Paclitaxel (formula 1) is a natural compound showing vide spectrum of antitumor activity, originally isolated from bark of yew Taxus brevifotia [Wani, M. C.; Taylor, H. L. ; Wall, M. E.; Coggen, P.; McPhail, A. T., J. Am. Chem. Soc. , 93,2325, (1971) ] occurring also in other natural products. Considering low concentrations and difficult regeneration of the natural resources, process of isolation Paclitaxel from plants is of marginal importance. The most effective procedure for production of Paclitaxel is semi-synthesis, based on suitable secured Baccatin III and also secured phenyl isoserine. Baccatin III (formula 3, where R2=H) is a heterocyclic compound, characterized by condensed ring arrangement in the [9. 3. 1. 0] 38pentadecane structure, configured identically as a fragment of Paclitaxel. Baccatin 111 is obtained from deacetobaccatin It, which occurs in dried needles of yew Taxus baccatain concentration approximating to 1 g in 1 kg of the material. Isolation of the substance is an economically sound process, and the resources (needles and shoots) are quite renewable within every one season of vegetation.

All the reported methods for semi-synthesis of Paclitaxel are based on the concept of formation of an ester type bound between suitable secured Baccatin III derivative and also secured phenyl isoserine derivatives. However, it should be pointed out, that both the esterification procedure and the product of esterification processing technique depend upon strategy of synthesis and on the type of the protective groups used.

Kingston, D. G. L ; Chaudhary, A. G. Gunatilaka, A. A. L. ; Middleton, M. L. in their paper published in Tetrahedron Lett., 35,4483-4484 (1994) and in the patent specification WO 97/00870 presented application of dicyclohexylcarboimide (DDC) in presence of 4- (1-pyrrolidin) pyridine for bounding of 7- (triethylsilyl) baccatin (formula 3; R1= Si (C2H5) 3] to 2, 4-diphenyl-4, 5-dihydrooxazol-5-carboxylic acid, what after removal of the protective groups, provides Paclitaxel at the overall yield of more than 70%.

Similar solution, based on dicyclohexylcarboimide (DDC) in presence of 4- (N, N- dimethylamino) pyridine (DMAP), described by Balogu, E. and Kingston, D. G. I in their paper published in J. Nat. Prod. 62, 1068-1071, (1999) proved to be considerable less effective, because product of condensation yielded 30% yield, only. Moreover, N, N'- dicyclohexylcarboimide was used for acylation of the 7-protected Baccatin derivatives with oxazolidynes and with other phenyl isoserine derivatives.

Drawbacks of all the N, N'- dicyclohexylcarboimide based procedures are difficulties encountered in removal of N, N'-dicyclohexylcarbamide, undesirable by- product, from the reaction medium. N, N'- dicyclohexylcarbamide is a troublesome impurity of the condensation product because it is sparingly soluble in most of organic solvents, therefore its effective separation from also sparingly soluble Paclitaxel derivatives is difficult. It complicates the process of isolation of intermediates from the final product and reduces effectiveness of utilization of the phenyl isoserine and Baccatin components. Another awkward drawback of DCC is its ability for developing of allergy, manifesting by pathological changes of epidermis. Relatively high vapor pressure of DCC at room temperature results in development of allergic symptoms even in persons, which have no direct contact with the compound.

There are known also other solutions, in which instead of N, N'- dicyclohexylcarboimide other condensing agents are used. Gennori, C.; Garcano, M.; Dughi, M.; Mongelli, N.; Vanatti, E.; Wulpetti, A. in their paper published in J. Or. Chem.

62,4746-4755, (1997), described condensation of 7- (triethylsililo) baccatin with thiophenyl ester of 2, 4-diphenyl-4, 5-dihydrooxazol-5-carboxylic acid in presence of bis- trimethylsililoamidolite (LHMDS). It yielded 89% of semi-finished product, structure of that was identical to that obtained by Kingston, D. G. et all. with use of N, N'- dicyclohexylcarboimide, as described in Tetrahedron Lett., 35,4483-4484 (1994).

Mukaiyama, T. et all. condensed 7-triethylsililobaccatin with phenylisoserine derivative (formula 4c, where R3=H, R4=p-C6H40CH3] in presence of di- (2-pyridil)-thionic carbonate reaching yield of 93%, as published in Chem. Europ. J.

Whereas Shiina, I. et all. described in Chem. Left., 1,204 (1998) that condensation of protected Baccatin and phenylisoserine derivative [formula 4b, where R2= CH2C6Hs] in presence of di- (2-pyridil)-thionic carbonate gives yields 66%, only.

Swindell, C. S. et all. in J. Med. Chem., 34,1176-1184 (1991) and Greene, A. E. et all. in J. Am. Chem. Soc. 110,5917 (1998) also described condensation of phenylisoserine derivative with protected Baccatin in presence of dipyridil carbonate and 4- (N, N- dimethylamino) pyridihe but the yields reported were moderate.

Patent specification US 6,150, 537 provides results of application of acyl chlorides and ketones, obtained from phenylisoserine derivatives, for acylation of the hydroxy group in Baccatin. Considerable drawback of the solution is difficult synthesis of the mentioned phenylisoserine derivatives and the risk of epimerization in course of synthesis of such reactive compounds.

