H) ; 4.10 (dd, 1H) ; 3.80 (d, 1H) ; 3.74 (s, 3H); 3.54 (s, 3H); 3.51 (d, 1H) ; 3.44 (s, 1H) ; 3.16- 3.05 (m, 1H) ; 2.99-2. 97 (m, 2H); 2.88-2. 79 (m, 1H) ; 2. 64-2. 58 (m, 1H) ; 2. 61 (t, 2H); 2. 51-2. 44 (m, 1H); 2. 49 (t, 2H); 2.35-2. 15 (m, 2H); 2.32 (s, 3H); 2.29 (s, 3H); 2. 15 (s, 3H); 2.03 (s, 3H); 1.88-1. 78 (m, 2H); 1.74-1. 56 (m, 4H); 1. 39- 1.24 (m, 20H).

13C-NMR (75 MHz, CDCIs) : 8 182.1, 172.2, 172.0 171.4, 148.7, 148.2, 145.7, 143.9, 141.5, 140.4, 138.9, 132.3, 131.7, 130.8, 128.8, 127.4, 124.6, 122.8, 121.0, 118.0, 114.1, 111.9, 102.2, 65.1, 61.3, 60.3, 60.2, 59.8, 59.4, 56.1, 55.3, 54.6, 42.6, 42.3, 41.8, 39.7, 34.4, 34.1, 33.8, 31.8, 29.9, 29.4, 29.2, 29.1, 29.0, 28.7, 25.4, 25.2, 24.9, 24.2, 22.7, 20.5, 16.0, 14.2, 9.8.

ESI-MS m/z : Calcd. for C56H70N4012S : 1022.4 Found (M+H+) : 1023.5.

Example 14 Compounds 16 and 17 were obtained using Method C.

16 : lH-NMR (300 MHz, CDCI3) : 8 6.61 (s, 2H); 6.56 (s, 1H); 6.00 (dd, 2H); 5.75 (s, 1H) ; 5.01 (d, 1H) ; 4.56 (s, 1H) ; 4.32 (s, 1H) ; 4.27 (dd, 1H) ; 4.17 (d, 1H) ; 4.09 (dd, 1H) ; 3.79 (s, 3H); 3.53 (s, 3H); 3.50 (d, 1H) ; 3.41 (s, 1H) ; 3.16- 3.05 (m, 1H) ; 2.95-2. 93 (m, 2H); 2.81-2. 75 (m, 1H) ; 2.68-2. 55 (m, 1H) ; 2.51- 2.44 (m, 1H) ; 2.49 (t, 2H); 2.39-2. 11 (m, 2H); 2.32 (s, 3H); 2.28 (s, 3H); 2.19 (s, 3H); 2.03 (s, 3H); 1.73-1. 64 (m, 2H); 1.40-1. 17 (m, 27H).

13C-NMR (75 MHz, CDC13) : 8 172.0, 171.8, 168.0, 148.4, 147.8, 145.3, 143.0, 141.3, 140.1, 138.6, 132.3, 130.8, 129.8, 129.3, 128.6, 122. 4, 121. 0, 120.7, 118.0, 114.0, 111.7, 101.8, 64.8, 61.0, 60.2, 60.0, 59.6, 59.5, 55.1, 54.6, 54.6, 42.2, 41.8, 41.5, 39.5, 33.9, 31.8, 29.7, 29.63, 29.60, 29.44, 29.30, 29.21, 29.07, 28.9, 28.5, 24.9, 24.1, 22.6, 20.3, 15.7, 14.0, 9.6.

ESI-MS m/z: Calcd. for C56H72N4011S : 1008.4 Found (M+H+) : 1009.5.

17 : lH-NMR (300 MHz, CDCl3) : 8 6.94 (s, 1H); 6.59 (s, 1H); 6.54 (s, 1H); 6.02 (dd, 2H); 5.01 (d, 1H) ; 4.45 (s, 1H) ; 4.33 (s, 1H) ; 4.18 (d 1H) ; 4.10 (dd, 1H) ; 3.79 (d, 1H); 3.75 (s, 3H); 3.54 (s, 3H); 3.52 (d, 1H); 3.49 (s, 1H); 3.15-3. 05 (m, 1H) ; 2.99-2. 97 (m, 2H); 2.83-2. 75 (m, 1H) ; 2.68-2. 55 (m, 1H) ; 2.62 (t, 2H); 2.51-2. 44 (m, 1H); 2.49 (t, 2H); 2.36-2. 11 (m, 2H); 2.32 (s, 3H); 2.29 (s, 3H); 2.16 (s, 3H); 2.04 (s, 3H); 1.86-1. 78 (m, 2H); 1.72-1. 75 (m, 2H); 1.40- 1.10 (m, 54H).

ESI-MS m/z: Calcd. for C72Hlo2N4O12S : 1246.7 Found (M+H+) : 1247.6.

Example 15 Compound 18 is obtained with 1.5 equiv. of acid, 2.5 equiv. of DMAP and 2.5 equiv. of EDC. HC1 (Method C) 18 lH-NMR (300 MHz, CDCIs) : 8 7.74 (d, 2H), 7.64 (t, 2H), 7.38 (t, 2H), 7. 31- 7.27 (m, 2H), 6.60 (s, 1H), 6.57 (s, 1H), 6.55 (s, 1H), 5.98 (d, 2H), 5.96-5. 83 (m, 1H), 5.72 (s, 1H), 5.58 (d, 1H), 5.37-5. 18 (m, 2H), 5.04 (d, 1H), 4.88-4. 79 (m, 1H), 4.58 (bd, 3H), 4.32 (s, 1H), 4.25 (d, 1H), 4.18 (d, 1H), 4.12-4. 08 (m, 2H), 3.79 (s, 3H), 3.51 (d, 1H), 3.45 (s, 3H), 3.45-3. 42 (m, 1H), 3.16-3. 11 (m, 5H), 2.95-2. 93 (m, 2H), 2.82-2. 75 (m, 1H), 2.63-2. 50 (m, 1H), 2.46-2. 41 (m, 1H), 2.32-2. 13 (m, 2H), 2.32 (s, 3H), 2.27 (s, 3H), 2.20 (s, 3H), 2.03 (s, 3H).

ESI-MS m/z: Calcd. for C61H6lN5013S2 : 1135.4 Found (M+H+) : 1136.3.

Example 16 0 HN NH H 0 H 0 s HO N 0 N I/NH OMe ON" \ ON" \ 0 s HoE5 l H Me H MeO9HO M H *D M AcO s I AcD S I AcO s I Me N--Me Biotin, 40 °C Ac0 O S \ + Ac0 O S N N--Me pCM/CHCN 1 : 1 Me N N'-Me Me I N N--Me O : p p ! . Oot CN p CN --0 CN 20 46% 31% A mixture of compopunds 19 and 20 were obtained with 1.5 equiv. of biotin, 2.5 equiv. of DMAP and 2.5 equiv. of EDC. HC1. (Method C) 19: 1H-NMR (300 MHz, CDCIs) : 8 6.59 (s, 2H), 6.56 (s, 1H), 6.00 (d, 2H), 5.81 (bs, 1H), 5.26 (bs, 1H), 5.02 (d, 1H), 4.83 (bs, 1H), 4.57 (bs, 3H), 4.51-4. 47 (m, 1H), 4.33-4. 29 (m, 3H), 4.18 (d, 1H), 4.14-4. 11 (m, 1H), 3.79 (s, 3H), 3.55 (s, 3H), 3.52-3. 50 (m, 1H), 3.49-3. 42 (m, 1H), 3.19-3. 13 (m, 2H), 2.94-2. 87 (m, 3H), 2.78-2. 70 (m, 2H), 2.62-2. 48 (m, 4H), 2.38-2. 16 (m, 2H), 2.32 (s, 3H), 2.27 (s, 3H), 2.20 (s, 3H), 2.03 (s, 3H), 1.79-1. 50 (m, 6H).

ESI-MS m/z: Calcd. for CsoH56N6012S2 : 996.3 Found (M+H+) : 997.3.

20: lH-NMR (300 MHz, CDC13) : 8 6.95 (s, 1H), 6.62 (s, 1H), 6.52 (bs, 1H), 6.01 (d, 2H), 5.57 (bs, 1H), 5.40 (bs, 1H), 5.01 (d, 1H), 4.99 (bs, 1H), 4.92 (bs, 1H), 4.51-4. 28 (m, 6H), 4.18 (d, 1H), 4.13-4. 09 (m, 1H), 3.80-3. 77 (m, 4H), 3.55 (s, 3H), 3.55-3. 52 (m, 1H), 3.46-3. 42 (m, 1H), 3.24-3. 12 (m, 3H), 3.02-2. 52 (m, 13H), 2.33-2. 15 (m, 2H), 2.33 (s, 6H), 2.15 (s, 3H), 2.05 (s, 3H), 1.87-1. 47 (m, 12H).

ESI-MS m/z: Calcd. for CeoHvoNsOSs : 1222.4 Found (M+H+) : 1223.3.

Example 17 21. Was obtained using Method C lH-NMR (300 MHz, CDC13) : 8 8.66 (s, 1H); 7.66-7. 59 (m, 2H); 7.35-7. 29 (m, 2H); 6.74 (s, 1H) ; 6.60 (s, 1H) ; 6.59 (s, 1H) ; 6.01 (d, 1H) ; 5.94 (d, 1H) ; 5.81 (s, 1H) ; 5.02 (d, 1H) ; 4.55 (s, 1H) ; 4.31 (s, 1H) ; 4.26 (d, 1H) ; 4.18 (d, 1H) ; 4.13-4. 06 (m, 2H); 3.77 (s, 3H); 3.55 (s, 3H); 3.50 (d, 1H); 3.41 (s, 1H); 3.15- 3. 06 (m, 1H) ; 2. 94 (d, 2H); 2. 80-2. 75 (m, 1H) ; 2. 68-2. 58 (m, 1H) ; 2. 52-2. 47 (m, 1H); 2. 37-2. 11 (m, 1H); 2. 31 (s, 3H); 2.26 (s, 3H); 2.18 (s, 3H); 2.02 (s, 3H).

ESI-MS m/z : Calcd. for C50H46N4013S : 942.8 Found (M+Na+) : 965.1.

Example 18 Compounds 22 and 23 are obtained using Method C as a mixture 3: 1 and described together in lH-RMN.

22, 23. 1H-NMR (300 MHz, CDCl3) : 8 7.46 (d, 1H); 7.43 (d, 1H); 6.89 (s, 1H) ; 6.64-6. 34 (m, 9H); 6.19 (s, 1H) ; 6.18 (s, 1H) ; 6.03 (s, 1H) ; 6.02 (d, 1H) ; 5.97 (d, 1H) ; 5.95 (d, 1H) ; 5.80 (s, 1H) ; 5.01 (d, 1H) ; 4.99 (d, 1H) ; 4.55 (s, 2H); 4.30 (s, 2H); 4.27-4. 23 (m 2H); 4.19-4. 15 (m, 2H); 4.10 (dd, 1H); 4.09 (dd, 1H) ; 4.01-3. 90 (m, 2H); 3.85 (s, 4H); 3.77 (s, 6H); 3.68 (s, 2H); 3.59 (s, 1H); 3.56-3. 46 (m, 2H); 3.49 (s, 6H); 3.40 (s, 2H); 3.13-3. 06 (m, 2H); 3.04 (s, 12H); 2.96 (s, 6H); 2.92 (d, 4H); 2.81-2. 73 (m, 2H); 2.63-2. 56 (m, 2H); 2.49- 2.41 (m, 2H); 2.30 (s, 3H); 2.28 (s, 3H); 2.25 (s, 3H); 2.18 (s, 3H); 2.10 (s, 3H); 2.09 (s, 3H); 2.02 (s, 3H); 2.01 (s, 3H).

ESI-MS m/z: Calcd. for C53H53N5O13S (22) 1000.08 and Calcd. for C66H64N6016S (23) 1229.3. Found (M+) : 1000.2 (22) and 1229.2 (23).

Example 19 24 was obtained using Method C. lH-NMR (300 MHz, CDC13) : 8 6.61 (s, 1H), 6.58 (s, 1H), 6.56 (s, 1H), 5.98 (d, 2H), 5.84 (s, 1H), 5.09 (bd, 1H), 5.00 (d, 1H), 4.54-4. 51 (m, 2H), 4.31 (s, 1H), 4.27 (d, 1H), 4.17 (d, 1H), 4.12-4. 07 (m, 1H), 3.77 (s, 3H), 3.53 (s, 3H), 3.50 (d, 1H), 3.42-3. 39 (m, 1H), 3.13-3. 04 (m, 1H), 2.94-2. 92 (m, 2H), 2.79-2. 75 (m, 1H), 2.66-2. 56 (m, 1H), 2.50-2. 45 (m, 1H), 2.35-2. 02 (m, 2H), 2.31 (s, 3H), 2.26 (s, 3H), 2.18 (s, 3H), 2.02 (s, 3H), 1.48 (d, 3H), 1.43 (s, 9H).

3C-NMR (75 MHz, CDC13) : 8 172.0, 171.5, 168.1, 154.9, 148.1, 147.8, 145.3, 142.9, 141.2, 140.0, 138.2, 132.7, 130.7, 129. 3, 128.6, 122.2, 120.9, 120.6, 118.0, 113.9, 113.3, 111.7, 101.8, 79.8, 64.8, 61.0, 60.2, 60.1, 59.5, 59.5, 55.1, 54.6, 54.5, 42.1, 41.8, 41. 5, 39.4, 28.5, 28.2, 24.1, 20.4, 18.7, 15.7, 9.6.

ESI-MS m/z: Calcd. for C48H55NsOl3S : 941.3 Found (M+H+) : 942.3.

Example 20 Method D: To a solution of 1 equiv. of starting material in CHaCb (0.032M) under Argon were added 2 equiv. of chloroformiate and 2 equiv. of base and the mixture was stirred at room temperature. The reaction was followed by TLC and quenched with NaHCOs, extracted with CH2Cl2 and the organic layers dried with Na2SO4. Flash chromatography gives pure compounds.

1 25 The reaction is performed with 3.3 equiv. of Alloc chloride and 3.3 equiv. of pyridine.

25. 1H-NMR (300 MHz, CDCIs) : 8 6.70 (s, 1H), 6.59 (s, 1H), 6.57 (s, 1H), 6.07-5. 89 (m, 1H), 6.00 (d, 2H), 5.76 (s, 1H), 5.42-5. 27 (m, 2H), 5.01 (d, 1H), 4.69-4. 66 (m, 2H), 4.56 (bs, 1H), 4.33 (s, 1H), 4.27 (d, 1H), 4.17 (d, 1H), 4.01 (dd, 1H), 3.79 (s, 3H), 3.58 (s, 3H), 3.51 (bd, 1H), 3.45-3. 40 (m, 1H), 3.16- 3.06 (m, 1H), 2.97-2. 91 (m, 2H), 2.85-2. 75 (m, 1H), 2.70-2. 57 (m, 1H), 2.53- 2.45 (m, 1H), 2.37-2. 12 (m, 2H), 2.32 (s, 3H), 2.27 (s, 3H), 2.20 (s, 3H), 2.04 (s, 3H).

ESI-MS m/z: Calcd. for C44H46N4012S : 854.3 Found (M+H+) : 855.0.

Example 21 The reaction was performed with excess of Alloc Chloride and pyridine and catalytic DMAP (method D). Some starting material was recovered after chromatographic purification.

26. 1H-NMR (300 MHz, CDC13) : 86. 96 (s, 1H), 6.70 (s, 1H), 6.56 (s, 1H), 6.06-5. 89 (m, 2H), 6.01 (d, 2H), 5.44-5. 27 (m, 4H), 5.00 (d, 1H), 4.82-4. 67 (m, 4H), 4.47 (bs, 1H), 4.34 (s, 1H), 4.19-4. 09 (m, 2H), 3.94 (d, 1H), 3.79 (s, 3H), 3.57 (s, 3H), 3.54-3. 45 (m, 2H), 3.15-3. 03 (m, 1H), 2.99-2. 97 (m, 2H), 2.84-2. 77 (m, 1H), 2.70-2. 59 (m, 1H), 2.53-2. 44 (m, 1H), 2.32-2. 17 (m, 8H), 2. 17 (s, 3H), 2.05 (s, 3H).

ESI-MS m/z: Calcd. for C48H5oN4014S : 938.3 Found (M+H+) : 939.3.

Example 22 The reaction was performed with 3.0 equiv. of pyridine (Method D).

27. 1H-NMR (300 MHz, CDCIs) : 8 7.38-7. 33 (m, 5H); 6.69 (s, 1H); 6.59 (s, 1H) ; 6.57 (s, 1H) ; 5.99 (dd, 2H); 5.75 (s, 1H) ; 5.21 (s, 2H); 5.00 (d, 1H) ; 4.56 (s, 1H) ; 4.32 (s, 1H) ; 4.27 (dd, 1H) ; 4.17 (d, 1H) ; 4.10 (dd, 1H) ; 3.78 (s, 3H); 3.54 (s, 3H); 3.51 (d, 1H) ; 3.41 (s, 1H) ; 3.16-3. 06 (m, 1H) ; 2.94-2. 93 (m, 2H); 2.81-2. 75 (m, 1H); 2.68-2. 58 (m, 1H); 2.49-2. 44 (m, 1H); 2.35-2. 13 (m, 2H); 2.31 (s, 3H); 2.26 (s, 3H); 2.19 (s, 3H); 2.03 (s, 3H).

13C-NMR (75 MHz, CDC13) : 8 172.0, 168.1, 148.4, 147.8, 145.3, 143.0, 141.3, 140.1, 138.9, 134.9, 132.8, 130.7, 129.3, 128.7, 128.5, 128.3, 121.9, 121.0, 120.7, 118.0, 114.0, 111.9, 101.8, 70.2, 64.8, 61.0, 60.3, 60.1, 59.6, 59.5, 55.1, 54.7, 54.6, 42.2, 41.8, 41. 5, 39.5, 29.6, 28.6, 24.1, 20.3, 15.7, 9.6.

ESI-MS m/z: Calcd. for C48H48N4012S : 904.3 Found (M+ H+) : 905.3.

Example 23 28: Was obtained following Method C using TEA as base.

1H-NMR (300 MHz, CDCl3) : 8 7.40-7. 34 (m, 10H) ; 6.95 (s, 1H); 6.69 (s, 1H) ; 6.54 (s, 1H) ; 5.99 (dd, 2H); 5.33 (d, 1H) ; 5.23 (s, 1H) ; 5.21 (s, 2H); 5.00 (d, 1H) ; 4.43 (s, 1H) ; 4.32 (s, 1H) ; 4.17 (d, 1H) ; 4.10 (dd, 1H) ; 3.90 (d, 1H) ; 3.75 (s, 3H); 3.53 (s, 3H); 3.50 (d, 1H) ; 3.44 (s, 1H) ; 3.20-3. 01 (m, 1H) ; 2.97-2. 96 (m, 2H); 2.82-2. 75 (m, 1H) ; 2.68-2. 56 (m, 1H) ; 2.51-2. 42 (m, 1H) ; 2.28-2. 00 (m, 2H); 2.31 (s, 3H); 2.19 (s, 3H); 2.12 (s. 3H); 2.03 (s, 3H).

13C-NMR (75 MHz, CDC13) : 8 172.2, 168.7, 153.4, 153.1, 148.6, 148.2, 145.7, 144.3, 141.5, 140.4, 139.1, 135.1, 132.8, 131.7, 130.8, 129.0, 128.9, 128.8, 128.7, 128.5, 128.4, 127.5, 124.5, 122.4, 122.2, 121.1, 117.9, 114.0, 113.6, 112.1, 102.1, 70.7, 70.5, 65.2, 61.3, 60.4, 60.2, 59.8, 59.4, 55.7, 55.3, 54.6, 42.4, 42.1, 41.7, 39.7, 28.8, 24.1, 20.2, 15.9, 9.8.

ESI-MS m/z: Calcd. for C56H54N4014S : 1038.3 Found (M+ H+) : 1039.8.

Example 24 1 29 29. was obtained using Method D.

H-NMR (300 MHz, CDCIs) : 5 7.08 (dd, 1H) ; 6.72 (s, 1H) ; 6.60 (s, 1H) ; 6.59 (s, 1H) ; 6.03 (s, 1H) ; 5.96 (s, 1H) ; 5.77 (s, 1H) ; 5.01 (d, 1H) ; 4.99 (dd, 1H) ; 4.63 (dd, 1H) ; 4.56 (s, 1H) ; 4.32 (s, 1H) ; 4.27 (d, 1H) ; 4.17 (d, 1H) ; 4.11 (dd, 1H) ; 3.78 (s, 3H); 3.58 (s, 3H); 3.51 (d, 1H) ; 3.42 (s, 1H) ; 3.15-3. 06 (m, 1H) ; 2.93 (d, 2H); 2.82-2. 75 (m, 1H) ; 2.68-2. 57 (m, 1H) ; 2.52-2. 46 (m, 1H) ; 2.36-2. 14 (m, 1H); 2.31 (s, 3H); 2.26 (s, 3H); 2.19 (s, 3H); 2.02 (s, 3H).

ESI-MS m/z: Calcd. for C43H44N4012S : 840.2 Found (M+ H+) : 841.3.

Example 25 The reaction was performed with 5.0 equiv. of TEA and 10 equiv. of vinylchloroformiate (method D).

30 : 1H-NMR (300 MHz, CDCl3) : 8 7.14 (dd, 1H) ; 7.08 (dd, 1H); 6.99 (s, 1H); 6.73 (s, 1H) ; 6.58 (s, 1H) ; 6.04 (d, 1H) ; 5.97 (d, 1H) ; 5.03-4. 97 (m, 2H); 4.70 (dd, 1H) ; 4.63 (dd, 1H) ; 4.48 (s, 1H) ; 4.33 (s, 1H) ; 4.17 (d, 1H) ; 4.13 (dd, 1H) ; 3.95 (d, 1H) ; 3.80 (s, 3H); 3.59 (s, 3H); 3.54 (d, 1H) ; 3.46 (s, 1H) ; 3.13-3. 05 (m, 1H) ; 2.99 (d, 2H); 2.88-2. 77 (m, 1H) ; 2.70-2. 59 (m, 1H) ; 2. 52-2. 46 (m, 1H); 2.27-2. 12 (m, 2H); 2.35 (s, 3H); 2.33 (s, 3H); 2.17 (s, 3H); 2.05 (s, 3H).

ESI-MS m/z: Calcd. for C46H46N4014S : 910.2 Found (M+ H+) : 911.2.

31 : 1H-NMR (300 MHz, CDCIs) : 8 7.17 (dd, 1H) ; 7.07 (dd, 1H) ; 7.02 (dd, 1H) ; 6.86 (s, 1H) ; 6.74 (s, 1H) ; 6.33 (s, 1H) ; 6.07 (d, 1H) ; 5.95 (d, 1H) ; 5.01 (dd, 1H) ; 4.99 (dd, 1H) ; 4.83 (d, 1H) ; 4.75 (dd, 1H) ; 4.68 (dd, 1H) ; 4.65 (dd, 1H) ; 4.51 (s, 1H) ; 4.43 (dd, 1H) ; 4.35 (s, 1H) ; 4.12 (d, 1H) ; 4.05 (dd, 1H) ; 3.92 (d, 1H) ; 3.83 (s, 3H); 3.56 (s, 3H); 3.52 (d, 1H) ; 3.46-3. 44 (m, 1H) ; 3.34 (d, 1H) ; 3.02-2. 88 (m, 2H); 2.77-2. 66 (m, 1H) ; 2.52-2. 27 (m, 3H); 2.41 (s, 3H); 2.23 (s, 3H); 2.14 (s, 3H); 2.04 (s, 3H).

ESI-MS m/z: Calcd. for C49H48N4016S : 980.2 Found (M+ Na+) : 1003.2.

Example 26 32 : 1H-NMR (300 MHz, CDCIs) : 8 7.07 (dd, 1H); 7.01 (dd, 1H); 6.72 (s, 1H) ; 6. 47 (s, 1H) ; 6.35 (s, 1H) ; 6.06 (s, 1H) ; 5.94 (s, 1H) ; 5.74 (s, 1H) ; 5.00 (dd, 1H) ; 4.84 (d, 1H) ; 4.72 (d, 1H) ; 4.65 (dd, 1H) ; 4.62 (s, 1H) ; 4.41 (dd, 1H) ; 4.34 (s, 1H) ; 4.25 (d, 1H); 4.15-3. 99 (m, 3H); 3.80 (s, 3H); 3.55 (s, 3H); 3.51-3. 27 (m, 3H); 2.96-2. 82 (m, 2H); 2.77-2. 66 (m, 1H) ; 2.54-2. 44 (m, 3H); 2.33 (s, 3H); 2.21 (s, 3H); 2.16 (s, 3H); 2.01 (s, 3H).

ESI-MS m/z: Calcd. for C46H46N4014S : 910.2 Found (M+ H+) : 911.2.

33 : 1H-NMR (300 MHz, CDC13) : 8 7.02 (dd, 1H); 6.46 (s, 1H); 6.46 (s, 1H); 6.17 (s, 1H) ; 6.06 (d, 1H) ; 5.95 (d, 1H) ; 5.75 (s, 1H) ; 5.47 (s, 1H) ; 4.82 (d, 1H) ; 4.72 (d, 1H) ; 4.62 (s, 1H) ; 4.40 (dd, 1H) ; 4.33 (s, 1H) ; 4.25 (d, 1H) ; 4.11 (d, 1H) ; 4.01 (dd, 1H) ; 4.03-3. 96 (m, 1H) ; 3.80 (s, 3H); 3.59 (s, 3H); 3.51-3. 38 (m, 3H); 3.22 (d, 1H); 2.96-2. 82 (m, 2H); 2.72-2. 62 (m, 1H); 2.52-2. 40 (m, 2H); 2.33 (s, 3H); 2.28-2. 18 (m, 1H); 2.22 (s, 3H); 2.16 (s, 3H); 2.03 (s, 3H).

ESI-MS m/z: Calcd. for C43H44N4012S : 840.2 Found (M+ Na+) : 863.2.

Example 27 Method E: To a solution of 1 equiv. of Et-770 (1), or compound 4 in DMF (0.032M) under Argon at room temperature were added 2 equiv. of Cs2COs and 2 equiv. of the alkyl halide. The reaction was followed by TLC and quenched with NaHCOs, extracted with CH2Cl2 and the organic layers dried with Na2SO4. Flash chromatography gives pure compounds.

This mixture of compounds is obtained with 1.5 equiv. of MeI and 1.0 equiv. of CS2CO3. After chromatographic purification is recovered 21% of starting material and a fraction of the mixture of the three compounds.

34 : 1H-NMR (300 MHz, CDC13) : 8 d 6.60 (s, 1H), 6.48 (s, 1H), 6.40 (s, 1H), 6.01 (d, 2H), 5.72 (s, 1H), 5.02 (d, 1H), 4.57 (bp, 1H), 4.34 (s, 1H), 4.28 (d, 1H), 4.18 (d, 1H), 4.13-4. 11 (m, 1H), 3.80 (s, 3H), 3.76 (s, 3H), 3.61 (s, 3H), 3. 51 (d, 1H), 3. 44-3. 41 (m, 1H), 3. 17-3.10 (m, 1H), 2.95-2. 94 (m, 2H), 2.82- 2.78 (m, 1H), 2.70-2. 62 (m, 1H), 2. 52-2. 47 (m, 1H), 2. 38-2. 04 (m, 2H), 2. 33 (s, 3H), 2.26 (s, 3H), 2.20 (s, 3H), 2.04 (s, 3H).

ESI-MS m/z: Calcd. for C41H44N40loS : 784.8 Found (M+H+) : 785.3.

35: 1H-NMR (300 MHz, CDC13) : 8 d 6.78 (s, 1H), 6. 46 (s, 1H), 6. 40 (s, 1H), 6.02 (d, 2H), 5.02 (d, 1H), 4.47 (bp, 1H), 4.34 (s, 1H), 4.23 (d, 1H), 4.20 (d, 1H), 4.13-4. 11 (m, 1H), 3.91 (s, 3H), 3.82 (s, 3H), 3.76 (s, 3H), 3.60 (s, 3H), 3.51 (d, 1H), 3.45-3. 42 (m, 1H), 3.17-3. 09 (m, 1H), 2.96-2. 93 (m, 2H), 2.85- 2.81 (m, 1H), 2.71-2. 61 (m, 1H), 2. 53-2. 48 (m, 1H), 2. 34-2. 01 (m, 2H), 2. 28 (s, 3H), 2.24 (s, 3H), 2.20 (s, 3H), 2.04 (s, 3H).

ESI-MS m/z: Calcd. for C42H46N401oS : 798.3 Found (M+H+) : 799.2 36: 1H-NMR (300 MHz, CDC13) : 5 6.76 (s, 1H), 6.47 (s, 1H), 6.42 (s, 1H), 6.01 (d, 2H), 5.41 (bs, 1H), 5.01 (d, 1H), 4.47 (bp, 1H), 4.33 (s, 1H), 4.22 (d, 1H), 4.20 (d, 1H), 4.12 (dd, 1H), 3.90 (s, 3H), 3.82 (s, 3H), 3.61 (s, 3H), 3.50 (d, 1H), 3.44-3. 42 (m, 1H), 3.14-3. 06 (m, 1H), 3.00-2. 87 (m, 2H), 2.82-2. 78 (m, 1H), 2. 67-2. 56 (m, 1H), 2. 50-2. 44 (m, 1H), 2.32-2. 11 (m, 2H), 2.28 (s, 3H), 2.23 (s, 3H), 2.20 (s, 3H), 2.04 (s, 3H).

13C-NMR (75 MHz, CDCIs) : 8 172.6, 168.1, 164.3, 151.7, 148.6, 145.3, 144.5, 144.2, 141.2, 140.1, 131.4, 130.2, 129.0, 127.6, 125.6, 124.3, 121.3, 118.1, 114.1, 109.7, 101.8, 64.7, 61.2, 60.0, 59.7, 59.4, 59.1, 55.1, 54.9, 54.5, 42.2, 41.9, 41.7, 39.5, 28.7, 24.1, 20.2, 15.8, 9.7.

ESI-MS m/z: Calcd. for C41H44N4OloS : 784.8 Found (M+H+) : 785.3.

Example 28 1 37 38 56% 45% 37. (Method E) 1H-NMR (300 MHz, CDCIs) : 86. 59 (s, 1H); 6.47 (s, 1H); 6.40 (s, 1H) ; 6.01 (dd, 2H); 5.76 (s, 1H) ; 5.02 (d, 1H) ; 4.55 (s, 1H) ; 4.32 (s, 1H) ; 4.27 (d, 1H); 4.19 (d, 1H); 4.12 (dd, 1H); 3.98 (q, 2H); 3.78 (s, 3H); 3.59 (s, 3H); 3. 51 (d, 1H) ; 3. 42 (s, 1H) ; 3. 15-3. 06 (m, 1H) ; 2. 94-2. 92 (m, 2H); 2. 81- 2. 75 (m, 1H) ; 2. 68-2. 58 (m, 1H) ; 2. 56-2. 42 (m, 1H) ; 2. 39-2. 10 (m, 2H); 2. 32 (s, 3H); 2.26 (s, 3H); 2.19 (s, 3H); 2.03 (s, 3H); 1.37 (t, 3H).

13C-NMR (75 MHz, CDCIs) : 8 172.8, 167.9, 148.0, 147.5, 146.3, 143.2, 141.7, 141.6, 141.5, 132.7, 131.0, 130.1, 129.5, 129.0, 128.6, 121.3, 120.9, 118.3, 114.2, 112.8, 111.3, 102.1, 68.3, 64.3, 61.3, 60.5, 60.2, 59.8, 55.4, 54.9, 54.8, 39.9, 29.6, 29.1, 24.4, 22.8, 20.6, 16.0, 14.3, 9.6.

ESI-MS m/z : Calcd. for C42H46N40ioS : 798.2 Found (M+H+) : 799.3.

38. (Method E) : 1H-NMR (300 MHz, CDC13) : 8 6. 72 (s, 1H); 6.47 (s, 1H); 6.40 (s, 1H) ; 6.02 (dd, 2H); 5.02 (d, 1H) ; 4.50 (s, 1H) ; 4.32 (s, 1H) ; 4.24 (d, 1H) ; 4.20 (d, 1H) ; 4.13 (dd, 1H) ; 3.99 (q, 2H); 3.96 (q, 2H); 3.83 (s, 3H); 3.60 (s, 3H); 3.51 (d, 1H); 3.42 (s, 1H); 3.15-3. 06 (m, 1H); 2. 96-2. 93 (m, 2H); 2. 84- 2. 78 (m, 1H) ; 2. 70-2. 58 (m, 1H) ; 2. 53-2. 42 (m, 1H) ; 2. 33-2. 11 (m, 2H); 2. 28 (s, 3H); 2.25 (s, 3H); 2.20 (s, 3H); 2.04 (s, 3H); 1.40 (t, 3H); 1.37 (s, 3H).

13C-NMR (75 MHz, CDCl3) : 8 172.8, 168.2, 151.0, 147.5, 147.0, 145.5, 141.4, 140.4, 131.4, 130.4, 129.0, 128.5, 128.4, 124.4, 121.5, 118.3, 114.2, 112.8, 111.0, 102.0, 68.3, 64.3, 61.5, 60.0, 59.4, 55.4, 55.3, 54.9, 54.5, 42.2, 42.1, 41.9, 39.8, 29.5, 29.2, 24.4, 22.8, 20.4, 16.4, 16.0, 14.3, 9.8.

ESI-MS m/z: Calcd. for C44H5oN4OlOS : 826.3 Found (M+H+): 827.3.

Example 29 1 39 40 53% 49% 39. (Method E) 1H-NMR (300 MHz, CDC13) : 8 6.59 (s, 1H); 6.48 (s, 1H); 6.40 (s, 1H) ; 6.01 (dd, 2H); 5.74 (s, 1H) ; 5.02 (d, 1H) ; 4.55 (s, 1H) ; 4.31 (s, 1H) ; 4.27 (d, 1H) ; 4.18 (d, 1H) ; 4.11 (dd, 1H) ; 3.84 (q, 2H); 3.78 (s, 3H); 3.59 (s, 3H); 3.51 (d, 1H); 3.41 (s, 1H); 3.16-3. 06 (m, 1H); 2.96-2. 92 (m, 2H); 2.81- 2.73 (m, 1H) ; 2.68-2. 58 (m, 1H) ; 2.54-2. 42 (m, 1H) ; 2.39-2. 10 (m, 2H); 2.31 (s, 3H); 2.25 (s, 3H); 2.19 (s, 3H); 2.03 (s, 3H); 1.80-1-71 (m, 2H); 0.96 (s, 3H).

13C-NMR (75 MHz, CDCIs) : 5 172.8, 167.9, 148.0, 147.5, 146.3, 143.2, 141.7, 141.6, 141.5, 131.0, 130.1, 129.5, 129.0, 128.6, 121.3, 120.9, 118.3, 114.2, 112.8, 111.3, 102.1, 70.5, 61.3, 60.5, 60.2, 60.0, 59.8, 59.7, 55.5, 54.9, 54.8, 42.3, 42.1, 41.8, 39.9, 29.9, 24.4, 22.5, 20.6, 16.0, 10.5, 9.9.

ESI-MS m/z: Calcd. for C43H48N40loS : 812.3 Found (M+H+) : 813.3.

40. (Method E). lH-NMR (300 MHz, CDCIs) : 8 6. 77 (s, 1H); 6.47 (s, 1H); 6.40 (s, 1H) ; 6.03 (dd, 2H); 5.02 (d, 1H) ; 4.52 (s, 1H) ; 4.32 (s, 1H) ; 4.22 (d, 1H) ; 4.19 (d, 1H) ; 4.12 (dd, 1H); 3.87-3. 80 (m, 4H); 3.82 (s, 3H); 3.59 (s, 3H); 3. 51 (d, 1H) ; 3.43 (s, 1H) ; 3.15-3. 06 (m, 1H) ; 2.96-2. 93 (m, 2H); 2.84-2. 74 (m, 1H) ; 2.68-2. 58 (m, 1H) ; 2.53-2. 42 (m, 1H) ; 2.38-2. 07 (m, 2H); 2.28 (s, 3H); 2.24 (s, 3H); 2.20 (s, 3H); 2.04 (s, 3H); 1.83-1. 72 (m, 4H); 1. 10 (t, 3H); 0.96 (s, 3H).

13C-NMR (75 MHz, CDCIs) : 8 172.8, 168.2, 151.2, 147.8, 147.1, 145.5, 141.7, 141.4, 131.4, 130.4, 128.6, 127.8, 125.4, 124.4, 121.5, 118.3, 114.2, 113.0, 111.3, 102.0, 74.3, 70.5, 61.4, 60.0, 59.6, 59.5, 55. 5, 55.4, 54.9, 42.2, 42.1, 41.9, 39.8, 31.7, 29.9, 24.4, 24.2, 22.8, 22.5, 20.4, 16.0, 14.3, 11.1, 10.5, 9.8.

ESI-MS m/z: Calcd. for C46H54N40loS : 854.3 Found (M+H+) : 855.3.

Example 30 Compounds 41 and 42 were obtained using Method E.

41 : 1H-NMR (300 MHz, CDCIs) : 5 6.59 (s, 1H); 6.48 (s, 1H); 6.40 (s, 1H); 6.04-5. 92 (m, 1H) ; 6.01 (dd, 2H); 5.72 (s, 1H) ; 5.31 (dd, 1H) ; 5.22 (dd, 1H) ; 5.02 (d, 1H) ; 4.55 (s, 1H) ; 4.49 (d, 2H); 4.32 (s, 1H) ; 4.27 (d, 1H) ; 4.18 (d, 1H) ; 4.12 (dd, 1H) ; 3.78 (s, 3H); 3.60 (s, 3H); 3.51 (d, 1H) ; 3.41 (s, 1H) ; 3.16- 3.06 (m, 1H) ; 2.95-2. 92 (m, 2H); 2.82-2. 74 (m, 1H) ; 2.67-2. 58 (m, 1H) ; 2. 52- 2.42 (m, 1H) ; 2.37-2. 10 (m, 2H); 2.32 (s, 3H); 2.26 (s, 3H); 2.19 (s, 3H); 2.03 (s, 3H).

13C-NMR (75 MHz, CDC13) : 8 172.8, 167.9, 148.0, 147.2, 143.2, 141.5, 140.3, 133.4, 131.0, 129.5, 128.6, 126.8, 121.3, 120.9, 118.4, 118.3, 117.9, 114.2, 113.4, 111.2, 102.1, 69.9, 64.7, 61.3, 60.5, 60.2, 59.8, 59.7, 55.5, 54.9, 54.8, 42.4, 42.0, 41.9, 41.8, 39.9, 29.9, 29.2. 24.4, 20.6, 16.0, 9.9.

ESI-MS m/z: Calcd. for C43H46N40loS : 810.2 Found (M+H+) : 811.2.

42 : 1H-NMR (300 MHz, CDCl3) : â 6.79 (s, 1H); 6.48 (s, 1H); 6.40 (s, 1H); 6.16-5. 92 (m, 2H); 6.03 (dd, 2H); 5.45 (dd, 1H) ; 5.31 (dd, 1H) ; 5.24 (dd, 1H) ; 5.21 (dd, 1H) ; 5.02 (d, 1H) ; 4.82-4. 77 (m, 1H) ; 4.53 (s, 1H) ; 4.49 (d, 2H); 4.37-4. 31 (m, 1H) ; 4.32 (s, 1H) ; 4.24 (d, 1H) ; 4.17 (d, 1H) ; 4.12 (dd, 1H) ; 3.82 (s, 3H); 3.60 (s, 3H); 3.51 (d, 1H) ; 3.42 (s, 1H) ; 3.15-3. 06 (m, 1H) ; 2.96-2. 93 (m, 2H); 2.84-2. 74 (m, 1H) ; 2.68-2. 58 (m, 1H) ; 2.53-2. 42 (m, 1H) ; 2.34-2. 11 (m, 2H); 2.28 (s, 3H); 2.23 (s, 3H); 2.19 (s, 3H); 2.03 (s, 3H).

13C-NMR (75 MHz, CDCIs) : 8 172.8, 169.5, 150.7, 149.0, 147.2, 146.3, 141.5, 140.3, 134.8, 133.4, 131.4, 130.5, 128. 5, 124.9, 124.7, 121.4, 118.2, 118. 0, 116. 9, 114. 2, 113. 4, 111. 2,102. 1,73. 1,69. 8, 61. 4,60. 0,59. 6,59. 5, 55.4, 55.3, 54.8, 42.3, 42.1, 41.9, 39.8, 29.9, 29.1, 24.4, 20.5, 16.0, 9.8.

ESI-MS m/z: Calcd. for C46H5oN40loS : 850.3 Found (M+H+) : 851.3.

Example 31 1 43 44 33% 62% Compounds 43 and 44 were obtained using Method E 43 : 1H-NMR (300 MHz, CDCIs) : 8 7.38-7. 26 (m, 5H) ; 6.59 (s, 1H); 6.51 (s, 1H); 6.41 (s, 1H); 6.02 (dd, 2H); 5.73 (s, 1H); 5.03 (s, 2H); 5.01 (d, 1H); 4.56 (s, 1H) ; 4.32 (s, 1H) ; 4.27 (d, 1H) ; 4.18 (d, 1H) ; 4.12 (dd, 1H) ; 3.78 (s, 3H); 3.61 (s, 3H); 3.51 (d, 1H) ; 3.42 (s, 1H) ; 3.13-3. 06 (m, 1H) ; 2.94-2. 92 (m, 2H); 2.80-2. 72 (m, 1H) ; 2.62-2. 53 (m, 1H) ; 2.47-2. 37 (m, 1H) ; 2.34-2. 10 (m, 2H); 2.32 (s, 3H); 2.26 (s, 3H); 2.19 (s, 3H); 2.03 (s, 3H).

13C-NMR (75 MHz, CDCIs) : 8 172.8, 169.5, 168.3, 148.0, 147.3, 145.5, 143.2, 141.5, 140.3, 137.3, 132.4, 131.0, 128.6, 127.9, 127.3, 127.0, 121.3, 120.9, 118.3, 114.2, 113.9, 111.4, 102.1, 70.9, 64.7, 61.3, 60.5, 60.2, 59.8, 59.7, 55.5, 54.9, 54.8, 42.3, 42.0, 41.8, 39.9, 29.9, 29.1, 24.4, 20.6, 16.0, 9.9.

ESI-MS m/z: Calcd. for C47H48N4OloS : 860.3 Found (M+H+) : 861.3.

44 : 1H-NMR (300 MHz, CDCl3) : 5 7. 47-7. 25 (m, 10H) ; 6.81 (s, 1H); 6.48 (s, 1H) ; 6.41 (s, 1H) ; 6.01 (dd, 2H); 5.32 (d, 1H) ; 5.03 (s, 2H); 5.01 (d, 1H) ; 4.84 (d, 1H) ; 4.50 (s, 1H) ; 4.32 (s, 1H) ; 4.21 (d, 1H) ; 4.19 (d, 1H) ; 4.13 (dd, 1H) ; 3.86 (s, 3H); 3.60 (s, 3H); 3.49 (d, 1H) ; 3.40 (s, 1H) ; 3.15-3. 06 (m, 1H) ; 2.96- 2.93 (m, 2H); 2.81-2. 71 (m, 1H) ; 2.64-2. 51 (m, 1H) ; 2.50-2. 40 (m, 1H) ; 2.33- 2.11 (m, 2H); 2.32 (s, 3H); 2.04 (s, 3H); 2.02 (s, 3H); 2.00 (s, 3H).

13C-NMR (75 MHz, CDC13) : 5 172.7, 168.3, 149.2, 147.4, 147.3, 145.5, 141.4, 140.3, 138.1, 137.2, 131.5, 130.3, 128.8, 128.7, 128.6, 128.2, 128.1, 127.9, 127.3, 127.0, 125.0, 124.9, 121.4, 118.2, 114.2, 114.0, 111.3, 102.0, 74.3, 70.9, 64.9, 61.4, 60.1, 60.0, 59.7, 59.5, 55.5, 55.4, 54.8, 42.2, 42.1, 41.7, 39.7, 31.7, 29.9, 24.4, 22.8, 20.1, 16.0, 14.3, 9.8.

ESI-MS m/z: Calcd. for C54H54N4OlOS : 950.3 Found (M+H+) : 951.3.

Example 32 The reaction was performed with 1.0 equiv. of MeI and 1.0 equiv. of Cs2CO3 (Method E). After chromatographic purification starting material (16%) was recuperated.

45. 1H-NMR (300 MHz, CDCIs) : d 6.76 (s, 1H), 6.47 (s, 1H), 6.42 (s, 1H), 6.01 (d, 2H), 5.41 (bs, 1H), 5.01 (d, 1H), 4.47 (bp, 1H), 4.33 (s, 1H), 4.22 (d, 1H), 4.20 (d, 1H), 4.12 (dd, 1H), 3.90 (s, 3H), 3.82 (s, 3H), 3.61 (s, 3H), 3.50 (d, 1H), 3.44-3. 42 (m, 1H), 3.14-3. 06 (m, 1H), 3.00-2. 87 (m, 2H), 2.82-2. 78 (m, 1H), 2.67-2. 56 (m, 1H), 2.50-2. 44 (m, 1H), 2.32-2. 11 (m, 2H), 2.28 (s, 3H), 2.23 (s, 3H), 2.20 (s, 3H), 2.04 (s, 3H).

