EP0764154A1 - New taxoids, preparation thereof and pharmaceutical compositions containing them - Google Patents

Abstract

New taxoids having general formula (I), (II) preparation thereof and pharmaceutical compositions containing them. In general formula (I): Ra is hydrogen, hydroxy, alkoxy, acyloxy, alkoxyacetoxy, and Rb is hydrogen or Ra and Rb form together with the carbon atom to which they are linked a ketone function, Z is a hydrogen atom or a radical having general formula (II) wherein R1 is an optionally substituted benzoyl radical, a thenyl or furoyl radical or a radical R2-O-CO- wherein R2 is an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, optionally substituted phenyl or heterocyclyl radical; R3 is an alkyl, alkenyl, alkynyl, cycloalkyl, phenyl, naphtyl or heterocyclic aromatic radical, and R4 and R5, similar or different, represent an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, aryl or heterocyclyl radical, with the condition that R5 does not represent a methyl radical. The new products having general formula (I) wherein Z is a radical having general formula (II) have remarkable antitumoral and antileukaemic properties.

Description

 NEW TAXOIDS. THEIR PREPARATION AND THE PHARMACEUTICAL COMPOSITIONS YES CONTAINING THEM

The present invention relates to new taxoids of general formula:

OCOR ₄ in which:

R _a represents a hydrogen atom or a hydroxy, alkoxy radical containing

1 to 4 carbon atoms, acyloxy containing 1 to 4 carbon atoms or alkoxyacetoxy in which the alkyl part contains 1 to 4 carbon atoms and R _D represents a hydrogen atom or R _a and R ^ form together with the atom carbon to which they are linked a ketone function,

Z represents a hydrogen atom or a radical of general formula:

in which :

Rj represents a benzoyl radical optionally substituted by one or more atoms or radicals, identical or different, chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms, alkoxy containing 1 to 4 carbon atoms or trifluoromethyl, thenoyl or furoyl, or an R2-O-CO- radical in which R2 represents: - an alkyl radical containing 1 to 8 carbon atoms, alkenyl containing 2 to 8 carbon atoms, alkynyl containing 3 to 8 carbon atoms, cycloalkyl containing 3 with 6 carbon atoms, cycloalkenyl containing 4 to 6 carbon atoms, bicycloalkyl containing 7 to 10 carbon atoms, these radicals being optionally substituted by one or more substituents chosen from halogen atoms and hydroxy radicals, alkoxy containing 1 to 4 carbon atoms, dialkoylamino, each alkyl part of which contains 1 to 4 carbon atoms, piperidino, morpholino, piperazinyl-1 (optionally substituted at -4 by an alkyl radical containing 1 to 4 carbon atoms or by a phenylalkyl radical the alkyl part of which contains 1 to 4 carbon atoms), cycloalkyl containing 3 to 6 carbon atoms, cycloalkenyl containing 4 to 6 carbon atoms, phenyl (optionally substituted by one or more atoms or radicals chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms or alkoxy containing 1 to 4 carbon atoms), cyano, carboxy or alkoxycarbonyl, the alkyl part of which contains 1 to 4 carbon atoms,

- a phenyl or α- or β-naphthyl radical optionally substituted by one or more atoms or radicals chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms or alkoxy containing 1 to 4 carbon atoms or a radical 5-membered aromatic heterocyclic preferably chosen from furyl and thienyl radicals,

- or a saturated heterocyclyl radical containing 4 to 6 carbon atoms optionally substituted by one or more alkyl radicals containing 1 to 4 carbon atoms, R3 represents a straight or branched alkyl radical containing 1 to 8 carbon atoms, straight or branched alkenyl containing 2 to 8 carbon atoms, straight or branched alkynyl containing 2 to 8 carbon atoms, cycloalkyl containing 3 to 6 carbon atoms, phenyl or α- or β-naphthyl optionally substituted by one or more atoms or radicals chosen from atoms '' halogen and alkyl, alkenyl, alkynyl, aryl, aralkyl, alkoxy, alkylthio, aryloxy, arylthio, hydroxy, hydroxyalkyl, mercapto, formyl, acyl, acylamino, aroylamino, alkoxycarbonylamino, aminoalkyl, carboxyalkoxy , carbamoyl, alkylcarbamoyl, dialcoylcarbamoyl, cyano, nitro and trifluoromethyl, or an aromatic heterocycle having 5 members and containing one or more rs heteroatoms, identical or different, chosen from nitrogen, oxygen or sulfur atoms and optionally substituted by one or more substituents, identical or different, chosen from halogen atoms and alkyl, aryl, amino radicals, alkyllamino, dialkoylamino, alkoxycarbonylamino, acyl, arylcarbonyl, cyano, carboxy, carbamoyl, alkylcarbamoyl, dialcoylcarbamoyl or alkoxycarbonyl, it being understood that in the substituents of the phenyl, α- or β-naphthyl and aryl alkyl radicals, and the aryl alkyls, other radicals contain 1 to 4 carbon atoms and the alkenyl and alkynyl radicals contain 2 to 8 carbon atoms and the aryl radicals are phenyl or α- or β-naphthyl radicals, and R4 and R5, identical or different, represent - a straight or branched alkyl radical containing 1 to 8 carbon atoms, straight or branched alkenyl containing 2 to 8 carbon atoms, straight or branched alkynyl containing 2 to 8 carbon atoms, cycloalkyl containing 3 to 6 carbon atoms, cycloalkenyl containing 4 to 6 carbon atoms or bicycloalkyl containing 7 to 11 carbon atoms, these radicals being optionally substituted by one or more substituents chosen from halogen atoms and hydroxy radicals, alkyloxy containing 1 to 4 carbon atoms, dialkoylamino each alkyl part contains 1 to 4 carbon atoms, piperidino, morpholino, piperazinyl-1 (optionally substituted in -4 by an alkyl radical containing 1 to 4 carbon atoms or by a phenylalkyl radical in which the alkyl part contains 1 to 4 carbon atoms ), cycloalkyl containing 3 to 6 carbon atoms, cycloalkenyl containing 4 to 6 carbon atoms, optionally substituted phenyl, cyano, carboxy or alkyloxycarbonyl in which the alkyl part contains 1 to 4 carbon atoms, - or an aryl radical optionally substituted by one or more atoms or radicals chosen from halogen atoms and alkyl, alkenyl, alkynyl, aryl, aralkyl, alkoxy, alkylthio radicals , aryloxy, arylthio, hydroxy, hydroxyalkyl, mercapto, formyl, acyl, acylamino, aroylamino, alkoxycarbonyl-amino, amino, alcoylamino, dialcoylamino, carboxy, alkoxycarbonyl, carbamoyl, alcoylcarbamoyl, dialcoylcaridoamyl, triano, a saturated or unsaturated heterocyclyl radical containing 4 to 6 members and optionally substituted by one or more alkyl radicals containing 1 to 4 carbon atoms, it being understood that R5 cannot represent a methyl radical, it being understood that the cycloalkyl, cycloalkenyl or bicycloalkyls may be optionally substituted by one or more alkyl radicals containing t 1 to 4 carbon atoms.

Preferably, the aryl radicals which can be represented by R3, R4 and / or R5 are phenyl or α- or β-naphthyl radicals optionally substituted by one or more atoms or radicals chosen from halogen atoms (fluorine, chlorine, bromine, iodine) and the radicals alkyl, alkenyls, alkynyls, aryls, arylalkyls, alkoxy, alkylthio, aryloxy, arylthio, hydroxy, hydroxyalkyl, mercapto, formyl, acyl, acylamino, aroylamino, alkoxycarbonylamino, amino, alkylamino carboxyalkyl , dialkoylcarbamoyl, cyano, nitro, azido, trifluoromethyl and trifluoromethoxy, it being understood that the alkyl radicals and the alkyl portions of the other radicals contain 1 to 4 carbon atoms, that the alkenyl and alkynyl radicals contain 2 to 8 carbon atoms and that the aryl radicals are phenyl or α- or β-naphthyl radicals, and that the radical R5 cannot not represent a methyl radical. Preferably the heterocyclic radicals which can be represented by R3,

R4 and / or R5 are aromatic heterocyclic radicals having 5 members and containing one or more atoms, identical or different, chosen from nitrogen, oxygen or sulfur atoms, optionally substituted by one or more substituents, identical or different , chosen from halogen atoms (fluorine, chlorine, bromine, iodine) and alkyl radicals containing 1 to 4 carbon atoms, aryls containing 6 to 10 carbon atoms, alkoxy containing 1 to 4 carbon atoms, aryloxy containing 6 with 10 carbon atoms, amino, alkylamino containing 1 to 4 carbon atoms, dialkoylamino in which each alkyl part contains 1 to 4 carbon atoms, acylamino in which the acyl part contains 1 to 4 carbon atoms, alkoxycarbonylamino containing 1 to 4 carbon atoms carbon, acyl containing 1 to 4 carbon atoms, arylcarbonyl of which the aryl part contains 6 to 10 carbon atoms, cyano, carboxy, carbamoyl, alkylcarbamoyl of which the alkyl part contains 1 to 4 a carbon tomes, dialkoylcarbamoyl in which each alkyl part contains 1 to 4 carbon atoms or alkoxycarbonyl in which the alkoxy part contains 1 to 4 carbon atoms.

More particularly, the present invention relates to the products of general formula (I) in which R _a represents a hydroxy radical, an alkoxy containing 1 to 4 carbon atoms, an acyloxy containing 1 to 4 carbon atoms or an alkoxyacetoxy in which the alkyl part contains 1 to 4 carbon atoms and R5 represents a hydrogen atom, Z represents a hydrogen atom or a radical of general formula (II) in which R ^ represents a benzoyl radical or an R2-O-CO- radical in which R2 represents a tert-butyl radical and R3 represents an alkyl radical containing 1 to 6 carbon atoms, alkenyl containing 2 to 6 carbon atoms, cycloalkyl containing 3 to 6 carbon atoms, phenyl optionally substituted by one or more atoms or radicals, identical or different chosen from halogen atoms (fluorine, chlorine) and alkyl (methyl), alkoxy (methoxy), dialkoylamino (dimethylamino), acylamino (acetylamino), _dcoxycarlx) nyl_- radicals mino (tert-butoxycarbonylamino) or trifluoromethyl or a furyl-2 or -3, thienyl-2 or -3 or thiazolyl-2, -4 or -5 radical and R4 represents a phenyl radical optionally substituted by one or more atoms or radicals, identical or different, chosen among the halogen atoms and the alkyl, alkoxy, amino, alkylamino, dialkoylamino, acylamino, alkoxycarbonylamino, azido, trifluoromethyl and trifluoro-methoxy radicals, or a thienyl-2 or -3 or furyl-2 or -3 radical and R5 represents an optionally substituted alkyl radical containing 1 to 4 carbon atoms, it being understood that R5 cannot represent a methyl radical.

More particularly still, the present invention relates to the products of general formula (I) in which R _a represents a hydrogen atom or a hydroxy or acetyloxy or methoxyacetoxy radical and R ^ represents a hydrogen atom, Z represents a atom hydrogen or a radical of general formula (H) in which Rj represents a benzoyl radical or an R2-O-CO- radical in which R2 represents a tert-butyl radical and R3 represents an isobutyl, isobutenyl, butenyl, cyclohexyl, phenyl radical, furyl-2, furyle-3, thienyl-2, thienyl-3, thiazolyl-2, thiazolyl-4 or thiazolyl-5 and R4 represents a phenyl radical optionally substituted by a halogen atom and R5 represents an alkyl radical containing 2 to 4 carbon atoms.

The products of general formula (I) in which Z represents a radical of general formula (II) have remarkable antitumor and antileukemic properties.

According to the present invention, the products of general formula (I) in which R _a represents a hydrogen atom or an alkoxy, acyloxy or alkoxyacetoxy radical, R ^ represents a hydrogen atom, R4, R5 and Z are defined as above can be obtained by the action of an alkali metal halide (sodium chloride, sodium iodide, potassium fluoride) or an alkali metal azide (sodium azide) or a quaternary ammonium salt or an alkali metal phosphate on a product of general formula:

OCOR ₄ in which Z, R4 and R5 are defined as above, R _a represents a hydrogen atom or an alkoxy, acyloxy, alkoxyacetoxy radical or a hydroxy radical protected, and R ^ represents a hydrogen atom, followed, if necessary, by the replacement of the protective group carried by R _a by a hydrogen atom.

Generally, the reaction is carried out in an organic solvent chosen from ethers (tetrahydrofuran, diisopropyl ether, methyl tert-butyl ether) and nitriles (acetonitrile) alone or as a mixture at a temperature between 20 ° C. and the boiling point of the mixture. reactive.

The product of general formula (III) in which Z represents a radical of general formula (II) can be obtained by esterification of a product of general formula:

^0C0R A in which R4, R5 are defined as above, and R _a represents a hydrogen atom or an alkoxy, acyloxy, alkoxyacetoxy radical or a protected hydroxy radical, and R ^ represents a hydrogen atom, by means of a acid of general formula:

No. O

(V)

R. OH

OR- in which Rj and R3 are defined as above, or else Rg represents a hydrogen atom and R7 represents a protective group for the hydroxy function, and either Rg and R7 together form a 5 or 6-membered saturated heterocycle, or of a derivative of this acid to obtain an ester of general formula:

^0C0R < in which R _a , R, Ri, R3, R4, R5, Rβ and R7 are defined as above, followed by the replacement of the protective groups represented by R7 and / or R and R7 by hydrogen atoms and optionally R _a , when 'It represents an acyloxy, alkoxyacetoxy radical or a hydroxy radical protected by a hydroxy radical. Esterification using an acid of general formula (V) can be carried out in the presence of a condensing agent (carbodiimide, reactive carbonate) and an activating agent (aminopyridines) in an organic solvent (ether, ester, ketones, nitriles, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, aromatic hydrocarbons) at a temperature between -10 and 90 ° C. Esterification can also be carried out using the acid of general formula (V) in the form of anhydride, operating in the presence of an activating agent (aminopyridines) in an organic solvent (ethers, esters, ketones, nitriles, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, aromatic hydrocarbons) at a temperature between 0 and 90 ° C. The esterification can also be carried out using the acid of general formula (V) in the form of halide or in the form of anhydride with an aliphatic or aromatic acid, optionally prepared in situ, in the presence of a base (aliphatic amine tertiary) by operating in an organic solvent (ethers, esters, ketones, nitriles, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, aromatic hydrocarbons) at a temperature between 0 and 80 ° C.

When R _a represents a protecting group for the hydroxy function, R _a is preferably a 2,2,2-trichloro-2,2 ethoxycarbonyloxy radical.

Preferably, R6 represents a hydrogen atom and R7 represents a protecting group for the hydroxy function or else R and R7 together form a 5 or 6-membered saturated heterocycle.

When Rβ represents a hydrogen atom, R7 preferably represents a methoxymethyl, 1-ethoxy-ethyl, benzyloxymethyl, trimethylsilyl, triethylsilyl, β-trimethylsilylethoxymethyl, benzyloxycarbonyl or tetrahydro-pyrannyl radical. When Rg and R7 together form a heterocycle, this is preferably an oxazolidine ring optionally mono-substituted or gem-disubstituted in position -2.

The replacement of the protective groups R7 and / or Rβ and R7 by hydrogen atoms and possibly of R _a by a hydroxy radical can be carried out, according to their nature, as follows: 1) when Rβ represents a hydrogen atom and R7 represents a protective group for the hydroxy function, R _a represents an alkoxy, acyloxy or alkoxyacetoxy radical, the replacement of the protective groups by hydrogen atoms is carried out by means of a mineral acid (hydrochloric acid, sulfuric acid, hydrofluoric acid) or organic acid (acetic acid, methanesulfonic acid, trifluoromethanesulfonic acid, p.toluenesulfonic acid) used alone or as a mixture while operating in an organic solvent chosen from alcohols, ethers , esters, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, aromatic hydrocarbons or nitriles at a temperature between -10 and 60 ° C,

2) when Rβ represents a hydrogen atom and R7 represents a protective group for the hydroxy function, R _a represents a 2,2,2,2-trichloroethoxycarbonyloxy radical, the replacement of the protective group R7 is carried out under the conditions described above under 1) and that of R _a by treatment with zinc, optionally combined with copper, in the presence of acetic acid at a temperature between 30 and 60 ° C or by means of a mineral or organic acid such as hydrochloric acid or acetic acid in solution in an aliphatic alcohol containing 1 to 3 carbon atoms (methanol, ethanol, propanol, isopropanol) or in an aliphatic ester (ethyl acetate, isopropyl acetate n.butyl acetate) in the presence of zinc possibly associated with copper,

3) when Rβ and R7 together form a saturated heterocycle with 5 or 6 members and more particularly an oxazolidine ring of general formula:

in which R is defined as above, Rg and R9, identical or different, represent a hydrogen atom or an alkyl radical containing 1 to 4 carbon atoms, or an aralkyl radical in which the alkyl part contains 1 to 4 carbon atoms and the aryl part preferably represents a phenyl radical optionally substituted by one or more alkoxy radicals containing 1 to 4 carbon atoms, or an aryl radical representing, preferably a phenyl radical optionally substituted by one or more alkoxy radicals containing 1 to 4 carbon atoms, or else Rg represents an alkoxy radical containing 1 to 4 atoms of carbon or a trihalomethyl radical such as trichloromethyl or a phenyl radical substituted by a trihalomethyl radical such as trichloromethyl and R9 represents a hydrogen atom, or else Rg and R9 form together with the carbon atom to which they are linked a ring having 4 with 7 links, and R _a represents an acyloxy or alkoxyacetoxy or 2,2,2-trichloroethoxycarbonyloxy radical, the replacement of the protective group formed by Rβ and R7 by hydrogen and R _a atoms by a hydroxy radical can be carried out , according to the meanings of R _a , Rj, Rg and R9, as follows: a) when R \ represents a tert-butoxycarbonyl radical, Rg and R9, identical or different, represent an alkyl radical or an aralkyl (benzyl) radical or aryl (phenyl), or else Rg represents a trihalomethyl radical or a phenyl radical substituted by a trihalomethyl radical, and R9 represents a hydrogen atom, or else Rg and R9 together form a cycle having from 4 to 7 links, the treatment of the ester of general formula (VI) with a mineral or organic acid optionally in an organic solvent such as an alcohol leads to the product of general formula:

in which R _a , Rb, R3, R4 and R5 are defined as above, which is acylated by means of benzoyl chloride in which the phenyl nucleus is optionally substituted, of thenoyl chloride, of furoyl chloride or of a product of general formula:

R2-O-CO-X (IX) in which R2 is defined as above and X represents a halogen atom (fluorine, chlorine) or a residue -O-R2 or -O-CO-O-R2, to obtain a product of general formula: R

in which R _a , R ^, Ri, R3, R4 and R5 are defined as above, in which the protective group R _a , when it represents a protected hydroxy radical, is replaced, if necessary, by a hydroxy radical. Preferably, the product of general formula (VI) is treated with formic acid at a temperature in the region of 20 ° C.

Preferably, the acylation of the product of general formula (VIII) by means of a benzoyl chloride in which the phenyl radical is optionally substituted, of thenoyl chloride or of furoyl chloride or of a product of general formula (IX ) is carried out in an inert organic solvent chosen from esters such as ethyl acetate, isopropyl acetate or n.butyl acetate and halogenated aliphatic hydrocarbons such as dichloromethane or 1-dichloro, 2 ethane in the presence of a mineral base such as sodium bicarbonate or organic such as Iriethylamine. The reaction is carried out at a temperature between 0 and 50 ° C, preferably close to 20 ° C.

Preferably, the replacement of the protective group of R _a , when it represents a 2,2,2,2-trichloroethoxycarbonyloxy radical, is carried out under the conditions described above under 2), b) when R represents an optionally substituted benzoyl radical, thenoyl or furoyl or an R2O-CO- radical in which R2 is defined as above, Rg represents a hydrogen atom or an alkoxy radical containing 1 to 4 carbon atoms or a phenyl radical substituted by one or more alkoxy radicals containing 1 to 4 carbon atoms and R9 represents a hydrogen atom, the replacement of the protective group formed by Rβ and R7 by hydrogen atoms is carried out in the presence of a mineral acid (hydrochloric acid, sulfuric acid) or organic acid (acetic acid , methanesulfonic acid, trifluoromethanesulfonic acid, p.toluenesulfonic acid) used alone or as a mixture in stoichiometric or catalytic amount, operating in a s organic solvent chosen from alcohols, ethers, esters, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons and aromatic hydrocarbons at a temperature between -10 and 60 ° C, preferably between 15 and 30 ° C and the replacement of the protective group of R _a , when it represents a 2,2,2-trichloroethoxycarbonyloxy radical with a hydrogen atom, is carried out under the conditions described above under 2).

4) when R _a represents an alkoxyacetyl radical and Rβ and R7 are defined as in point 1) above, the protective group R7 is replaced by a hydrogen atom first, operating under the acid conditions described in point 1) above, then optionally replaces R _a with a hydroxy radical by treatment in an alkaline medium or by the action of a zinc halide under conditions which do not affect the rest of the molecule. Generally, the alkaline treatment is carried out by the action of ammonia in a hydro-alcoholic medium at a temperature in the region of 20 ° C. Generally, the treatment with a zinc halide, preferably zinc iodide is carried out in methanol at a temperature in the region of 20 ° C.