Holton et all. (J. Am. Chem. Soc, 116,1599-1600, (1994), W093/06079) in many examples documented suitability of 4-phenyl-3-hydroxyazetydinone-2 derivatives (fui- laktam derivatives) for acylation of Baccatin (usually protected in the 7. position with the triethtlsilyl group). Application if the p-taktam derivatives provides the possibility for highly effective acylation, however preparation of these derivatives is a very complex and multistage process.

There are also known applications of phenylisoserine derivatives transformed into a six-membered oxazine ring [US Pat. No 5, 015, 744, and Beckwermist et all. in J. Org.

Chem., 61,9038-9040 (19996)], however the overall yield of the process is not satisfactory.

According to the invention, the method for bonding of phenylisoserine and baccatine components consists of utilization of an another condensing agent, what effectively eliminates the troubles usually encountered when dicyclohexylcarboimide was used, acylic chlorides, ketenes, thiol esters, di- (2-pyridyl) carbonate, di (2- pyridyl) thiocarbonate, etc.

The method for production of semi-finished products useful in synthesis of Paclitaxel, with the generalized formula 2, where Ri denotes a group with formula 7, or a group with formula 8, or a group with formula 9, or a group with formula 10, R2 denotes hydrogen, alkylsilol group or substituted alkylsilol group, arylsilol group or substituted arylsilol group, alkilarylsilol group or substituted alkylarylsilol group, alkoksycarbonyl group or substituted alkoksycarbonyl group, alkoksymethyl group or substituted alkoksymethyl group, R3 and R4 denote hydrogem, alkyl group or substituted alkyl group, aryl group or substituted aryl group groups arylowa, and X denotes C=O, C=S, S=O, SO2, (C=O) 2, P (aryi) 3, P-N (alkyl) 2, (P=O)-N (alkyl) 2, (P=S)-N (alkyl) 2, by reaction of Baccatin III derivatives and phenylisoserine derivatives, consists in reaction of phenylisoserine derivatives, with the generalized formulas 4a-d, where R2, R3, R4 and X have above specified meanings, or a mixture of their epimers having various configurations in the carbon 2', or their salts, with triazin based condensing agent with the generalized formula 5, where R5 and R6 denote chlorine, alkoxy group, substituted akoxy group, aryloxy group or substituted aryloxy group, whereas R7 denotes fluorine, chlorine or a quarternary ammonia group, possible in the presence of a tertiary amine group, in anhydrous organic solvent medium, foloowed by reaction of such obtained triazine esters of phenylisoserine, with the generalized formulas 6a-d, where R2, R3, R4 and X have above specified meanings, with Baccatin with the generalized formula 3, where R2 denotes hydrogen or a group which protects functional hydroxy group in the position 7., in anhydrous organic solvent, if need be in presence of a catalyst.

Beneficially, phenyl isoserine derivatives are used, in which R3 and R4 denote hydrogen, methyl group, phenyl group, metoxyphenyl group or dimetoxy phenyl group.

Beneficially, the hydroxyl group in the 7. position of Baccatin Ill is protected by alkylsilol group or substituted alkylsilol group, arylsilol group or substituted arylsilol group, alkilarylsilol group or substituted alkylarylsilol group, alkoksycarbonyl group or substituted alkoksycarbonyl group, alkoksymethyl group or substituted alkoksymethyl group.

Beneficially, salts of phenyl izoserine are salts of metals, particularly of alkali metals or salts of tertiary amines, beneficially of N-methylmorpholine, N, N-dimethylaminopyridyne or 1, 8-diazabicyclo [5. 4. 0.] undec-7-ene (DBU).

Beneficially, as the triazine based condensing reagent there is used 2-chloro-4, 6- dimethoxy-1, 3,5-triazine or quarternary triazinyl ammonium salts, obtained by reaction of 2-chloro-4, 6-dimethoxy-1, 3, 5-triazine with ternary amines.

Beneficially, the tertiary amine is N-methylmorpholine, tetramethylguanidyne, 1,4- dimethylpiperazyne, N-methylpyrolidyne, N, N'-tetramethylethylodiamine, N- methylpiperidine, pyridine, pyridine derivatives substitutes in the 4. Position of the pyridine ring, 1, 8-diazabicyclo [5. 4.0.] undec-7-en.

Beneficially, the solvent is an a-proton solvent, particularly aromatic hydrocarbons, chlorinated hydrocarbons, ethers, acid amides, nitriles of acids. Particularly beneficial is application of toluene, dichlormethane, dichlorethane, tetrahydrofurane, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide and N, N', N'-hexamethylamide of phosphoric acid, acetonitrile.

Beneficially, the reaction of acylation of Baccatin III proceeds in presence of Lewis-type acid and particularly in presence of anhydrous magnesium bromide.

Beneficially, reaction of acylation of Baccatin III is accomplished in presence of a base, particularly of tertiary amine, and the best in presence of 4- (N, N-dialkylamino) pyridine or DBU.

If the need be, triazine esters of phenyl isoserine may be removed from the reaction medium, before reaction with Baccatin tit.

Next, the semi-fihished products obtained with the method of invention are transformed into Paclitaxel with known methods, selected accordingly to the nature of the protective group used in reaction of Baccatin and phenyl isoserine. These known methods for transformation of the semi-finished products obtained with the method of invention into Paclitaxel are described e. g. in the publication, Protective Group in Organic Synthesis", ed. 2, J. Wiley and Son, 1991.

