Patent ID: 6232477
Filing Date: 2001-05-15
Classification: C07D

Abstract:
A method of preparing a taxoid of general formula: ##STR36##in which:Z represents a hydrogen atom or a radical of general formula: ##STR37##in which:R.sub.1 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 R.sub.2 --O--C(.dbd.O)--, in whichR.sub.2 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;R.sub.3 represents a phenyl radical;R.sub.4 represents an alkanoyloxy radical in which the alkanoyl portion contains 2 to 6 carbon atoms in an unbranched or branched chain; andR.sub.5 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) ##STR38##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; anddeprotecting said methylthiomethylether derivative with an acid to produce the desired taxoid.