FIELD OF THE INVENTION The present invention is directed to novel compounds useful for the synthesis of biologically active compounds. More particularly, the present invention is related to novel reagents that give rise to new and useful protecting groups. The present invention is also directed to methods of forming these novel reagents and protecting groups and using the same in the synthesis of important pharmaceutical intermediates. BACKGROUND OF THE INVENTION Oftentimes during the synthesis of complex molecules, one functional group of the molecule interferes with an intended reaction on a second functional group elsewhere in the same molecule. Typically, this problem can be circumvented by temporarily masking or "protecting" the more reactive functional group thereby encouraging the desired reaction. Protection essentially involves three steps: 1) introducing the protecting group onto the functional group to be protected by means of a protecting group carrying reagent; 2) carrying out the desired reaction; and 3) removing the protecting group. Protection and deprotection are inevitable requirements of a lengthy synthetic sequence to generate synthetic chemical products, fine chemical intermediates, or important industrial or pharmaceutical organic materials. Accordingly, many protective groups and reagents capable of introducing them into synthetic processes have been and are continuing to be developed today. However, not every molecule can serve as a useful protecting group. Rather, a protecting group must fulfill a number of requirements in order to be useful in carrying out selected syntheses. First, a protecting group needs to react selectively and be easily attached to the functional group it is supposed to protect. Also, there must be a good yield of the protected compound. Further, a protecting group needs to be resistant to the certain reagents that would otherwise attack the group it protects, and it must not harm the other functional groups in the molecule. In other words, the protected compound needs to remain stable as it proceeds through the multiple steps in the synthetic sequence. Finally, a protecting group needs to be easily removed under conditions that will not adversely react with the regenerated functional group. Protecting groups exist for various functional moieties and have their own pattern of chemoselectivity during deprotection. In molecules with multiple discrete simultaneous protections, a careful strategy exists for specific removal and modification of the exposed functionality. Thus, elaborately protected, highly functional templates can serve as total synthetic intermediates. To date, a remarkable variety of protecting reagents has been reported, and the preparation of the reagents as well as the protection and deprotection strategies under a variety of conditions have been summarized nicely in the literature. In addition, as should be appreciated, more elaborate syntheses cannot be accomplished with only a few protecting groups. Rather, such elaborate syntheses can typically only succeed with the use of a large number of mutually complementary protecting groups. Accordingly, great strides have been made to synthesize new protecting groups that complement existing protecting groups. Examples of protecting groups and the corresponding reagents can be found in Green et al., "Protective Groups in Organic Chemistry", (Wiley, 2.sup.nd ed. 1991) and Harrison et al., "Compendium of Synthetic Organic Methods", VoIs. 1-8 (John Wiley and Sons, 1971-1996). For example, protecting groups have been developed for the protection of hydroxy groups, amine groups, carbonyl groups, and carboxyl groups, to name a few. Representative hydroxy protecting groups include, but are not limited to, those where the hydroxy group is either acylated or alkylated such as benzyl, and trityl ethers as well as alkyl ethers, tetrahydropyranyl ethers, trialkylsilyl ethers and allyl ethers. Among the hydroxy protecting groups, benzyl ethers are highly robust and are often employed so that they can be removed at later stages in a synthetic sequence. Thus, benzyl ether protection is often employed as a "long-term" protecting group carried through multiple steps in a synthetic sequence. On the other hand, substituted benzyl ethers are deliberately less stable, can be cleaved easily and are employed as temporary protecting groups that can be removed conveniently at earlier stages of the synthesis when more delicate functionality is present. A number of esoterically substituted benzyl ethers have been reported in the literature such as various mono or multiple methoxylated benzyl ethers, or for example, a p-NO2 benzyl ether. In general, the conditions employed during protection and deprotection are less compatible with other protecting groups and also require longer reaction times and produce lower yields. Many protecting groups have also been developed for the amino group. Representative amino protecting groups include, but are not limited to, formyl, acetyl, trifluoroacetyl, benzyl, benzyloxycarbonyl ("CBZ"), tert-butoxycarbonyl ("t-BOC"), trimethylsilyl ("TMS"), 2-trimethylsilyl-ethanesulfonyl ("SES"), trityl and substituted trityl groups, allyloxycarbonyl, 9-fluorenylmethyloxycarbonyl ("FMOC"), nitro- veratryloxycarbonyl ("NVOC") and the like. Although numerous and effective protecting groups exist, there is still a need for new reagents that give rise to new protecting groups that discriminate among different functional groups and suppress reactivity at the site they protect. Further, there is a need for new protecting groups that complement those protecting groups already in existence so as to assist in the more elaborate syntheses of important pharmaceutical compounds. SUMMARY OF THE INVENTION An object of the present invention is to provide novel and useful reagents that give rise to new protecting groups for the synthesis of biologically active organic compounds; Another object of the present invention is to provide new reagents that can easily introduce new protecting groups onto a desired functional site under mild conditions; It is also an object of the present invention to provide new protecting groups that may be easily added and removed from the functional site they protect under mild conditions; Yet another object of the present invention is to provide a new class of protecting groups for alcohols, amines, and thiols. According to the present invention, then, a new and useful protecting reagents are provided that allow for the selective placement of the protecting group they carry onto a reactive site of a multifunctional molecule. The present invention further contemplates methods of forming these protecting reagents and use of the protecting group in the synthesis of pharmaceutical compounds and intermediates therefor. The protecting reagents of the present invention generally have the formula TIX-Y wherein Y is selected from the group consisting of OCNHCCI3, Cl1 Br, I1 NCO, OCOCI, OCH2CI, OTs, OMs, ONs and OTf. Structurally, TIX-Y may be selected from the following general formulas: and

wherein R', R" and R'" are each an alkyl group, an aryl group or a combination thereof. More particularly, TIX-Y may have be selected from the group consisting of:

Once the TIX protecting group is attached to at least one site of the targeted multifunctional compound, the overall formula can generally be represented as R-Z- TIX wherein R is the targeted multifunctional compound and Z is either oxygen, nitrogen or sulfur. Structurally, the compound R-Z-TIX may selected from the following general formulas:

Further, R-Z-TIX may be an ether, a urethane, a carbonate, an acetal, a carbamate or a urea and may particularly have a formula selected from the group consisting of:

wherein Ri is selected from the group consisting of an alkyl, an alkenyl, an alkynyl, an aryl and a cyclic form involving R. R-Z-TIX may specifically be selected from the group consisting of:

A process for producing a TIX protecting reagent useful for introducing a protecting group onto a selected reactive site of a multifunctional molecule is further provided. The process comprises converting a first compound of a general formula TIX-OH to a second compound of a general formula TIX-Y, wherein Y is selected from the group consisting of OCNHCCI3, Cl, Br, I, MCO, OCOCI, OCH2CI, OTs1 OMs, OTf and ONs. In this process the first compound may be

while the second compound may be selected from the group consisting of:

An intermediate compound may be formed before the formation of the second compound generally having the formula TIX-Q wherein Q is selected from the group consisting of OMs, OTs, ONs, and OTf. The present invention also provides a method of protecting a selected site on a multifunctional compound. The method comprises reacting a first compound of the formula TIX-Y with a second compound of the formula R-ZH thereby to form a third compound of the formula R-Z-TIX, wherein R is a multifunctional compound; Y is selected from the group consisting of OCNHCCI3, Cl, Br, I, NCO, OCOCI, OCH2CI, OTs, OMs, OTf and ONs; and Z is oxygen, nitrogen, or sulfur. More specifically, in this process of protecting the reactive site, the second compound and third compounds may have the respective formulas:

The third compound may then be converted into a fourth compound having the formula:

Alternatively, the second and third compounds may have the following respective formulas:

Again, the third compound may be converted to the fourth compound shown above. Yet another alternative of this process is to provide a second and third compound of the following respective formulas:

Here again, the third compound may be then converted into a fourth compound of the formula shown above. As is also provided, the present invention is directed to a method for use in producing epothilones and analogs and derivatives thereof. The method comprises reacting a first compound of the formula:

with an aldehyde of the formula:

thereby to form a first intermediate compound of the formula: wherein:

Ri5 is either or ; P is a hydroxyl protecting group; P3 and Pis are each H or a hydroxyl protecting group and wherein at least one of P3 and Pi5 is a TIX protecting group. This first intermediate compound may thereafter be converted into a second intermediate compound of the formula:

wherein:

R15 is either or P is a hydroxyl protecting group; Pi and P7 are each hydroxyl protecting groups; P3 and Pis are each H or a hydroxyl protecting group; and wherein at least one of P1, P3, P7 and P15 is a TIX protecting group. Thereafter, the second intermediate compound may be cyclized to form a third intermediate compound of the formula

The third intermediate compound may then be converted into a fourth compound selected from the group consisting of:

and

Another method for use in producing epothilones and analogs and derivatives thereof that is contemplated comprises cyclizing a first compound of the formula:

thereby to form a second compound of a formula:

wherein:

Ri5 is either or ; P is a hydroxyl protecting group; P3 and P7 are each H or a hydroxyl protecting group and wherein at least one is a TIX protecting group. Alternatively, in the above cyclization of the first compound to form the second compound, the formulas could be defined as follows: P3 is H, a hydroxyl group, or R3 when P7 is TIX; P7 is H, a hydroxyl group, or R7 when P3 is TIX; and R3 and R7 are each H, an ester, an ether, a carbonate, or a carbamate; The present invention also relates to chemical compounds, which may be formed according to the above method or by other methods, and in particular to compounds of the formulas:

wherein: R3 and R7 are each selected from H, an ester, an ether, a carbonate, and a carbamate;

Ri5 is either

P, P3, and P7 are each hydroxyl groups wherein at least one is a TIX protecting group.