Triazine type condensing reagents are easily available, of low toxicity and not develop of allergy. They activate the carboxylic function in mild conditions, and process of acilation of the carboxyl function may be accelerated by introduction of suitable catalysts, if required. Both the triazine type condensing reagents, triazine esters and all by-products formed are weak bases in character and after the end of the process, may be readily removed by washing out with diluted acid solutions. The fact makes purification of Paclitaxel and its derivatives, easier and is conductive to high yield of the process.

Very reactive triazine esters my be isolated from the mixture but more convenient is synthesis directly before, or in course of coupling of the phenyl isoserine and the Baccatin components. Such procedure is advantageous, because most of the phenyl isoserine derivatives suitable for semi-synthesis of Paclitaxel and the triazine condensation agents are stable and may be easily stored, without any decomposition trace until will be used for coupling with suitable protected Baccatin lil.

The method of invention is illustrated by following practicable examples.

1. Example Solution of 2-chloro-4, 6-dimethoxy-1,3, 5-triazyne (CDMT) (7.71 g, 44 mmoles) in 100 mi THF was mixed with N-methylmorpholine (4.84 ml, 44 mmoles) for 30 minutes at temperature of 0-5°C. Then, there was added mixture of diastereomeres of the 4b acid, where R3=H and R4=3, 4-dimethoxyphenyl (19. 05 g, 44 mmoles) and further mixed for 4 hours at temperature of 0-5°C, followed by mixing for 8 hours at room temperature.

Precipitate was filtered off and to the filtrate (without separation of triazine ester) protected Baccatin III of the 3. formula, where R2=Si (C2H5) 3 (28. 1g, 40 mmoles), DMAP (0.24 g, 2 mmoles) MgFr2 (0.36 g, 2 mmoles) and triethylamine (3.84 g, 38 mmoles) were added. After reaction was completed, solvent was removed under reduced pressure, and the residue was dissolved in ethyl acetate and washed in turn with: H2O, 1M KHS04, H2O, 1M NaHCO3, H20 by 20 mi each. TLC: (acetone: benzene 1: 4) Rf=0. 75 and 0.8.

The process yielded 44.6 g (quantitative yield) of the product with the formula 2, where Ri is defined with the formula 8, R2 is the triethylsilol group, R3=H, and R4=3,4- dimethoxyphenyl. Raw product of condensation was dissolved in the mixture methanol/THF (80 ml/450 ml, respectively) and for 40 minutes treated with concentrated hydrochloric acid (30 mi). The mixture was poured into ice water and ethyl acetate mix, the layers separated, then the water phase was extracted with ethyl acetate. The organic phases were connected together and washed with saturated water solution of sodium bicarbonate, dried with magnesium sulfate and concentrated under reduced pressure until dry. Dry residue was chromatographed in a column filled with silica gel. Finally, the product was eluted with the mixture of ethyl acetate/hexane 1: 1 (v/v). It gave 28.5 g Paclitaxel with melting point of 221-223°C. The yield amounted to 82%.

[α]D20 = -49 (c=0.45, MeOH).

1H-NMR : (250 MHz, CDCf3) : 5=1. 14 (s, 3H); 1.24 (s, 3H); 1.69 (s, 3H) ; 1.79 (s, 3H), 1.82 (s, 1H) ; 1.88 (m, 1H) ; 2.24 (s, 3H), 2.25-2. 40 (m, 2H) ; 2.39 (s, 3H); 2.49 (d, J=4.0 Hz, 1H), 2.50-2. 55 (m, 1H) ; 3.59 (d, J=5.0 Hz, 1H) ; 4.17 (d, J=9.0 Hz, 1H) ; 4.29 (d, J=9.0 Hz, 1 H) ; 4.37-4. 40 (m, 1 H) ; 4.75-4. 79 (m, 1 H) ; 4.95 (m, 1 H) ; 5. 67 (d, J=7.0 Hz, 1 H) ; 5.77-5. 80 (m, 1H) ; 6.22 (t, J=8.0 Hz, 1H) ; 6.25 (s, 1H) ; 7.05 (d, J=9.5 Hz, 1H) ; 7.31-7. 55 (m, 7H); 7.61-7. 65 (m, 1H) ; 7.71-7. 75 (m, 2H) ; 8.09-8. 15 (m, 2H) [ppm] 3C-NMR : (250 MHz, CDCI3) : 6=9. 4 ; 15.0 ; 20.8 ; 21.7 ; 22.6 ; 26.7 ; 35.5 ; 35.5 ; 43.2 ; 45.5 ; 55.1 ; 58.7 ; 72. 2; 72.4 ; 73.3 ; 75.0 ; 75.5 ; 76. 6 ; 79.1 ; 81. 2; 84.5 ; 127.2 ; 127. 4 ; 128.5 ; 138.8 ; 128.8 ; 129.1 ; 129.2 ; 130.3 ; 132.1 ; 133.1 ; 133.7 ; 133.8 ; 133.9, 142.0 ; 167.1 ; 167.1 ; 170.7 ; 171.5 ; 172.9 ; 203.7 [ppm].

IR : 1240,1550, 166, 0; 2970; 3480 [cm~1].

FAB-MS: 854 [MH] t ; 794 [MH-AcOH] +, 776 [M-AcOH-H2O]+.