3C-NMR (75 MHz, CDCIs) : 172.6, 168.1, 164.3, 151.7, 148.6, 145.3, 144.5, 144.2, 141.2, 140.1, 131.4, 130.2, 129.0, 127.6, 125.6, 124.3, 121.3, 118.1, 114.1, 109.7, 101.8, 64.7, 61.2, 60.0, 59.7, 59.4, 59.1, 55.1, 54.9, 54.5, 42.2, 41.9, 41.7, 39.5, 28.7, 24.1, 20.2, 15.8, 9.7.

ESI-MS m/z: Calcd. for C46H52N4012S : 884.3 Found (M+H+) : 985.3.

Example 33 Compound 46 was obtained with 15 equiv. of isopropyl bromide and 15 equiv, of CsaCOs (Method E) 46. 1-H-NMR (300 MHz, CDCIs) : d 6.75 (s, 1H), 6.68 (s, 1H), 6.57 (s, 1H), 6.03 (d, 1H), 5.96 (d, 1H) ; 4.99 (d, 1H), 4.86-4. 80 (m, 1H) ; 4.51 (s, 1H), 4.35- 4.31 (m, 2H), 4.18 (s, 1H), 4.11 (d, 1H), 3.80 (s, 3H), 3.58 (s, 3H), 3.48 (d, 1H), 3.41 (s, 1H), 3.15-3. 08 (m, 1H), 2.95-2. 93 (m, 2H), 2.82-2. 74 (m, 1H), 2.68-2. 48 (m, 2H); 2.27 (s, 3H), 2.26 (s, 3H), 2.23 (s, 3H), 2.17-2. 12 (m, 1H); 2.04 (s, 3H); 1.50 (s, 9H); 1.45 (d, 3H); 1.14 (d, 3H).

ESI-MS m/z: Calcd. for C48H56N4012S : 912.3 Found (M+H+) : 913.3.

Example 34 Method F: To a solution of 1 equiv. of starting material in CH2Cl2/H20/TFA 2: 1: 3.3 (0.013M) was stirred at room temperature for 15 min. The reaction was followed by TLC and neutralised with NaHCOs, extracted with CH2C12 and the organic layers dried with Na2SO4. Flash chromatography gives pure compounds. 47. was obtained using Method F 1H-NMR (300 MHz, CDCIs) : 8 6.93 (s, 1H); 6.48 (s, 1H) ; 6.42 (s, 1H) ; 6.02 (dd, 2H); 5.39 (s, 1H) ; 5.02 (d, 1H) ; 4.47 (s, 1H) ; 4.33 (s, 1H) ; 4.18 (d, 1H) ; 4.13 (dd, 1H) ; 3.93 (d, 1H) ; 3.79 (s, 3H); 3.62 (s, 3H); 3.52 (d, 1H); 3.46-3. 44 (m, 1H); 3.12-3. 04 (m, 1H); 2.98 (d, 2H); 2.83-2. 76 (m, 1H) ; 2.64-2. 57 (m, 1H) ; 2.51-2. 46 (m, 1H) ; 2.24-2. 03 (m, 2H); 2.32 (s, 3H); 2.31 (s, 3H); 2.17 (s, 3H); 2.06 (s, 3H); 1.56 (s, 9H).

13C-NMR (75 MHz, CDCI3) : 8 172.0, 168.4, 151.3, 148.3, 145.6, 144.8, 144.5, 141.5, 140.4, 131.6, 130.5, 129.4, 127.1, 125.7, 124.5, 121.4, 118.1, 114.3, 114.2, 113.6, 109.9, 102.0, 83.4, 67.4, 61.4, 60.2, 60.0, 59.8, 59.3, 55.9, 55.8, 54.7, 42.4, 42.1, 41.8, 39.8, 29.9, 29.0, 27.8, 24.2, 20.3, 16.0, 9.8.

ESI-MS m/z: Calcd. for C45H, 5oN4012S : 870.3 Found (M+H+) : 871.3.

Example 35 48 was obtained using Method F. 1H-NMR (300 MHz, CDCIs) : d 6.76 (s, 1H), 6.46 (s, 1H), 6.44 (s, 1H), 6.04 (d, 1H), 5.97 (d, 1H) ; 5.42 (s, 1H) ; 5.01 (d, 1H), 4.89-4. 80 (m, 1H) ; 4.53 (s, 1H), 4.34 (dd, 1H) ; 4.31 (s, 1H), 4.19 (d, 1H), 4.12 (dd, 1H), 3.80 (s, 3H), 3.61 (s, 3H), 3.49 (d, 1H), 3.42 (s, 1H), 3.12- 3.04 (m, 1H), 2.95 (d, 2H), 2.78-2. 73 (m, 1H), 2.64-2. 47 (m, 2H); 2.30-2. 10 (m, 2H); 2.28 (s, 3H), 2.25 (s, 3H), 2.23 (s, 3H), 2.04 (s, 3H); 1.45 (d, 3H); 1.14 (d, 3H).

ESI-MS m/z: Calcd. for C43H48N4OloS : 812.3 Found (M+H+) : 813.3.

Example 36 After chromatographic purification, starting material (33%) was recuperated.

Compound 36 has been previously described.

Other chemical transformations: Example 37 Compound 47 was acylated following method B. 49. 1H-NMR (300 MHz, CDC13) : 8 7. 80 (d, 1H); 7.56-7. 54 (m, 2H); 7.41-7. 39 (m, 3H); 6.93 (s, 1H) ; 6.69 (s, 1H) ; 6.60 (d, 1H) ; 6.57 (s, 1H) ; 6.00 (dd, 2H); 5.02 (d, 1H) ; 4.45 (s, 1H) ; 4.34 (s, 1H) ; 4.18 (d, 1H) ; 4.13 (dd, 1H) ; 3.93 (d, 1H) ; 3.80 (s, 3H); 3.56 (s, 3H); 3.52 (d, 1H) ; 3.46-3. 43 (m, 1H) ; 3.15-3. 06 (m, 1H) ; 2.98-2. 96 (m, 2H); 2.86-2. 80 (m, 1H); 2.64-2. 59 (m, 1H); 2.54-2. 46 (m, 1H) ; 2.35-2. 05 (m, 2H); 2.33 (s, 3H); 2.31 (s, 3H); 2.18 (s, 3H); 2.05 (s, 3H); 1.53 (s, 9H).

ESI-MS m/z: Calcd. for C54H56N4013S : 1000.3 Found (M+H+) : 1001.3.

Example 38 To a solution of compound 42 in THF/MeOH 1: 1 were added 2 equiv of KOH. The reaction mixture was stirred at room temperature for 5 h. After this time the reaction was quenched with NaCI or diluted aqueous solution of HCI, extracted with CH2Cl2. The organic layer was dried with Na2SO4.

Chromatography gives pure compound 50 (79%).

50. lH-NMR (300 MHz, CDCIs) : S 6.81 (s, 1H), 6.47 (s, 1H), 6.43 (s, 1H), 6.17-5. 90 (m, 2H), 5.94 (d, 2H), 5.45-5. 22 (m, 4H), 4.98 (d, 1H), 4.83-4. 77 (m, 1H), 4.56-4. 27 (m, 5H), 4.16-4. 02 (m, 3H), 3.84 (s, 3H), 3.58 (bs, 4H), 3.44-3. 40 (m, 1H), 3.20-2. 16 (m, 8H), 2.31 (s, 3H), 2.25 (s, 3H), 2.19 (s, 3H).

ESI-MS m/z: Calcd. for C44H48N409S : 808.3 Found (M+H+) : 809.2.

Example 39 To a solution of compound 6 in MeOH/THF 3: 4 (0. 011M) at room temperature were added 150 equiv. of Et3N. After 7 days the solvent was evaporated. Flash chromatography gives pure compound 51.

51. 1H-NMR (300 MHz, CDCIs) : 8 6.95 (s, 1H), 6.49 (s, 1H), 6.40 (bs, 1H), 6.02 (dd, 2H), 5.42 (bs, 1H), 5.02 (d, 1H), 4.45 (bs, 1H), 4.35 (s, 1H), 4.21- 4.10 (m, 2H), 3.84-3. 68 (m, 4H), 3.62 (s, 3H), 3.53 (bd, 1H), 3.48-3. 44 (m, 1H), 3.16-2. 75 (m, 4H), 2.67-2. 14 (m, 4H), 2.38 (s, 3H), 2.35 (s, 3H), 2.31 (s, 3H), 2.16 (s, 3H), 2.01 (s, 3H).

ESI-MS m/z: Calcd. for C42H44N4011S : 812.3 Found (M+H+) : 813.3.

Example 40 To a solution of Et-770 (1) (1.0 equiv. ) in MeOH (0.032M) at room<BR> temperature under Argon, were added RuCl2 (PPh3) 3 (0.1 equiv. ) and H202 (8<BR> equiv. ). The reaction mixture was stirred at room temperature for 4 h.

After this time, it was diluted with CH2C12, washed with brine and the organic layer was dried over Na2SO4. Flash chromatography gives compound 52.

52. 1H-NMR (300 MHz, CDCIs) : 8 6.48 (s, 1H); 6.43 (s, 1H); 6.05 (s, 1H); 5.99 (s, 1H) ; 5.42 (s, 1H) ; 4.92 (d, 1H) ; 4.50 (s, 1H) ; 4.22 (s, 1H) ; 4.18-4. 15 (m, 1H); 4.12-3. 98 (m, 2H); 4.10 (s, 3H); 3.61 (s, 3H); 3.58-3. 55 (m, 1H); 3.42- 3.37 (m, 2H); 3.12-3. 03 (m, 1H); 2.90-2. 59 (m, 3H); 2. 55-2. 27 (m, 4H); 2. 24 (s, 3H); 2. 21 (s, 3H); 2.04 (s, 3H); 2.02 (s, 3H).

ESI-MS m/z : Calcd. for C40H40N4°11S : 784.2. Found (M+Na+) : 807.2.

Example 41 1 53 A suspension of 1, coevaporated twice with anhydrous toluene, in CH3CN (0.03M) under Argon was cooled at-10 °C. At this temperature were added 5 equiv. of CCl4, 2.1 equiv. of iPr2NEt, 0.1 equiv. of DMAP and 1.45 equiv of dibenzyl phosphite. After 1 h the reaction was quenched with 1.2 equiv. of KH2PO4 (0.5M). The reaction mixture was warmed up to room temperature, stirred for 5 min, diluted with EtOAc and washed with water. The organic layers were dried with Na2SO4. Flash chromatography gives pure compound 53 (75%).

53. 1H-NMR (300 MHz, CDCIs) : 8 7.29 (s, 10H), 6.71 (s, 1H), 6.59 (s, 1H), 6.52 (s, 1H), 6.00 (d, 2H), 5.76 (s, 1H), 5.12-5. 07 (m, 2H), 5.02 (d, 1H), 4.57 (bs, 1H), 4.32 (s, 1H), 4.27 (d, 1H), 4.18 (d, 1H), 4.11 (bd, 1H), 3.78 (s, 3H), 3.50 (bs, 4H), 3.44-3. 39 (m, 1H), 3.12-3. 03 (m, 1H), 2.95-2. 92 (m, 2H), 2.81- 2.72 (m, 1H), 2.60-2. 04 (m, 4H), 2.32 (s, 3H), 2.27 (s, 3H), 2.20 (s, 3H), 2.04 (s, 3H).

ESI-MS m/z: Calcd. for C54H55N4013PS : 1030.3 Found (M+H+) : 1031.3.

Example 42 Method G: To a solution of Et-770 (1) in CH3CN (0.016M) at room temperature under Argon, were added 200 equiv. of the aldehyde (37 wt. % in water) and 10 equiv. of NaCNBH3. After 1 h 10 min 40 equiv. of acetic acid were added. The reaction mixture was stirred for 2 h more. After this time, it was diluted with CHzCb, neutralised with NaHCOs and extracted with CH2Cl2. The organic layers were dried over Na2SO4. Flash chromatography gives pure compounds.

1 54 54 was obtained following method G. 1H-NMR (300 MHz, CDCIs) : 8 6.47 (s, 1H), 6.45 (s, 1H), 6.17 (s, 1H), 6.02 (dd, 2H), 5.73 (bs, 1H), 5.44 (bs, 1H), 4.94 (d, 1H), 4.60 (bs, 1H), 4.35 (d, 1H), 4.26 (d, 1H), 4.07 (d 1H), 3.88-3. 82 (m, 1H), 3.79 (s, 3H), 3.56 (s, 3H), 3.52 (bd, 1H), 3.42-3. 39 (m, 1H), 3.20 (bp, 1H), 3.00-2. 44 (m, 5H), 2.35-2. 16 (m, 2H), 2.31 (s, 3H), 2.24 (s, 3H), 2.21 (bs, 3H), 2.16 (s, 3H), 2.02 (s, 3H).

ESI-MS m/z: Calcd. for C41H44N4OloS : 784.3. Found (M+H+) : 785.2.

Example 43 1 55 55 was obtained following method G 1H-NMR (300 MHz, CD3OD) : 8 6.41 (s, 1H), 6.35 (s, 1H), 6.21 (s, 1H), 6.09 (d, 2H), 4.97 (d, 1H), 4.67 (bs, 1H), 4.36 (bs, 2H), 4.27 (d, 1H), 3.95 (dd 1H), 3.73 (s, 3H), 3. 53 (s, 3H), 3. 45-3. 41 (m, 2H), 2. 98-2. 47 (m, 6H), 2. 37-2. 03 (m, 4H), 2.33 (s, 3H), 2.25 (s, 3H), 2.07 (s, 3H), 2.03 (s, 3H), 0.88 (t, 3H).

ESI-MS m/z : Calcd. for C42H46N40loS : 798.3. Found (M+H+) : 799.2.

Example 44 1 56 56 was obtained following method G. 1H-NMR (300 MHz, CDCI3) : 5 6.46 (s, 1H), 6.43 (s, 1H), 6.23 (s, 1H), 6.03 (d, 2H), 5.86 (s, 1H), 5.43 (s, 1H), 4.96 (d, 1H), 4.63 (bs, 1H), 4.46 (d, 1H), 4.27 (d, 1H), 4.08 (d 1H), 3.95-3. 85 (m, 1H), 3.84 (s, 3H), 3.56 (d, 1H), 3.52 (s, 3H), 3.46-3. 41 (m, 1H), 3.00-2. 85 (m, 3H), 2.72-2. 64 (m, 2H), 2.50-2. 42 (m, 1H), 2.36-2. 03 (m, 4H), 2.33 (s, 6H), 2.07 (s, 3H), 2.03 (s, 3H), 1.35-1. 24 (m, 2H), 0.87 (t, 3H).

ESI-MS m/z: Calcd. for C43H48N40loS : 812.3. Found (M+H+) : 813.3.

Example 45 Method H: To a solution of 1 equiv. of starting material in CH3CN/H20 3: 2 (0.009M) were added 30 equiv. of AgNO3. After 24 h the reaction was quenched with a mixture 1: 1 of saturated solutions of brine and NaHC03, stirred for 10 min and diluted and extracted with CH2C12. The organic layer was dried over Na2SO4. Chromatography gives pure compounds.

57 was obtained using Method H. IH-NMR (300 MHz, CDCIs) : 8 6.60 (s, 2H); 6.57 (s, 1H) ; 5.97 (dd, 2H); 5.70 (s, 1H) ; 5.12 (d, 1H) ; 4.82 (s, 1H) ; 4.48 (d, 1H) ; 4.47 (s, 1H) ; 4.16 (d, 1H) ; 4.04 (dd, 1H) ; 3.79 (s, 3H); 3.58 (d, 1H) ; 3.54 (s, 3H); 3.23-3. 20 (m, 1H); 3.18-3. 09 (m, 1H); 2.88-2. 86 (m, 2H); 2.86- 2.78 (m, 1H) ; 2.66-2. 58 (m, 1H) ; 2.52-2. 44 (m, 1H) ; 2.35-2. 12 (m, 2H); 2.32 (s, 3H); 2.27 (s, 3H); 2.23 (s, 3H); 2.17 (s, 3H); 2.01 (s, 3H).

13C-NMR (75 MHz, CDCIs) : 8 172.0, 168.9, 148.3, 147.6, 145.1, 141.2, 140.4, 139.1, 138.4, 131.4, 130.8, 128.7, 128.6, 122.9, 122.3, 121.6, 120.9, 120.6, 115.8, 111.7, 101.6, 82.0, 64.9, 61.4, 60.3, 57.8, 57.6, 55.9, 55.0, 54.9, 42.1, 41.3, 39.5, 29.6, 24.0, 20.5, 15.7, 9.6.

ESI-MS m/z: Calcd. for C4lH45N3012S : 803.2 Found (M-H20+H+) : 786.2.

Example 46 58 was obtained using Method H lH-NMR (300 MHz, CDC13) : 8 6.60 (s, 1H); 6.59 (s, 1H) ; 6.57 (s, 1H) ; 5.97 (dd, 2H); 5.72 (s, 1H) ; 5.12 (d, 1H) ; 4.81 (s, 1H) ; 4.47 (d, 1H) ; 4.47-4. 45 (m, 1H) ; 4.16 (d, 1H) ; 4.03 (dd, 1H) ; 3.79 (s, 3H); 3.58 (d, 1H) ; 3.53 (s, 3H); 3.26-3. 20 (m, 1H) ; 3.18-3. 09 (m, 1H) ; 2.88-2. 86 (m, 2H); 2.86-2. 78 (m, 1H) ; 2.69-2. 58 (m, 1H) ; 2.52-2. 44 (m, 1H) ; 2.48 (t, 2H); 2.35-2. 12 (m, 2H); 2.32 (s, 3H); 2.27 (s, 3H); 2.17 (s, 3H); 2.01 (s, 3H); 1.78-1. 67 (m, 2H); 1. 00 (t, 3H).

13C-NMR (75 MHz, CDCIs) : 8 171.8, 167.2, 148.6, 147.9, 145.4, 141.5, 141.5, 140.7, 138.7, 132.9, 132.4, 131.7, 131.0, 130.5, 128.8, 127.8, 122.6, 121.1, 120.8, 116.2, 112.0, 101.9, 82.3, 65.1, 61.6, 60.5, 58.0, 56.1, 55.3, 55.1, 42.5, 41.6, 39.8, 29.9, 28.9, 24.3, 22.8, 20.6, 18.7, 16.0, 14.3, 13.7, 9.8.

ESI-MS m/z: Calcd. for C43H49N3012S : 814.3 Found (M+-H20) : 796.3.

Example 47 14 59 59 was obtained using Method H lH-NMR (300 MHz, CDCl3) : 8 6.59 (s, 1H); 6.58 (s, 1H) ; 6.55 (s, 1H) ; 5.96 (dd, 2H); 5.69 (s, 1H) ; 5.11 (d, 1H) ; 4.80 (s, 1H) ; 4.47-4. 45 (m, 2H); 4.14 (d, 1H) ; 4.02 (dd, 1H) ; 3.78 (s, 3H); 3.56 (d, 1H) ; 3.53 (s, 3H); 3.24-3. 18 (m, 1H) ; 3.14-3. 04 (m, 1H) ; 2.86-2. 84 (m, 2H); 2.86- 2.78 (m, 1H) ; 2.69-2. 58 (m, 1H) ; 2.52-2. 44 (m, 1H) ; 2.48 (t, 2H); 2.35-2. 12 (m, 2H); 2.31 (s, 3H); 2.26 (s, 3H); 2.16 (s, 3H); 2.01 (s, 3H); 1.73-1. 61 (m, 2H); 1.40-1. 14 (m, 11H).

13C-NMR (75 MHz, CDCIs) : 5 172.0, 171.8, 148.4, 147.7, 145.1, 142.9, 141.3, 140.5, 138.5, 132.7, 131.5, 129.9, 128.6, 122.4, 121.7, 120.9, 115.8, 111.7, 101.6, 82.1, 64.9, 61.4, 60.3, 57.8, 57.7, 55.9, 55.1, 54.9, 42.2, 41.4, 39.6, 33.9, 31.6, 29.6, 28.9, 28.6, 21.0, 24.0, 22.5, 20.4, 15.7, 14.0, 9.6.

ESI-MS m/z: Calcd. for C47Hs7N3O12S : 888.0 Found (M+-H20): 870.3.

Example 48 60 was obtained using Method H lH-NMR (300 MHz, CDC13) : 8 6.60 (s, 1H) ; 6.58 (s, 1H) ; 6.56 (s, 1H) ; 5.96 (dd, 2H); 5.72 (s, 1H) ; 5.12 (d, 1H) ; 4.81 (s, 1H); 4.48 (d, 1H); 4.47-4. 45 (m, 1H); 4.16 (d, 1H); 4.03 (dd, 1H); 3.79 (s, 3H); 3.58 (d, 1 H) ; 3.53 (s, 3H); 3.24-3. 19 (m, 1H) ; 3.14-3. 09 (m, 1 H) ; 2.87-2. 84 (m, 2H); 2.86-2. 78 (m, 1H) ; 2.69-2. 58 (m, 1H) ; 2.52-2. 44 (m, 1H) ; 2.49 (t, 2H); 2.37-2. 12 (m, 2H); 2.31 (s, 3H); 2.27 (s, 3H); 2.17 (s, 3H); 2.01 (s, 3H); 1.73-1. 62 (m, 2H); 1.40-1. 20 (m, 27H).

13C-NMR (75 MHz, CDC13) : 5 172.2, 172.0, 168.5, 148.6, 147.9, 145.4, 143.2, 141.5, 140.7, 138.8, 132.8, 131.7, 129.4, 128.8, 125.3, 122.6, 121.9, 121.1, 116.0, 111.9, 101.9, 82.3, 65.1, 61.6, 60.5, 58.0, 57.8, 56.1, 55.3, 55.1, 53.6, 42.4, 41.5, 39.8, 34.2, 32.1, 31.7, 29.89, 29.85, 29.82, 29.7, 29.5, 29.4, 29.3, 29.2, 28.8, 25.3, 22.9, 22.8, 20.6, 16.0, 14.3, 9.8.

ESI-MS m/z: Calcd. for C, 55H73N3012S : 1000.2 Found (M+-H20) : 982.4.

Example 49 61 was obtained using Method H. lH-NMR (300 MHz, CDCls) : 8 7.80 (d, 1H) ; 7.57-7. 54 (m, 2H); 7.40-7. 38 (m, 3H); 6.68 (s, 1H) ; 6.60 (s, 2H); 6.59 (d, 1H) ; 5.96 (dd, 2H); 5.70 (s, 1H) ; 5.13 (d, 1H) ; 4.82 (s, 1H) ; 4.48 (d, 1H) ; 4.48- 4.46 (m, 1H); 4.16 (d, 1H); 4.05 (dd, 1H); 3.79 (s, 3H); 3.59 (d, 1H); 3.55 (s, 3H); 3.25-3. 20 (m, 1H) ; 3.18-3. 09 (m, 1H) ; 2.88-2. 85 (m, 2H); 2.86-2. 78 (m, 1H) ; 2.70-2. 60 (m, 1H) ; 2.56-2. 44 (m, 1H) ; 2.35-2. 08 (m, 2H); 2.32 (s, 3H); 2.28 (s, 3H); 2.17 (s, 3H); 2.01 (s, 3H).

ESI-MS m/z: Calcd. for C48H49N3O12S : 892.3 Found (M+-H20) : 874.3.

Example 50 62 was obtained using Method H lH-NMR (300 MHz, CDC13) : 8 7.75-7. 73 (d, 2H), 7.66-7. 61 (m, 2H), 7.40-7. 33 (t, 2H), 7.30-7. 27 (m, 2H), 6.63 (s, 1H), 6.57 (s, 1H), 6.54 (s, 1H), 5.96 (d, 2H), 5.98-5. 85 (m, 1H), 5.58 (d, 1H), 5.30- 5.18 (m, 2H), 5.10 (d, 1H), 4.87-4. 02 (m, 9H), 3.80 (s, 3H), 3.64-3. 57 (m, 1H), 3.44 (s, 3H), 3.16-2. 42 (m, 11 H), 2. 34-2. 17 (m, 2H), 2.34 (s, 3H), 2.27 (s, 3H), 2.17 (s, 3H), 2.04 (s, 3H).

ESI-MS m/z: Calcd. for C6oH62N4014S2 : 1126.4 Found (M-H20+H+) : 1109.3.

Example 51 63 was obtained using Method H 1H-NMR (300 MHz, CDCl3) : 8 6.59 (s, 2H), 6.56 (s, 1H), 5.96 (d, 2H), 5.96 (bs, 1H), 5.77 (s, 1H), 5.13 (s, 1H), 5.11 (d, 1H), 4.80 (bs, 1H), 4.47-4. 43 (m, 3H), 4.28 (dd, 1H), 4.16 (d, 1H), 4.03 (dd, 1H), 3.78 (s, 3H), 3.57 (d, 1H), 3.53 (s, 3H), 3.22-3. 10 (m, 3H), 2.92-2. 46 (m, 9H), 2.36-2. 17 (m, 2H), 2.31 (s, 3H), 2.26 (s, 3H), 2.17 (s, 3H), 2.01 (s, 3H), 1.76-1. 65 (m, 3H), 1.50-148 (m, 3H).

3C-NMR (75 MHz, CDCls) : 8 172.0, 171.7, 168.5, 163.3, 148.2, 147.7, 145.1, 142.9, 141.2, 140.4, 138.3, 132.8, 131.5, 129.2, 128.6, 122.4, 121.6, 120.8, 118.0, 115.8, 111.6, 101.7, 82.0, 64.9, 61.9, 61.4, 60.3, 60.0, 57.7, 57.6, 55.9, 55.4, 55.1, 54.8, 42.2, 41.4, 40.5, 39.5, 33.5, 28.6, 28.1, 24.7, 24.0, 20.4, 15.8, 9.6.

ESI-MS m/z: Calcd. for C49H57N5O13S2 : 987.3 Found (M-H20+H+) : 970.2.

Example 52 64 was obtained using Method H 1H-NMR (300 MHz, CDCl3) : 8 6.70 (s, 1H), 6.60 (s, 1H), 6.59 (s, 1H), 6.04-5. 89 (m, 1H), 5.97 (dd, 2H), 5.69 (s, 1H), 5.42-5. 27 (m, 2H), 5.12 (d, 1H), 4.81 (s, 1H), 4.68 (d, 2H), 4.48-4. 45 (m, 2H), 4.16 (d, 1H), 4.03 (dd, 1H), 3.79 (s, 3H), 3.57 (s, 3H), 3.59-3. 57 (m, 1H), 3.21-3. 10 (m, 2H), 2.93-2. 79 (m, 3H), 2.68-2. 60 (m, 1H), 2.52-2. 47 (m, 1H), 2.32 (s, 3H), 2.38-2. 17 (m, 2H), 2.27 (s, 3H), 2.17 (s, 3H), 2.02 (s, 3H).

3C-NMR (75 MHz, CDCi3) : 8 172.0, 168.4, 153.1, 148.3, 147.7, 145.1, 142.9, 141.3, 140.5, 138.7, 133.2, 131.5, 131.2, 129.1, 128.6, 122.0, 121.7, 120.9, 119.1, 117.9, 115.8, 111.9, 101.7, 82.1, 69.1, 64.9, 61.5, 60.3, 57.7, 57.7, 55.9, 55.2, 54.9, 42.2, 41.4, 39.5, 28.7, 24.0, 20.4, 15.8, 9.6.

ESI-MS m/z: Calcd. for C43H47N3013S : 845.3 Found (M-H20+H+) : 828.3.

Example 53 65 was obtained using Method H lH-NMR (300 MHz, CDCl3) : 8 7.40-7. 33 (m, 5H); 6.69 (s, 1H); 6.60 (s, 1H); 6.57 (s, 1H); 5.96 (dd, 2H); 5.70 (s, 1H) ; 5.21 (s, 2H); 5.11 (d, 1H) ; 4.81 (s, 1H) ; 4.47 (d, 1H) ; 4.47-4. 45 (m, 1H) ; 4.15 (d, 1H) ; 4.03 (dd, 1H) ; 3.79 (s, 3H); 3.58 (d, 1H) ; 3.54 (s, 3H); 3.23-3. 20 (m, 1H) ; 3.18-3. 09 (m, 1H) ; 2.87-2. 85 (m, 2H); 2.86-2. 78 (m, 1H) ; 2.69. 2.58 (m, 1H) ; 2.52-2. 44 (m, 1H) ; 2.36-2. 12 (m, 2H); 2.31 (s, 3H); 2.27 (s, 3H); 2.17 (s, 3H); 2.01 (s, 3H).

13C-NMR (75 MHz, CDC13) : 5 172.0, 168.9, 148.3, 147.6, 145.1, 141.2, 140.4, 139.1, 138.7, 131.4, 130.8, 128.7, 128.5, 122.1, 121.9, 121.1, 120.9, 120.6, 116.0, 112.1, 101.9, 82.3, 70.5, 65.1, 61.7, 60.5, 58.0, 57.9, 56.1, 55.3, 55.1, 42.4, 41.6, 39.7, 29.9, 29.5, 24.2, 22.9, 20.6, 16.0, 9.8.

ESI-MS m/z: Calcd. for C47H49N3013S : 895.9 Found (M-H20+H+) : 878.6.

Example 54 66 was obtained using Method H lH-NMR (300 MHz, CDC13) : 8 6.68 (s, 1H) ; 6.60 (s, 1H) ; 6.57 (s, 1H) ; 5.97 (dd, 2H); 5.70 (s, 1H) ; 5.11 (d, 1H) ; 4.81 (s, 1H) ; 4.47 (d, 1H) ; 4.46 (s, 1H) ; 4.16 (d, 1H) ; 4.02 (dd, 1H) ; 3.79 (s, 3H); 3.58- 3.56 (m, 1H) ; 3.57 (s, 3H); 3.23-3. 20 (m, 1H) ; 3.18-3. 09 (m, 1H) ; 2.87-2. 84 (m, 2H); 2.86-2. 78 (m, 1H) ; 2.66-2. 58 (m, 1H) ; 2.52-2. 44 (m, 1H) ; 2. 36-2. 12 (m, 2H); 2.32 (s, 3H); 2.27 (s, 3H); 2.17 (s, 3H); 2.02 (s, 3H); 1.50 (s, 9H).

13C-NMR (75 MHz, CDCIs) : 8 172.2, 168.6, 151.8, 148.7, 147.9, 145.4, 143.1, 141.5, 140.7, 139.0, 133.0, 131.7, 129.4, 128.8, 122.3, 121.8, 121. 1, 116.0, 112.1, 101.9, 83.6, 82.3, 65.1, 61.6, 60.5, 58.0, 57.8, 56.1, 55.4, 55.1, 42.4, 41.2, 39.8, 29.9, 28.9, 27.8, 24.2, 20.6, 16.0, 9.8.

ESI-MS m/z: Calcd. for C44H51N3013S : 861.9 Found (M-H20+H+) : 844.2.

Example 55 34 67 67 was obtained using Method H 1H-NMR (300 MHz, CDCIs) : 8 6.61 (s, 1H), 6.47 (s, 1H), 6.40 (s, 1H), 5.98 (dd, 2H), 5.70 (s, 1H), 5.13 (d, 1H), 4.82 (s, 1H), 4.49-4. 46 (m, 2H), 4.17 (bd, 1H), 4.05 (dd, 1H), 3.80 (s, 3H), 3.76 (s, 3H), 3.60 (s, 3H), 3.60-3. 51 (m, 1H), 3.22-3. 13 (m, 2H), 2.94-2. 82 (m, 3H), 2.70-2. 62 (m, 1H), 2.53-2. 47 (m, 1H), 2.39-2. 07 (m, 2H), 2.32 (s, 3H), 2.26 (s, 3H), 2.18 (s, 3H), 2.02 (s, 3H).

13C-NMR (75 MHz, CDC13) : 8 172.7, 148.0, 147.9, 146.7, 145.3, 143.1, 141.4, 140.7, 131.7, 129.3, 128.5, 126.6, 121.9, 121.1, 118.2, 116.0, 111.2, 110.6, 101.9, 82.3, 64.8, 61.5, 60.5, 58.0, 57.9, 56.1, 55.9, 55.1, 42.3, 41.6, 39.9, 29.2, 24.2, 20.6, 16.0, 9.8.

ESI-MS m/z: Calcd. for C40H4sN3OllS : 775.8 Found (M-H20+H+) : 758.2.

Example 56 37 68 68 was obtained using Method H lH-NMR (300 MHz, CDCIs) : 5 6.61 (s, 1H); 6.47 (s, 1H) ; 6.40 (s, 1H) ; 5.97 (dd, 2H); 5.69 (s, 1H) ; 5.12 (d, 1H) ; 4.82 (s, 1H) ; 4.48 (d, 1H) ; 4.47 (s, 1H) ; 4.16 (d, 1H) ; 4.04 (dd, 1H) ; 3.97 (q, 2H); 3.79 (s, 3H); 3.65 (d, 1H) ; 3.58 (s, 3H); 3.23-3. 20 (m, 1H) ; 3.18-3. 09 (m, 1H) ; 2.88- 2.86 (m, 2H); 2.86-2. 78 (m, 1H) ; 2.66-2. 58 (m, 1H) ; 2.52-2. 44 (m, 1H) ; 2.35- 2.12 (m, 2H); 2.32 (s, 3H); 2.26 (s, 3H); 2.17 (s, 3H); 2.02 (s, 3H); 1.37 (t, 3H).

13C-NMR (75 MHz, CDCIs) : 8 172.2, 168.8, 165.4, 148.1, 145.8, 143. 4, 141.2, 141.0, 135.0, 131.4, 130.1, 129.8, 129.0, 127.9, 121.0, 120.9, 120.7, 118.6, 115.4, 112.9, 102.0, 81.7, 61.9, 60.6, 58.0, 57.9, 57.7, 56.2, 55. 2, 52.2, 42.4, 41.5, 32.9, 32.8, 23.8, 20.7, 19.4, 18.2, 16.6, 9.7.

ESI-MS m/z: Calcd. for C41H47N3011S : 789.8 Found (M-H20+ H+) : 772.2.

Example 57 69 was obtained using Method H H-NMR (300 MHz, CDCIs) : 8 6.60 (s, 1H); 6.48 (s, 1H) ; 6.40 (s, 1H) ; 5.97 (dd, 2H); 5.69 (s, 1H) ; 5.12 (d, 1H) ; 4.81 (s, 1H) ; 4.48 (d, 1H) ; 4.47-4-46 (m, 1H) ; 4.16 (d, 1H) ; 4.04 (dd, 1H) ; 3.84 (q, 2H); 3.79 (s, 3H); 3.61-3. 54 (m, 1H); 3.58 (s, 3H); 3.22-3. 18 (m, 1H); 3.18-3. 09 (m, 1H) ; 2.88-2. 84 (m, 2H); 2.86-2. 78 (m, 1H) ; 2.68-2. 58 (m, 1H) ; 2.52-2. 44 (m, 1H) ; 2.39-2. 12 (m, 2H); 2.32 (s, 3H); 2.26 (s, 3H); 2.17 (s, 3H); 2.02 (s, 3H); 1.80-1. 73 (m, 2H); 0.96 (t, 3H).

13C-NMR (75 MHz, CDCl3) : 8 172.9, 147.9, 147.6, 147.0, 145.4, 143.1, 141.4, 140.7, 131.7, 128.5, 126.6, 121.9, 121.1, 116.0, 112.7, 111.1, 101.9, 82.3, 70.4, 64.8, 61.5, 60.5, 58.0, 57.8, 56.1, 55.4, 55.1, 42.3, 41.6, 39.9, 32.1, 28.8, 29.2, 24.2, 22.9, 22.5, 20.6, 16.0, 14.3, 10.6, 9.8.

ESI-MS m/z: Calcd. for C42H49N3O11S : 803.9 Found (M-H20+H+): 786.2.

Example 58 70 was obtained using Method H lH-NMR (300 MHz, CDC13) : 8 6.60 (s, 1H); 6.48 (s, 1H) ; 6.40 (s, 1H) ; 6.03-5. 94 (m, 1H) ; 5.97 (dd, 2H); 5.72 (s, 1H) ; 5.32 (dd, 1H) ; 5.21 (dd, 1H) ; 5. 12 (d, 1H) ; 4.81 (s, 1H) ; 4.50-4. 47 (m, 4H); 4.16 (d 1H) ; 4.04 (dd, 1H) ; 3.79 (s, 3H); 3.61 (d, 1H) ; 3.59 (s, 3H); 3.22-3. 18 (m, 1H) ; 3.18-3. 09 (m, 1H) ; 2.88-2. 84 (m, 2H); 2.86-2. 78 (m, 1H) ; 2.68-2. 58 (m, 1H) ; 2.52-2. 44 (m, 1H) ; 2.33-2. 12 (m, 2H); 2.32 (s, 3H); 2.26 (s, 3H); 2.17 (s, 3H); 2.02 (s, 3H).

ESI-MS m/z: Calcd. for C42H47N3011S : 801.2 Found (M-H20+H+) : 784.2.

Example 59 43 71 71 was obtained using Method H lH-NMR (300 MHz, CDCls) : 5 7.36-7. 25 (m, 5H); 6.60 (s, 1H) ; 6.50 (s, 1H) ; 6.41 (s, 1H) ; 5.98 (dd, 2H); 5.69 (s, 1H) ; 5.12 (d, 1H) ; 5.02 (s, 2H); 4.81 (s, 1H) ; 4.48 (d, 1H) ; 4.48-4. 46 (m, 1H) ; 4.16 (d 1H); 4.04 (dd, 1H); 3.78 (s, 3H); 3.60 (s, 3H); 3.22-3. 18 (m, 1H); 3.18-3. 09 (m, 1H) ; 2.88-2. 84 (m, 2H); 2.86-2. 78 (m, 1H) ; 2.64-2. 58 (m, 1H) ; 2.46-2. 40 (m, 1H); 2.34-2. 12 (m, 2H); 2.31 (s, 3H); 2.26 (s, 3H); 2.17 (s, 3H); 2.03 (s, 3H).

ESI-MS m/z: Calcd. for C46H47N3011S : 851.9 Found (M-H20+H+) : 834. 3.

Example 60 11 72 Compound 11 (31%) was recovered after chromatographic purification.

72 was obtained using Method H lH-NMR (300 MHz, CDC13) : 5 7.31-7. 20 (m, 5H); 6.60 (s, 1H) ; 6.55 (s, 1H) ; 6.53 (s, 1H) ; 6.00 (d, 1H) ; 5.93 (d, 1H) ; 5.70 (s, 1H) ; 5.11 (d, 1H) ; 4.81 (s, 1H) ; 4.47 (d, 1H) ; 4.16 (d, 1H) ; 4.02 (dd, 1H) ; 3.79 (s, 3H); 3.58 (d, 1H); 3.50 (s, 3H); 3.21-3. 08 (m, 2H); 3.02 (t, 2H); 2.87-2. 80 (m, 5H); 2.66-2. 44 (m, 3H); 2.36-2. 22 (m, 1H); 2.31 (s, 3H); 2.27 (s, 3H); 2.17 (s, 3H); 2.01 (s, 3H).

ESI-MS m/z: Calcd. for C48H5iN3012S : 893.2 Found (M-H20+H+) : 876.5.

Example 61 12 73 73 was obtained using Method H. lH-NMR (300 MHz, CDCl3) : 8 6.61 (s, 1H) ; 6.60 (s, 1H) ; 6.57 (s, 1H) ; 6.00 (d, 1H) ; 5.93 (d, 1H) ; 5.73 (s, 1H) ; 5.11 (d, 1H) ; 4.82 (s, 1H) ; 4.84 (s, 2H); 4.17-4. 15 (m, 1H) ; 4.03 (dd, 1H) ; 3.80 (t, 2H); 3.79 (s, 3H); 3.65-3. 58 (m, 1H) ; 3.54 (s, 3H); 3.23-3. 10 (m, 2H); 2.99 (t, 2H); 2.88-2. 80 (m, 4H); 2.68-2. 46 (m, 3H); 2.37-2. 17 (m, 1H) ; 2.31 (s, 3H); 2.26 (s, 3H); 2.18 (s, 3H); 2.01 (s, 3H).

13C-NMR (75 MHz, CDCI3) : 8 172.2, 168.6, 148.4, 147.9, 145.4, 143.2, 141.5, 140.7, 138.3, 133.3, 131.6, 129.8, 129.7, 129.5, 128.8, 122.5, 121.8, 121.1, 115.9, 112.0, 101.9, 82.3, 65.1, 61.6, 60.5, 58.0, 57.8, 56.1, 55.3, 55.1, 42.4, 41.5, 39.7, 39.0, 37.5, 29.9, 28.8, 27.1, 24.3, 20.6, 16.0, 9.9.

ESI-MS m/z: Calcd. for C42H46CIN3012S : 851.2 Found (M-H20+H+) : 834.2.

Example 62 74 was obtained using Method H. lH-NMR (300 MHz, CDC13) : 5 6.60 (s, 1H) ; 6.46 (s, 1H) ; 6.44 (s, 1H) ; 6.01 (d, 1H) ; 5.93 (d, 1H) ; 5.73 (s, 1H) ; 5.12 (d, 1H) ; 4.81 (s, 1H) ; 4.48 (s, 2H); 4.16 (d, 1H) ; 4.04 (dd, 1H) ; 3.78 (s, 3H); 3.60 (s, 3H); 3.58-3. 56 (m, 1H) ; 3.22-3. 08 (m, 2H); 2.93-2. 75 (m, 3H); 2.65- 2.44 (m, 2H); 2.37-2. 14 (m, 1H); 2.31 (s, 3H); 2.25 (s, 3H); 2.17 (s, 3H); 2.02 (s, 3H).

13C-NMR (75 MHz, CDC13) : 8 172.7, 147.9, 145.3, 144.6, 144.4, 143.1, 141.4, 140.7, 131.7, 131.1, 129.4, 129.2, 129.0, 122.0, 121.1, 116.1, 114.2, 110.0, 101.8, 82.3, 65.7, 64.8, 61.5, 60.5, 58.0, 57.9, 56.1, 55.3, 55.1, 42.3, 41.6, 39.8, 29.9, 29.5, 29.0, 24.2, 22.9, 20.6, 19.4, 16.0, 14.3, 9.8.

ESI-MS m/z: Calcd. for C43H42F7N3012S : 957.2 Found (M-C4F70-H20+2H+) : 744.2.

Example 63 75 was obtained using Method H. lH-NMR (300 MHz, CDCIs) : 8 7.08 (dd, 1H) ; 6.71 (s, 1H) ; 6.60 (s, 2H); 6.00 (d, 1H) ; 5.92 (d, 1H) ; 5.74 (s, 1H) ; 5. 12, (d, 1H) ; 4.99 (dd, 1H) ; 4.81 (s, 1H) ; 4.63 (dd, 1H) ; 4.48 (d, 2H); 4.17 (dd, 1H) ; 3.79 (s, 3H); 3.60-3. 57 (m, 1H) ; 3.57 (s, 3H); 3.24-3. 22 (m, 1H) ; 3.17-3. 09 (m, 1H); 2.93-2. 78 (m, 3H); 2.68-2. 46 (m, 2H); 3.37-2. 22 (m, 1H); 2.31 (s, 3H); 2.26 (s, 3H); 2.17 (s, 3H); 2.01 (s, 3H). 13C-NMR (75 MHz, CDC13) : 8 172.1, 151.0, 148.4, 147.9, 145.4, 142.9, 141.5, 140.7, 138.5, 133.7, 131.6, 129.5, 128.9, 122.0, 121.8, 121.1, 118.0, 116.0, 112.2, 101.9, 98.7, 82.3, 65.1, 61.7, 60.5, 58.0, 57.8, 56.1, 55. 4, 55.1, 42.2, 41.6, 39.7, 29.9, 28.8, 24.2, 20.6, 16.0, 9.8.

ESI-MS m/z: Calcd. for C42H45N3013S : 831.2 Found (M-H20+H+) : 814.2.

Example 64 21 76 Compound 21 (17%) was recovered after chromatographic purification.

76 was obtained using Method H. lH-NMR (300 MHz, CDCls) : 8 8.66 (s, 1H) ; 7.67-7. 70 (m, 2H); 7.36-7. 29 (m, 2H); 6.74 (s, 1H) ; 6.60 (s, 2H); 5.99 (d, 1H) ; 5.92 (d, 1H) ; 5.76 (s, 1H) ; 5.13 (d, 1H) ; 4.81 (s, 1H) ; 4.47 (s, 2H); 4.15 (d, 1H); 4.04 (d, 1H); 3.78 (s, 3H); 3.57-3. 56 (m, 1H); 3.54 (s, 3H); 3.47-3. 44 (m, 1H); 3.21-3. 10 (m, 2H); 2.92-2. 79 (m, 3H); 2.70-2. 48 (m, 2H); 2.38-2. 19 (m, 1H); 2.31 (s, 3H); 2.27 (s, 3H); 2.16 (s, 3H); 2.01 (s, 3H).

