Taxoids, their preparation and pharmaceutical compositions containing them

Claim 1

A method of preparing a compound of the formula II: ##STR28## in which Ar represents an aryl radical, R 1 represents a benzoyl radical or a radical R 2 --O--CO-- in which R 2 represents: a straight or branched 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 or a bicycloalkyl radical containing 7 to 11 carbon atoms, these radicals being unsubstituted or substituted by one or more substituents chosen from halogen atoms or hydroxy radicals, alkyloxy radicals containing 1 to 4 carbon atoms, dialkylamino radicals in which each alkyl portion contains 1 to 4 carbon atoms, piperidino radicals, morpholino radicals, 1-piperazinyl radicals, cycloalkyl radicals containing 3 to 6 carbon atoms, cycloalkenyl radicals containing 4 to 6 carbon atoms, phenyl radicals, cyano radicals, carboxy radicals or alkyloxycarbonyl radicals whose alkyl portion contains 1 to 4 carbon atoms, or a phenyl radical being unsubstituted or substituted by one or more atoms or radicals chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms or alkyloxy radicals containing 1 to 4 carbon atoms, or a saturated or unsaturated 4- to 6-membered nitrogen-containing heterocyclyl radial being unsubstituted or substituted by one or more alkyl radicals containing 1 to 4 carbon atoms, said cycloalkyl, cycloalkenyl or bicycloalkyl radicals for R 2 may also be substituted by one or more alkyl radicals containing 1 to 4 carbon atoms; R 3 and R 4 , which are identical or different, represent a hydrogen atom or an alkyl radical containing 1 to 4 carbon atoms, or an aralkyl radical whose alkyl portion contains 1 to 4 carbon atoms a phenyl radical or an aryl radical or R 3 represents an alkoxy radical containing 1 to 4 carbon atoms or a trihalomethyl radical or a phenyl radical substituted by a trihalomethyl radical and R 4 represents a hydrogen atom, or R 3 and R 4 form, together with the carbon atom to which they are attached, a 4- to 7-membered ring, and G 1 represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical or a hydroxy-protecting group, comprising the steps of reacting a compound of the formula (XXIII): ##STR29## with an alkali metal halide or an alkali metal azine or a quaternary ammonium salt or an alkali metal phosphate in an organic solvent and isolating the compound of formula (II).

Claim 2

A method of preparing a compound of the formula II: ##STR28## in which Ar represents an aryl radical, R 1 represents a benzoyl radical or a radical R 2 --O--CO-- in which R 2 represents: a straight or branched 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 or a bicycloalkyl radical containing 7 to 11 carbon atoms, these radicals being unsubstituted or substituted by one or more substituents chosen from halogen atoms or hydroxy radicals, alkyloxy radicals containing 1 to 4 carbon atoms, dialkylamino radicals in which each alkyl portion contains 1 to 4 carbon atoms, piperidino radicals, morpholino radicals, 1-piperazinyl radicals, cycloalkyl radicals containing 3 to 6 carbon atoms, cycloalkenyl radicals containing 4 to 6 carbon atoms, phenyl radicals, cyano radicals, carboxy radicals or alkyloxycarbonyl radicals whose alkyl portion contains 1 to 4 carbon atoms, or a phenyl radical being unsubstituted or substituted by one or more atoms or radicals chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms or alkyloxy radicals containing 1 to 4 carbon atoms, or a saturated or unsaturated 4- to 6-membered nitrogen-containing heterocyclyl radial being unsubstituted or substituted by one or more alkyl radicals containing 1 to 4 carbon atoms, said cycloalkyl, cycloalkenyl or bicycloalkyl radicals for R 2 may also be substituted by one or more alkyl radicals containing 1 to 4 carbon atoms; R 3 and R 4 , which are identical or different, represent a hydrogen atom or an alkyl radical containing 1 to 4 carbon atoms, or an aralkyl radical whose alkyl portion contains 1 to 4 carbon atoms a phenyl radical or an aryl radical or R 3 represents an alkoxy radical containing 1 to 4 carbon atoms or a trihalomethyl radical or a phenyl radical substituted by a trihalomethyl radical and R 4 represents a hydrogen atom, or R 3 and R 4 form, together with the carbon atom to which they are attached, a 4- to 7-membered ring, and G 1 represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical or a hydroxy-protecting group, comprising the steps of reacting a compound of the formula (XXIII): ##STR29## with an alkali metal halide or an alkali metal azine or a quaternary ammonium salt or an alkali metal phosphate in an organic solvent and isolating the compound of formula (II).