These and other objects of the present invention will become more readily appreciated and understood from a consideration of the following detailed description of the exemplary embodiments. DETAILED DESCRIPTION OF THE INVENTION The present invention is directed toward novel reagents giving rise to novel protecting groups that may be used to protect selected functional groups on a multifunctional compound. The present invention is further directed to novel protecting groups that can be attached to hydroxyl groups, and as further anticipated, to amine groups and thiol groups, and thereafter be selectively removed in the presence of other groups under mild conditions. More particularly, the present invention provides 2, 3, and 4-trialkylsilylxylyl, triarylsilylxylyl or a combination of alkyl-aryl silylxylyl reagents, which can collectively be referred to as TIX reagents. The TIX reagents carry the TIX protecting groups, which are capable of protecting alcohols as ethers, urethanes, carbonates, or acetals, and as anticipated capable of protecting amines as carbamates or ureas and thiols as ethers or esters. The present invention is also directed to methods of forming these new 2, 3, and 4-TIX reagents; methods of introducing the new TIX protecting groups to molecules bearing hydroxyl groups, amine groups, or thiol groups; methods of removing the TIX protecting groups; and intermediate compounds formed during any one of these methods. As will be appreciated from the discussion provided below, the 2, 3, and 4 TIX carrying reagents give rise to TIX protecting groups that have unique chemoselective protection and deprotection behavior. Furthermore, these protecting groups may be used to protect selected functional groups of simple multifunctional substrates, or in the alternative, may complement existing benzyl ether, ester, carbonate, carbamate or urea based protecting groups for more elaborate substrates. Indeed, it is suggested that the 2, 3, and 4-TIX protecting reagents contemplated will occupy a unique niche in protecting group methodology because the protection and deprotection can occur by methods without affecting other common or sensitive functionalities. As used herein, the abbreviations listed below have the following meaning. List of Abbreviations:

TMSMB Trimethylsilylmethylbenzyl Cbz Benzyloxycarbonyl tBoc tert-Butoxycarbonyl TMS Trimethylsilyl OdO 2-Trimethylsilyl-ethanesulfonyl Fmoc 9-fIuorenylmethyloxycarbonyl Nvoc Nitroveratryloxycarbonyl OMs Methanesulfonyloxy OTs p-ToIuenesulfonlyoxy OTf Trifluoromethanesulfonyloxy DBU 1 ,8-Diazabicylco[5,4,0]undec-7-ene pTSA p-Toluenesulfonic acid PPTS Pyridinium p-toluenesulfonate TBDMS tert-Butyldimethylsilyl TBDPS tert-Butyldiphenylsilyl SEM 2-(Trimethylsilyl)ethoxymethyl PMB p-Methoxybenzyl MBn p-Methylbenzyl Bn Benzyl Bz Benzoyl Ac Acetyl MEM Methoxyethoxy methyl TFA Trifluoro acetic acid DDQ 2,3-Dichloro-5,6-dicyano-1 ,4-benzoquinone CAN Ammonium cerium(iV)nitrate TBAF Tetrabutylammonium fluoride

I. GENERALIZED PROCESS FOR PROVIDING THE PROTECTED SUBSTRATE

Generally, the 2, 3, and 4-TIX protecting reagents are prepared, respectively, from 2, 3, and 4-TIX alcohols. Here again, "TIX alcohols" collectively refers to 2, 3, and 4-trialkylsilylxyIyl, triarylsilylxylyl or a combination of alkyl-aryl silylxylyl alcohols. The protecting group may then be introduced to a multifunctional compound to selectively protect hydroxyl or amine groups and then later cleaved therefrom at an appropriate time during the synthetic sequence of the substrate compound. The 2, 3, and 4-TIX alcohols, which are useful starting compounds for the production of the TIX protecting reagents have the following respective general formulas:

2-TIX alcohol 3-TIX alcohol 4-TIX alcohol Here, R', R" and R"' can selectively be an alkyl, an aryl group or a combination thereof. The preparation of 2, 3, and 4-TIX alcohols is known. For example, Alessandro and Albini describe a process for making the 4-TIX alcohol, which is shown and described with respect to Scheme IV of their report entitled "Methylbenzene Cation Radical α-Fragmentation Selectivities Revealed in SET- Photoadditions of p-Xylene Derivates to 1 ,4 Dicyanonaphthalene". J. Org. Chem., 1993, 58, 939 and 941. The 2, 3, and 4-TIX protecting reagents derived from the 2, 3, or 4-TIX alcohols have the following respective formulas:

2-TIX protecting 3-TIX protecting 4-TIX protecting reagent reagent reagent Here, R', R" and R'" can selectively be an alkyl, an aryl group or a combination thereof and Y is selected from the group consisting of OCNHCCI3, Cl, Br, I, NCO, OCOCI, OCH2CI, OTs, OTf, OMs, and ONs. As will be discussed in greater detail below, the TIX protecting group that is carried by any one of the above TIX protecting reagents, is that structure attached to Y. Further, if desired, the TIX protecting reagents may be incorporated onto a solid phase resin, which could provide for the chemoselective deprotection of different functional groups. The 2, 3, and 4-TIX protecting reagents may then be reacted with alcohols where the TIX protecting group is attached thereto to form ethers, urethanes, carbonates, or acetals. Alternatively, the TIX protecting reagents may be reacted with amines such that the TIX protecting group forms carbamates or ureas or with thiols such that the TIX protecting group forms ethers or esters. The formation of the TIX protecting reagents from their respective alcohols, the introduction of the TIX protecting groups onto a multifunctional molecule bearing either a hydroxy! or amine group, and the subsequent cleavage of the protecting group therefrom can be generalized as follows: Deprotected Multifunctional Cmpd

R-ZH / 2, 3, 4-TIX-OH 2, 3, 4-TIX-Y _μ R-ZH R-ZTIX

2, 3, 4-TIX-OH TIX τιx Multifunctional TIX Protected Alcohol Protecting Cmpd Multifunctional Reagent Compound TIX Alcohol

In the above generalized process, R represents any multifunctional compound, Y is selected from the group consisting of is selected from the group consisting of OCNHCCI3, Cl1 Br, I1 NCO, OCOCI, OCH2CI, OTs, OMs, and ONs, and Z is either O or N such that ZH is representative of the hydroxyl or amine group targeted for protection by the TIX protecting group. It is anticipated that the TIX carrying reagent could introduce a TIX protecting group capable of protecting thiol groups in which case Z would represent S, for sulfur. The methods contemplated by the present invention are illustrated in more detail below using exemplary processes for the formation of 4-TIX protecting reagents, as wells as exemplary protection and deprotection reactions involving the 4-TIX protecting reagents and the TIX protecting groups they carry. For the sake of simplicity, the following examples show the compounds and processes using 2, 3, or 4-trimethylsilylxylyl, but should not be construed as limited thereto. Further, the invention should not be construed as limited to the specific examples provided herein. Before describing the compounds and methods of the present invention in more detail, it is noted at the outset that, as above, "R" represents any multifunctional compound in the processes described below with respect to Schemes [-Xl. Tables 1 and 3, however, specifically define "R" as a particular multifunctional compound bearing either a hydroxyl group or an amine group targeted for protection. A. Alcohols Protected As Ethers Generally, there are three different routes for protecting alcohols as ethers according to the present invention. Scheme I provides a generalized reaction of an ether formed from an alcohol under acidic conditions while Schemes Il and III provide for ethers that are anticipated to be formed from alcohols under basic conditions. Each Scheme can generally be divided into two parts - the formation reaction whereby the TIX protecting reagent is formed, and the TIX protection reaction whereby the ether is formed with the TIX protecting group. Scheme I is outlined as follows: SCHEME I

A B1 C As shown above, the 4-TIX alcohol A can be converted to its trichloroimidate, which is the 4-TIX^ protecting reagent B-i. The 4-TIX protecting reagent Bi may then be reacted with selected alcohols to form ethers C using catalytic methods. The 4- TIX protecting reagent B1 can be prepared on large scale and distilled, and is a stable liquid under inert atmosphere. Furthermore, it should be noted that the formation of the 4-TIX protecting reagent Bi may involve a polymer-supported reagent. Accordingly, the 4-TIX protecting reagent Bi can also be beneficially applied to solution phase parallel chemistry using solid phase reagents during generation of parallel libraries. As mentioned above, alternative reactions, such as those shown in Schemes and ill, can provide for the protection reaction to occur under basic conditions. SCHEME Il

SCHEME III

A B2 C In Schemes Il and III above, Q is selected from the group consisting of OMs, OTs, and OTf and Yi is selected from the group consisting of Cl, Br, and I. Conversion of the alcohol A to the intermediate compound W and then to the 4-TIX protecting reagent B2, consisting of halides, is straightforward and allows for base catalyzed ether formation. In the alternative, the interconversion of alcohol A to the 4-TIX protecting reagent B2 should also provide for base catalyzed ether formation C. The 4-TIX protecting reagent B2 provides alternatives to the chloroimidate protecting reagent Bi (Scheme I) methodology under acidic conditions. B. Alcohols Protected As Urethanes It is anticipated that alcohols can be protected as urethanes according to two different routes as shown below in Schemes IV and V. SCHEME IV