13C-NMR (75 MHz, CDCIs) : 8 172.2, 160.9, 156.5, 155.6, 150.0, 148.4, 147.9, 145.3, 143.1, 141.5, 140.7, 138.3, 134.9, 133.5, 131.7, 129.9, 129.4, 128.9, 125.1, 122.6, 121.9, 121.1, 118.2, 118.0, 117.4, 117.0, 116.0, 112.0, 101.9, 82.3, 65.2, 61.7, 60.5, 58.0, 57.9, 56.1, 55.4, 55.1, 42.4, 41.6, 39.7, 29.9, 28.8, 24.2, 20.6, 16.0, 9.8.

ESI-MS m/z: Calcd. for C49H47N3014S : 933.2 Found (M-H20+H+) : 916.3.

Example 65 The reaction was performed with a mixture of compound 22 and 23 (3: 1) using Method H, thus compounds 77 and 78 were isolated after chromatographic as pure compounds.

77 : lH-NMR (300 MHz, CDCIs) : 8 7.44 (d, 1H); 6.61-6. 51 (m, 5H); 6.19 (s, 1H) ; 6.00 (s, 1H) ; 5.92 (s, 1H) ; 5.73 (s, 1H) ; 5.10 (d, 1H) ; 4.79 (s, 1H) ; 4.45 (s, 2H); 4.15-4. 14 (m, 1H); 4.01 (d, 1H); 3.85 (s, 2H); 3.78 (s, 3H); 3.57-3. 56 (m, 1H) ; 3.49 (s, 3H); 3.21-3. 00 (m, 3H); 3.04 (s, 6H); 2.86-2. 78 (m, 3H); 2.64- 2.43 (m, 2H); 2.30 (s, 3H); 2.25 (s, 3H); 2.16 (s, 3H); 2.00 (s, 3H).

13C-NMR (75 MHz, CDC13) : 5 171.9, 167.1, 161.6, 155.8, 152.9, 148.0, 147.9, 147.6, 145.1, 142.9, 141.2, 140.4, 138.1, 133.2, 131.5, 129.1, 128.6, 125.2, 122.0, 121.6, 120.8, 117.8, 115.7, 111.7, 110.7, 108.8, 108.4, 101.6, 98.3, 82.0, 64.9, 61.4, 60.3, 57.7, 55.9, 55.0, 54.8, 42.1, 41.3, 40.1, 39.4, 37.6, 29.6, 28.6, 24.0, 20.4, 15.7, 14.1, 9.6.

ESI-MS m/z: Calcd. for C52H54N4014S : 990.3 Found (M-H20+H+) : 973.3. 78 : lH-NMR (300 MHz, CDC13) : 8 7.69 (s, 1H) ; 7.51 (d, 1H) ; 7.45 (d, 1H) ; 6.92 (s, 1H) ; 6.61-6. 48 (m, 5H); 6.33 (s, 1H) ; 6.21 (s, 1H) ; 6.19 (s, 1H) ; 6.01 (s, 1H) ; 5.94 (s, 1H) ; 5.08 (d, 1H) ; 4.74 (s, 1H) ; 4.47 (s, 1H) ; 4.32-4. 28 (m, 2H); 4.04-3. 94 (m, 3H); 3.85 (s, 2H); 3.67 (s, 3H); 3.61 (d, 1H); 3.47 (s, 3H); 3.26- 2.80 (m, 5H); 3.05 (s, 6H); 2.97 (s, 6H); 2.60-2. 42 (m, 2H); 2.29 (s, 6H); 2.19 (s, 3H); 2.06 (s, 3H).

ESI-MS m/z: Calcd. for C65H65N5017S : 1220.3 Found (M+H+) : 1221.3.

Example 66 79 was obtained using Method H lH-NMR (300 MHz, CDC13) : 8 6.62 (s, 1H), 6.61 (s, 1H), 6.57 (s, 1H), 5.97 (d, 2H), 5.72 (s, 1H), 5.12 (d, 1H), 5.08 (bd, 1H), 4.82 (s, 1H), 4.55-4. 44 (m, 3H), 4.17 (d, 1H), 4.03 (dd, 1H), 3.79 (s, 3H), 3.59 (d, 1H), 3.53 (s, 3H), 3.25-3. 20 (m, 1H), 3.15-3. 09 (m, 1H), 2.92-2. 78 (m, 3H), 2.67-2. 59 (m, 1H), 2.52-2. 47 (m, 1H), 2.37-2. 18 (m, 2H), 2.32 (s, 3H), 2.27 (s, 3H), 2.18 (s, 3H), 2.02 (s, 3H), 1.50 (d, 3H), 1.44 (s, 9H).

ESI-MS m/z: Calcd. for C47H56N4O14S : 932.3 Found (M-H20+H+) : 915.3.

Example 67 6 80 Compound 6 (42%) was recuperatd after chromatographic purification.

80 was obtained using Method H lH-NMR (300 MHz, CDCIs) : 8 6.96 (s, 1H), 6.61 (s, 1H), 6.54 (s, 1H), 5.98 (dd, 2H), 5.12 (d, 1H), 4.83 (s, 1H), 4.49 (d, 1H), 4.33 (bs, 1H), 4.03 (dd, 1H), 3.78 (s, 3H), 3.70 (d, 1H), 3.60 (d, 1H), 3.55 (s, 3H), 3.29-3. 24 (m, 1H), 3.18-3. 09 (m, 1H), 3.03-2. 80 (m, 3H), 2.69-2. 59 (m, 1H), 2.53-2. 05 (m, 1H), 2.42-2. 13 (m, 2H), 2.37 (s, 3H), 2.33 (s, 3H), 2.31 (s, 3H), 2.24 (s, 3H), 2.13 (s, 3H), 2.03 (s, 3H).

ESI-MS m/z: Calcd. for C43H47N3013S : 845.3 Found (M +H+) : 846.3.

Example 68 9 81 Compound 9 was recovered (25%) after chromatographic purification.

81 was obtained using Method H lH-NMR (300 MHz, CDCIs) : 8 6.95 (s, 1H); 6.59 (s, 2H); 6.54 (d, 1H) ; 6.01 (dd, 1H) ; 5.94 (dd, 2H); 5.12 (d, 1H) ; 4.81 (s, 1H) ; 4.49 (d, 1H) ; 4.34 (s, 1H) ; 4.02 (dd, 1H) ; 3.75 (s, 3H); 3.67 (d, 1H) ; 3.58 (d, 1H) ; 3.53 (s, 3H); 3.25-3. 23 (m, 1H) ; 3.17-3. 12 (m, 1H) ; 2.92-2. 80 (m, 3H); 2.69-2. 63 (m, 1H); 2.60 (t, 2H); 2.54-2. 50 (m, 1H); 2.48 (t, 2H); 2.32 (s, 3H); 2.29 (s, 3H); 2.13 (s, 3H); 2.03 (s, 3H); 1.91-1. 80 (m, 2H); 1.79-1. 68 (m, 2H); 1.09 (t, 3H); 1.00 (t, 3H).

13C-NMR (75 MHz, CDCl3) : 8 172.1, 171.9, 171.4, 148.6, 148.0, 145.5, 143.7, 141.4, 140.8, 138.8, 132.7, 131.6, 131.5, 128.8, 127.6, 124. 5, 122.6, 121.7, 116.0, 111.9, 102.0, 82.0, 65.2, 61.5, 60.3, 57.9, 57.8, 56.4, 56.2, 55.2, 42.6, 41.6, 39.8, 36.3, 36.0, 29.9, 29.5, 28.8, 24.2, 20.5, 18.9, 18.7, 16.0, 14.0, 13.7, 9.8.

ESI-MS m/z: Calcd. for C47H55N3013S : 901.3 Found (M-H20 +H+) : 884.5.

Example 69 82 was obtained using Method H lH-NMR (300 MHz, CDCI3) : 8 6.95 (s, 1H); 6.59 (s, 1H) ; 6.54 (s, 1H) ; 6.02 (d, 1H) ; 5.94 (s, 1H) ; 5.12 (d, 1H) ; 4.81 (s, 1H) ; 4.49 (s, 1H) ; 4.35 (s, 1H) ; 4.02 (d, 1H) ; 3.75 (s, 3H); 3.68-3. 67 (m, 1H) ; 3.58- 3.56 (m, 1H) ; 3.53 (s, 3H); 3.26-3. 24 (m, 1H) ; 3.14-3. 08 (m, 1H) ; 2. 92-2. 80 (m, 3H); 2.61 (t, 2H); 2.49 (t, 2H); 2.32 (s, 3H); 2.29 (s, 3H); 2.13 (s, 3H); 2.03 (s, 3H); 1.83-1. 59 (m, 4H); 1.42-1. 14 (m, 20H).

ESI-MS m/z: Calcd. for C5sH71N3013S : 1013.4 Found (M-H20 +H+) : 996. 5.

Example 70 17 83 83 was obtained using Method H lH-NMR (300 MHz, CDCIs) : 5 6.95 (s, 1H); 6.59 (s, 1H) ; 6.54 (s, 1H) ; 5.98 (dd, 2H); 5.12 (d, 1H) ; 4.81 (s, 1H) ; 4.48 (d, 1H) ; 4.47-4. 45 (m, 1H) ; 4.17 (d, 1H) ; 4.01 (dd, 1H) ; 3.75 (s, 3H); 3.66 (d, 1H) ; 3.59-3. 56 (m, 1H) ; 3.53 (s, 3H); 3.26-3. 21 (m, 1H) ; 3.18-3. 09 (m, 1H) ; 2.93- 2.90 (m, 2H); 2.86-2. 78 (m, 1H) ; 2.69-2. 58 (m, 1H) ; 2.61 (t, 2H); 2.52-2. 44 (m, 1H); 2.49 (t, 2H); 2.37-2. 12 (m, 2H); 2.31 (s, 3H); 2.29 (s, 3H); 2.12 (s, 3H); 2.03 (s, 3H); 1.84-1. 80 (m, 2H); 1.71-1. 64 (m, 2H); 1.40-1. 17 (m, 54H).

Example 71 84 was obtained using Method H lH-NMR (300 MHz, CDCIs) : 8 7.94 (d, 1H); 7.81 (d, 1H); 7.61-7. 53 (m, 4H); 7.45-7. 39 (m, 6H); 6.99 (s, 1H); 6.67 (d, 1H); 6.66 (d, 1H) ; 6.60 (s, 1H) ; 6.57 (d, 1H) ; 6.02 (s, 1H) ; 5.94 (d, 1H) ; 5.15 (d, 1H) ; 4. 83 (s, 1H) ; 4. 51 (d, 1H) ; 4. 48-4. 46 (m, 1H) ; 4. 05 (dd, 1H) ; 3. 79 (s, 3H); 3.62-3. 61 (m, 1H); 3.56 (s, 3H); 3.27-3. 16 (m, 1H); 2.96-2. 88 (m, 3H); 2. 70- 2.50 (m, 2H); 2.43-2. 39 (m, 2H); 2.35 (s, 3H); 2.234 (s, 3H); 2.17 (s, 3H); 2.05 (s, 3H).

13C-NMR (75 MHz, CDC13) : 8 172.0, 164.9, 164.5, 148.5, 148.0, 146.8, 146.5, 145.3, 143.4, 141.2, 140.6, 138.5, 134.2, 134.0, 131.4, 130.8, 130.5, 129.0, 128.9, 128.7, 128.2, 127.5, 125.0, 124.4, 122.5, 116.9, 115.8, 111.7, 101.7, 81.7, 67.6, 65.0, 61.2, 60.2, 57.7, 56.0, 55.1, 42.5, 41.4, 39.6, 32.6, 31.9, 29.6, 26.3, 28.6, 23.9, 22.6, 20.4, 15.8, 14.1, 9.6.

ESI-MS m/z : Calcd. for C57H55N3013S : 1021.4 Found (M-H20+H+) : 1004.6.

Example 72 85 was obtained using Method H lH-NMR (300 MHz, CDC13) : 8 7.41-7. 34 (m, 10H) ; 6.95 (s, 1H) ; 6.69 (s, 1H) ; 6.54 (s, 1H) ; 6.01 (d, 1H) ; 5.93 (s, 1H) ; 5.35- 5.25 (m, 2H); 5.11 (d, 1H) ; 4.80 (s, 1H) ; 4.47 (s, 1H) ; 4.32 (s, 1H) ; 4.03 (dd, 1H) ; 3.75 (s, 3H); 3.52 (s, 3H); 3.24 (s, 1H) ; 3.14-3. 06 (m, 1H) ; 2.90-2. 78 (m, 3H); 2.66-2. 45 (m, 2H); 2.31 (s, 3H); 2.26-2. 16 (m, 2H); 2.20 (s, 3H); 2.09 (s, 3H); 2.02 (s, 3H).

13C-NMR (75 MHz, CDCI3) : 5 172.1, 153.5, 153.2, 148.5, 148.0, 145.5, 144.1, 141.5, 140.7, 139.0, 135.2, 135.1, 133.1, 131.6, 128.9, 128.8, 128.8, 128.7, 128.6, 128.4, 127.7, 122.2, 115.8, 112.0, 101.9, 82.0, 70.6, 70. 5, 65.3, 61.6, 60.4, 57.8, 56.2, 55.9, 55.3, 42.4, 41.5, 39.7, 31.8, 29.9, 28.8, 24.1, 22.8, 20.3, 15.9, 14.3, 9.8.

ESI-MS m/z: Calcd. for CssHssN301sS : 1029.3 Found (M-H20 +H+) : 1012.4.

Example 73 86 was obtained using Method H lH-NMR (300 MHz, CDCIs) : 8 6.92 (s, 1H); 6.69 (s, 1H) ; 6.55 (s, 1H) ; 5.97 (dd, 2H); 5.12 (d, 1H) ; 4.81 (s, 1H) ; 4.49 (d, 1H) ; 4.33 (s, 1H) ; 4.03 (dd, 1H) ; 3.80 (s, 3H); 3.60-3. 56 (m, 1H) ; 3.57 (s, 3H); 3.26-3. 24 (m, 1H) ; 3.16-3. 06 (m, 1H) ; 2.90-2. 89 (m, 2H); 2.88-2. 78 (m, 1H) ; 2.69-2. 58 (m, 1H) ; 2.53-2. 44 (m, 1H) ; 2.34-2. 26 (m, 2H); 2.33 (s, 3H); 2.31 (s, 3H); 2.14 (s, 3H); 2.04 (s, 3H); 1.53 (s, 9H); 1.50 (s, 9H).

13C-NMR (75 MHz, CDCIs) : 6 172.2, 151.8, 151.4, 148.7, 148.1, 145.5, 141.2, 141.5, 140.8, 139.0, 132.8, 131.3, 128.9, 127.3, 124.4, 122.4, 121. 9, 116.0, 112.1, 101.9, 83.5, 83.2, 82.0, 65.4, 61.5, 60.2, 57.9, 56.3, 56.0, 55.4, 42.4, 41.6, 39.5, 29.9, 28.9, 27.8, 27.7, 24.1, 20.3, 15.9, 14.3, 9.7.

ESI-MS m/z: Calcd. for C49H59N3015S : 961.4 Found (M-H20+H+) 944.4.

Example 74 87 was obtained using Method H lH-NMR (300 MHz, CDC13) : 8 6.76 (s, 1H); 6.45 (s, 1H) ; 6.39 (s, 1H) ; 6.02 (d, 1H) ; 5.93 (d, 1H) ; 5.13 (d, 1H) ; 4.81 (s, 1H) ; 4.49 (d, 1H) ; 4.36 (s, 1H) ; 4.18 (d, 1H) ; 4.11 (d, 1H) ; 4.03 (d, 1H) ; 3.90 (s, 3H); 3.81 (s, 3H); 3.75 (s, 3H); 3.58 (s, 3H); 3.58-3. 56 (m, 1H); 3.23-3. 11 (m, 2H); 2.94-2. 81 (m, 3H); 2.71-2. 61 (m, 1H); 2.53-2. 47 (m, 1H); 2.35-2. 27 (m, 1H); 2.27 (s, 3H); 2.22 (s, 3H); 2.16 (s, 3H); 2.01 (s, 3H).

13C-NMR (75 MHz, CDC13) : 8 172.7, 151.8, 148.7, 148.0, 146.6, 145.4, 141.4, 140.7, 131.4, 131.3, 128.5, 126.6, 124.6, 124.4, 122.0, 116.1, 111.2, 110.6, 101.9, 81.7, 64.9, 61.3, 60.2, 59.6, 58.0, 57.9, 56.2, 55.9, 55.3, 55.2, 42.3, 41.7, 39.9, 31.8, 29.9, 29.2, 24.3, 22.8, 20.4, 16.0, 14.3, 9.8.

ESI-MS m/z: Calcd. for C4lH47N3011S : 789.2 Found (M-H20+ H+) : 772.2.

Example 75 88 was obtained using Method H 1H-NMR (300 MHz, CDCIs) : 8 6.77 (s, 1H); 6.46 (s, 1H) ; 6.40 (s, 1H) ; 5.97 (dd, 2H); 5.13 (d, 1H) ; 4.81 (s, 1H) ; 4.49 (d, 1H) ; 4. 39 (s, 1H) ; 4. 10 (d 1H) ; 4. 03 (dd, 1H) ; 3. 99 (q, 2H); 3. 96 (q, 2H); 3. 83 (s, 3H); 3.61-3. 54 (m, 1H); 3.58 (s, 3H); 3.24-3. 18 (m, 1H); 3. 18-3. 09 (m, 1H); 2.88-2. 85 (m, 2H); 2.86-2. 78 (m, 1H) ; 2. 69-2. 58 (m, 1H) ; 2. 54-2. 44 (m, 1H) ; 2.35-2. 12 (m, 2H); 2.28 (s, 3H); 2.25 (s, 3H); 2.17 (s, 3H); 2.03 (s, 3H); 1.40 (t, 3H); 1.36 (t, 3H).

ESI-MS m/z : Calcd. for C43H5iN30nS : 817.3 Found (M-H2O+H+) : 800.3.

Example 76 89 was obtained using Method H lH-NMR (300 MHz, CDCIs) : 8 6.79 (s, 1H); 6.48 (s, 1H) ; 6.40 (s, 1H) ; 5.98 (dd, 2H); 5.13 (d, 1H) ; 4.81 (s, 1H) ; 4.48 (d, 1H) ; 4.42 (s, 1H) ; 4.10 (d, 1H) ; 4.04 (dd, 1H) ; 3.86 (q, 2H); 3.84 (q, 2H); 3.79 (s, 3H); 3.60 (s, 3H); 3.60-3. 58 (m, 1H) ; 3.24-3. 18 (m, 1H) ; 3.18-3. 09 (m, 1H) ; 2.88-2. 84 (m, 2H); 2.86-2. 78 (m, 1H) ; 2.68-2. 58 (m, 1H) ; 2.52-2. 44 (m, 1H) ; 2.39-2. 12 (m, 2H); 2.28 (s, 3H); 2.25 (s, 3H); 2.18 (s, 3H); 2.02 (s, 3H); 1.84- 1.74 (m, 4H); 1.10 (t, 3H); 0.96 (t, 3H).

ESI-MS m/z: Calcd. for C45H55N30liS : 845.3 Found (M-H20+H+) : 828.0.

Example 77 90 was obtained using Method H lH-NMR (300 MHz, CDC13) : 8 6.79 (s, 1H); 6.47 (s, 1H) ; 6.40 (s, 1H); 6.16-5. 92 (m, 2H); 5.97 (dd, 2H); 5.45 (dd, 1H); 5.31 (dd, 1H) ; 5.24 (dd, 1H) ; 5.50 (dd, 1H) ; 5.12 (d, 1H) ; 4.80 (s, 1H) ; 4.78 (dd, 1H) ; 4.49 (d, 2H); 4.30 (s, 1H) ; 4.35 (dd, 1H) ; 4.11 (d, 1H) ; 4.04 (dd, 1H) ; 3.83 (s, 3H); 3.59 (s, 3H); 3.59-3. 58 (m, 1H) ; 3.24-3. 18 (m, 1H) ; 3.18-3. 09 (m, 1H) ; 2.90-2. 88 (m, 2H); 2.88-2. 78 (m, 1H) ; 2.68-2. 58 (m, 1H) ; 2.52-2. 44 (m, 1H); 2.37-2. 12 (m, 2H); 2.28 (s, 3H); 2.23 (s, 3H); 2.16 (s, 3H); 2.02 (s, 3H).

ESI-MS m/z: Calcd. for C4sH5iN30nS : 841.3 Found (M-H20+H+) : 824.3.

Example 78 44 91 91 was obtained using Method H lH-NMR (300 MHz, CDCIs) : 8 7.48-7. 25 (m, 10H) ; 6.82 (s, 1H) ; 6.48 (s, 1H) ; 6.41 (s, 1H) ; 5.98 (dd, 2H); 5.32 (d, 1H) ; 5.12 (d, 1H) ; 5.02 (s, 2H); 4.84 (d, 1H) ; 4.80 (s, 1H) ; 4.48 (d, 1H) ; 4.45 (s, 1H) ; 4.50-4. 00 (m, 2H); 3.85 (s, 3H); 3.61-3. 57 (m, 1H); 3.60 (s, 3H); 3.24-3. 18 (m, 1H); 3.18-3. 09 (m, 1H); 2.88-2. 84 (m, 2H); 2.86-2. 78 (m, 1H); 2.64-2. 58 (m, 1H); 2.46-2. 40 (m, 1H); 2.36-2. 12 (m, 2H); 2.30 (s, 3H); 2.03 (s, 9H). 13C-NMR (75 MHz, CDCIs) : 8 172.6, 150.5, 149.1, 147.3, 145.4, 141.4, 140.7, 138.4, 137.3, 131.4, 131.3, 128.7, 128.6, 128.5, 128.1, 128.0, 127.9, 127.3, 125.1, 124.9, 122.1, 116.2, 116.1, 113.9, 11.3, 101.8, 82.0, 74.2, 71.0, 64.9, 61.4, 59.8, 58.1, 58.0, 56.2, 55.7, 55.4, 42.4, 42.2, 41.5, 39.8, 29.9, 29.1, 24.3, 20.1, 16.0, 9.8.

ESI-MS m/z: Calcd. for C53H55N3O11S : 941.4 Found (M-H20+H+) : 924.3.

Example 79 Compound 30 (15%) was recovered after chromatographic purification.

92 was obtained using Method H lH-NMR (300 MHz, CDC13) : 8 7.17 (dd, 1H); 7.08 (dd, 1H); 6.96 (s, 1H); 6.72 (s, 1H); 6.58 (s, 1H); 6.02 (d, 1H); 5.94 (d, 1H) ; 5.12 (d, 1H) ; 4.99 (dd, 2H); 4.82 (s, 1H) ; 4.69 (dd, 1H) ; 4.63 (dd, 1H) ; 4.50-4. 48 (m, 1H) ; 4.39-4. 37 (m, 1H) ; 4.05 (dd, 1H) ; 3.84-3. 79 (m, 1H) ; 3.80 (s, 3H); 3.61-3. 59 (m, 1H) ; 3.58 (s, 3H); 3.29-3. 26 (m, 1H) ; 3.18-3. 09 (m, 1H); 2.93-2. 80 (m, 3H); 2.70-2. 47 (m, 2H); 2.53 (s, 3H); 2.33 (s, 3H); 2.30- 2.24 (m, 1H); 2.15 (s, 3H); 2.04 (s, 3H).

13C-NMR (75 MHz, CDCIs) : 8 172.1, 168.8, 151.0, 150.8, 148.4, 147.9, 145.5, 143.8, 143.1, 142.9, 141.5, 140.8, 138.5, 133. 5, 131.8, 129.0, 128. 1, 124.2, 122.1, 121.6, 115.8, 112.8, 112.2, 102.0, 98.7, 82.0, 65.3, 61.6, 60.6, 57.8, 56.2, 56.0, 55.3, 42.5, 41.5, 39.7, 29.9, 28.9, 24.1, 20.4, 15.9, 9.8.

ESI-MS m/z: Calcd. for C45H47N3015S : 901.2 Found (M-H20+H+) : 884.3.

Example 80 54 93 93 was obtained using Method H 1H-NMR (300 MHz, CDCIs) : 8 6.47 (s, 1H), 6.44 (s, 1H), 6.19 (s, 1H), 5.98 (dd, 2H), 5.70 (bp, 1H), 5.01 (d, 1H), 4.83 (d, 1H), 4.48 (bp, 1H), 4.42 (d, 1H), 4.14 (dd, 1H), 3.79 (s, 3H), 3.78 (dd, 1H), 3.58 (d, 1H), 3.53 (s, 3H), 3.23-3. 20 (m, 2H), 2. 91-2. 70 (m, 2H), 2. 63-2. 47 (m, 5H), 2.30 (s, 3H), 2.23 (s, 6H), 2. 15 (s, 3H), 2. 01 (s, 3H).

13C-NMR (75 MHz, CDC13) : 8 168.7, 147.4, 145.4, 144.4, 144.1, 142.6, 141.7, 140.8, 131.3, 129.6, 129.1, 127.1, 122.1, 121.3, 118.0, 116.1, 113.8, 111.6, 110.5, 101.7, 83.2, 71.2, 62.5, 60.1, 59.2, 57.7, 55.3, 54.9, 49.0, 43.1, 42.1, 41.6, 38.9, 28.5, 24.8, 20.3, 15.6, 9.7.

ESI-MS m/z : Calcd. for C4oH4, 5N3011S : 775.3. Found (M+H+) : 776.1.

Example 81 55 94 94 was obtained using Method H 1H-NMR (300 MHz, CDC13) : 8 6.48 (s, 1H), 6.44 (s, 1H), 6.21 (s, 1H), 5.98 (d, 2H), 5.69 (bs, 1H), 4.99 (d, 1H), 4.87 (d, 1H), 4.50-4. 44 (m, 2H), 4.17-4. 12 (m, 1H), 3.89-3. 84 (m 1H), 3.80 (s, 3H), 3.58-3. 55 (m, 1H), 3.55 (s, 3H), 3.26-3. 22 (m, 1H), 3.02-2. 42 (m, 6H), 2.37- 2.02 (m, 4H), 2.31 (s, 3H), 2.28 (s, 3H), 2.12 (s, 3H), 2.05 (s, 3H), 0.88 (t, 3H).

ESI-MS m/z: Calcd. for C41H47N3011S : 789.3. Found (M-H20+H+) : 772.3.

Example 82 Compound 32 was recovered after chromatographic purification (15%).

95 was obtained using Method H 1H-NMR (300 MHz, CDC13) : 8 7.05 (dd, 1H); 6.48 (s, 1H) ; 6.46 (s, 1H) ; 6.15 (s, 1H) ; 6.03 (s, 1H) ; 5.92 (s, 1H) ; 5.73 (s, 1H) ; 4.91 (dd, 1H) ; 4.83 (s, 1H) ; 4.72 (dd, 1H) ; 4.45-4. 48 (m, 3H); 4.13 (d, 1H) ; 4.01-3. 94 (m, 2H); 3.81 (s, 3H); 3.71-3. 66 (m, 2H); 3.59 (s, 3H); 3.23-3. 20 (m, 3H); 2.83-2. 81 (m, 2H); 2.72-2. 62 (m, 1H) ; 2.54-2. 42 (m, 2H); 2.33 (s, 3H); 2.22 (s, 3H); 2.14 (s, 3H); 2.02 (s, 3H).

ESI-MS m/z: Calcd. for C42H45N3013S : 831.3. Found (M-H20+H+) : 814.2.

Example 83 51 96 96 was obtained using Method H. 1H-NMR (300 MHz, CDC13) : 8 7.00 (bs, 1H), 6.49 (s, 1H), 6.42 (bs, 1H), 6.00 (dd, 2H), 5.40 (bs, 1H), 5.12 (d, 1H), 4.84-3. 69 (m, 4H), 3.84-3. 50 (m, 5H), 3.50 (s, 3H), 3.24-2. 57 (m, 7H), 2.42- 2.13 (m, 2H), 2.40 (s, 3H), 2.33 (s, 3H), 2.29 (s, 3H), 2.13 (s, 3H), 2.03 (s, 3H).

ESI-MS m/z: Calcd. for C4lH45N3012S : 803.3 Found (M-H20+H+) : 804.

Example 84 97 was obtained using Method H 1H-NMR (300 MHz, CDCIs) : 8 6.93 (s, 1H); 6.47 (s, 1H); 6.42 (s, 1H); 5.98 (dd, 2H); 5.13 (d, 1H) ; 4.81 (s, 1H); 4.50 (d, 1H); 4.36 (s, 1H); 4.05 (dd, 1H); 3.79 (s, 3H); 3.62-3. 58 (m, 1H); 3.61 (s, 3H); 3.27-3. 24 (m, 1H) ; 3.18-3. 06 (m, 1H) ; 2.91-2. 89 (m, 2H); 2.86-2. 78 (m, 1H) ; 2.68-2. 56 (m, 1H); 2.52-2. 44 (m, 1H); 2.33-2. 12 (m, 2H); 2.32 (s, 3H); 2.31 (s, 3H); 2.14 (s, 3H); 2.04 (s, 3H); 1.53 (s, 9H). 3C-NMR (75 MHz, CDCl3) : 8 172.6, 151.4, 148.1, 145.4, 144.6, 144.4, 144.2, 141.5, 140.0, 131.4, 131.3, 129.4, 127.3, 126.1, 124.4, 122.1, 116.0, 114.2, 110.0, 101.8, 83.2, 82.0, 65.1, 61.4, 60.2, 57.9, 56.3, 56.1, 55.3, 42.4, 41.3, 39.8, 32.1, 30.6, 29.9, 29.5, 29.0, 27.8, 24.1, 22.8, 20.3, 15.5, 14.2, 9.8.

ESI-MS m/z: Calcd. for C44H5lN3013S : 861.2 Found (M-H20+H+) : 844.2.

Example 85 Compound 36 (11%) was recovered after chromatographic purification.

98 was obtained using Method H 1H-NMR (300 MHz, CDC13) : 8 d 6.77 (s, 1H), 6.47 (s, 1H), 6.42 (s, 1H), 5.98 (dd, 2H), 5.40 (bp, 1H), 5.13 (d, 1H), 4.81 (s, 1H), 4.49 (bs, 1H), 4.37 (bp, 1H), 4.11 (d, 1H), 4.03 (dd, 1H), 3.91 (s, 3H), 3.82 (s, 3H), 3.60 (s, 3H), 3.58-3. 56 (m, 1H), 3.23-3. 21 (m, 1H), 3.16-3. 09 (m, 1H), 2.95-2. 79 (m, 3H), 2.67-2. 57 (m, 1H), 2.50-2. 45 (m, 1H), 2.34-2. 13 (m, 2H), 2.28 (s, 3H), 2.23 (s, 3H), 2.17 (s, 3H), 2.03 (s, 3H).

13C-NMR (75 MHz, CDCl3) : 5 172.5, 168.1, 151.6, 148.5, 145.1, 144.4, 144.2, 141.2, 140.5, 131.2, 131.0, 129.1, 126.0, 124.5, 124.2, 122.0, 115.9, 114.0, 109.8, 101.6, 81.7, 64.8, 61.1, 60.0, 59.4, 57.8, 57.7, 56.0, 55.1, 55.1, 42.2, 42.2, 41.5, 39.6, 28.8, 24.1, 20.2, 15.8, 9.6.

ESI-MS m/z: Calcd. for C4oH4sN3OlS : 775.8 Found (M-H20+H+) : 758.7.

Example 86 99 was obtained using Method H lH-NMR (300 MHz, CDCl3) : 8 7.18 (dd, 1H); 7.08 (dd, 1H) ; 7.04 (dd, 1H) ; 6.87 (s, 1H) ; 6.73 (s, 1H) ; 6.31 (s, 1H) ; 6.04 (d, 1H) ; 5.91 (d, 1H) ; 5.01 (dd, 1H) ; 4.99 (dd, 1H) ; 4.92 (d, 1H) ; 4.83 (s, 1H) ; 4.75 (d, 1H); 4.69-4. 63 (m, 2H); 4.45-4. 42 (m, 2H); 4.01-3. 96 (m, 2H); 3.84 (s, 3H); 3.81-3. 89 (m, 1H) ; 3.60-3. 57 (m, 1H) ; 3.55 (s, 3H); 3.37-3. 25 (m, 2H); 2.90-2. 87 (m, 2H); 2.77-2. 67 (m, 1H); 2.53-2. 28 (m, 3H); 2.41 (s, 3H); 2.23 (s, 3H); 2.12 (s, 3H); 2.03 (s, 3H).

ESI-MS m/z: Calcd. for C48H49N3017S : 971.2 Found (M-H20+H+) : 954.3.

Example 87 100 was obtained using Method H lH-NMR (300 MHz, CDCIs) : 8 7.08 (dd, 1H) ; 7.04 (dd, 1H) ; 6.72 (s, 1H) ; 6.49 (s, 1H) ; 6.34 (s, 1H) ; 6.04 (s, 1H) ; 5.91 (s, 1H) ; 5.73 (s, 1H) ; 5.00 (dd, 1H) ; 4.93 (dd, 1H) ; 4.83 (s, 1H) ; 4.73 (d, 1H) ; 4.64 (dd, 1H) ; 4.51 (s, 1H) ; 4.44-4. 40 (m, 2H); 4.14 (d, 1H) ; 4.07-4. 01 (m, 1H) ; 3.96 (dd, 1H) ; 3.81 (s, 3H); 3.58-3. 49 (m, 2H); 3.55 (s, 3H); 3.35-3. 20 (m, 2H); 2.81 (d, 2H); 2.76-2. 66 (m, 1H) ; 2.56-2. 46 (m, 2H); 2.33 (s, 3H); 2.22 (s, 3H); 2.14 (s, 3H); 2.01 (s, 3H).

ESI-MS m/z: Calcd. for C45H47N3015S : 901.9 Found (M-H20+H+) : 884.2.

Example 88 Compound 52 (19%) was recovered after chromatographic purification.

101 was obtained using Method H 1H-NMR (300 MHz, CDCIs) : 8 6.48 (s, 1H); 6.44 (s, 1H) ; 6.03 (d, 1H) ; 5.93 (d, 1H) ; 5.39 (s, 1H) ; 5.01 (d, 1H) ; 4.72 (s, 1H); 4.41-4. 39 (m, 2H); 4.11-3. 99 (m, 3H); 4.10 (s, 3H); 3.64-3. 61 (m, 1H); 3.61 (s, 3H); 3.26-3. 06 (m, 3H); 2.81-2. 29 (m, 8H); 2.23 (s, 3H); 2.18 (s, 3H); 2.05 (s, 3H); 2.03 (s, 3H).

ESI-MS m/z: Calcd. for C39H4lN3012S : 775.2 Found (M +Na+) : 798.2.

Example 89 102 was obtained using Method H. 1H-NMR (300 MHz, CDCIs) : 5 6.77 (s, 1H), 6.46 (s, 1H), 6.44 (s, 1H), 6.01 (d, 1H), 5.94 (d, 1H) ; 5.13 (d, 1H), 4.89- 4.80 (m, 1H) ; 4.80 (s, 1H), 4.48 (d, 1H) ; 4.42 (s, 1H), 4.21 (d, 1H), 4.05 (dd, 1H), 3.81 (s, 3H), 3.61 (s, 3H), 3.55 (d, 1H), 3.20 (s, 1H), 3.16-3. 08 (m, 1H), 2.89-2. 86 (m, 2H), 2.80-2. 76 (m, 1H), 2.64-2. 47 (m, 2H); 2.32-2. 12 (m, 2H); 2.28 (s, 3H), 2.25 (s, 3H), 2.20 (s, 3H), 2.03 (s, 3H); 1.45 (d, 3H); 1.14 (d, 3H).

3C-NMR (75 MHz, CDC13) : 8 172.7, 168.5, 149.3, 148.8, 145.2, 144.6, 144.4, 141.3, 140.7, 135.8, 131.1, 129.2, 128.6, 126.3, 124.3, 116.1, 114.2, 109.9, 101.8, 81.9, 73.3, 64.9, 61.2, 59.1, 58.2, 58.1, 56.2, 55.3, 42.2, 42.1, 41.7, 39.6, 31.8, 29.9, 29.0, 24.2, 23.8, 22.8, 20.5, 16.0, 14.3, 9.8.

ESI-MS m/z: Calcd. for C42H49N3011S : 803.4 Found (M +H+) : 804.4.

Example 90 Method I : To a solution of 1 equiv. of compound 3 in THF/H20 4.5 : 0.5 (0.0052M) were added 5 equiv. of CuBr. After 24 h the reaction was quenched with NaHCOs, diluted and extracted with CH2Cl2. The organic layer was dried with Na2SO4. Chromatography gives pure compound 104 (50%).

104 was obtained using Method I 1H-NMR (300 MHz, CDCIs) : 8 6.47 (s, 2H); 6.45 (s, 1H) ; 5.98 (dd, 2H); 5.68 (s, 1H) ; 4.87 (s, 1H) ; 4.77 (d, 1H) ; 4.57 (s, 1H) ; 4.45 (d, 1H) ; 4.15 (d, 1H) ; 4.05 (dd, 1H) ; 3.79 (s, 3H); 3.64 (d, 1H) ; 3.58 (s, 3H); 3.25-3. 20 (m, 2H); 2.80-2. 82 (m, 3H); 2.67-2. 63 (m, 2H); 2.52-2. 44 (m, 1H); 2.32-2. 12 (m, 2H); 2.31 (s, 3H); 2.24 (s, 3H); 2.12 (s, 3H); 2.02 (s, 3H).

13C-NMR (75 MHz, CDC13) : 8 172.0, 168.9, 148.3, 147.6, 145.1, 141.2, 140.4, 139.1, 138.4, 131.4, 130.8, 128.7, 128.6, 122.9, 122.3, 121.6, 120.9, 120.6, 115.8, 111.7, 101.6, 82.0, 64.9, 61.4, 60.3, 57.8, 57.6, 55.9, 55.0, 54.9, 42.1, 41.3, 39.5, 29.6, 24.0, 20.5, 15.7, 9.6.

ESI-MS m/z: Calcd. for C41H42F3N3012S : 857.8 Found (M-H20+H+) : 840.2.

Example 91 To a solution of compound 4 in THF/H20 3: 1 (0.027M) were added 15 equiv. of KOH. The reaction mixture was stirred at room temperature for 5 h.

After this time the reaction was quenched with NaCI or diluted aqueous solution of HCI, extracted with CH2C12. The organic layer was dried with Na2SO4. Chromatography gives pure compound 106.

106. 1H-NMR (300 MHz, CDCIs) : 8 6.70 (s, 1H); 6.61 (s, 1H); 6.53 (s, 1H); 5.92 (dd, 2H); 5.84 (s, 1H) ; 5.41 (s, 1H) ; 4.97 (d, 1H) ; 4.48 (d, 1H) ; 4.34 (s, 1H) ; 4.31 (dd, 1H) ; 4.16 (d 1H) ; 4.03 (dd, 1H) ; 3.80 (s, 3H); 3.59 (d, 1H) ; 3.55 (s, 3H); 3.43-3. 40 (m, 1H); 3.18-3. 08 (m, 1H); 2.95-2. 93 (m, 2H); 2.81-2. 75 (m, 1H) ; 2.69-2. 58 (m, 1H) ; 2.45-2. 24 (m, 2H); 2.34 (s, 3H); 2.19 (s, 3H); 2.15 (s, 3H); 1.50 (s, 9H).

13C-NMR (75 MHz, CDCIs) : 8 171.7, 148.6, 148.0, 146.2, 146.0, 143.1, 139.0, 136.1, 132.4, 130.7, 129.4, 128.7, 122.4, 122.7, 118.2, 118.1, 113.1, 111.6, 101.2, 83.5, 64.4, 60.9, 60.7, 60.4, 59.8, 59.3, 55.2, 54.7, 54.6, 51.7, 43.1, 41.5, 39.5, 30.1, 29.8, 29.7, 28.6, 27.6, 25.5, 24.2, 15.9, 8.7.

ESI-MS m/z: Calcd. for C43H48N4011S : 828.9 Found (M+H+) : 829.3.

Example 92 Method A: To a solution of 1 equiv. of compound 106 in CH2C12 (0.032M) under Argon were added 2 equiv. of the anhydride and 2 equiv. of pyridine.

The reaction was followed by TLC and quenched with NaHCOs, extracted with CH2Cl2 and the organic layers dried with Na2SO4. Flash chromatography gives pure compounds.

106 107 107 was obtained using Method A. 1H-NMR (300 MHz, CDCIs) : 8 6.70 (s, 1H) ; 6.59 (s, 1H) ; 6.58 (s, 1H) ; 6.04 (dd, 2H); 5.69 (s, 1H) ; 5.02 (d, 1H) ; 4.58 (s, 1H) ; 4.34 (s, 1H) ; 4.29 (dd, 1H) ; 4.21 (d 1H) ; 4.13 (dd, 1H) ; 3.76 (s, 3H); 3.59 (s, 3H); 3.50 (dd, 1H) ; 3.44-3. 41 (m, 1H) ; 3.19-3. 10 (m, 1H) ; 2.94 (d, 2H); 2.81-2. 73 (m, 1H) ; 2.69-2. 58 (m, 1H) ; 2.54-2. 46 (m, 1H) ; 2.34-2. 04 (m, 2H); 2.31 (s, 3H); 2.20 (s, 3H); 2.06 (s, 3H); 1.50 (s, 9H).

13C-NMR (75 MHz, CDCIs) : 8 172.0, 168.0, 157.9, 151.7, 149.0, 148.2, 145.8, 143.4, 141.4, 139.4, 130.7, 122.7, 120.7, 118.1, 117.8, 114.7, 113. 1, 112.0, 102.5, 97.6, 83.7, 64.7, 61.3, 60.4, 60.0, 59.4, 55.7, 54.8, 54.6, 41.8, 41.7, 39.6, 32.1, 29.9, 29.5, 27.8, 24.1, 20.8, 16.0, 14.3, 9.4.

ESI-MS m/z: Calcd. for C4sH47F3N4Ol2S : 924.3 Found (M+H+) : 925.3.

Example 93 108 was obtained using Method A. 1H-NMR (300 MHz, CDC13) : 8 6.69 (s, 1H) ; 6.60 (s, 1H) ; 6.58 (s, 1H) ; 6.03 (d, 1H) ; 5.96 (d, 1H) ; 5.69 (s, 1H) ; 5.00 (d, 1H); 4.68 (s, 1H); 4.29-4. 27 (m, 2H); 4.16-4. 09 (m, 2H); 3.78 (s, 3H); 3.59 (s, 3H); 3.50 (d, 1H) ; 3.41 (s, 1H) ; 3.15-3. 06 (m, 1H) ; 2.98-2. 94 (m, 2H); 2.80- 2.74 (m, 1H) ; 2.69-2. 59 (m, 1H) ; 2.50-2. 45 (m, 1H) ; 2.37-2. 21 (m, 2H); 2.31 (s, 3H); 2.18 (s, 3H); 2.08 (s, 3H); 1.51 (s, 9H); 1.47 (s, 9H).

ESI-MS m/z: Calcd. for C48H56N4013S : 928.4 Found (M+H+) : 929.3.

Example 94 106 109 If the acylation reaction of compound 106 is performed with TEA (10 equiv.) as base instead of pyridine compound 109 is obtained (Method A).

109. 1H-NMR (300 MHz, CDC13) : 8 6.89 (s, 1H); 6.72 (s, 1H); 6.18 (s, 1H); 6.16 (d, 1H) ; 6.04 (d, 1H) ; 4.76 (d, 1H) ; 4.54 (s, 1H) ; 4.41 (s, 1H) ; 4.12 (d, 1H) ; 4.08 (dd, 1H) ; 3.79-3. 70 (m, 2H); 3.77 (s, 3H); 3.57 (d, 1H) ; 3.55 (s, 3H); 3.47 (d, 1H) ; 3.29 (d, 1H) ; 2.97 (d, 2H); 2.73-2. 68 (m, 2H); 2.54 (d, 1H) ; 2.26 (s, 3H); 2.24-2. 12 (m, 1H); 2.08 (s, 3H); 2.05 (s, 3H); 1.51 (s, 9H).

13C-NMR (75 MHz, CDC13) : 8 167.0, 151.5, 149.8, 147.4, 146.2, 142.1, 141.9, 139.8, 139.7, 132.8, 132.6, 131.1, 129.2, 126.7, 123.3, 122.7, 121.5, 117.9, 114.4, 112.4, 111.3, 102.8, 84.1, 71.5, 62.0, 60.6, 60.3, 59.6, 55.4, 54.5, 42.7, 42.2, 41.8, 39.0, 29.0, 27.7, 24.4, 15.8, 9.6.

ESI-MS m/z: Calcd. for C47H46F6N4013S : 1020.2 Found (M+H+) : 1021.3.

Example 95 106 110 The reaction is performed with 6 equiv. of anhydride and 9 equiv. of base (Method A). Traces of compound 110 is also obtained when the acylation reaction is performed with pyridine as base and compound 108 is the main product.