CI (isobutane) MS: 854 [MH] + ; 836 [MH-H2O] ; 818 [MH-2H2O] 2. Example N- (4, 6-dimethoxy-1, 3, 5-triazin-2-ylo)-N-methylmorpholine chloride (0.278 g, 1 mmole), cooled down to temperature of 0-5°C in 5 mi chloroform was connected with mixture of epimerides of the 4b acid, where R3=H and R4=3, 4-dimethoxyphenyl (0. 433 g, 1 mmole) and mixed for 12 hours. N-methylmorpholine chloride was washed off with ice water, and organic phase was dried with MgS04, the drying agent was filtered off and the filtrate was evaporated under reduced pressure until dry. It gave respective triazine ester of the formula 6b, where R3=H, R4=3, 4-dimethoxyphenyl, and R5=R6=OCH3, with the quantitative yield.

TLC: eluent CHC13, RrO. 55 1H-NMR (250 MHz, CDCI3) : b= 3.54 (s, 6H); 3.80 (s, 3H); 3.85 (s, 3H); 5.34 (d, J=, 1H); 6.19 (d, J=, 1H), 6.74 (bs, 1H) ; 7.07 (bs, 1H) ; 7.14 (bs, 1H) ; 7.21 (bs, 1H) ; 7.28-7. 80 (m, 10H) [ppm] IR (CCI4) : 1750 [cm-1] The triazine ester was used for reaction with protected Bacctain of the generalized formula 3, where R2=Si (C2H5) 3 (28. 1g, 40 mmoles), DMAP (6 pg, 0.05 mmole) MgBr2 (9 pg, 0.05 mmole) and triethylamine (96 ug, 0.95 mmole). After the reaction was finished, solvent was removed by evaporation under reduced pressure whereas the residue was dissolved in ethyl acetate and washed in turn with: H2O, 1M KHS04, H20, 1M NaHC03, H20 by 20 ml each. TLC: (acetone : benzene 1: 4) Rf=0. 75,0. 8. It gave 1.1 g (yield 95%) of the product with the formula 2, where Ri is defined with the formula 8, R2= Si (C2H5) 3, R3=H, and R4=3, 4-dimethoxyphenyl.

'H-NMR : (250 MHz, CDCI3) : b=0. 51 (q, J=8.0 Hz, 6H); 1.23 (s, 3H); 1.22 (t, J=8.0 Hz, 9H); 1.35 (s, 3H); 1.85 (s, 1H) ; 1.95 (s, 3H); 2.08 (s, 3H); 2.14 (s, 3H); 2.16-2. 28 (m, 1H) ; 2.41-2. 45 (m, 1 H), 2.55-2. 58 (m, 1 H) ; 2.59 (s, 3H); 2.65-2. 85 (m, 1 H) ; 3.28 (s, 3H); 3.38 (s, 3H) ; 4.25 (d, J=7.0 Hz, 1H) ; 4.41 (d, J=9.0 Hz, 1H) ; 4.48 (d, J=9.0 Hz, 1H) ; 4.85 (s, 1H) ; 4.92-4. 96 (m, 1H) ; 5.07 (d, J=8.5Hz, 1H) ; 6.02 (s, 1H) ; 6.15 (d, J= 7.5Hz, 1H) ; 6.62- 6.68 (m, 1H) ; 6.85-6. 95 (m, 3H), 6.98-7. 08 (m, 2H) ; 7.12-7. 38 (m, 7H); 7.39-7. 45 (m, 2H); 7.51 (s, 1H) ; 7.61 (d, J=7.5Hz, 1H) ; 7.77-7. 87 (m, 2H); 8.28-8. 35 (m, 2H) [ppm] 3. Example Solution of 2-chlor-4, 6-dimethoxy-1, 3,5-triazine (CDMT) (0.175 g, 1 m-mole) in 5 ml THF was mixed with N-methylmorpholine (0.11 ml, 1 mmole) for 30 minutes at temperature of 0-5°C. Then, easily migrated epimeride 4b, where R3=H, and R4=3, 4-dimethoxyphenyl (0.433 g, 1 mmol) was added and mixed for 12 hours. N-methylmorpholine chloride was filtered off, and filtrate was evaporated until dry under reduced pressure. It gave respective triazine ester of the formula 6b, where R3=H, R4=3, 4-dimethoxyphenyl, and R=R6=OCH3, with the quantitative yield.

TLC: eluent CHCI3, Rf=0, 7.

1H-NMR (250 MHz, CDC13) : 5= 3.52 (s, 6H); 3.80 (s, 3H); 3.85 (s, 3H); 5.34 (d, J=, 1H); 6.19 (d, J=, 1H), 6.74 (bs, 1H) ; 7.07 (bs, 1H) ; 7.11 (bs, 1H) ; 7.21 (bs, 1H) ; 7.28-7. 80 (m, 10H) [ppm] IR (CCI4) : 1750 [cm-'] The triazine ester, in the presence of 4-(pyrolidin) pyridine, was coupled with protected Bacctain of the generalized formula 3, where R2=Si (C2H5) 3. After the reaction was finished, raw product was extracted as described in the 1. Example. After removal of protective groups and chromatography it gave Paclitaxel with melting point of 220-223°C and chromatographic and spectral characteristics identical to those described in the 1.

Example.

4. Example Solution of 2-chlor-4, 6-dimethoxy-1,3, 5-triazine (CDMT) (0.175 g, 1 mmole) in 5 ml THF was mixed with N-methylmorpholine (0.11 ml, 1 mmole) for 30 minutes at temperature of 0-5°C. Then, hardly migrating epimeride 4b, where R3=H, and R4=3, 4-dimethoxyphenyl (0.433 g, 1 mmol) was added and mixed for 12 hours. N-methylmorpholine chloride was filtered off, and filtrate was evaporated until dry under reduced pressure. It gave respective triazine ester of the formula 6b, where R3=H, R4=3, 4-dimethoxyphenyl, and R5=R6=OCH3, with the quantitative yield.