Here again, Q is selected from the group consisting of OMs, OTs, and OTf and Yi is selected from the group consisting of Cl, Br, and I. As anticipated, the conversion of 4-TIX alcohol A to 4-TIX protecting reagent B3 may proceed through intermediate W and protecting reagent B2 to provide access to the 4-TIX isocyanate protecting reagent B3 via simple SN2 displacement with KNCO, and the like. In the alternative, the reaction may proceed without first forming intermediate W. The 4-TIX protecting reagent B3 reacts with alcohols and expected to form 4-TIX urethanes D. C. Alcohols Protected As Carbonates It is anticipated that alcohols can be protected as carbonates according to the following scheme: SCHEME Vl

COCIp ROH

A B4 E Here, 4-TIX alcohol A can be converted to a chloroformate, the 4-TIX protecting reagent B4 with phosgene, which is expected to form carbonate E. D. Alcohols Protected As Acetals It is anticipated that alcohols can be protected as acetals according to the following scheme: SCHEME VII

A B5 F Here, the alcohol A reacts with formaldehyde and HCI to give a chloromethyl ether, the 4-TIX protecting reagent B5, which is expected to form acetal F from the alcohols to be protected under basic conditions. Here, stability should be greater and SEM-like removal conditions would be more appropriate (e.g. MgBr2, n-BuSH). E. Amines Protected As Carbamates It is anticipated that amines can be protected as carbamates according to the following Scheme VIII: SCHEME VIII

Here, Ri above may be selected from the group consisting of an alkyl, an alkenyl, an alkynyl, an aryl and a cyclic form involving R. As shown, 4-TIX alcohol A is converted to a chloroformate, the 4-TIX protecting reagent B4, by reacting alcohol A with phosgene. The 4-TIX protecting reagent B4 may be reacted with an amine having the formula RNH2 and is expected to form the protected 4-TIX carbamate G. Alternatively, the 4-TIX protecting reagent B4 may be reacted with an amine having the formula RRiNH and is expected to form carbamate H. Similar but milder cleavage conditions can be used for these groups.

F. Amines Protected As Ureas It is anticipated that amines can be protected as ureas according to Scheme IX:

The formation of protecting reagent B3 was shown and described above with respect to Schemes IV and V. Here , however, the 4-TIX protecting reagent B3 reacts with an amine having the formula RNH2 and is expected to form the protected 4-TIX urea J. Alternatively, the 4-TIX protecting reagent B3 may be reacted with an amine having the formula RR1NH, where R1 may again, for example, be selected from the group consisting of an alkyl, an alkenyl, an alkynyl, an aryl and a cyclic form involving R, and is expected to form the protected 4-TIX urea K. II. EXAMPLES Schemes I - IX above provide generalized methods for forming ethers, urethanes, carbonates, acetals, carbamates, and ureas by introducing a 4-TIX protecting group according to the present invention. More specific exemplary reactions related to the formation, protection, and deprotection reactions were conducted by inventors associated with the present disclosure and have been described below. Again, as should be appreciated, the present invention should not be construed as limited to the exemplary reactions discussed herein.

A. Formation and Protection Reactions Overall, the experiments conducted demonstrated that the 4-TIX protecting reagent Bi was easily introduced onto the hydroxyl moiety of the desired alcohol using a one-pot trichloroacetimidate protocol. Beginning with the formation reaction wherein the 4-TIX alcohol A is converted to the TIX protecting reagent Bi, by combining the 4-TIX alcohol A, CI3CCN, and DBU and converting the 4-TIX alcohol A to the trichloroacetimidate B-|. In one study, the trichloroacetimidate 4-TIX protecting reagent Bi was purified by chromatography or distillation before being introduced to the alcohol to be protected. However, since the 4-TIX protecting reagent B1 was insufficiently stable to silica gel chromatography, this particular method produced low yields of the protected alcohol. In an effort to increase yields, the trichloroacetimidate 4-TIX protecting reagent Bi was introduced to the alcohol to be protected without purification. In this procedure, after reacting the 4-TIX alcohol A with DBU, the solution was treated with the alcohol to be protected (R-OH) followed by a slight excess (over DBU) of p- toluenesulfonic acid (pTSA) or its pyridinium salt (PPTS). The yields according to this method were moderate to good; however, the presence of unreacted alcohols (4-TIX alcohol A and the alcohol to be protected , R-OH) was noted. As an alternative to the procedures described above, further experimentation demonstrated that solid supported chemistries, now readily available, eliminated lengthy low yielding purifications of the 4-TIX protecting reagent B1. According to this procedure, the 4-TIX alcohol A and CI3CC IM were reacted with a commercially available polymer supported base related to 1 ,8-diazabicyclo[5,4,0]-undec-7-ene (DBU), 1 ,5,7-triazabicyclo[4,4,6]dec-5-ene (PS-TBD) in dichloromethane at O0C. Thereafter, simple filtration furnished essentially pure 4-TIX protecting reagent B-ι. Since no DBU was present, catalysis of the ensuing ether formation with the alcohol to be protected, R-OH, did not require harsh, hygroscopic sulfonic acids. As a result, a catalytic amount of a mild Lewis acid such as scandium triflate could be usefully employed to furnish the protected TIX ethers C i n good to excellent yields. To check for generality and functional group compatibility, the protection reaction generalized in Scheme I was performed on a variety of alcohols, e.g. 1°, 2°, 3°, benzylic, allylic and anomeric; bearing functionalities such as a β-keto group, an enone, olefin, acetylenic unit, or a variety of other protecting groups. Accordingly, as specified in Table 1 , "R" represents a specific multifunctional compound bearing a hydroxyl group targeted for protection. The protection reaction tested and the resulting yields of the respective ethers are provided in Table 1 : TABLE 1

Sample No. Ether Product Isolated Yield (%)

Sample No. Ether Product Isolated Yield (%)

The chemoselectivity of these protection conditions was examined with 1 ,6- hexanediol, which was differentially protected on one side with TBDMS, TBDPS, SEM, benzyl, PMB, as specified by P in column 2 of Table 2 , and the remaining alcohol subjected to the protection protocol. The studies conducted demonstrated that the TIX reagent was installed without affecting the other protecting groups. The protection reaction tested and the resulting yields of the respective ethers are provided in Table 2. TABLE 2

Isolated Example No. P Ether Product Yield (%)

3 PMB 78

8 TBDMS TBDWiso "S*^ OTIX 85

TBDPS 80

B. Deprotection Reaction The selective removal or cleavage of the protecting group from the substrate compound was also investigated. Many reagents, conditions and solvents were evaluated, including TFA, DDQ, CAN, Lewis acids (such as MgBr2, BF3-OEt2, ZnCI2) and fluoride reagents (including TBAF, LiBF4, and HF-Pyr). Among these, DDQ provided a mild and chemoselective oxidative cleavage of the TIX moiety in the presence of other functionalities and protecting groups. This deprotection method resulted in high yields, adding an advantage to the use of this protecting group compared to its removal under acidic conditions. Using, again, the reaction shown in Scheme I, the 4-TIX ethers C may be cleaved back to alcohols, under mild conditions, with DDQ in aq ueous dichloromethane. Here again, "R" is used to represent a specific multifunctional compound bearing a hydroxyl group that was targeted for protection. The deprotection reactions tested using DDQ and the resulting yields of the alcohols are provided in Tables 3 and 4. TABLE 3

Yield of Example No. R-OTIX Alcohol (%)

TABLE 4

"DDQ conditions at -200C **Reaction conducted using TFA/CH2CI2

Treatment of TIX ethers with TFA instead of DDQ led to variable yields of the deprotected alcohol product, and, in some instances, difficult to remove contaminants. Among the by-products were highly non-polar aromatic compounds that presumably resulted from facile polymerization of p-quinone dimethide (p- xylylene). Nonetheless, as shown in Table 4 above, selectivity in the cleavage of the PMB group over TIX was achieved for Entry No. 3 using TFA instead of DDQ, with 2% TFA at 0°C for 2 h. As shown in Table 4, the PMB group was selectively removed in the presence of the TIX group to afford HO-(CH2)6-OTIX in 80% yield. Alternatively, in Table 4, Entry No. 2, it was the TIX group that selectively cleaved with DDQ at -200C leaving the PMB in place, giving PMB-(CH2)S-OH in 74% yield. III. ROLE OF THE SILYL GROUP IN THE PROTECTION AND DEPROTECTION REACTIONS

Mechanistically, the cleavage of the TIX group by DDQ is likely to be similar to that of the PMB protecting group for, in most cases, p-trimethylsilylmethyl benzaldehyde L was isolated as a by-product. As illustrated below in Scheme X, treatment of ether C with DDQ and H2O produced the transition state complex 1. SCHEME X

Compared to p-methylbenzyl or benzyl ethers, the formation of 1 indicates that the role of the silyl group is to facilitate the DDQ deprotection rate by stabilizing the partial carbonium ion of transition state 1 by an otherwise generally accepted β- effect. Further, as shown in the transition states 1 and 2, a benzylic proton is abstracted and an α-elimination of hydride occurs to reduce the quinone reagent, leading to a benzylic, oxonium stabilized transition state complex 2 that is quenched by water to furnish hemiacetal 3. Simple elimination of ROH completes the ether cleavage by the extrusion of ROH with simultaneous unveiling of the oxidized silyl bearing ring to again form the 4-TIX aldehyde L. The fact that silicon is not eliminated in this process is important in ensuring higher yields as 1 ,6-desilylative elimination would lead to the unstable p-quinone dimethide. The role of the silyl group in both protection and deprotection steps was further assessed with a few representative p-methylbenzyl ethers. Surprisingly, while p-methylbenzyl alcohol readily underwent imidate formation, it was reluctant to undergo acid catalyzed ether formation with comparable or even marginally similar efficacy compared to the TIX group. This fact implied that the protection step was promoted by the presence of the 1 ,6-silyl group, and presumably by a mechanism reminiscent of the deprotection step outlined in Scheme X. Thus, the fact that p-xylyl ethers (MBn ethers) would not form in acceptable yields or at acceptable rates with either 0.02 or even 0.10 molar equivalents of scandium triflate (Table 2, Entry 2), while the cholorimidate 4-TIX protecting reagent Bi reacted rapidly and cleanly with 0.02 M equivalents, strongly implicated a silyl assisted transition state for the protection step. Furthermore, removal of the MBn ether with DDQ in the presence of TIX ether showed great selectivity for rapid removal of the TIX group, as had been the case for the benzyl ether (Table 4, Entry 1 and 2). The putative involvement of the silyl group of the 4-TIX imidate protecting reagent Bi during acid catalyzed ether formation with ROH is shown in Scheme Xl. SCHEME Xl