5) when R _a represents an alkoxyacetoxy radical and Rβ and R7 are defined as in point 2-a) above, the radical R a _is replaced by a hydroxy radical by treatment in an alkaline medium or by treatment with a halide of zinc under the conditions described in point 3) above, then treats the product of general formula (VI) obtained under the deprotection and acylation conditions described in point 2-a) above.

6) when R _a represents an alkoxyacetoxy radical and Rβ and R7 are defined as in point 2-b) above, the radical R a _is replaced by a hydroxy radical by treatment in an alkaline medium or by treatment with a halide of zinc under the conditions described in point 3) above, then treats the product obtained under the conditions described in point 2-b) above.

According to the invention, the products of general formula (III) in which R4 and R5 are defined as above, R _a represents a hydrogen atom or an alkoxy, acyloxy or alkoxyacetoxy radical, and R _D represents a hydrogen atom, or although R _a and R ^ form together with the carbon atom to which they are linked, a ketone function and Z represents a hydrogen atom can be obtained by the action of a derivative of trifluoromethanesulfonic acid such as the anhydride or N-phenyl trifluorométhanesiilf onimide on a product of general formula:

OCOR ₄ in which R _a , R ^, R4 and R5 are defined as above

Generally, the reaction is carried out in an inert organic solvent (aliphatic hydrocarbons optionally halogenated, aromatic hydrocarbons) in the presence of an organic base such as an aliphatic tertiary amine (triethylamine) or pyridine at a temperature between -50 and + 20 ° C.

The products of general formula (XI) in which R4 and R5 are defined as above, R _a represents a hydrogen atom or an alkoxy, acyloxy or alkoxyacetoxy radical or a protected hydroxy radical, Rb represents a hydrogen atom, can be obtained by the action of hydrofluoric acid or trifluoroacetic acid in a basic organic solvent, such as pyridine optionally substituted by one or more alkyl radicals containing 1 to 4 carbon atoms, or triethylamine optionally in combination with an organic solvent inert such as methylene chloride or racetonitrile or tetrahydrofuran at a temperature between 20 and 80 ° C on a product of general formula:

OCOR ₄ in which R4 and R5 are defined as above, R _a represents a hydrogen atom or an alkoxy, acyloxy or alkoxyacetoxy radical or a protected hydroxy radical, R represents a hydrogen atom, and the symbols Gj, which are identical represent a triacoylsilyl radical. The product of general formula (XII) can be obtained by the action of a product of general formula:

R-Y (XIII) in which R represents an alkyl, alkanoyl or alkoxyacetyl radical or a protecting group for the hydroxy function and Y represents a halogen atom on a product of general formula:

OCOR ₄ in which R4, R5 and Gi are defined as above

When R represents an alkyl or alkoxyacetyl radical, it is particularly advantageous to operate in a basic organic solvent such as pyridine or in an inert organic solvent such as methylene chloride, chloroform or 1,2-dichloroethane in the presence of 'a tertiary amine such as triethylamine or pyridine at a temperature in the region of 0 ° C.

When R represents an alkyl radical, it is particularly advantageous to metallize the hydroxy function in -10 beforehand by means of an alkali hydride (sodium hydride) or a metal alkyl (butyllithium).

The product of general formula (XIV) and optionally the product of general formula (XII) can be obtained by the action of an organometallic derivative of general formula: R4-M (XV) in which R4 is defined as above and M represents an atom metallic, preferably a lithium or magnesium atom, on a product of general formula: in which R _a , Rb, R5 and Gi are defined as above.

Generally, the reaction is carried out in an organic solvent such as an ether (tetrahydrofuran) at a temperature below -50 ° C, preferably close to -78 ° C.

The product of general formula (XVI) can be obtained by esterification of a product of general formula:

in which R _a , Rb and Gi are defined as above, by means of an acid of general formula:

R5-COOH (XVIII) in which R5 is defined as above, or a derivative of this acid such as a halide or an anhydride in the presence of a condensing agent or an inorganic or organic base. The product of general formula (XVII) can be obtained by the action of a product of general formula (XIII) on a product of general formula: in which G is defined as above under the conditions described above for the action of a product of general formula (XIII) on a product of general formula (XIV).

The product of general formula (XIX) can be prepared by the action of phosgene or one of its derivatives such as triphosgene on a product of general formula:

in which Gi is defined as above by operating in a basic organic solvent such as pyridine at a temperature below -50 ° C, preferably close to -78 ° C.

The product of general formula (XX) can be prepared by the action of a halotrialcoylsilane on a product of general formula:

in which Gi is defined as above by operating in a basic organic solvent.

The product of general formula (XXI) can be prepared under the conditions described by DGI Kingston et al., Journal of Nat Prod. , 5__L 884 (1993). The products of general formula (I) in which R _a and Rb each represent a hydrogen atom can be obtained by electrolytic reduction of a product of general formula (I) in which R _a represents a hydroxy radical or an acyloxy radical or alkoxyacetoxy or under the conditions described in international PCT application WO 93/06093.

The products of general formula (I) in which R _a and Rb form together with the carbon atom to which they are linked a ketone function can be obtained by oxidation of a product of general formula (I) in which R _a represents a hydroxy radical and Rb represents a hydrogen atom by means, for example, of pyridinium chlorochromate, pyridinium dichromate, potassium dichromate, ammonium dichromate or manganese dioxide.

The new products of general formula (I) obtained by implementing the methods according to the invention can be purified according to known methods such as crystallization or chromatography. The products of general formula (I) in which Z represents a radical of general formula (II) have remarkable biological properties.

In vitro, the measurement of the biological activity is carried out on the tubulin extracted from pig brain by the method of M.L. Shelanski et al., Proc. Natl. Acad. Sci. USA, 7J_, 765-768 (1973). The study of the depolymerization of microtubules into tubulin is carried out according to the method of G. Chauvière et al., C.R. Acad. Sci., 222, series II, 501-503 (1981). In this study, the products of general formula (I) in which Z represents a radical of general formula (II) have been shown to be at least as active as taxol and Taxotere.

In vivo, the products of general formula (I) in which Z represents a radical of general formula (II) have been shown to be active in mice grafted with melanoma B16 at doses of between 1 and 10 mg / g intraperitoneally, as well as other liquid or solid tumors.

The new products have anti-tumor properties and more particularly an activity on tumors which are resistant to Taxol® or Taxotère®. Such tumors include colon tumors which have high expression of the mdr 1 gene (multi-drug resistance gene). Multi-drug resistance is a common term referring to the resistance of a tumor to different products with different structures and mechanisms of action. Taxoids are generally known to be highly recognized by experimental tumors such as P388 / DOX, a cell line selected for its resistance to doxorubicin (DOX) which expresses mdr 1.

The following examples illustrate the present invention.

EXAMPLE 1

To a solution of 0.193 g of tert-butoxycarbonylamino-3 hydroxy-2 phenyl-4 propionate- (2R, 4S) of benzoyloxy-2 epoxy-5β, 20 hydroxy-lβ methoxy-acetoxy-lOβ oxo-9 propanoyloxy-4 trifluoromethanesulfonyloxy- 7β taxene-11 yl-13α in 2.5 cm3 of acetonitrile and 0.250 cm3 of tetrahydrofuran, 0.096 g of powdered 4A molecular sieve, 0.290 g of sodium chloride are successively added. The reaction medium is kept stirring at a temperature in the region of 75 ° C for 5 hours then, at a temperature in the region of 20 ° C, supplemented with 75 cm3 of dichloromethane and 50 cm3 of a saturated aqueous sodium chloride solution. The organic phase is decanted, washed with 2 times 40 cm3 of a saturated aqueous solution of sodium chloride, then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 0.150 g of a product is obtained which is purified by chromatography on 80 g of silica (0.063-0.2 mm) contained in a column 1 cm in diameter (eluent: dichloromethane-methanol: 98/2 by volume) collecting 10 cm3 fractions. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. We obtain 0.080 g of tert-butoxycarbonylamino-3 hydroxy-2 phenyl-3 propionate- (2R, 4S) of benzoyloxy-2α epoxy-5β, 20 hydroxy-lβ methoxy-acetoxy-10β methylene-7β, 8 nor-19 oxo- 9 propanoyloxy-4α taxene-11 yle-13α, the characteristics of which are as follows: - 1 H NMR spectrum (400 MHz, CDC1 ₃ , δ in ppm): 1.24 (t, J = 7.5 Hz, 3H: CH ₃ ethyl); 1.24 (s, 6H: CH ₃ ); 1.27 (s, 9H: C (CH-) ₃ ); 1.42 (mt, 1H: H 7); 1.68 and 2.24 (2 mis. 1 H each: CH ₂ in 19); 1.86 (s, 1H OH in 1); 1.86 (s, 3H: CH ₃ ); 2.12 and 2.86 (respectively d and dt, J = 16 and J = 16 and 5 Hz, 1 H each: CH ₂ in 6); from 2.15 to 2.30 and 2.41 (respectively mt and dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 2.64 (mt, 2H: CH ₂ ethyl); 3.26 (mt, 1H: OH in 2 '); 3.52 (s, 3H: OCH ₃ ); 4.07 (d, J = 7 Hz, 1 H: H at 3); 4.04 and 4.33 (2d, J = 9 Hz, 1H each: CH ₂ in 20); 4.22 (limit AB, J = 16 Hz, 2H: OCOCH ₂ O); 4.62 (mt, 1H: H in 2 '); 4.70 (d, J = 4 Hz, 1 H: H at 5); 5.28 (md, 2H: H in 3 'and CONH); 5.67 (d, J = 7 Hz, 1H: H in 2); 6.26 (broad t, J = 9 Hz, 1 H: H at 13); 6.42 (s, 1H: H at 10); from 7.25 to 7.45 (mt, 5H: aromatic H in 3 "); 7.52 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.62 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.16 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

Tert-butoxycarbonylamino-3 hydroxy-2 phenyl-4 propionate- (2R, 4S) of benzoyloxy-2α epoxy-5β, 20 hydroxy-lβ methoxyacetoxy-lOβ oxo-9 propanoyloxy- A trifluoromethanesulfonyloxy-7β taxene-11 yle-13α can be prepared as follows:

A solution of 0.760 g of tert-butoxycarbonyl-3 (4-methoxy-phenyl) -2 phenyl-4 oxazolidine-1,3 carboxylate-5 (2R, 4S, 5R) of benzoyloxy-2α epoxy-5β, 20 hydroxy-lβ methoxyacetoxy -10β oxo-9 propanoyloxy-4α trifluoromethanesulfonate- 7β taxene-11 yl-13α in 6.6 cm3 of a 0.1N solution of hydrochloric ethanol is stirred at a temperature in the region of 0 ° C for 22 hours. The reaction medium is concentrated to dryness under reduced pressure (2.7 kPa) at 20 ° C. The crude reaction product is dissolved in 80 cm3 of dichloromethane and 80 cm3 of a saturated aqueous solution of sodium bicarbonate. The organic phase is separated by decantation and then extracted with 2 times 50 cm3 of dichloromethane. The organic phases are combined, washed with 50 cm3 of distilled water and then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 20 ° C. 0.9 g of a white meringue is obtained which is purified by chromatography on 150 g of silica (0.063-0.2 mm) contained in a column 3 cm in diameter (eluent: dichloromethane-methanol: 95-5 by volume) by collecting 15 cm3 fractions. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 20 ° C. 0.456 g of tert-butoxyc_ιrbonyl__mino-3 hydroxy-2 phenyl-4 propionate- (2R, 4S) of benzoyloxy-2α epoxy-5β, 20 hydroxy-lβ methoxyacetoxy-lOβ oxo-9 propanoyloxy-4α trifluoromethanesulfonyloxy-7β are obtained. -11 yle-13α and whose physical characteristics are the following:

- NMR spectrum ^* Α (400 MHz, CDC1 ₃ , δ in ppm): 1.24 (s, 9H ,: CH ₃ and CH ₃ ethyl); 1.34 (s, 9H: C (CH ₃ ) ₃ ); 1.74 (s, 1H: 0H in 1); 1.88 (s, 3H: CH ₃ ); 2.05 (broad s, 3H: CH ₃ ); 2.24 and 2.86 (2 mis, 1H each: CH ₂ in 6); 2.33 (d, J = 9 Hz, 2H: CH ₂ at 14); 2.68 (mt, 2H: CH ₂ ethyl); 3.30 (mt, 1H: OH in 2 '); 3.52 (s, 3H: OCH ₃ ); 3.93 (mt, 1H: H at 3); 4.19 (limit AB, J = 16 Hz, 2H: OCOCH ₂ O); 4.20 and 4.36 (2d, J = 9 Hz, 1H each: CH ₂ in 20); 4.64 (broad d, J = 5.5 Hz, 1H: H in 2 '); 4.86 (broad d, J = 10 Hz, 1 H: H at 5); 5.22 (mt, 1H: H in 3 '); 5.30 (d, J = 10 Hz, 1 H: CONH); 5.51 (dd, J = 10 and 7.5 Hz, 1H: H at 7); 5.75 (d, J = 7 Hz, 1H: H in 2); 6.20 (mt, 1H: H at 13); 6.71 (s, 1H: H at 10); from 7.30 to 7.45 (mt, 5H: H aromatic in 3 '); 7.52 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.64 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.13 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

Tert-butoxycarbonyl-3 (4-methoxy-phenyl) -2 4-phenyl-oxazolidine- 1,3-carboxylate-5 (2R.4S.5R) of benzoyloxy-2α epoxy-5β, 20 hydroxy-lβ methoxy-acetoxy-lOβ oxo -9 propanoyloxy-4α trifluorOmethanesulfonyloxy-7β taxene-11 yle-13α can be prepared as follows:

To a solution of 0.590 g of benzoyloxy-2α dihydroxy-lβ, 13 epoxy-5β, 20 methoxyacetoxy-lOβ oxo-9 propanoyloxy-4α trifluoromethanesulfonyloxy-7β taxene-11 in 0.4 cm3 of anhydrous ethyl acetate, 0.463 is successively added g of tert-butoxycarbonyl-3 (4-methoxyphenyl) -2 phenyl-4 oxazolidine-1,3 carboxylic-5 (2R.4S.5R) acid, 0.319 g of dicyclohexylcaiixxJiimide and 0.028 g of 4-dimethylamino-pyridine. The reaction mixture is stirred for 15 hours, under an argon atmosphere, at a temperature in the region of 20 ° C., then added with 75 cm3 of dichloromethane and 50 cm3 of a saturated aqueous solution of ammonium chloride. The organic phase is decanted, washed with 2 times 40 cm3 of a saturated aqueous solution of sodium chloride and then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 0.980 g is obtained which is purified by chromatography on 150 g of silica (0.063-0.2 mm) contained in a column 3 cm in diameter (eluent: dichloromethane-methanol: 95-5 by volume), collecting fractions of 15 cm3. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 0.740 g of tert-butoxycarbonyl-3 (4-methoxyphenyl) -2 phenyl-4 oxazolidine-1,3 carboxylate-5 (2R, 4S, 5R) of benzoyloxy-2α epoxy-5β, 20 hydroxy-lβ methoxy- are obtained. acetoxy-10β oxo-9 propanoyloxy-4α trifluorOmethanesulfonyloxy-7β taxene-11 yle-13α in the form of a white meringue and the physical characteristics of which are as follows:

- 1 H NMR spectrum (400 MHz, CDC1 ₃ , δ in ppm): 1.06 (s, 12H: CH ₃ and C (CH ₃ ) ₃ ); 1.20 (s, 3H ,: CH ₃ ); 1.27 (t, J = 7.5 Hz, 3H: CH ₃ ethyl); 1.67 (s, 1H: 0H in 1); 1.71 (s, 3H: CH ₃ ); 1.83 (s, 3H: CH ₃ ); from 2.00 to 2.30 and 2.83 (2 mt, 1H each: CH ₂ in 6); 2.00 to 2.30 (mt, 2H: CH ₂ ethyl); 2.08 and 2.22 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 3.52 (s, 3H: OCH ₃ ); 3.82 (s, 3H: ArOCH-); 3.82 (mt, 1H: H at 3); 4.12 and 4.29 (2d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.18 (limit AB, J = 16 Hz, 2H: OCOCH ₂ O); 4.51 (d, J = 5 Hz, 1H: H in 2 '); 4.80 (broad d, J = 10 Hz, 1 H: H 5); 5.35 to 5.45 (mt, 1H: H in 3 '); 5.43 (dd, J = 10.5 and 7.5 Hz, 1H: H at 7); 5.68 (d, J = 7 Hz, 1H: H in 2); 6.01 (mt, 1H: H at 13); 6.38 (mt, 1H: H in 5 '); 6.60 (s, 1H: H at 10); 6.92 (d, J = 8.5 Hz, 2H: aromatic H in ortho of OCH ₃ ); 7.39 (d, J = 8.5 Hz, 2H: aromatic H in meta of OCH ₃ ); from 7.30 to 7.45 (mt, 5H: 3 'aromatic H); 7.50 (t, J ≈ 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.65 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.03 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

Benzoyloxy-2α dihyd_x.xy-lβ, 13α epoxy-5β, 20 methoxyacetoxy- lOβ oxo-9 propanoyloxy-4cc trifluoromemanesulfonyloxy-7β taxene-11 can be prepared as follows:

To a solution of 0.660 g of benzoyloxy-2α epoxy-5β, 20 methoxyacetoxy lOβ oxo-9 propanoyloxy-4α trihyd_Oxy-lβ, 7β, 13α taxene-11 in 6.6 cm3 of anhydrous dichloromethane and 0.338 cm3 of pyridine, kept under atmosphere of argon, at a temperature in the region of 0 ° C., 0.354 cm3 of trifluoromethanesulfonic anhydride is added dropwise. The orange solution obtained is stirred for 10 minutes at a temperature close to 0 ° C, 30 minutes at a temperature close to 20 ° C, then added with 3 cm3 of water and 50 cm3 of dichloromethane. The organic phase is decanted, washed with 2 times 40 cm3 of a saturated aqueous solution of sodium chloride and then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 0.800 g is obtained which is purified by chromatography on 100 g of silica (0.063-0.2 mm) contained in a column 2 cm in diameter (eluent: dichloromethane-methanol: 95-5 by volume), collecting fractions of 15 cm3. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 0.591 g of benzoyloxy-2α d__hydroxy-lβ, 13α epoxy-5β, 20 methoxyacetoxy- lOβ oxo-9 propanoyloxy-4α trifluoromethanesulfonyloxy-7β taxene-11 are obtained in the form of a white meringue and the physical characteristics of which are as follows:

- ^Ï H NMR spectrum (400 MHz, CDC1 _3, δ in ppm): 1.05 (s, 3H: _CH3); 1.19 (s, 3H: CH ₃ ); 1.23 (t, J = 7.5 Hz, 3H: CH ₃ ethyl); 1.62 (s, 1H: 0H in 1); 1.89 (s, 3H: CH ₃ ); 2.12 (d, J = 5 Hz, 1H: OH at 13); 2.24 and 2.90 (2 mts, 1 H each: CH ₂ in 6); 2.25 (s, 3H: CH ₃ ); 2.30 (AB limit, 2H: CH ₂ in 14); 2.64 (mt, 2H: CH ₂ ethyl); 3.52 (s, 3H: OCH ₃ ); 4.02 (d, J, = 7 Hz, 1H: H at 3); 4.15 and 4.35 (2d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.20 (limit AB, J = 16 Hz, 2H: OCOCH-O); 4.85 (mt, 1H: H at 13); 4.91 (broad d, J = 10 Hz, 1 H: H at 5); 5.57 (dd, J = 10 and 7 Hz, 1H: H at 7); 5.69 (d, J = 7 Hz, 1H: H in 2); 6.73 (s, 1H: H at 10); 7.50 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.63 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.11 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho). Benzoyloxy-2α epoxy-5β, 20 methoxyacetoxy-lOβ oxo-9 propanoyloxy- Aa trihydroxy-lβ, 7β, 13 taxene-11 can be prepared as follows:

To a solution of 1.21 g of 2-benzoyloxy ditriethylsilyloxy-7β, 13 epoxy-5β, 20 hydroxy-lβ methoxyacetoxy 10β oxo-9 propanoyloxy-4α taxene-11 in 15 cm3 of dichloromethane, a temperature close to 20 ° C, 23 cm3 of triethylamine-hydrofluoric acid complex. The reaction mixture is stirred for 20 hours at a temperature in the region of 20 ° C., then 50 cm3 of dichloromethane and 100 cm3 of a saturated aqueous solution of sodium hydrogencarbonate are added. The organic phase is decanted, washed with 2 times 50 cm3 of a saturated aqueous solution of sodium chloride then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 1.04 g of benzoyloxy-2α epoxy-5β, 20 methoxyacetyl-10β oxo-9 propanoyloxy-4 trihydroxy-lβ, 7β, 13α taxene-11 are obtained in the form of a white meringue, the physical characteristics of which are as follows: - 1 H NMR spectrum (400 MHz, CDCl ₃ , δ in ppm): 1.11 (s, 6H: CH ₃ ); 1.25 (t, J = 7.5 Hz, 3H: CH ₃ ethyl); 1.65 (s, 1H: 0H in 1); 1.70 (s, 3H: CH ₃ ); 1.88 and 2.60 (2 mts, 1 H each: CH ₂ in 6); 2.08 (s, 3H: CH _j ); 2.30 (AB limit, 2H: CH ₂ in 14); 2.39 (d, J = 4 Hz, 1H: OH at 7); 2.63 (mt, 2H: CH ₂ ethyl); 3.55 (s, 3H: OCH ₃ ); 3.90 (d, J = 7 Hz, 1 H: H at 3); 4.17 and 4.32 (2d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.25 (AB Umite, J = 16 Hz, 2H: OCOCH ₂ O); 4.51 (mt, 1H: H at 7); 4.89 (mt, 1H: H at 13); 4.95 (broad d, J = 10 Hz, 1 H: H at 5); 5.64 (d, J = 7 Hz, 1H: H in 2); 6.43 (s, 1H: H at 10); 7.48 (t, J = 8 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.61 (t, J = 8 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.13 (d, J = 8 Hz, 2H: OCOC ₆ H ₅ H in ortho).