TLC: eluent CHCI3, Rf=0. 6 1H-NMR (250 MHz, CDCl3) : zu 3.56 (s, 6H); 3. 80 (s, 3H); 3.85 (s, 3H); 5.34 (d, J=, 1H); 6.19 (d, J=, 1H), 6.74 (bs, 1H) ; 7.07 (bs, 1H) ; 7.14 (bs, 1H) ; 7.21 (bs, 1H) ; 7.28-7. 80 (m, 10H) [ppm] IR (CCI4) : 1740 [cm~11 The triazine ester, in the presence of magnesium bromide and 4-(pyrolidin) pyridine, was coupled with protected Bacctain III of the generalized formula 3, where R2=Si (C2H5) 3.

After the reaction was finished, raw product was extracted as described in the 1.

Example. After removal of protective groups and chromatography it gave Paclitaxel with melting point of 220-223°C and chromatographic and spectral characteristics identical to those described in the 1. Example.

5. Example Solution of 2-chlor-4, 6-diphenoxy-1, 3,5-triazine (CDPhT) (0.3 g, 1 mmole) in 5 ml THF was mixed with N-methylmorpholine (0.11 ml, 1 mmole) for 30 minutes at temperature of 0-5°C to obtain N- (4, 6- diphenoxy-1, 3, 5-triazine-2-yl)-N-methylmorpholine chloride.

Then, mixture of epimerides of acids 4b, where R3=H, and R4=3, 4-dimethoxyphenyl (0.433 g, 1 mmol) was added and mixed for 12 hours. After N-methylmorpholine chloride was filtered off, and filtrate was evaporated it gave respective triazine ester of the formula 6b, where R3=H, R4=3, 4-dimethoxyphenyl, and R5=R6=OCH3, with the quantitative yield.

TLC: eluent CHCl3, Rf=0. 45, H-NMR (250 MHz, CDCI3) : 5=3. 80 (s, 3H); 3.85 (s, 3H); 5.34 (d, J=, 1H); 6.19 (d, J=, 1H), 6. 74 (bs, 1H) ; 7.07 (bs, 1H) ; 7.09 (bs, 1H) ; 7.10 (bs, 1H) ; 7.11-7. 76 (m, 20H) [ppm] IR (KBr): 1770 [cm-1] The triazine ester, in the presence of magnesium bromide and 4- (pyrofidin) pyridine, was coupled with protected Bacctain III of the generalized formula 3, where R2=SitC2H5) 3. The product was chromatographically and spectrally identical to that described in the 2.

Example.

6. Example Solution of 2, 4-dichlor-1, 3,5-triazine (DCMT) (0.09 g, 0.5 mmole) in 5 ml THF was mixed with N-methylmorpholine (0.11 ml, 1 mmole) for 30 minutes at temperature of 0-5°C to form respective quaternary triazinammonium salt. Then, mixture of epimerides 4b, where R3=H, and R4=3, 4-dimethoxyphenyl (0.433 g, 1 mmol) was added and mixed for 12 hours, first at temperature of 0-5°C next at room temperature. N-methylmorpholine hydrochloride was filtered off, and solvent from filtrate was evaporated. It gave respective triazine ester of the formula 6b, where R3=H, R4=3, 4-dimethoxyphenyl, and R5=OCH3, with the quantitative yield.

TLC: eluent CHCI3, Rif=0. 45 H-NMR (CDCI3) : #=3. 63 (s, 3H); 3.80 (s, 3H); 3.85 (s, 3H); 5.34 (d, J=, 1H) ; 6.19 (d, J=, 1H), 6.74 (bs, 1H) ; 7.07 (bs, 1H) ; 7.14 (bs, 1H) ; 7.21 (bs, 1H) ; 7.28-7. 80 (m, 10H) [ppm] IR (KBr): 1760 [cm~1] The triazine ester, in the presence of magnesium bromide, was coupled with protected Baccatin III of the generalized formula 3, where R2=Si (C2H5) 3. The product was chromatographically and spectrally identical to that described in the 2. Example.

7. Example Solution of 2-chlor-4, 6-dimethoxy-1,3, 5-triazine (CDMT) (0.175 g, 1 mmole) in 5 mi acetonitrile was mixed with tetramethyloguanidyne (0.126 ml, 1 mmole) for 30 minutes at temperature of 0-5°C. Then, mixture of epimerides of acids 4b, where R3=H, and R4=3, 4- dimethoxyphenyl (0.433 g, 1 mmol) was added and mixed for 12 hours.

Tetramethyloguanidyne hydrochloride was washed off with ice water, filtrate was dried over MgS04, next the drying agent was filtered off and the residue was evaporated until dry under reduced pressure. It gave respective triazine ester of the formula 6b, where R3=H, R4=3, 4-dimethoxyphenyl, and Rs=R6=OCH3, with the quantitative yield.

The triazine ester, in the presence of magnesium bromide, was coupled with protected Bacctain 111 of the generalized formula 3, where R2=Si (C2H5) 3. The product was chromatographically and spectrally identical to that described in the 2. Example.