110. 1H-NMR (300 MHz, CDCIs) : 8 6.92 (s, 1H); 6.69 (s, 1H); 6.58 (s, 1H); 6.03 (d, 1H) ; 5.96 (d, 1H) ; 4.99 (d, 1H) ; 4.64 (s, 1H) ; 4.27 (s, 2H); 4.13 (s, 1H); 4.12 (dd, 1H); 3.97 (d, 1H); 3.80 (s, 3H); 3.59 (s, 3H); 3.53 (d, 1H); 3.43-3. 41 (m, 1H) ; 3.15-3. 05 (m, 1H) ; 2.97-2. 95 (m, 2H); 2.80-2. 74 (m, 1H) ; 2.70-2. 60 (m, 1H) ; 2.50-2. 45 (m, 1H) ; 2.37-2. 18 (m, 1H) ; 2.31 (s, 3H); 2.17 (s, 3H); 2.09 (s, 3H); 1.53 (s, 9H); 1.51 (s, 9H); 1.48 (s, 9H).

ESI-MS m/z: Calcd. for C53H64N4015S : 1028.4 Found (M+H+) : 1029.3.

Example 96 Method B: To a solution of 1 equiv. of compound 106 in CH2Cl2 (0.032M) under Argon at room temperature were added 2 equiv. of base and 2 equiv. of the acid chloride. The reaction was followed by TLC and quenched with NaHC03, extracted with CHsCb and the organic layers dried with Na2SO4.

Flash chromatography gives pure compounds.

106 111 111 was obtained using Method B. 1H-NMR (300 MHz, CDCI3) : 8 6.68 (s, 1H) ; 6.58 (s, 1H) ; 6.56 (s, 1H) ; 6.00 (dd, 2H); 5.67 (s, 1H) ; 5.00 (d, 1H) ; 4.58 (s, 1H) ; 4.36 (s, 1H) ; 4.27 (dd, 1H) ; 4.19 (d 1H) ; 4.12 (dd, 1H) ; 3.77 (s, 3H); 3.59 (s, 3H); 3. 51 (d, 1H) ; 3.43-3. 40 (m, 1H) ; 3.17-3. 08 (m, 1H) ; 2.92 (d, 2H); 2.86-2. 78 (m, 1H) ; 2.72-2. 60 (m, 1H) ; 2.52-2. 44 (m, 1H) ; 2.50 (t, 2H); 2.34- 2.04 (m, 2H); 2.32 (s, 3H); 2.18 (s, 3H); 2.01 (s, 3H); 1.82-1. 67 (m, 2H); 1.50 (s, 9H); 1.00 (t, 3H).

ESI-MS m/z: Calcd. for C47H54N4012S : 898.3 Found (M+H+) : 899.3.

Example 97 Compound 111 is also isolated as minor compound in these reaction conditions (10 equiv. of butyryl chloride and 10 equiv. of TEA).

112 was obtained using Method B. 1H-NMR (300 MHz, CDCIs) : 8 6.93 (s, 1H) ; 6.69 (s, 1H) ; 6.54 (s, 1H) ; 6.05 (s, 1H) ; 5.97 (s, 1H) ; 4.99 (d, 1H) ; 4.54 (s, 1H) ; 4.32 (s, 1H) ; 4.16 (d, 1H) ; 4.07 (dd, 1H) ; 3.79 (d, 1H) ; 3.74 (s, 3H); 3.69- 3.31 (m, 1H) ; 3.58 (s, 3H); 3.52 (d, 1H) ; 3.43 (s, 1H) ; 3.18-3. 08 (m, 1H) ; 2.98 (d, 2H); 2.85-2. 79 (m, 1H) ; 2.68-2. 44 (m, 2H); 2.60 (t, 2H); 2.55 (t, 2H); 2.31 (s, 3H); 2.14 (s, 3H); 2.02 (s, 3H); 1.89-1. 74 (m, 4H); 1.50 (s, 9H); 1.08 (t, 3H); 1.01 (t, 3H).

13C-NMR (75 MHz, CDCIs) : 8 172.1, 171.3, 151.8, 148.8, 148.2, 145.7, 143.9, 141.5, 140.3, 139.1, 132.4, 131.7, 130.9, 128.8, 127.4, 124.6, 122.4, 120.8, 119.9, 118.1, 114.0, 112.0, 105.0, 102.2, 83.7, 61.2, 60.3, 59.9, 59.6, 56.1, 55.4, 54.5, 42.6, 42.2, 41.8, 39.8, 36.3, 36.0, 29.9, 28.7, 27.8, 24.3, 18.9, 18.5, 16.0, 14.1, 14.0, 10.0.

ESI-MS m/z: Calcd. for C5lH6oN4013S : 968.3 Found (M+H+) : 969.3.

Example 98 106 113 113 was obtained using Method B. lH-NMR (300 MHz, CDC13) : 8 7.88 (d, 1H) ; 7.62-7. 58 (m, 2H); 7.47-7. 44 (m, 3H); 6.70 (s, 1H) ; 6.59 (d, 1H) ; 6.58 (s, 1H) ; 6.54 (s, 1H) ; 6.03 (dd, 2H); 5.42 (s, 1H) ; 5.01 (d, 1H) ; 4.58 (s, 1H) ; 4.36 (s, 1H) ; 4.26 (dd, 1H) ; 4.19 (d 1H) ; 4.12 (dd, 1H) ; 3.61 (s, 3H); 3.55 (d, 1H) ; 3.46 (s, 3H); 3.43-3. 40 (m, 1H); 3.16-3. 08 (m, 1H); 2.92 (d, 2H); 2. 86-2. 78 (m, 1H); 2.72-2. 60 (m, 1H); 2.52-2. 44 (m, 1H); 2.34-2. 04 (m, 2H); 2.47 (s, 3H); 2.17 (s, 3H); 2.08 (s, 3H); 1.50 (s, 9H).

13C-NMR (75 MHz, CDCls) : 8 172.2, 151.8, 148.8, 147.9, 145.6, 143.2, 141.3, 141.6, 140.4, 139.1, 134.4, 132.6, 131.0, 129.6, 129.3, 129.1, 128.8, 128.4, 122.4, 121.5, 120.7, 118.3, 118.1, 116.8, 114.3, 112.1, 102.1, 83.6, 65.2, 61.4, 60.2, 59.9, 59.5, 55.4, 54.8, 54.7, 42.4, 42.3, 41.8, 39.8, 29.9, 28.7, 27.8, 24.3, 15.9, 10.0.

ESI-MS m/z: Calcd. for C52H54N4012S : 958.3 Found: (M+H+) : 959.3.

Example 99 106 114 114 was obtained using Method B. 1H-NMR (300 MHz, CDCIs) : 8 7.85 (d, 2H); 7.55-7. 21 (m, 10H) ; 6.93 (s, 1H) ; 6.73 (s, 1H) ; 6.70-6. 50 (m, 2H); 6.56 (s, 1H) ; 6.09 (s, 1H) ; 5.99 (s, 1H) ; 5.03 (d, 1H) ; 4.53 (s, 1H) ; 4.39 (s, 1H) ; 4.21 (d, 1H) ; 4.11 (dd 1H) ; 3.91 (d, 1H) ; 3.61 (s, 3H); 3.45 (s, 3H); 3.20-3. 11 (m, 1H); 2.99 (d, 2H); 2.74-2. 65 (m, 1H); 2.53-2. 47 (m, 1H); 2.28 (s, 3H); 2. 17 (s, 3H); 2.11 (s, 3H); 1.52 (s, 9H).

13C-NMR (75 MHz, CDC13) : 8 172.1, 164.7, 164.3, 151.8, 148.8, 148.4, 147.5, 147.4, 145.9, 143.5, 141.5, 140.6, 139.1, 134.3, 133.9, 132.4, 131. 7, 131.2, 131.0, 130.9, 129.2, 129.1, 128.9, 128.5, 128.3, 127.3, 124.5, 122.5, 121.3, 118.0, 116.6, 116.2, 114.3, 112.0, 102.2, 83.7, 65.4, 61.4, 60.2, 59.7, 59.2, 55.7, 55.3, 54.6, 42.7, 41.8, 39.9, 32.1, 31.8, 29.9, 29.6, 28.8, 27.8, 22.8, 16.0, 14.3, 10.1.

ESI-MS m/z: Calcd. for C61H6oN4013S : 1088.3 Found (M+H+): 1089.4.

Example 100 115 was obtained using Method B. 1H-NMR (300 MHz, CDCIs) : 8 6.69 (s, 1H) ; 6.58 (s, 2H); 6.04 (d, 1H) ; 5.99 (d, 1H) ; 5.96-5. 85 (m, 1H) ; 5.71 (s, 1H) ; 5.38 (dd, 1H) ; 5.27 (dd, 1H) ; 5.00 (d, 1H) ; 4.67 (s, 1H) ; 4.64-4. 61 (m, 2H); 4.30 (s, 1H) ; 4.28 (dd, 1H) ; 4.17 (d, 1H) ; 4.11 (dd, 1H) ; 3.77 (s, 3H); 3.58 (s, 3H); 3.50 (d, 1H); 3.41 (s, 1H); 3.16-3. 08 (m, 1H); 2.93 (d, 2H); 2.81-2. 74 (m, 1H); 2.69-2. 59 (m, 1H); 2.51-2. 45 (m, 1H); 2.39 (d, 1H); 2.31 (s, 3H); 2.21- 2.16 (m, 1H); 2.19 (s, 3H); 2.09 (s, 3H); 1.50 (s, 9H).

13C-NMR (75 MHz, CDC13) : 5 172.3, 15.5, 151.8, 148.7, 148.1, 145.6, 143.2, 141.4, 140.5, 139.1, 132.7, 131.4, 130.9, 129.5, 128.8, 122.5, 121.5, 120. 7, 119.1, 118.3, 118.2, 114.2, 113.5, 112.0, 102.2, 83.7, 69.4, 64.9, 61.3, 60.5, 60.2, 59.8, 55.4, 54.9, 54.8, 42.6, 41.8, 41.7, 39.7, 29.9, 28.8, 27.8, 24.3, 16.0, 9.5.

ESI-MS m/z: Calcd. for C47H52N4013S : 912.3 Found (M+H+) : 913.3.

Example 101 106 116 116 was obtained using Method B. 1H-NMR (300 MHz, CDCl3) : 5 6.69 (s, 1H) ; 6.58 (s, 1H) ; 6.56 (s, 1H) ; 6.05 (d, 1H) ; 5.98 (d, 1H) ; 5.74 (s, 1H) ; 5.00 (d, 1H) ; 4.52 (s, 1H) ; 4.32 (s, 1H) ; 4.27 (d, 1H) ; 4.17 (d, 1H) ; 4.09 (dd, 1H) ; 3.84 (ddd, 2H); 3.79 (s, 3H); 3.58 (s, 3H); 3. 50 (d, 1H) ; 3.41 (s, 1H) ; 3.12-3. 02 (m, 1H) ; 3.04 (t, 2H); 2.93 (d, 2H); 2.81-2. 75 (m, 1H) ; 2.69-2. 58 (m, 1H) ; 2.50-2. 44 (m, 1H); 2.31 (s, 3H); 2.18 (s, 3H); 2.04 (s, 3H); 1.50 (s, 9H).

ESI-MS m/z: Calcd. for C46H51CIN4012S : 918.3 Found (M+H+) : 919.7.

Example 102 106 117 117 was obtained using Method B. 1H-NMR (300 MHz, CDC13) : 8 6.70 (s, 1H) ; 6.58 (s, 1H) ; 6.54 (s, 1H) ; 6.11 (d, 1H) ; 6.04 (d, 1H) ; 5.67 (s, 1H) ; 5.02 (d, 1H) ; 4.46 (s, 1H) ; 4.33 (s, 2H); 4.29 (d, 1H) ; 4.20 (s, 1H) ; 4.11 (dd, 1H) ; 3.73 (s, 3H); 3.58 (s, 3H); 3.51 (d, 1H) ; 3.44 (s, 1H) ; 3.21-3. 11 (m, 1H) ; 3.05- 2.93 (m, 2H); 2.84-2. 78 (m, 1H) ; 2.68-2. 60 (m, 1H) ; 2.52-2. 47 (m, 1H) ; 2.35 (s, 3H); 2.20 (s, 2H); 2.14 (s, 3H); 2.04 (s, 3H); 1.50 (s, 9H).

ESI-MS m/z: Calcd. for C47H47F7N4012S : 1024.3 Found (M+H+) : 1025.2.

Example 103 106 118 118 was obtained using Method B 1H-NMR (300 MHz, CDCIs) : 8 6.98 (dd, 1H) ; 6.70 (s, 1H) ; 6.59 (s, 1H) ; 6.58 (s, 1H) ; 6.06 (d, 1H) ; 5.99 (d, 1H) ; 5.74 (s, 1H) ; 5.01 (d, 1H) ; 4.98 (dd, 1H) ; 4.65 (s, 1H) ; 4.60 (dd, 1H) ; 4.31 (s, 2H); 4.28 (d, 1H) ; 4.18 (s, 1H) ; 4.12 (dd, 1H) ; 3.75 (s, 3H); 3.58 (s, 3H); 3.50 (d, 1H) ; 3.41 (s, 1H); 3.18-3. 10 (m, 1H); 2.93 (d, 2H); 2.81-2. 74 (m, 1H); 2.68-2. 58 (m, 1H) ; 2.51-2. 46 (m, 1H) ; 2.38 (d, 1H) ; 2.31 (s, 3H); 2.20 (s, 3H); 2.10 (s, 3H); 1.50 (s, 9H).

ESI-MS m/z: Calcd. for C46H5oN4013S : 898.3 Found (M+H+) : 899.3.

Example 104 Method C: To a solution of 1 equiv. of compound 106 in CH2C12 (0.032M) under Argon were added 2 equiv. of acid, 2 equiv. of DMAP and 2 equiv. of EDC. HCI. The reaction was stirred at room temperature for 2 h. After this time was diluted with CH2Cl2, washed with brine and the organic layer dried with Na2SO4. Flash chromatography gives pure compounds.

106 119 119 was obtained using Method C. 1H-NMR (300 MHz, CDCIs) : 8 6.68 (s, 1H) ; 6.58 (s, 1H) ; 6.56 (s, 1H) ; 6.00 (dd, 2H); 5.66 (s, 1H) ; 4.99 (d, 1H) ; 4.53 (s, 1H) ; 4.31 (s, 1H) ; 4.26 (dd, 1H) ; 4.16 (d, 1H) ; 4.09 (dd, 1H) ; 3.77 (s, 3H); 3.57 (s, 3H); 3.51 (d, 1H); 3.42-3. 40 (m, 1H); 3.16-3. 05 (m, 1H); 2.93 (d, 2H); 2.82-2. 74 (m, 1H); 2.69-2. 58 (m, 1H); 2.51-2. 44 (m, 1H); 2.53 (t, 2H); 2.34- 2.14 (m, 2H); 2.31 (s, 3H); 2.18 (s, 3H); 2.01 (s, 3H); 1.75-1. 70 (m, 2H); 1.50 (s, 9H); 1.35-1. 25 (m, 11H).

13C-NMR (75 MHz, CDCIs) : 8 172.0, 170.8, 151.5, 148.5, 147.7, 145.3, 143.0, 141.4, 141.3, 140.0, 138.9, 132.4, 130.8, 129.2, 128.6, 122.1, 121. 0, 120.6, 118.2, 118.0, 113.9, 111.9, 101.9, 83.3, 64.8, 61.0, 60.2, 60.1, 59.7, 59.6, 55.2, 54.7, 54.6, 42.3, 41.8, 41.5, 39.6, 33.9, 31.6, 29.6, 29.3, 28.9, 28.6, 27.5, 24.8, 24.2, 22.5, 15.7, 14.0, 9.7.

ESI-MS m/z: Calcd. for C5lH62N4012S : 954.4 Found (M+H+) : 955.5.

Example 105 106 120 120 is obtained with 10 equiv. of each reagent (Method C).

1H-NMR (300 MHz, CDCIs) : 8 6.93 (s, 1H) ; 6.69 (s, 1H) ; 6.54 (s, 1H) ; 6.00 (dd, 2H); 4.99 (d, 1H) ; 4.44 (s, 1H) ; 4.31 (s, 1H) ; 4.16 (d, 1H) ; 4.09 (dd, 1H) ; 3.86 (d, 1H) ; 3.73 (s, 3H); 3.57 (s, 3H); 3.50 (d, 1H) ; 3.44-3. 42 (m, 1H) ; 3.16-3. 05 (m, 1H) ; 2.97 (d, 2H); 2.84-2. 79 (m, 1H) ; 2.64-2. 44 (m, 6H); 2.35-2. 15 (m, 2H); 2.31 (s, 3H); 2.14 (s, 3H); 2.02 (s, 3H); 1.94-1. 58 (m, 8H); 1.50 (s, 9H); 1.38-1. 18 (m, 18H).

13C-NMR (75 MHz, CDCI3) : 8 172.2, 171.4 170.8, 151.8, 148.8, 148.2, 145.7, 143.9, 141.5, 140.4, 139.1, 132.5, 131.6, 130.8, 128.8, 127.4, 124.7, 122.4, 120.9 118.0, 114.1, 112.1, 102.2, 83.6, 65.1, 61.3, 60.3, 60.2, 59.9, 59.5, 56.1, 55.4, 54.6, 42.6, 42.2, 41.8, 39.8, 34.4, 34.1, 31.8, 29.6, 29.5, 29.2, 29.1, 29.0, 28.8, 27.8, 25.4, 24.9, 22.8, 16.0, 14.2, 9.9.

ESI-MS m/z: Calcd. for C59H76N4013S : 1080.5 Found (M+H+) : 1081.3.

Example 106 It was used 1 equiv. of palmitic acid (Method C).

121 : 1H-NMR (300 MHz, CDC13) : 8 6.68 (s, 1H); 6.58 (s, 1H); 6.56 (s, 1H); 6.00 (dd, 2H); 5.66 (s, 1H) ; 4.99 (d, 1H) ; 4.53 (s, 1H) ; 4.31 (s, 1H) ; 4.26 (dd, 1H) ; 4.16 (d, 1H) ; 4.09 (dd, 1H) ; 3.77 (s, 3H); 3.58 (s, 3H); 3.51 (d, 1H) ; 3.42- 3.40 (m, 1H) ; 3.16-3. 08 (m, 1H) ; 2.93 (d, 2H); 2.84-2. 76 (m, 1H) ; 2.69-2. 44 (m, 2H); 2.53 (t, 2H); 2.35-2. 15 (m, 2H); 2.31 (s, 3H); 2.18 (s, 3H); 2.01 (s, 3H); 1.74-1. 69 (m, 2H); 1.50 (s, 9H); 1.38-1. 10 (m, 27H).

13C-NMR (75 MHz, CDC13) : 8 172.0, 171.8, 148.4, 148.0, 145.5, 143.2, 141.6, 140.2, 139.1, 137.4, 132.6, 131.0, 129.5, 128.8, 122.4, 121.2, 120.9, 118.3, 114.2, 112.1, 102.0, 65.1, 61.3, 60.5, 60.3, 59.9, 59.8, 55.4, 54.9, 54.8, 42.5, 42.0, 41.8, 39.8, 34.2, 32.1, 29.9, 29.7, 29.6, 29.5, 28.8, 27.8, 25.1, 24.4, 22.8, 16.0, 14.3, 9.9.

ESI-MS m/z: Calcd. for C59H78N4012S : 1066.5 Found (M+H+) : 1067.4.

122: 1H-NMR (300 MHz, CDC13) : 8 6.94 (s, 1H) ; 6.70 (s, 1H); 6.55 (s, 1H); 6.02 (dd, 2H); 5.00 (d, 1H); 4.46 (s, 1H); 4.33 (s, 1H); 4.18 (d, 1H); 4.09 (dd, 1H) ; 3.79 (d, 1H) ; 3.74 (s, 3H); 3.58 (s, 3H); 3.52 (d, 1H) ; 3.46-3. 43 (m, 1H) ; 3.15-3. 05 (m, 1H) ; 2.99-2. 97 (m, 2H); 2.68-2. 45 (m, 7H); 2.36-2. 11 (m, 2H); 2.32 (s, 3H); 2.15 (s, 3H); 2.03 (s, 3H); 1.86-1. 60 (m, 4H); 1.50 (s, 9H); 1.40- 1.10 (m, 54H).

ESI-MS m/z: Calcd. for C75H1o8N4013S : 1302.7 Found (M+H+) : 1303.6.

Example 107 Compound 124 is isolated impurified with DMAP.

123 was obtained using Method C : 1H-NMR (300 MHz, CDCl3) : 8 7.74 (s, 1H) ; 6.96 (s, 1H) ; 6.69 (s, 1H) ; 6.54 (s, 2H); 6.04 (d, 1H) ; 5.96 (d, 1H) ; 5.09 (s, 1H) ; 5.00 (d, 1H) ; 4.51-4. 48 (m, 2H); 4.34 (s, 2H); 4.30 (d, 1H) ; 4.19 (d, 1H) ; 4.06 (dd, 1H) ; 3.75 (s, 3H); 3.57 (s, 3H); 3.52 (d, 1H); 3.41 (s, 1H); 3.19-3. 08 (m, 2H); 2.92-2. 80 (m, 3H); 2.75-2. 44 (m, 5H); 2.29 (s, 3H); 2.17 (s, 3H); 2.01 (s, 3H); 2.82-1. 66 (m, 6H); 1.50 (s, 9H).

ESI-MS m/z: Calcd. for C53H62N6O13S2 : 1055.2 Found (M+H+) : 1056.3.

124 was obtained using Method C: ESI-MS m/z: Calcd. for C63H76N8015S3 : 1281.5 Found (M+H+) : 1282.4.

Example 108 106 125 125 was obtained using Method C 1H-NMR (300 MHz, CDCIs) : 8 6.69 (s, 1H); 6.55 (s, 2H); 6.05 (d, 1H) ; 5.97 (d, 1H) ; 5.00 (d, 1H) ; 4.61 (t, 1H) ; 4.51 (s, 1H) ; 4.34 (s, 1H) ; 4.27 (d, 1H) ; 4.18 (d, 1H) ; 4.12-4. 06 (m, 2H); 3.76 (s, 3H); 3.57 (s, 3H); 3. 50 (d, 1H) ; 3.42 (s, 1H) ; 3.14-3. 06 (m, 1H) ; 2.92 (d, 1H) ; 2.84-2. 80 (m, 1H); 2.69-2. 60 (m, 1H); 2.50-2. 45 (m, 1H); 2.30 (s, 3H); 2.17 (s, 3H); 2.02 (s, 3H); 1.61 (d, 3H); 1.50 (s, 9H); 1.43 (s, 9H).

ESI-MS m/z: Calcd. for C5lH61N. 5014S : 999.4 Found (M+H+) : 1000.3.

Example 109 Method E: To a solution of 1 equiv. of compound 106 in DMF (0.032M) under Argon at room temperature were added 2 equiv. of Cs2CO3 and 2 equiv. of the alkyl bromide. The reaction was followed by TLC and quenched with NaHC03, extracted with CH2Cl2 and the organic layers dried with Na2SO4. Flash chromatography gives pure compounds.

126: was obtained using Method E lH-NMR (300 MHz, CDC13) : 8 6.70 (s, 1H); 6.58 (s, 2H); 5.97 (d, 1H) ; 5.90 (d, 1H) ; 5.79 (s, 1H) ; 5.00 (d, 1H) ; 4.88 (s, 1H); 4.30-4. 29 (m, 3H); 4.15-4. 11 (m, 2H); 3.85-3. 82 (m, 2H); 3.80 (s, 3H); 3.58 (s, 3H); 3.51 (d, 1H) ; 3.40 (s, 1H) ; 3.12-3. 00 (m, 1H); 2.92 (d, 2H); 2.83- 2.79 (m, 1H) ; 2.67-2. 60 (m, 1H) ; 2.50-2. 44 (m, 1H) ; 2.31 (s, 3H); 2.28-2. 37 (m, 1H); 2.20 (s, 3H); 2.18 (s, 3H); 1.50 (s, 9H).

ESI-MS m/z: Calcd. for C44H5oN4011S : 842.3 Found (M+H+) : 843.4.

127 was obtained using Method E : lH-NMR (300 MHz, CDCIs) : 8 6.75 (s, 1H) ; 6.71 (s, 1H) ; 6.58 (s, 1H) ; 5.98 (s, 1H) ; 5.91 (s, 1H) ; 5.01 (d, 1H) ; 4.81 (s, 1H); 4.29 (s, 1H) ; 4.26 (dd, 1H); 4.15 (s, 1H); 4.13 (dd, 1H); 3.96 (s, 3H); 3.85-3. 74 (m, 1H); 3.83 (s, 3H); 3.74 (s, 3H); 3.58 (s, 3H); 3.50 (d, 1H); 3.41 (s, 1H) ; 3.10-3. 04 (m, 1H) ; 2.93 (d, 2H); 2.85-2. 80 (m, 1H) ; 2.70-2. 59 (m, 1H); 2.51-2. 44 (m, 1H); 2.31-2. 20 (m, 1H); 2.28 (s, 3H); 2.24 (s, 3H); 2.18 (s, 3H); 1.51 (s, 9H).

ESI-MS m/z: Calcd. for C45H52N4O11S : 856.3 Found (M+H+) : 857.3.

Example 110 Compound 106 (15%) is recovered after chromatographic purification.

128: was obtained using Method E. lH-NMR (300 MHz, CDCIs) : 8 6.70 (s, 1H) ; 6.59 (s, 1H) ; 6.58 (s, 1H) ; 5.97 (s, 1H) ; 5.90 (s, 1H) ; 5.75 (s, 1H) ; 5.01 (d, 1H); 4.91 (s, 1H); 4.29 (s, 2H); 4.16 (s, 1H); 4.14 (dd, 1H); 3.82 (q, 2H); 3.80 (s, 3H); 3.58 (s, 3H); 3.50 (d, 1H) ; 3.41 (s, 1H) ; 3.11-3. 03 (m, 1H) ; 2.92 (d, 2H); 2.84-2. 80 (m, 1H) ; 2.70-2. 60 (m, 1H) ; 2.50-2. 45 (m, 1H) ; 2.31 (s, 3H); 2.23 (s, 2H); 2.20 (s, 3H); 2.17 (s, 3H); 1.50 (s, 9H); 1.39 (t, 3H).

ESI-MS m/z: Calcd. for C4sHs2N4011S : 856.3 Found (M+H+) : 857.3.

129 was obtained using Method E : 1H-NMR (300 MHz, CDCIs) : S 6.75 (s, 1H) ; 6.70 (s, 1H) ; 6.58 (s, 1H) ; 5.97 (d, 1H) ; 5.91 (d, 1H) ; 5.00 (d, 1H) ; 4.87 (s, 1H) ; 4.29-4. 26 (m, 2H); 4.1-4. 13 (m, 2H); 3.89-3. 81 (m, 4H); 3.85 (s, 3H); 3.58 (s, 3H); 3.50 (d, 1H); 3.42 (s, 1H); 3. 11-3. 04 (m, 1H) ; 2. 94 (d, 2H); 2. 85- 2.80 (m, 1H) ; 2.70-2. 60 (m, 1H) ; 2.52-2. 44 (m, 1H) ; 2.27 (s, 3H); 2.22 (s, 2H); 2.20 (s, 3H); 2.17 (s, 3H); 1.51 (s, 9H); 1.41 (t, 3H); 1.40 (t, 3H).

13C-NMR (75 MHz, CDC13) : 5 172.0, 151.8, 151.0, 149.6, 149.0, 148.7, 145.8, 139.0, 138.7, 132.6, 131.4, 130.5, 129.0, 124.7, 124.3, 122. 5, 122.0, 118.3, 114.0, 113.2, 111.9, 101.7, 83.7, 69.2, 68.2, 65.6, 61.7, 60.6, 60.3, 59.7, 59.6, 55.3, 54.9, 42.9, 42.1, 41.9, 39.8, 29.9, 28.9, 27.8, 24.5, 16.4, 16.0, 15.6, 9.8.

ESI-MS m/z : Calcd. for C47H56N4011S : 884.3 Found (M+H+): 885.5.

Example 111 Compound 106 (33%) is recovered after chromatographic purification.

130 was obtained using Method E : lH-NMR (300 MHz, CDC1s) : 8 6.70 (s, 1H) ; 6.58 (s, 2H); 5.96 (s, 1H) ; 5.90 (s, 1H) ; 5.68 (s, 1H) ; 5.00 (d, 1H) ; 4.90 (s, 1H) ; 4.29 (s, 2H); 4.15 (s, 1H) ; 4.13 (dd, 1H) ; 3.85-3. 78 (m, 2H); 3.79 (s, 3H); 3.58 (s, 3H); 3. 50 (d, 1H) ; 3.40 (s, 1H) ; 3.12-3. 04 (m, 1H) ; 2.92 (d, 2H); 2.86- 2.80 (m, 1H) ; 2.71-2. 60 (m, 1H) ; 2.50-2. 43 (m, 1H) ; 2.30 (s, 3H); 2.23 (s, 2H); 2.19 (s, 3H); 2.16 (s, 3H); 1.83-1. 76 (m, 2H); 1.50 (s, 9H); 1.06 (t, 3H).

ESI-MS m/z: Calcd. for C46H54N4O11S : 871.3 Found (M+H+) : 872.5.

131 was obtained using Method E : lH-NMR (300 MHz, CDCIs) : 8 6.75 (s, 1H) ; 6.70 (s, 1H) ; 6.58 (s, 1H) ; 5.97 (d, 1H) ; 5.90 (d, 1H) ; 5.00 (d, 1H) ; 4.88 (s, 1H); 4.28-4. 11 (m, 4H); 3.85 (s, 3H); 3.82-3. 64 (m, 4H); 3.58 (s, 3H); 3.51 (d, 1H) ; 3.41 (s, 1H) ; 3.12-3. 05 (m, 1H) ; 2.94 (d, 2H); 2.86-2. 80 (m, 1H) ; 2.74-2. 62 (m, 1H) ; 2.51-2. 46 (m, 1H) ; 2.27 (s, 3H); 2.22 (s, 2H); 2.20 (s, 3H); 2.16 (s, 3H); 1.81-1. 75 (m, 4H); 1.50 (s, 9H); 1.07 (t, 3H); 1.02 (t, 3H).

3C-NMR (75 MHz, CDCIs) : 8 170.9, 150.6, 150.0, 148.3, 147.8, 147.4, 144.6, 137.8, 137.4, 131.4, 130.1, 129.3, 127.8, 123.4, 123.1, 121.3, 120.7, 117.1, 112.7, 112.0, 110.7, 100.4, 82.4, 73.6, 73.3, 64.4, 60.4, 59.5, 59.1, 58.6, 58.5, 54.1, 54.0, 53.6, 41.8, 40.8, 40.7, 38.6, 28.6, 27.7, 26.5, 23.3, 22.9, 22.4, 14.7, 9.9, 9.4, 8.5.

ESI-MS m/z: Calcd. for C49H60N4O11S : 912.4 Found (M+H+) : 913.5.

Example 112 With 1 equiv. of allyl bromide and 1 equiv. of cesium carbonate the reaction is complete and other fraction is isolated after chromatographic purification which is a mixture of compound 131 and compound 132 (Method E).

132 : lH-NMR (300 MHz, CDCIs) : 8 6.70 (s, 1H); 6.58 (s, 2H); 6.15-6. 02 (m, 1H) ; 5.98 (d, 1H) ; 5.91 (d, 1H) ; 5.69 (s, 1H) ; 5.43 (dd, 1H) ; 5.26 (d, 1H) ; 5.01 (d, 1H); 4.91 (s, 1H); 4.48 (dd, 1H); 4.29-4. 28 (m, 2H); 4.23-4. 12 (m, 3H); 3.80 (s, 3H); 3.58 (s, 3H); 3.50 (d, 1H) ; 3.41 (s, 1H) ; 3.12-3. 03 (m, 1H) ; 2.95- 2.91 (m, 2H); 2.88-2. 80 (m, 1H); 2.70-2. 60 (m, 1H); 2.50-2. 45 (m, 1H); 2.31 (s, 3H); 2.24 (s, 2H); 2.20 (s, 3H); 2.18 (s, 3H); 1.51 (s, 9H).

3C-NMR (75 MHz, CDCIs) : 8 172.3, 168.5, 152.0, 149.7, 148.9, 148.2, 146.0, 143.5, 139.3, 139.0, 134.0, 132.8, 131.3, 129.7, 129.3, 129.2, 122.7, 122.2, 121.0, 118.5, 118.4, 117.9, 114.2, 113.4, 112.1, 101.9, 83.9, 74.5, 65.8, 61.8, 60.8, 60.6, 60.0, 55.5, 55.1, 55.1, 43.1, 42.3, 42.0, 40.1, 30.1, 29.1, 28.0, 24.6, 16.2, 14. 5, 10.1.

ESI-MS m/z: Calcd. for C46H52N4011S : 868.3 Found (M+H+) : 869.3.

Compound 133 : lH-NMR (300 MHz, CDC13) : 8 6.77 (s, 1H); 6.70 (s, 1H); 6.58 (s, 1H) ; 6.14-6. 01 (m, 2H); 5.97 (s, 1H) ; 5.91 (s, 1H) 5.43 (dd, 1H) ; 5.37 (dd, 1H) ; 5.23 (dd, 1H) ; 5.19 (dd, 1H) ; 5.00 (d, 1H) ; 4.89 (s, 1H) ; 4.78 (dd, 1H) ; 4.71-4. 36 (m, 2H); 4.28-4. 12 (m, 4H); 3.84 (s, 3H); 3.58 (s, 3H); 3.50 (d, 1H); 3.41 (s, 1H) ; 3.12-3. 03 (m, 1H) ; 2.93 (d, 2H); 2.86-2. 80 (m, 1H) ; 2.72-2. 60 (m, 1H); 2.51-2. 46 (m, 1H); 2.28 (s, 3H); 2.23 (s, 2H); 2.18 (s, 3H); 2.17 (s, 3H); 1.50 (s, 9H).

13C-NMR (75 MHz, CDC13) : 8 172.1, 151.8, 150.8, 149.3, 149.0, 148.7, 145.8, 139.1, 138.8, 134.7, 133.6, 132.5, 131.4, 130.5, 129.0, 124.7, 124. 5, 122. 5, 122.0, 118.3, 118.0, 117.2, 113.9, 113.2, 111.8, 101.7, 83.7, 74.2, 73.3, 65.6, 61.6, 60.5, 60.3, 59.8, 59.7, 55.3, 54.8, 43.0, 42.0, 41.9, 39. 8, 38.9, 27.8, 24.5, 16.0, 9.9.

ESI-MS m/z: Calcd. for C49H56N4011S : 909.1 Found (M+H+) : 910.3.

Example 113 134 was obtained using Method E : 1H-NMR (300 MHz, CDCIs) : 6 7.52-7. 50 (m, 2H); 7.43-7. 37 (m, 3H); 6.70 (s, 1H) ; 6.61 (s, 1H) ; 6.57 (s, 1H) ; 5.97 (dd, 2H); 5.56 (s, 1H); 5.01 (d, 1H); 4.99 (d, 1H); 4.87 (s, 1H); 4.74 (d, 1H); 4.30 (s, 1H) ; 4.20-4. 14 (m, 3H); 3.76 (s, 3H); 3.60 (s, 3H); 3.41 (d, 2H); 3.13-3. 02 (m, 1H); 2.90-2. 88 (m, 2H); 2.88-2. 78 (m, 1H); 2.64-2. 58 (m, 1H); 2.51-2. 44 (m, 1H); 2.34-2. 10 (m, 2H); 2.30 (s, 3H); 2.24 (s, 3H); 2.17 (s, 3H); 1.50 (s, 9H).

3C-NMR (75 MHz, CDCI3) : 8 172.1, 149.0, 148.7, 148.0, 145.9, 139.0, 137.4, 132.6, 131.1, 129.5, 129.1, 128.7, 128.6, 128.3, 128.2, 122.5, 120.8, 118. 3, 118. 2, 114. 1, 113. 4, 112. 0,101. 8,83. 7,74. 8,65. 6,61. 8,60. 6,60. 4, 59.7, 55.4, 54.8, 43.0, 42.2, 41.8, 39.9, 29.9, 29.0, 27.8, 24.4, 16.0, 9.9.

ESI-MS m/z: Calcd. for C5oH54N4011S : 918.3 Found (M+H+) : 919.3.

135 was obtained using Method E: 1H-NMR (300 MHz, CDCIs) : 8 7.47-7. 43 (m, 2H); 7.32-7. 20 (m, 8H); 6.79 (s, 1H) ; 6.71 (s, 1H) ; 6.62 (s, 1H) ; 5.96 (dd, 2H); 5.24 (d, 1H) ; 5.03-4. 93 (m, 4H); 4.68 (d, 1H) ; 4.28 (s, 1H) ; 4.18-4. 08 (m, 3H); 3.87 (s, 3H); 3.60 (s, 3H); 3.43 (d, 1H) ; 3.35-3. 32 (m, 1H) ; 3.15-3. 08 (m, 1H) ; 2.92-2. 91 (m, 2H); 2.88-2. 80 (m, 1H) ; 2.72-2. 60 (m, 1H) ; 2.54-2. 46 (m, 1H) ; 2.32 (s, 3H); 2.23 (s, 3H); 2.22 (d, 1H) ; 2.05 (d, 1H) ; 1.84 (s, 3H); 1.51 (s, 9H).

ESI-MS m/z: Calcd. for C57H6oN4011S : 1008.4 Found (M+H+) : 1009.3.

Example 114 Method F: To a solution of 1 equiv. of starting material in CH2Cl2/H20/TFA 2: 1: 3.3 (0.013M) was stirred at room temperature for 15 min. The reaction was followed by TLC and neutralised with NaHCOs, extracted with CH2C12 and the organic layers dried over Na2SO4. Flash chromatography gives pure compounds.

136 was obtained using Method F. lH-NMR (300 MHz, CDCIs) : 8 6.61 (s, 1H) ; 6.49 (s, 1H) ; 6.39 (s, 1H) ; 5.92 (dd, 2H); 5.69 (s, 1H) ; 4.90 (d, 1H) ; 4.48 (s, 1H) ; 4.34 (s, 1H) ; 4.31 (dd, 1H) ; 4.16 (d, 1H) ; 4.03 (dd, 1H) ; 3.79 (s, 3H); 3.63-3-59 (m, 1H) ; 3.60 (s, 3H); 3.44-3. 40 (m, 1H) ; 3.16-3. 08 (m, 1H) ; 2.94 (d, 2H); 2.82-2. 73 (m, 1H); 2.69-2. 54 (m, 1H); 2.51-2. 46 (m, 1H); 2.41-2. 24 (m, 2H); 2.39 (s, 3H); 2.19 (s, 3H); 2.16 (s, 3H).

13C-NMR (75 MHz, CDCIs) : 8 172.0, 148.2, 146.4, 144.5, 136.3, 130.8, 129.6, 125.9, 120.9, 118.3, 114.5, 113.4, 109.7, 101.4, 64.2, 61.1, 60. 7, 60.0, 59.3, 55.4, 54.9, 54.8, 43.3, 41.7, 41.5, 39.8, 29.9, 29.5, 28.9, 24.4, 16.1, 14.3, 8.9.

ESI-MS m/z: Calcd. for C38H4oN409S : 728.2 Found (M+H+) : 729.3.

Example 115 po 70 Ho /NH OMe/NH OMe MeO Me Me0 p '-I HO Me S w So\ s I 11 wo\ s 2 IJ 99% I N-Me O/N t : N \-O bN 113 137 137 was obtained using Method F. 1H-NMR (300 MHz, CDCIs) : 8 7.87 (d, 1H) ; 7.60-7. 57 (m, 2H); 7.46-7. 44 (m, 3H); 6.58 (d, 1H) ; 6.54 (s, 1H) ; 6.49 (s, 1H); 6.45 (s, 1H); 6.03 (dd, 2H); 5.42 (s, 1H); 5.02 (d, 1H); 4.60 (s, 1H); 4.36 (s, 1H); 4.26 (dd, 1H); 4.19 (d, 1H); 4.13 (dd, 1H); 3.64 (s, 3H); 3.55 (d, 1H); 3.44 (s, 3H); 3.44-3. 40 (m, 1H) ; 3.16-3. 08 (m, 1H) ; 2.92 (d, 2H); 2.84-2. 78 (m, 1H); 2.69-2. 58 (m, 1H); 2.49-2. 42 (m, 1H); 2.38-2. 29 (m, 2H); 2.24 (s, 3H); 2.17 (s, 3H); 2.09 (s, 3H).

13C-NMR (75 MHz, CDCIs) : 8 172.2, 147.9, 146.7, 145.6, 144.7, 144.5, 143.2, 141.6, 134.4, 131.0, 129.5, 129.3, 128.4, 125.9, 121.7, 120.8, 118.3, 118.1, 116.9, 114.4, 114.2, 110.0, 102.0, 65.0, 61.4, 60.2, 60.1, 59.9, 59.5, 55.3, 54.9, 54.8, 42.5, 42.3, 41.8, 39.9, 32.1, 31.7, 30.6, 29.9, 29.0, 24.3, 22.8, 15.9, 14.3, 10.0.

ESI-MS m/z: Calcd. for C47H46N401o : 858.2 Found (M+H+) : 859.3.

Example 116 114 138 138 was obtained using Method F lH-NMR (300 MHz, CDCl3) : 5 7.87 (d, 1H); 7.82 (d, 1H) ; 7.56-7. 53 (m, 4H); 7.46-7. 31 (m, 6H); 6.93 (s, 1H) ; 6.64 (d, 1H) ; 6.52 (d, 1H) ; 6.51 (s, 1H) ; 6.43 (s, 1H) ; 6.10 (s, 1H) ; 6.00 (s, 1H) ; 5.43 (s, 1H) ; 5.04 (d, 1H) ; 4.55 (s, 1H) ; 4.40 (s, 1H) ; 4.23 (d, 1H) ; 4.13 (dd, 1H) ; 3.92 (d, 1H) ; 3.65 (s, 3H); 3.59 (d, 1H) ; 3.51-3. 46 (m, 1H) ; 3.44 (s, 3H); 3.19-3. 11 (m, 1H); 3.00 (d, 2H); 2.93-2. 86 (m, 1H); 2.74-2. 63 (m, 1H); 2.50-2. 45 (m, 1H); 2.36-2. 24 (m, 2H); 2.28 (s, 3H); 2.17 (s, 3H); 2.13 (s, 3H).

ESI-MS m/z: Calcd. for C56H52N4O11S : 989.1 Found (M+H+) : 990.2.

Example 117 111 139 139 was obtained using Method F lH-NMR (300 MHz, CDCIs) : 5 6.58 (s, 1H); 6.47 (s, 1H) ; 6.43 (s, 1H) ; 6.04 (d, 1H) ; 5.97 (d, 1H) ; 5.67 (s, 1H) ; 5.41 (s, 1H) ; 5.01 (d, 1H) ; 4.55 (s, 1H) ; 4.32 (s, 1H) ; 4.26 (d, 1H) ; 4.18 (d, 1H) ; 4.11 (dd, 1H) ; 3.78 (s, 3H); 3.61 (s, 3H); 3.51 (d, 1H) ; 3.41 (s, 1H) ; 3.15-3. 08 (m, 1H) ; 2.93 (d, 2H); 2.82-2. 76 (m, 1H); 2.61-2. 42 (m, 2H); 2.53 (t, 2H); 2.31 (s, 3H); 2.18 (s, 3H); 2.02 (s, 3H); 1.79-1. 72 (m, 2H); 1.02 (t, 3H).

ESI-MS m/z: Calcd. for C42H46N4OloS : 798.3 Found (M+H+) : 799.3.

Example 118 140 was obtained using Method F lH-NMR (300 MHz, CDC13) : 8 6.94 (s, 1H); 6.48 (s, 1H) ; 6.41 (s, 1H) ; 6.06 (d, 1H) ; 5.98 (d, 1H) ; 5.42 (s, 1H) ; 5.01 (d, 1H) ; 4.47 (s, 1H) ; 4.32 (s, 1H) ; 4.18 (d, 1H) ; 4.11 (dd, 1H) ; 3.81-3. 66 (m, 2H); 3.74 (s, 3H); 3.61 (s, 3H); 3.51 (d, 1H) ; 3.44 (s, 1H) ; 3.16-3. 06 (m, 1H) ; 2.98 (d, 2H); 2.83-2. 79 (m, 1H); 2.64-2. 48 (m, 2H); 2.60 (t, 2H); 2.55 (t, 2H); 2.32 (s, 3H); 2.15 (s, 3H); 2.03 (s, 3H); 1.93-1. 73 (m, 4H); 1.09 (t, 3H); 1.01 (t, 3H).

13C-NMR (75 MHz, CDCIs) : 8 171.4, 170.0, 147.0, 144.4, 143.5, 143.2, 142.6, 140.3, 139.1, 130.4, 129.6, 128.1, 126.2, 124.4, 123.4, 119.8, 116.8, 113.0, 112.9, 108.7, 100.7, 63.7, 60.1, 59.0, 58.9, 58.7, 58.3, 54.9, 54.0, 53.4, 41.4, 40.9, 40.6, 38.7, 35.0, 34.8, 28.6, 27.7, 23.0, 17.6, 17.2, 14.8, 12.9, 12.8, 8.7.