As shown, the 4-TIX protecting reagent B1 is reacted with the selected alcohol to be protected, ROH, in the presence of scandium triflate to form the intermediate compound of 4. As shown, the scandium (III) exerts a coordinating effect on the protecting reagent B1 nitrogen lone pair of electrons, weakening the benzylic C-O bond. Thus, the benzylic position begins to bear partial positive charge that is stabilized by the p-TMSCH2- moiety, 4. Meanwhile, ROH, also complexed to Sc(III), is available to donate a proton to the departing amide moiety while simultaneously attacking and replacing the benzylic imidate group to form the intermediate compound of 5. With the ether bond now formed, Sc (III) is free to continue its catalytic action to form ether C. IV. Application of 2, 3, and 4-TIX protecting reagents in the synthesis of epothilones Since their discovery in 1993, certain epothilones have evoked strong interest from the scientific community because of their anticancer activity. For example, exemplary epothilones A-D have the following respective formulas:

Epothilone A, Rj2 = H Epothiloiie B, K]2 = Me Epothilone C, RJ2 = H Epothilone D, Rj2 = Me One strategy for the total synthesis of such epothilones includes construction of a C1-C6 synthon, such as a keto-acid of formula:

where P is an alcohol protecting group that undergoes aldol condensation with an aldehyde to set important stereochemical features of the epothilone architecture. This keto-acid could be prepared as reported in our work via an Evans enantioselective aldol condensation. Panicker, B.; Karle, J. M.; Avery, M. A. Tetrahedron, 2000, 56,7859-7868 and references therein. As shown in Scheme XII below, the dibutylboron enolate of the reported oxazolidinone 18 reacted with keto- aldehyde 19 to give an α-thiomethyl amide aldol intermediate. Desulfuration was readily accomplished using Raney Ni, providing the corresponding R: S aldol adducts 20 in a 23:77 ratio, respectively (70% yield). After silylation with TBDMSOTf, compound 21 was obtained. Removal of the auxiliary group produced 23 in good overall yield. SCHEME XII

21 23

Key: (a)(i) Bu2BOTf, DIPEA, CH2Cl2, 0 0C then add 18 at -78 0C; (ii) Raney Ni, acetone, 60 0C, 45 min, 70% combined; (b) TBDMSOTf, pyridine, CH2Cl2, O 0C to rt, 95%; (c) LiOH, H2O2, THF-H2O, rt, 82%.

The TIX protecting reagents and protecting groups discussed herein, as applied to the Epothilone system, can be uniquely fashioned to provide selective protection and deprotection schemes using a novel, proprietary protecting moiety. Specific examples using the 4-TIX protecting reagent B-i, hereafter structure number 10, are discussed below with respect to Schemes XIII-XVIII. First, as shown in Scheme XIII below, the aldol adduct 20 was prepared according the procedure described above with respect to Scheme XII. Next, as shown in Scheme XIII, the aldol adduct 20 was reacted with protecting reagent 10 forming the compound corresponding to 22, with further reaction, designated "c" in Scheme XIII, leading to the TIX keto-acid corresponding to 24, a heretofore unknown compound. Aldol adduct 20 can be used in the next aldol coupling reaction either directly or after being converted into the TIX keto-acid 24. SCHEME XIII

22 24

Key: (a) (i) Bu2BOTf, DIPEA, CH2CI2, O 0C then add 18 at -78 0C; (Ii) Raney Ni, acetone, 60 0C, 45 min, 70% combined; (b) protecting reagent 10, Sc(OTf)3, CH2CI2, O 0C to rt, 90%; (c) LiOH, H2O2, THF-H2O, rt, 82%.

Alternatively, the TIX keto-acid 24 can be made from the chiral sultam 27 as

shown in Scheme XIV below. Once the TIX protecting group is installed, the TIX

chiral sultam 28 may furnish TIX keto-acid 24 in high yields. The TIX keto-acid 24

may then be used for aldol condensation with, for example, an epothilone C7-C15

aldehyde synthon (shown, for example as structure no 3 in Avery, M. A et al Org.

Lett., 2001, 3(23), 3607). SCHEME XIV

Other optional routes to synthesis of the TIX keto-acid 24 or related compounds like 28 is to prepare the acid 24 from the enone in Table 1 , Entry 7, having the structure

hereafter, structure 29. The free acid end, with alcohol protected as the TiX ether, can now be converted to any number of derivatives for optimization of the ensuing aldol chemistry directed towards total synthesis of epothilones (eg. 30). This is shown in Scheme XV: Once the TIX keto acid 24 is formed, it may then under aldol condensation with an aldehyde 50 to form various intermediate compounds useful in the synthesis of epothilones. Generally, then, a keto acid of the formula is reacted with an aldehyde of the formula:

thereby to form a first intermediate compound which can be generalized as:

wherein and P, P3, and Pi5 are each H or a hydroxyl protecting group. The hydroxyl protecting group can be any suitable protecting group, but may further be a TIX protecting group as described here. Formation of the aldehyde having the general formula provided above is generally described in a previously filed application, S.N. 09/981 ,312, entitled "Synthesis of Epothilones and Related Analogs" filed October 15, 2001. This first intermediate compound may then subsequently be converted to various other intermediate compounds in the process having the general formula:

This general reaction is exemplified in Scheme XV.

SCHEME XV

In Schemes XV-XVII, R is any multifunctional compound and R15 could be either

or

where P is a hydroxyl protecting group. As should be appreciated, then, TIX acid 24

may be used as an alternative to the TBDMS ketoacid 23 to provide protection

schemes not available previously. As shown, aldol condensation of the ketoacid 24

leads to the aldol adduct 32. The C-7 aldol alcohol can be readily protected as TIX ether to afford the tri-TIX derivative 33, which may thereafter be saponified to afford the free acid 35. In this route [24 -> 32 -> 33 -> 35], 32 is likely to be formed as a mixture of diastereomers whose ratio improving production of 32 can be influenced by a number of factors such as counter ions, solvent and temperature. A striking result is obtained by using an auxiliary (chiral or achiral) attached to the acid moiety, e.g. compound 30, shown in Scheme XV, when TIX acid 24 is treated with AUX-NH2 to form compound 30. When AUX NH of compound 30 is used instead of the chiral sultam as shown in compound 28 in Scheme XIV, the aldol reaction can be conducted to afford high yields of the desired syn diastereomer 31. Furthermore, leaving the AUX group in place allows for the installation of the TIX protecting group at C-7 without esterification, or the need for saponification, thus saving a reaction in the overall process. Once the bis-TIX ether 34, having the AUX group has been constructed, the AUX group can be saponified by aqueous base to give the free acid 35. To ready the material for macrolactonization, the SEM protecting group is then removed to afford the bis-TIX hydroxyacid 36. This material can be cyclized using Yamaguchi conditions to give bis-TIX epothilone D, 37, as shown in Scheme XVI. After formation of the intermediate compound of formula:

it may then subsequently be cyclized to form yet another intermediate compound having the general formula:

Thereafter, the cyclized compound may be converted to various intermediate compounds useful in the synthesis of epothilones. This is exemplified in Scheme XVI, wherein reactions with bis-TIX epothilone D, 37 allows for the formation of those compounds corresponding to 38, 39, 40, 41 and 42. More specifically, as shown, 37 may undergo reaction "b" to form compound 38 with subsequent reaction "c" to form compound 40. In addition, 37 could undergo reaction "c" directly to form compound 39. Finally, as shown 37 could undergo reaction "d" to form a mixture of compounds 41 and 42.

SCHEME XVI

Key: (a) CI3C6H2COCI, Et3NATHF, DMAP/toluene; (b) 3,3-dimethyldioxirane, CH2CI2; (c) 2DDQ, H2O, CH2CI2; d) 1 DDQ, H2O, CH2CI2..