8. Example Solution of 2-chlor-4, 6-dimethoxy-1,3, 5-triazine (CDMT) (0.175 g, 1 mmole) in 5 ml toluene was mixed with 1, 4-dimethylpiperazyne (0.135 ml, 1 mmo4e) for 30 minutes at temperature of 0-5°C. Then, mixture of epimerides of acids 4b, where R3=H, and R4=3,4- dimethoxyphenyl (0. 433 g, 1 mmol) was added and mixed for 12 hours. 1,4- dimethylpiperazyne hydrochloride was filtered'off, filtrate was evaporated until dry under reduced pressure. It gave respective triazine ester of the formula 6b, where R3=H, R4=3, 4-dimethoxyphenyl, and R5=R6=OCH3, with the quantitative yield.

The triazine ester, in the presence of 4-(N, N-dimethylamin) pyridyne, was coupled with protected Bacctain III of the generalized formula 3, where R2=Si (C2H5) 3. The product was chromatographically and spectrally identical to that described in the 2. Example.

9. Example Solution of 2-chlor-4, 6-dimethoxy-1,3, 5-triazine (CDMT) (0.175 g, 1 mmole) in 5 mi DMF was mixed with N-methylpiperidine (0.104 ml, 1 mmole) for 30 minutes at temperature of 0-5°C. Then, mixture of epimerides of acids 4b, where R3=H, and R4=3,4- dimethoxyphenyl (0.433 g, 1 mmol) was added, mixed for 12 hours and evaporated until dry under reduced pressure. After washing off, respective triazine ester of the formula 6b, where R3=H, R4=3, 4-dimethoxyphenyl, and R5=R6=OCH3 was obtained with the quantitative yield. The triazine ester, in the presence of magnesium bromide and 4- (N, N- dimethylamin) pyridyne, was coupled with protected Bacctain III of the generalized formula 3, where R2=Si (C2HS) 3. The product was chromatographically and spectrally identical to that described in the 2. Example.

10. Example Solution of 2-chlor-4, 6-dimethoxy-1,3, 5-triazine (CDMT) (0.175 g, 1 mmole) in 5 ml dichloroethane was mixed with N-methylpyrolidyne (0.104 ml, 1 mmole) for 30 minutes at temperature of 0-5°C. Then, mixture of salts of epimerides of acids 4b, where R3=H, and R4=3, 4-dimethoxyphenyl (0.455 g, 1 mmol) was added and mixed for 12 hours. After washing off and evaporation of solvent, respective triazine ester of the formula 6b, where R3=H, R4=3, 4-dimethoxyphenyl, and Rs=R6=OCH3 was obtained with the quantitative yield.

The triazine ester, in the presence of magnesium bromide and 4- (N, N- dimethylamin) pyridyne, was coupled with protected Bacctain III of the generalized formula 3, where R2=Si (C2HS) 3. The product was chromatographically and spectrally identical to that described in the 2. Example.

11. Example Solution of 2-chlor-4, 6-dimethoxy-1,3, 5-triazine (0.175 g, 1 mmole) in 5 ml THF was mixed with N-methylmorpholine (D ml, 1 mmole) for 30 minutes at temperature of 0- 5°C, to form respective quaternary triazinilammonium salt. Then, phenyl isoserine of the formula 4b, where R3= R4=CH3 (0 325 g, 1 mmol) was added and mixed for 12 hours, first at temperature of 0-5°C, next at room temperature. N-methylmorpholine was filtered off and solvent was removed from the filtrate. It gave respective triazine ester of the formula 6b, where R3=R4=CH3, R5=R6=OCH3, with the quantitative yield.

TLC : eluent CHCI3, Rf=0. 50 'H-NMR (COCI3) : 5= 1.76 (s, 3H); 1.79 (s, 3H); 3.76 (s, 6H); 5.20 (d, J= 7.5 Hz, 1H) ; 5.59, (d, J= 7.5 Hz, 1 H) ; 7.43-7. 56 (m, 8H) ; 7.70-7. 43 (m, 2H) [ppm].

IR (KBr): 1790 [cm~1] The triazine ester was coupled with protected Baccatin (it of generalized formula 3, where R2=Si (C2Hs) 3, in the presence of magnesium bromide and diazobicycloundekane. It gave 0.945 g of the final product (93.8%) with the melting temperature of 171-173°C.

TLC: eluent (acetone: benzene 1: 4), Rf=0. 85 1H-NMR (CDCI3) : 6=0. 55 (q, J=8. 5 Hz, 6H); 0.94 (t, J=8.5 Hz, 9H); 1.17 (s, 3H) ; 1.22 (s, 3H); 1.67 (s, 3H); 1.77 (s, 1H) ; 1.83-1. 85 (m, 1H) ; 1.87 (s, 3H); 1.94 (s, 3H); 2.02 (s, 3H); 2.07 (s, 3H); 2.02-2. 18 (m, 2H); 2.19 (s, 3H); 2.07-2. 20 (m, 2H); 2.48-2. 50 (m, 2H); 3.77 (d, J=7.5 Hz, 1H) ; 4.07 (d, J=8.5 Hz, 1H) ; 4.25 (d, J=8.5 Hz, 1H) ; 4.42-4. 46 (m, 1H) ; 4.58 (d, J=7.5 Hz, 1H) ; 4.88-4. 93 (m, 1H) ; 5.28 (d, J=6. 5 Hz, 1H) ; 5.68 (d, J=7.5 Hz, 1H) ; 6.21- 6.25 (m, 1H) ; 6.49 (s, 1H) ; 6.91-6. 96 (m, 1H) ; 7.07-7. 22 (m, 8H); 7.44-7. 48 (m, 2H) ; 7.61- 7.65 (m, 1 H) ; 8.02 (d, J=7.5 Hz, 2H) [ppm] The product of condensation was treated with formic acid in THF, and the final product was chromatographically purified on silica gel with the system of hexane: ethyl acetate 2: 1. It gave 0.621 g (yield 76%) of a product spectroscopically and chromatographically identical to Paclitaxel.