Benzoyloxy-2α ditriethylsilyloxy-7β, 13α epoxy-5β, 20 hydroxy-lβ methoxyacetoxyl-lOβ oxo-9 propanoyloxy-4α taxene-11 can be prepared as follows:

To a solution of 0.900 g of benzoyloxy-2α dihydroxy-lβ.lOβ bis (triethylsilyloxy) -7β, 13α epoxy-5β, 20 oxo-9 propanoyloxy-4α taxene-11 in 15 cm3 of pyridine, 0.520 cm3 of chloride of chloride are added methoxyacetyl at a temperature close to 0 ° C. The reaction mixture is stirred for 2 hours at a temperature in the region of 20 ° C. and then 100 cm 3 of dichloromethane and 50 cm 3 of a saturated aqueous ammonium chloride solution are added. The organic phase is decanted, washed with 2 times 40 cm3 of a saturated aqueous solution of ammonium chloride, then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 1.3 g are obtained which are purified by chromatography on 150 g of silica (0.063-0.2 mm) contained in a column 2.5 cm in diameter (eluent: ethyl acetate-cyclohexane: 25-75 by volume), collecting 10 cm 3 fractions. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 0.780 g of benzoyloxy-2α bis (triethyls_lyloxy) -7β, 13α epoxy-5β, 20 hydroxy-lβ methoxyacetoxy- lOβ oxo-9 propanoyloxy-4α taxene-11 are obtained in the form of a white meringue, the physical characteristics of which are following: - H NMR spectrum (400 MHz, CDC1 ₃ , δ in ppm): from 0.50 to 0.70 (mt, 12 H: CH ₂ ethyl); 0.92 (t, J = 7.5 Hz, 9H: CH ₃ ethyl); 1.00 (t, J = 7.5 Hz, 9H: CH ₃ ethyl); 1.10 (s, 3H: CH ₃ ); 1.17 (s, 3H: CH ₃ ); 1.29 (t, J = 7.5 Hz, 3H: CH ₃ ethyl in 4); 1.61 (s, 1H: 0H in 1); 1.68 (s, 3H: CH ₃ ); 1.84 and 2.51 (2 mts, 1 H each CH ₂ in 6); 2.09 and 2.21 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 2.10 (s, 3H CH ₃ ); 2.60 (mt, 2H: CH ₂ ethyl 4); 3.50 (s, 3H: OCH ₃ ); 3.78 (d, J = 7 Hz, 1 H H at 3); 4.12 and 4.30 (2d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.15 (limit AB, J = 16 Hz, 2H: OCOCH ₂ O); 4.49 (dd, J = 11 and 7 Hz, 1H: H at 7); 4.90 (mt, 2H: H at 5 and H at 13); 5.62 (d, J = 7 Hz, 1H: H in 2); 6.52 (s, 1H: H at 10); 7.45 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.58 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.09 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

Benzoyloxy-2 dihydroxy-lβ.lOβ bis (ditriethylsilyloxy) -7β, 13 epoxy-5β, 20 oxo-9 propanoyloxy-4α taxene-11 can be prepared as follows:

To a solution of 1.105 g of carbonate- lβ, 2α bis (triethylsilyloxy) -7β, 13α epoxy-5β, 20 methoxyacetoxy-lOβ oxo-9 propanoyloxy-4α taxene-11 in 50 cm3 of tetrahydrofuran anhydride, 1.8 cm3 of a 1M solution of phenyllithium in tetrahydrofuran at a temperature in the region of -78 ° C. The reaction mixture is stirred for 15 minutes at a temperature in the region of -78 ° C. and then 10 cm 3 of a saturated aqueous solution of ammonium chloride are added. At a temperature in the region of 20 ° C., 20 cm 3 of a saturated aqueous solution of ammonium chloride and 50 cm 3 of dichloromethane are added. The organic phase is decanted, washed with 2 times 10 cm3 of a saturated aqueous solution of sodium chloride and then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 1.3 g are obtained which are purified by chromatography on 150 g of silica (0.063-0.2 mm) contained in a column 5 cm in diameter (eluent: ethyl acetate-cyclohexane: 10-90 by volume ) by collecting fractions of 18 cm3. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 0.840 g of benzoyloxy-2α dihydroxy- is obtained lβ, 10β bis (triethylsilyloxy) -7β, 13α epoxy-5β, 20 oxo-9 propanoyloxy-4α taxene-11 in the form of a white meringue and the physical characteristics of which are as follows:

- 1 H NMR spectrum (400 MHz, CDC1 ₃ , δ in ppm): 0.53 (mt, 6 H: ethyl CH ₂ ); 0.65 (mt, 6H: CH ₂ ethyl); 0.92 (t, J = 7.5 Hz, 9H: CH ₃ ethyl); 1.00 (t, J = 7.5 Hz, 9H: CH ₃ ethyl); 1.07 (s, 3H: CH ₃ ); 1.14 (s, 3H: CH ₃ ); 1.26 (t, J = 7.5 Hz, 3H: CH ₃ ethyl in 4); 1.40 (s, 1H: 0H in 1); 1.71 (s, 3H: CH ₃ ); 1.88 and 2.45 (2 mis, 1 H each: CH ₂ in 6); 2.00 (s, 3H: CH-); 2.06 and 2.18 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 2.60 (q, J = 7.5 Hz, 2H: CH ₂ ethyl in 4); 3.84 (d, J = 7 Hz, 1H: H at 3); 4.14 and 4.30 (2d, J = 8.5 Hz, 1 H each: CH ₂ in 20); 4.26 (d, J = 0.5 Hz, 1 H: OH at 10); 4.40 (dd, J = 11 and 7 Hz, 1H: H at 7); 4.90 (broad d, J = 10 Hz, 1 H: H at 5); 4.94 (wide t, J = 9 Hz, 1H: H at 13); 5.12 (d, J = 0.5 Hz, 1 H: H at 10); 5.58 (d, J = 7 Hz, 1H: H in 2); 7.45 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.60 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.09 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

Carbonate-lβ, 2α bis (triethylsilyloxy) -7β, 13α epoxy-5β, 20 methoxy¬ acetoxy- lOβ oxo-9 propanoyloxy-4α taxene-11 can be prepared in the following manner:

To a solution of 2.0 g of carbonate-lβ, 2α bis (triethylsilyloxy) -7β, 13α epoxy-5β, 20 hydroxy-4α methoxyacetoxy lOβ oxo-9 taxene-11 in 90 cm3 of dichloromethane, 3.37 g is added of 4-dimemylaminopyridine and 3.64 cm3 of propionic anhydride. The reaction medium is heated to a temperature in the region of 42 ° C for 8 hours. 50 cm3 of a saturated aqueous solution of sodium chloride and 50 cm3 of dichloromethane are added. The organic phase is decanted, washed with 2 times 40 cm3 of a saturated aqueous solution of sodium chloride and then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 2.6 g are obtained which are purified by chromatography on 100 g of silica (0.063-0.2 mm) contained in a column 3 cm in diameter (eluent: ethyl acetate-cyclohexane: 5-95 by volume ) by collecting fractions of 12 cm3. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 1.97 g of carbonate-lβ, 2α bis (triethylsilyloxy) -7β, 13α epoxy-5β, 20 methoxyacetoxy lOβ oxo-9 propanoyl-oxy-4 taxene-11 are obtained in the form of a white meringue and the physical characteristics of which are obtained. are the following : - 1 H NMR spectrum (400 MHz, CDCl ₃ , δ in ppm): from 0.50 to 0.75 (mt, 12 H: CH ₂ ethyl); 0.94 (t, J = 7.5 Hz, 9H: CH ₃ ethyl); 1.03 (t, J = 7.5 Hz, 9H: CH ₃ ethyl); 1.21 (mt, 6H: CH ₃ and CH ₃ ethyl); 1.28 (s, 3H: CH ₃ ); 1.75 (s, 3H: CH ₃ ); 1.90 and 2.60 (2 mts, 1 H each CH ₂ in 6); 2.13 (s, 3H: CH ₃ ); 2.15 and 2.38 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 2.43 (mt, 2H: CH ₂ ethyl); 3.43 (d, J = 5.5 Hz, 1 H: H at 3); 3.51 (s, 3H: OCH ₃ ); 4.18 (s, 2H: OCOCH ₂ O); 4.46 (dd, J = 11 and 7 Hz, 1H: H at 7); 4.48 and 4.65 (2d, J = 9Hz, 2H: CH ₂ in 20); 4.51 (d, J = 5.5 Hz, 1H: H in 2); 4.93 (broad d, J = 10 Hz, 1 H: H at 5); 5.02 (t, J = 9 Hz, 1H: H at 13); 6.51 (s, 1H: H at 10). Carbonate-lβ, 2α bis (triethylsilyloxy) -7β, 13α epoxy-5β, 20 hydroxy-4 methoxyacetoxy-lOβ oxo-9 taxene-11 can be prepared in the following manner:

To a solution of 4.12 g of carbonate-lβ, 2 dihydroxy-4, 10β bis (triethylsilylo__y) -7β, 13α epoxy-5β, 20 oxo-9 taxene-11 in 80 cm3 of pyridine, is added, with stirring and at a temperature in the region of 0 ° C., 2 g of powdered 4Â molecular sieve and 2.86 cm3 of methoxyacetyl chloride. The reaction mixture is stirred for 15 minutes at a temperature in the region of 0 ° C and then the temperature of the reaction medium is allowed to rise slowly to a temperature in the region of 20 ° C. After 4 hours of stirring at a temperature in the region of 20 ° C., 50 cm3 of a saturated aqueous solution of ammonium chloride and 100 cm3 of dichloromethane are added. The organic phase is decanted, washed with 2 times 40 cm3 of a saturated aqueous solution of ammonium chloride, 2 times 25 cm3 of a saturated aqueous solution of copper sulfate and 2 times 25 cm3 of a saturated aqueous solution of sodium chloride then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 5.3 g are obtained which are purified by chromatography on 200 g of silica (0.063-0.2 mm) contained in a column 4 cm in diameter (eluent: ethyl acetate-cyclohexane: 25-75 by volume ) by collecting fractions of 12 cm3. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 4.21 g of carbonate-lβ, 2α bis (triethylsilyloxy) -7β, 13α epoxy-5β, 20 hydroxy-4α methoxyacetoxy-lOβ oxo-9 taxene-11 are obtained in the form of a white meringue, the physical characteristics of which are the following :

- NMR spectrum * H (400 MHz, CDC1 ₃ , δ in ppm): 0.59 (mt, 6H: CH ₂ ethyl); 0.73 (mt, 6H: CH ₂ ethyl); 0.91 (t, J = 7.5 Hz, 9H: CH ₃ ethyl); 1.02 (t, J = 7.5 Hz, 9H: CH ₃ ethyl); 1.15 (s, 3H: CH ₃ ); 1.18 (s, 3H: CH ₃ ); 1.65 (s, 3H: CH ₃ ); 1.98 and 2.51 (2 mts, 1 H each: CH ₂ in 6); 2.15 (s, 3H: CH ₃ ); 2.54 and 2.72 (2 dd, respectively J = 16 and 9 Hz and J = 16 and 3 Hz, 1 H each: CH ₂ at 14); 2.93 (s, 1H: OH at 4); 3.03 (d, J = 5 Hz, 1 H: H at 3); 3.51 (s, 3H: OCH ₃ ); 4.16 (mt, 1H: H at 7); 4.17 (AB, J = 18 Hz, 2H: OCOCH ₂ O); 4.37 (d, J = 5 Hz, 1H: H in 2); 4.54 (AB, J = 9 Hz, 2H: CH ₂ in 20); 4.76 (broad d, J = 10 Hz, 1 H: H at 5); 4.81 (dd, J = 9 and 3 Hz, 1H: H at 13); 6.51 (s, 1H: H at 10).

Carbonate-lβ, 2α dihydroxy-4α, 10β bis (triethylsilyloxy) -7β, 13α epoxy- 5β, 20 oxo-9 taxene-11 can be prepared as follows:

To a solution of 0.400 g of bis (triethylsilyloxy) -7β, 13α epoxy-5β, 20 oxo-9 tetrahydroxy-lβ, 2, 4α, 10β taxene-11 in 10 cm3 of dichloromethane, is added, with stirring and at a temperature close to -78 ° C, 1 cm3 of pyridine and 0.560 g of triphosgene. The reaction mixture is stirred for 2 hours at a temperature in the region of -78 ° C and then the reaction medium is allowed to rise gently to a temperature in the region of 20 ° C. 30 cm3 of a saturated aqueous solution of ammonium chloride and 20 cm3 of dichloromethane are added. The organic phase is decanted, washed with 2 times 40 cm3 of a saturated aqueous solution of sodium chloride and then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 0.400 g of a yellow meringue is obtained which is purified by chromatography on 25 g of silica (0.063-0.2 mm) contained in a column of

2 cm in diameter (eluent: ethyl acetate-cyclohexane: 20-80 by volume), collecting 10 cm 3 fractions. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 0.330 g of carbonate-lβ, 2α dihydroxy-4α, 10β bis (triethylsilyloxy) -7β, 13α epoxy- 5β, 20 oxo-9 taxene-11 are obtained in the form of a white meringue, the physical characteristics of which are as follows: - 1 H NMR spectrum (400 MHz, CDC1 ₃ , δ in ppm): 0.54 (mt, 6H: CH ₂ ethyl); 0.63 (mt, 6H: CH ₂ ethyl); 0.92 (t, J = 7.5 Hz, 9H: CH ₃ ethyl); 1.03 (t, J = 7.5 Hz, 9H: CH ₃ ethyl); 1.11 (s, 3H: CH ₃ ); 1.19 (s, 3H: CH ₃ ); 1.72 (s, 3H: CH ₃ ); 1.98 and 2.46 (2 mts, 1 H each: CH ₂ in 6); 2.06 (s, 3H: CH ₃ ); 2.55 and 2.66 (2 dd, respectively J = 16 and 9 Hz and J = 16 and 3 Hz, 1 H each: CH ₂ at 14); 3.00 (s, 1H: OH 4); 3.13 (d, J = 5 Hz, 1 H: H at 3); 4.06 (dd, J = 11 and 7 Hz, 1H: H at 7); 4.20 (d, J = 2.5 Hz, 1 H: OH at 10); 4.33 (d, J = 5 Hz, 1H: H in 2); 4.55 (AB, J = 9 Hz, 2H: CH ₂ in 20); 4.76 (broad d, J = 10 Hz, 1 H: H at 5); 4.82 (dd, J = 9 and

3 Hz, 1 H: H at 13); 5.19 (d, J = 2.5 Hz, 1 H: H at 10).

Bis (triethylsilyloxy) -7β, 13 eρoxy-5β, 20 oxo-9 tetrahydroxy-lβ, 2α, 4α, lOβ taxene-11 can be prepared as follows: To a solution of 3.80 g of epoxy-5β, 20 oxo-9 pentahydroxy-lβ, 2α, 4α, 10β, 13 triethylsilyloxy-7β taxene-11 in 100 cm3 of dichloromethane, is added, with stirring and at a similar temperature at 0 ° C, 1.20 cm3 of pyridine and 2.48 cm3 of chlorotriethylsilane. The reaction mixture is stirred for 3 hours at a temperature in the region of 0 ° C. 100 cm 3 of a saturated aqueous sodium chloride solution are added. The organic phase is decanted, washed with 2 times 100 cm3 of a saturated aqueous solution of sodium chloride and then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 5.34 g of an orange oil are obtained which is purified by chromatography on 300 g of silica (0.063-0.2 mm) contained in a column 3 cm in diameter (eluent: ethyl acetate-cyclohexane: 25-75 by volume) by collecting 40 cm3 fractions. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 4.18 g of bis (triethylsilyloxy) -7β, 13α epoxy- 5β, 20 oxo-9 tetrahydroxy-lβ, 2α, 4α, 10β taxene-11 are obtained in the form of a white meringue, the physical characteristics of which are as follows :

- NMR spectrum * H (400 MHz, CDC1 ₃ , δ in ppm): 0.53 (mt, 6H: CH ₂ ethyl); 0.75 (mt, 6H: CH ₂ ethyl); 0.91 (t, J = 7.5 Hz, 9H: CH ₃ ethyl); 1.01 (s, 3H: CH ₃ ); 1.03 (t, J = 7.5 Hz, 9H: CH ₃ ethyl); 1.09 (s, 3H: CH ₃ ); 1.63 (s, 3H: CH ₃ ); 1.97 (s, 3H: CH ₃ ); from 1.95 to 2.10 and 2.40 (2 mts, 2H each: CH ₂ at 14 and CH _{2 at} 6); 3.17 (s, 1H: OH); 3.18 (d, J = 5.5 Hz, 1 H: H at 3); 3.43 (d, J = 10 Hz, 1H: OH in 2); 3.76 (dd, J = 10 and 5.5 Hz, 1H: H in 2); 3.96 (dd, J = 11 and 6 Hz, 1H: H at 7); 4.10 (s, 1H: OH); 4.18 (d, J = 3 Hz, 1 H: OH at 10); 4.44 and 4.73 (2d, J = 9 Hz, 1H each: CH ₂ in 20); 4.64 (broad d, J = 10 Hz, 1 H: H at 5); 4.74 (mt, 1H: H at 13); 5.14 (d, J = 3 Hz, 1 H: H at 10).

EXAMPLE 2

To a solution of 20.5 mg of tert-butoxycarbonylamino-3 hydroxy-2 phenyl-3 propionate- (2R, 3S) of epoxy-5β, 20 hydroxy-lβ methoxyacetoxy- lOβ oxo-9 propanoyloxy-4α (thénoyloxy-2 ) -2α trifluoromethanesulfonyloxy-7β taxene-11 yle 13 in 0.2 cm3 of acetonitrile and 0.025 cm3 of tetrahydrofuran, 45 mg of sodium chloride and a spatula of 4A activated molecular sieve are added. The mixture obtained is brought to reflux, under an argon atmosphere, for 2 hours. After cooling to a temperature in the region of 20 ° C, the solvents are evaporated under reduced pressure (0.27 kPa) to a temperature in the region of 40 ° C, the solid residue is taken up in 5 cm3 of dichloromethane, filtered through cotton and rinsed with 5 cm3 of ethyl acetate-dichloromethane mixture (50-50 by volume). The organic phases are concentrated under reduced pressure (0.27 kPa) at a temperature in the region of 40 ° C. 17.1 mg of a yellow meringue are thus obtained which is purified by preparative thin layer chromatography [2 Merck preparative plates, Kieselgel 60F254, thickness 0.25 mm, deposit in solution in dichloromethane, eluent: ^' methanol mixture -dichloromethane (6-94 by volume)]. After elution of the zone corresponding to the main product by a methanol-dichloromethane mixture (10-90 by volume), filtration through sintered glass, then evaporation of the solvents under reduced pressure (0.27 kPa) at a temperature in the region of 40 ° C, 10.0 mg of tert-butoxycarbonylamino-3 hydroxy-2 phenyl-3 propionate- (2R, 3S) of epoxy-5β, 20 hydroxy-lβ methoxyacetoxy- 10β methylene-7,8β oxo-9 propanoyloxy-4α are obtained thenoyloxy-2) -2α nor-19 taxene-11 yle-13 in the form of a white lacquer, the characteristics of which are as follows: - 1 H NMR spectrum (400 MHz, CDCI3, δ in ppm): 1.18 ( t, J = 7.5 Hz, 3H: ethyl CH3); 1.22 (s, 6H: CH3); 1.32 (s, 9H: C (CH ₃ ) ₃ ); 1.41 (mt, 1H: H at 7); 1.69 and 2.23 (2 mts, 1 H each: CH2 in 19); 1.81 (s, 1H: 0H in 1); 1.85 (s, 3H: CH3); 2.12 and 2.50 (respectively d and dt, J = 16 and J = 16 and 4.5 Hz, 1 H each: CH2 at 6); 2.25 and 2.39 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 2.63 (mt, 2H: CH ₂ ethyl); 3.23 (mt, 1H: OH in 2 '); 3.52 (s, 3H: OCH3); 4.03 (d, J = 7 Hz, 1 H: H at 3); 4.12 and 4.44 (2d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.20 (AB limit, J = 16 Hz, 2H: OCOCH ₂ O); 4.62 (mt, 1H: H in 2 '); 4.70 (d, J = 4 Hz, 1 H: H at 5); 5.22 (mt, 1H: H in 3 '); 5.28 (d, J = 10 Hz, 1 H: CONH); 5.58 (d, J = 7 Hz. 1H: H in 2); 6.23 (broad t, J = 9 Hz, 1 H: H at 13); 6.41 (s, 1H: H at 10); 7.18 (dd, J = 5 and 3.5 Hz, 1H: H in 4 of thenoyl-2); from 7.30 to 7.50 (mt, 5H: aromatic H in 3 '); 7.67 (broad d, J = 5 Hz, 1H: H at 5 of thenoyl-2); 7.96 (broad d, J = 3.5 Hz, 1H: H at 5 of thenoyl-2).

