Process for the esterification of baccatin III and of 10-deacety

Details Process for the esterification of baccatin III and of 10-deacety Process for the esterification of baccatin III and of 10-deacety

1995-04-05

1998-02-10

Trinh, Ba K.

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

549510, 549511, C07D26306, C07D30514

Patent

active

057171033

DESCRIPTION:

BRIEF SUMMARY
DESCRIPTION OF THE INVENTION

The present invention relates to the preparation of esters of baccatin III and of 10-deacetylbaccatin III of general formula: ##STR2## by esterification of suitably protected baccatin III or 10-deacetylbaccatin III of general formula: ##STR3## using an activated acid of general formula: ##STR4##
In the general formulae (I), (II) and (III), the various symbols are defined in the following way: R.sub.4 --O--CO-- in which R.sub.4 represents: 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 or a bicycloalkyl radical containing 7 to 10 carbon atoms, these radicals optionally being substituted by one or a number of substituents chosen from halogen atoms and hydroxyl radicals, alkyloxy radicals containing 1 to 4 carbon atoms, dialkylamino radicals in which each alkyl part contains 1 to 4 carbon atoms, piperidino radicals, morpholino radicals, 1-piperazinyl radicals (optionally substituted in 4- by an alkyl radical containing 1 to 4 carbon atoms or by a phenylalkyl radical whose alkyl part contains 1 to 4 carbon atoms), cycloalkyl radicals containing 3 to 6 carbon atoms, cycloalkenyl radicals containing 4 to 6 carbon atoms, phenyl radicals, cyano radicals, carboxyl radicals or alkyloxycarbonyl radicals in which the alkyl part contains 1 to 4 carbon atoms, radicals chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms or alkyloxy radicals containing 1 to 4 carbon atoms, to 6 members and optionally substituted by one or a number of alkyl radicals containing 1 to 4 carbon atoms, radicals can optionally be substituted by one or a number of alkyl radicals containing 1 to 4 carbon atoms, represent a hydrogen atom, R.sub.2 and R.sub.3 together form a 5- or 6-membered saturated heterocycle, functional group,
More particularly, Ar and the aryl portion of the aroyl radical represented by R.sub.1, which are identical or different, represent an optionally substituted phenyl or .alpha.- or .beta.-naphthyl radical, it being possible for the substituents to be chosen from halogen atoms (fluorine, chlorine, bromine, iodine) and alkyl, alkenyl, alkynyl, aryl, arylalkyl, alkoxy, alkylthio, aryloxy, arylthio, hydroxyl, hydroxyalkyl, mercapto, formyl, acyl, acylamino, aroylamino, alkoxycarbonylamino, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, carbamoyl, dialkylcarbamoyl, cyano, nitro and trifluoromethyl radicals, it being understood that the alkyl radicals and the alkyl portions of the other radicals contain 1 to 4 carbon atoms, the alkenyl and alkynyl radicals contain 3 to 8 carbon atoms and that the aryl radicals are phenyl or .alpha.- or .beta.-naphthyl radicals.
More particularly still, Ar and the aryl portion of the aroyl radical represented by R.sub.1, which are identical or different, represent a phenyl radical optionally substituted by a chlorine or fluorine atom or by an alkyl (methyl), alkyloxy (methoxy), dialkylamino (dimethylamino), acylamino (acetylamino) or alkyloxycarbonylamino (t-butoxycarbonylamino) radical.
More particularly, R.sub.3 represents a protective group of the hydroxyl functional group chosen from methoxymethyl, 1-ethoxyethyl, benzyloxymethyl, .beta. -trimethylsilylethoxymethyl, tetrahydropyranyl, 2,2,2-trichloroethoxymethyl, 2,2,2-trichloroethoxycarbonyl or --CH.sub.2 --Ph radicals, in which Ph represents a phenyl radical optionally substituted by one or a number of atoms or radicals, which are identical or different, chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms or alkyloxy radicals containing 1 to 4 carbon atoms.
More particularly, when R.sub.2 and R.sub.3 together form a 5- or 6-membered saturated heterocycle, the latter represents an oxazolidine ring substituted in the 2-position by 1 or 2 substituents, which are identical or different, chosen from hydrogen atoms and alkyl radicals containing 1 to 4 carbon atoms, alkoxy radicals containing 1 to 4 carbon atoms, aralkyl radicals whose alkyl part contains 1

REFERENCES:
patent: Re34277 (1993-06-01), Denis et al.
patent: 4924011 (1990-05-01), Denis et al.
patent: 4942184 (1990-07-01), Haugwitz et al.
patent: 5476954 (1995-12-01), Bourzat et al.
Jerry March, Advanced Organic Chemistry-Reactions, Mechanism, and Structure (3rd Edition) 346-348, 1985.
Denis et al., Journal of the American Chemical Society 110 (17): 5917-5919 (Aug. 1988).
Denis et al., The Journal of Organic Chemistry 51 (1): 46-50 (Jan. 1986).
H. Pielartzik et al. "Carbonsaure-erter", pp. 656-684, 1995.

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