Claims
- 1. A method of preparing a taxoid of general formula: in which:Z represents a hydrogen atom or a radical of general formula: in which:R1 represents a benzoyl radical unsubstituted or substituted with one or more identical or different atoms or radicals selected from halogen atoms, and alkyl radicals containing 1 to 4 carbon atoms, alkoxy radicals containing 1 to 4 carbon atoms or trifluoromethyl radicals, a thenoyl radical, a furoyl radical, and a radical R2—O—C(═O)—, in which R2 represents an alkyl radical containing 1 to 8 carbon atoms, an alkenyl radical containing 2 to 8 carbon atoms, an alkynyl radical containing 3 to 8 carbon atoms, a cycloalkyl radical containing 3 to 6 carbon atoms, a cycloalkenyl radical containing 4 to 6 carbon atoms, a phenyl atoms, alkyl radicals containing 1 to 4 carbon atoms, and alkoxy radicals containing 1 to 4 carbon atoms), cyano radicals, carboxyl radicals, and alkoxycarbonyl radicals in which the alkyl portion contains 1 to 4 carbon atoms; R3 represents a phenyl radical; R4 represents an alkanoyloxy radical in which the alkanoyl portion contains 2 to 6 carbon atoms in an unbranched or branched chain; and R5 represents an alkoxy radical containing 1 to 4 carbon atoms in an unbranched or branched chain, substituted by an alkylthio radical containing 1 to 4 carbon atoms, comprising: silylating a baccatin of formula (IX) to obtain a silylated baccatin, where the silylation occurs at position 7;acetylating said silylated baccatin to obtain a protected baccatin, wherein said acetylation occurs at position 10; coupling the protected baccatin with an oxazolidine ring optionally monosubstituted or gem-disubstituted at position 2 to produce a coupled ester; deprotecting said coupled ester with an acid to produce a desilylated taxoid; reacting said desilylated taxoid in a Pummerer reaction to produce a methylthiomethylether derivative; and deprotecting said methylthiomethylether derivative with an acid to produce the desired taxoid.
- 2. The method for preparing a taxoid according to claim 1 in which Z represents a radical of general formula (II), in whichR1 represents a benzoyl radical or a radical R2—O—C(═O)— in which R2 represents a tert-butyl radical; R3 represents a phenyl radical; R4 represents an alkanoyloxy radical in which the alkanoyl portion contains 2 to 4 carbon atoms; and R5 represents an alkoxy radical containing 1 to 4 carbon atoms substituted by a methylthio radical.
- 3. The method for preparing a taxoid according to claim 1 for which Z represents a hydrogen atom or a radical of general formula (II) in which R1 represents a benzoyl radical or a radical R2—O—C(═O)— in whichR2 represents a tert-butyl radical; R3 represents a phenyl radical; R4 represents an acetoxy or methoxyacetoxy radical; and R5 represents a methylthiomethoxy radical.
- 4. The method of preparing a taxoid of claim 1, wherein R4 is acetoxy.
- 5. The method of claim 1 wherein the taxoid (2R,3S)-3-benzoyl-2-hydroxy-3-phenyl propionate of 4,10β-diacetoxy-2α-benzoyloxy-5β,20-epoxy-1,13α-dihydroxy-7β-methylthiomethyloxy-9-oxo-tax-11-ene (XXXIV) is prepared.
- 6. The method of claim 1 wherein the taxoid (2R,4S,5R) -3-benzoyl-2-(4-methoxyphenyl)-4-phenyloxazolidine-5-carboxylate of 4,10β-diacetoxy-2α-benzoyloxy-5β,20-epoxy-1,13α-dihydroxy-7β-methylthiomethyloxy-9-oxo-tax-11-ene (XXXIII) is prepared.
- 7. A method of preparing a pharmaceutical composition, comprising preparing least one taxoid by the method of claim 1, in which Z represents a radical of general formula (II), and combining said at least one taxoid with one or more pharmaceutically acceptable carriers.
- 8. A method of preparing a pharmaceutical composition, comprising preparing at least one taxoid by the method of claim 5 or claim 6, and combining said at least one taxoid with one or more pharmaceutically acceptable carriers.
- 9. The method of claim 8, wherein the pharmaceutically acceptable carrier is a diluent or adjuvant.
- 10. The method of claim 8, further comprising another pharmacologically active compound.
- 11. The method of claim 9, further comprising another pharmacologically active compound.
- 12. A method of preparing a taxoid of general formula (XIV) comprising:silylating the baccatin of formula (IX) to obtain a silylated baccatin wherein said silylation occurs at position 7;acetylating said silylated baccatin to obtain a protected baccatin of formula (XXX), wherein said acetylation occurs at position 10; coupling the protected baccatin of formula (XXX) with a compound of formula (XXXa) to produce a coupled ester of formula (XXXI); deprotecting said coupled ester with an acid to produce a desilylated taxoid of formula (XXXII); reacting said desilylated taxoid in a Pummerer reaction to produce a methylthiomethylether derivative of formula (XXXIII); anddeprotecting said methylthiomethylether derivative with an acid to produce a compound of formula (XXXIV).
Parent Case Info
This is a continuation-in-part of U.S. patent application Ser. No. 09/271,300, filed Mar. 17, 1999, now U.S. Pat. No. 6,040,466, which is a continuation-in-part of U.S. patent application Ser. No. 08/913,972, filed on Sep. 26, 1997, now U.S. Pat. No. 5,889,043; and a continuation of PCT/FR96/00441, filed Mar. 25, 1996, all of which are incorporated herein by reference.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
5646176 |
Golik et al. |
Jul 1997 |
|
Foreign Referenced Citations (4)
Number |
Date |
Country |
0639577A1 |
Feb 1995 |
EP |
0694539 |
Jan 1996 |
EP |
WO9418164 |
Aug 1994 |
WO |
WO9600724 |
Jan 1996 |
WO |
Continuations (1)
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Number |
Date |
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Parent |
PCT/FR96/00441 |
Mar 1996 |
US |
Child |
08/913972 |
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US |
Continuation in Parts (2)
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Number |
Date |
Country |
Parent |
09/271300 |
Mar 1999 |
US |
Child |
09/528448 |
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US |
Parent |
08/913972 |
Sep 1997 |
US |
Child |
09/271300 |
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US |