T-butoxycarbonylamino-3 hydroxy-2 phenyl-3 propionate- (2R, 3S) epoxy-5β, 20 hydroxy-lβ methoxyacetoxy-lOβ oxo-9 propanoyloxy-4 (thénoyloxy-2) -2α trifluorométhanesulfonyloxy-7β taxene- 11 yle-13α can be prepared as follows:

A solution of 75 mg of tert-butoxycarbonyl-3 (4-methoxyphenyl) -2 phenyl-4 oxazolidine-1,3 carboxylate-5 (2R.4S.5R) of epoxy-5β, 20 hydroxy-lβ methoxyacetoxy-lOβ oxo-9 propanoyloxy-4α (thenoyloxy-2) -2α trifluoromethane- sulfonyloxy-7β taxene-11 yl-13α in 0.77 cm3 of a 0.1N hydrochloric acid solution in ethanol is stirred at a neighboring temperature at 5 ° C for 2 hours. The the reaction mixture is then diluted with 10 cm3 of dichloromethane, washed with 2 times 1 cm3 of distilled water. After extraction of the aqueous phase with 1 cm 3 of dichloromethane, the organic phases are combined, dried over magnesium sulfate, filtered through sintered glass and concentrated under reduced pressure (0.27 kPa) at a temperature in the region of 40 ° C. 74.4 mg of a yellow lacquer is thus obtained which is purified by chromatography at atmospheric pressure on 8 g of silica (0.063-0.2 mm) contained in a column 1.5 cm in diameter (gradient of elution: ethyl acetate-dichloromethane from 5-95 to 20-80 by volume), collecting 8 cm 3 fractions. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (0.27 kPa) at 40 ° C for 2 hours. This gives 56.3 mg of tert-butoxycarbonylamino-3 hydroxy-2 phenyl-3 propionate- (2R.3S) of epoxy-5β, 20 hydroxy-lβ methoxyacetoxy-lOβ oxo-9 propanoyloxy-4 (thénoyloxy-2) -2α trifluoromethanesulfonyloxy-7β taxene-11 yle-13 in the form of a pale yellow meringue the characteristics of which are as follows: - 1 H NMR spectrum (400 MHz, CDC1 ₃ , δ in ppm): 1.20 (s, 6H: CH ₃ ); 1.22 (t, J = 7.5 Hz, 3H: CH ₃ ethyl); 1.36 (s, 9H: C (CH ₃ ) ₃ ); 1.71 (s, 1H,: 0H in 1); 1.89 (s, 3H: CH ₃ ); 2.05 (s, 3H: CH ₃ ); 2.25 and 2.86 (2 mts, 1 H each: CH ₂ in 6); 2.33 (d, J = 9 Hz, 2H: CH ₂ at 14); 2.66 (mt, 2H: CH ₂ ethyl); 3.28 (d, J = 5 Hz, 1H: OH in 2 '); 3.52 (s, 3H: OCH3); 3.90 (d, J = 7 Hz, 1 H: H at 3); 4.20 (AB Umite, J = 16 Hz, 2H: OCOCH ₂ O); 4.27 and 4.50 (2d, J = 9 Hz, 1 H each: CH2 in 20); 4.61 (mt, 1H: H in 2 '); 4.88 (broad d, J = 10 Hz, 1 H: H at 5); 5.20 (broad d, J = 10 Hz, 1H: H in 3 '); 5.30 (d, J = 10 Hz, 1 H: CONH); 5.50 (dd, J = 10 and 7 Hz, 1H: H at 7); 5.65 (d, J = 7 Hz. 1 H: H in 2); 6.18 (large t, J = 9 Hz, 1 H: H at 13); 6.70 (s, 1H: H at 10); 7.18 (dd, J = 5 and 3.5 Hz, 1H: H in 4 of thenoyl-2); from 7.30 to 7.50 (mt, 5H: aromatic H in 3 '); 7.69 (dd, J = 5 and 1.5 Hz, 1H: H at 5 of thenoyl-2); 7.92 (dd, J = 3.5 and 1.5 Hz, 1H: H at 5 of thenoyl-2).

Tert-butoxycarbonyl-3 (4-methoxy-phenyl) -2 4-phenyl-oxazolidine- 1,3-carboxylate-5 (2R.4S.5R) of epoxy-5β, 20 hydroxy-lβ methoxyacetoxy-10O oxo-9 propanoyloxy- 4α (2-thenoyloxy) -2α trifluoromethanesulfonylo> _y-7β taxene-11 yle-13α can be prepared as follows:

To a solution of 55.2 mg of epoxy-5β, 20 dihydroxy-lβ, 13α methoxyacetoxy-lOβ oxo-9 propanoyloxy-4α (2-thenoyloxy) -2α trifluoromethane-sulfonyloxy-7β taxene-11 in 0.1 cm3 of anhydrous toluene, 41 mg of tert-butoxycarbonyl-3 (4-methoxyphenyl) -2 phenyl-4 oxazolidine- 1,3 carboxyUque-5 (2R.4S.5R), 26 mg of dicyclohexylcarbodiimide are added successively mg of N, N-4-dimethylamino pyridine. The reaction mixture is stirred for 2 hours, under an argon atmosphere, at a temperature in the region of 20 ° C., then deposited on a chromatography column at atmospheric pressure (15 g of SiUce (0.063-0.2 mm) contained in a column 1.5 cm in diameter (elution gradient: ethyl acetate-dichloromethane from 5-95 to 10-90 by volume), collecting fractions of 10 cm3). The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (0.27 kPa) at 40 ° C for 2 hours. 75.3 mg of tert-butoxycarbonyl-3 (4-methoxy-phenyl) -2 phenyl-4-oxazoUdine-1,3 carboxylate-5 (2R.4S.5R) of epoxy-5β, 20 hydroxy-1β methoxy are thus obtained. - acetoxy-10β oxo-9 propanoyloxy-4α (2-thenoyloxy) -2α trifluoromethanesulfonyl-oxy-7β taxene-11 yle-13α in the form of a white meringue the characteristics of which are as follows:

- 1 H NMR spectrum (400 MHz, CDCI3, δ in ppm): 1.04 (s, 9H: C (CH) 3); 1.04 (t, J = 7.5 Hz, 3H: CH3 ethyl); 1.14 (s, 3H: CH ₃ ); 1.16 (s, 3H: CH ₃ ); 1.61 (s, 1H: 0H in 1); 1.68 (s, 3H: CH3); 1.81 (s, 3H: CH ₃ ); from 2.00 to 2.30 (mt, 4H: ethyl CH2 and CH2 at 14); 2.03 and 2.80 (2 mts, 1 H each: CH2 in 6); 3.50 (s, 3H: OCH3); 3.77 (d, J = 7 Hz, 1 H: H at 3); 3.81 (s, 3H: ArOCH ₃ ); 4.13 (AB limit, J = 16 Hz, 2H: OCOCH ₂ O); 4.18 and 4.39 (2d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.48 (d, J = 4 Hz, 1H: H in 2 '); 4.78 (broad d, J = 10 Hz, 1 H: H at 5); 5.35 to 5.50 (mt, 2H: H in 3 "and H in 7); 5.55 (d, J = 7 Hz, IH: H in 2); 5.96 (t wide, J = 9 Hz, 1H: H at 13); 6.34 (mt, 1H: H at 5 '); 6.56 (s, 1H: H at 10); 6.88 (d, J = 8 Hz, 2H: H aromatic in ortho of OCH3); 7.13 (dd, J = 5 and 3.5 Hz, IH: H in 4 of thénoyl-2); from 7.30 to 7.45 (mt, 5H: H aromatic in 3 '); 7.36 (d, J = 8 Hz, 2H: aromatic H in meta of OCH3); 7.62 (d wide, J = 5 Hz, 1H: H in 5 of thenoyl- 2); 7, 80 (broad d, J = 3.5 Hz, 1H: H at 5 of thenoyl-2).

Epoxy-5β, 20 dihydroxy-lβ, 13α methoxyacetoxy- lOβ oxo-9 propanoyloxy- Λa (thenoyloxy-2) -2α trifluoromethanesulfonyloxy-7β taxene-11 can be prepared as follows:

To a solution of 50 mg of epoxy-5β, 20 methoxyacetoxy-10β oxo-9 propanoyloxy-4α (2-thenoyloxy) -2α trihydrOxy-1β, 7β, 13α taxene-11 in 0.5 cm3 of anhydrous dichloromethane and 0, 0255 cm3 of pyridine, maintained under an argon atmosphere, at a temperature close to 0 ° C., 0.0265 cm3 of trifluoromethanesulfonic anhydride is added dropwise. The orange solution obtained is stirred for 10 minutes at a temperature close to 0 ° C, 45 minutes at a temperature close to 20 ° C, then added with 0.1 cm3 of a methanol / dichloromethane mixture (5/95 in volumes). The solution is deposited on an atmospheric pressure chromatography column (10 g of silica (0.063-0.2 mm) contained in a column 1.5 cm in diameter (elution gradient: methanol-dichloromethane from 2-98 to 5-95 by volume) by collecting fractions of 8 cm3). The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (0.27 kPa) at 40 ° C for 2 hours. 55.2 mg of epoxy-5β, 20 dihydroxy-lβ, 13α methoxyacetoxy-lOβ oxo-9 propanoyloxy-4α (2-thénoyloxy) -2 trifluoromethane-sulfonyloxy-7β taxene-11 are thus obtained in the form of a white meringue. .

Epoxy-5β, 20 trihydroxy-lβ, 7β, 13 methoxyacetoxy-10O oxo-9 propanoyl-oxy-4α (2-thenoyloxy) -2α taxene-11 can be prepared as follows:

To a solution of 0.302 g of epoxy-5β, 20 hydroxy-lβ methoxyacetoxy-lOβ oxo-9 propanoyloxy-4α (thénoyloxy-2) -2α bis (triethylsilyloxy) -7β, 13 taxene-11 in 5 cm3 of dichloromethane, we add, at a temperature in the region of 20 ° C, 6 cm3 of triethylamine-hydrofluoric acid complex (Et3N.3HF). The reaction mixture is stirred for 24 hours at a temperature in the region of 20 ° C., then 50 cm 3 of dichloromethane and 100 cm 3 of a saturated aqueous solution of sodium hydrogen carbonate are added. The organic phase is decanted, washed with 2 times 40 cm3 of a saturated aqueous solution of sodium chloride, then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 0.24 g of epoxy-5β, 20 trihydroxy-lβ, 7β, 13α methoxyacetoxy-lOβ oxo-9 propanoyl-oxy-4α (thénoyloxy-2) -2α taxene-11 are thus obtained in the form of a white meringue, the characteristics are as follows:

- NMR spectrum (400 MHz, CDCI3, δ in ppm): 1.07 (s, 3H: CH3); 1.10 (s, 3H: CH3); 1.22 (t. J = 7.5 Hz, 3H: ethyl CH3); 1.62 (s, 1H: OH in 1); 1.69 (s, 3H: CH3); 1.89 and 2.63 (2 mts, 1 H each: CH ₂ in 6); 2.03 (d, J = 5.5 Hz, 1H: OH at 13); 2.07 (s, 3H: CH3); 2.27 (d, J = 9 Hz, 2H: CH ₂ at 14); 2.35 (d, J = 4.5 Hz, IH: OH at 7); 2.59 (mt, 2H: CH ₂ ethyl); 3.52 (s, 3H: OCH3); 3.84 (d. J = 7 Hz, 1 H: H at 3); 4.23 and 4.43 (2d, J = 9 Hz, 1H each: CH ₂ in 20); 4.25 (limit AB, J = 16 Hz, 2H: OCOCH ₂ O); 4.49 (mt, 1H: H at 7); 4.87 (mt, 1H: H at 13); 4.95 (broad d, J = 10 Hz, 1 H: H at 5); 5.53 (d, J = 7 Hz, 1H: H in 2); 6.42 (s, 1H: H at 10); 7.14 (dd, J = 4.5 and 3.5 Hz, 1H: H in 4 of thenoyl-2); 7.61 (dd, J = 4.5 and 1.5 Hz, 1H: H at 5 of thenoyl-2); 7.83 (dd, J = 3.5 and 1.5 Hz, 1H: H in 3 of thenoyl-2). Epoxy-5β, 20 hydroxy-lβ methoxyacetoxy-10β oxo-9 propanoyloxy-4α (thenoyloxy-2) -2α bis (triethylsilyloxy) -7β, 13α taxene-11 can be prepared as follows:

To a solution of 0.5 g of epoxy-5β, 20 dihydroxy-lβ.lOβ oxo-9 propanoyl-oxy-4 (thenoyloxy-2) -2α bis (triethylsUyloxy) -7β, 13α taxene-11 in 10 cm3 of pyridine, 0.286 cm 3 of methoxyacetyl chloride is added at a temperature in the region of 0 ° C. The reaction mixture is stirred for 10 hours at a temperature in the region of 20 ° C. and then 100 cm 3 of dichloromethane and 50 cm 3 of a saturated aqueous ammonium chloride solution are added. The organic phase is decanted, washed with 2 times 40 cm3 of a saturated aqueous solution of ammonium chloride, then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. The residue obtained (0.6 g) is purified by chromatography on 50 g of SiUce (0.063-0.2 mm) contained in a column 2 cm in diameter (eluent: ethyl acetate-cyclohexane: 5-95 by volume ) by collecting 10 cm3 fractions. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (0.27 kPa) at 40 ° C. 0.320 g of epoxy-5β, 20 hydroxy-lβ methoxyacetoxy-lOβ oxo-9 propanoyloxy-4cc (thénoyloxy-2) -2α bis (triethylsilyloxy) - 7β, 13 taxene-11 are obtained in the form of a white meringue. physical characteristics are as follows: - NMR spectrum * H (400 MHz, CDC1 ₃ , δ in ppm): from 0.50 to 0.70 (mt, 12 H ,: CH ₂ ethyl): 0.92 (t, J = 7.5 Hz, 9H: CH ₃ ethyl); 0.98 (t, J = 7.5 Hz, 9H: CH ₃ ethyl); 1.09 (s, 3H: CH ₃ ); 1.15 (s, 3H: CH ₃ ); 1.27 (t, J = 7.5 Hz, 3H: CH ₃ ethyl in 4); 1.59 (s, 1H: OH in 1); 1.65 (s, 3H: CH ₃ ); 1.85 and 2.52 (2 mts, 1H each CH ₂ in 6); 2.07 and 2.18 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 2.08 (s, 3H CH ₃ ); 2.58 (mt, 2H: CH ₂ ethyl 4); 3.50 (s, 3H: OCH _j ); 3.73 (d, J = 7 Hz, 1 H H at 3); 4.13 (AB limit, J = 16 Hz, 2H: OCOCH ₂ O); 4.20 and 4.41 (2d, J = 9 Hz, 1H each: CH ₂ in 20); 4.49 (dd, J = 11 and 7 Hz, 1H: H at 7); 4.89 (broad t, J = 9 Hz, 1H: H at 13); 4.91 (broad d, J = 10 Hz, 1 H: H at 5); 5.53 (d. J = 7 Hz, 1H: H in 2); 6.51 (s, 1H: H at 10); 7.12 (dd, J = 4.5 and 3 Hz, 1H: H 4 of thienoyl-2); 7.61 (d, J = 4.5 Hz, 1H: H at 5 of thienoyl-2); 7.83 (d, J = 3 Hz, 1 H: H at 3 thienoyl-2).

Epoxy-5β, 20 dihydroxy-lβ, 10β oxo-9 propanoyloxy-4α (2-thenoyloxy) -2 bis (triethylsilyloxy) -7β, 13α taxene-11 can be prepared as follows:

To a solution of 0.5 g of carbonyldioxy-lβ, 2α epoxy-5β, 20 methoxyacetoxy-lOβ oxo-9 propanoyloxy-4α bis (triethylsilyloxy) -7β, 13α taxene-11 in 20 cm3 of tetrahydrofuran, under an argon atmosphere, at a temperature in the region of -78 ° C., 1.5 cm3 of a 1M solution of 2-thienyllithium in tetrahydrofuran are added. The reaction mixture is stirred for 35 minutes at a temperature in the region of -78 ° C. and then 1 cm 3 of a saturated aqueous solution of ammonium chloride is added. At a temperature in the region of 20 ° C., 10 cm 3 of a saturated aqueous solution of ammonium chloride and 50 cm 3 of dichloromethane are added. The organic phase is decanted, washed with 2 times 10 cm3 of a saturated aqueous solution of sodium chloride and then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 0.65 g of a solid is obtained which is purified by chromatography on 90 g of silicon (0.063-0.2 mm) contained in a column 1 cm in diameter (eluent: ethyl acetate-cyclohexane: 10 -90 by volume) by collecting fractions of 10 cm3. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (0.27 kPa) at 40 ° C. We obtain 0.511 g of epoxy-5β, 20 dihydroxy-lβ, 10β oxo-9 propanoyloxy-4α (thénoyloxy-2) -2α bis (triéthyls_lyloxy) -7β, 13α taxene-11 in the form of a white meringue whose characteristics The physical properties are as follows: H NMR spectrum (600 MHz, CDC1 ₃ , δ in ppm): 0.57 (mt, 6 H: CH ₂ ethyl); 0.68 (mt, 6H: CH ₂ ethyl); 0.95 (t, J = 7.5 Hz, 9H: CH ₃ ethyl); 1.01 (t, J = 7.5 Hz, 9H: CH ₃ ethyl); 1.07 (s, 3H: CH ₃ ); 1.17 (s, 3H: CH ₃ ); 1.27 (t. J = 7.5 Hz, 3H: CH ₃ ethyl in 4); 1.73 (s, 3H: CH ₃ ); 1.90 and 2.47 (2 mts, 1 H each: CH ₂ in 6); 2.02 (s, 3H: CH ₃ ); 2.09 and 2.18 (2 dd, J = 16 and 9 Hz. 1 H each: CH ₂ in 14); 2.60 (mt, 2H: CH ₂ ethyl in 4); 3.82 (d, J = 7 Hz, 1H: H at 3); 4.24 and 4.44 (2d, J = 9 Hz. 1 H each: CH ₂ in 20); 4.26 (d, J = 0.5 Hz, 1 H: OH at 10); 4.42 (dd, J = 11 and 7 Hz, 1H: H at 7); 4.93 (broad d, J = 10 Hz, 1 H: H at 5); 4.97 (wide t, J = 9 Hz, 1H: H at 13); 5.13 (d, J = 0.5 Hz, 1 H: H at 10); 5.53 (d, J = 7 Hz, 1H: H in 2); 7.15 (dd, J = 4.5 and 3 Hz, 1H: H 4 of thienoyl-2); 7.63 (d, J = 4.5 Hz, 1H: H at 5 of thenoyl-2); 7.85 (d, J = 3 Hz, 1H: H in 3 of thienoyl-2).