ESI-MS m/z: Calcd. for C46H52N4O11S : 868.3 Found (M+H+) : 869.3.

Example 119 115 141 141 was obtained using Method F lH-NMR (300 MHz, CDC13) : 8 6.58 (s, 1H); 6.47 (s, 1H) ; 6.45 (s, 1H) ; 6.05 (d, 1H) ; 5.98 (d, 1H) ; 5.72 (s, 1H) ; 5.37 (dd, 1H) ; 5.26 (dd, 1H) ; 5.01 (d, 1H) ; 4.67 (s, 1H) ; 4.62 (d, 1H) ; 4.31 (s, 1H) ; 4.26 (d, 1H) ; 4.18 (d, 1H) ; 4.13 (dd, 1H) ; 3.77 (s, 3H); 3.61 (s, 3H); 3.50 (d, 1H) ; 3.41 (s, 1H) ; 3.16-3. 08 (m, 1H) ; 2.93 (d, 2H); 2.80-2. 74 (m, 1H) ; 2.68-2. 56 (m, 1H); 2.48-2. 36 (m, 2H); 2.31 (s, 3H); 2.19 (s, 3H); 2.18-2. 14 (m, 2H); 2.09 (s, 3H).

ESI-MS m/z: Calcd. for C42H44N4011S : 812.3 Found (M+H+) : 813.3.

Example 120 H-NMR (300 MHz, CDCIs) : 8 6.59 (s, 1H); 6.47 (s, 1H); 6.43 (s, 1H); 6.06 (d, 1H) ; 5.99 (d, 1H) ; 5.75 (s, 1H) ; 5.41 (s, 1H) ; 5.01 (d, 1H) ; 4.53 (s, 1H) ; 4.33 (s, 1H) ; 4.27 (d, 1H) ; 4.18 (d, 1H) ; 4.11 (dd, 1H) ; 3.83 (ddd, 2H); 3.78 (s, 3H); 3.62 (s, 3H); 3. 51 (d, 1H) ; 3.42 (s, 1H) ; 3.16-3. 08 (m, 1H) ; 3.04 (t, 2H); 2.93 (d, 2H); 2.82-2. 76 (m, 1H) ; 2.68-2. 58 (m, 1H) ; 2.48. 2.42 (m, 1H) ; 2.31 (s, 3H); 2.18 (s, 3H); 2.05 (s, 3H).

ESI-MS m/z: Calcd. for C41H43CIN4OloS : 818.2 Found (M+H+) : 819.2.

Example 121 143 was obtained using Method F lH-NMR (300 MHz, CDC13) : 8 6.59 (s, 1H) ; 6.49 (s, 1H) ; 6.45 (s, 1H) ; 6.10 (d, 1H) ; 6.03 (d, 1H) ; 5.68 (s, 1H) ; 5.47 (s, 1H) ; 5.04 (d, 1H) ; 4.57 (s, 1H) ; 4.34 (s, 1H) ; 4.29 (d, 1H) ; 4.21 (d, 1H) ; 4.14 (dd, 1H) ; 3.75 (s, 3H); 3.62 (s, 3H); 3.50 (d, 1H) ; 3.43 (s, 1H) ; 3.18-3. 09 (m, 1H) ; 2.94 (d, 2H); 2.80-2. 72 (m, 1H) ; 2.68-2. 56 (m, 1H) ; 2.52-2. 45 (m, 1H) ; 2.35-2. 04 (m, 2H); 2.31 (s, 3H); 2.20 (s, 3H); 2.04 (s, 3H).

ESI-MS m/z: Calcd. for C42H3sF7N4OloS : 924.2 Found (M+H+) : 925.2.

Example 122 144 was obtained using Method F. lH-NMR (300 MHz, CDC13) : 8 6.59 (s, 1H) ; 6.47 (s, 1H) ; 6.43 (s, 1H) ; 6.01 (dd, 2H); 5.68 (s, 1H) ; 5.01 (d, 1H) ; 4.56 (s, 1H) ; 4.32 (s, 1H) ; 4.27 (dd, 1H) ; 4.18 (d, 1H) ; 4.12 (dd, 1H) ; 3.78 (s, 3H); 3.62 (s, 3H); 3.51 (d, 1H); 3.43-3. 40 (m, 1H); 3.18-3. 06 (m, 1H); 2.93 (d, 2H); 2.82-2. 76 (m, 1H) ; 2.63-2. 44 (m, 2H); 2.53 (t, 2H); 2.36-2. 15 (m, 2H); 2.32 (s, 3H); 2.19 (s, 3H); 2.02 (s, 3H); 1.75-1. 70 (m, 2H); 1.40-1. 21 (m, 11H).

13C-NMR (75 MHz, CDC13) : 8 172.5, 170.9, 147.7, 145.2, 144.5, 144.2, 143.0, 141.3, 140.0, 130.7, 129.2, 129.1, 127.1, 125.7, 121.1, 120.7, 118.1, 114.0, 113.2, 109.8, 101.7, 64.6, 61.1, 60.3, 60.0, 59.7, 59.6, 55.1, 54.7, 54.6, 42.2, 41.7, 41.5, 39.7, 34.0, 31.6, 29.6, 29.3, 28.9, 28.7, 24.8, 24.2, 22.5, 15.7, 14.0, 9.7.

ESI-MS m/z: Calcd. for C46H54N4OloS : 854.3 Found (M+H+) : 855.3.

Example 123 120 145 145 was obtained using Method F. 1H-NMR (300 MHz, CDCl3) : 8 6.94 (s, 1H); 6.47 (s, 1H) ; 6.41 (s, 1H) ; 6.01 (dd, 2H); 5.01 (d, 1H) ; 4.47 (s, 1H) ; 4.32 (s, 1H) ; 4.18 (d, 1H) ; 4.11 (dd, 1H) ; 3.79 (d, 1H) ; 3.73 (s, 3H); 3.61 (s, 3H); 3.50 (d, 1H) ; 3.45-3. 42 (m, 1H) ; 3.16-3. 04 (m, 1H) ; 2.99-2. 97 (m, 2H); 2.82-2. 78 (m, 1H) ; 2.64-2. 54 (m, 5H); 2.48-2. 42 (m, 1H) ; 2.36-2. 09 (m, 2H); 2.31 (s, 3H); 2.14 (s, 3H); 2.03 (s, 3H); 1.85-1. 77 (m, 2H); 1.73-1. 66 (m, 2H); 1.44- 1.18 (m, 22H).

13C-NMR (75 MHz, CDCl3) : 8 172.6, 171.5, 148.2, 145.6, 144.8, 144.5, 143.9, 141.5, 140.3, 131.7, 130.8, 129.3, 127.4, 125.6, 124.6, 121.0, 118.1, 115.0, 114.9, 114.2, 114.1, 109.9, 102.1, 64.8, 61.1, 60.3, 60.1, 59.9, 59.5, 56.1, 55.2, 54.6, 42.6, 42.1, 41.8, 39.9, 34.5, 34.1, 32.0, 31.9, 29.9, 29.6, 29.5, 29.2, 29.1, 28.9, 25.4, 24.9, 24.2, 22.8, 16.0, 14.2, 9.9.

ESI-MS m/z: Calcd. for C46H54N401OS : 980.5 Found (M+H+) : 981.5.

Example 124 121 146 146 was obtained using Method F. 1H-NMR (300 MHz, CDC13) : 5 6.59 (s, 1H) ; 6.47 (s, 1H) ; 6.43 (s, 1H) ; 6.01 (dd, 2H); 5.66 (s, 1H) ; 5.39 (s, 1H) ; 5.02 (d, 1H) ; 4.55 (s, 1H) ; 4.31 (s, 1H) ; 4.26 (dd, 1H) ; 4.17 (d, 1H) ; 4.11 (dd, 1H) ; 3.77 (s, 3H); 3.61 (s, 3H); 3.51 (d, 1H) ; 3.42-3. 40 (m, 1H) ; 3.16-3. 04 (m, 1H) ; 2.94-2-92 (m, 2H); 2.82-2. 74 (m, 1H) ; 2.66-2. 44 (m, 2H); 2.53 (t, 2H); 2.36- 2. 15 (m, 2H); 2.31 (s, 3H); 2.18 (s, 3H); 2.02 (s, 3H); 1.78-1. 59 (m, 4H); 1.40- 1.16 (m, 25H).

13C-NMR (75 MHz, CDCIs) : 8 172.0, 148.0, 144.7, 144.5, 143.2, 141.5, 140.5, 138.7, 137. 5, 131.0, 129.5, 129.3, 129.0, 125.9, 121.4, 120.9, 118.3, 114.2, 102.0, 64.8, 61.3, 60.5, 60.2, 59.9, 59.8, 55.3, 54.9, 54.8, 42.5, 42.0, 41.8, 39.9, 34.2, 32.1, 31.7, 29.9, 29.7, 29.6, 29.5, 29.4, 29.0, 25.0, 24.4, 22.8, 16.0, 14.2, 9.9.

ESI-MS m/z: Calcd. for C54H7oN40ioS : 966.4 Found (M+H+) : 967.5.

Example 125 123 147 147 was obtained using Method F. 1H-NMR (300 MHz, CDCIs) : 8 7.58 (s, 1H) ; 6.91 (s, 1H) ; 6.54 (s, 1H) ; 6.46 (s, 1H) ; 6.40 (s, 1H) ; 6.04 (d, 1H) ; 5.96 (d, 1H) ; 5.66 (s, 1H) ; 5.26 (s, 1H) ; 5.01 (d, 1H) ; 4.50-4. 46 (m, 2H); 4.34 (s, 1H) ; 4.31-4. 26 (m, 2H); 4.18 (d, 1H); 4.08 (dd, 1H); 3.74 (s, 3H); 3.60 (s, 3H); 3.51 (d, 1H) ; 3.40 (s, 1H) ; 3.17-3. 08 (m, 2H); 2.92-2. 80 (m, 4H); 2.74-2. 35 (m, 5H); 2.28 (s, 3H); 2.17 (s, 3H); 2.02 (s, 3H); 1.80-1. 70 (m, 6H).

ESI-MS m/z : Calcd. for C48Hs4N6OllS2 : 954.4 Found (M+H+) : 955.4.

Example 126 ESI-MS m/z: Calcd. for CssH6aNsOl3S3 : 1180.4 Found (M+H+) : 1181.3.

Example 127 149 was obtained using Method F. 1H-NMR (300 MHz, CDCl3) : 8 6.58 (s, 1H) ; 6.49 (s, 1H) ; 6.44 (s, 1H) ; 5.99 (s, 1H) ; 5.91 (s, 1H) ; 5.78 (s, 1H) ; 5.41 (s, 1H) ; 5.00 (d, 1H) ; 4.87 (s, 1H) ; 4.30-4. 29 (m, 2H); 4.15-4. 13 (m, 2H); 3.80 (s, 3H); 3.65 (s, 3H); 3.62 (s, 3H); 3.51 (d, 1H); 3.40 (s, 1H); 3.12-3. 02 (m, 1H); 2.93 (d, 2H); 2.82-2. 78 (m, 1H); 2.66-2. 58 (m, 1H); 2.48-2. 43 (m, 1H); 2.32 (s, 3H); 2.20 (s, 3H); 2.18 (s, 3H).

ESI-MS m/z: Calcd. for C39H42N409S : 742.3 Found (M+H+) : 743.3.

Example 128 150 was obtained using Method F. 1H-NMR (300 MHz, CDC13) : 8 6.75 (s, 1H) ; 6.50 (s, 1H) ; 6.44 (s, 1H) ; 6.00 (s, 1H) ; 5.92 (s, 1H) ; 5.39 (s, 1H) ; 5.01 (d, 1H); 4.81 (s, 1H); 4.30-4. 25 (m, 2H); 4.16-4. 13 (m, 2H); 3.95 (s, 3H); 3.83 (s, 3H); 3.74 (s, 3H); 3.62 (s, 3H); 3.51 (d, 1H) ; 3.41 (s, 1H) ; 3.12-3. 02 (m, 1H) ; 2.93 (d, 2H); 2.87-2. 80 (m, 1H); 2.66-2. 58 (m, 1H); 2.49-2. 43 (m, 1H); 2.28 (s, 3H); 2.23 (s, 3H); 2.18 (s, 3H).

ESI-MS m/z: Calcd. for C4oH44N409S : 756.3 Found (M+H+) : 757.3.

Example 129 151 was obtained using Method F. 1H-NMR (300 MHz, CDCIs) : 8 6.58 (s, 1H) ; 6.49 (s, 1H) ; 6.44 (s, 1H) ; 5.99 (s, 1H) ; 5.91 (s, 1H) ; 5.75 (s, 1H) ; 5.00 (d, 1H); 4.90 (s, 1H); 4.30 (d, 2H); 4.17 (s, 1H); 4.15 (dd, 1H); 3.88 (q, 2H); 3.80 (s, 3H); 3.62 (s, 3H); 3.51 (d, 1H) ; 3.40 (s, 1H) ; 3.12-3. 02 (m, 1H) ; 2.93 (d, 2H); 2.86-2. 80 (m, 1H) ; 2.68-2. 56 (m, 1H) ; 2.48-2. 42 (m, 1H) ; 2.31 (s, 3H); 2.23-2. 21 (m, 2H); 2.20 (s, 3H); 2.17 (s, 3H); 1.39 (t, 3H).

ESI-MS m/z: Calcd. for C4oH44N409S : 756.3 Found (M+H+) : 757.5 Example 130 152 was obtained using Method F 1H-NMR (300 MHz, CDCl3) : 5 6.76 (s, 1H); 6.50 (s, 1H) ; 6.44 (s, 1H) ; 5.99 (d, 1H) ; 5.92 (d, 1H) ; 5.42 (s, 1H) ; 5.001 (d, 1H) ; 4.87 (s, 1H) ; 4.35-4. 27 (m, 3H); 4.18 (s, 1H) ; 4.16 (dd, 1H) ; 3.97-3. 80 (m, 4H); 3.85 (s, 3H); 3.63 (s, 3H); 3.51 (d, 1H) ; 3.43 (s, 1H) ; 3.14-3. 06 (m, 1H) ; 2.95 (d, 2H); 2.88-2. 80 (m, 1H) ; 2.70-2. 58 (m, 1H) ; 2.50-2. 45 (m, 1H) ; 2.28 (s, 3H); 2.21 (s, 3H); 2.18 (s, 3H); 1.41 (t, 3H); 1.40 (t, 3H).

ESI-MS m/z: Calcd. for C42H48N409S : 784.3 Found (M+H+) : 785.3.

Example 131 130 153 153 was obtained using Method F. 1H-NMR (300 MHz, CDCIs) : 8 6.58 (s, 1H) ; 6.49 (s, 1H) ; 6.43 (s, 1H) ; 5.98 (s, 1H) ; 5.91 (s, 1H) ; 5.70 (s, 1H) ; 5.40 (s, 1H) ; 5.01 (d, 1H) ; 4.90 (s, 1H) ; 4.30 (s, 2H); 4.17 (s, 1H) ; 4.15 (dd, 1H) ; 3.85- 3.73 (m, 2H); 3.79 (s, 3H); 3.62 (s, 3H); 3.51 (d, 1H) ; 3.41 (s, 1H) ; 3.14-3. 04 (m, 1H) ; 2.93 (d, 2H); 2.86-2. 82 (m, 1H) ; 2.70-2. 60 (m, 1H) ; 2.48-2. 42 (m, 1H) ; 2.31 (s, 3H); 2.23 (s, 2H); 2.19 (s, 3H); 2.17 (s, 3H); 1.82-1. 76 (m, 2H); 1.06 (t, 3H).

ESI-MS m/z: Calcd. for C4lH46N4O9S : 770.3 Found (M+H+) : 771.3.

Example 132 154 was obtained using Method F. 1H-NMR (300 MHz, CDC13) : 8 6.76 (s, 1H) ; 6.50 (s, 1H) ; 6.43 (s, 1H) ; 5.98 (d, 1H) ; 5.91 (d, 1H) ; 5.40 (s, 1H) ; 5.01 (d, 1H) ; 4.88 (s, 1H) ; 44.32-4. 12 (m, 5H); 3.85 (s, 3H); 3.82-3. 59 (m, 4H); 3.62 (s, 3H); 3.51 (d, 1H) ; 3.43 (s, 1H) ; 3.14-3. 06 (m, 1H) ; 2.94 (d, 2H); 2.87- 2.80 (m, 1H); 2.71-2. 60 (m, 1H); 2.49-2. 44 (m, 1H); 2.27 (s, 3H); 2.21 (s, 3H); 2.17 (s, 3H); 1.82-1. 67 (m, 4H); 1.07 (t, 3H); 1.02 (t, 3H).

ESI-MS m/z: Calcd. for C44H52N409S : 812.3 Found (M+H+) : 813.3.

Example 133 132 155 155 was obtained using Method F. 1H-NMR (300 MHz, CDC13) : 8 6.58 (s, 1H) ; 6.49 (s, 1H) ; 6.44 (s, 1H) ; 6.15-6. 02 (m, 1H) ; 5.99 (s, 1H) ; 5.92 (s, 1H) ; 5.70 (s, 1H) ; 5.43 (dd, 1H) ; 5.26 (dd, 1H) ; 5.01 (d, 1H) ; 4.91 (s, 1H) ; 4.49 (dd, 1H) ; 4.32-4. 28 (m, 2H); 4.21-4. 13 (m, 3H); 3.79 (s, 3H); 3.62 (s, 3H); 3.50 (d, 1H); 3.41 (s, 1H) ; 3.12-3. 04 (m, 1H) ; 2.93 (d, 2H); 2.86-2. 82 (m, 1H) ; 2.67-2. 58 (m, 1H) ; 2.48-2. 43 (m, 1H) ; 2.31 (s, 3H); 2.24 (s, 2H); 2.20 (s, 3H); 2.18 (s, 3H).

ESI-MS m/z: Calcd. for C41H44N409S : 768.3 Found (M+H+) : 769.2 Example 134 156 was obtained using Method F. 1H-NMR (300 MHz, CDCIs) : 8 6.77 (s, 1H) ; 6.49 (s, 1H) ; 6.43 (s, 1H) ; 6. 15-6. 01 (m, 2H); 5.99 (d, 1H) ; 5.92 (d, 1H) ; 5.43 (dd, 1H) ; 5.37 (dd, 1H) ; 5.24-5. 18 (m, 2H); (dd, 1H) ; 5.01 (d, 1H) ; 4.89 (s, 1H); 4.78 (dd, 1H); 4.48-4. 35 (m, 2H); 4.29-4. 26 (m, 2H); 4.23-4. 13 (m, 3H); 3.84 (s, 3H); 3.62 (s, 3H); 3.50 (d, 1H) ; 3.41 (s, 1H) ; 3.14-3. 05 (m, 1H) ; 2.94 (d, 2H); 2.86-2. 82 (m, 1H) ; 2.70-2. 60 (m, 1H) ; 2.49-2. 43 (m, 1H) ; 2.28 (s, 3H); 2.23 (s, 2H); 2.19 (s, 3H); 2.18 (s, 3H).

13C-NMR (75 MHz, CDCIs) : 8 172.2, 150.8, 149.4, 149.0, 145.8, 144.7, 144.4, 138.8, 134.7, 133.6, 131.4, 130.5, 129. 5, 124.7, 124.5, 122.2, 118.3, 118.0, 117.2, 114.4, 114.0, 113.2, 109.7, 101. 7, 74.2, 73.3, 65.4, 61.6, 60. 5, 60.3, 59.8, 59.7, 55.3, 55.2, 54.8, 42.9, 42.0, 41.9, 40.0, 29.9, 29.0, 24.5, 16.0, 9.8.

ESI-MS m/z: Calcd. for C44H48N409S : 808.3 Found (M+H+) : 809.5.

Example 135 157 was obtained using Method F. 1H-NMR (300 MHz, CDC13) : 8 7.53- 7.50 (m, 2H); 7.44-7. 37 (m, 3H); 6.57 (s, 1H); 6.49 (s, 1H); 6.47 (s, 1H); 5.97 (dd, 2H); 5.56 (s, 1H) ; 5.02 (d, 1H) ; 5.00 (d, 1H) ; 4.87 (s, 1H) ; 4.76 (d, 1H) ; 4.31 (s, 1H) ; 4.20-4. 14 (m, 3H); 3.76 (s, 3H); 3.64 (s, 3H); 3.41 (d, 2H); 3.13- 3.05 (m, 1H) ; 2.92 (d, 2H); 2.84-2. 78 (m, 1H) ; 2.69-2. 58 (m, 1H) ; 2.49-2. 42 (m, 1H); 2.35-2. 04 (m, 2H); 2.31 (s, 3H); 2.25 (s, 3H); 2.17 (s, 3H).

13C-NMR (75 MHz, CDC13) : 6 72.5, 148.9, 148.0, 145.9, 144.4, 143.3, 139.0, 137.3, 131.0, 129.6, 128.6, 128.4, 128.2, 120.8, 118.4, 118.2, 114.9, 114.4, 114.2, 113.3, 109.8, 101.8, 92.6, 65.4, 61.6, 60.6, 60.4, 59.7, 55.2, 54. 8, 42.9, 42.02, 41.8, 40.0, 31.8, 29.9, 24.4, 22.8, 16.0, 14.3, 9.9.

ESI-MS m/z: Calcd. for C45H46N409S : 818.3 Found (M+H+) : 819.2.

Example 136 158 was obtained using Method F 1H-NMR (300 MHz, CDCl3) : 8 7.51-7. 47 (m, 2H); 7.30-7. 25 (m, 5H) ; 7.22-7. 18 (m, 3H); 6.79 (s, 1H) ; 6.50 (s, 1H) ; 6.47 (s, 1H) ; 6.01 (d, 1H) ; 5.93 (d, 1H) ; 5.43 (s, 1H) ; 5.24 (d, 1H) ; 5.02 (d, 1H) ; 5.01 (s, 2H); 4.95 (d, 1H); 4.66 (d, 1H); 4.28 (s, 1H); 4.18-4. 09 (m, 3H); 3.88 (s, 3H); 3.64 (s, 3H); 3.43 (d, 2H); 3.36-3. 34 (m, 1H); 3.16-3. 07 (m, 1H); 2.91 (d, 2H); 2.88-2. 80 (m, 1H) ; 2.69-2. 59 (m, 1H) ; 2.50-2. 45 (m, 1H) ; 2.37-2. 29 (m, 2H); 2.32 (s, 6H); 2.23 (s, 3H).

13C-NMR (75 MHz, CDCl3) : 8 172.7, 150.8, 149.3, 148.9, 146.1, 144.9, 144.6, 139.2, 138.0, 137.3, 131.6, 131.2, 130.8, 128.7, 128.6, 128.5, 128.4, 128.3, 126.0, 125.1, 124.8, 122.6, 118.6, 114.6, 114.4, 113.6, 110.0, 101.9, 74.8, 74.6, 65.5, 61.9, 60.7, 60.1, 59.9, 55.4, 55.0, 53.8, 43.3, 42.2, 41. 7, 40.1, 29.3, 24.7, 16.2, 10.0.

ESI-MS m/z: Calcd. for C52H52N409S : 908.3 Found (M+H+) : 909.3.

Example 137 Method J: To a solution of 1 equiv. of starting material in CH3CN/CH2C12 1.2 : 1 were added NaI (6 equiv. ) and TMSC1 (6 equiv. ). After 1 h the reaction was quenched with brine, the aqueous phase was extracted with CH2Cl2.

The organic layer was dried over Na2SO4. Chromatography gives pure compounds.

159 was obtained using Method J. lH-NMR (300 MHz, CDCl3) : 8 6.59 (s, 1H) ; 6.49 (s, 1H) ; 6.46 (s, 1H) ; 6.10 (d, 1H) ; 6.03 (d, 1H) ; 5.69 (s, 1H) ; 5.04 (d, 1H) ; 4.58 (s, 1H) ; 4.34 (s, 1H) ; 4.29 (d, 1H) ; 4.21 (d, 1H) ; 4.14 (dd, 1H) ; 3.76 (s, 3H); 3.63 (s, 3H); 3.50 (d, 1H) ; 3.43 (s, 1H) ; 3.20-3. 08 (m, 1H) ; 2.95 (d, 2H); 2.90-2. 84 (m, 1H) ; 2.78-2. 72 (m, 1H) ; 2.91-2. 48 (m, 1H) ; 2.34-2. 03 (m, 2H); 2.31 (s, 3H); 2.20 (s, 3H); 2.06 (s, 3H).

ESI-MS m/z: Calcd. for C4oH39F3N40ioS : 824.2 Found (M+H+) : 825.2.

Example 138 160 was obtained using Method J. lH-NMR (300 MHz, CDCIs) : 5 6.89 (s, 1H) ; 6.50 (s, 1H) ; 6.13 (d, 1H) ; 6.04 (d, 1H) ; 6.01 (s, 1H) ; 5.50 (s, 1H) ; 4.80 (d, 1H) ; 4.56 (s, 1H) ; 4.21 (s, 1H) ; 4.14-4. 10 (m, 2H); 3.79-3. 65 (m, 2H); 3.77 (s, 3H); 3.59 (s, 3H); 3.47 (s, 1H); 3.20 (d, 1H); 2.98 (d, 2H); 2.67 (t, 3H); 2.51 (d, 1H); 2.26 (s, 3H); 2.08 (s, 3H); 2.06 (s, 3H).

ESI-MS m/z: Calcd. for C42H38F6N4Oi1S : 920.2 Found (M+H+): 921.3.

Example 139 Method H: To a solution of 1 equiv. of starting material in CH3CN/H20 3: 2 (0.009M) were added 30 equiv. of AgNOs. After 24 h the reaction was quenched with a mixture 1: 1 of saturated solutions of brine and NaHC03, stirred for 10 min and diluted and extracted with CH2Cl2. The organic layer was dried over Na2SO4. Chromatography gives pure compounds.

161 was obtained using Method H. 1H-NMR (300 MHz, CDCIs) : 8 7.89 (d, 1H) ; 7.60-7. 56 (m, 2H); 7.46-7. 44 (m, 3H); 6.57 (d, 1H); 6.56 (s, 1H); 6.48 (s, 1H) ; 6.44 (s, 1H) ; 5.99 (dd, 2H); 5.43 (s, 1H) ; 5.14 (d, 1H) ; 4.86 (s, 1H) ; 4.52- 4.50 (m, 2H); 4.19 (d, 1H) ; 4.06 (dd, 1H) ; 3.63 (s, 3H); 3.46 (s, 3H); 3.25-3. 02 (m, 3H); 2.88-2. 85 (m, 3H); 2.73-2. 59 (m, 1H) ; 2.50-2. 24 (m, 3H); 2.25 (s, 3H); 2.17 (s, 3H); 2.07 (s, 3H).

ESI-MS m/z: Calcd. for C46H47N3011S : 849.3 Found (M+H+) : 850.3.

Example 140 162 was obtained using Method H. 1H-NMR (300 MHz, CDCl3) : 8 7.88 (d, 1H) ; 7.85 (d, 1H) ; 7. 45-7. 31 (m, 10H) ; 6.94 (s, 1H) ; 6.63 (d, 1H) ; 6.52 (d, 1H) ; 6.51 (s, 1H) ; 6.43 (s, 1H) ; 6.07 (s, 1H) ; 5.97 (s, 1H) ; 5.42 (s, 1H) ; 5.16 (d, 1H) ; 4.88 (s, 1H) ; 4.54 (s, 1H) ; 4.45 (s, 1H) ; 4.06 (d, 1H) ; 3.80-3. 78 (m, 1H) ; 3.64 (s, 3H); 3.46 (s, 3H); 3.28-3. 15 (m, 2H); 3.00-2. 88 (m, 3H); 2.76-2. 66 (m, 1H); 2.50-2. 17 (m, 4H); 2.28 (s, 3H); 2.14 (s, 3H); 2.11 (s, 3H).

13C-NMR (75 MHz, CDC13) : 8 172.3, 164.5, 164.2, 148.0, 147.2, 146.9, 145.4, 144.5, 144.2, 143.1, 141.2, 140.7, 134.1, 133.7, 131.3, 130.9, 130.7, 129.1, 129.0, 128.9, 128.2, 128.1, 127.3, 125.6, 124.1, 121.8, 116.6, 116.1, 116.0, 114.0, 112.5, 109.7, 101.7, 81.6, 64.9, 61.1, 59.9, 57.7, 57.6, 56.1, 55.8, 54.9, 42.7, 42.5, 41.4, 39.8, 29.6, 28.7, 23.9, 22.6, 15.8, 9.7.

ESI-MS m/z: Calcd. for C55H53N3O12S : 979.3 Found (M+H+) : 980.3.

Example 141 163 was obtained using Method H. 1H-NMR (300 MHz, CDC13) : 8 6.59 (s, 1H) ; 6.47 (s, 1H) ; 6.43 (s, 1H) ; 6.02 (d, 1H) ; 5.93 (d, 1H) ; 5.64 (s, 1H) ; 5.12 (d, 1H) ; 4.81 (s, 1H) ; 4.47 (s, 1H) ; 4.15 (d, 1H) ; 4.03 (dd, 1H) ; 3.78 (s, 3H); 3.60 (s, 3H); 3.60-3. 59 (m, 1H); 3.58 (d, 1H); 3.21-3. 10 (m, 2H); 2.87-2. 79 (m, 3H); 2.68-2. 58 (m, 2H); 2.54-2. 38 (m, 2H); 2.52 (t, 2H); 2.31 (s, 3H); 2.16 (s, 3H); 2.01 (s, 3H); 1.81-1. 73 (m, 2H); 1.02 (t, 3H).

ESI-MS m/z : Calcd. for C41H47N3011S : 789.3 Found (M+H+) : 790.1.

Example 142 164 was obtained using Method H 1H-NMR (300 MHz, CDC13): 8 7.96 (s, 1H); 6.47 (s, 1H) ; 6.42 (s, 1 H) ; 6.02 (d, 1 H) ; 5.93 (d, 1 H) ; 5.40 (s, 1 H) ; 5.12 (d, 1 H) ; 4.81 (s, 1 H) ; 4.47 (s, 1 H) ; 4.18-4. 16 (m, 1 H) ; 4.03 (d, 1H); 3.78 (s, 3H); 3.71-3. 70 (m, 2H); 3.61 (s, 3H); 3.23-3. 10 (m, 2H); 2.87-2. 79 (m, 3H); 2.68- 2.40 (m, 3H); 2.60 (t, 2H); 2.60 (t, 2H); 2.31 (s, 3H); 2.16 (s, 3H); 2.01 (s, 3H); 1.84-1. 73 (m, 4H); 1-09 (t, 3H); 1.03 (t, 3H).

ESI-MS m/z: Calcd. for C45H53N3012S : 859.3 Found (M+H+) : 860.3.

Example 143 165 was obtained using Method H 1H-NMR (300 MHz, CDCIs) : 8 6.59 (s, 1H) ; 6.47 (s, 1H) ; 6.45 (s, 1H) ; 6.03 (d, 1H) ; 5.98-5. 85 (m, 1); 5.95 (d, 1H) ; 5.70 (s, 1H) ; 5.37 (dd, 1H) ; 5.26 (dd, 1H) ; 5.12 (d, 1H) ; 4.80 (s, 1H) ; 4.64-4. 62 (m, 2H); 4.58 (s, 1H) ; 4.48 (d, 1H) ; 4.17 (d, 1H) ; 4.05 (dd, 1H) ; 3.77 (s, 3H); 3.60 (s, 3H); 3.57 (d, 1H) ; 3.22-3. 10 (m, 2H); 2.87-2. 78 (m, 3H); 2.68-2. 58 (m, 1H); 2.49-2. 20 (m, 2H); 2.31 (s, 3H); 2.17 (s, 3H); 2.08 (s, 3H).

13C-NMR (75 MHz, CDCIs) : 8 172.7, 152.7, 147.9, 145.3, 144.6, 144.4, 143.1, 141.3, 140.9, 131.5, 129.4, 129.2, 126.2, 122.3, 121.0, 119.0, 116.1, 114.2, 112.6, 109.9, 101.9, 82.3, 69.3, 64.7, 61.4, 60. 5, 57.9, 57.8, 56.2, 55.3, 55.0, 42.5, 42.0, 41.6, 39.8, 29.9, 28.9, 24.2, 16.0, 9.5.

ESI-MS m/z: Calcd. for C4lH45N3012S : 803.3 Found (M+H+): 804.3.

Example 144 166 was obtained using Method H. 1H-NMR (300 MHz, CDCl3) : 8 6.60 (s, 1H) ; 6.47 (s, 1H) ; 6.32 (s, 1H) ; 6.03 (d, 1H) ; 5.95 (d, 1H) ; 5.72 (s, 1H) ; 5.12 (d, 1H) ; 4.82 (s, 1H) ; 4.48 (d, 1H) ; 4.43 (s, 1H) ; 4.17-4. 14 (m, 1H) ; 4.04 (dd, 1H); 3.85 (ddd, 2H); 3.79 (s, 3H); 3.61 (s, 3H); 3.60-3. 57 (m, 1H); 3.24-3. 10 (m, 2H); 3.03 (t, 2H); 2.88-2. 78 (m, 3H); 2.68-2. 56 (m, 1H); 2.49-2. 43 (m, 1H); 2.38-2. 13 (m, 2H); 2.31 (s, 3H); 2.17 (s, 3H); 2.04 (s, 3H).

3C-NMR (75 MHz, CDC13) : 5 172.6, 167.8, 147.8, 145.4, 144.6, 144.4, 143.2, 141.1, 140.9, 131.6, 129.3, 126.1, 121.8, 114.2, 109.9, 101.9, 82.2, 64.7, 61.5, 60.6, 58.0, 57.8, 56.1, 55.3, 55.1, 42.5, 42.3, 41.6, 39.9, 38.8, 37.7, 29.9, 29.5, 29.0, 24.3, 22.9, 16.0, 14.3, 9.9.

ESI-MS m/z: Calcd. for C40H44CIN3O11S : 809.2 Found (M+H+) : 810.3.

Example 145 143 167 167 was obtained using Method H 1H-NMR (300 MHz, CDCIs) : 8 6.60 (s, 1H); 6.49 (s, 1H) ; 6.46 (s, 1H) ; 6.07 (s, 1H) ; 6.00 (s, 1H) ; 5.64 (s, 1H) ; 5.39 (s, 1H) ; 5.16 (d, 1H) ; 4.83 (s, 1H) ; 4.49 (s, 1H) ; 4.19-4. 18 (m, 1H) ; 4.06 (dd, 1H) ; 3.76 (d, 1H) ; 3.62 (s, 3H); 3.57-3. 56 (m, 1H) ; 3.24-3. 12 (m, 2H); 2.89-2. 85 (m, 2H); 2.79-2. 73 (m, 1H) ; 2.68-2. 58 (m, 1H) ; 2.52-2. 45 (m, 1H) ; 2.37-2. 10 (m, 2H); 2.31 (s, 3H); 2.18 (s, 3H); 2.03 (s, 3H).

ESI-MS m/z: Calcd. for C4iH4oF7N30nS : 915.2 Found (M+H+) : 916.2.

Example 146 144 168 168 was obtained using Method H. 1H-NMR (300 MHz, CDCIs) : 8 6.60 (s, 1H) ; 6.47 (s, 1H) ; 6. 43 (s, 1H) ; 5.97 (dd, 2H); 5.64 (s, 1H) ; 5.32 (s, 1H) ; 5.12 (d, 1H) ; 4.81 (s, 1H) ; 4.48 (s, 1H) ; 4.48-4. 45 (m, 1H) ; 4.16 (d, 1H) ; 4.03 (dd, 1H) ; 3.78 (s, 3H); 3.60 (s, 3H) ; 3.58 (d, 1H) ; 3.24-3. 08 (m, 2H); 2.94-2. 78 (m, 3H); 2.66-2. 42 (m, 2H); 2.53 (t, 2H); 2. 38-2. 12 (m, 2H); 2.31 (s, 3H); 2.16 (s, 3H); 2.01 (s, 3H); 1.80-1. 68 (m, 2H); 1.42-1. 23 (m, 11H).

13C-NMR (75 MHz, CDCIs) : 8 172.6, 171.3, 147.8, 145.3, 144.6, 144.4, 143.1, 141.5, 140.6, 131.6, 129.3, 129.2, 121.9, 121.1, 114.2, 110.0, 101.8, 82.3, 64.9, 61.6, 60.5, 58.0, 57.9, 56.1, 55.2, 55.1, 42.3, 41.6, 39.9, 34.2, 31.9, 29.9, 29.6, 29.2, 25.1, 24.3, 22.8, 16.0, 14.3, 9.9.

ESI-MS m/z: Calcd. for C45H55N30liS : 845.4 Found (M+H+): 846.7.

Example 147 145 169 169 was obtained using Method H. 1H-NMR (300 MHz, CDC13) : 8 6.94 (s, 1H) ; 6.47 (s, 1H) ; 6.41 (s, 1H) ; 6.03 (s, 1H) ; 5.94 (s, 1H) ; 5. 12 (d, 1H) ; 4.81 (s, 1H) ; 4.49 (s, 1H) ; 4.37 (s, 1H) ; 4.03 (d, 1H) ; 3.74 (s, 3H); 3.67-3. 57 (m, 2H); 3.60 (s, 3H); 3.24-3. 10 (m, 2H); 2.92-2. 80 (m, 3H); 2.68-2. 44 (m, 2H); 2.61 (t, 2H); 2.56 (t, 2H); 2.38-2. 18 (m, 2H); 2.31 (s, 3H); 2.12 (s, 3H); 2.02 (s, 3H); 1.84-1. 68 (m, 4H); 1.42-1. 20 (m, 22H).

ESI-MS m/z: Calcd. for C53H69N3O12S : 971.5 Found (M+H+) : 972.7.

Example 148 170 was obtained using Method H. 1H-NMR (300 MHz, CDCls) : 8 6.59 (s, 1H) ; 6.47 (s, 1H) ; 6.43 (s, 1H) ; 6.01 (dd, 2H); 5.66 (s, 1H) ; 5.39 (s, 1H) ; 5.02 (d, 1H) ; 4.55 (s, 1H) ; 4.31 (s, 1H) ; 4.26 (dd, 1H) ; 4.17 (d, 1H) ; 4.11 (dd, 1H) ; 3.77 (s, 3H); 3.61 (s, 3H); 3.51 (d, 1H) ; 3.42-3. 40 (m, 1H) ; 3.16-3. 04 (m, 1H) ; 2.94-2. 92 (m, 2H); 2.82-2. 74 (m, 1H) ; 2.66-2. 44 (m, 2H); 2.53 (t, 2H); 2.36- 2.15 (m, 2H); 2.31 (s, 3H); 2.18 (s, 3H); 2.02 (s, 3H); 1.78-1. 59 (m, 2H); 1.40- 1.16 (m, 27H).

ESI-MS m/z: Calcd. for CssHviNsOnS : 957.5 Found (M+H+): 958.4.

Example 149 Compound 147 was recovered (19%) after chromatographic purification.

171 was obtained using Method H. 1H-NMR (300 MHz, CDC13) : 8 7.50 (s, 1H) ; 6. 81 (s, 1H) ; 6.56 (s, 1H) ; 6.45 (s, 1H) ; 6.40 (s, 1H) ; 6.02 (d, 1H) ; 5.93 (d, 1H) ; 5.21 (s, 1H) ; 5.12 (d, 1H) ; 4.84 (s, 1H) ; 4.51-4. 46 (m, 2H); 4.41 (s, 1H) ; 4.32-4. 21 (m, 3H); 4.01 (dd, 1H); 3.75 (s, 3H); 3.75-3. 71 (m, 1H); 3.65 (s, 3H); 3.59 (s, 3H); 3.23 (s, 1H) ; 3.17-3. 10 (m, 2H); 2.89-2. 80 (m, 3H); 2.74- 2.37 (m, 4H); 2.29 (s, 3H); 2.17 (s, 3H); 2.00 (s, 3H); 1.80-1. 68 (m, 4H); 1.55-1. 39 (m, 2H).

13C-NMR (75 MHz, CDCIs) : 8 172.6, 171.4, 164.5, 148.4, 145.4, 144.7, 144.6, 143.4, 141.5, 140.7, 131.1, 129.2, 129.0, 122.0, 120.6, 116.2, 114.3, 110.1, 101. 9,82. 1,70. 7,65. 0,62. 4,61. 8,60. 5,60. 3,58. 1,57. 9,56. 1,55. 2, 55.0, 42.5, 41.6, 40.8, 40.1, 33.7, 32.1, 29.9, 29.5, 28.7, 28.2, 24.7, 24.3, 16.1, 14.3, 9.9.

ESI-MS m/z: Calcd. for C47H55N5O12S2 : 945.3 Found (M-H20+H+) : 928.3.

Example 150 148 172 172 was obtained using Method H. 1H-NMR (300 MHz, CDCl3) : 8 6.94 (s, 1H) ; 6.46 (s, 1H) ; 6.39 (s, 1H) ; 6.26 (s, 1H) ; 6.02 (d, 1H) ; 5.94 (d, 1H) ; 5.57- 5.55 (m, 2H); 5.11 (d, 1H) ; 4.82 (s, 1H) ; 4.48-4. 45 (m, 3H); 4.32-4. 22 (m, 3H); 4.01 (dd, 1H) ; 3.75 (s, 3H); 3.75-3. 71 (m, 1H); 3.67-3. 64 (m, 6H); 3.59 (s, 3H); 3.25-3. 24 (m, 1H) ; 3. 19-3. 10 (m, 3H); 2.92-2. 83 (m, 4H); 2.74-2. 60 (m, 6H); 2.46-2. 14 (m, 2H); 2.31 (s, 3H); 2.11 (s, 3H); 2.03 (s, 3H); 1.91-1. 66 (m, 8H); 1.59-1. 44 (m, 4H).

ESI-MS m/z: Calcd. for C47H55N5012S2 : 1171.4 Found (M-H20+H+) : 1154.3.

Example 151 173 was obtained using Method H. 1H-NMR (300 MHz, CDCIs) : 8 6.69 (s, 1H) ; 6.60 (s, 1H) ; 6.59 (s, 1H) ; 6.00 (s, 1H) ; 5.92 (s, 1H) ; 5.66 (s, 1H) ; 5.11 (d, 1H) ; 4.78 (s, 1H) ; 4.59 (s, 1H) ; 4.46 (d, 1H) ; 4.15 (d, 1H) ; 4.04 (dd, 1H) ; 3.79 (s, 3H); 3.57 (s, 3H); 3.56-3. 52 (m, 1H); 3.21-3. 09 (m, 2H); 2.87-2. 75 (m, 3H); 2.69-2. 38 (m, 3H); 2.31 (s, 3H); 2.30-2. 10 (m, 2H); 2.16 (s, 3H); 2.06 (s, 3H); 1.50 (s, 9H); 1.48 (s, 9H).

13C-NMR (75 MHz, CDCIs) : 8 172.2, 151.8, 150.9, 148.6, 147.9, 145.3, 143.1, 141.3, 140.6, 138.9, 133.1, 131.7, 129.3, 128.8, 122.3, 121.0, 118.1, 115.9, 112.7, 112.1, 101.8, 83.6, 83.3, 82.3, 65.1, 61.6, 60.4, 57.9, 56. 2, 55.4, 55.1, 42. 5, 42.0, 41.6, 39.7, 29.9, 28. 8, 27.9, 27.8, 24.3, 16.0, 9.5.

ESI-MS m/z: Calcd. for C47Hs7N3Ol4S : 919.4 Found (M+H+) : 920.3 Example 152 174 was obtained using Method H. 1H-NMR (300 MHz, CDC13) : 8 6.92 (s, 1H) ; 6.69 (s, 1H) ; 6.58 (s, 1H) ; 6.01 (s, 1H) ; 5.93 (s, 1H) ; 5.10 (d, 1H) ; 4.76 (s, 1H) ; 4.55 (s, 1H) ; 4.46 (d, 1H) ; 4.04 (dd, 1H) ; 3.84 (d, 1H) ; 3.81 (s, 3H); 3.61-3. 58 (m, 1H) ; 3.58 (s, 3H); 3.24-3. 10 (m, 2H); 2.99-2. 77 (m, 3H); 2.70- 2.60 (m, 1H) ; 2.51-2. 17 (m, 3H); 2.30 (s, 3H); 2.14 (s, 3H); 2.07 (s, 3H); 1.55 (s, 9H); 1.51 (s, 9H); 1.49 (s, 9H).

ESI-MS m/z: Calcd. for C52H65N3O16S : 1019.4 Found (M+H+) : 1020.4 Example 153 175 was obtained using Method H. 1H-NMR (300 MHz, CDCIs) : 8 6.69 (s, 1H) ; 6.57 (s, 1H) ; 6.55 (s, 1H) ; 6.02 (d, 1H) ; 5.94 (d, 1H) ; 5.12 (d, 1H) ; 5.02 (d, 1H) ; 4.82 (s, 1H) ; 4.61 (t, 1H) ; 4.49 (d, 1H) ; 4.41 (s, 1H) ; 4.17 (d, 1H) ; 4.00 (dd, 1H) ; 3.77 (s, 3H); 3.57-3. 55 (m, 1H) ; 3.56 (s, 3H); 3.22-3. 09 (m, 2H); 2.86-2. 80 (m, 3H); 2.69-2. 60 (m, 1H); 2.50-2. 36 (m, 2H); 2.30 (s, 3H); 2.15 (s, 3H); 2.01 (s, 3H); 1.61 (d, 3H); 1.50 (s, 9H); 1.43 (s, 9H).