Claim 12

A method for preparing a taxoid of formula I: ##STR31## in which R represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical, R 1 represents a benzoyl radical or a radical R 2 --O--CO-- in which R 2 represents alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, phenyl or heterocyclyl radical, and Ar represents an aryl radical, comprising the steps of reacting a compound of the formula XXIV: ##STR32## in which G 1 represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical or a hydroxy-protecting group, R 3 represents a hydrogen atom or an alkoxy radical containing 1 to 4 carbon atoms or an unsubstituted or substituted aryl radical, and R 4 represents a hydrogen atom, with trifluoromethane acid or a derivative thereof, to give a compound of the formula XXIII: ##STR33## treating the compound of the formula XXIII with an alkali metal halide or an alkali metal azide or a quaternary ammonium salt or an alkali metal phosphate in an organic solvent to give a a compound of the formula II: ##STR34## isolating the treating the compound of formula II with an inorganic or organic acid in an organic solvent at a temperature of between -10° and 60° C. to give a product of the formula I or a compound of formula III: ##STR35## wherein G 1 represents a protecting group that is removed to give a product of formula I.

Claim 13

A method for preparing a taxoid of formula I: ##STR31## in which R represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical, R 1 represents a benzoyl radical or a radical R 2 --O--CO-- in which R 2 represents alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, phenyl or heterocyclyl radical, and Ar represents an aryl radical, comprising the steps of reacting a compound of the formula XXIV: ##STR32## in which G 1 represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical or a hydroxy-protecting group, R 3 represents a hydrogen atom or an alkoxy radical containing 1 to 4 carbon atoms or an unsubstituted or substituted aryl radical, and R 4 represents a hydrogen atom, with trifluoromethane acid or a derivative thereof, to give a compound of the formula XXIII: ##STR33## treating the compound of the formula XXIII with an alkali metal halide or an alkali metal azide or a quaternary ammonium salt or an alkali metal phosphate in an organic solvent to give a a compound of the formula II: ##STR34## isolating the treating the compound of formula II with an inorganic or organic acid in an organic solvent at a temperature of between -10° and 60° C. to give a product of the formula I or a compound of formula III: ##STR35## wherein G 1 represents a protecting group that is removed to give a product of formula I.

Claim 18

A method for preparing a taxoid of formula I: ##STR36## in which R represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical, R 1 represents a benzoyl radical or a radical R 2 --O--CO-- in which R 2 represents alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, phenyl or heterocyclyl radical, and Ar represents an aryl radical, comprising the steps of reacting a compound of the formula XXIV: ##STR37## in which G 1 represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical or a hydroxy-protecting group, R 3 and R 4 , which are identical or different, represent an alkyl radical containing 1 to 4 carbon atoms or an aralkyl radical whose alkyl portion contains 1 to 4 carbon atoms or an aryl radical, or R 3 represents a hydrogen atom, or R 3 and R 4 form, together with the carbon atom to which they are attached, a 4-7-membered ring, with trifluoromethanesulfonic acid or a derivative thereof, to give a compound of the formula XXIII: ##STR38## treating the compound of the formula XXIII with an alkali metal halide, an alkali metal azide, a quaternary ammonium salt, or an alkali metal phosphate in an organic solvent to give a a compound of the formula II: ##STR39## isolating the treating the compound of formula II with an inorganic or organic acid in an organic solvent at a temperature ranging from 0° to 50° C. to give a compound of formula IV: ##STR40## acylating the compound of formula IV using benzoyl chloride or a reactive derivative of the formula R 2 --O--CO--X in which R 2 is as defined above and X represents a halogen atom or a residue --O--R 2 or --O--CO--O--R 2 , to give a taxoid of formula I or a compound of formula III ##STR41## wherein G 1 represents a protecting group that is removed to form a taxoid of formula I.

Claim 19

A method for preparing a taxoid of formula I: ##STR36## in which R represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical, R 1 represents a benzoyl radical or a radical R 2 --O--CO-- in which R 2 represents alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, phenyl or heterocyclyl radical, and Ar represents an aryl radical, comprising the steps of reacting a compound of the formula XXIV: ##STR37## in which G 1 represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical or a hydroxy-protecting group, R 3 and R 4 , which are identical or different, represent an alkyl radical containing 1 to 4 carbon atoms or an aralkyl radical whose alkyl portion contains 1 to 4 carbon atoms or an aryl radical, or R 3 represents a hydrogen atom, or R 3 and R 4 form, together with the carbon atom to which they are attached, a 4-7-membered ring, with trifluoromethanesulfonic acid or a derivative thereof, to give a compound of the formula XXIII: ##STR38## treating the compound of the formula XXIII with an alkali metal halide, an alkali metal azide, a quaternary ammonium salt, or an alkali metal phosphate in an organic solvent to give a a compound of the formula II: ##STR39## isolating the treating the compound of formula II with an inorganic or organic acid in an organic solvent at a temperature ranging from 0° to 50° C. to give a compound of formula IV: ##STR40## acylating the compound of formula IV using benzoyl chloride or a reactive derivative of the formula R 2 --O--CO--X in which R 2 is as defined above and X represents a halogen atom or a residue --O--R 2 or --O--CO--O--R 2 , to give a taxoid of formula I or a compound of formula III ##STR41## wherein G 1 represents a protecting group that is removed to form a taxoid of formula I.