EXAMPLE 3

To a solution of 154 mg of tert-butoxycarbonylamino-3 hydroxy-2 phenyl-3 propionate- (2R, 3S) of benzoyloxy-2α butanoyloxy-4α epoxy-5β, 20 hydroxy-lβ methoxyacetoxy- lOβ oxo-9 trifluoromethanesulfonyloxy-7β taxene -11 yl-13α in 2 cm3 of acetonitrile and 200 μl of tetrahydrofuran, 96 mg of powdered 4A molecular sieve, 225 mg of sodium chloride are successively added. The reaction mixture is kept under stirring at a temperature in the region of 75 ° C. for 5 hours then, at a temperature in the region of 20 ° C, added with 15 cm3 of dichloromethane and 10 cm3 of a saturated aqueous solution of sodium chloride. The organic phase is decanted, washed with 2 times 20 cm3 of a saturated aqueous solution of sodium chloride and then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 133 mg is obtained which is purified by chromatography on 80 g of silica (0.063-0.2 mm) contained in a column 1 cm in diameter, eluting with a dichloromethane-methanol mixture (98-2 by volume) and in collecting 10 cm3 fractions. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. We obtain 63 mg of tert-butoxycarbonylamino-3 hydroxy-2 phenyl-3 propionate- (2R, 3S) of benzoyloxy-2α but__noyloxy-4α epoxy-5β, 20 hydroxy-lβ methoxyacetoxy-lOβ methylene-7β, 8 nor-19 oxo -9 taxene-11 yle-13α in the form of a white meringue and the physical characteristics of which are as follows: - 1 H NMR spectrum (400 MHz; CDC1 ₃ ; δ in ppm): 0.92 (t, J = 7.5 Hz, 3H: propyl CH ₃ ); 1.26 (s, 6H: CH ₃ ); 1.31 (s, 9H: C (CH ₃ ) ₃ ); 1.42 (mt, 1H: H at 7); 1.71 and 2.26 (2 mts, 1 H each: CH ₂ in 19); from 1.60 to 1.85 (mt, 2H: propyl CH ₂ ); 1.86 (s, 3H: CH ₃ ); 1.88 (s, 1H: OH in 1); 2.12 and 2.50 (respectively d wide and mt, J = 16 Hz, IH each: CH ₂ in 6); 2.23 and 2.39 (respectively mt and dd, J = 16 and 9 Hz, 2H: CH ₂ at 14); 2.49 and 2.65 (2 mts, 1 H each: OCOCH ₂ of propyl); 3.25 (mt, 1H: OH in 2 '); 3.51 (s, 3H: OCH ₃ ); 4.05 and 4.32 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.10 (d, J = 7 Hz, 1 H: H at 3); 4.16 and 4.22 (2 d, J = 16 Hz, 1 H each: OCOCH ₂ O); 4.62 (mt, 1H: H in 2 '); 4.68 (broad d, J = 4.5 Hz, 1 H H in 5); 5.25 (broad d, J = 10 Hz, 1 H: H in 3 '); 5.30 (d, J = 10 Hz, 1 H: CONH) 5.65 (d, J = 7 Hz, 1 H: H in 2); 6.23 (broad t, J = 9 Hz, 1 H: H at 13); 6.42 (s, 1H H at 10); from 7.25 to 7.45 (mt, 5H: aromatic H in 3 '); 7.51 (t, J = 7.5 Hz, 2H OCOC ₆ H ₅ H in meta); 7.62 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.16 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

Tert-butoxycarbonylamino-3 hydroxy-2 phenyl-3 propionate- (2R, 3S) benzoyloxy-2α butanoyloxy-4α epoxy-5β, 20 hydroxy-lβ methoxyacetoxy-lOβ oxo-9 trifluoromethanesulfonyloxy-7β taxene-11 yle-13α can be prepared as follows:

A solution of 400 mg of tert-butoxycarbonyl-3 (4-methoxyphenyl) -2 phenyl-4 oxazolidine-1,3 carboxylate-5 (2R.4S.5R) of benzoyloxy-2α butanoyloxy-4 epoxy-5β, 20 hydroxy -lβ methoxyacetoxy-lOβ oxo-9 trifluoromethanesulfonyloxy-7β taxene-11 yle-13α in 6.4 cm3 of a 0.1N solution of hydrochloric ethanol is maintained under stirring at a temperature close to 0 ° C for 6 hours and then at a temperature close to 20 ° C for 15 hours. The reaction medium is concentrated to dryness under reduced pressure (2.7 kPa) at 20 ° C. The crude reaction product is dissolved in 20 cm3 of dichloromethane and 10 cm3 of a saturated aqueous solution of sodium bicarbonate. The aqueous phase is separated by decantation and then extracted with 2 times 20 cm3 of dichloromethane. The organic phases are combined, washed with 30 cm3 of distilled water and then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 20 ° C. 410 mg of a product are obtained which is purified by chromatography on 60 g of SiUce (0.063-0.2 mm) contained in a column 1 cm in diameter, eluting with a mixture (dichloromethane-methanol 98.5- 1.5 by volume) and collecting 10 cm3 fractions. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 20 ° C. We obtain 307 mg of tert-butoxycarbonylamino-3 hydroxy-2-phenyl-3 propionate- (2R, 3S) of benzoyloxy-2α butanoyloxy-4α epoxy- 5β, 20 hydroxy-lβ methoxyacetoxy- lOβ oxo-9 trifluoromethanesulfonyloxy-7β taxene-11 yle-13cc in the form of a white meringue and the physical characteristics of which are as follows:

- NMR spectrum * H (400 MHz; CDC1 ₃ ; δ in ppm): 0.93 (t, J = 7.5 Hz, 3H: CH ₃ of propyl); 1.22 (s, 3H: CH ₃ ); 1.24 (s, 3H: CH ₃ ); 1.35 (s, 9H: C (CH ₃ ) ₃ ); from 1.65 to 1.85 (mt, 2H: CH ₂ of propyl); 1.74 (s, 1H: OH in 1); 1.88 (s, 3H: CH ₃ ); 2.04 (s, 3H: CH ₃ ); 2.25 and 2.86 (2 mts, 1 H each: CH ₂ in 6); 2.33 (d, J = 9 Hz, 2H: CH ₂ at 14); 2.52 and 2.66 (2 mts, J = 14.5 and 6.5 Hz, 1 H each: OCOCH ₂ of propyl); 3.33 (d, J = 4 Hz, 1H: OH in 2 '); 3.52 (s, 3H: OCH ₃ ); 3.94 (d, J = 7 Hz, 1H: H at 3); 4.16 and 4.21 (2 d, J = 16 Hz, 1 H each: OCOCH ₂ O); 4.19 and 4.35 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.62 (mt, 1H: H in 2 '); 4.86 (broad d, J = 10 Hz, 1 H: H at 5); 5.22 (broad d, J = 10 Hz, 1H: H in 3 '); 5.33 (d, J = 10 Hz, 1 H: CONH); 5.50 (dd, J = 11 and 8 Hz, 1H: H at 7); 5.73 (d, J = 7 Hz, 1H: H in 2); 6.16 (broad t, J = 9 Hz, 1H: H at 13); 6.71 (s, 1H: H at 10); from 7.25 to 7.45 (mt, 5H: aromatic H in 3 '); 7.51 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.63 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.12 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

Tert-butoxycarbonyl-3 (4-methoxy-phenyl) -2 4-phenyl-oxazolidine- 1,3-carboxylate-5 (2R, 4S, 5R) of benzoyloxy-2α butanoyloxy-4α epoxy-5β, 20 hydroxy- lβ methoxyacetoxy-lOβ oxo-9 trifluoromethanesulfonyloxy-7β taxene-11 yle-13α can be prepared as follows: To a solution of 400 mg of 2-benzoyloxy-butanoyloxy-4α dihydroxy-lβ, 13α epoxy-5β, 20 methoxyacetoxy-lOβ oxo-9 trifluoromethanesulfonyloxy-7β taxene-11 is added successively 247 mg of tert-butoxycarbonyl-3 (4-methoxyphenyl) -2 phenyl-4 oxazolidine-1,3 carboxyUque-5 (2R, 4S, 5R), 186 mg of dicyclohexylc_ιrt> cdiimide and 12.5 mg of 4- d-meΛylarninopyridine. The reaction mixture is stirred for 15 hours, under an argon atmosphere, at a temperature in the region of 20 ° C., then concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 1 g of a product is obtained which is purified by chromatography on 100 g of silicon (0.063-0.2 mm) contained in a column 3 cm in diameter, eluting with a dichloromethane-methanol mixture (95-5 in volumes) and collecting 12 cm3 fractions. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 410 mg of tert-butoxycarbonyl-3 (4-methoxy-phenyl) -2 phenyl-4 oxazoUdine-1,3 carboxylate-5 (2R, 4S, 5R) of benzoyloxy-2α butanoyloxy-4α epoxy- 5β, 20 hydroxy- are obtained. lβ methoxyacetoxy-lOβ oxo-9 tri_luorométhanesulfonyloxy-7β taxene-11 yle-13α in the form of a white meringue and whose physical characteristics are the following:

- NMR spectrum * H (400 MHz; CDC1 ₃ ; δ in ppm): 0.92 (t, J = 7.5 Hz, 3H: CH ₃ of propyl); 1.07 (s, 9H: C (CH ₃ ) ₃ ); 1.17 (s, 6H: CH ₃ ); 1.55 to 1.70 (mt, 3H: propyl CH ₂ and OH in 1); 1.64 (s, 3H: CH ₃ ); 1.84 (s, 3H: CH ₃ ); 2.08 and 2.15 to 2.30 (respectively dd and mt, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); from 2.15 to 2.30 and 2.82 (2 mts, 1 H each: CH ₂ in 6); 2.15 to 2.30 (mt, 2H: propyl OCOCH ₂ ); 3.51 (s, 3H: OCH ₃ ); 3.82 (s, 3H: ArOCH ₃ ); 3.83 (d, J = 7 Hz, 1 H: H at 3); 4.12 and 4.28 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.14 and 4.22 (2 d, J = 16 Hz, 1 H each: OCOCH ₂ O); 4.52 (broad d, J = 4.5 Hz, 1H: H in 2 '); 4.79 (broad d, J = 10 Hz, 1 H: H at 5); 5.35 to 5.50 (mt, 1H: H in 3 '); 5.44 (dd, J = 9 and 7 Hz. 1H: H at 7); 5.67 (d, J = 7 Hz, 1H: H in 2); 5.99 (wide t, J = 9 Hz, 1 H: H at 13); 6.40 (mf, 1H: H in 5 "); 6.59 (s, 1H: H in 10); 6.92 (d, J = 8.5 Hz, 2H: H aromatic in OCH- ortho); 7.25 to 7.45 (mt, 5H: aromatic H in 3 '); 7.37 (d, J = 8.5 Hz, 2H: H aromatic in OCH ₃ meta); 7.48 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.63 (t. J = 7.5 Hz, IH: OCOC ₆ H ₅ H in para); 8.11 (d, J = 7 , 5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

Benzoyloxy-2α butanoyloxy-4α dihydroxy-lβ, 13α epoxy-5β, 20 methoxyacetoxy-lOβ oxo-9 trifluoromethanesulfonyloxy-7β taxene-11 can be prepared as follows: To a solution of 389 mg of 2-benzoyloxy-4-butanoyloxy-epoxy-5β, 20 methoxyacetoxyl-10β oxo-9 trihydroxy-lβ, 7β, 13α taxene-11 in 6 cm3 of anhydrous dichloromethane and 390 μl of pyridine, maintained under an atmosphere of 'argon, at a temperature close to 0 ° C, 410 μl of trifluoromethanesulfonic anhydride are added dropwise. The orange solution obtained is stirred for 15 minutes at a temperature close to 0 ° C. and then added with 3 cm 3 of water and 50 cm 3 of dichloromethane. The organic phase is decanted, washed with 2 times 40 cm3 of a saturated aqueous solution of sodium chloride and then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 510 mg is obtained which is purified by chromatography on 70 g of silica (0.063-0.2 mm) contained in a column 1 cm in diameter, eluting with a dichloromethane / methanol mixture (95-5 by volume) and in collecting 10 cm3 fractions. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 410 mg of benzoyloxy-2 butanoyloxy-4 dihydroxy-lβ, 13α epoxy-5β, 20 methoxyacetoxy-lOβ oxo-9 trifluoromethane-sulfonyloxy-7β taxene-11 are obtained in the form of a white meringue, the physical characteristics of which are as follows :

- NMR spectrum H (400 MHz; CDC1 ₃ ; δ in ppm): 1.06 (t, J = 7.5 Hz, 3H: CH ₃ of propyl); 1.06 (s, 3H: CH ₃ ); 1.20 (s, 3H: CH ₃ ); 1.63 (s, 1H: OH in 1); 1.77 (mt, 2H: propyl CH ₂ ); 1.87 (s, 3H: CH ₃ ); 2.18 (d, J = 5 Hz, 1 H: OH at 13); 2.15 to 2.40 (AB Umite, 2H: CH ₂ 14); 2.15 to 2.40 and 2.89 (2 mts, 1 H each: CH ₂ 6); 2.25 (s, 3H: CH ₃ ); 2.59 (limit AB, J = 16 and 7.5 Hz, 2H: propyl OCOCH ₂ ); 3.51 (s, 3H: OCH ₃ ); 4.03 (d, J = 7 Hz, 1H: H 3); 4.16 and 4.24 (2 d, J = 16 Hz, 1 H each: OCOCH ₂ O); 4.18 and 4.35 (2 d, J = 9 Hz, 1 H each: CH ₂ 20); 4.85 (mt, 1H: H 13); 4.92 (broad d, J = 10 Hz, 1 H: H 5); 5.57 (dd, J = 10.5 and 7 Hz, 1H: H 7); 5.68 (d, J = 7 Hz, 1H: H 2); 6.73 (s, 1H: H 10); 7.51 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H meta); 7.63 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H para); 8.10 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H ortho).

Benzoyloxy-2 butanoyloxy-4α epoxy-5β, 20 methoxyacetoxy-10β oxo-9 trihydroxy- 1 β, 7β, 13α taxene-11 can be prepared as follows:

To a solution of 580 mg of benzoyloxy-2α butanoyloxy-4α bis (triethylsilyloxy) -7β, 13α epoxy-5β, 20 hydroxy-lβ methoxyacetoxy-lOβ oxo-9 taxene-11 in 5 cm3 of dichloromethane, one adds, at a temperature near 20 ° C, 5.5 cm3 of triethylamine-hydrofluoric acid complex. The reaction mixture is stirred for 23 hours at a temperature in the region of 20 ° C., then 50 cm 3 are added. dichloromethane and 100 cm3 of a saturated aqueous solution of sodium hydrogencarbonate. The organic phase is decanted, washed with 2 times 20 cm3 of a saturated aqueous solution of sodium chloride and then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 520 mg is obtained which is purified by chromatography on 70 g of SiUce (0.063-0.2 mm) contained in a column 2 cm in diameter, eluting with a methanol-dichloromethane mixture (5-95 by volume) and in collecting fractions of 10 cm3. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 389 mg of benzoyloxy-2α butanoyloxy-4α epoxy-5β, 20 methoxyacetoxy-10β oxo-9 trihydroxy-lβ, 7β, 13α taxene-11 are obtained in the form of a white meringue, the physical characteristics of which are as follows: 1 H NMR (400 MHz; CDC1 ₃ ; δ in ppm): 1.05 (t, J = 7.5 Hz, 3H: propyl CH ₃ ); 1.11 (s, 6H: CH ₃ ); 1.67 (s, 3H: CH ₃ ); 1.71 (s, 1H: OH in 1); 1.75 (mt, 2H: propyl CH ₂ ); 1.85 and 2.45 to 2.65 (2 mts, 1 H each: CH ₂ in 6); 2.05 (s, 3H: CH ₃ ); 2.24 (d, J = 5 Hz, 1H: OH); 2.28 (limit AB, J = 16 and 9 Hz, 2H: CH ₂ in 14); 2.40 (d. J = 4 Hz, 1H: OH); 2.56 (AB limit, 2H: propyl OCOCH ₂ ); 3.51 (s, 3H: OCH ₃ ); 3.88 (d, J = 7 Hz, 1 H: H at 3); 4.15 and 4.32 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.23 (limit AB, J = 16 Hz, 2H: OCOCH ₂ O); 4.48 (mt, 1H: H at 7); 4.86 (mt, 1H: H at 13); 4.94 (broad d, J = 10 Hz, 1 H: H at 5); 5.62 (d. J = 7 Hz. 1H: H in 2); 6.43 (s, 1H: H at 10); 7.49 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.62 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.12 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

Benzoyloxy-2α butanoyloxy-4α bis (triethylsilyloxy) -7β, 13 epoxy-5β, 20 hydroxy-lβ methoxyacetoxy-lOβ oxo-9 taxene-11 can be prepared as follows:

To a solution of 906 mg of 2-benzoyloxy-butanoyloxy-4α dihydroxy-lβ, 10β bis (triethylsilyloxy) -7β, 13α epoxy-5β, 20 oxo-9 taxene-11 in 18 cm3 of pyridine, 1.03 cm3 of methoxyacetyl chloride at a temperature close to 0 ° C. The reaction mixture is stirred for 14 hours at a temperature in the region of 20 ° C., then 20 cm 3 of dichloromethane and 20 cm 3 of a saturated aqueous ammonium chloride solution are added. The organic phase is decanted, washed with 4 times 20 cm3 of a saturated aqueous solution of copper sulphate, 2 times 40 cm3 of a saturated aqueous solution of ammonium chloride then dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 800 mg of a product are obtained which is purified by chromatography on 100 g of SiC (0.063-0.2 mm) contained in a column 2.5 cm in diameter, eluting with a methanol-dichloromethane mixture (2-98 by volume) and collecting 15 cm 3 fractions. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 580 mg of benzoyloxy-2α butanoyloxy-4α bis (ditriethylsilyloxy) -7β, 13α epoxy-5β, 20 hydroxy-lβ methoxyacetoxy-10β oxo-9 taxene-11 are obtained in the form of a white meringue, the physical characteristics of which are following:

- H NMR spectrum (400 MHz; CDC1 _3. δ in ppm): 0.60 and 0.68 (2 mts, 6H each: ethyl CH ₂ ); 0.95 and 1.04 (2 1, J = 7.5 Hz, 9H each: ethyl CH ₃ ); 1.09 (t, J = 7.5 Hz, 3H: propyl CH ₃ ); 1.13 (s, 3H: CH ₃ ); 1.18 (s, 3H: CH _j ); 1.64 (s, 1H: OH enl); 1.68 (s, 3H: CH ₃ ); 1.84 (mt, 2H: propyl CH ₂ ); 1.89 and 2.50 (2 mts, 1 H each: CH ₂ in 6); 2.11 and 2.23 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 2.13 (s, 3H: CH ₃ ); 2.55 (mt, 2H: propyl OCOCH ₂ ); 3.53 (s, 3H: O CH ₃ ); 3.82 (d, J = 7 Hz, 1H: H at 3); 4.13 and 4.31 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.16 (limit AB, J = 16 Hz, 2H: OCOCH ₂ O); 4.52 (dd, J = 11 and 7 Hz, 1H: H at 7); 4.91 (mt, 1H: H at 13); 4.93 (broad d, J = 10 Hz, 1 H: H at 5); 5.64 (d, J = 7 Hz, 1H: H in 2); 6.54 (s, 1H: H at 10); 7.47 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.61 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.11 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho). Benzoyloxy-2 butanoyloxy-4α dihydroxy-lβ, 10β bis (triethylsilyloxy) -

7β, 13α epoxy-5β, 20 oxo-9 taxene-11 can be prepared as follows:

To a solution of 907 mg of butanoyloxy-4α carbonate-lβ, 2 bis (triethylsilyloxy) -7β, 13α epoxy-5β, 20 methoxyacetoxy- lOβ oxo-9 taxene-11 in 50 cm3 of anhydrous tetrahydrofuran, 2.34 cm3 are added. of a 1M solution of phenyUithium in tetrahydrofuran at a temperature in the region of -78 ° C. The reaction mixture is stirred for 1 hour at a temperature in the region of -78 ° C. and then 10 cm 3 of a saturated aqueous solution of ammonium chloride are added. At a temperature in the region of 20 ° C., 20 cm 3 of a saturated aqueous solution of ammonium chloride and 50 cm 3 of dichloromethane are added. The organic phase is decanted, washed with 2 times 10 cm3 of a saturated aqueous solution of sodium chloride and then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 1.3 g are obtained which are purified by chromatography on 150 g of silica (0.063-0.2 mm) contained in a column 5 cm in diameter, eluting with an ethyl acetate-cyclohexane mixture (10-90 by volume) and by collecting fractions of 18 cm3. Fractions containing only the product sought are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 906 mg of benzoyloxy-2α butanoyloxy-4α dihydroxy-lβ.lOβ ditriethylsUyloxy- 7β, 13α epoxy-5β, 20 oxo-9 taxene-11 are obtained in the form of a white meringue, the physical characteristics of which are as follows: 1 H NMR (400 MHz; CDCl ₃ ; δ in ppm): 0.56 and 0.67 (2 mts, 6H each: ethyl CH ₂ ); 0.95 and 1.03 (2 1, J = 7.5 Hz, 9H each: ethyl CH ₃ ); 1.08 (s, 3H: CH ₃ ); 1.10 (t, J = 7.5 Hz, 3H: propyl CH ₃ ); 1.18 (s, 3H: CH ₃ ); 1.60 (s, 1H: OH in 1); 1.73 (s. 3H: CH ₃ ); 1.84 (mt, 2H: propyl CH ₂ ); 1.91 and 2.48 (2 mts, 1 H each: CH ₂ in 6); 2.03 (s, 3H: CH ₃ ); 2.11 and 2.22 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 2.58 (mt, 2H: propyl OCOCH ₂ ); 3.87 (d, J = 7 Hz, 1 H: H at 3); 4.18 and 4.32 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.28 (d, J = 2 Hz, 1 H: OH at 10); 4.42 (dd, J = 10.5 and 6.5 Hz, 1H: H at 7); 4.93 (broad d, J = 10 Hz, 1 H: H at 5); 4.98 (t. J = 9 Hz, 1H: H at 13); 5.17 (d, J = 2 Hz, 1 H: H at 10); 5.62 (d, J = 7 Hz, 1H: H in 2); 7.49 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.61 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.12 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ in ortho).