13C-NMR (75 MHz, CDCIs) : 8 172.2, 171.3, 155.5, 151.8, 148.7, 147.9, 145.5, 143.3, 140.9, 139.0, 132.8, 131.7, 129.6, 128.8, 122.4, 122.0, 120.9, 118.1, 116.2, 112.1, 102.0, 83.6, 82.1, 65.3, 61.5, 60.6, 58.0, 56.2, 55.4, 54.9, 49.3, 42.4, 41.6, 39.9, 29.9, 28.9, 28.5, 27.8, 24.2, 18.6, 16.0, 9.8.

ESI-MS m/z: Calcd. for C5oH62N4015S : 990.4 Found (M+H+) : 991.4.

Example 154 176 was obtained using Method H. 1H-NMR (300 MHz, CDCIs) : 8 6.99 (dd, 1H) ; 6.69 (s, 1H) ; 6.60 (s, 1H) ; 6.59 (s, 1H) ; 6.03 (d, 1H) ; 5.95 (d, 1H) ; 5.70 (s, 1H) ; 5.12 (d, 1H) ; 4.97 (dd, 1H) ; 4.80 (s, 1H) ; 4.60 (dd, 1H) ; 4.56 (s, 1H) ; 4.48 (d, 1H) ; 4.18 (d, 1H) ; 4.04 (dd, 1H) ; 3.76 (s, 3H); 3.58 (s, 3H); 3.58-3. 56 (m, 1H) ; 3.47 (d, 1H) ; 3.24-3. 12 (m, 2H); 2.87-2. 78 (m, 3H); 2.68-2. 58 (m, 1H) ; 2.52-2. 47 (m, 1H) ; 2.43-2. 20 (m, 2H); 2.31 (s, 3H); 2.18 (s, 3H); 2.08 (s, 3H); 1.50 (s, 9H).

13C-NMR (75 MHz, CDCIs) : 8 172.3, 151.8, 150.5, 148.7, 148.0, 145.4, 143.1, 141.1, 140.9, 139.0, 133.1, 131.6, 129.4, 128.8, 122.4, 122.3, 120.9, 116.1, 112.6, 112.0, 102.0, 98.6, 86.6, 82.2, 64.8, 61.4, 60.5, 57.9, 57.7, 56.2, 55.5, 55.0, 42.5, 42.0, 41.6, 39.7, 29.9, 28.8, 27.8, 24.1, 16.0, 9.5.

ESI-MS m/z: Calcd. for C4sHs1N3014S : 889.3 Found (M+H+) : 890.2 Example 155 Method I : To a solution of 1 equiv. of starting material in THF/H20 4: 1 (0.009M) were added 5 equiv. of BrCu. After 24 h the reaction was quenched with NH4C1, diluted with CH2C12, washed with brine and NaHCOs and extracted with CH2C12. The organic layer was dried over Na2SO4.

Chromatography gives pure compounds.

177 was obtained using Method 1. ESI-MS m/z: Calcd. for C39H45N3OlOS : 747.3 Found (M+H+): 748.1.

Example 156 153 178 178 was obtained using Method I. 1H-NMR (300 MHz, CDCIs) : 8 6.59 (s, 1H) ; 6.49 (s, 1H) ; 6.44 (s, 1H) ; 5.96 (s, 1H) ; 5.87 (s, 1H) ; 5.67 (s, 1H) ; 5.12 (d, 1H) ; 4.85 (s, 1H) ; 4.78 (s, 1H) ; 4.49 (s, 1H) ; 4.20-4. 18 (m, 1H) ; 4.08 (dd, 1H) ; 3.79 (s, 3H); 3.61 (s, 3H); 3.23-3. 10 (m, 2H); 2.87-2. 80 (m, 2H); 2.70-2. 58 (m, 1H); 2.49-2. 42 (m, 1H); 2.31 (s, 3H); 2.26-2. 22 (m, 2H); 2.18 (s, 3H); 2.15 (s, 3H).

ESI-MS m/z: Calcd. for C40H47N3OloS : 761.3 Found (M+H+) : 762.3.

Example 157 156 179 179 was obtained using Method I. 1H-NMR (300 MHz, CDC13) : 8 6.79 (s, 1H) ; 6.50 (s, 1H) ; 6.45 (s, 1H) ; 6.15-6. 02 (m, 2H); 5.97 (d, 1H) ; 5.88 (d, 1H) ; 5.46-5. 35 (m, 3H); 5.20 (dd, 2H); 5.13 (d, 1H) ; 4.84 (s, 1H); 4.78-4. 74 (m, 2H); 4. 49-4. 38 (m,-3H) ; 4.21-4. 08 (m, 3H); 3.84 (s, 3H); 3.62 (s, 3H); 3.57 (d, 1H) ; 3.49 (s, 1H) ; 3.22-3. 08 (m, 2H); 2.92-2. 82 (m, 3H); 2.72-2. 60 (m, 1H) ; 2.52-2. 46 (m, 1H); 2.28 (s, 3H); 2.26-2. 23 (m, 2H); 2.17 (s, 6H).

ESI-MS m/z: Calcd. for G3H4sN3OloS : 799.3 Found (M+H+) : 800.2.

Example 158 157 180 180 was obtained using Method I. 1H-NMR (300 MHz, CDC13) : 8 7.54-7. 51 (m, 2H); 7.40-7. 29 (m, 3H); 6.58 (s, 1H) ; 6.49 (s, 1H) ; 6.48 (s, 1H) ; 5.99 (d, 1H) ; 5.91 (d, 1H) ; 5.34 (s, 1H) ; 5.14 (d, 1H) ; 5.01 (d, 1H) ; 4.84 (s, 1H) ; 4.79 (s, 1H) ; 4.72 (d, 1H) ; 4.49 (d, 1H) ; 4.12-4. 07 (m, 2H); 3.77 (s, 3H); 3.64 (s, 3H); 3.50 (d, 1H); 3.22-3. 10 (m, 2H); 2.87-2. 82 (m, 2H); 2.70-2. 60 (m, 1H); 2.49-2. 43 (m, 1H); 2.34-2. 10 (m, 2H); 2.31 (s, 3H); 2.24 (s, 3H); 2.15 (s, 3H).

ESI-MS m/z: Calcd. for C44H47N3OloS : 809.3 Found (M+H+): 810.3.

Example 159 158 181 181 was obtained using Method I. ESI-MS m/z: Calcd. for CslHs3N3OloS : 899.4 Found (M+H+) : 900.3.

Example 160 Method K: To a solution of 1 equiv. of starting material in THF/H20 4: 1 (0.009M) were added 5 equiv. of CICu. After 24 h the reaction was quenched with NH4Cl, diluted with CH2C12, washed with brine and NaHCOs and extracted with CH2Cl2. The organic layer was dried over Na2SO4.

Chromatography gives pure compounds.

149 182 182 was obtained using Method I. 1H-NMR (300 MHz, CDCIs) : 8 6.60 (s, 1H) ; 6.49 (s, 1H) ; 6.45 (s, 1H) ; 5.97 (s, 1H) ; 5.88 (s, 1H) ; 5.76 (s, 1H) ; 5.11 (d, 1H) ; 4.80 (s, 1H) ; 4.48-4. 46 (m, 1H) ; 4.20-4. 18 (m, 1H) ; 4.07 (dd, 1H) ; 3.80 (s, 3H); 3.74 (s, 3H); 3.74-3. 60 (m, 2H); 3.61 (s, 3H); 3.22-3. 08 (m, 2H); 2.87- 2.78 (m, 3H); 2.66-2. 58 (m, 1H); 2.49-2. 44 (m, 1H); 2.32 (s, 3H); 2.31-2. 24 (m, 2H); 2.18 (s, 3H); 2.17 (s, 3H).

ESI-MS m/z: Calcd. for C38H43N3OloS : 733.3 Found (M+H+) : 734.2.

Example 161 183 was obtained using Method I. 1H-NMR (300 MHz, CDC13) : 8 6.59 (s, 1H) ; 6.49 (s, 1H) ; 6.45 (s, 1H) ; 6.15-6. 02 (m, 1H) ; 5.97 (d, 1H) ; 5.88 (d, 1H) ; 5.69 (s, 1H) ; 5.43 (dd, 1H) ; 5.24 (dd, 1H) ; 5.12 (d, 1H) ; 4.85 (s, 1H) ; 4.78 (s, 1H); 4.52-4. 47 (m, 2H); 4.21-4. 15 (m, 2H); 4.08 (dd, 1H); 3.80 (s, 3H); 3.64- 3.57 (m, 2H); 3.61 (s, 3H); 3.22-3. 20 (m, 1H) ; 3.16-3. 08 (m, 1H) ; 2.87-2. 80 (m, 3H); 2.68-2. 58 (m, 1H) ; 2.49-2. 43 (m, 1H) ; 2.31 (s, 3H); 2.26 (d, 2H); 2.18 (s, 3H); 2.17 (s, 3H).

13C-NMR (75 MHz, CDC13) : 8 172.5, 149.4, 147.9, 145.6, 144.6, 144.4, 143.2, 139.2, 134.0, 129.5, 122.9, 121.0, 117.5, 115.9, 114.3, 112.4, 109.8, 101.8, 82.3, 74.1, 65.4, 61.7, 60.6, 58.4, 58.0, 56.5, 55.2, 55.1, 43.1, 42.3, 41.6, 40.0, 29.9, 29.5, 29.1, 24.4, 22.9, 16.0, 14.3, 9.8.

ESI-MS m/z: Calcd. for C40H45N3OloS : 759.3 Found (M+H+) : 760.3.

Example 162 To a solution of Et-743 in MeOH (0.19M) were added 15 equiv. of KOH. The reaction mixture was stirred at room temperature for 1 h 30 minutes. After this time the reaction was quenched with NH4C1, diluted and extracted with CH2C12. The organic layer was dried over Na2SO4. Chromatography gives pure Et-701.

Et-701 1H-NMR (300 MHz, CDCl3) : 5 6.60 (s, 1H) ; 6.47 (s, 1H) ; 6.40 (s, 1H) ; 5.93 (d, 2H); 5.84 (d, 1H) ; 5.08 (d, 1H) ; 4.82 (s, 1H) ; 4.46 (d, 1H) ; 4.43 (d, 1H) ; 4.18 (d, 1H) ; 3.97 (dd, 1H) ; 3.70 (s, 3H); 3.65 (d, 1H) ; 3.57 (s, 3H); 3.23- 3.08 (m, 2H); 2.88-2. 78 (m, 3H); 2.65-2. 55 (m, 1H); 2.49-2. 36 (m, 2H); 2.30 (s, 3H); 2.14 (s, 3H); 2.13 (s, 3H).

ESI-MS m/z: Calcd. for C37H41N3OloS : 719.3 Found (M-H20+H+) : 702.2.

Example 163 Et-729 184 To a solution of ET-729 in MeOH (0.005M) at room temperature under Argon, were added 30 equiv. of KCN. The reaction mixture was stirred for 6h. After this time the reaction was diluted with CH2Cl2, washed with NaCI, extracted with CH2Cl2. The organic layers were dried over Na2SO4. Flash chromatography gives pure compound 184 (20%).

184. 1H-NMR (300 MHz, CDCIs) : 8 6.64 (s, 1H), 6.50 (s, 1H), 6.39 (s, 1H), 5.94 (d, 2H), 5.42 (bs, 1H), 5.00 (d, 1H), 4.54 (d, 1H), 4.48 (s, 1H), 4.36 (s, 1H), 4.19 (d, 1H), 4.04 (dd 1H), 3.88-3. 83 (m, 1H), 3.78 (s, 3H), 3.60 (bs, 4H), 3.17-3. 06 (m, 2H), 2.99 (dd, 1H), 2.82-2. 74 (m, 1H), 2.66-2. 55 (m, 1H), 2.54- 2.04 (m, 3H), 2.34 (s, 3H), 2.16 (s, 3H).

ESI-MS m/z: Calcd. for C37H38N409S : 714.2. Found (M+H+): 715.2.

Example 164 Et-729 185 To a solution of ET-729 in acetonitrile (0.016M) at room temperature under Argon, were added 200 equiv. of formaline and 10 equiv. of NaBH3CN. The reaction mixture was stirred for 1 h, then acetic acid (40 equiv. ) was added and the reaction was left for 1 hour more. After this time the reaction was diluted with CH2C12, a saturated aqueous solution of NaHCOs was added and the aqueous phase was extracted with CH2Clz. The organic layers were dried over Na2SO4. Flash chromatography gives pure compound 185 (60%).

185. 1H-NMR (300 MHz, CD30D) : 8 6.40 (s, 1H), 6.35 (s, 1H), 6.23 (s, 1H), 6.06 (d, 2H), 5.01 (d, 1H), 4.63 (bs, 1H), 4.26 (d, 1H), 3.88-3. 85 (m, 2H), 3.74 (s, 3H), 3.52 (s, 3H), 3.32-3. 11 (m, 4H), 3.00-2. 79 (m, 3H), 2.66-2. 51 (m, 3H), 2.50-2. 20 (m, 2H), 2.33 (s, 3H), 2.24 (s, 3H), 2.20 (s, 3H), 2.12 (s, 3H), 2.03 (s, 3H).

ESI-MS m/z: Calcd. for C4oH45N30ioS : 759.3. Found (M+H+) : 760.2.

Example 165 Et-729 186 To a solution of ET-729 in MeOH (0.005M) at room temperature under Argon, were added 4.2 equiv. of KCN and 4.2 equiv. of acetic acid. The reaction mixture was stirred for 1 h 30 min. After this time the reaction was diluted with CHaCh, quenched with NaHCOs, extracted with CH2C12.

The organic layers were dried over Na2SO4. Flash chromatography gives pure compound 186 (93%).

186. 1H-NMR (300 MHz, CDC13) : 8 6.60 (s, 1H), 6.43 (s, 1H), 6.42 (s, 1H), 6.00 (d, 2H), 5.96 (bs, 1H), 5.01 (d, 1H), 4.55 (bs, 1H), 4.49 (d, 1H), 4.32 (s, 1H), 4.18 (d, 1H), 4.10 (dd 1H), 3.82 (bd, 1H), 3.74 (s, 3H), 3.57 (s, 3H), 3.50 (d, 1H), 3.12-2. 92 (m, 3H), 2.79-2. 75 (m, 1H), 2.61-2. 53 (m, 1H), 2.46-2. 41 (m, 1H), 2.37-2. 03 (m, 2H), 2.30 (s, 3H), 2.24 (s, 3H), 2.03 (s, 3H).

13C-NMR (75 MHz, CDCIs) : 8 172.5, 168.1, 145.7, 145.2, 144.5, 144.3, 142.7, 141.2, 140.0, 131.2, 129.4, 129.0, 125.5, 124.3, 121.2, 121.0, 118. 0, 114.1, 113.8, 113.3, 109.8, 101.8, 64.5, 61.1, 60.2, 59.8, 58.9, 58. 7, 55.0, 48.5, 47.5, 42.0, 41.8, 39.6, 28.7, 28.0, 20.3, 15.6, 9.6.

ESI-MS m/z: Calcd. for C39H4oN40loS : 756.2. Found (M+H+): 757.2.

Example 166 186 187 To a solution of 1 equiv. of compound 186 in CH2C12 (0.036M) under Argon at room temperature, were added 40 equiv. of Pyr, 20 equiv. of Allyl chloroformate and a catalityc amount of DMAP in small portions during 26h. Then the reaction was quenched with water/ice. The aqueous layer was extracted with CH2Cl2 and the organic layer was dried over Na2SO4.

Flash cromatography gives pure compound 187 (88%).

187. 1H-NMR (300 MHz, CDCIs) : 8 6.72 (s, 1H), 6.60 (s, 1H), 6.56 (bs, 1H), 6.02 (d, 2H), 6.04-5. 76 (m, 2H), 5.69-5. 57 (m, 1H), 5.42-4. 97 (m, 6H), 4.69- 4.49 (m, 5H), 4.34-4. 29 (m, 1H), 4.22-4. 09 (m, 2H), 3.78 (s, 3H), 3.57 (s, 3H), 3.78-3. 48 (m, 2H), 3.22-3. 05 (m, 3H), 2.89-2. 43 (m, 3H), 2.36-2. 16 (m, 2H), 2.31 (s, 3H), 2.29 (s, 3H), 2.05, 2.04 (2s, 3H).

ESI-MS m/z: Calcd. for C47H48N4014S : 924.3. Found (M+H+): 925.3.

Example 167 Method A: To a solution of 1 equiv. of starting material in CH2Cl2 (0.032M) under Argon were added 2 equiv. of the anhydride and 2 equiv. of base.

The reaction was followed by TLC and quenched with NaHCOs, extracted with CH2Cl2 and the organic layers dried over Na2S04. Flash chromatography gives pure compounds.

Compound 188 is obtained with 1.5 equiv. of ((CH3) 3COCO) 20 without base in CH3CN). Compounds 189 and 190 are obtained with 1 equiv. of ((CH3) 3COCO) 20 and 4 equiv. of iPr2NEt in CH3CN. The ratio of these two compounds can be modified using other experimental conditions (reaction time and equiv. of reagents); even compound 190 can be obtained (78%) after 5 days when the reaction is performed with 7 equiv. of (CH3) sCOCO) 20 and 21 equiv. of iPr2NEt.

188: lH-NMR (300 MHz, CDC13) : 8 6.58 (s, 1H), 6.46 (s, 1H), 6.45, 6.43 (2s, 1H), 6.36, 5.80 (bs, s, 1H), 6.05-5. 97 (m, 2H), 5.79, 5.44 (2d, 1H), 5.48 (bs, 1H), 5.05-4. 94 (m, 2H), 4.67, 4.61 (2bs, 1H), 4.31 (s, 1H), 4.23-4. 10 (m, 2H), 3.76, 3.75 (2s, 3H), 3.61 (s, 3H), 3.52-3. 46 (m, 1H), 3.18-3. 05 (m, 3H), 2.78- 2.04 (m, 5H), 2.29 (s, 3H), 2.27 (s, 3H), 2.04, 1.98 (2s, 3H), 1.46, 1.32 (2s, 9H).

13C-NMR (75 MHz, CDC13) : 8 172.8, 172.4, 168.1, 154.5, 152.9, 146.9, 145.9, 145.3, 144.9, 144.5, 144.3, 143.2, 142.7, 141.2, 141.1, 140.0, 139.6, 131.0, 130.4, 130. 1, 129.7, 129.0, 128.9, 125.5, 125.3, 121.6, 121.3, 121.1, 121.0, 120.6, 120. G, ~116. 8,116. 4,114. 1,113. 6,113. 3,109. 8,101. 7,81. 1, 80.7, 64.3, 61.2, 60.8, 60.2, 60.1, 59.9, 59.3, 58.3, 58.2, 58.1, 57.4, 55.0, 48.4, 48.2, 47.2, 45.8, 42.0, 41.7, 41.4, 39.6, 39.4, 28.6, 28.0, 27.9, 27.2, 20.7, 20.2, 15.7, 14.0, 9.6, 9.4.

ESI-MS m/z : Calcd. for C44H48N4O12S : 856.3. Found (M+H+) : 857.2.

189: 1H-NMR (300 MHz, CDCIs) : 8 6.68 (s, 1H), 6.61 (s, 1H), 6.57 (s, 1H), 6.01 (dd, 2H), 5.78 (bs, 1H), 5.02 (d, 1H), 4.54 (bs, 1H), 4.50 (d, 1H), 4.35 (s, 1H), 4.18 (d 1H), 4.09 (dd, 1H), 3.87-3. 82 (m, 1H), 3.77 (s, 3H), 3.58 (s, 3H), 3.53 (bd, 1H), 3.13-3. 07 (m, 2H), 2.98 (dd, 1H), 2.83-2. 75 (m, 1H), 2.68- 2.57 (m, 1H), 2.52-2. 43 (m, 1H), 2.37-2. 16 (m, 2H), 2.30 (s, 3H), 2.27 (s, 3H), 2.03 (s, 3H), 1.50 (s, 9H).

ESI-MS m/z: Calcd. for C44H48N4012S : 856.3. Found (M+H+) : 857.3.

190: 1H-NMR (300 MHz, CDCIs) : 8 6.69 (s, 1H), 6.59-6. 56 (m, 2H), 6.05-5. 97 (m, 2H), 5.93, 5.77 (2s, 1H), 5.68, 5.43 (2d, 1H), 5.04-4. 99 (m, 2H), 4.64- 4.58 (m, 1H), 4.32-4. 08 (m, 3H), 3.77 (s, 3H), 3.59 (s, 3H), 3.47-3. 44 (m, 1H), 3.11-3. 06 (m, 3H), 2.83-2. 02 (m, 11H), 2.04, 2.02 (2s, 3H), 1.50, 1.45, 1.33 (3s, 18H).

ESI-MS m/z: Calcd. for C49H56N4014S : 956.3. Found (M+H+): 957.2.

Example 168 Compound 191 is obtained using 3 equiv. of acetic anhydride as the anhydride and 5 equiv. of pyr as base (Method A).

191. lH-NMR (300 MHz, CDC13) : 5 6.61, 6.60 (2s, 1H), 6.57, 6.56 (2s, 2H), 6.40, 5.81 (bs, s, 1H), 6.04-5. 97 (m, 2H), 5.79, 5.44 (2d, 1H), 5.05-5. 00 (m, 1H). 4.94-4. 90 (m, 1H), 4.67, 4.60 (2bs, 1H), 4.31 (s, 1H), 4.22-4. 08 (m, 2H), 3.77, 3.76 (2s, 3H), 3.55 (s, 3H), 3.51-3. 46 (m, 1H), 3.18-3. 10 (m, 3H), 2.79- 2.72 (m, 1H), 2.66-2. 56 (m, 1H), 2.51-2. 45 (m, 1H), 2.39-2. 03 (m, 2H), 2.29 (s, 3H), 2.28, 2. 27 (2s, 3H), 2.24 (s, 3H), 2.03, 1.97 (2s, 3H), 1.46, 1.32 (2s, 9H).

13C-NMR (75 MHz, CDC13) : 8 172.3, 172.1, 169.0, 168.1, 156.6, 152.9, 148.4, 146.6, 145.9, 145.2, 143.2, 142.8, 141.4, 138.6, 132.5, 131.2, 130.7, 130.0, 129.8, 128.7, 122.5, 121.7, 121.3, 120.8, 120.5, 116.6, 116.4, 113.4, 111.8, 101.9, 81.2, 80.9, 64. 7, 61.2, 60.9, 60.3, 60.1, 59.8, 58.4, 58.2, 57.9, 55.1, 48.5, 48.2, 47.3, 45.9, 42.3, 41.5, 39.6, 39.5, 28.6, 28.3, 28.2, 28.1, 27.4, 20.6, 20.4, 15.8, 9.7.

ESI-MS m/z: Calcd. for C46HsoN4013S : 898.3. Found (M+H+) : 899.3.

Example 169 Method B: To a solution of 1 equiv. of starting material in CH2C12 (0.032M) under Argon at room temperature were added 2 equiv. of base and 2 equiv. of the acid chloride. The reaction was followed by TLC and quenched with NaHCOs, extracted with CH2C12 and the organic layers dried over Na2SO4.

Flash chromatography gives pure compounds.

188 192 Compound 192 is obtained with 2.5 equiv. of butyryl chloride and 3.5 equiv. of pyridine. Some starting material (11 %) was recovered after chromatographic purification (Method B).

192. lH-NMR (300 MHz, CDC13) : 8 6.60-6. 55 (m, 3H), 6.47, 5.82 (2bs, 1H), 6.04-5. 97 (m, 2H), 5.81, 5.44 (2d, 1H), 5.05-5. 00 (m, 1H), 4.95-4. 93 (m, 1H), 4.67, 4.59 (2bs, 1H), 4.31 (s, 1H), 4.21 (s, 1H), 4.15-4. 08 (m, 1H), 3.77, 3.76 (2s, 3H), 3.54 (s, 3H), 3.52-3. 46 (m, 1H), 3.18-3. 10 (m, 3H), 2.79-2. 75 (m, 1H), 2.65-2. 55 (m, 1H), 2.50-2. 45 (m, 1H), 2.48 (t, 2H), 2.38-2. 03 (m, 2H), 2.29 (s, 3H), 2.28, 2.27 (2s, 3H), 2.04, 1.96 (2s, 3H), 1.79-1. 67 (m, 2H), 1.47, 1.32 (2s, 9H), 1.00 (t, 3H).

13C-NMR (75 MHz, CDCIs) : 6 172.3, 172.1, 171.6, 168.0, 154.6, 152.9, 148.5, 146.7, 145.9, 145.2, 143.2, 142.8, 141.4, 138.7, 132.3, 131.2, 130. 7, 130.0, 129.8, 128.6, 122.5, 121.7, 121.3, 120.8, 120.5, 116.7, 116.4, 113.7, 113.4, 111.8, 101.9, 81.2, 80.9, 64.7, 61.2, 60.9, 60.3, 60.3, 60.1, 59.8, 58.4, 58.2, 57.9, 55.1, 48.5, 48.2, 47.3, 45.9, 42.3, 41.5, 39.6, 39. 5, 35. 8, 28.6, 28.3, 28.2, 28.1, 27.4, 20.6, 20.4, 18.5, 15.8, 13.5, 9.7, 9.6.

ESI-MS m/z: Calcd. for C48H54N4013S : 926.3. Found (M+H+) : 927.3.

Example 170 192 193 Compound 193 is obtained using 10 equiv. of butyryl chloride as the acid chloride and 10 equiv of Et3N as base (Method B). Compound 192 (13%) is recovered after chromatographic purification.

193. lH-NMR (300 MHz, CDCIs) : 8 6.94 (s, 1H), 6.61 (s, 1H), 6.55 (s, 1H), 6.01 (d, 2H), 5.34-5. 32 (m, 0.4H), 5.11-4. 93 (m, 2.6H), 4.52-4. 50 (m, 1H), 4.32-4. 30 (m, 1H), 4.21 (d, 1H), 4.13-4. 09 (m, 1H), 3.75, 3.74 (2s, 3H), 3.55 (s, 3H), 3.48-3. 46 (m, 1H), 3.22-3. 08 (m, 3H), 2.82-2. 78 (m, 1H), 2.66-2. 59 (m, 1H), 2.62 (t, 2H), 2.51-2. 46 (m, 1H), 2.49 (t, 2H), 2.35-2. 17 (m, 2H), 2.32, 2.31 (2s, 6H), 2.04 (s, 3H), 2.01-1. 85 (m, 2H), 1.80-1. 67 (m, 2H), 1.44, 1.37 (2s, 9H), 1.12 (t, 3H), 1.00 (t, 3H).

ESI-MS m/z: Calcd. for C52H6oN4014S : 996.4. Found (M+H+): 997.3.

Example 171 Compound 194 is obtained using 2.5 equiv. of cinnamoyl chloride as the acid chloride and 3.5 equiv. of pyr as base (Method B). Compound 188 (8%) is recovered after chromatographic purification.

194 1H-NMR (300 MHz, CDCI3) : 5 7.80 (d, 1H), 7.68-7. 54 (m, 2H), 7.50-7. 38 (m, 3H), 6.69-6. 57 (m, 4H), 6.47, 5.84 (2bs, 1H), 6.04-5. 97 (m, 2H), 5.81, 5.45 (2d, 1H), 5.06-5. 01 (m, 1H), 4.95-4. 93 (m, 1H), 4.68, 4.61 (2bs, 1H), 4.32 (s, 1H), 4.23-4. 10 (m, 2H), 3.77, 3.76 (2s, 3H), 3.57 (s, 3H), 3.52-3. 47 (m, 1H), 3.19-3. 09 (m, 3H), 2.82-2. 78 (m, 1H), 2.69-2. 62 (m, 1H), 2.54-2. 47 (m, 1H), 2.41-2. 20 (m, 2H), 2.30, 2.28 (2s, 6H), 2.04, 1.97 (2s, 3H), 1.47, 1.33 (2s, 9H).

13C-NMR (75 MHz, CDC13) : 8 172.3, 172.1, 168.1, 164.9, 152.9, 148.6, 146.7, 146.5, 145.9, 145.5, 143.2, 142.8, 138.6, 134.2, 132.3, 131.2, 130.7, 130.6, 130.3, 130.0, 129.8, 128.9, 128.7, 128.2, 128.1, 122.6, 121.3, 120.8, 120.5, 116.9, 116.7, 116.5, 113.7, 113.4, 111.8, 101.9, 81.2, 64.8, 61.2, 60.9, 60.3, 60.3, 60.2, 59.8, 58.4, 58.2, 57.9, 55.2, 48.5, 48.2, 47.3, 45.9, 42.3, 41.5, 39.6, 39.5, 28.6, 28.3, 28.2, 28.1, 27.4, 20.6, 20.4, 15.8, 9.7, 9.6.

ESI-MS m/z: Calcd. for C53H54N4013S : 986.3. Found (M+H+) : 987.3.

Example 172 Method C: To a solution of 1 equiv. of starting material in CH2C12 (0.032M) under Argon were added 2 equiv. of acid, 2 equiv. of DMAP and 2 equiv. of EDC. HC1. The reaction was stirred at room temperature for 2 h. After this time was diluted with CHaCb, washed with brine and the organic layer dried over Na2SO4. Flash chromatography gives pure compounds. Using 1.5 equiv. of octanoic acid as the acid, we obtain a mixture of compounds 195 and 196.

195 : lH-NMR (300 MHz, CDC13) : 8 6.59-6. 55 (m, 3H), 6.08, 5.78 (bs, s, 1H), 6.04-5. 97 (m, 2H), 5.72, 5.44 (2d, 1H), 5.05-4. 99 (m, 1H), 4.95-4. 92 (m, 1H), 4.65, 4.60 (2bs, 1H), 4.31, 4.30 (2s, 1H), 4.22-4. 18 (m, 1H), 4.14-4. 09 (m, 1H), 3.77 (1s, 3H), 3.54 (s, 3H), 3.47 (d, 1H), 3.18-3. 06 (m, 3H), 2.79-2. 75 (m, 1H), 2.65-2. 55 (m, 1H), 2.52-2. 44 (m, 1H), 2.49 (t, 2H), 2.37-2. 14 (m, 2H), 2.30 (s, 3H), 2.28, 2.27 (2s, 3H), 2.04, 2.00 (2s, 3H), 1.74-1. 64 (m, 2H), 1.46, 1.33 (2s, 9H), 1.37-1. 28 (m, 8H), 0.87 (t, 3H).

13C-NMR (75 MHz, CDCIs) : 8 172. 3,172. 1,171. 8,168. 1,154. 6,152. 9, 148.5, 146.6, 145.9, 145.5, 145.3, 143.1, 142.8, 141.4, 140.1, 139.9, 138.7, 132.3, 132.1, 131.2, 130.8, 129. 9,129. 8,128. 7,122. 5,121. 7,121. 3,120. 7, 120.6, 116.6, 116.5, 114. 7, 113.7, 113.4, 111.8, 102.0, 81.2, 80.9, 64. 8, 61.2, 60.9, 60.4, 60.1, 59.9, 58.4, 58.2, 58.0, 55. 1, 48.5, 48. 2, 47.3, 45.9, 42.3, 41.6, 41.5, 39.6, 39.5, 34.0, 31.6, 28.9, 28.9, 28.6, 28.4, 28.2, 28.1, 27.4, 25.0, 22.6, 20.5, 20.4, 15.8, 14.0, 9.7.

ESI-MS m/z: Calcd. for C52H62N4013S : 982.4. Found (M+H+) : 983.3.

196 : lH-NMR (300 MHz, CDCIs) : 8 6.94 (s, 1H), 6.60 (s, 1H), 6.55 (s, 1H), 6.01 (d, 2H), 5.34-5. 30,5. 11-4.93 (2m, 3H), 4.52-4. 49 (m, 1H), 4.34-4. 32 (m, 1H), 4.22-4. 09 (m, 2H), 3.74, 3.73 (2s, 3H), 3.55 (s, 3H), 3.48-3. 45 (m, 1H), 3.22-3. 07 (m, 3H), 2.82-2. 79 (m, 1H), 2.65-2. 60 (m, 1H), 2.62 (t, 2H), 2.52- 2.45 (m, 1H), 2.50 (t, 2H), 2.37-2. 17 (m, 2H), 2.31, 2.30 (2s, 6H), 2.04 (s, 3H), 1.89-1. 82 (m, 2H), 1.75-1. 65 (m, 2H), 1.59-1. 23 (m, 16H), 1.44, 1.37 (2s, 9H), 0.90-0. 85 (m, 6H).

13C-NMR (75 MHz, CDCIs) : 8 172.2, 171.8, 170.1, 167.7, 153.1, 148.5, 147.8, 145.6, 141.3, 140.2, 138.8, 132.1, 131.9, 131.3, 128.8, 127.7, 126. 6, 125.1, 122.5, 120.5, 116.2, 114.7, 113.7, 113.6, 111.7, 102.0, 81.5, 64.8, 61.2, 60.0, 59.9, 58.6, 58.4, 58.0, 55.1, 48.5, 47.8, 46.4, 42.5, 41.6, 39.6, 34.3, 34.0, 31.7, 29. 3, 29.2, 28.9, 28.9, 28.6, 28.1, 28.0, 27.5, 25.2, 25.0, 22.6, 20.3, 15.9, 14.0, 9.7.

ESI-MS m/z : Calcd. for C6oH76N4014S : 1108.5. Found (M+H+) : 1109.4.

Example 173 188 197 198 56% 26% Using 1.5 equiv. of palmitic acid as the acid, we obtain a mixture of compounds 197 and 198 (Method C).

197 : 1H-NMR (300 MHz, CDCIs) : 8 6.59-6. 55 (m, 3H), 6.25, 5.78 (bs, s, 1H), 6.04-5. 97 (m, 2H), 5.77, 5.44 (2bd, 1H), 5.05-5. 00 (m, 1H), 4.96-4. 93 (m, 1H), 4.66, 4.60 (2bs, 1H), 4.31 (bs, 1H), 4.23-4. 19 (m, 1H), 4.15-4. 09 (m, 1H), 3.77, 3.76 (2s, 3H), 3.54 (s, 3H), 3.50-3. 47 (m, 1H), 3.18-3. 07 (m, 3H), 2.79-2. 75 (m, 1H), 2.66-2. 57 (m, 1H), 2.52-2. 47 (m, 1H), 2.49 (t, 2H), 2.39- 2.13 (m, 2H), 2.30, 2.28, 2.27 (3s, 6H), 2.04, 1.98 (2s, 3H), 1.71-1. 64 (m, 2H), 1.46, 1.33 (2s, 9H), 1.46-1. 25 (m, 24H), 0.88 (t, 3H).

13C-NMR (75 MHz, CDCIs) : 8 172.3, 172.1, 171.8, 168.1, 154.6, 152.9, 148.5, 146.6, 145.9, 145.5, 143.1, 142.7, 141.4, 140.1, 138.7, 132.3, 131.2, 130.8, 129.8, 128.6, 122.5, 121.7, 121.3, 120.6, 116.6, 116.5, 113.7, 113.4, 111.8, 102.0, 81.2, 80.9, 64.8, 61.2, 60.9, 60.4, 60.1, 59.9, 58.4, 58.2, 58.0, 55.1, 53.4, 48.5, 48.2, 47.3, 45.9, 42.3, 41.6, 41. 5, 39.6, 39.5, 34.0, 31. 6, 29.7, 29.6, 29.6, 29.5, 29.3, 29.3, 29.0, 28.6, 28.2, 28.1, 27.4, 25.0, 22.7, 20.5, 20.4, 15.8, 14.1, 9.7.

ESI-MS m/z: Calcd. for C6oH78N4013S : 1094.5. Found (M+H+) : 1095.4.

198 : lH-NMR (300 MHz, CDCIs) : 8 6.94 (s, 1H), 6.60 (s, 1H), 6.54 (s, 1H), 6.01 (d, 2H), 5.34-5. 33,5. 11-4.93 (2m, 3H), 4.53-4. 52 (m, 1H), 4.32-4. 29 (m, 1H), 4.22-4. 09 (m, 2H), 3.74, 3.73 (2s, 3H), 3.55 (s, 3H), 3.48-3. 46 (m, 1H), 3.22-3. 09 (m, 3H), 2.82-2. 78 (m, 1H), 2.65-2. 60 (m, 1H), 2.62 (t, 2H), 2.52- 2.47 (m, 1H), 2.50 (t, 2H), 2.37-2. 17 (m, 2H), 2.31 (s, 3H), 2.30 (s, 3H), 2.04 (s, 3H), 1.89-1. 81 (m, 2H), 1.72-1. 64 (m, 2H), 1.44-1. 25 (m, 48H), 1.44, 1.37 (2s, 9H), 0.90-0. 85 (m, 6H).

13C-NMR (75 MHz, CDCIs) : 8 172.1, 171.8, 170.4, 170.1, 167.7, 153.1, 148.5, 147.9, 145.6, 141.3, 140.2, 138.8, 132.1, 131.9, 131.3, 128.8, 127.7, 126.6, 125.1, 122.5, 120. 5,116. 2,114. 7, 113.6, 111.7, 102.0, 81.5, 64.8, 61.2, 60.0, 58.6, 58.1, 55. 1, 48. 5, 47.8, 46.4, 42.5, 41.6, 39.6, 34.3, 34.0, 31.9, 29.7, 29.7, 29.5, 29.5, 29.3, 29. 3, 29.0, 28.6, 28.1, 28.0, 27.4, 25.2, 25.0, 22.7, 20.3, 15.9, 14.1, 9.7.

ESI-MS m/z: Calcd. for C76HlosN4Ol4S : 1332.8. Found (M+H+): 1333.6.

Example 174 190 199 To a solution of 1 equiv. of compound 190 in DMF (0.02M) under Argon at room temperature, were added 0.7 equiv. of Cs2CO3 and 2 equiv. of allyl bromide. The reaction was stirred for 72 h and then quenched with AcOH.

The crude was diluted with Hex/EtOAc 1: 3, washed with a saturated solution of NaCI, the aqueous layers extracted with Hex/EtOAc 1: 3, and the organic layers dried over Na2SO4. Flash cromatography gives pure compound 199 (66%).

199. lH-NMR (300 MHz, CDCIs) : 8 6.79 (s, 1H), 6.69 (s, 1H), 6.57, 6.56 (2s, 1H), 6.28-6. 01 (m, 1H), 6.01 (d, 1H), 5.56-5. 24 (m, 3H), 5.07-4. 43 (m, 5H), 4.31-4. 29 (m, 1H), 4.20-4. 08 (m, 2H), 3.84, 3.81 (2s, 3H), 3.58 (s, 3H), 3.48- 3.45 (m, 1H), 3.17-3. 06 (m, 3H), 2.83-2. 77 (m, 1H), 2.69-2. 59 (m, 1H), 2.55- 2.47 (m, 1H), 2.36-2. 17 (m, 2H), 2.28 (s, 3H), 2.24 (s, 3H), 2.04 (s, 3H), 1.50, 1. 43, 1.40 (3s, 18H).

ESI-MS m/z: Calcd. for C52H6oN4014S : 996.4. Found (M+H+) : 997.2.

Example 175 188 200 To a solution of compound 188 in CHsCN (0.016M) at room temperature under Argon, were added 100 equiv. of formaline (37 wt. % in water) and 5 equiv. of NaCNBH3. After 1 h 20 equiv. of acetic acid were added. The reaction mixture was stirred for 2 h more. After this time, it was diluted with CH2Cl2, neutralise with NaHC03 and extracted with CH2Cl2. The organic layers were dried over Na2S04. Flash chromatography gives pure compound (86%).

200 lH-NMR (300 MHz, CDCIs) : 8 6.47-6. 45 (m, 2H), 6.18 (s, 1H), 6.09-5. 96 (m, 2H), 5.77, 5.42 (2s, 1H), 5.66, 5.43 (2d, 1H), 4.99-4. 87 (m, 2H), 4.66, 4.62 (2bs, 1H), 4.35-4. 32 (m, 1H), 4.13, 4.05 (2d, 1H), 3.90-3. 83 (m, 1H), 3.77 (s, 3H), 3.55 (s, 3H), 3.49-3. 44 (m, 1H), 3.23-3. 13 (m, 2H), 3.04-2. 93 (m, 1H), 2.71-2. 56 (m, 3H), 2.47-2. 17 (m, 2H), 2.32, 2.30 (2s, 3H), 2.2. 20, 2.17 (2s, 6H), 2.02, 2.01 (2s, 3H), 1.46, 1.32 (2s, 9H).

ESI-MS m/z: Calcd. for C45H, 5oN4012S : 870.3. Found (M+H+) : 871.2.

Example 176 Method F: To a solution of 1 equiv. of starting material in CH2C12/H20/TFA 2: 1: 3.3 (0.013M) was stirred at room temperature for 15 min. The reaction was followed by TLC and neutralised with NaHCOs, extracted with CH2C12 and the organic layers dried with Na2SO4. Flash chromatography gives pure compounds. 201 was obtained using Method F. 1H-NMR (300 MHz, CDC13) : 8 6.82 (s, 1H), 6.49 (s, 1H), 6.41 (bs, 1H), 6.16-5. 98 (m, 1H), 6.03 (d, 2H), 5.46-5. 23 (m, 2H), 5.03 (d, 1H), 4.86-4. 79 (m, 1H), 4.56-3. 81 (m, 7H), 3.63 (s, 3H), 3.55-3. 52 (m, 1H), 3.49 (s, 3H), 3.14-2. 96 (m, 3H), 2.86-2. 17 (m, 8H), 2.25 (bs, 3H), 2.04 (1s, 3H).

ESI-MS m/z: Calcd. for C42H44N4OloS : 796.3. Found (M+H+) : 797.3.

Example 177 202 was obtained using Method F. lH-NMR (300 MHz, CDCI3) : 8 6.62 (s, 1H), 6.61 (s, 1H), 6.56 (s, 1H), 6.00 (dd, 2H), 5.78 (bs, 1H), 5.02 (d, 1H), 4.56 (bs, 1H), 4.50 (d, 1H), 4.34 (s, 1H), 4.19 (d 1H), 4.11 (dd, 1H), 3.86-3. 83 (m, 1H), 3.78 (s, 3H), 3.56 (s, 3H), 3.53 (bd, 1H), 3.14-3. 09 (m, 2H), 2.99 (dd, 1H), 2.83-2. 73 (m, 1H), 2.68-2. 59 (m, 1H), 2.51-2. 45 (m, 1H), 2.38-2. 17 (m, 2H), 2.31 (s, 3H), 2.27 (s, 3H), 2.24 (s, 3H), 2.03 (s, 3H). 13C-NMR (75 MHz, CDCIs) : 5 172.0, 169.0, 168.2, 148.4, 145.7, 145.4, 142.7, 141.3, 140.1, 138.5, 132.4, 131.3, 129.5, 128.6, 124.3, 122.5, 121. 3, 120.9, 118.1, 113.9, 111.7, 101.9, 64.8, 61.2, 60.4, 60.0, 59.0, 58.8, 55.1, 48.6, 47.6, 41.9, 39.6, 28.6, 28.1, 20.6, 20.4, 15.8, 9.7.

ESI-MS m/z: Calcd. for C41H42N4011S : 798.3. Found (M+H+) : 799.3.

Example 178 192 203 203 was obtained using Method F. lH-NMR (300 MHz, CDCIs) : 8 6.62 (s, 1H), 6.60 (s, 1H), 6.57 (s, 1H), 5.97 (dd, 2H), 5.78 (bs, 1H), 5.02 (d, 1H), 4.56 (bs, 1H), 4.50 (d, 1H), 4.34 (s, 1H), 4.19 (d 1H), 4.10 (dd, 1H), 3.86- 3.83 (m, 1H), 3.78 (s, 3H), 3.55 (s, 3H), 3.53 (bd, 1H), 3.14-3. 09 (m, 2H), 2.99 (dd, 1H), 2.82-2. 75 (m, 1H), 2.63-2. 55 (m, 1H), 2.52-2. 46 (m, 1H), 2.48 (t, 2H), 2.38-2. 17 (m, 2H), 2.31 (s, 3H), 2.27 (s, 3H), 2.03 (s, 3H), 1.79-1. 67 (m, 2H), 1.00 (t, 3H).

ESI-MS m/z: Calcd. for C43H46N4011S : 826.3. Found (M+H+) : 827.3.