The cyclization of the bis-TIX hydroxyacid 36 to the bis-TIX epothilone D, 37 can be generalized according to the following reaction:

Here again, the R15, In addition to Schemes XIII thru XVI above, it is anticipated that the TIX protecting group can be used selectively for both protection and deprotection in combination with other protecting groups, which may be particularly useful in various other Epothilone related systems such as in the combinations shown below in Scheme XVII. SCHEME XVII

Key: (a) CI3C6H2COCI, Et3N/THF,, DIVIAP/toluene; (b) 3,3-dimethyldioxirane, CH2CI2;; (c) 1 DDQ, H2O, CH2CI2, O0C; (d) HF-pyridine, CH2CI2, O0C; (e) Derivatization of the alcohol; (f) HF-pyridine, CH2CI2, O0C; (g) 1 DDQ, H2O, CH2CI2, O0C. For example, in Scheme XVII, when the TIX ketoacid 24 (shown for example in Scheme XIII) is used to form the compound corresponding to 43, P7 could be any suitable hydroxyl protecting group other than TIX. For example, as contemplated, P7 could be any suitable ethers, esters, carbonates or carbamates. Alternatively, if the TBDMS ketoacid 23 is used to form 43, P7 could be the TIX protecting group or any suitable hydroxyl protecting group other than TBDMS such any suitable ethers, esters, carbonates or carbamates. Further, if either P3 or P7 is a TIX protecting group, the other protecting group (P3 or P7) can be a different silyl ether and be selectively used as shown in the case of examples of Table 2. In Scheme XVII, R3 and R7 could be H, an ester, ether, carbonate or a carbamate. These are a result of using either 23 or 24 for the Aldol reaction, and protecting the aldol adduct C7 OH with the alternate, nonidentical protecting group. Hence, two lactones 44 ensue wherein a first lactone has TBDMS at the C3 position and TIX at the C7 and a second lactone has TIX at the C3 position and TBDMS at the C7 position. These protections in schematic form are P3 or P7, denoting chain position. Deprotection of one over the other then is a simple matter of using DDQ, which does not touch the TBDMS group, furnishing mono-TBDMS ethers 46 or 47 (P3 Or P7 = TBDMS). Alternatively, selective desilylation is possible providing the mono-TIX lactones 46 or 47 (P3 or P7 = TIX). A specific scheme illustrating this is shown in Scheme XVIII. Here, the chemistry is identical to Scheme XVI except C-7 is protected as the silyl derivative (TBDMS), while the C-3 is the TIX ether. The yields for these mixed protecting reagents is quite acceptable, providing a suitable approach to the ring system whether the intact thiazole side chain is in place, or the protected ethanol side chain is in place adjacent to the lactone O. SCHEME XVIII

TBSOTf 1 DIPEA

With either mono TBDMS at C3 or C7, one can modify C7 or C3, respectively, and deprotect to give the mono-modified epothilone at C7 or C3. These modifications are only limited by chemosθlectivity and reactivity considerations but can include standard reactions of alcohols such as esterification, etherification, urethanation or carbonation using RCOCI, RX, RNCO or ROCOCI. In conclusion, a new efficient hydroxyl protecting group has been reported, which can be installed into 1°, 2° or 3° alcohols and chemoselectively cleaved under mild conditions. The pattern of selective removal in the presence of a benzyl ether, or the selective removal of the PMB ether in the presence of the TIX group allows this new protection method to occupy a niche in the milieu of benzyl ether protection that complements both benzyl and PMB groups. EXPERIMENTAL General Procedure for Protection of Alcohols: PS-TBD was taken (250 mg/mmol of A) along with dry dichloromethane (5 mL/mmol of A) under argon at 0° C, to which silyl alcohol A (1 molar equivalent) was added. After stirring for 5 min at 0° C, trichloroacetonitrile (1 molar equivalent) was added. The reaction mixture was brought to room temperature and stirred for 15 min. The organic solution was separated from the polymer beads, and the clear dichloromethane solution of B1 was then cooled to 0° C. At this time, 1 molar equivalent of a representative alcohol (e.g. Table 1 ) was added followed by scandium triflate (0.02 molar equivalents). The reaction mixture was stirred at room temperature for 15 min and diluted with dichloromethane (15 mL/mmol). The organic layer was washed with water, brine, dried (anhydrous Na2SO4), and concentrated. Simple purification was accomplished by flash column chromatography over silica gel using EtOAc/hexanes, providing the TIX ethers in excellent yields (Table 1). General Procedure for Deprotection of TIX Ethers: The TIX ether (1 molar equivalent C) was taken into dichloromethane:water (18:2 or 5 mL/mmoi). To this well stirred solution was added DDQ (1 molar equivalent) at room temperature. After completion of the reaction (as monitored by TLC for disappearance of starting material), the reaction mixture was filtered, and the filtrate was washed with dichloromethane. The combined organic layers were washed with a saturated aqueous solution of NaHCOs, brine, d ried (anhydrous Na2SO4), filtered and concentrated to furnish the alcohol along with byproducts. Purification was readily achieved by flash column chromatography (silica gel 60, EtOAc/hexanes) affording the alcohols in excellent yields (Table 3). Specific Examples

1. 2,2,2-Trichloro-acetimidic acid 4-trimethylsilanylmethyl-benzyl ester:

MoI. : C13H18Q3NOSi (338.7) Formula IR(cm-1) : 645, 841, 1074, 1294, 1662,2953. 1H NMR : 8.41 (bs, IH); 7.32 (d, 2H, J= 7.9Hz); 7.05 (d, 2H, J= 7.9Hz); 5.32 (s, (CDCl3, 2H); 2.13 (s, 2H); 0.04(s, 9H) 400MHz)

2. (4-Benzyloxymethyl-benzyl)-trimethyl-silane:

MoI. Formula C18H24OSi (284) IR (cm"1) 851, 1069, 1250,2887,2951 1H NMR 7.41-7.19 (m, 7H), 6.96 (d, 2H,J= 7.6Hz), 4.6 (s, 2H),4.5 (s, 2H), 2.08 (CDCl3, (s,2H),-0.01 (s,9H) 400MHz)

3. Trimethyl-(4-phenethyloxymethyl-benzyl)-silane:

MoI. Formula C19H26OSi (298) IR (cm"1) 847, 1079, 1245,2987 1H NMR 7.31-7.19 (m, 5H), 7.16 (d, 2H,J=7.6Hz), 6.98 (d, 2H,J=7.6Hz), 4.65 (CDCl3, (s, 2H), 3.69 (t, 2H, J= 7.2Hz), 2.94 (t, ZH, J= 7.2Hz), 2.07 (s, 2H, (s, 400MHz) 2H),-0.01 (s,9H)

4. Trimethyl-[4-(3-phenyl-propoxymethyl)-benzyl]-silane:

MoI. Formula C20H28OSi (312) IR (cm4) 851, 1099, 1246,2921,2951 1H NMR 7.21-7.32 (m, 7H), 7.02 (d, J=7.6Hz, 2O), 4.48 (s, 2H), 3.52 (t, J= 6 (CDCl3, Hz, 11.6Hz, 2H), 2.75 (t, J= 7.6 Hz, 15.2 Hz, 2H), 2.11 (s, 2H), 1.96- 400MHz) 2.01 (m,2H),0.033 (d,J=0.8Hz,9H) 5. (^Cyclohexyloxymethyl-benzyO-trimethyl-silane:

MoI. Formula C17H28OSi (276) IR (cm"1) 844, 1082, 1252, 2928 1H NMR 7.19 (d, J = 7.6 Hz, 2H), 6.95 (d, / = 7.6 Hz, 2H), 4.48 (d, J = 3.6 Hz, (CDCl3, 2H), 3.30-3.36 (m, IH), 2.056 (s, 2H), 1.21-1.96 (m, 10H), -0.019 (s, 400MHz) 9H)

6. [4-(CycIohex-2-enyloxymethyl)-benzyl]-trimethylsilane:

MoI. Formula C17H26OSi (274) IR (cm"1) 845, 1076, 1246, 1504, 2951 1R NMR 7.19 (d, / = 7.6 Hz, 2H), 6.15 (d, J = 8 Hz, 2H), 5,78-5.86 (m, 2H), 4.51 (CDCl3, (dd, J = 11.6 Hz, 2H), 3.94 (bs, IH), 2.05 (s, 2H>, 1.96-1.70 (m, 6H), 400MHz) 0.01 (s, 9H)

7. [4-(1 -methyl-cyclohexyloxymethyO-benzyl]- Trimethyl s ilane:

MoI. C18H30OSi (290) Formula IR (cm"1) : 847, 1068, 1123, 1245, 2856, 2921 H NMR : 7.20 (d, J = 1.6 Hz, 2H), 6.95 (d, / = 7.6 Hz, 2H), 4.34 (s, 2H), 2.04 (CDCl3, (s, 2H), 1.89-1.25 (m, 10H), 1.21 (s, 3H), -0.02 (s, 9H) 400MHz)

8. 3-Ethyl-4,4-dimethyl-5-(4-trimethylsilanylmethyl-benzyloxy&g t;-cyclohex-2- enone:

MoI. C21H32O2Si (344) Formula IR (cm"1) 850, 1075, 1245, 1664, 2921, 2951. 1H NMR 7.15 (d, / = 8 Hz, 2H), 6.95 (d, J = 7.6 Hz, 2H), 5.83 (s, IH), 4.59 (d, (CDCl3, J =11.6 Hz, IH), 4.36 (d, 7 = 11.2 Hz, IH), 3.54 (dd, / = 4, 8 Hz, IH), 400MHz) 2.73 (dd, J = 4 Hz, 16 Hz, IH), 2.57 (dd, J = 8.8 Hz, 16.8 Hz, IH), 2.26 (distorted doublet J = 6.8 Hz, 2H), 2.063 (s, 2H), 1. 16 (d, / = 4.8 Hz, 6H), 1.08 (t, J = 7.2, 14.4 Hz, 3H), -0.024 (s, 9H).