Butanoyloxy-4 carbonate- lβ, 2α bis (triethylsUyloxy) -7β, 13α epoxy-

5β, 20 methoxyacetoxy-10β oxo-9 taxene-11 can be prepared as follows:

To a solution of 870 mg of carbonate-lβ, 2c. bis (triethylsUyloxy) -7β, 13α epoxy-5β, 20 hydroxy-4α methoxyacetoxy-10β oxo-9 taxene-11 in 15 cm3 of dichloromethane, 1.46 g of 4-dimemylaminopyridine and 3.90 cm3 of butyric anhydride are added . The reaction medium is heated to a temperature in the region of 42 ° C for 45 hours. 50 cm3 of a saturated aqueous solution of sodium chloride and 50 cm3 of dichloromethane are added. The organic phase is decanted, washed with 2 times 40 cm3 of a saturated aqueous solution of sodium chloride and then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 2.0 g are obtained which are purified by chromatography on 170 g of SiUce (0.063-0.2 mm) contained in a column 3 cm in diameter, eluting with an ethyl acetate-cyclohexane mixture (5-95 by volume) and collecting 15 cm3 fractions. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 1.00 g of butanoyloxy-4α carbonate- lβ, 2 ditriethylsilyloxy-7β, 13α epoxy-5β, 20 methoxyacetoxy-lOβ oxo-9 taxene-11 are obtained in the form of a white meringue, the physical characteristics of which are as follows: - ¹ H NMR spectrum (400 MHz; CDC1 _3: δ in ppm): from 0.50 to 0.70 (mt, 12H: ethyl CH ₂ ); from 0.90 to 1.10 (mt, 21H: CH _3, ethyl and propyl CH _3); 1.18 (s, 3H: CH ₃ ); 1.28 (s, 3H: CH ₃ ); 1.73 (mt, 2H: propyl CH ₂ ); 1.75 (s, 3H: CH ₃ ); 1.92 and 2.59 (2 mts, 1 H each: CH ₂ in 6); 2.13 (s, 3H: CH ₃ ); 2.14 and 2.35 to 2.45 (respectively dd and mt, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); from 2.35 to 2.45 (mt, 2H: propyl OCOCH ₂ ); 3.42 (d, J = 6.5 Hz, 1 H: H at 3); 3.51 (s, 3H: OCH ₃ ); 4.18 (s, 2H: OCOCH ₂ O); 4.46 (dd, J = 10 and 6.5 Hz, 1H: H at 7); 4.50 and 4.63 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.51 (d, J = 6.5 Hz, 1H: H in 2); 4.93 (broad d, J = 10 Hz, 1 H: H at 5); 5.02 (broad t, J = 9 Hz, 1 H: H at 13); 6.51 (s, 1H: H at 10).

EXAMPLE 4

By operating as in Example 3, and starting from tert-butoxycarbonyl-3-amino-2-hydroxy-3-phenyl-propionate- (2R, 3S) of benzoyloxy-2α phenylacetoxy-4α epoxy-5β, 20 hydroxy-1β methoxyacetoxy- 10β oxo-9 trifluoromethanesulfonyloxy-7β taxene-11 yle-13α, we obtain tert-butoxycarbonylamino-3 hydroxy-2 phenyl-3 propionate- (2R, 3S) of benzoyloxy-2α epoxy-5β, 20 hydroxy-lβ methoxyacetoxy-lOβ methylene-7β, 8 nor-19 oxo-9 phenylacetoxy-4α taxene-11 yle-13α the characteristics of which are as follows:

- 1 H NMR spectrum (400 MHz; CDC1 ₃ ; δ in ppm): 1.24 (s, 15H: CH ₃ - CH ₃ and C (CH ₃ ) ₃ ); 1.40 (mt, 1H: H at 7); 1.66 and 2.24 (2 dd, J = 6 and 5 Hz and J = 10 and 6 Hz,

IH each: CH ₂ in 19); 1.92 (s, 1H: OH in 1); 1.96 (s. 3H: CH ^; 2.07 and 2.46 (respectively d large and dt, J = 16 Hz and J = 16 and 4.5 Hz, IH each: CH ₂ in 6); 2, 32 and 2.54 (respectively dd and dd large, J = 16 and 9 Hz, IH each: CH ₂ in 14); 3.24 (mt, IH: OH in 2 '); 3.53 (s, 3H: OCH ₃ ); 3.90 and 4.14 (2 d, J = 15 Hz, IH each: OCOCH-Ar); 4.00 and 4.16 (2 d, J = 9 Hz, IH each: CH ₂ in 20); 4.20 and 4.26 (2 d, J = 16 Hz, IH each: OCOCH ₂ O); 4.23 (d, J = 7 Hz, IH: H in 3); 4.55 (d wide, J = 4.5 Hz. IH: H in 5); 4.63 (mt, IH: H in 2 '); 5.31 (AB limit, 2H: H in 3' and CONH); 5.71 (d, J = 7 Hz, IH: H in 2); 6.34 (wide t, J = 9 Hz, IH: H in 13); 6.44 (s, IH: H in 10); from 7, 10 to 7.45 (mt, 10H: aromatic H and aromatic H in 3 '); 7.51 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.63 (t, J = 7.5 Hz, IH: OCOC ₆ H ₅ H in para); 8.16 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

By operating under conditions analogous to those described in Example 3, tert-butoxycarbonylamino-3-hydroxy-3-phenyl-propionate- (2R, 3S) is prepared. benzoyloxy-2α epoxy-5β, 20 hydroxy-lβ methoxyacetoxy- lOβ oxo-9 phenylacetoxy- A trifluoromethanesulfonyloxy-7β taxene-11 yl-13α, the characteristics of which are as follows:

- 1 H NMR spectrum (400 MHz; CDC1 ₃ ; δ in ppm): 1.24 (s, 6H: CH ₃ ); 1.36 (s, 9H: C (CH ₃ ) ₃ ); 1.74 (s, 1H: OH in 1); 1.87 (s, 3H: CH ₃ ); 2.14 (s, 3H: CH _j ); 2.19 and 2.83 (2 mts, 1 H each: CH ₂ in 6); 2.39 and 2.48 (2 broad dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 3.38 (d, J = 4.5 Hz, 1H: OH in 2 '); 3.53 (s, 3H: OCH,); 3.90 and 4.14 (2 d, J = 15 Hz, 1 H each: OCOCH ₂ Ar); 4.01 (d, J = 7 Hz, 1 H: H at 3); 4.11 and 4.20 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.17 and 4.25 (2 d, J = 16 Hz, 1 H each: OCOCH ₂ O); 4.65 (mt, 1H: H in 2 '); 4.68 (d wide, J = 10 Hz, IH: H in

5); 5.28 (broad d, J = 10 Hz, 1 H: H in 3 '); 5.35 (d, J = 10 Hz, 1 H: CONH); 5.50 (dd, J = 10 and 7 Hz, 1H: H at 7); 5.77 (d, J = 7 Hz, 1H: H in 2); 6.28 (broad t, J = 9 Hz, 1 H: H at 13); 6.74 (s, 1H: H at 10); from 7.15 to 7.45 (mt, 10H: aromatic H and aromatic H in 3 '); 7.51 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.66 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.08 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

By operating under conditions analogous to those described in Example 3, tert-butoxycarbonyl-3 (4-methoxy-phenyl) -2 phenyl-4-oxazolidine-1,3 carboxylate-5 (2R.4S.5R) is prepared. benzoyloxy-2α epoxy-5β, 20 hydroxy-lβ methoxy¬ acetoxy- lOβ oxo-9 phenylacetoxy-4α trifluoromethanesulfonyloxy-7β taxene-11 yle-13α, the characteristics of which are as follows:

- 1 H NMR spectrum (400 MHz; CDC1 ₃ ; a temperature of 333 ° K, δ in ppm): 1.06 (s, 9H: C (CH ₃ ) ₃ ); 1.12 (s, 3H: CH ₃ ); 1.24 (s, 3H: CH ₃ ); 1.66 (s, 1H: OH in 1); 1.83 (s, 3H: CH ₃ ); 1.86 (s, 3H: CH ₃ ); 2.14 and 2.79 (2 mts, IH each: CH ₂ in

6); 2.24 and 2.30 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 3.45 and 3.58 (2 d, J = 15 Hz, 1 H each: OCOCH-Ar); 3.54 (s, 3H: OCH ₃ ); 3.85 (s, 3H: ArOCH ₃ );

3.94 (d, J = 7 Hz, 1H: H at 3); 4.08 and 4.17 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.14 and 4.22 (2 d, J = 16 Hz, 1 H each: OCOCH ₂ O); 4.59 (broad d, J = 10 Hz, 1 H: H at 5); 4.63 (d, J = 5.5 Hz, 1H: H in 2 '); 5.45 (d, J = 5.5 Hz, 1H: H in 3 '); 5.47 (mt, 1H: H at 7); 5.72 (d, J = 7 Hz, 1H: H in 2); 6.14 (broad t, J = 9 Hz, 1 H: H at 13); 6.34 (s, 1H: H in 5 '); 6.65 (s, 1H: H at 10); 6.94 (d, J = 8.5 Hz, 2H: H aromatic in ortho of OCH ₃ ); from 7.20 to 7.45 (mt, 12H: aromatic H and aromatic H in meta of OCH ₃ and aromatic H in 3 '); 7.48 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.64 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 7.98 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho) By operating under conditions analogous to those described in Example 3, benzoyloxy-2α dihydroxy-lβ, 13α epoxy-5β, 20 methoxyacetoxy-lOβ oxo-9 phenylacetoxy-4α trifluoromethanesulfonyloxy-7β taxene-11 are prepared, the characteristics of which are the following: - 1 H NMR spectrum (400 MHz; CDC1 ₃ ; δ in ppm): 1.07 (s, 3H: CH ₃ ); ^' 1.21 (s, 3H: CH ₃ ); 1.64 (s, 1H: OH in 1); 1.87 (s, 3H: CH ₃ ); 2.18 (d, J = 4.5 Hz, 1H: OH enl3); 2.20 and 2.88 (2 mts, 1 H each: CH ₂ in 6); 2.30 (s, 3H: CH ₃ ); from 2.25 to 2.35 (mt, 2H: CH ₂ in 14); 3.52 (s, 3H: OCH ₃ ); 3.90 and 3.97 (2 d, J = 15 Hz, 1 H each: OCOCH ₂ Ar); 4.08 (d, J = 7 Hz, 1 H: H at 3); 4.12 and 4.27 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.16 and 4.24 (2 d, J = 16 Hz, 1 H each: OCOCH ₂ O); 4.80 (broad d, J = 10 Hz, 1 H: H at 5); 4.92 (mt, 1H: H at 13); 5.55 (dd, J = 10 and 6.5 Hz, 1H: H at 7); 5.71 (d, J = 7 Hz, 1H: H in 2); 6.74 (s, 1H: H at 10); from 7.25 to 7.45 (mt, 5H: aromatic H); 7.48 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.64 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.03 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

By operating under conditions analogous to those described in Example 3, benzoyloxy-2α epoxy-5β, methoxyacetoxy-10β oxo-9 phenylacetoxy-Ao is prepared. trihydroxy-lβ, 7β, 13 taxene-11, the characteristics of which are as follows: - 1 H NMR spectrum (400 MHz; CDC1 _3; Ô in ppm): 1.12 (s, 3H: CH ₃ ); 1.14 (s, 3H: CH ₃ ); 1.66 (s, 1H: OH in 1); 1.67 (s, 3H: CH ₃ ); 1.84 and 2.56 (2 mts, 1 H each: CH ₂ in 6); 2.11 (s, 3H: CH ₃ ); from 2.20 to 2.45 (2 mts, 1 H each: OH); 2.35 and 2.42 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 3.54 (s, 3H: OCH ₃ ); 3.94 (AB limit, J = 15 Hz, 2H: OCOCH ₂ Ar); 3.94 (d, J = 7 Hz, 1H: H at 3); 4.12 and 4.25 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.26 (AB Umite, J = 16 Hz, 2H: OCOCH ₂ O); 4.50 (mt, 1H: H at 7); 4.87 (broad d, J = 10 Hz, 1 H: H at 5); 4.96 (mt, 1H: H at 13); 5.66 (d, J = 7 Hz, 1H: H in 2); 6.44 (s, 1H: H at 10); from 7.25 to 7.45 (mt, 5H: aromatic H); 7.47 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.62 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.04 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

By operating under conditions analogous to those described in Example 3, benzoyloxy-2α bis (triethylsilyloxy) -7β, 13α epoxy-5β, 20 hydroxy-lβ methoxyacetoxy-lOβ oxo-9 phenylacetoxy-4α taxene-11 is prepared. the characteristics are as follows: - 1 H NMR spectrum (400 MHz; CDC1 ₃ ; δ in ppm): 0.60 and 0.72 (2 mts, 6H each: ethyl CH ₂ ); 0.94 and 1.05 (2 1, J = 7.5 Hz, 9H each: ethyl CH ₃ ); 1.15 (s, 3H: CH ₃ ); 1.22 (s, 3H: CH ₃ ); 1.66 (s, 3H: CH ₃ ); 1.69 (broad s, 1H: OH in 1); 1.84 and 2.51 (2 mts, 1 H each: CH ₂ in 6); 2.20 (s, 3H: CH ₃ ); 2.24 and 2.36 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 3.54 (s, 3H: OCH ₃ ); 3.82 and 3.96 (2 d, J = 15 Hz, 1 H each: OCOCH-Ar); 3.89 (d, J = 7 Hz, 1H: H at 3); 4.06 and 4.16 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.20 (AB Umite, J = 16 Hz, 2H: OCOCH ₂ O); 4.52 (dd, J = 10 and 6 Hz, 1H: H at 7); 4.79 (broad d, J = 10 Hz, 1 H: H at 5); 4.96 (wide t, J = 9 Hz, 1H: H at 13); 5.66 (d, J = 7 Hz, 1H: H in 2); 6.58 (s, 1H: H at 10); from 7.25 to 7.45 (mt, 7H: aromatic H and OCOC ₆ H ₅ H in eta); 7.61 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.00 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

By operating under conditions analogous to those described in Example 3, benzoyloxy-2α dihydroxy-lβ.lOβ bis (triethylsUyloxy) -7β, 13 epoxy-5β, 20 oxo-9 phenylacetoxy-4α taxene-11 are prepared. characteristics are as follows: - 1 H NMR spectrum (600 MHz; CDC1 ₃ ; δ in ppm): 0.53 and 0.72 (2 mts, 6H each: ethyl CH ₂ ); 0.94 and 1.05 (2 1, J = 7.5 Hz, 9H each: ethyl CH ₃ ); 1.10 (s, 3H: CH ₃ ); 1.20 (s, 3H: CH ₃ ); 1.64 (s, 1H: OH in 1); 1.70 (s. 3H: CH _j ); 1.86 and 2.45 (2 mts, 1 H each: CH ₂ in 6); 2.10 (s, 3H: CH ₃ ); 2.20 and 2.32 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 3.80 and 3.96 (2 d, J = 16 Hz, 1 H each: OCOCH ₂ Ar); 3.95 (d, J = 7 Hz, 1H: H at 3); 4.07 and 4.17 (2 d. J = 9 Hz, 1 H each: CH ₂ in 20); 4.29 (br s, 1H: OH at 10); 4.43 (dd, J = 11 and 7 Hz, 1H: H at 7); 4.79 (broad d, J = 10 Hz, 1 H: H at 5); 5.03 (broad t, J = 9 Hz, 1 H: H at 13);

5.19 (broad s, 1 H: H at 10); 5.63 (d, J = 7 Hz, 1H: H in 2); from 7.25 to 7.45 (mt, 7H: aromatic H and OCOC ₆ H ₅ H in meta); 7.60 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.00 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

By operating under conditions analogous to those described in Example 3, carbonate-lβ, 2 bis (triethylsilyloxy) -7β, 13α epoxy-5β, 20 methoxyacetoxy- lOβ oxo-9 phenylacetoxy-4α taxene-11 is prepared, the characteristics are as follows: - 1 H NMR spectrum (400 MHz; CDC1 ₃ ; δ in ppm): 0.61 and 0.74 (2 mts, 6H each: ethyl CH ₂ ); 0.92 and 1.05 (2 1, J = 7.5 Hz, 9H each: ethyl CH ₃ );

1.20 (s, 3H: CH ₃ ); 1.30 (s, 3H: CH ₃ ); 1.73 (s, 3H: CH ₃ ); 1.83 and 2.54 (2 mts, 1 H each: CH ₂ in 6); 2.18 (s, 3H: CH ₃ ); 2.27 and 2.48 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 3.50 (d, J = 6.5 Hz, 1 H: H at 3); 3.53 (s, 3H: OCH ₃ ); 3.65 (AB limit, J = 14 Hz, 2H: OCOCH-Ar); 4.18 (AB limit, 2H: OCOCH ₂ O); 4.45 and 4.53 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.46 (mt, 1H: H at 7); 4.53 (d, J = 6.5 Hz, 1H: H in 2); 4.68 (broad d, J = 10 Hz, 1 H: H at 5); 5.06 (broad t, J = 9 Hz, 1 H: H at 13); 6.53 (s, 1H: H at 10); from 7.25 to 7.45 (mt, 5H: aromatic H).

EXAMPLE 5

By operating as in Example 3, and starting from tert-butoxycarbonyl-amino-3-hydroxy-2-phenyl-propionate- (2R, 3S) of benzoyloxy-2 bis (methoxyacetoxy) -4α, 10β epoxy-5β , 20 hydroxy-lβ oxo-9 trifluoromethanesulfonyloxy-7β taxene-11 yle-13α, preparing tert-butoxycarbonylamino-3 hydroxy- 2 phenyl-3 propionate- (2R, 3S) of benzoyloxy-2α bis (methoxyacetoxy) -4α, 10β epoxy-5β, 20 hydroxy-lβ methylene-7β, 8 nor-19 oxo-9 taxene-11 yle-13cc the characteristics of which are as follows:

- H NMR spectrum (400 MHz; CDC1 ₃ ; temperature of 333 ° K, δ in ppm): 1.26 (s, 3H: CH ₃ ); 1.29 (s, 3H: CH ₃ ); 1.35 (s, 9H: C (CH ₃ ) ₃ ); 1.42 (mt, 1H: H at 7); 1.71 and 2.29 (respectively dd and mt, J = 6.5 and 5 Hz, 1 H each: CH ₂ in 19); 1.81 (s, 1H: OH in 1); 1.91 (s, 3H: CH ₃ ); 2.15 and 2.54 (respectively d large and dt, J = 16 Hz and J = 16 and 4.5 Hz, 1 H each: CH ₂ in 6); 2.32 (limit AB, 2H: CH ₂ at 14); 3.50 and 3.53 (2 s, 3H each: OCH ₃ ); 3.60 (mf, 1H: OH in 2 '); 4.11 and 4.56 (2 d, J = 16 Hz, 1 H each: OCOCH ₂ O); 4.12 and 4.31 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.17 (d, J = 7 Hz, 1 H: H at 3); 4.19 and 4.24 (2 d, J = 16 Hz, 1 H each: OCOCH ₂ O); 4.67 (mt, 1H: H in 2 '); 4.78 (d, J = 4.5 Hz, 1H: H at 5); 5.29 (broad d, J = 10 Hz, 1H: H in 3 '); 5.47 (d, J = 10 Hz, 1 H: CONH); 5.70 (d, J = 7 Hz, 1H: H in 2); 6.21 (broad t, J = 9 Hz, 1 H: H at 13); 6.44 (s, 1H: H at 10); 7.30 (t, J = 7.5 Hz, 1H: H in para of the 3 'aromatic); 7.39 (t, J = 7.5 Hz, 2H: H in meta of the aromatic in 3 '); 7.45 (d, J = 7.5 Hz, 2H: H ortho to the aromatic in 3 '); 7.51 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.61 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.12 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

By operating under conditions analogous to those described in Example 3, the tert-butoxycarbonylamino-3-hydroxy-3-phenyl-propionate- (2R, 3S) of benzoyloxy-2α bis (methoxyacetoxy) -4α, 10β epoxy- is prepared. 5β, 20 hydroxy-lβ oxo-9 trifluoromethanesulfonyloxy-7β taxene-11 yle-13α, the characteristics of which are as follows:

- NMR spectrum * H (400 MHz; CDC1 ₃ ; temperature of 333 ° K, δ in ppm): 1.22 (s, 3H: CH ₃ ); 1.27 (s, 3H: CH ₃ ); 1.38 (s, 9H: C (CH ₃ ) ₃ ); 1.64 (s, 1H: OH in 1); 1.92 (s, 3H: CH ₃ ); 2.11 (s, 3H: CH ₃ ); 2.25 and 2.92 (2 mts, 1 H each: CH ₂ in 6); 2.26 and 2.36 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 3.47 and 3.52 (2 sec, 3H each: OCH ₃ ); 3.66 (broad s, 1H: OH in 2 '); 3.99 (d, J = 7 Hz, 1H: H at 3); 4.15 and 4.57 (2 d, J = 16 Hz, 1 H each: OCOCH ₂ O); 4.19 (limit AB, J = 16 Hz, 2H: OCOCH ₂ O); 4.24 and 4.35 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.70 (mt, 1H: H 2 '); 4.95 (broad d, J = 10 Hz, 1 H: H at 5); 5.29 (broad d, J = 10 Hz, 1H: H in 3 '); 5.49 (d, J = 10 Hz, 1 H: CONH); 5.53 (dd, J = 11 and 8 Hz, 1H: H at 7); 5.76 (d, J = 7 Hz, 1H: H in 2); 6.18 (large t, J = 9 Hz, 1 H: H at 13); 6.74 (s, 1H: H at 10); 7.30 (t, J = 7.5 Hz, 1H: H in para of the 3 'aromatic); 7.38 (t, J = 7.5 Hz, 2H: H in meta of the aromatic in 3 '); 7.45 (d, J = 7.5 Hz, 2H: H ortho to the aromatic in 3 '); 7.49 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.63 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.09 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