Example 179 194 204 204 was obtained using Method F 1H NMR (300 MHz, CDC13) : 8 7.81 (d, 1H), 7. 58-7. 54 (m, 2H), 7. 41-7. 39 (m, 3H), 6.66 (d, 1H), 6.63 (s, 1H), 6.60 (s, 1H), 6.57 (s, 1H), 6.01 (d, 2H), 5.79 (bs, 1H), 5.04 (d, 1H), 4.57 (bs, 1H), 4.51 (d, 1H), 4.34 (s, 1H), 4.20 (d 1H), 4.12 (dd, 1H), 3. 87-3. 84 (m, 1H), 3. 79 (s, 3H), 3.57 (s, 3H), 3.54 (bd, 1H), 3.15-3. 09 (m, 2H), 3. 00 (dd, 1H), 2. 83-2. 78 (m, 1H), 2. 75-2. 62 (m, 1H), 2. 54-2. 48 (m, 1H), 2.41-2. 19 (m, 2H), 2.32 (s, 3H), 2.28 (s, 3H), 2.03 (s, 3H).

13C-NMR (300 MHz, CDCIs) : 8 172.2, 168.2, 164.9, 148.6, 146.5, 145.8, 145.4, 142.8, 141.4, 140.1, 138.6, 134.2, 132.5, 131.3, 130.6, 129.6, 128. 9, 128.7, 128.3, 124.4, 122.6, 121.0, 118.1, 116.9, 113.9, 113.4, 111.8, 101.9, 64.9, 61.2, 60.4, 60.0, 59.1, 58.8, 55.2, 48.6, 47.6, 42.2, 42.0, 39.6, 28.7, 28.2, 20.4, 15.8, 9.7.

ESI-MS m/z : Calcd. for C48H46N4011S : 886.3. Found (M+H+): 887.2.

Example 180 205 was obtained using Method F 1H-NMR (300 MHz, CDCIs) : 8 6.62 (s, 1H), 6.60 (s, 1H), 6.56 (s, 1H), 6.02 (d, 2H), 5.79 (bs, 1H), 5.03 (d, 1H), 4.57 (bs, 1H), 4.51 (d, 1H), 4.34 (s, 1H), 4.20 (d 1H), 4.12 (dd, 1H), 3. 87-3. 84 (m, 1H), 3.79 (s, 3H), 3.55 (s, 3H), 3.54 (bd, 1H), 3.15-3. 09 (m, 2H), 3. 00 (dd, 1H), 2. 82-2. 78 (m, 1H), 2. 68-2. 60 (m, 1H), 2. 53-2. 46 (m, 1H), 2. 50 (t, 2H), 2. 39- 2.18 (m, 2H), 2.32 (s, 3H), 2.28 (s, 3H), 2.04 (s, 3H), 1. 73-1. 65 (m, 2H), 1. 39- 1.24 (m, 8H), 0. 88 (t, 3H).

ESI-MS m/z : Calcd. for C47H54N4011S : 882.3. Found (M+H+) : 883. 3.

Example 181 196 206 206 was obtained using Method F. lH-NMR (300 MHz, CDC13) : 8 6.95 (s, 1H), 6.60 (s, 1H), 6.53 (s, 1H), 6.02 (dd, 2H), 5.02 (d, 1H), 4.45 (bs, 1H), 4.35 (s, 1H), 4.20 (d, 1H), 4.11 (dd, 1H), 4.04 (d, 1H), 3.88-3. 85 (m, 1H), 3.74 (s, 3H), 3.54 (bs, 4H), 3.17-3. 08 (m, 2H), 3.01 (dd, 1H), 2.83-2. 78 (m, 1H), 2.64-2. 59 (m, 1H), 2.62 (t, 2H), 2.52-2. 47 (m, 1H), 2.50 (t, 2H), 2.38-2. 17 (m, 2H), 2.31 (s, 3H), 2.29 (s, 3H), 2.04 (s, 3H), 1.87-1. 77 (m, 2H), 1.72-1. 64 (m, 2H), 1.49-1. 23 (m, 16H), 0.89-0. 85 (m, 6H).

ESI-MS m/z: Calcd. for C55H68N4012S : 1008.5. Found (M+H+) : 1009.4.

Example 182 207 was obtained using Method F. lH-NMR (300 MHz, CDCIs) : 8 6.62 (s, 1H), 6.59 (s, 1H), 6.55 (s, 1H), 6.01 (dd, 2H), 5.78 (bs, 1H), 5.02 (d, 1H), 4.56 (bs, 1H), 4.50 (d, 1H), 4.33 (s, 1H), 4.19 (d 1H), 4.10 (dd, 1H), 3.86-3. 83 (m, 1H), 3.78 (s, 3H), 3.54 (s, 3H), 3.53 (bd, 1H), 3.14-3. 08 (m, 2H), 2.99 (dd, 1H), 2.81-2. 78 (m, 1H), 2.68-2. 55 (m, 1H), 2.52-2. 45 (m, 1H), 2.49 (t, 2H), 2.38- 2.17 (m, 2H), 2.31 (s, 3H), 2.27 (s, 3H), 2.03 (s, 3H), 1.72-1. 64 (m, 2H), 1.38- 1.25 (m, 24H), 0.87 (t, 3H).

ESI-MS m/z: Calcd. for CssH70N4OllS : 994.5. Found (M+H+): 995.5.

Example 183 208 was obtained using Method F. lH-NMR (300 MHz, CDCIs) : 8 6.96 (s, 1H), 6.60 (s, 1H), 6.53 (s, 1H), 6.02 (dd, 2H), 5.02 (d, 1H), 4.45 (bs, 1H), 4.35 (s, 1H), 4.20 (d, 1H), 4.10 (dd, 1H), 4.05 (d, 1H), 3.88-3. 85 (m, 1H), 3.74 (s, 3H), 3.55 (bs, 4H), 3.17-3. 07 (m, 2H), 3.01 (dd, 1H), 2.84-2. 80 (m, 1H), 2.69-2. 59 (m, 1H), 2.62 (t, 2H), 2.52-2. 47 (m, 1H), 2.50 (t, 2H), 2.37-2. 19 (m, 2H), 2.32 (s, 3H), 2.29 (s, 3H), 2.04 (s, 3H), 1.87-1. 77 (m, 2H), 1.74-1. 64 (m, 2H), 1.45-1. 25 (m, 48H), 0.88 (t, 6H). 13C-NMR (75 MHz, CDCIs) : 8 172.1, 171.9, 171.3, 167.6, 148.4, 147.6, 145.6, 141.4, 141.3, 140.2, 138.7, 132.1, 131.6, 131.3, 130.1, 128.6, 128.0, 122.5, 120.7, 117.8, 113.8, 111.7, 102.0, 72.5, 65.0, 64.9, 61.2, 60.2, 59.9, 58.9, 58.4, 55.1, 48.7, 48.4, 42.3, 42.2, 39.6, 34.2, 34.0, 31.9, 29.7, 29.6, 29.5, 29.3, 29.2, 29.0, 28.6, 27.7, 25.2, 25.0, 22.7, 20.3, 15.8, 14.1, 9.7.

ESI-MS m/z: Calcd. for C7lHlooN40i2S : 1232.7. Found (M+H+) : 1233.6.

Example 184 200 209 209 was obtained using Method F. 1H-NMR (300 MHz, CDCIs) : 8 6.50 (s, 1H), 6.44 (s, 1H), 6.19 (s, 1H), 6.02 (d, 2H), 5.77 (bp 1H), 5.46 (bp, 1H), 4.96 (d, 1H), 4.59 (bp, 1H), 4.50 (d, 1H), 4.35 (s, 1H), 4.10 (d, 1H), 3.87-3. 82 (m, 2H), 3.78 (s, 3H), 3.54 (s, 3H), 3.53 (d, 1H), 3.30-3. 15 (m, 1H), 3.07-2. 91 (m, 2H), 2.69-2. 55 (m, 3H), 2.46-2. 39 (m, 2H), 2.30 (s, 3H), 2.23 (s, 3H), 2.19 (s, 3H), 2.02 (s, 3H).

ESI-MS m/z : Calcd. forC4oH42N40ioS : 770.3. Found (M+H+) : 771.3.

Example 185 Method H: To a solution of 1 equiv. of starting material in CH3CN/H20 3: 2 (0.009M) were added 30 equiv. of AgNO3. After 24 h the reaction was quenched with a mixture 1: 1 of saturated solutions of brine and NaHC03, stirred for 10 min and diluted and extracted with CH2C12. The organic layer was dried over Na2SO4. Chromatography gives pure compounds. 210 was obtained using Method H. lH-NMR (300 MHz, CDC13) : 8 6.62 (s, 1H), 6.60 (s, 1H), 6.56 (s, 1H), 5.99, 5.97 (2d, 2H), 5.13 (d, 1H), 4.84, 4.74 (2s, 1H), 4.52 (d, 1H), 4.45 (bs, 1H), 4.38 (d 1H), 4.02 (dd, 1H), 3.78 (s, 3H), 3.64-3. 54 (m, 2H), 3.54 (s, 3H), 3.17-3. 00 (m, 2H), 2.92-2. 80 (m, 2H), 2.69- 2.46 (m, 2H), 2.40-2. 17 (m, 2H), 2.31 (s, 3H), 2.27 (s, 3H), 2.24 (s, 3H), 2.02 (s, 3H).

ESI-MS m/z: Calcd. for C4oH43N3012S : 789.3. Found (M-H20+H+) : 772.3.

Example 186 203 211 211 was obtained using Method F. lH-NMR (300 MHz, CDC13) : 8 6.62 (s, 1H), 6.59 (s, 1H), 6.56 (s, 1H), 5.99, 5.98 (d, dd, 2H), 5.76 (bp, 1H), 5.14 (d, 1H), 4.84, 4.74 (2s, 1H), 4.52-4. 37 (m, 3H), 1.06-4. 00 (m, 1H), 3.78 (s, 3H), 3.67-3. 54 (m, 2H), 3.54 (s, 3H), 3.12-3. 00 (m, 2H), 2.92-2. 80 (m, 2H), 2.68- 2.60 (m, 1H), 2.51-2. 46 (m, 1H), 2.48 (t, 2H), 2.40-1. 99 (m, 2H), 2.31 (s, 3H), 2.27 (s, 3H), 2.02 (s, 3H), 1.80-1. 67 (m, 2H), 1.00 (t, 3H).

ESI-MS m/z: Calcd. for C42H47N3012S : 817.3. Found (M-H20+H+) : 800.2.

Example 187 204 212 212 was obtained using Method F. lH-NMR (300 MHz, CDC13) : 8 7.81 (d, 1H), 7.57-7. 54 (m, 2H), 7.41-7. 39 (m, 3H), 6.66 (d, 1H), 6.63 (s, 1H), 6.60 (s, 1H), 6.58 (s, 1H), 5.99, 5.98 (2d, 2H), 5.75 (bp, 1H), 5.15 (d, 1H), 4.85, 4.75 (2s, 1H), 4.54-4. 38 (m, 3H), 4.06-4. 03 (m, 1H), 3.79 (s, 3H), 3.65-3. 56 (m, 2H), 3.56 (s, 3H), 3.18-3. 02 (m, 2H), 2.93-2. 80 (m, 2H), 2.66-2. 62 (m, 1H), 2.54-2. 49 (m, 1H), 2.42-2. 20 (m, 2H), 2.32 (s, 3H), 2.28 (s, 3H), 2.02 (s, 3H).

ESI-MS m/z: Calcd. for C47H47N3012S : 877.3. Found (M-H20+H+) : 860.3.

Example 188 213 was obtained using Method F. lH-NMR (300 MHz, CDC13) : 8 6.62 (s, 1H), 6.59 (s, 1H), 6.56 (s, 1H), 5.99, 5.98 (2d, 2H), 5.72 (bs, 1H), 5.14 (d, 1H), 4.84, 4.74 (2s, 1H), 4.51-4. 37 (m, 3H), 4.06-4. 04 (m, 1H), 7.78, 3.76 (2s, 3H), 3.64-3. 54 (m, 2H), 3.54, 3.53 (2s, 3H), 3.15-3. 00 (m, 2H), 2.92- 2.83 (m, 2H), 2.68-2. 47 (m, 2H), 2.49 (t, 2H), 2.40-2. 27 (m, 2H), 2.31 (s, 3H), 2.27 (s, 3H), 2.02 (s, 3H), 1.72-1. 65 (m, 2H), 1.39-1. 24 (m, 8H), 0.88 (t, 3H).

ESI-MS m/z: Calcd. for C46H55N3012S : 873.4. Found (M-H20+H+) : 856.3.

Example 189 214 was obtained using Method F. 1H-NMR (300 MHz, CDCIs) : 8 6.96 (s, 1H), 6.60 (s, 1H), 6.54 (s, 1H), 5.99 (d, 2H), 5.14 (d, 1H), 4.84, 4.77 (2s, 1H), 4.54 (bp, 1H), 4.36 (bp, 1H), 4.02 (dd, 1H), 3.90 (d, 1H), 3.75 (s, 3H), 3.62- 3.49 (m, 2H), 3.54 (s, 3H), 3. 15-2. 86 (m, 4H), 2.64-2. 47 (m, 2H), 2.62 (t, 2H), 2.50 (t, 2H), 2.41-2. 17 (m, 2H), 2.32 (s, 3H), 2.29 (s, 3H), 2.03 (s, 3H), 1.85-1. 67 (m, 4H), 1.50-1. 25 (m, 16H), 0.90-0. 85 (m, 6H).

ESI-MS m/z: Calcd. for C54H69N3013S : 999.5. Found (M-H20+H+) : 982.4.

Example 190 215 was obtained using Method F. lH-NMR (300 MHz, CDCIs) : 8 6.62 (s, 1H), 6.59 (s, 1H), 6.55 (s, 1H), 5.99, 5.98 (2d, 2H), 5.13 (d, 1H), 4.84, 4.74 (2s, 1H), 4.52 (d, 1H), 4.45 (bs, 1H), 4.38 (d 1H), 4.02 (dd, 1H), 3.78 (s, 3H), 3.76-3. 53 (m, 2H), 3.53 (s, 3H), 3.16-3. 00 (m, 2H), 292-2.80 (m, 2H), 2.63- 2.58 (m, 1H), 2.52-2. 47 (m, 3H), 2.40-2. 19 (m, 2H), 2.31 (s, 3H), 2.27 (s, 3H), 2.02 (s, 3H), 1.72-1. 67 (m, 2H), 1.38-1. 25 (m, 24H), 0.87 (t, 3H).

ESI-MS m/z: Calcd. for C54H7lN3012S : 986.2. Found (M-H20 +) : 968.5.

Example 191 216 was obtained using Method F. lH-NMR (300 MHz, CDCIs) : 8 6.96 (s, 1H), 6.60 (s, 1H), 6.54 (s, 1H), 6.00, 5.99 (d, dd, 2H), 5.14 (d, 1H), 4.85, 4.78 (2s, 1H), 4.54 (bp, 1H), 4.35 (bp, 1H), 4.02 (dd, 1H), 3.90 (d, 1H), 3.75 (s, 3H), 3.62-3. 49 (m, 2H), 3.54 (s, 3H), 3.17-2. 86 (m, 4H), 2.70-2. 59 (m, 3H), 2.52-2. 47 (m, 3H), 2.40-2. 17 (m, 2H), 2.32 (s, 3H), 2.29 (s, 3H), 2.03 (s, 3H), 1.85-1. 67 (m, 4H), 1.45-1. 25 (m, 48H), 0.88 (t, 6H).

ESI-MS m/z: Calcd. for C7oHlolN3013S : 1224.6. Found (M-H20+) : 1206.6.

Example 192 217 was obtained using Method F. lH-NMR (300 MHz, CD30D) : 8 6.43 (s, 1H), 6.36 (s, 1H), 6.20 (s, 1H), 6.06 (d, 2H), 5.04 (d, 1H), 4.75 (d, 1H), 4.60 (bp, 1H), 4.42 (d 1 H), 4.10 (d, 1 H), 3.81 (dd, 1H), 3.72 (s, 3H), 3.65-3. 60 (m, 2H), 3.51 (s, 3H), 3.13-3. 01 (m, 2H), 2.86 (d, 1H), 2.65-2. 32 (m, 5H), 2.32 (s, 3H), 2.21 (s, 3H), 2.19 (s, 3H), 2.01 (s, 3H).

ESI-MS m/z: Calcd. for C39H43N3O11S : 761.3 Found (M+H +) : 762.3.

Example 193 A solution of N-methyl pyridine-4-carboxaldehyde iodide in anhydrous DMF (0.26M) was treated with anhydrous toluene (2x5 mL). A solution of compound 218 (118.7 mg, 1 equiv) (previously treated with anhydrous toluene 2x5mL) in anhydrous CHaCb (0.03M) was added, via cannula, at 23 oc to the solution of N-methyl pyridine-4-carboxaldehyde iodide. The reaction mixture was stirred at 23 oc for 4 hours. After this time DBU (1.0 equiv) was dropwise added at 23 °C and was stirred for 15 minutes at 23 °C.

A freshly aqueous saturated solution of oxalic acid (5.4 mL) was added to the reaction mixture and was stirred for 30 minutes at 23 °C. Then the reaction mixture was cooled to 0 °C and NaHCOs was portionwise added followed by addittion of aqueous saturated solution of NaHCO3. The mixture was extracted with Et20. The combined organic layers were dried over Na2SO4, filtered and the solvent was removed under reduced pressure. Flash chromatography gives pure compound 219 (54%). O H 0 NH2 OH p '' HO OH Me HO OH MeX Se ,,, c, o ; s I O me Mu N--Me pgU, I/N N--Me oxalic acid \-O CN \0 CN 218 219 219. 1H-NMR (300 MHz, CDCIs) : 8 6.46 (s, 1H), 6.06 (dd, 2H), 5.59 (s, 1H), 5.08 (d, 1H), 4.66 (bs, 1H), 4.54 (bs, 1H), 4.38 (s, 1H), 4.28 (dd, 1H), 4.20 (dd, 1H), 4.14 (d, 1H), 3.54 (d, 1H), 3.43-3. 40 (m, 1H), 2.93-2. 82 (m, 2H), 2.71-2. 55 (m, 2H), 2.34 (s, 3H), 2.19 (s, 3H), 2.13 (s, 3H), 2.04 (s, 3H).

13C-NMR (75 MHz, CDC13) : 8 186.5, 168.7, 160.5, 146.4, 143.5, 141.6, 140.6, 138.2, 127.2, 123.3, 121.0, 120.0, 118.0, 117.5, 113.4, 113. 3, 102.2, 61.8, 61.3, 59.8, 59.0, 54.6, 54.5, 43.1, 41.6, 36. 9, 23.9, 20.4, 15.7, 9.7.

ESI-MS m/z: Calcd. for C3oH29N309S : 607.3 Found (M+H+) : 608.2.

Example 194 To a solution of 1 equiv. of compound 219 in EtOH (0.03M) were added 5 equiv. of AcOH and 3.5 equiv. of 2- [3-hydroxy-4-methoxyphenyl] ethylamine.

The reaction was stirred overnight. Then the solvent was eliminated under reduced pressure. Flash chromatography gives pure compound (62%).

220. 1H-NMR (300 MHz, CDC13) : 8 6.54 (s, 1H), 6.44 (s, 1H), 6.41 (s, 1H), 6.01 (d, 2H), 4.98 (d, 1H), 4.58-4. 40 (bm, 4H), 4.29 (s, 1H), 4.26 (d, 1H), 4.13-4. 09 (m, 2H), 3.61 (s, 3H), 3.51-3. 49 (m, 1H), 3.41-3. 38 (m, 1H), 3.21 (dt, 1H), 3.00-2. 85 (m, 3H), 2.71-2. 60 (m, 1H), 2.42-1. 97 (m, 3H), 2.28 (s, 6H), 2.21 (s, 3H), 2.04 (s, 3H).

13C-NMR (75 MHz, CDC13) : 8 172.1, 145.6, 145.3, 144.7, 144.5, 141.4, 140.0, 138.5, 128.7, 127.8, 124.9, 120.8, 119.8, 118.1, 118.0, 114.0, 113.8, 109.8, 101.8, 64.3, 60.9, 60.6, 60.2, 59. 6, 55.2, 54.9, 54.6, 42.2, 41.7, 41.6, 28.3, 24.2, 20.5, 15.9, 9.7. ?? ? ESI-MS m/z: Calcd. for C39H4oN40loS : 756.3 Found (M+H+) : 757.2.

Example 195 To a solution of 1 equiv. of compound 220 in CH3CN/H20 3: 2 (0.015M) were added 30 equiv. of AgNOs. The reaction was stirred for 24 h protected from the light. After this time, 2 mL of a saturated solution of NaCI and 2 mL of a saturated solution of NaHCOs were added and the crude was stirred for 10 min. Then it was diluted with CH2Cl2, washed with 15 mL of brine and extracted with CH2C12. The organic layer was dried over Na2S04, filtered and the solvent was eliminated under reduced pressure. Preparative chromatography gives pure compound (11%).

221 lH-NMR (300 MHz, CDC13) : 8 6.57 (s, 1H), 6.49 (s, 1H), 6.44 (s, 1H), 5.99 (d, 2H), 5.10 (d, 1H), 4.80 (s, 1H), 4.50-4. 46 (m, 2H), 4.16 (d, 1H), 4.07 (m, 1H), 3.62 (s, 3H), 3. 58-3. 57 (m, 1H), 3.23-3. 19 (m, 1H), 3.00-2. 83 (m, 3H), 2.71-2. 60 (m, 1H), 2.48-1. 97 (m, 4H), 2.32 (s, 3H), 2.29 (s, 3H), 2.20 (s, 3H), 2.03 (s, 3H).

ESI-MS m/z: Calcd. for C38H4lN3011S : 747.3 Found (M-H20+H+) : 730.2.

Example 196 To a solution of 1 equiv. of compound 222 in EtOH (0.064M) under Argon at room temperature were added 3.5 equiv. of a-ethyl-3-hydroxy-4- methylphenethylamine chlorhydrate and 2 equiv. of K2CO3 and silica gel.

The reaction was stirred at room temperature for 7 hours. Then the solvent was eliminated under reduced pressure. Flash chromatography gives pure compound (68%). Compound 223 is isolated as a mixture of two isomers.

These compounds can also be obtained when the reaction is performed with acetic acid as solvent and heating at 50 oc for 24 hours (99%).

222 223 223. 1H-NMR (300 MHz, CDCl3) : 8 6.79 (s, 1H), 6.57 (s, 1H), 6.54 (s, 1H), 6.51 (s, 1H), 6.19 (s, 1H), 6.13-6. 08 (m, 3H), 6.03-6. 02 (m, 2H), 5.74 (s, 1H), 5.71 (d, 1H) ; 5.03 (d, 1H) ; 4.94 (d, 1H), 4.56 (s, 2H), 4.34-4. 08 (m, 10H) ; 3.77 (s, 3H), 3.76 (s, 3H), 3.51-3-49 (m, 2H), 3.41 (s, 2H), 2.96-2. 87 (m, 4H), 2.51- 2.37 (m, 2H), 2.29 (s, 3H), 2.28 (s, 3H), 2.26 (s, 3H), 2.24 (s, 3H), 2.15 (s, 3H), 2.09 (s, 3H), 2.06 (s, 3H), 2.04 (s, 3H), 2.00 (s, 3H), 1.47-1. 34 (m, 4H); 0.98 (t, 6H).

ESI-MS m/z: Calcd. for C42H46N4O9S : 782.3 Found (M+H+): 783.3.

Example 197 To a solution of 1 equiv. of compound 223 in CH3CN/H20 3: 2 (0. 01M) were added 30 equiv. of AgN03. The reaction was stirred at room temperature for 24 h protected from the light. After this time, the reaction was quenched with a mixture 1: 1 of an aqueous saturated solutions of NaCl and NaHCOs, stirred for 10 min and diluted and extracted with CH2Cl2. The organic layer was dried over Na2SO4, filtered and the solvent was eliminated under reduced pressure. Chromatography gives a mixture of the two isomers compound 224 (72%).

223 224 224A First isomer : lH-NMR (300 MHz, CDC13) : 8 6.59 (s, 1H); 6.52 (s, 1H); 6.29 (s, 1H) ; 6.06 (d, 1H) ; 6.01 (d, 1H) ; 5.68 (s, 1H) ; 5.06 (d, 1H) ; 4.80 (s, 1H); 4.48 (m, 2H); 4.16 (d, 1H); 4.07 (dd, 1H); 3.78 (s, 3H); 3.59 (d, 3H); 3.23-3. 21 (m, 1H); 3.05-3. 01 (m, 1H); 2.87-2. 84 (m, 2H); 2.44-2. 20 (m, 2H); 2.28 (s, 3H); 2.25 (s, 3H); 2.14 (s, 3H); 2. 06 (s, 3H), 2.01 (s, 3H), 1.45 (m, 2H), 1.01 (t, 3H).

ESI-MS m/z: Calcd. for C4iH47N3OioS : 773.3 Found (M-H20+H+) : 756.2. 224B Second isomer: 1H-NMR (300 MHz, CDCIs) : S 6.80 (s, 1H); 6.55 (s, 1H); 6.26 (s, 1H) ; 6.09 (d, 1H) ; 6.00 (d, 1H) ; 5.66 (s, 1H) ; 5.12 (d, 1H) ; 4.82 (s, 1H) ; 4.48 (m, 2H); 4.20-4. 13 (m, 3H); 3.77 (s, 3H); 3.57 (d, 1H) ; 3.21 (s, 1H) ; 2.83-2. 80 (m, 2H); 2.55-2. 50 (m, 1H); 2.33-2. 06 (m, 2H), 2. 30 (s, 3H); 2.27 (s, 3H); 2.08 (s, 3H), 2.03 (s, 6H), 1.45-1. 37 (m, 2H), 1.01 (t, 3H).

ESI-MS m/z: Calcd. for C41H47N3OloS : 773.3 Found (M-H20+H+) : 756.3.

BIOASSAYS FOR ANTITUMOR SCREENING The finality of these assays is to interrupt the growth of a"in vitro" tumor cell culture by means a continued exhibition of the cells to the sample to be testing.

CELL LINES Name N ATCC Species Tissue Characteristics ascites P-388 CCL-46 mouse fluid lymphoid neoplasm erythroleukemia (pleural K-562 CCL-243 human leukemia effusion) A-549 CCL-185 human lung lung carcinoma"NSCL" SK-MEL-28 HTB-72 human melanoma malignant melanoma HT-29 HTB-38 human colon colon adenocarcinoma LoVo CCL-229 human colon colon adenocarcinoma LoVo-Dox human colon colon adenocarcinoma (MDR) colon adenocarcinoma SW620 CCL-228 human colon (lymph node metastasis) DU-145 HTB-81 human prostate prostate carcinoma, not androgen receptors prostate adenocarcinoma, LNCaP CRL-1740 human prostate with androgen receptors breast adenocarcinoma, SK-BR-3 HTB-30 human breast Her2/neu+, (pleural effusion) breast adenocarcinoma, MCF-7 HTB-22 human breast (pleural effusion) breast adenocarcinoma, MDA-MB-231 HTB-26 human breast Her2/neu+, (pleural effusion) IGROV-1 human ovary ovary adenocarcinoma ovary adenocarcinoma, characterized as ET-743 IGROV-ET human ovary resistant cells ovary adenocarcinoma SK-OV-3 HTB-77 human ovary (malignant ascites) OVCAR-3 HTB-161 human ovary ovary adenocarcinoma HeLa CCL-2 human cervix cervix epitheloid carcinoma cervix epitheloid carcinoma, characterized as aplidine HeLa-APL CCL-3 human cervix resistant cells A-498 HTB-44 human kidney kidney carcinoma pancreatic epitheloid PANC-1 CRL-1469 human pancreas carcinoma endotheliu HMEC 1 human m 1°.-Inhibition of cell growth by counting cells.

This form of the assay employs 24 well multidishes of 16 mm diameter (Bergeron, 1984; Schroeder, 1981). The tumor cell lines employed are: P-388 (ATCC CCL 46), suspension culture of a lymphoid neoplasm from a DBA/2 mouse; A-549 (ATCC CCL 185), monolayer culture of a human lung carcinoma; HT-29 (ATCC HTB-38), monolayer culture of a human colon carcinoma; MEL-28 (ATCC HTB-72), monolayer culture of a human melanoma and DU-145 (ATCC HTB-81), monolayer culture of a human prostate carcinoma.

Cells were maintained, in logarithmic phase of growth in Eagle's Minimum Essential Medium, with Earle's Balanced Salts, with non-essential amino acids, with 2.0 mM L-Glutamine, without sodium bicarbonate (EMEM/neaa), supplemented with 10% Fetal Calf Serum (FCS), 10-2 M. sodium bicarbonate and 0.1 U/1 penicillin G + 0.1 g/1 streptomycin sulfate.

For the experiments, cells are harvested from subconfluent cultures using trypsin and resuspended in fresh medium before plating.

P-388 cells were seeded into 16 mm diameter wells at 1 x 104 cells per well in 1 ml aliquots of EMEM 5% FCS containing different concentrations of the sample to be tested. A separate set of cultures without drug was seeded as control of growth, to ensure that cells remained in exponential phase of growth. All determinations are carrying out in duplicate. After three days of incubation at 37°C, 5% C02 in a 98% humid atmosphere, an approximately IC50 was determined by comparing the growth in wells with drug to the growth in wells control.

A-549, HT-29, MEL-28 and DU-145 cells were seeded into 16 mm diameter wells at 1 x 104 cells per well in 1 ml aliquots of EMEM 5% FCS containing different concentrations of the sample to be tested. A separate set of cultures without drug was seeded as control of growth, to ensure that cells remained in exponential phase of growth. All determinations are carrying out in duplicate. After three days of incubation at 37°C, 5% C02 in a 98% humid atmosphere cells were stained with 0.1 % crystal violet. An approximately IC50 was determined by comparing the growth in wells with drug to the growth in wells control.

For quantifying the activity, after the incubation time, cells are trypsinized and counted in a Coulter Counter ZM. All counts (net cells per well), represent the average of duplicate wells. % G, percent of growth relative to cultures without drug. The results of these assays are used to generate dose-response curves from which more precise IC50 values are determined (sample concentration which produces 50% cell growth inhibition).

Obtained results may predict the usefulness of a certain drug as a potential cancer treatment. For this technique, compounds which show IC50 values smaller than 1 llg/ml are selected to continue with further studies.

IC50's data allow to predict that not only could a drug be cystostatic, but also it could have a potential in terms of tumor reduction.

2°.-Inhibition of cells growth by colorimetric assay.

A colorimetric type of assay, using sulforhodamine B (SRB) reaction has been adapted for a quantitative measurement of cell growth and viability [following the technique described by Philip Skehan, et al. (1990), New colorimetric cytotoxicity assay for anticancer drug screening, J. Natl. Cancer Inst., 82: 1107-1112] This form of the assay employs 96 well cell culture microplates of 9 mm diameter (Faircloth, 1988; Mosmann, 1983). Most of the cell lines are obtained from American Type Culture Collection (ATCC) derived from different human cancer types.

Cells are maintained in RPMI 1640 10% FBS, supplemented with 0.1 g/1 penicillin and 0.1 g/1 streptomycin sulfate and then incubated at 37°C, 5% C02 and 98% humidity. For the experiments, cells were harvested from subconfluent cultures using trypsin and resuspended in fresh medium before plating.

Cells are seeded in 96 well microtiter plates, at 5 x 103 cells per well in aliquots of 195 ul medium, and they are allowed to attach to the plate surface by growing in drug free medium for 18 hours. Afterward, samples are added in aliquots of 5 ul in a ranging from 10 to 10-8 llg/ml, dissolved in DMSO/EtOH/PBS (0.5 : 0.5 : 99). After 48 hours exposure, the antitumor effect are measured by the SRB methodology: cells are fixed by adding 50 PI of cold 50% (wt/vol) trichloroacetic acid (TCA) and incubating for 60 minutes at 4°C. Plates are washed with deionized water and dried. One hundred ul of SRB solution (0.4% wt/vol in 1% acetic acid) is added to each microtiter well and incubated for 10 minutes at room temperature. Unbound SRB is removed by washing with 1% acetic acid. Plates are air dried and bound stain is solubilized with Tris buffer. Optical densities are read on a automated spectrophotometric plate reader at a single wavelength of 490 nm.

The values for mean +/-SD of data from triplicate wells are calculated.

Some parameters for cellular responses can be calculated: GI = growth inhibition, TGI = total growth inhibition (cytostatic effect) and LC = cell killing (cytotoxic effect).

Obtained results may predict the usefulness of a certain drug as a potential cancer treatment. For this technique, compounds which show GI50 values smaller than 10 ug/ml are selected to continue with further studies.

GI50's data allow to predict that not only could a drug be cystostatic, but also it could have a potential in terms of tumor reduction.