9. δjδ-Dimethyl^^-trimethylsilanylmethyl-benzyloxyJ-octane^jÎ ²-dione:

MoI. C21H34O3Si (362) Formula IR (cm"1) 847, 1075, 1245, 1705, 2951. 1H NMR 7.08(d, J = 8 Hz, 2H), 6.93 (d, J = 8 Hz, 2H), 4.42 (dd, J = 11.2, 29.6 (CDCl3, Hz, 2H), 4.25 (dd, J= 3.2, 7.2Hz, IH), 2.62 (dd, J = 7.6, 17.2 Hz, IH), 400MHz) 2.46-2.54 (m, 3H), 2.14 (s, 3H), 2.04 (s, 2H), 1.15 (s, 3H), 1.10 (s, 3H), 0.98 (t, J= 6.8, 14, 7.2 Hz, 3H), -0.03 (s, 9H) 10. Trimethyl-[4-(3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahy dro-pyran-2- yloxymethyl)-benzyl]-silane:

MoI. Formula C45H52O6Si (716.9) IR (cm"1) 702, 845, 1078, 1245, 1458, 2892. 1H NMR 7.23-7.33 (m, 20H), 7.12 (d, J = 7.2 Hz, 2H), 6.95 (d, J = 7.2 Hz, 2H), (CDCl3, 4.4-5.0 (m, 10H), 4.35-4.04 (m, 7H), 2.07 (s, 2H), -0.017 (s, 9H). 400MHz)

11. Trimethyl-[4-(1 -phenyl-ethoxymethyl)-benzyl]-silane:

MoI. C19H26OSi(298) Formula IR (cm"1) 760,845, 1107, 1246, 1511,2889. 1H NMR 7.38 (d, 2H); 7.30 (t, 2H); 7.23 (t, IH); 7.16 (d, 2H, J= 1.6Hz); 6.97 (CDCl3, (d,2H,J=1.6Hz);4.51(m, IH);4.40 (d, IH,J= 11.4Hz);4.25 (d, 1Η, 400MHz) /= 11.6Hz); 2.07(s,2Η); 1.48(d,3H,/=6.4Hz);-0.006(s,9Η).

12. Trimethyl-[4-(1 -methyl-prop-2-ynyloxymethyl)-benζyl]-silane:

MoI. C15H22OSi (246) Formula IR (cm"1) 850, 1103, 1250, 1516, 2962. 1H NMR 7.24 (d, 2H, J= 7.6Hz); 7.01 (d, 2Η, J= 7.6Hz); 4.76(d, 1Η, J= (CDCl3, 11.2Hz); 4.47(d, 1Η, J= 11.2Hz); 4.24 (m, 1Η); 2.48 (s, 1Η); 2.10 (s, 400MHz) 2Η); 1.93 (d, 3H, J= 6.8Hz); 0.013 (s, 9Η).

13. [4-(6-benζyloxy-hexyloxymethyl)-benζyl]-trimethyl-silane:

MoI. Formula : C24H36O2Si (384) IR(cm"1) : 847, 1099, 1242,2853,2931 1H NMR : 7.25-7.34 (m, 5H), 7.18 (d, J = 8 Hz, 2H), 6.96 (d, J = 8 Hz, 2H), 4.50 (CDCl3, (s, 2H), 4.43 (s, 2H), 3.43-3.48 (m, 4H), 2.069 (s, 2H), 1.61 (m, 4H), 400MHz) 1.38 (m, 4H), -0.015 (s, 9H)

14. 2,2,2-Trichloro-acetimidic acid 4-methyl-benzyl ester:

MoI. : CIOH10C13NO (266.5) Formula IR (cm"1) : 645, 829, 1009, 1082, 1303, 1670, 3317. 1H NMR : 8.37 (bs, IH); 7.33 (d, 2H); 7.21 (d, 2H); 5.31 (s, 2H); 2.36 (s, 3H). (CDCl3, 400MHz)

15. Trimethyl-{4-[6-(4-methyl-benzyloxy)-hexyloxymethyl]-benzyl} -silane:

MoI. C25H38O2Si (398.6) Formula IR (cm"1) 694, 857, 1098, 1245, 1507, 2949. 1H NMR 7.23 (d, 2H, J= 7.6Hz); 7.18 (d, 2Η, J= 7.6Hz); 7.15 (d, 2Η, /= (CDCl3, 7.6Hz); 6.97 (d, 2Η, J= 7.6Hz); 4.46(s, 2Η); 4.44(s, 2H); 3.45 (dd, 4H, 400MHz) J= 6.4Hz); 2.34 (s, 3Η); 2.07 (s, 2H); 1.60 (m, 4H); 1.38 (m, 4H); - 0.02 (s, 9H).

16. {4-[6-(4-Methoxy-benzyloxy)-hexyloxymethyl]-benzyl}-trimethy l-silane:

MoI. : C25H38O3Si (414.65) Formula TR (cm"1) : 845, 1099, 1246, 1511, 2856, 2933 1H NMR : 7.29 (d, 2H, J= 8.4Hz); 7.21 (d, 2Η, /= 7.6Hz); 6.99 (d, 2Η, J= (CDCl3, 7.6Hz); 6.90 (d, 2Η, J= 8.4Hz); 4.46(s, 4Η); 3.83(s, 3H); 3.46(dd, 4H, 400MHZ) J= 6.4, 13.2Hz); 2.09(s, 2Η); 1.65(m, 4H); 1.40(m, 4H); 0.01(s, 9H).

17. 1 -[6-(2-Trimethylsilanyl-ethoxymethoxy)-hexyloxymethyl]-4- trimethylsilanyl-methyl-benzene:

MoI. Formula : C23H44O3Si2 (424) IR (cm"1) : 854, 1061, 1106, 12.52, 2863, 2945 1H NMR : 7.17 (d, J = 7.6 Hz, 2H), 6.96 (d, J = 7.6 Hz, 2H), 4.65 (s, 2H), 4.431 (s, (CDCl3, 2H), 3.60 (t, J = 8.4 Hz, 16.8 Hz, 2H), 3.52 (t, J = 6.8 Hz, 13.2 Hz, 2H), 400MHz) 3.45 (t, J = 6.8 Hz, 13.2 Hz, 2H), 2.06 (s, 2H), 1.58-1.61 (m, 4H), 1.25- 1.379 (m, 4H), 0.93 (t, / = 8.4 Hz, 16.8 Hz, 2H), 0.018 (s, 9H), -0.024 (s, 9H)

1 δ. Acetic acid 6-(4-trimethylsilanylmethyl-benzyloxy)-hexyl ester:

MoI. : C19H32O3Si (336) Formula IR(cm"1) : 854, 1103, 1246, 1740,2860,2950. 1H NMR : 7.20 (d, 2H, J= 1.6Hz); 6.99 (d, 2H, J= 7.6Hz); 4.46(s, 2Η); 4.07 (t, (CDCl3, 2H, J= 6.4Hz); 3.48 (t, 2Η, J= 6.4Hz); 2.09 (s, 2Η); 2.06 (s, 3H); 1.65 400MHz) (m, 4H); 1.40(m, 4H); 0.003 (s, 9H).

19. Benzoic acid 6-(4-trimethylsilanylmethyl-benzyloxy)-hexyl ester:

MoI. : C24H34O3Si (398) Formula IR (cm"1) : 711, 854, 1107, 1275, 1720,2856,2946. 1H NMR : 8.07 (d,2H,J=7.2Hz); 7.58 (t, 1Η,J=7.6Hz);7.46 (t, 2Η,J=7.2Hz); (CDCl3, 7.20 (d, 2Η, J= 7.6Hz); 6.99 (d, 2Η, J= 7.6Hz); 4.47 (s, 2Η); 4.34 (t, 400MHz) 2H,J=6.4Hz); 3.50(t,2Η,J=6.4Hz);2.09(s,2Η); 1.80(m,2H); 1.66 (m,2H); 1.49(m,4H);0.006(s,9H).

20. 1 -[6-(terf-Butyldimethylsilanyloxy)-hexyloxymethyl]-4- trimethylsilanylmethyl-benzene:

MoI. Formula : C23H44O2Si2 (408) IR (cm"1) : 776, 858, 1099, 1250, 2856, 2933. 1H NMR : 7.17 (d, 2H, J= 7.6Hz); 6.96 (d, 2Η, J= 7.6Hz); 4.43 (s, 2Η); 3.60 (t, 2H, (CDCl3, J= 6.4Hz); 3.45 (t, 2Η, J= 6.4Hz); 2.07 (s, 2Η); 1.61 (m, 2H); 1.53 (m, 400MHZ) 2H); 1.35 (m, 4H); -0.02 (s, 9H).

21. [6-(tert-Butyl-diphenyl-silanyloxy)-hexyloxymethyl]-4-trimet hylsilanyl- methyl-benzene:

MoI. : C33H48O2Si2 (532) Formula IR (cm"1) : 702, 845, 1107, 1246, 1511, 2852, 2933 1H NMR : 7.70 (m, 4H); 7.41 (m, 6H); 7.21 (d, 2H, J= 1.6Hz); 6.99 (d, 2H, J= (CDCl3, 8.4Hz); 4.46(s, 2Η); 3.68 (t, 2H, /= 6.4Hz); 3.47 (t, 2Η, J= 6.4Hz); 400MHZ) 2.09 (s, 2H); 1.60 (m, 4H); 1.39 (m, 4H); 1.07 (s, 9H); 0.01(s, 9H).

22. {4-[6-(2-Methoxy-ethoxymethoxy)-hexyloxymethyl]-benζyl}-tri methyl- silane:

MoI. Formula : C21H38O4Si (382) IR (cm"1) : 853. 1045, 1106, 1249, 1511, 2933. 1H NMR : 7.17 (d, 2H, J= 7.6Hz); 6.96 (d, 2Η, J= 7.6Hz); 4.70 (s, 2Η); 4.42 (s, (CDCl3, 2H); 3.68 (t, 2H, J= 6.4Hz); 3.53 (m, 4Η); 3.45 (t, 2H, J= 6AHz); 2.06 400MHZ) (S, 2H); 1.60 (m, 4H); 1.38 (m, 4H); -0.023 (s, 9H).