12. Example Solution of 2-chlor-4, 6-diphenoxy-1, 3,5-triazine (CDPhT) (0. 3 g, 1 mmole) in 5 mi THF was mixed with N-methylmorpholine (0.11 ml, 1 mmole) for 30 minutes at temperature of 0-5°C to obtain N- (4, 6- diphenoxy-1, 3, 5-triazine-2-yl)-N- methylmorpholine chloride.

Then, phenyl isoserine derivative with the formula 4b, where R3= R4=CH3 (0.325 g, 1 mmol) was added and mixed for 12 hours. After N-methylmorpholine hydochloride was filtered off, and solvent was evaporated it gave respective triazine ester of the formula 6b, where R3= R4=CH3, and R5=R6= OCeHg, with the quantitative yield.

TLC: eluent CHCI3, Rr0. 65 1H-NMR (CDCI3) : 6=1. 76 (s, 3H); 1.79 (s, 3H) ; 5.19 (d, J=8.0 Hz, 1H); 5.27 (d, J= 8. 0 Hz, 1H) ; 7.19-7. 22 (m, 2H); 7.40-7. 74 (m, 18 H) ppm] JR (KBr): 1780 [cm~1] The triazine ester, in the presence of magnesium bromide and pyrolidinpyridine, was coupled with protected Baccatin III of the generalized formula 3, where R2=Si (C2H5) 3. The product was chromatographically and spectrally identical to that described in the 11.

Example.

13. Example Solution of 2, 4-dichlor-1, 3,5-triazine (DCMT) (0.09 g, 0.5 mmole) in 5 ml THF was mixed with N-methylmorpholine (0.11 ml, 1 mmole) for 30 minutes at temperature of 0-5°C to form respective quaternary triazinammonium salt. Then, phenyl isoserine derivative with the formula 4b, where R3= R4=CH3 (0.325 g, 1 mmol) was added and mixed for 12 hours, first at temperature of 0-5°C next at room temperature. N-methylmorpholine hydrochloride was filtered off, and solvent from filtrate was evaporated. It gave respective triazine ester of the formula 6b, where R3= R4= CH3, and R5=OCH3, with the quantitative yield.

TLC: eluent CHCl3, Rf=0. 60 H-NMR (CDCI3) : 6=1. 76 (s, 6H); 1. 79 (s, 6H) ; 3.76 (s, 3H); 5.27 (d, J= 7.5 Hz, 2H); 5.49, (d, J= 7.5 Hz, 2H); 7.20-7. 22 (m, 2H); 7.43-7. 56 (m, 14H); 7.43-7. 70 (m, 4H) [ppm] IR (KBr) 1800 [cm~11 The triazine ester, in the presence of pyrotidinpyridine, was coupled with protected Baccatin III of the generalized formula 3, where R2=Si (C2H5) 3. The product was chromatographically and spectrally identical to that described in the 11. Example.

14. Example Solution of 2-chlor-4, 6-dimethoxy-1,3, 5-triazine (0.175 g, 1 mmole) in 5 mi THF was mixed with N-methylmorpholine (0.11 ml, 1 mmole) for 30 minutes at temperature of 0- 5°C, to form respective quaternary triazinilammonium salt. Then, phenyl isoserine of the formula 4c (0.267 g, 1 mmol) was added and mixed for 12 hours, first at temperature of 0- 5°C, next at room temperature. N-methylmorpholine hydrochloride was filtered off and solvent was removed from the filtrate. It gave respective triazine ester of the formula 6c, where R5=R6=OCH3, with the quantitative yield.

TLC: eluent CHCI3, Rf=0.50 H-NMR (CDCI3) : #=3, 76 (s, 6H) ; 5.31 (d, J=7.5 Hz, 1H); 5.56 (d, J=7.5 Hz, 1H); 7.35- 7.48 (m, 6H) ; 7. 75-7.77 (m, 2H) ; 8.04 (d, J=8.0 Hz; 2H) [ppm] IR (KBr): 1785 [cm~11 The triazine ester, in the presence of DMAP, was coupled with protected Baccatin III of the generalized formula 3, where R2=Si (C2H5) 3. It gave 0.885 g of the final product (yield 91. 5%) with the formula 2, where Ri is defined by the formula 9, R2 = Si (C2H5) 3.