Activity Data ICso (molar) Compound P-388 A-549 HT-29 MEL-2t8 DU-145 2 1. 48E-10 1. 48E-10 1. 48E-10 1. 48E-10 3 1. 15E-09 1. 15E-09 1. 15E-09 1. 15E-09 1. 15E-09 4 1. 15E-10 1. 15E-10 1. 15E-10 1. 15E-10 1. 15E-10 5 5. 15E-10 5. 15E-10 5. 15E-10 5. 15E-10 5. 15E-10 6 1. 41E-09 2. 93E-09 2. 93E-09 2. 93E-09 7 1. 19E-10 1. 19E-10 5. 95E-10 1. 19E-10 5. 95E-10 8 1. 11E-10 1. 11E-10 5. 56E-10 1. 11E-10 5. 56E-10 9 1. 10E-10 1. 10E-10 1. 10E-10 1. 10E-10 1. 10E-10 10 9. 70E-09 9. 70E-09 9. 70E-09 9. 70E-09 9. 70E-09 11 5. 54E-10 5. 54E-10 12 1. 16E-10 1. 16E-10 14 1. 11 E-09 1. 11 E-09 1. 11 E-09 1. 11 E-09 1. 11 E-09 15 9. 78E-08 9. 78E-08 9. 78E-08 9. 78E-08 9. 78E-08 16 9. 91E-09 9. 91 E-09 9. 91 E-09 9. 91 E-09 9. 91E-09 17 8. 02E-08 8. 02E-08 8. 02E-08 8. 02E-08 8. 02E-08 18 4. 41E-10 4. 41E-10 4. 41E-10 4. 41E-10 4. 41E-10 19 5. 02E-10 5. 02E-10 5. 02E-10 5. 02E-10 5. 02E-10 20 8. 18E-09 8. 18E-09 8. 18E-09 8. 18E-09 8. 18E-09 24 5. 31E-10 5. 31E-10 25 1. 41E-10 1. 41E-10 1. 41E-10 1. 41E-10 26 5. 33E-09 5. 33E-09 5. 33E-09 5. 33E-09 27 1. 11E-10 1. 11E-10 1. 11E-10 1. 11E-10 1. 11E-10 28 9. 62E-09 9. 62E-09 9. 62E-09 9. 62E-09 9. 62E-09 37 1. 25E-10 1. 25E-10 1. 25E-10 1. 25E-10 38 1. 21E-08 1. 21E-08 1. 21E-08 1. 21E-08 1. 21E-08 39 6. 16E-10 6. 16E-10 6. 16E-10 6. 16E-10 40 1. 17E-06 1. 17E-06 1. 17E-06 1. 17E-06 1. 17E-06 41 1. 23E-09 1. 23E-09 1. 23E-09 1. 23E-09 1. 23E-09 42 1. 18E-08 1. 18E-08 1. 18E-08 1. 18E-08 1. 18E-08 43 1. 16E-09 1. 16E-09 1. 16E-09 1. 16E-09 1. 16E-09 44 1. 05E-07 1. 05E-07 1. 05E-07 1. 05E-07 1. 05E-07 45 1. 13E-10 1.13E-10 47 1. 15E-09 1.15E-09 1. 15E-09 1.15E-09 1. 15E-09 49 9. 99E-10 9. 99E-10 9.99E-10 9.99E-10 9.99E-10 ICso (molar) | Compound P-388 A-549 HT-29 MEL-28 DU-145 50 1. 24E-07 1. 24E-07 1. 24E-07 1. 24E-07 1. 24E-07 51 6. 16E-10 1. 23E-09 1. 23E-09 1. 23E-09 52 1. 27E-09 1. 27E-09 I 53 4. 85E-09 9. 71 E-09 9. 71 E-09 9. 71 E-09 54 1. 28E-10 1. 28E-10 1. 28E-10 1. 28E-10 55 3. 13E-09 3. 13E-09 3. 13E-09 6. 26E-09 56 1. 23E-10 1. 23E-10 1. 23E-10 1. 23E-10 57 1. 49E-10 1. 49E-10 1. 49E-10 1. 49E-10 58 1. 20E-10 1. 20E-10 1. 20E-10 1. 20E-10 1. 20E-10 59 1. 13E-10 1. 13E-10 1. 13E-10 1. 13E-10 1. 13E-10 60 1. 00 E-08 5. 00E-09 5. 00E-09 5. 00E-09 5. OOE-09 61 1. 12E-10 1. 12E-10 1. 12E-10 1. 12E-10 1. 12E-10 62 8. 88E-10 8. 88E-10 8. 88E-10 8. 88E-10 8. 88E-10 63 5. 06E-10 5. 06E-10 5. 06E-10 5. 06E-10 5. 06E-10 64 1. 18E-10 5. 92E-10 5. 92E-10 5. 92E-10 65 1. 12E-10 1. 12E-10 1. 12E-10 1. 12E-10 1. 12E-10 66 1. 16E-10 1. 16E-10 1. 16E-10 1. 16E-10 1. 16E-10 68 6. 33E-10 6. 33E-10 69 1. 25E-10 6. 23E-10 6. 23E-10 6. 23E-10 6. 23E-10 70 1. 25E-10 1. 25E-10 1. 25E-10 1. 25E-10 1. 25E-10 71 5. 88E-10 5. 88E-10 5. 88E-10 5. 88E-10 5. 88E-10 79 1. 07E-10 1. 07E-10 F l 80 2. 96E-09 5. 92E-09 5. 92E-09 5. 92E-09 81 5. 54E-09 5. 54E-09 82 9. 86E-08 9. 86E-08 83 8. 08E-08 8. 08E-08 8. 08E-08 8. 08E-08 8. 08E-08 84 4.89E-08 4. 89E-08 85 9. 71 E-09 9. 71 E-09 86 5. 20E-10 5.20E-10 5.20E-10 5.20E-10 5.20E-10 88 1.22E-08 1.22E-08 1.22E-08 1.22E-08 1.22E-08 89 5. 91E-07 5.91E-07 5.91E-07 5.9 E-07 5.91E-07 90 1. 19E-08 1. 19E-08 1. 19E-08 1. 19E-08 1. 19E-08 91 1.06E-07 1.06E-07 1.06E-07 1.06E-07 1.06E-07 94 1. 52E-10 1.52E-10 1.52E-10 1.52E-10 ICso (molar) Compound P-388 A-549 HT-29 MEL-28 DU-145 l 96 1. 25E-09 1. 25E-09 1. 25E-09 1. 25E-09 I 98 1. 29E-10 1. 29E-10 104 1. 17E-10 5. 83E-10 5. 83E-10 5. 83E-10 5. 83E-10 106 1. 21E-09 1. 21E-09 1. 21E-09 1. 21E-09 1. 21E-09 I 107 1. 08E-09 1. 08E-09 1. 08E-09 1. 08E-09 1. 08E-09 108 1. 08E-10 1. 08E-10 1099. 80E-10 9. 80E-10 I 11 9. 72E-11 9. 72E-11 111 1. 11 E-09 1. 11 E-09 1. 11 E-09 1. 11 E-09 1. 11 E-09 112 1. 03E-08 1. 03E-08 113 1. 04E-08 1. 04E-08 1. 04E-08 1. 04E-08 1. 04E-08 114 9. 18E-09 9. 18E-09 115 1. 10E-10 1. 10E-10 116 1. 09E-10 1. 09E-10 119 1. 05E-08 1. 05E-08 1. 05E-08 1. 05E-08 1. 05E-08 I 120 4. 63E-07 4. 63E-07 4. 63E-07 4. 63E-07 4. 63E-07 121 4. 69E-07 4. 69E-07 4. 69E-07 4. 69E-07 4. 69E-07 122 8. 30E-07 8. 30E-07 8. 30E-07 8. 30E-07 8. 30E-07 126 1. 19E-10 1. 19E-10 127 1. 17E-10 1. 17E-10 128 1. 17E-09 1. 17E-09 129 1.13E-08 1. 13E-08 130 1. 15E-09 1. 15E-09 | 131 1. 10E-07 1.10E-07 132 1.15E-09 1. 15E-09 133 1. 1 OE-07 1. 10E-07 134 5.44E-10 5.44E-10 5. 44E-10 5. 44E-10 5. 44E-10 135 4.96E-09 4.96E-09 4.96E-09 4.96E-09 4. 96E-09 136 1.37E-10 1. 37E-10 1.37E-10 1. 37E-10 1.37E-10 137 1.17E-10 1.17E-10 1.17E-10 1.17E-10 1. 17E-10 138 1. 01 E-09 1.01E-09 139 1.25E-09 1.25E-09 14 1.15E-09 1.15E-09 141 1. 23E-10 1. 23E-10 ICso (molar) Compound p. 388A-549 HT-29 MEL-28 DU-145 142 1. 22E-09 1. 22E-09 14 1. 17E-09 1. 17E-09 1. 17E-09 1. 17E-09 1. 17E-09 145 1. 02E-07 1. 02E-07 146 1. 03E-07 1. 03E-07 1. 03E-07 1. 03E-07 1. 03E-07 149 1. 35E-10 1. 35E-10 15 1. 32E-09 1. 32E-09 151 1. 32E-10 1. 32E-10 152 1. 28E-08 1. 28E-08 153 1. 30E-10 1. 30E-10 15 1. 23E-08 1. 23E-08 155 1. 30E-09 1. 30E-09 156 1. 24E-08 1. 24E-08 15 1. 22E-10 1. 22E-10 158 1. 10E-09 1. 10E-09 159 1. 37E-09 1. 37E-09 1. 37E-09 1. 37E-09 1. 37E-09 161 1. 09E-09 1. 09E-09 161 1. 18E-10 1. 18E-10 1. 18E-10 1. 18E-10 1.18E-10 162 5. 10E-09 5. 10E-09 164 1.16E-08 1.16E-08 168 5. 91E-10 5. 91E-10 5. 91E-10 5.91E-10 5.91E-10 169 1. 03E-09 1. 03E-09 17 5.22E-08 5.22E-08 5.22E-08 5.22E-08 5.22E-08 17 1. 34E-10 1. 34E-10 178 1. 31 E-09 1.31E-09 179 1. 25E-08 1.25E-08 18 6. 18E-10 6.18E-10 181 1. 1 1E-08 1. 1 1E-08 183 1. 32E-10 1. 32E-10 184 6. 99E-10 6. 99E-10 6. 99E-10 6.99E-10 185 1. 32E-08 1.32E-08 1. 32E-08 1.32E-08 186 1. 59E-10 1. 59E-10 1. 59E-10 1. 59E-10 187 1. 08E-09 1.08E-09 1. 08E-09 1. 08E-09 ICso (molar) Compound p-388A-549 HT-29 MEL-28 DU-145 188 5. 83E-10 5. 83E-10 5. 83E-10 5. 83E-10 189 5. 83E-10 5. 83E-10 5. 83E-10 5. 83E-10 190 5. 22E-09 5. 22E-09 5. 22E-09 5. 22E-09 191 1. 11 E-09 1. 1 lE-05 1. 11 E-09 1. 11 E-09 1. 11 E-09 192 5. 39E-09 5. 39E-09 5. 39E-09 5. 39E-09 5. 39E-09 194 5. 07E-08 5. 07E-08 5. 07E-08 5. 07E-08 5. 07E-08 195 1. 02E-08 1. 02E-08 1. 02E-08 1. 02E-08 1. 02E-08 196 9. 02E-06 9. 02E-06 9. 02E-06 9. 02E-06 9. 02E-06 197 9. 13E-06 9. 13E-06 9. 13E-06 9. 13E-06 9. 13E-06 198 7. 50E-06 7. 50E-06 7. 50E-06 7. 50E-06 7. 50E-06 201 1.26E-08 1.57E-08 1.57E-08 1.57E-08 202 1.25E-10 1. 25E-10 1.25E-10 6. 25E-11 6. 25E-11 203 1. 21E-10 1. 21E-10 1. 21E-10 1.21E-10 1. 21E-10 204 1.13E-10 1. 13E-10 1.13E-10 1.13E-10 1.13E-10 205 1.13E-10 1. 13E-10 1.13E-10 1.13E-10 1. 13E-10 206 4.96E-08 4.96E-08 4.96E-08 4.96E-08 4.96E-08 207 5.03E-09 5.03E-09 5.03E-09 5.03E-09 5.03E-09 208 8. 11 E-06 8. 11 E-06 8. 11 E-06 8. 11 E-06 8. 11 E-06 213 1. 14E-10 1.14E-10 2 14 _ 5. 00E-09 5. 00E-09 21 8. 16E-08 8. 16E-08 221 1. 34E-09 1.34E-09 Compound 13 Compound 21 Compound 29 GIso1. 08E-093. 34E-09 2. 16E-09 A-549 TGI 3.24E-09 1.06E-08 4.32E-09 LCso 8.65E-09 1. 06E-05 1. 08E-08 GIso 3. 24E-10 5. 3 lE-09 2. 16E-09 H-T29 TGI 3. 24E-10 1. 06E-07 2.16E-09 LCso 1. 08E-08 1. 06E-05 1. 08E-06 GIso SW-620 TGI LCso GIso MEL-28 TGI LCso GIso OVCAR TGI LCso GIso A-498 TGI LCso GIso DU-145 TGI LCso GIso MCF TGI LCso GI50 MB-231 TGI LC50 GI50 HMEC-1 TGI LC50 GI50 LNCAP TGI LCso GI50 SK-OV3 TGI LCso GI50 IGROV TGI LCso GI50 IGROV-ET TGI LCso GI50 SK-BR3 TGI =LC50 GIso K-562 TGI LCso GIso PANC-1 TGI LCso GIso LOVO TGI LCso GIso LOVO-DOX TGI LCso GI50 HELA TGI LCso GI50 HELA-APL TGI LCso Compound 30 Compound 31 Compound 32 GI50 3.29E-08 4.08E-08 2.20E-09 A-549 TGI 5.49E-08 9.17E-08 6.59E-09 LCso 3.29E-06 1. 02E-06 1.10E-08 GIso8. 78E-088. 15E-081. 10E-09 H-T29 TGI 8. 78E-08 8.15E-08 6. 60E-09 LCso 1.10E-05 1.02E-05 9. 88E-09 GI50 SW-620 TGI LC50 GI50 MEL-28 TGI LCso GI50 OVCAR TGI LCso GI50 A-498 TGI LCso GI50 DU-145 TGI LCso GIso MCF TGI LCso GI50 MB-231 TGI LCso GI50 HMEC-1 TGI LC50 GI50 LNCAP TGI LCso GI50 SK-OV3 TGI LC50 GI50 IGROV TGI LC50 GIso IGROV-ET TGI LCso GI50 SK-BR3 TGI LCso GIso K-562 TGI LCso GIso PANC-1 TGI LCso GIso LOVO TGI LCso GI50 LOVO-DO TGI LCso GI50 HELA TGI LCso GI50 HELA-APL TGI LCso Compound 33 Compound 34 Compound 35 GIso4. 37E-097. 64E-10 5.68E-09 A-549 TGI 2.50E-08 2.84E-09 7.22E-08 LCso 1. 27E-05 9. 06E-09 2. 15E-06 GIso 3.42E-08 8.09E-10 5. 41E-09 H-T29 TGI 1.25E-07 1.29E-08 1. 25E-08 LCso 1.25E-05 1.27E-05 1. 25E-05 GIso SW-620 TGI LCso GIso MEL-28 TGI LCso GIso OVCAR TGI LCso GIso A-498 TGI LCso GIso DU-145 TGI LCso GI50 MCF TGI LC50 GI50 MB-231 TGI LCso GI50 HMEC-1 TGI LCso GIso LNCAP TGI . LCso GIso SK-OV3 TGI LCso GIso IGROV TGI LCso GI50 IGROV-ET TGI LCso GIso SK-BR3 TGI LCso GIso K-562 TGI LC50 GI50 PANC-1 TGI LCso GI50 LOVO TGI LC50 GI50 LOVO-DOX TGI LCso GI50 HELA TGI LC50 GI50 HELA-APL TGI LCso Compound 36 Compound 46 Compound 48 GIso6. 26E-091. 79E-072. 72E-07 A-549 TGI 1.03E-07 4. 06E-07 7.50E-07 LCso 4.14E-06 9. 27E-07 3.89E-06 GI50 5.67E-09 3.98E-07 1.97E-06 H-T29 TGI 2.55E-08 1. 95E-06 1.23E-05 LCso 1. 27E-05 1. 10E-05 1. 23E-05 Also SW-620 TGI LCso GIso 1. 10E-06 MEL-28 TGI 2.87E-06 LCso 7.06E-06 GIso OVCAR TGI LCso GIso A-498 TGI LCso GIso6. 14E-07 DU-145 TGI 3. 20E-06 LCso 1. 23E-05 GI50 MCF TGI LCso GIso MB-231 TGI LCso GIso 1.52E-07 HMEC-1 TGI 5.18E-07 LCso 1. 10E-05 GIso LNCAP TGI LCso GI50 6.14E-07 SK-OV3 TGI 3. 40E-06 LCso 1. 23E-05 GI50 4.39E-07 IGROV TGI 1. 78E-06 LCso 7. 98E-06 _ GIso 6. 78E-0 IGROV-ET TGI 2. 93E-06 LC50 1. 23E-05 GI50 4.43E-07 SK-BR3 TGI 1. 54E-06 LCso 6. 97E-06 GIso 2. 23E-0 K-562 TGI 5. 47E-07 LCso 1. 23E-06 GIso9. 10E-07 PANC-1 TGI 5. 1 oye-06 LCso 1. 23E-05 GI50 7.13E-07 LOVO TGI 2. 95E-06 LCso 1. 23E-05 GIso7. 90E-07 LOVO-DOX TGI 4. 18E-06 LCso 1. 23E-05 Also | HE LA TGI LCso GIso HELA-APL TGI LCso Compound 67 Compound 72 Compound 73 GIso1. 31E-091. 12E-09 3.52E-10 A-549 TGI 3.63E-09 3.36E-09 2.35E-09 LCso 1. OlE-08 7. 83E-09 5.87E-09 GI50 7.41E-10 2.24E-09 9.39E-10 HT-29 TGI 5.59E-09 7. 83E-09 7.04E-09 LCso 1. 29E-05 1. 12E-08 1. 06E-08 GIso2. 24E-093. 52E-10 SW-620 TGI 3. 36E-09 1. 17E-09 LCso 1. 12E-08 9. 39E-09 GI50 4.11E-10 2.24E-09 8.22E-10 MEL-28 TGI 9. 90E-10 3. 36E-09 9. 39E-10 LCso 6.24E-09 7. 83E-09 3. 52E-09 GIso OVCAR TGI LCso GIso2. 24E-093. 52E-10 A-498 TGI 4.47E-09 7. 04E-10 LCso 1. 12E-08 3. 52E-09 GIso 4. 33E-10 2. 24E-09 2. 35E-10 DU-145 TGI 8. 61E-10 3.36E-09 3. 52E-10 LCso 4.47E-06 8. 95E-09 9.39E-10 GIso 2. 24E-09 7. 04E-10 MCF TGI 4. 47E-09 3.52E-09 LCso 1. 12E-08 1.17E-08 GIso2. 24E-092. 35E-10 MB-231 TGI 3. 36E-09 4. 69E-11 LCso 1. 12E-08 1.17E-09 GI50 1.02E-09 HMEC-1 TGI 8.49E-09 LCso 5.05E-06 GIso 3. 07E-10 LNCAP TGI 5.09E-10 LCso 8. 44E-10 GIso3. 85E-10 SK-OV3 TGI 8.52E-10 LCso 7.94E-06 GIso 2. 66E-10 IGROV TGI 5.67E-10 LCso 1.21E-09 GIso 1. 88E-05 IGROV-ET TGI 7.02E-09 LCso 4. 96E-06 GI50 3.94E-10 SK-BR3 TGI 1.11E-09 LCso 7. 48E-09 GIso 1. 18E-1 K-562 TGI 2.85E-10 LCso 8.00E-10 GIso 4. 43E-10 PANC-1 TGI 1.09E-09 LCso 2.67E-06 GIso 6. 02E-10 LOVO TGI 3.34E-09 LCso 1. 77E-08 GI50 4.21E-09 LOVO-DOX TGI 3. 65E-08 LCso 1. 28E-05 Also HELA TGI LCso GIso HELA-APL TGI LCso Compound 74 Compound 75 Compound 76 GIso 3. 99E-10 4. 26E-09 2. 06E-09 A-549 TGI 9. 04E-10 8. 23E-09 4. 31E-09 LCso 6. 38E-09 4. 90E-08 9. 07E-09 GIso3. 54E-103. 89E-091. 28E-09 HT-29 TGI 8. 35E-10 1. 18E-08 6.18E-09 LCso 1. 04E-05 1.20E-07 4.52E-06 GIso SW-620 TGI LCso GIso 2. 75E-10 2. OOE-09 6. 22E-10 MEL-28 TGI 5. 22E-10 4. 82E-09 2. 51E-09 LCso 9. 94E-10 1. 17E-08 8. 28E-09 GIso OVCAR TGI LCso GIso A-498 TGI LCso GISO 3. 66E-10 5. 63E-10 2. 49E-10 DU-145 TGI 7. 61E-10 9. 47E-10 6. 16E-10 LCso 2.79E-06 8.33E-06 2. 14E-06 GIso MCF TGI LCso GIso MB-231 TGI LCso GI50 5.98E-10 6.97E-05 1.83E-09 HMEC-1 TGI 1.45E-08 5. 77E-08 6. 55E-09 LCso 4.70E-06 1.20E-05 1. 86E-07 GIso 1. 29E-10 5. 79E-10 2. 17E-10 LNCAP TGI 2. 69E-10 8.31E-10 4. 40E-10 LCso 5. 64E-10 1. 19E-09 8. 91E-10 GIso 2. 48E-10 2. 19E-09 2. 93E-10 SK-OV3 TGI 4. 76E-10 1. 04E-08 8. 93E-10 LCso 1. 11 E-09 1. 20E-05 4.81E-06 GIso 2. 37E-10 5. 20E-10 1. 92E-10 IGROV TGI 4. 65E-10 1.63E-09 4. 56E-10 LCso 9. 11E-10 1. OOE-0 | 1. 66E-09 GI50 1.76E-09 3.38E-09 1.52E-09 IGROV-ET TGI 4.69E-09 6.58E-09 3. 92E-09 LCso 1.97E-08 1. 20E-08 2.10E-08 GIso2. 75E-101. 20E-093. 37E-10 SK-BR3 TGI 7. 64E-10 3. 21E-09 1. 24E-09 LCso 4. 18E-09 8. 58E-09 6. 17E-09 GIso 5. 26E-11 3. 64E-10 2. 78E-12 K-562 TGI 2. 10E-10 7. 42E-10 3. 78E-11 LCso 6. 61E-10 4. 16E-09 3. 51E-10 GIso3. 13E-103. 04E-091. 22E-09 PANC-1 TGI 6. 77E-10 8. 45E-09 4.68E-09 LCso 2. 55E-09 3. 59E-08 4. 41E-08 GIso3. 69E-102. 25E-091. 03E-09 LOVO TGI 1.16E-09 4.82E-09 3. 30E-09 LCso 1. 10E-08 1. 20E-08 1. 08E-08 GIso6. 31E-094. 26E-081. 39E-08 LOVO-DOX TGI 6. 33E-08 1. 23E-07 4.70E-08 LCso 3. 59E-07 1. 20E-05 1. 07E-07 GIso HELA TGI LCso GIso HELA-APL TGI LCso Compound 77 Compound 78 Compound 87 GI5o 2. 11E-09 9. 59E-09 2.38E-08 A-549 TGI 3. 64E-09 1. 99E-08 4.77E-08 LCso 6. 29E-09 4. 11E-08 9. 58E-08 GIso2. 96E-091. 71E-082. 44E-08 HT-29 TGI 9.52E-09 1. 10E-07 1. 12E-07 LCso 1. 01E-05 8.19E-06 3. 80E-07 GIso SW-620 TGI LCso GIso 2. 66E-10 2.15E-09 1.92E-08 MEL-28 TGI 5. 06E-10 4.48E-09 4.57E-08 LCso 9.62E-10 1.69E-08 1.09E-07 GIso OVCAR TGI LCso GIso A-498 TGI LCso GIso 4. 88E-10 3. 2 lE-09 1. 35E-0E DU-145 TGI 1.45E-09 8.52E-09 5.22E-08 LC50 1.01E-05 8.19E-06 1.80E-07 GIso MCF TGI LCso Also MB-231 TGI LCso GI50 5.28E-09 2.83E-08 1.67E-08 HMEC-1 TGI 5.28E-08 2.35E-07 9.65E-08 LCso 1. 01E-05 8.19E-06 1.27E-05 GIso3. 28E-102. 74E-094. 73E-09 LNCAP TGI 6.12E-10 4.05E-09 1.12E-08 LCso 1.58E-09 5.99E-09 4.05E-08 GIso2. 55E-093. 79E-092. 16E-08 SK-OV3 TGI 7.76E-09 6.27E-08 6. 56E-08 LCso 1. 01E-05 8.19E-06 8. 99E-06 GIso4. 54E-102. 38E-094. 80E-09 IGROV TGI 1.53E-09 6.27E-09 1.63E-08 LCso 8. 82E-09 5. 39E-08 8.04E-08 GIso 4.22E-09 1.14E-07 2. 84E-08 IGROV-E TGI 9.57E-08 7.42E-07 7. 77E-08 LCso 3.03E-07 8.19E-06 5. 84E-06 GIso4. 75E-104. 31E-091. 65E-08 SK-BR3 TGI 2.04E-09 1.70E-08 4. 08E-08 LCso 8.12E-09 6. 33E-08 1. 01E-07 GI50 2.77E-10 1.24E-09 8.71E-10 K-562 TGI 7. 77E-10 2. 56E-09 2. 96E-09 LCso 3.79E-08 7. 50E-09 7. 15E-09 GIso3. 27E-095. 42E-092. 53E-08 PANC-1 TGI 9.14E-09 3. 24E-08 7. 39E-08 LCso 6. 30E-06 4. 90E-06 8. 76E-07 GI50 1.91E-09 1.07E-08 2.27E-08 LOVO TGI 3.96E-09 2. 83E-08 5. 27E-08 LCso 8. 21E-09 7.43E-08 1. 23E-07 GIso3. 13E-088. 85E-083. 87E-08 LOVO-DO TGI 9.39E-08 8.77E-07 1. 42E-07 LCso 1. 01E-05 8.19E-06 1. 27E-05 GIso HELA TGI Also GIso HELA-APL TGI LCso Compound 92 Compound 93 Compound 95 GIso3. 33E-094. 63E-102. 68E-08 A-549 TGI 7.77E-09 2. 90E-09 5.55E-08 LCso 3. 33E-08 1. 29E-08 1. 47E-07 GIso 1. 11 E-09 6. 35E-10 4.04E-08 HT-29 TGI 1.29E-08 1.27E-07 LCso 5. 55E-08 1.29E-05 1.20E-05 GIso SW-620 TGI LCso GIso2. 81E-102. 52E-08 MEL-28 TGI 6.24E-10 4.58E-08 LCso 3. 58E-09 8.32E-08 GIso OVCAR TGI LCso GI50 A-498 TGI LCso GIso 3.31E-10 3.76E-08 DU-145 TGI 6. 30E-10 8. 92E-08 LCso 1.29E-09 1. 0 lE-0 GIso MCF TGI LCso GIso MB-231 TGI LCso GI50 3.70E-11 9.36E-09 HMEC-1 TGI 1. 55E-10 2. 80E-08 LCso 4. 87E-10 7. 56E-08 GIso 2. 85E-09 1. 77E-08 LNCAP TGI 6.77E-09 3. 41 E-08 LC50 1.29E-07 6.60E-08 GIso 4.09E-10 2. 81E-08 SK-OV3 TGI 1.29E-09 6. 59E-08 LCso 1. 29E-05 3.68E-07 v GIso 2. 14E-10 2. 80E-0 IGROV TGI 6. 46E-10 6. 67E-08 LCso 1.29E-07 1. 09E-06 GIso2. 15E-085. 05E-08 IGROV-ET TGI 1.31E-07 1. 16E-07 LCso 1. 29E-05 1. 20E-05 GIso 4. 45E-1 1 2. 98E-0 SK-BR3 TGI 1. 96E-09 7. 62E-08 LCso 9. 50E-09 5.22E-07 GI50 6.11E-10 1.53E-08 K-562 TGI 1. 29E-08 5.30E-08 LCso 9. 54E-06 2.22E-06 GIso 3. 14E-10 3. 88E-08 PANC-1 TGI 1. 29E-09 1.08E-07 LCso 1. 29E-05 1. 09E-06 GI50 7.68E-10 2.62E-08 LOVO TGI 4. 58E-09 5.40E-08 LCso 1. 29E-05 1. 11E-07 GI50 7.71E-09 2.40E-07 LOVO-DOX TGI 9. 87E-08 8.68E-07 LCso 1. 29E-05 GIso HELA TGI LCso GIso HELA-APL TGI LCso Compound 97 Compound 99 Compound 100 GI5o 3. 48E-10 4. 35E-08 2.98E-08 A5-49 TGI 9.28E-10 9.96E-08 6.20E-08 LCso 3. 48E-09 1.03E-05 1. 12E-07 GIso9. 28E-103. 43E-083. 50E-08 HT-29 TGI 2.32E-09 1.03E-07 8.07E-08 LCso 9.28E-09 1.03E-05 1. 11 E-05 GI50 5. 80E-10 SW-620 TGI 2.32E-09 LCso 9. 28E-09 GI50 3.48E-10 2.65E-08 MEL-28 TGI 9. 28E-10 5.04E-08 LCso 3.48E-09 9.59E-08 GIso OVCAR TGI LCso GIso 5. 80E-10 A-498 TGI 2. 32E-09 LCso 9. 28E-09 GIso2. 32E-104. 31E-08 DU-145 TGI 3. 48E-10 1.03E-07 LCso 9. 28E-10 8. 32E-06 GI5o 1. 16E-09 MCF TGI 3. 48E-09 LCso 1. 16E-08 GIso3. 48E-10 MB-231 TGI 6. 96E-10 LCso 3. 48E-08 GIso 2. 75E-08 HMEC-1 TGI 5. 14E-08 LCso 9. 61E-08 GIso 2. 15E-08 LNCAP TGI 3.79E-08 LCso 6. 65E-08 GIso2. 82E-08 SK-OV3 TGI 5.74E-08 LCso 1.11E-07 GIso3. 51E-08 IGROV TGI 6.54E-08 LCso 9. 15E-07 GIso6. 32E-08 IGROV-ET TGI 7.41E-07 LCso 1. 11 E-05 GISO 4. 05E-08 SK-BR3 TGI 9. 87E-08 LCso 1. 72E-06 GIso 3. 64E-08 K-562 TGI 6. 20E-08 LCso 1.06E-07 GI5o 4. 14E-08 PANC-1 TGI 1. 14E-08 LCso 8. 32E-06 GIso 2. 44E-0 LOVO TGI 4. 48E-08 LCso 8. 23E-08 GIso 3. 92E-0 LOVO-DOX TGI 2. 73E-06 LCso 1. 1 lE-0' GIso HELA TGI LCso GI50 HELA-APL TGI LCso Compound 101 Compound 102 Compound 118 GI50 3.69E-09 1.52E-07 3.34E-OC A5-49 TGI 6.52E-09 4.24E-07 8. 90E-08 LCso 1. 15E-08 1. 19E-06 2. 22E-06 GIso3. 57E-098. 70E-087. 79E-09 HT-29 TGI 1. 03E-08 2. 19E-06 7.79E-09 LCso 1. 29E-05 1. 24E-05 1.11E-05 GI5o SW-620 TGI LCso GIso3. 35E-093. 79E-08 MEL-28 TGI 7. 02E-09 6.89E-08 LCso 2. 60E-08 1.28E-07 GIso OVCAR TGI LCso GI50 A-498 TGI LCso GIso3. 74E-093. 98E-08 DU-145 TGI 7. 46E-09 7.84E-08 LCso 1. 79E-08 1. 24E-07 GIso MCF TGI LCso GIso MB-231 TGI LCso GI50 3. 05E-09 HMEC-1 TGI 1. 17E-08 LCso 1.29E-05 GIso2. 50E-091. 75E-08 LNCAP TGI 4.40E-09 4.09E-08 LC50 7.71E-O9 9.54E-08 GIso4. 49E-094. 13E-08 SK-OV3 TGI 9. 77E-09 1.10E-07 LCso 1. 29E-05 1.24E-07 GI50 2.50E-09 3.53E-OF IGROV TGI 5. 17E-09 7. 63E-08 LCso 1.07E-08 1.34E-07 GI50 3.05E-08 1.01E-07 IGROV-ET TGI 6.88E-08 1. 53E-06 LCso 2. 46E-07 7. 81 E-06 Gist 2. 63E-09 SK-BR3 TGI 6.44E-09 LCso 4.68E-08 GIso 2. 50E-10 1. 02E-08 K-562 TGI 6.20E-10 4. 35E-08 LCso 1.92E-08 1.26E-07 GIso5. 66E-095. 54E-08 PANC-1 TGI 2.27E-08 1. 39E-07 LCso 1.34E-06 1. 24E-05 GIso 1.34E-08 6. 98E-08 LOVO TGI 4.68E-08 4.58E-07 LCso 2. 19E-07 1. 24E-05 GIso2. 51E-074. 17E-07 LOVO-DOX TGI 9.29E-07 1.02E-06 LCso 1.29E-05 1. 24E-05 GIso HELA TGI LCso GIso HELA-APL TGI LCso Compound 123 Compound 124 Compound 125 GI50 7.33E-09 6.87E-09 1.00E-09 A-549 TGI 2. 09E-08 7. 33E-07 3.00E-09 LCso 7. 33E-08 7. 80E-06 8.00E-09 GI50 3.14E-09 3.56E-09 2.00E-10 HT-29 TGI 3.14E-09 7. 80E-08 2.00E-10 LCso 3. 14E-08 7. 80E-06 3. OOE-09 Also SW-620 TGI LCso GIso MEL-28 TGI LCso GI50 OVCAR TGI LCso GIso A-498 TGI LCso GI50 DU-145 TGI LCso GIso MCF TGI LCso GIso MB-231 TGI LCso GI50 HMEC-1 TGI LCso GIso LNCAP TGI LCso GI50 SK-OV3 TGI LCso GI50 IGROV TGI LCso GI50 IGROV-E TGI LCso GI50 SK-BR3 TGI LCso GIso K-562 TGI LCso GIso PANC-1 TGI LCso GI50 LOVO TGI LCso GIso LOVO-DO TGI LCso GI50 HELA TGI LCso GI50 HELA-APL TGI LCso Compound 143 Compound 147 Compound 148 GIso2. 16E-083. 26E-082. 55E-07 A-549 TGI 4.32E-08 6. 84E-08 5. 19E-07 LCso 1.08E-07 1. 05E-06 2.88E-06 GI50 1.08E-08 1.97E-08 1.40E-07 HT-29 TGI 1.08E-08 1.05E-07 3.32E-07 LCso 1.08E-05 1. 05E-05 7.86E-07 GIso SW-620 TGI LCso GI50 MEL-28 TGI LCso GI50 OVCAR TGI LCso GIso A-498 TGI LCso GI50 DU-145 TGI LCso GI50 MCF TGI LCso GIso MB-231 TGI LCso GIso HMEC-1 TGI LCso GIso LNCAP TGI LCso GI50 SK-OV3 TGI LCso GI50 IGROV TGI LC50 GI50 IGROV-ET TGI LCso GIso SK-BR3 TGI LCso GI50 K-562 TGI LC50 GIso PANC-1 TGI LCso GIso LOVO TGI LCso GIso LOVO-DOX TGI LCso GIso HELA TGI LCso GIso HELA-APL TGI LCso Compound 163 Compound 165 Compound 166 GI50 3.80E-10 1.24E-10 9.88E-10 A-549 TGI 2.53E-09 3.73E-10 3.70E-09 LCso 8.86E-09 1. 24E-09 9.88E-09 GIso 3.80E-10 2. 49E-10 1.23E-09 HT-29 TGI 1.14E-09 3.73E-10 3. 70E-09 LCso 3.80E-09 9. 95E-10 9. 88E-09 GI50 3. 80E-10 1. 24E-10 3. 70E-10 SW-620 TGI 2.53E-09 4.98E-10 3. 70E-09 LC5o 1. 01E-08 6. 22E-09 1.11E-08 GI50 2. 53E-10 1. 24E-10 4. 94E-10 MEL-28 TGI 1. 01E-09 3. 73E-10 1. 23E-09 LCso 3.80E-09 9. 95E-10 4. 94E-09 GIso OVCAR TGI LC50 GI50 3. 80E-10 2. 49E-10 1. 23E-09 A-498 TGI 1.27E-09 6. 22E-10 4. 94E-09 LCso 1.27E-08 2. 49E-09 1.11E-08 GIso 2. 53E-10 2. 49E-11 3. 70E-10 DU-145 TGI 3.80E-10 6. 22E-11 4.94E-10 LCso 1.01E-09 2. 49E-10 1.23E-09 GIso2. 53E-099. 95E-102. 47E-09 MCF TGI 5.06E-09 4. 98E-09 8. 64E-09 LCso 1. 27E-08 1. 12E-08 1. 1 lE-08 GI50 2. 53E-10 2. 49E-10 4. 94E-10 MB-231 TGI 6.33E-10 1.24E-09 2.47E-09 LCso 1. 27E-08 1. 12E-08 1.23E-08 GIso HMEC-1 TGI LCso GI50 LNCAP TGI LCso GIso SK-OV3 TGI LCso GIso IGROV TGI LCso GIso IGROV-E TGI LCso GI50 SK-BR3 TGI LCso GI50 K-562 TGI LC50 GI50 PANC-1 TGI LC50 GI50 LOVO TGI LCso GI50 LOVO-DOX TGI LCso GIso HELA TGI LCso GI50 HELA-APL TGI LC50 Compound 167 Compound 171 Compound 172 GI50 2.83E-08 2.28E-08 2.41E-07 A-549 TGI 6.54E-08 4.68E-08 4.59E-07 LC5o 4.82E-07 9.60E-08 8. 53E-07 GI50 2.89E-08 3.91E-09 3.88E-08 HT-29 TGI 3.24E-08 1.43E-07 LCso 1. 09E-05 1.06E-05 8. 53E-06 Also SW-620 TGI LCso GI50 2.38E-08 5.65E-09 1.31E-09 MEL-28 TGI 5. 06E-08 2.33E-08 3. 22E-09 LCso 1.07E-07 1.02E-07 7. 97E-09 GIso OVCAR TGI LCso GIso A-498 TGI LCso GIso4. 88E-085. 05E-093. 79E-08 DU-145 TGI 1. 01E-07 2. 96E-08 8. 31E-08 LCso 1. 09E-05 1. 06E-05 8. 53E-06 GIso MCF TGI LCso GIso MB-231 TGI LCso GIso 5.15E-08 2.94E-09 4.32E-07 HMEC-1 TGI 3.49E-07 6.90E-09 8.53E-06 LCso 1.09E-05 1.06E-05 8.53E-06 GI50 1.97E-08 1.66E-09 2.77E-08 LNCAP TGI 3.80E-08 3.14E-09 4. 31 E-08 LCso 7.36E-08 5.94E-09 6.68E-08 GIso 4. 02E-08 6. 89E-09 2. 19E-07 SK-OV3 TGI 1.48E-07 9.73E-08 5.09E-07 LCso 1. 09E-05 1.06E-05 8.53E-07 GIso 6. 46E-09 1. 93E-09 1. 42E-08 IGROV TGI 2.49E-08 4. 12E-09 3. 01E-08 LCso 8.92E-08 8.80E-09 6. 36E-08 GIso 7. 76E-08 2. 25E-07 1. 65E-07 IGROV-ET TGI 9. 05E-07 7.08E-07 4. 18E-07 LCso 5. 24E-06 1. 06E-05 8.53E-07 GIso 1. 76E-0 2. 47E-09 5. 02E-08 SK-BR3 TGI 5. 19E-08 6.54E-09 2.00E-07 LCso 2. 38E-07 3.75E-08 7.85E-07 GIs0 7. 00E-0 2. 43E-10 6. 03E-09 K-562 TGI 9. 64E-09 4.88E-10 9. 98E-09 LCso 7. 17E-08 9.82E-10 3. 53E-08 GI50 4.65E-0 7.30E-09 3.26E-07 PANC-1 TGI 1. 09E-07 4.63E-08 8.34E-07 LCso 1. 09E-05 1.06E-06 8. 53E-06 GIso 3. 36E-08 2. 37E-08 2. 26E-07 LOVO TGI 6. 74E-08 7.66E-08 4.61E-07 LCso 1. 90E-07 1.06E-05 8.53E-07 GIso 4. 16E 0 9. 38E-07 2. 88E-Of LOVE-DO TGI 1. 58E-06 1.23E-06 7. 23E-06 LCso 1. 09E-05 1. 06E-05 8. 53E-06 GIso HELA TGI LCso GI50 HELA-APL TGI LCso Compound 173 Compound 174 Compound 175 GI50 3.26E-09 9.80E-10 2.25E-09 A-549 TGI 4. 35E-09 2. 94E-09 4.24E-09 LCso 1. 09E-08 9. 80E-09 7. 97E-09 GIso2. 17E-091. 96E-094. 15E-09 HT-29 TGI 6.52E-09 6.86E-09 1. 54E-08 LCso 9. 78E-09 9. 80E-09 1. 01E-05 GI50 3.26E-09 9.80E-10 SW-620 TGI 6.52E-09 6. 86E-09 LCso 2. 17E-08 6.86E-07 GI50 2.17E-09 1.96E-09 3.28E-09 MEL-28 TGI 5.43E-09 4.90E-09 6.63E-09 LCso 1. 09E-08 9. 80E-09 2. 52E-08 GIso OVCAR TGI LCso GIso2. 17E-091. 96E-09 A-498 TGI 4.35E-09 3.92E-09 LCso 2. 17E-08 9. 80E-09 GI5o 1. 09E-09 2. 94E-10 3. 67E-09 DU-145 TGI 2.17E-09 9.80E-10 9.20E-09 LCso 3. 26E-09 3. 92E-09 1. 0lE-05 GIso 3. 26E-09 3. 92E-09 MCF TGI 9.78E-09 1.96E-08 LCso 1.09E-07 8.82E-08 GIso2. 17E-099. 80E-10 MB-231 TGI 5.88E-09 LCso 2.17E-08 9.80E-08 GIso 3. 54E-09 HMEC-1 TGI 1.29E-08 LCso 1.01E-05 GIso 3. 82E-10 LNCAP TGI 1.12E-09 LCso 3.64E-09 GIso 3. 56E-09 SK-OV3 TGI 8.77E-09 LCso 1.01E-05 GIso 6. 41E-10 IGROV TGI 2.37E-09 LCso 8.13E-09 GIso3. 97E-09 IGROV-ET TGI 9. 56E-09 LCso 1.72E-06 GIso1. 31E-09 SK-BR3 TGI 3. 78E-09 LCso 1.32E-08 GIso 2. 93E-10 K-562 TGI 4. 76E-10 LCso 7.75E-10 GIso 4. 38E-09 PANC-1 TGI 1.33E-08 LCso 1. 01 E-05 GIso 2. 30E-09 LOVO TGI 4.38E-09 LCso 8. 33E-09 GIso 4. 33E-08 LOVO-DOX TGI 1.55E-07 LCso 1. 01E-05 GIso HELA TGI LCso GIso HELA-APL TGI LCso Compound 176 Compound 182 Et-701 GI50 2. 75E-09 4. 09E-10 2. 99E-O9| A-549 TGI 6. 01E-09 1.36E-09 7. 06E-09 LCso 1.12E-08 6. 81E-08 1.39E-08 GI5o 3. 83E-09 2. 72E-10 4. 24E-09 HT-29 TGI 7. 96E-09 1. 09E-09 3.72E-08 LCso 1.12E-05 1.36E-09 9.56E-06 GIso1. 09E-09 SW-620 TGI 4.09E-09 LCso 1.36E-08 GIso2. 58E-084. 09E-109. 74E-09 MEL-28 TGI 4.97E-08 1.36E-09 3.50E-08 LCso 9.56E-08 5.45E-09 1.22E-07 GIso OVCAR TGI LCso GIso 4. 09E-10 A-498 TGI 1.36E-09 LCso 5. 45E-09 GI50 5.24E-09 2.72E-10 4.04E-09 DU-145 TGI 1.10E-08 4.09E-10 9.70E-09 LCso 8.36E-06 1.09E-09 2.97E-06 GIso2. 72E-09 MCF TGI 5.45E-09 LCso 1. 36E-08 GI50 2.72E-10 MB-231 TGI 6. 81E-10 LCso 8. 17E-09 GI50 3.46E-09 3.99E-09 HMEC-1 TGI 1. 48E-07 1. 35E-08 LCso 1. 12E-05 4. 57E-06 GIso1. 62E-093. 24E-10 LNCAP TGI 3. 25E-09 1. 56E-09 LCso 6. 49E-09 5. 28E-09 GIs0 3. 26E-0 l 2. 10E-0 SK-OV3 TGI 8. 07E-09 1. 08E-08 LCso 1. 10E-08 9. 85E-06 GI50 1.74E-09 2.33E-09 IGROV TGI 4. 30E-09 5. 08E-09 LCso 1. 07E-08 1. 1 lE-OF GI50 4. 88E-0 l 1. 64E-O IGROV-ET TGI 3. 38E-08 7. 78E-08 LCso 3. 45E-06 3. 75E-06 GISO 2. 70E-09 2. 21 E-09 SK-BR3 TGI 7. 73E-09 6. 25E-09 LCso 4. 06E-08 2. 75E-08 GIso 7.37E-10 1.33E-09 K-562 TGI 1.52E-09 3.50E-09 LCso 6.89E-09 1.13E-08 GIso 5. 31 E-09 4. 61 E-09 PANC-1 TGI 1.97E-08 1. 19E-08 LCso 3.20E-06 2.06E-07 GIso 1. 11 E-08 4. 56E-09 LOVO TGI 5.12E-08 1.18E-08 LCso 1.12E-07 3.75E-06 GIso4. 73E-085. 06E-08 LOVO-DOX TGI 1. 15E-06 5.46E-07 LCso 1. 12E-05 1.39E-05 GIso HELA TGI LCso GIso HELA-APL TGI LCso Compound 193 Compound 200 Compound 209 GIso 01E-102. 30E-089. 09E-11 A-549 TGI 4. 01E-09 3. 45E-08 3.90E-10 LC5o 1. OOE-07 1. 15E-07 1. 17E-09 GIsol. OOE-102. 30E-087. 79E-11 HT-29 TGI 2. 01E-08 8.05E-09 3.90E-10 LCso 2. 01E-05 1. 15E-06 1.17E-09 GIso7. 79E-11 SW-620 TGI 3.90E-10 LCso 1.30E-09 GIso 6. 49E-11 MEL-28 TGI 2. 60E-10 LCso 1.30E-09 GIso OVCAR TGI LCso GIso1. 30E-10 A-498 TGI 3. 90E-10 LCso 1.30E-09 GI50 1.30E-11 DU-145 TGI 3. 90E-11 LCso 1.30E-10 GI50 2.60E-10 MCF TGI 7.79E-10 LCso 5. 19E-09 GIso 1. 30E-11 MB-231 TGI 2. 60E-10 LCso 1.30E-09 GIso HMEC-1 TGI LCso GI50 LNCAP TGI LCso GIso SK-OV3 TGI LCso GIso IGROV TGI LCso GIso IGROV-ET TGI LCso Iso SK-BR3 TGI LCso GI50 K-562 TGI LCso GIso PANC-1 TGI LCso GI50 LOVO TGI LCso GIso LOVO-DOX TGI LCso GI50 HELA TGI LCso GI50 HELA-APL TGI LCso Compound 210 Compound 211 Compound 212 GIso 6. 33E-14 3. 67E-12 9. 11 E-09 A-549 TGI 5. 06E-13 6. 11 E-09 2.28E-08 LCso 3. 80E-05 6. 11E-05 1. 14E-07 GIso 6. 33E-14 1.22E-12 2.28E-09 HT-29 TGI 6.33E-08 1.22E-12 4.56E-09 LCso 6.33E-05 6.11E-05 1. 14E-08 GIso2. 28E-11 SW-620 TGI 1. 14E-08 LCso 2.28E-06 GIso 1. 14E-09 MEL-28 TGI 3.42E-09 LCso 9.11E-09 GIso 3. 42E-10 OVCAR TGI 3.42E-09 LCso 2. 28E-06 GIso 2. 28E-09 A-498 TGI 1. 14E-08 LCso 1. 14E-06 GIso1. 14E-10 DU-145 TGI 6. 83E-10 LCso 1. 14E-08 GIso 3. 42E-10 MCF TGI 1. 14E-08 LCso 3.42E-07 GIso 2. 28E-10 MB-231 TGI 5.69E-09 LCso 1.14E-07 GIso HMEC-1 TGI LCso GIso LNCAP TGI LCso GIso SK-OV3 TGI LCso GI50 IGROV TGI LCso GIso IGROV-ET TGI LCso GIso SK-BR3 TGI LCso GIso K-562 TGI LCso GIso PANC-1 TGI LCso GIso LOVO TGI LCso GI50 LOVO-DO TGI LCso GI50 HELA TGI LCso GIso HELA-APL TGI LCso Compound 215 Compound 217 Compound 219 GIso 9. 24E-08 2. 10E-09 8.24E-09 A-549 TGI 1. 01E-05 6.16E-09 1.65E-06 LC5o 1.01E-05 4.57E-08 1.65E-05 GIso8. 68E-081. 31E-088. 24E-08 H-T29 TGI 1.65E-06 LCso 1.01E-05 1.31E-05 1.65E-05 Also SW-620 TGI LCso GI50 1.97E-08 5.37E-10 MEL-28 TGI 4.54E-08 1. 48E-09 LCso 1. 19E-07 9. 39E-09 GI50 OVCAR TGI LCso GIso A-498 TG, I LCso GI50 4.22E-08 5.03E-1 DU-145 TGI 8. 06E-08 8. 77E-10 LCso 1. 01 E-05 1. 31E-09 GIso MCF TGI LC50 GIso MB-231 TGI LCso GIso 6.76E-10 1. 82E-10 HMEC-1 TGI 7. 95E-10 4. 08E-10 LCso 1. 01E-09 9. 19E-10 GIso3. 65E-083. 44E-09 LNCAP TGI 5. 50E-08 9.78E-09 LCso 1. 01E-07 6. 60E-06 GI50 3.45E-08 4.76E-10 SK-OV3 TGI 1.29E-07 1. 31E-09 LCso 1.01E-05 1.31E-05 GIso2. 68E-082. 63E-08 IGROV TGI 5. 82E-08 6.35E-08 LCso 1. 01E-07 1. 31E-07 GIso 2. 87E-07 2. 44E-0 IGROV-E TGI 7. 32E-07 1. 31E-07 LCso 1. 01E-05 1. 31E-05 GIso1. 62E-084. 94E-10 SK-BR3 TGI 4. 85E-08 2. 14E-09 LCso 3.88E-07 8. 34E-09 GIso3. 39E-073. 68E-10 K-562 TGI 2. 79E-06 1. 42E-09 LCso 01E-05 4. 27E-06 GIso 2. 92E-08 6. 05E-10 PANC-1 TGI 1. 74E-07 9. 32E-09 LCso 1. OlE-OC 1. 31E-05 GIso2. 35E-081. 38E-09 LOVO TGI 5. 19E-08 5. 47E-09 LCso 1. 01E-07 1. 31E-08 GIso6. 07E-073. 85E-08 LOVO-DOX TGI 1.01E-05 1.31E-07 LCso 1. 01E-05 1. 31E-05 GI50 HELA TGI LCso GI50 HELA-APL TGI LCso Compound 220 Compound 223 Compound 224 GI50 1.32E-07 3.87E-09 5.32E-09 A-549 TGI 3.96E-07 1.01E-08 1.10E-08 LCso 6.61E-06 1. 28E-05 1.29E-05 GI50 1.32E-07 6.54E-09 5.19E-09 H-T29 TGI 5. 28E-07 1. 28E-07 1.36E-08 LC5o 1. 32E-06 1. 28E-05 1.26E-05 GIso SW-620 TGI LCso GI50 2.79E-09 MEL-28 TGI 5.35E-09 1. 02E-08 GIso OVCAR TGI LCso GIso A-498 TGI LCso GIso5. 07E-09 DU-145 TGI 1. 08E-08 LCso 3. 32E-08 GIso MCF TGI LCso GI50 MB-231 TGI LCso GIso1. 01E-09 HMEC-1 TGI 2. 58E-09 LCso 6.91E-09 GIso1. 83E-09 LNCAP TGI 3. 62E-09 LCso 7. 16E-09 GI50 4. 47E-09 SK-OV3 TGI 8. 33E-09 LCso 6. 60E-06 GIso3. 55E-09 IGROV TGI 8. 61E-09 LCso 4. 35E-06 GIso4. 16E-08 IGROV-ET TGI 1.11 E-07 LCso 1. 29E-05 GIso4. 61E-09 SK-BR3 TGI 1. 27E-06 LCso 3. 06E-07 GIso 1. 72E-09 K-562 TGI 3. 44E-09 LCso 5. 94E-08 GIso 3. 49E-09 PANC-1 TGI 1. 01E-08 LCso 5. 12E-07 GIso 5.07E-09 LOVO TGI 2.57E-08 LCso 4. 19E-06 GIso6. 41E-08 LOVO-DOX TGI 7. OOE-07 LCso 1.29E-05 GIso HELA TGI LCso GIso HELA-APL TGI LCso TOXICITY DATA Toxicity was asssessed by the methods reported in Toxicology in Vitro, 15 (2001) 571-577, J. Luber Narod et al. :"Evaluation of the use of in vitro methodologies as tools for screening new compounds for potential in vivo toxicity". ComnmjndI, ivfrHartMvelo SkeletalKidnfv 57 4.66E-09 3.48E-09 1.85E-08 REDO 3. 35E-09 59 2.53E-08 8.14E-08 4. 18E-08 1.46E-07 2.87E-08 61 1.32E-08 2.76E-08 1.69E-08 1.47E-08 5.12E-09 63 1.44E-08 6.66E-08 1.52E-08 3.06E-09 1.58E-08 64 2.57E-08 5. 50E-08 1.93E-08 1.66E-09 1.77E-08 65 5. 30E-09 9. OOE-09 1.70E-08 3.77E-09 3. 15E-09 67 3.20E-08 4.54E-08 3.27E-08 2.37E-08 5.36E-08 68 1.76E-08 1. 13E-08 1. 89E-08 1.27E-08 5. 10E-09 70 3. 16E-08 2.20E-07 6. 61E-08 3. 67E-08 1.07E-07 72 1.55E-08 3.78E-08 2.15E-08 1.32E-08 1.85E-08 74 3.07E-08 2.86E-08 3.30E-08 8. 30E-10 3.05E-08 75 4. 11 E-08 8.17E-08 5.85E-08 4.06E-09 3.86E-08 76 1.35E-08 1.62E-08 8.19E-09 2.15E-09 3.20E-09 77 9.53E-09 1.64E-08 8.52E-09 2.20E-09 3.22E-09 78 5.88E-08 8.19E-07 NT 1. 96E-08 2.59E-07 79 2.28E-08 3.46E-08 1.35E-08 2.75E-09 1. 74E-08 86 1.47E-08 8.16E-08 8.35E-08 3.88E-08 1.37E-08 87 6.18E-08 3.60E-08 2.44E-07 2. OOE-07 8. 09E-08 92 2.30E-08 2.80E-08 1.92E-08 1. 21E-08 1.35E-08 93 1.13E-08 4. 46E-08 3.35E-09 5. 52E-10 6.32E-08 94 1.24E-08 6.66E-08 1.13E-08 1.44E-09 3.49E-09 97 1.57E-08 9.63E-08 1.77E-08 4.62E-09 1.43E-08 98 4. 21 E-08 4.98E-08 3.79E-08 1.24E-08 1.08E-06 99 4.80E-08 1.13E-07 1.45E-07 9. 71E-08 2. 56E-08 101 5.40E-08 7.67E-08 1.96E-08 3.40E-09 3.17E-08 104 4.16E-09 3.44E-09 1.93E-08 4. 10E-07 2.67E-09 161 8.58E-09 1.13E-08 2.27E-08 1.65E-08 2.60E-09 163 9.80E-07 4.80E-07 2.38E-07 2.53E-06 6.33E-07 165 1.68E-08 2.79E-08 2.87E-08 1.47E-08 1.89E-08 167 4.83E-07 4.28E-07 1. 01E-06 1.09E-07 2.77E-07 170 3. 58E-07 NT NT 3.29E-07 3. 01E-07 171 8.37E-08 3.13E-08 1.37E-07 3.58E-08 2.70E-08 172 2.47E-07 7.52E-07 3. 81E-07 8.53E-07 7.93E-07 173 4.03E-08 1. 19E-07 4.98E-06 2.49E-06 7.09E-08 174 1.34E-08 2.76E-08 7.27E-08 9.80E-07 1.24E-08 175 3. 87E-09 2. 82E-09 1.59E-08 2.12E-07 2.84E-09 176 2.95E-08 1.98E-08 1.42E-08 2. 41E-08 2. 80E-09 182 3.98E-09 3.95E-08 3.19E-08 1.49E-08 1. 26E-08 183 3.03E-08 3.72E-08 2.39E-08 2.67E-08 6.72E-03 212 8. 68E-08 3.20E-08 8. 58E-09 2. 21E-08 3.34E-09 213 3.93E-08 1.82E-07 2.70E-08 1.72E-07 1.48E-08 217 1.07E-09 TT TT 3. 37E-12 2. 66E-13