23. 6-(4-Trimethylsilanylmethyl-benζyloxy)-hexan-1 -ol:

MoI. : C17H30O2Si (294) Formula IR (cm"1) : 858, 1107, 1246, 1687, 2856, 2938, 3370. 1H NMR : 7.19 (d, 2H, J= 7.6Hz); 6.98 (d, 2Η, J= 7.6Hz); 4.46 (s, 2Η); 3.65 (t, (CDCl3, 2H, J= 6.4Hz); 3.48 (t, 2Η, /= 6.4Hz); 2.07 (s, 2Η); 1.62 (m, 4H); 1.40 400MHZ) (m, 4H); 0.00 (s, 9H).

24. 6-(4-Methyl-benζyloxy)-hexan-1 -ol:

MoI. : C14H22O2 (222) Formula IR (cm"1) : 681, 804, 1074, 1262, 2945, 3374. 1H NMR : 7.22 (d, 2H, J= 1.6Hz); 7.15 (d, 2H, J= 7.6Hz); 4.45(s, 2Η); 3.62 (t, (CDCl3, 2H, J= 6.4Hz); 3.44 (t, 2Η, J= 6.4Hz); 2.34 (s, 3Η); 2.07 (s, 2H); 400MHZ) 1.60 (m, 4H); 1.38 (m, 4H). 25. 1 -Methyl-4-(3-phenyl-propoxymethyl)-benζene:

MoI. C17H20O (240) Formula IR (Cm"1) 702, 845, 1107, 1246, 1511, 2852, 2933 1H NMR 7.34 (m, 4H); 7.24 (m, 5H); 4.54 (s, 2H); 3.54 (t, 2H, J= 6.4Hz); (CDCl3, 2.78 (t, 2Η, J= 7.2Hz); 2.42 (s, 3Η); 2.09 (s, 2H). 400MHz)

26. 1 -(10,10-Dimethyl-3,3-dioxo-3l6-thia-4-aζa-tricyclo[5.2.1.01 ,5]dec-4-yl)- 4,4-dimethyl-3-(4-trimethylsilanylmethyl-benzyloxy)-heptane- 1 ,5-dione:

To a stirred solution of keto sultam 27 (0.39 g, 1.0 mmol) in dry dichloromethane (10 ml_) was added 4-(trimethylsilyl)benzyltrichloroacetimidate (0.4 g, 1.2 mmol), followed by addition of scandium triflate (10 mg, 0.02 mmol) at 0 QC and the mixture was stirred at same temperature for 10 min. The reaction mixture was diluted with dichloromethane (6 ml_) and washed with water (5 mL). The organic layer was separated, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, elution with 20% ethyl acetate in hexanes) to give 28 (0.3 g, 53%) as a colorless oil. MoI. : C30H47NO5SSi (561.8) Formula IR(cm"1) : 534, 845, 1078, 1131, 1613, 1695,2953. 1R NMR : 7.09(d, 2H, /=8.0Hz); 6.90(d, 2H, /=8.0Hz); 4.55(d, IH, J= (CDCl3, 11.OHz); 4.35(dd, IH, J= 4.5, 7.0Hz); 4.29(d, IH, Z=ILOHz); 400MHz) 3.86(dd, IH, 7=4.5, 7.0Hz); 3.45(dd, 2H, J= 13.5, 29Hz); 2.89(dd, IH, J= 4.5, 5.5Hz); 2.80(dd, IH, J= 4.5, 5.5Hz); 2.45(m, 2H); 2.12(m, IH); 2.05(m, IH); 2.02(s, 2H); 1.85(m, 3H); 1.36(m, 2H); 1.15(s, 3H); I.l4(s, 3H); 1.06(s, 3H); 0.95(s, 3H); 0.93(t, 3H); - 0.06(s,9H).

27. 4,4-Dimethyl-5-oxo-3-(4-trimethylsilanylmethyl-benzyloxy)-he ptanoic acid:

To a solution of keto sultam 28 (0.56 g, 1.0 mmol) in THFiH2O (4 ml_/1 mL) was added lithium hydroxide (0.05 g, 2.0 mmol) followed H2O2 (0.8 mL, 7.0 mmol, 30% aqueous solution) at O9C. The resulting mixture was stirred at room temperature for 7 h. The mixture was quenched with sodium sulfite (0.8 g) at 0QC and the THF was evaporated. To the remaining aqueous suspension was added ethyl acetate (10 mL) and the pH was adjusted to 6.0 by addition of 1 N HCI (0.7 mL). The aqueous phase was extracted with ethyl acetate (2 x 5 mL). The combined organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure to give keto acid, which was purified by flash column chromatography (silica gel, 3% methanol in dichloromethane) to afford pure keto acid 24 (0.26 g, 72%) as a viscous, colorless oil.

MoL : C20H32O4Si (364.5) Formula IR (cm-1) 645, 837, 1111, 1609, 1691,2953,3370. 1H NMR 7.09(d, 2H, /=7.6Hz); 6.92(d, 2H, /=7.6Hz); 4.59(d, IH, J= (CDCl3, 11.2Hz); 4.4(d, IH, J= 11.2Hz); 4.23(m, IH); 3.19-2.74(m, 2H); 400MHz) 2.52-2.48(m, 2H); 2.04(s,2H); 1.18(s, 3H); 1.15(s,3H); 0.98(t, 3H); -0.04(s,9H).

28. (35,6/7,7S5SS512Z,15S,16£)-3-{[(4-Trimethylsilyl)xylyl]oxy- 7-hydroxy-15- (2-trimethylsilyl-ethoxymethoxy)-4,4,6,8,12,16-hexamethyl-17 -(2-methyl-1 ,3- thiazol-4-yl)-5-oxoheptadeca-12,16-dienoic acid (32) and its (6S,7/?)~ diastereomer.

32 A solution of keto acid 24 (0.28 g, 0.76 mmol) in THF (0.7 ml_) was added dropwise to a freshly prepared solution of LDA [diisopropylamine (0.26 mL, 1.8 mmol) was added to π-BuLi (1.6 mL, 1.6 M solution in hexanes, 1.8 mmol) in 3 mL of THF at - 59C] at -789C. The reaction mixture was stirred at -789C for 15 min and warmed to - 409C for 1 h. The mixture was re-cooled to -78eC, and ZnCI2 (1.8 mL, 1.0 M solution in ether, 1.5 mmol) was added dropwise over 10 min. A solution of aldehyde [(+)- (2S,6Z,9S,10£)-2,6)1 O-Trimethyl-11-(2-methyl-1 ,3-thiazol-4-yl)-9-(2- trimethylsilylethoxymethoxy)undeca-6,10-dienal] (0.27 g, 0.6 mmol) was added dropwise, and the resulting mixture was stirred for 15 min and quenched by slow addition of sat'd aqueous NH4CI solution (3 ml_). The mixture was warmed to 0-C, and AcOH (0.2 ml_, 3.4 mmol) was added, followed by addition of ethyl acetate (2 ml_). The organic phase was separated, and the aqueous layer was extracted with ethyl acetate (3 x 3 mL). The combined organic phases were dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to give the aldol products as a diastereomeric mixture (2.0:1.0 by HPLC), which was purified by column chromatography (ethyl acetate/hexanes/methanol, 15:80:5) to give 7-hydroxy acids 32 and its (βSJ/^-diastereomer (0.34 g, 72% combined yield) as colorless oil.

MoI. Formula : C44H73NO7SSi2 (SlS) IR (cm"1) : 3501, 2954, 2895, 1710, 1614, 1469, 1248, 1058, 854. 1H NMR : 7.09 (d, J=7.80 Hz, 2 H), 6.96 (s, 1 H), 6.92 (d, /=7.80 Hz, 2 H), 6.55 (CDCl3, (s, 1/3 H), 6.51 (s, 2/3 H), 5.19 (dd, J=6.60 Hz, 7.20 Hz, 2/3 H), 5.15 (t, 400MHz) 7=7.20 Hz, 1/3 H), 4.64-4.60 (m, 4 H), 4.43 (dd, J=5.40 Hz, 4.80 Hz, 1 H), 4.21 (dd, /=4.20 Hz, 4.20 Hz, 1 H), 4.06 (dd, /=4.20 Hz, 5.40 Hz, 1 H), 3.70-3.74 (m, 2 H), 3.53 (dd, /=3.00 Hz, 3.00 Hz, 1 H), 3.36 (d, /=9.00 Hz, 1 H), 3.24 (q, /=7.20 Hz, 1 H), 2.75 (s, 2/3 x 3 H), 2.73 (s, 1/3 x 3 H), 2.51-2.47 (m, 3 H), 2.30-2.21 (m, 2 H), 2.04-2.00 (m, 5 H), 1.96 (s, 2/3 x 3 H), 1.94 (s, 1/3 x 3 H), 1.67 (s, 2/3 x 3 H), 1.66 (s, 1/3 x 3 H), 1.52-1.45 (m, 3 H), 1.35-1.27 (m, 1 H), 1.20 (s, 2/3 x 3 H), 1.19 (s, 1/3 x 3 H), 1.10 (d, /=6.00 Hz, 3 H), 0.99 (d, /=6.00 Hz, 3 H), 0.92 (s, 2/3 x 3 H), 0.91 (s, 1/3 x 3 H), -0.01 (s, 1/3 x 9 H), -0.02 (s, 2/3 x 9 H), -0.03 (s, 2/3 x 9 H), -0.04 (s, 1/3 x 9 H).

29. {3S,6R,7S,8S^2Z,Λ5S,Λ6E)-3-{[(4-Trimethγls\\y\)xγ\y\]oxÎ ³-7-{[tert- butyl(dimethyl)silyl]oxy}-15-(2-trimethyIsilylethoxymethoxy) -4,4,658,12,16- hexamethyl-17-(2-methyl-1 ,3-thiazol-4-yl)-5-oxoheptadeca-12,16-dienoic acid (35) and its (6S,7/?)-diastereomer.