By operating under conditions analogous to those described in Example 3, tert-butoxycarbonyl-3 (4-methoxy-phenyl) -2 phenyl-4-oxazolidine-1,3 carboxylate-5 (2R.4S.5R) is prepared. benzoyloxy-2α bis (methoxyacetoxy) -4α, 10β epoxy- 5β, 20 hydroxy-lβ oxo-9 trifluoromethanesu_fonyloxy-7β taxene-11 yle-13α, the characteristics of which are as follows:

- 1 H NMR spectrum (400 MHz; CDC1 ₃ ; temperature of 333 ° K, δ in ppm): 1.10 (s, 9H: C (CH ₃ ) ₃ ); 1.18 (s, 3H: CH ₃ ); 1.20 (s, 3H: CH ₃ ); 1.64 (s, 1H: OH in 1); 1.75 (s, 3H: CH ₃ ); 1.86 (s, 3H: CH ₃ ); 2.12 and 2.26 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 2.24 and 2.86 (2 mts, 1 H each: CH ₂ in 6); 3.33 and 3.53 (2 sec, 3H: OCH ₃ ); 3.65 and 4.10 (2 d, J = 16 Hz, 1 H each: OCOCH ₂ O); 3.83 (s, 3H: ArOCH ₃ ); 3.86 (d, J = 7 Hz, 1H: H at 3); 4.14 and 4.20 (2 d, J = 16 Hz, 1 H each: OCOCH ₂ O); 4.19 and 4.32 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.72 (broad d, J = 4.5 Hz, 1H: H in 2 '); 4.89 (broad d, J = 10 Hz, 1 H: H at 5); 5.46 (mt, 1H: H in 3 '); 5.45 (dd, J = 11 and 8 Hz, 1H: H at 7); 5.69 (d, J = 7 Hz, 1H: H in 2); 5.94 (broad t, J = 9 Hz, 1H: H at 13); 6.40 (broad s, 1H: H in 5 '); 6.63 (s, IH: H in 10)

6.93 (d, J = 8.5 Hz, 2H: H aromatic in ortho of OCH ₃ ); from 7.30 to 7.45 (mt, 5H H aromatic in 3 '); 7.38 (d, J = 8.5 Hz, 2H: aromatic H in meta of OCH _j ) 7.48 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.63 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.08 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

By operating under conditions analogous to those described in Example 3, benzoyloxy-2α bis (methoxyacetoxy) -4α, 10β dihydroxy-lβ, 13α epoxy- is prepared. 5β, 20 oxo-9 trifluoromethanesulfonyloxy-7β taxene-11, the characteristics of which are as follows:

- 1 H NMR spectrum (400 MHz; CDC1 ₃ ; δ in ppm): 1.06 (s, 3H: CH ₃ ); 1.20 (s, 3H: CH ₃ ); 1.61 (s, 1H: OH in 1); 1.89 (s, 3H: CH ₃ ); 2.23 (d, J = 5 Hz, 1H: OH at 13); from 2.20 to 2.35 and 2.92 (2 mts, 1 H each: CH ₂ in 6); 2.26 (s, 3H: CH ₃ ); 2.32 (d, J = 9 Hz, 2H: CH ₂ at 14); 3.52 and 3.58 (2 sec, 3H each: OCH ₃ ); 4.04 (d, J = 7 Hz, 1 H: H at 3); 4.19 and 4.32 (2 AB limit, J = 16 Hz, 2H each: OCOCH ₂ O); 4.20 and 4.38 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.82 (mt, 1H: H at 13); 4.99 (broad d, J = 10 Hz, 1 H: H at 5); 5.55 (dd, J = 10 and 7 Hz, 1H: H at 7); 5.69 (d, J = 7 Hz, 1H: H in 2); 6.73 (s, 1H: H at 10); 7.51 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.64 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.13 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

By operating under conditions analogous to those described in Example 3, benzoyloxy-2α bis (methoxyacetoxy) -4α, 10β epoxy-5β, 20 oxo-9 trihydroxy-lβ, 7β, 13α taxene-11 are prepared, the characteristics of which are are the following :

- 1 H NMR spectrum (400 MHz; CDC1 _3: δ in ppm): 1.11 (s, 6H: CH ₃ ); 1.63 (s, 1H: OH in 1); 1.70 (s, 3H: CH ₃ ); 1.92 and 2.63 (2 mts, 1 H each: CH ₂ in 6); 2.08 (s, 3H: CH ₃ ); from 2.20 to 2.30 (mt, 3H: CH ₂ at 14 and OH); 2.40 (d, J = 4 Hz, 1H: OH); 3.54 and 3.59 (2 sec, 3H each: OCH ₃ ); 3.92 (d, J = 7 Hz, 1H: H at 3); 4.20 and 4.35 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.24 and 4.28 (2 AB limit, J = 16 Hz, 2H each: OCOCH ₂ O); 4.50 (mt, 1H: H at 7); 4.86 (mt, 1H: H at 13); 5.03 (broad d, J = 10 Hz, 1 H: H at 5); 5.65 (d, J = 7 Hz, 1H: H in 2); 6.44 (s, 1H: H at 10); 7.49 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.63 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.14 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

By operating under conditions analogous to those described in Example 3, benzoyloxy-2α bis (methoxyacetoxy) -4α, 10β bis (triethylsilyloxy) - 7β, 13α epoxy-5β, 20 hydroxy-lβ oxo-9 taxene are prepared. 11, the characteristics of which are as follows:

- H NMR spectrum (400 MHz; CDC1 ₃ ; δ in ppm): 0.60 and 0.70 (2 mts, 6H each: ethyl CH ₂ ); 0.94 and 1.02 (2 1, J = 7.5 Hz, 9H each: ethyl CH ₃ );

1.12 (s, 3H: CH ₃ ); 1.20 (s, 3H: CH ₃ ); 1.64 (s, 1H: OH in 1); 1.70 (s, 3H: CH ₃ ); 1.91 and 2.57 (2 mts, 1 H each: CH ₂ in 6); 2.12 (s, 3H: CH ₃ ); 2.13 and 2.23 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 3.53 and 3.57 (2 sec, 3H each: OCH ₃ ); 3.83 (d, J = 7 Hz, 1 H: H at 3); 4.15 and 4.40 (2 d, J = 16 Hz, 2H: OCOCH ₂ O); 4.19 (AB limit, J = 16 Hz, 2H: OCOCH ₂ O); 4.21 and 4.37 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.51 (dd, J = 11 and 7 Hz, 1H: H at 7); 4.93 (t, J = 9 Hz, 1H: H at 13); 5.02 (broad d, J = 10 Hz, 1 H: H at 5); 5.64 (d, J = 7 Hz, 1H: H in 2); 6.56 (s, 1H: H at 10); 7.48 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.63 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.19 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

By operating under conditions analogous to those described in Example 3, benzoyloxy-2α dihydroxy-lβ, 10β bis (triethylsUyloxy) -7β, 13α epoxy- 5β, 20 methoxyacetoxy-9 oxo-9 taxene are prepared. characteristics are the following: - ^Î H NMR spectrum (400 MHz; CDC1 ₃ ; δ in ppm): 0.57 and 0.69 (2 mts, 6H each: ethyl CH ₂ ); 0.94 and 1.03 (2 1, J = 7.5 Hz, 9H each: ethyl CH ₃ ); 1.09 (s, 3H: CH ₃ ); 1.17 (s, 3H: CH ₃ ); 1.58 (s, 1H: OH in 1); 1.75 (s, 3H: CH ₃ ); 1.93 and 2.49 (2 mts, 1 H each: CH ₂ in 6); 2.03 (s, 3H: CH ₃ ); 2.09 and 2.18 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 3.57 (s, 3H: OCH ₃ ); 3.88 (d, J = 7 Hz, 1 H: H at 3); 4.16 and 4.40 (2 d, J = 16 Hz, 1 H each: OCOCH ₂ O); 4.20 and 4.36 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.28 (broad s, 1 H: OH at 10); 4.42 (mt, 1H: H at 7); 4.97 (t, J = 9 Hz, 1H: H at 13); 5.01 (broad d, J = 10 Hz, 1 H: H at 5); 5.17 (br s, 1H: H at 10); 5.62 (d, J = 7 Hz, 1H: H in 2); 7.47 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.61 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.18 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

By operating under conditions analogous to those described in Example 3, the bis (methoxyacetoxy) -4α, 10β carbonate- lβ, 2α bis (triethylsUyloxy) - 7β, 13α epoxy-5β, 20 oxo-9 taxene-11 are prepared. the characteristics of which are as follows: - H NMR spectrum (400 MHz; CDC1 ₃ ; δ in ppm): 0.60 and 0.68 (2 mts, 6H each: ethyl CH ₂ ); 0.92 and 1.01 (2 1, J = 7.5 Hz, 9H each: ethyl CH ₃ ); 1.19 (s, 3H: CH ₃ ); 1.27 (s, 3H: CH ₃ ); 1.75 (s, 3H: CH ₃ ); 1.91 and 2.63 (2 mts, 1 H each: CH ₂ in 6); 2.08 and 2.41 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 2.12 (s, 3H: CH ₃ ); 3.44 (d, J = 6.5 Hz, 1 H: H at 3); 3.46 and 3.50 (2 s, 3H each: OCH ₃ ); 4.06 and 4.14 (2 d, J = 16 Hz, 1 H each: OCOCH ₂ O); 4.16 (s, 2H: OCOCH ₂ O); 4.46 (dd, J = 10 and 7 Hz, 1H: H at 7); 4.50 and 4.66 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.51 (d, J = 6.5 Hz, 1H: H in 2); 4.99 (mt, 1H: H at 13); 5.00 (broad d, J = 10 Hz, 1 H: H at 5); 6.51 (s, 1H: H at 10). EXAMPLE 6

By operating as in Example 3, and starting from tert-butoxycarbonyl-amino-3-hydroxy-2-phenyl-propionate- (2R, 3S) of benzoyloxy-2α cyclopranoyloxy- 4 epoxy-5β, 20 hydroxy-lβ oxo- 9 methoxyacetoxy-10β trifluoromethanesulfonyloxy- 7β taxene-11 yle-13α, we prepare tert-butoxycarbonylamino-3 hydroxy-2 phenyl-3 propionate- (2R, 3S) benzoyloxy-2α cyclopropanoyloxy-4α epoxy-5β, 20 hydroxy- lβ methoxyacetoxy-10β methylene-7β, 8 nor-19 oxo-9 taxene-11 yle-13α the characteristics of which are as follows:

- NMR spectrum (400 MHz; CDC1 ₃ ; temperature in the region of 333 ° K, δ in ppm): from 0.80 to 1.40 (mt, 4H: CH ₂ CH ₂ of cyclopropyl); 1.30 (s, 6H: CH ₃ ); 1.35

(s, 9H: C (CH ₃ ) ₃ ); from 1.30 to 1.40 (mt, 1H: H at 7); 1.70 and 2.23 (2 dd, respectively J = 6 and 5.5 Hz and J = 10 and 5.5 Hz, 1 H each: CH ₂ in 19); 1.80 (mt, 1H: CH of cyclopropyl); 1.85 (s, 1H: OH in 1); 1.86 (s, 3H: CH ₃ ); 2.11 and 2.44 (respectively d large and dt, J = 16 Hz and J = 16 and 4.5 Hz, IH each: CH ₂ in 6); 2.34 and 2.50 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 3.22 (d, J = 4 Hz, 1H: OH in 2 '); 3.52 (s, 3H: OCH ₃ ); 4.08 and 4.28 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.13 (d, J = 7 Hz, 1 H: H at 3); 4.16 and 4.24 (2 d, J = 16 Hz, 1 H each: OCOCH ₂ O); 4.62 (d, J = 4.5 Hz, 1H: H at 5); 4.70 (broad d, J = 4 Hz, 1H: H in 2 '); 5.28 (AB limit, 2H: H3 'and CONH); 5.70 (d, J = 7 Hz, 1H: H in 2); 6.23 (broad t, J = 9 Hz, 1 H: H at 13); 6.42 (s, 1H: H at 10); from 7.20 to 7.45 (mt, 5H: aromatic H in 3 '); 7.52 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.61 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.14 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

By operating under conditions analogous to those described in Example 3, tert-butoxycarbonylamino-3-hydroxy-2-phenyl-3-propionate (2R, 3S) of benzoyloxy-2α cyclopropanoyloxy-4α epoxy-5β, 20 hydroxy- is prepared. lβ methoxyacetoxy-lOβ oxo-9 trifluoromethanesulfonyloxy-7β taxene-11 yle-13, the characteristics of which are as follows:

- H NMR spectrum (400 MHz; CDC1 ₃ ; δ in ppm): from 0.85 to 1.40 (mt, 4H CH ₂ CH ₂ of cyclopropyl); 1.22 (s, 3H: CH ₃ ); 1.24 (s, 3H: CH ₃ ); 1.39 (s, 9H C (CH ₃ ) ₃ ); 1.70 (s, 1H: OH in 1); 1.83 (mt, 1H: cyclopropyl CH); 1.88 (s, 3H CH ₃ ); 2.05 (s, 3H: CH _j ); 2.23 and 2.84 (2 mts, 1 H each: CH ₂ in 6); 2.34 and 2.42 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 3.35 (d, J = 5.5 Hz, 1H: OH in 2 '); 3.52 (s, 3H: OCH ₃ ); 3.96 (d, J = 7 Hz, 1 H: H at 3); 4.16 and 4.25 (2 d, J = 16 Hz, 1 H each: OCOCH ₂ O); 4.17 and 4.28 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.72 (mt, 1H: H in 2 '); 4.81 (broad d, J = 10 Hz, 1 H: H at 5); 5.28 (broad d, J = 10 Hz, 1 H: H in 3 '); 5.36 (d, J = 10 Hz, 1 H: CONH); 5.48 (dd, J = 10.5 and 7 Hz, 1H: H at 7); 5.72 (d, J = 7 Hz, 1H: H in 2); 6.11 (mt, 1H: H at 13); 6.71 (s, 1H: H at 10); from 7.25 to 7.45 (mt, 5H: aromatic H in 3 '); 7.52 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.65 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.08 (d, J = 7.5 ^' Hz, 2H: OCOC ₆ H ₅ H in ortho).

By operating under conditions analogous to those described in Example 3, tert-butoxycarbonyl-3 (4-methoxyphenyl) -2 phenyl-4 oxazolidine-1,3 carboxylate-5 (2R, 4S, 5R) is prepared. benzoyloxy-2α cyclopropanoyloxy-4α epoxy-5β, 20 hydroxy-lβ methoxyacetoxy-lOβ oxo-9 trifluoromethanesulfonyloxy-7β taxene-11 yle-13α, the characteristics of which are as follows:

- 1 H NMR spectrum (400 MHz; CDC1 ₃ ; δ in ppm): from 0.50 to 1.50 (mt, 5H: CH and CH ₂ of cyclopropyl); 1.04 (s, 9H: C (CH ₃ ) ₃ ); 1.17 (s, 3H: CH ₃ ); 1.19 (s, 3H: CH ₃ ); 1.65 (s, 1H: OH in 1); 1.72 (s, 3H: CH ₃ ); 1.84 (s, 3H: CH ₃ ); 2.14 and 2.32 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 2.16 and 2.79 (2 mts, 1 H each: CH ₂ in 6); 3.52 (s, 3H: OCH ₃ ); 3.82 (s, 3H: ArOCH ₃ ); 3.86 (d, J = 7 Hz, 1H: H at 3); 4.11 and 4.24 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.15 and 4.22 (2 d, J = 16 Hz, 1 H each: OCOCH ₂ O); 4.60 (d, J = 4.5 Hz, 1H: H in 2 '); 4.74 (broad d, J = 10 Hz, 1 H: H at 5); 5.44 (dd, J = 10.5 and 8 Hz, 1H: H at 7); 5.50 (mt, 1H: H in 3 '); 5.67 (d, J = 7 Hz, 1H: H in 2); 5.88 (mt, 1H: H at 13); 6.41 (mf, IH: H in 5 "); 6.61 (s, IH: H in 10); 6.92 (d, J = 8.5 Hz, 2H: H aromatic in OCH ₃ ortho) ; 7.38 (d, J = 8.5 Hz, 2H: aromatic H in meta of OCH ₃ ); from 7.25 to 7.45 (mt, 5H: aromatic H in 3 '); 7.49 (t , J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.63 (t, J = 7.5 Hz, IH: OCOC ₆ H ₅ H in para); 8.02 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

By operating under conditions analogous to those described in Example 3, benzoyloxy-2α cyclopropanoyloxy-4α dihydroxy-lβ, 13α epoxy-5β, 20 methoxyacetoxy- lOβ oxo-9 trifluoromethanesulfonyloxy-7β taxene-11 are prepared, the characteristics of which are the following:

- NMR spectrum * H (400 MHz; CDC1 ₃ ; temperature of 333 ° K, δ in ppm): from 0.90 to 1.40 (mt, 4H: CH ₂ CH ₂ of cyclopropyl); 1.10 (s, 3H: CH ₃ ); 1.22 (s, 3H:

CH ₃ ); 1.61 (s, 1H: OH in 1); from 1.70 to 1.85 (mt, 2H: CH of cyclopropyl and OH at 13); 1.90 (s, 3H: CH ₃ ); 2.22 and 2.86 (2 mts, 1 H each: CH ₂ in 6); 2.26 (s, 3H: CH ₃ ); 2.36 (d, J = 9 Hz, 2H: CH ₂ at 14); 3.52 (s, 3H: OCH ₃ ); 4.05 (d, J = 7 Hz, 1 H: H at 3); 4.14 and 4.22 (2 d, J = 16 Hz, 1 H each: OCOCH ₂ O); 4.20 and 4.36 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.84 (mt, 1H: H at 13); 4.85 (broad d, J = 10 Hz, 1 H: H at 5); 5.54 (dd, J = 11 and 8 Hz, 1H: H at 7); 5.72 (d, J = 7 Hz, 1H: H in 2); 6.73 (s, 1H: H at 10); 7.51 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.63 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.12 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho)

By operating under conditions analogous to those described in Example 3, the benzoyloxy-2α cyclopropanoyloxy-4α dihydroxy-lβ, 13α epoxy-5β, 20 methoxyacetoxy- lOβ oxo-9 trifluoromethanesulfonyloxy-7β taxene-11, the characteristics of which are the following: - NMR spectrum * H (400 MHz; CDC1 ₃ ; temperature of 333 ° K, δ in ppm): from 0.90 to 1.40 (mt, 4H: CH ₂ CH ₂ of cyclopropyl); 1.10 (s, 3H: CH ₃ ); 1.22 (s, 3H: CH ₃ ); 1.61 (s, 1H: OH in 1); from 1.70 to 1.85 (mt, 2H: CH of cyclopropyl and OH at 13); 1.90 (s, 3H: CH ₃ ); 2.22 and 2.86 (2 mts, 1 H each: CH ₂ in 6); 2.26 (s, 3H: CH ₃ ); 2.36 (d, J = 9 Hz, 2H: CH ₂ at 14); 3.52 (s, 3H: OCH ₃ ); 4.05 (d, J = 7 Hz, 1 H: H at 3); 4.14 and 4.22 (2 d, J = 16 Hz, 1 H each: OCOCH ₂ O); 4.20 and 4.36 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.84 (mt, 1H: H at 13); 4.85 (broad d, J = 10 Hz, 1 H: H at 5); 5.54 (dd, J = 11 and 8 Hz, 1H: H at 7); 5.72 (d, J = 7 Hz, 1H: H in 2); 6.73 (s, 1H: H at 10); 7.51 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.63 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.12 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho)

By operating under conditions analogous to those described in Example 3, benzoyloxy-2α cyclopropanoyloxy ~ 4α bis (triethylsUyloxy) -7β, 13α epoxy-5β, 20 hydroxy-lβ methoxyacetoxy-lOβ oxo-9 taxene is prepared. the characteristics are as follows: - 1 H NMR spectrum (400 MHz; CDC1 ₃ ; δ in ppm): 0.60 and 0.68 (2 mts, 6H each: ethyl CH ₂ ); from 0.90 to 1.35 (mt, 4H: CH ₂ CH ₂ of cyclopropyl); 0.94 and 1.03 (2 1, J = 7.5 Hz, 9H each: ethyl CH ₃ ); 1.14 (s, 3H: CH ₃ ); 1.20 (s, 3H: CH ₃ ); 1.64 (s, 1H: OH in 1); 1.71 (s, 3H: CH ₃ ); 1.73 (mt, 1H: CH of cyclopropyl); 1.87 and 2.50 (respectively dd large and mt, J = 14 and 11 Hz, 1H each: CH ₂ in 6); 2.11 and 2.29 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 2.15 (s, 3H: CH ₃ ); 3.53 (s, 3H: OCH ₃ ); 3.86 (d, J = 7 Hz, 1H: H at 3); 4.14 and 4.26 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.19 (limit AB, J = 16 Hz, 2H: OCOCH ₂ O); 4.52 (dd, J = 11 and 7 Hz, 1H: H at 7); 4.84 (broad d, J = 10 Hz, 1 H: H at 5); 4.95 (broad t, J = 9 Hz, 1 H: H at 13); 5.65 (d, J = 7 Hz, 1H: H in 2); 6.56 (s, IH: H in 10); 7.50 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.62 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.09 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

By operating under conditions analogous to those described in Example 3, benzoyloxy-2α cyclopropanoyloxy-4α dihydroxy-lβ.lOβ bis (triethyl- sUyloxy) -7β, 13α epoxy-5β, 20 oxo-9 taxene-11 are prepared. whose characteristics are as follows:

- ^X H NMR spectrum (400 MHz; CDC1 ₃ δ in ppm.): 0.58 and 0.68 (2 mts, 6H each: CH ₂ of ethyl); from 0.90 to 1.35 (mt, 4H: CH ₂ CH ₂ of cyclopropyl); 0.94 and 1.03 (2 1, J = 7.5 Hz, 9H each: ethyl CH ₃ ); 1.12 (s, 3H: CH ₃ ); 1.22 (s, 3H: CH ₃ ); 1.59 (s, 1H: OH in 1); 1.67 (mt, 1H: CH of cyclopropyl); 1.73 (s, 3H: CH ₃ ); 1.90 and 2.44 (2 mts, 1 H each: CH ₂ in 6); 2.06 (s, 3H: CH ₃ ); 2.10 and 2.25 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 3.91 (d, J = 7 Hz, 1 H: H at 3); 4.16 and 4.26 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.28 (d, J = 1.5 Hz, 1H: OH at 10); 4.42 (dd, J = 11 and 6 Hz, 1H: H at 7); 4.84 (broad d, J = 10 Hz, 1 H: H at 5); 5.00 (t, J = 9 Hz, 1H: H at 13); 5.16 (d, J = 1.5 Hz, 1H: H at 10); 5.62 (d, J = 7 Hz, 1H: H in 2); 7.50 (t, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in meta); 7.62 (t, J = 7.5 Hz, 1 H: OCOC ₆ H ₅ H in para); 8.09 (d, J = 7.5 Hz, 2H: OCOC ₆ H ₅ H in ortho).