TLC: eluent (acetone: benzene 1: 4), Rf=0. 75 'H-NMR (CDCI3) : b= 0.57 (m, 6H); 0.95 (t, J= 8.0 Hz, 9H) ; 1.21 (s, 3H); 1.23 (s, 3H) ; 1.67 (s, 3H) ; 1.75 (s, 1H) ; 1.86-1. 89 (m, 1H); 1.99 (s, 3H); 2.08 (s, 3H) ; 2.17 (s, 3H); 2.23-2. 26 (m, 1H) ; 2.35-2. 37 (m, 1H) ; 2.54-2. 57 (m, 1H) ; 3.84 (d, J=7.5 Hz, 1H) ; 4.16 (d, J=8.5 Hz, 1 H) ; 4.31 (d, J=8.5 Hz, 1 H) ; 4.47-4. 50 (m, 1 H) ; 4.93-4. 96 (m, 2H); 5.60 (d, J=6.5 Hz, 1 H) ; 5.67 (d, J=7.5 Hz, 1H) ; 6.15-6. 19 (m, 1H) ; 6.43 (s, 1H) ; 7.35-7. 39 (m, 5H); 7.47-7. 51 (m, 4H); 7.59 (t, J=7.5 Hz, 1 H) ; 7.64 (t, J= 7.5 Hz, 1H) ; 8.08 (d. J=7.5 Hz, 2H); 8.25 (d, J= 7.5 Hz, 2H) [ppm] The product of condensation was treated with 0.1 N HCI in methanol, and the final product was chromatographically purified on silica gel with the system of hexane: ethyl acetate 1.5 : 1. It gave 0. 594 g (i. e. yield 76%) of a product spectroscopically and chromatographically identical to Paclitaxel.

15. Example Solution of 2-chlor-4, 6-diphenoxy-1,3, 5-triazine (0.3 g, 1 mmole) in 5 ml THF was mixed with N-methylmorpholine (0. 11 ml, 1 mmole) for 30 minutes at temperature of 0-5°C to obtain N- (4, 6- diphenoxy-1, 3, 5-triazine-2-yl)-N- methylmorpholine chloride. Then, phenyl isoserine derivative with the formula 4c, (0.267 g, 1 mmol) was added and mixed for 12 hours. After N-methylmorpholine hydochloride was filtered off, and solvent was evaporated, it gave respective triazine ester of the formula 6c, where R5=R6= OC6H5, with the quantitative yield.

TLC: eluent CHC13, Rf=0. 65 'H-NMR (250 MHz, CDCI3) : o=5. 31 (d, J=7.5 Hz, 1H); 5.57 (d, J=7.5 Hz, 1H); 7.12-7. 50 (m, 18H); 8.13 (d, J=8.0 Hz, 2H) [ppm] (R (KBr): 1790 [cm~11 The triazine ester, in the presence of 4-pyrofidinpyridine, was coupled with protected Baccatin III of the generalized formula 3, where R2=Si (C2H5) 3. The product was chromatographically and spectrally identical to that described in the 14. Example.

16. Example Solution of 2, 4-dichlor-6-methoxy-1, 3,5-triazine (0.09 g, 0.5 mmole) in 5 ml THF was mixed with N-methylmorpholine (0. 11 ml, 1 mmole) for 30 minutes at temperature of 0- 5°C to obtain respective quaternary triazinammonium salt. Then, phenyl isoserine derivative with the formula 4c, (0.267 g, 1 mmol) was added and mixed for 12 hours, first at temperature of 0-5°C, next at room temperature. After N-methylmorpholine hydochloride was filtered off, and solvent was evaporated, it gave respective triazine ester of the formula 6c, where R5 = OC6H5, with the quantitative yield.

TLC: eluent CHCI3, Rf=0.55 1H-NMR (CDCI3) : o=3, 76 (s, 3H); 5.31 (d, J=7.5 Hz, 2H); 5.56 (d, J=7.5 Hz, 2H); 7.35- 7.47 (m, 12H); 7.75-7. 77 (m, 4H); 8.04 (d, J=8.0 Hz; 4H) [ppm] IR (KBr): 1785 [cm-1] The triazine ester was coupled with protected Baccatin If of generalized formula 3, where R2=Si (C2H5) 3, in the presence of magnesium bromide and diazobicycloundekane. It gave product chromatographically and spectrally identical to that of the 14 Example.

17. Example Solution of 2-chlor-4, 6-methoxy-1, 3,5-triazine (0.175 g, 1 mmole) in 5 ml THF was mixed with N-methylmorpholine (0.11 ml, 1 mmole) for 30 minutes at temperature of 0-5°C to obtain respective quaternary triazinammonium salt. Then, phenyl isoserine derivative with the formula 4a, where R2 = H (0. 267 g, 1 mmol) was added and mixed for 12 hours, first at temperature of 0-5°C, next at room temperature. After N-methylmorpholine hydochloride was tittered off, and solvent was evaporated, it gave respective triazine ester of the formula 6a, where R2=H, R5 = OC6H5, with the quantitative yield.

TLC: eluent CHCb, R¢0. 4 H-NMR (CDCl3) : o= 5=3, 86 (s, 6H); 5.41 (d, J=7. 8 Hz, 1H); 5.72 (d, J=7.8 Hz, 1H); 7.00- 7.38 (m, 8H); 7.44 (d, J=8.0 Hz ; 2H) [ppm] IR (KBr): 1795 [cm~11 For 5 days the triasine ester, in the presence of 4- (N, N-dimethylamino) pyridine and magnesium bromide was coupled with protected Baccatin III of the generalized formula 3, where R2=Si (C2H5) 3. it gave 0.800 g (yield 81%) of the product characterized by Rf=0. 65 (eluent acetone: benzene 1: 4), which without purification was treated with concentrated hydrochloric acid in tetrahydrofurane for 10 min. After purification on silica gel in a chromatographic column in the mixture of hexane and ethyl acetate 1: 1 as the movable phase, it was obtained 0. 482 g (yield 70%) of the product spectroscopically and chromatographically identical to Paclitaxel described in the 1. Example.