To a stirred solution of 3-OTIX-7-OH-15-OSEM acids 32 and its (6SJR)- diastereomer (0.16 g, 0.2 mmol) in dichloromethane (3 ml_), 2,6-lutidine (0.17 g, 1.6 mmol) and fe/f-butyldimethylsilyl trifluoromethanesulfonate (0.26 g, 1.0 mmol) were sequentially added dropwise at 0QC, and the reaction mixture was stirred for 2 h. After completion of the reaction, aqueous 10% HCI solution (1.2 ml_) was added, and the organic layer was separated. The aqueous phase was extracted with dichloromethane (2 x 3 ml_). The combined organic phases were washed with brine (8 ml_), dried over anhydrous MgSCU, filtered, and concentrated under reduced pressure. The residue was dissolved in methanol (3 ml_), and potassium carbonate (0.16 g, 1.2 mmol) was added at room temperature. The mixture was vigorously stirred for 15 min. The reaction mixture was filtered, and the residue was washed with methanol (2 ml_). The solution was acidified with ion-exchange resin (DOWEX 50WX4-50) to pH 4-5 and filtered again. The solution was evaporated under reduced pressure, and the resulting residue was dissolved in ethyl acetate (8 ml_). The organic layer was washed with sat'd aqueous NH4CI solution (5 ml_), and the aqueous phase was extracted with ethyl acetate (3 x 3 ml_). The combined organic phases were washed with brine (10 ml_), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, ethyl acetate/hexanes/methanol, 15:80:5) to give 3- OTIX-7-OTBS-15-OSEM acid 35s and its (6S,7ft)-diastereomer (0.13 g, 72%) as colorless oil. . MoI. Formula C50H87NO7SSi3 (929) IR (cm"1) 2954, 2894, 2858, 170O, 1616, 1472, 1249, 1057, 854. 1H NMR 7.14 (d, /=6.40 Hz, 2 H), 6.98 (s, 1 H), 6.94 (d, J=5.60 Hz, 2 H), 6.59 (CDCl3, (s, 2/3 H), 6.56 (s, 1/3 H), 5.17 (t, /=4.80 Hz, 1 H), 4.71-4.60 (m, 4 H), 400MHz) 4.46 (dd, /=10.8 Hz, 10.8 Hz, 1 H), 4.32-4.24 (m, 1 H), 4.12 (dd, /=5.40, 5.40 Hz, 1 H), 3.88 (dd,J=6.60Hz, 6.60 Hz, 1/3 x 2H), 3.79 (dd, J=7.80 Hz, 7.80 Hz, 2/3 x 2 H), 3.55 (dd, J=8.40 Hz, 8.40 Hz, 1 H), 3.14-3.21 (m, 1 H), 2.78 (s, 1/3 x 3 H), 2.77 (s, 2/3 x 3 H), 2.57- 2.49 (m,3H), 2.43-2.36 (m, 1 H), 2.34-2.28 (m, 1 H), 2.07 (s, 1/3 x3 H),2.06(s, 2/3 x3 H), 2.02-1.84(m,4H), 1.71 (s, 1/3 x3 H), 1.70 (s, 2/3 x3H), 1.51-1.43 (m, 2H), 1.38-1.32 (m, 3H), 1.22(s,2/3 x3H), 1.19 (s, 1/3 x 3 H), 1.16 (s, 2/3 x 3 H), 1.12 (s, 1/3 x 3 H), 1.06 (d, 7=7.50Hz, 3 H), 0.98 (d, J=7.00Hz, 3 H), 0.92 (s, 9H), 1.00 (s, 2/3 x 9H), 0.93 (s, 1/3 x 9H), 0.04 (s, 3 H), 0.03 (s, 3 H),-0.00 (s, 1/3 x 9 H),-0.01 (s,2/3 x9H).

30. (4S57/?J8S59SJ13ZJ16S)-4-{[(4-Trimethylsilyl)xylyl]oxy}-8-{[ terf- Butyl(dimethyl)silyl]oxy}-5,5,7,9513-pentamethyl-16[(E)-1 -methyl-(2-methyl-1 ,3- thiazol-4-yl)ethenyl]oxacyclohexadec-13-ene-2,6-dione (44).

Desired lactone (44) Undesired lactone

To a stirred suspension of magnesium bromide (0.48 g, 2.5 mmol) in ether (3 ml_) nitromethane (0.32 g, 5.2 mmol), 1-butanethiol (0.05 g, 0.52 mmol) were added at room temperature and the mixture was stirred that temperature for 20 min. The resulting solution was added to a stirred solution of 7-TIX acids 35s and its (6SJR)- diastereomer (0.24 g, 0.26 mmol) in ether (3 ml_) at room temperature and the resulting mixture was stirred that temperature for 1 h. The reaction mixture was diluted with ether (20 mL), dichloromethane (10 ml_) and was quenched with water (10 mL). The organic layer was separated, and the aqueous phase was extracted with ether (20 mL) and dichloromethane (10 ml_). The combined organic phases were dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to give the 15-OH acids 36s and its (δS^/^-diastereomer, which were reacted to macrolactonization without purification. To a stirred solution of 15-OH acids 36s and its (6S,7R)-diastereomer (0.2 g, 0.26 mmol) in THF (7 mL) was added triethyl amine (0.16 g, 1.6 mmol) and followed by addition of 2,4,6-trichlorobenzoyl chloride (0.32 g, 1.3 mmol) at -52C. The mixture was stirred at 0QC for 1 h. The reaction mixture was added dropwise to a solution of 4-DMAP (0.32 g, 2.6 mmol) in toluene (70 mL) at room temperature, and the resulting mixture was stirred for 4 h. The mixture was concentrated under reduced pressure to a small volume and filtered through silica gel. The residue was washed with 40% ether in /7-hexanes. The resulting solution was evaporated under reduced pressure. The residue was purified by column chromatography (silica gel, 15% ethyl acetate/hexanes) to give desired lactone 44 (0.14 g, 33%) and undesired lactone (0.14 g, 17%) as colorless oil.

Desired lactone (44):

MoL Formula : C44H71NO5SSi2 (781) IR (cm"1) : 2955, 2894, 1771, 1733, 1653, 1436, 1249, 1068, 853. 1H NMR : 7.10 (d, J=8.00 Hz, 2 H), 6.94 (s, 1 H), 6.91 (d, J=5.50 Hz, 2 H), 6.55 (s, (CDCl3, 1 H), 5.30 (t, /=6.50 Hz, 1 H), 5.08 (dd, J=9.00 Hz, 9,00 Hz, 1 H), 4.62 400MHz) (dd, /=6.00 Hz, 10.5 Hz, 1 H), 4.40 (dd, /=11.0 Hz, 10.5 Hz, 1 H), 4.19 (t, /=8.00 Hz, 1 H), 3.87 (dd, /=7.20 Hz, 7.20 Hz, 1 H), 3.17-3.10 (m, 1 H), 2.72 (s, 3 H), 2.59-2.47 (m, 4 H), 2.44-2.38 (m, 1 H), 2.11 (s, 3 H), 2.06 (s, 2 H), 1.98-1.87 (m, 2 H), 1.64-1.63 (m, 1 H), 1.62 (s, 3 H), 1.43-1.33 (m, 3 H), 1.24 (s, 3 H), 1.18 (s, 3 H), 1.05 (d, /=6.50 Hz, 3 H), 1.00 (d, /=6.50 Hz, 3 H), 0.92 (s, 9 H), 0.08 (s, 3 H), 0.06 (s, 3 H), 0.00 (s, 9 H).

Undesired lactone: MoI. Formula : C44H71NO5SSi2 (TSl) IR (cm"1) : 2954, 2895, 1735, 1697, 1616, 1471, 1249, 1081, 852. 1H NMR (CDCl3, 400MHz) : δ 6.97 (d, 7=7.80 Hz, 2 H), 6.94 (s, 1 H), 6.90 (d, J=7.80 Hz, 2 H), 6.49 (s, 1 H), 5.37 (dd, /=8.40 Hz, 8.40 Hz, 1 H), 5.06 (dd, /=7.00 Hz, 7.00 Hz, 1 H), 4.61 (dd, /=9.60 Hz, 9.60 Hz, 1 H), 4.48 (t, /=10.8 Hz,l H), 4.16 (dd, /=3.60 Hz, 3.60 Hz, 1 H), 3.83 (dd, /=10.8 Hz, 10.8 Hz, 1 H), 3.13-3.05 (m, 1 H), 2.75 (s, 3 H), 2.58-2.48 (m, 3 H), 2.40-2.29 (m, 2 H), 2.16 (s, 3 H), 2.09 (s, 2 H), 2.00- 1.86 (m, 2 H), 1.72-1.68 (m, 1 H), 1.65-1.61 (m, 3 H), 1.62 (s, 3 H), 1.23 (s, 3 H), 1.16 (s, 3 H), 1.08 (d, /=7.00 Hz, 3 H), 1.04 (d, /=7.00 Hz, 3 H), 0.94 (s, 9 H), 0.10 (s, 3 H), 0.06 (s, 3 H), 0.0O (s, 9 H)

Accordingly, the present invention has been described with some degree of particularity directed to the exemplary embodiments of the present invention. It should be appreciated, though, that the present invention is defined by the following claims construed in light of the prior art so that modifications or changes may be made to the exemplary embodiments of the present invention without departing from the inventive concepts contained herein.