Carbonate-lβ, 2 cyclopropanoyloxy-4α bis (triethylsUyloxy) -7β, 13α epoxy-5β, 20 methoxyacetoxy- 10β oxo-9 taxene-11 can be prepared as follows:

To a solution of 100 mg of carbonate-lβ, 2α bis (triethylsilyloxy) -7β, 13α epoxy-5β, 20 hydroxy-4α methoxyacetoxy-lOβ oxo-9 taxene-11 in 7 cm3 of tetrahydrofuran, is added dropwise, 345 μl of a 1M solution of Uthium hexamethyldisilazane in hexane, at a temperature in the region of -30 ° C. The reaction mixture is stirred for 15 minutes at this temperature and then 39 μl of cyclopropanoyl chloride are added dropwise. The reaction mixture is stirred for 30 minutes at a temperature in the region of 0 ° C. and then hydrolyzed by the addition of 1 cm 3 of a saturated solution of ammonium chloride and 50 cm 3 of dichloromethane. The organic phase is decanted, washed with 2 times 40 cm3 of a saturated aqueous solution of sodium chloride and then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 120 mg of a product are obtained which is purified by chromatography on 70 g of silicon (0.063-0.2 mm) contained in a column 2 cm in diameter, eluting with an ethyl acetate-cyclohexane mixture (20 -80 by volume) and collecting 10 cm3 fractions. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. 31 mg of carbonate-lβ, 2α cyclopropanoyloxy-4α bis (triethylsUyloxy) -7β, 13α epoxy-5β, 20 methoxyacetoxy-10β oxo-9 taxene-11 are obtained in the form of a white meringue, the physical characteristics of which are as follows:

- 1 H NMR spectrum (400 MHz; CDC1 ₃ ; δ in ppm): 0.60 and 0.66 (2 mts, 6H each: ethyl CH ₂ ); from 0.90 to 1.35 (mt, 4H: CH ₂ CH ₂ of cyclopropyl); 0.92 and 1.02 (2 t, J = 7.5 Hz, 9H each: ethyl CH ₃ ); 1.19 (s, 3H: CH ₃ ); 1.29 (s, 3H: CH ₃ ); 1.60 (s, 1H: OH in 1); 1.62 (mt, 1H: CH of cyclopropyl); 1.73 (s, 3H: CH ₃ ); 1.88 and 2.57 (respectively dd large and mt, J = 15 and 10 Hz, 1 H each: CH ₂ in 6); 2.15 (s, 3H: CH ₃ ); 2.19 and 2.37 (2 dd, J = 16 and 9 Hz, 1 H each: CH ₂ at 14); 3.48 (d, J = 7 Hz, 1H: H at 3); 3.51 (s, 3H: OCH ₃ ); 4.16 (s, 2H: OCOCH ₂ O); 4.44 (mt, 1H: H at 7); 4.45 and 4.54 (2 d, J = 9 Hz, 1 H each: CH ₂ in 20); 4.49 (d, J = 7 Hz, 1H: H in 2); 4.85 (broad d, J = 10 Hz, 1 H: H at 5); 5.02 (broad t, J = 9 Hz, 1 H: H at 13); 6.52 (s, 1H: H at 10).

The new products of general formula (I) in which Z represents a radical of general formula (II) manifest a significant inhibitory activity of abnormal cell proliferation and have therapeutic properties allowing the treatment of patients with pathological conditions associated with cell proliferation abnormal. The pathological conditions include abnormal cell proliferation of skin or non-skin cells of various tissues and / or organs, including, but not limited to, muscle, bone or connective tissue, skin, brain, lungs, sexual organs, the lymphatic or renal systems, the mammary or blood cells, the liver, the digestive system, the pancreas and the thyroid or adrenal glands. These pathological conditions may also include psoriasis, solid tumors, ovarian, breast, brain, prostate, colon, stomach, kidney or testicular cancer, Kaposi's sarcoma, cholangiocarcinoma, choriocarcinoma, neuroblastoma, Wilms tumor, Hodgkin's disease, melanomas, multiple myelomas, chronic lymphocytic leukemias, acute or chronic granulocytic lymphomas. The new products according to the invention are particularly useful for the treatment of ovarian cancer. The products according to the invention can be used to prevent or delay the onset or recurrence of pathological conditions or to treat these pathological conditions. The products according to the invention can be administered to a patient in different forms adapted to the chosen route of administration which, preferably, is the parenteral route. Parenteral administration includes intravenous, intraperitoneal, intramuscular or subcutaneous administration. More particularly preferred is intraperitoneal or intravenous administration.

The present invention also comprises the pharmaceutical compositions which contain at least one product of general formula (I) in a sufficient amount suitable for use in human or veterinary therapy. The compositions can be prepared according to the usual methods using one or more pharmaceutically acceptable adjuvants, carriers or excipients. Suitable carriers include diluents, sterile aqueous media and various non-toxic solvents. Preferably, the compositions are in the form of aqueous solutions or suspensions, injectable solutions which may contain emulsifying agents, dyes, preservatives or stabilizers. The choice of adjuvants or excipients can be determined by the solubility and chemical properties of the product, the particular mode of administration and good pharmaceutical practices.

For parenteral administration, sterile aqueous or non-aqueous solutions or suspensions are used. For the preparation of nonaqueous solutions or suspensions can be used natural vegetable oils such as olive oil, sesame oil or paraffin oil or injectable organic esters such as ethyl oleate . The sterile aqueous solutions can consist of a solution of a pharmaceutically acceptable salt dissolved in water. The aqueous solutions are suitable for intravenous administration as long as the pH is suitably adjusted and the isotonicity is achieved, for example, by a sufficient amount of sodium chloride or glucose. The sterilization can be carried out by heating or by any other means which does not alter the composition.

It is understood that all the products entering into the compositions according to the invention must be pure and non-toxic for the quantities used. The compositions can contain at least 0.01% of therapeutically active product. The amount of active ingredient in a composition is such that a suitable dosage can be prescribed. Preferably, the compositions are prepared in such a way that a unit dose contains from 0.01 to 1000 mg approximately of active product for parenteral administration. Therapeutic treatment can be carried out concurrently with other therapeutic treatments including antineoplastic drugs, monoclonal antibodies, immunological therapies or radiotherapies or modifiers of biological responses. Response modifiers include, but are not limited to, lymphokines and cytokines such as interleukins, interferons (α, β or δ) and TNF. Other chemotherapeutic agents useful in the treatment of disorders due to abnormal proliferation of cells include, but are not limited to, alkylating agents such as nitrogen mustards such as mechloretamine, cyclophosphamide, melphalan and chlorambucU, alkyl sulfonates such as busulfan, nitrosoureas such as carmustine, lomustine, semustin and streptozocin, triazenes such as dacarbazine, antimetabolites such as folic acid analogs such as methotrexate, pyrimidine analogs such as fluorouracil and cytarabine, purine analogs like mercaptopurine and thioguanine, natural products like vinca alkaloids like vinblastine, vincristine and vendesine, epipodophyUotoxins like etoposide and teniposide, antibiotics like dacώiomycin , daunorubicin, doxorubicin, bleomycin, plicamycin and mitomycin, enzymes com me L-asparaginase, various agents such as platinum coordination complexes such as cisplatin, substituted ureas such as hydroxyurea, methylhydrazine derivatives such as procarbazine, adrenocorticoid suppressants such as mitotane and aminoglutethymide, hormones and antagonists like adrenocorticosteroids like prednisone, progestins like hydroxyprogesterone caproate, methoxyprogesterone acetate and megestrol acetate, estrogens like diethylstilbestrol and rethynylestradiol, antioestrogens like tamoxifen, androgens like androgens testosterone and fluoxymesterone.

The doses used to implement the methods according to the invention are those which allow a prophylactic treatment or a maximum therapeutic response. The doses vary according to the form of administration, the particular product selected and the specific characteristics of the subject to be treated. In general, the doses are those which are therapeutically effective for the treatment of disorders due to abnormal cell proliferation. The products according to the invention can be administered as often as necessary to obtain the desired therapeutic effect. Some patients may respond quickly to relatively large or low doses and may require low or no maintenance doses. Generally, from low doses will be used at the start of treatment and, if necessary, increasing doses will be administered until an optimum effect is obtained. For other patients it may be necessary to administer maintenance doses 1 to 8 times a day, preferably 1 to 4 times, depending on the physiological needs of the patient concerned. It is also possible that for some patients it may be necessary to use only one or two daily administrations.

In humans, the doses are generally between 0.01 and 200 mg / kg. Intraperitoneally, the doses will generally be between 0.1 and 100 mg / kg and, preferably between 0.5 and 50 mg / kg and, even more specifically between 1 and 10 mg / kg. Intravenously, the doses are generally between 0.1 and 50 mg / kg and, preferably between 0.1 and 5 mg / kg and, even more specifically between 1 and 2 mg / kg. It is understood that, in choosing the most appropriate dosage, the route of administration, the weight of the patient, his general state of health, his age and all the factors which may influence the efficacy will have to be taken into account. of treatment.

The following example illustrates a composition according to the invention.

EXAMPLE

40 mg of the product obtained in Example 1 are dissolved in 1 cm 3 of Emulphor EL 620 and 1 cm 3 of ethanol then the solution is diluted by adding 18 cm 3 of physiological saline.

The composition is administered by infusion for 1 hour by introduction into physiological saline.

Claims

1 - New taxoids of general formula:

OCOR ₄ in which: R _a represents a hydrogen atom or a hydroxy radical, alkoxy containing 1 to 4 carbon atoms, acyloxy containing 1 to 4 carbon atoms or alkoxyacetoxy in which the alkyl part contains 1 to 4 carbon atoms and Rb represents a hydrogen atom or else R _a and Rb together form with the carbon atom to which they are linked a ketone function, Z represents a hydrogen atom or a radical of general formula:

in which :

R represents a benzoyl radical optionally substituted by one or more atoms or radicals, identical or different, chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms, alkoxy containing 1 to 4 carbon atoms or trifluoromethyl, thenoyl or furoyl, or an R2-O-CO- radical in which R2 represents:

- an alkyl radical containing 1 to 8 carbon atoms, alkenyl containing 2 to 8 carbon atoms, alkynyl containing 3 to 8 carbon atoms, cycloalkyl containing 3 to 6 carbon atoms, cycloalkenyl containing 4 to 6 carbon atoms, bicycloalkyl containing 7 to 10 carbon atoms, these radicals being optionally substituted by one or more substituents chosen from halogen atoms and hydroxy, alkoxy radicals containing 1 to 4 carbon atoms, dialkoylamino each alkyl part of which contains 1 to 4 carbon atoms , piperidino, morpholino, pipérazinyl-1 (optionally substituted at -4 by an alkyl radical containing 1 to 4 carbon atoms or by a phenylalkyl radical the alkyl part of which contains 1 to 4 carbon atoms), cycloalkyl containing 3 to 6 carbon atoms, cycloalkenyl containing 4 to 6 carbon atoms, phenyl (optionally substituted by one or more atoms or radicals chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms or alkoxy containing 1 to 4 carbon atoms), cyano, carboxy or alkoxycarbonyl, the alkyl part of which contains 1 to 4 carbon atoms,

- a phenyl or α- or β-naphthyl radical optionally substituted by one or more atoms or radicals chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms or alkoxy containing 1 to 4 carbon atoms or a radical 5-membered aromatic heterocyclic preferably chosen from furyl and thienyl radicals,

- or a saturated heterocyclyl radical containing 4 to 6 carbon atoms optionally substituted by one or more alkyl radicals containing 1 to 4 carbon atoms, R3 represents a straight or branched alkyl radical containing 1 to 8 carbon atoms, straight or branched alkenyl containing 2 to 8 carbon atoms, straight or branched alkynyl containing 2 to 8 carbon atoms, cycloalkyl containing 3 to 6 carbon atoms, phenyl or a- or β-naphthyl optionally substituted by one or more atoms or radicals chosen from atoms '' halogen and alkyl, alkenyl, alkynyl, aryl, aralkyl, alkoxy, alkylthio, aryloxy, arylthio, hydroxy, hydroxyalkyl, mercapto, formyl, acyl, acylamino, aroylamino, alkoxycarbonylamino, aminoalkyl, carboxyalkoxy , carbamoyl, alkylcarbamoyl, dialcoylcarbamoyl, cyano, nitro and trifluoromethyl, or an aromatic heterocycle having 5 members and containing one or more s heteroatoms, identical or different, chosen from nitrogen, oxygen or sulfur atoms and optionally substituted by one or more substituents, identical or different, chosen from halogen atoms and alkyl, aryl, amino radicals, alkyllamino, dialkoylamino, alkoxycarbonylamino, acyl, arylcarbonyl, cyano, carboxy, carbamoyl, alkylcarbamoyl, dialcoylcarbamoyl or alkoxycarbonyl, it being understood that in the substituents of the phenyl, α- or β-naphthyl and aryl alkyl radicals, and the aryl alkyls, other radicals contain 1 to 4 carbon atoms and the alkenyl and alkynyl radicals contain 2 to 8 carbon atoms and the aryl radicals are identical or different phenyl or ce- or β-naphthyl radicals, and R4 and R5, represent - a straight or branched alkyl radical containing 1 to 8 carbon atoms, straight or branched alkenyl containing 2 to 8 carbon atoms, straight or branched alkynyl containing 2 to 8 carbon atoms, cycloalkyl containing 3 to 6 carbon atoms, cycloalkenyl containing 4 to 6 carbon atoms or bicycloalkyl containing 7 to 11 carbon atoms, these radicals being optionally substituted by one or more substituents chosen from halogen atoms and hydroxy radicals, alkyloxy containing 1 to 4 carbon atoms, dialkoylamino each alkyl part contains 1 to 4 carbon atoms, piperidino, morpholino, piperazinyl-1 (optionally substituted in -4 by an alkyl radical containing 1 to 4 carbon atoms or by a phenylalkyl radical in which the alkyl part contains 1 to 4 carbon atoms ), cycloalkyl containing 3 to 6 carbon atoms, cycloalkenyl containing 4 to 6 carbon atoms, optionally substituted phenyl, cyano, carboxy or alkyloxycarbonyl, the alkyl part of which contains 1 to 4 carbon atoms, or an aryl radical optionally substituted by one or more atoms or radicals chosen from halogen atoms and alkyl, alkenyl, alkynyl, aryl, aralkyl, alkoxy, alkylthio radicals , aryloxy, arylthio, hydroxy, hydroxyalkyl, mercapto, formyl, acyl, acylamino, aroylamino, alkoxycarbonyl-amino, amino, alcoylamino, dialcoylamino, carboxy, alkoxycarbonyl, carbamoyl, alcoylcarbamoyl, dialcoylcaridoamyl, triano, it being understood that R5 cannot represent a methyl radical or a saturated or unsaturated heterocyclyl radical containing 4 to 6 members and optionally substituted by one or more alkyl radicals containing 1 to 4 carbon atoms, it being understood that R5 cannot represent a radical methyl, it being understood that the cycloalkyl, cycloalkenyl or bicycloalkyl radicals may be optional Lement substituted by one or more alkyl radicals containing 1 to 4 carbon atoms.

2 - New taxoids according to claim 1 for which R _a represents a hydroxy radical, an alkoxy containing 1 to 4 carbon atoms, an acyloxy containing 1 to 4 carbon atoms or an alkoxyacetoxy in which the alkyl part contains 1 to 4 carbon atoms and Rb represents a hydrogen atom, Z represents a hydrogen atom or a radical of general formula (II) in which Ri represents a benzoyl radical or an R2-O-CO- radical in which R2 represents a tert-butyl radical and R3 represents an alkyl radical containing 1 to 6 carbon atoms, alkenyl containing 2 to 6 carbon atoms, cycloalkyl containing 3 to 6 carbon atoms, phenyl optionally substituted by one or more identical or different atoms or radicals chosen from halogen atoms (fluorine, chlorine) and alkyl, alkoxy, dialkoylamino, acylamino, al∞xycarlx ylamino or trifluoromethyl radicals or a furyl-2 radical or - 3, thienyl-2 or -3 or thiazolyl-2, -4 or -5 and R4 represents a phenyl radical optionally substituted by one or more atoms or radicals, identical or different, chosen from halogen atoms and alkyl radicals, alkoxy, amino, alkyllamino, dialkoylamino, acylamino, alkoxycarbonylamino, azido, trifluoromethyl and trifluoromethoxy, or a thienyl-2 or -3 or furyl-2 or -3 radical and R5 represents an optionally substituted alkyl radical containing 1 to 4 carbon atoms, it being understood that R5 cannot represent a methyl radical.

3 - New taxoids according to claim 1 for which R _a represents a hydrogen atom or a hydroxy or acetyloxy or methoxyacetoxy radical and Rb represents a hydrogen atom, Z represents a hydrogen atom or a radical of general formula (II ) in which Ri represents a benzoyl radical or an R2-O-CO- radical in which R2 represents a tert-butyl radical and R3 represents an isobutyl, isobutenyl, butenyl, cyclohexyl, phenyl, furyl-2, furyl-3, thienyl radical -2, thienyl-3, thiazolyl-2, thiazolyl-4 or thiazolyl-5 and R4 represents a phenyl radical optionally substituted by a halogen atom and R5 represents an alkyl radical containing 2 to 4 carbon atoms.

4 - Process for preparing a product according to one of claims 1 to 3 characterized in that it is treated with an alkali metal halide or an alkali metal azide or a quaternary ammonium salt or a metal phosphate alkaline a product of general formula:

OCOR ₄ in which Z, R4 and R5 are defined in one of claims 1 to 3, R _a represents a hydrogen atom or an alkoxy, acyloxy, alkoxyacetoxy radical or a protected hydroxy radical, and Rb represents an atom hydrogen and then replaces optionally the protective group represented by R _a by a hydrogen atom.

5 - Process for the preparation of a product according to one of claims 1 to 3 for which R4 and R5 are defined as in one of claims 1 to 3 and R _a and Rb each represent a hydrogen atom characterized in that that a product according to one of claims 1 to 3 is electrolytically reduced for which R _a represents a hydroxy, acyloxy or alkoxyacetoxy radical.

6 - Process for preparing a product according to one of claims 1 to 3 for which R4 and R5 are defined as in one of claims 1 to 3, R _a and Rb form together with the carbon atom to which they are linked a ketone function characterized in that one oxidizes a product according to one of claims 1 to 3 for which R _a represents a hydroxy radical and Rb represents a hydrogen atom.

7 - Pharmaceutical composition characterized in that eUe contains at least one product according to one of claims 1 to 3 for which Z represents a radical of general formula (II) in association with one or more pharmaceutically acceptable products whether they are inert or pharmacologically active.