Patent ID: 6043359
Filing Date: 2000-03-28
Classification: C07D

Abstract:
A process for preparing predominantly enantiomerically enriched (+) galanthamine, (-) galanthamine, (+) epigalanthamine, (-) epigalanthamine, or derivatives thereof, comprising the steps of:(A) condensing a compound of formula (III): ##STR16## where X.sub.1 is halogen; or an alkyl, an aralkyl, an aryloxyalkyl, a formyl, an alkylcarbonyl, an arylcarbonyl, an aralkylcarbonyl, an alkyloxycarbonyl, an aryloxycarbonyl, an aralkyloxycarbonyl, an alkylsulfonyl, an aralkylsulfonyl or arylsulfonyl group, optionally substituted by at least one halogen;R.sub.1 and R.sub.2 are independently hydrogen; or an alkyl, an alkenyl, an alkynyl, an aryl, an aralkyl, an aryloxyalkyl, a formyl, an alkylcarbonyl, an arylcarbonyl, an aralkylcarbonyl, an alkyloxycarbonyl, an aryloxycarbonyl, an aralkyloxycarbonyl, an alkylsulfonyl, an aralkylsulfonyl, or arylsulfonyl group, optionally substituted by at least one halogen; and,A is hydrogen; halogen; or a lower alkyl, a lower alkenyl, an alkynyl, an alkoxy, aralkyl, or an alkyl substituted by at least one halogen, hydroxyl, a primary amino, a secondary amino, a tertiary amino, a nitro, a nitrile, an alkylamino, an arylamino, an aldehyde, a carboxylic acid, an ester, an amide or an acyl halide;with a compound of formula (IV): ##STR17## where X.sub.2 is hydrogen; halogen; hydroxyl; or is an alkoxy, an alkyl, an alkenyl, an alkynyl, an aryl, an aralkyl, an aryloxyalkyl, a formyl, an alkylcarbonyl, an arylcarbonyl, an aralkylcarbonyl, an alkyloxycarbonyl, an aryloxycarbonyl, an aralkyloxycarbonyl, an alkylsulfonyl, an aralkylsulfonyl or arylsulfonyl group, optionally substituted by at least one halogen;R.sub.3 is hydrogen; or an alkyl, an alkenyl, an aryl, an aralkyl, an alkylcarbonyl, an arylcarbonyl or aralkylcarbonyl group, optionally substituted by least one halogen; andR.sub.4 is hydrogen;to form a Schiff base;(B) reducing the Schiff base to produce a compound of formula (V): ##STR18## (C) optionally, reacting the compound of formula (V) with a reactive compound selected from the group comprising an acid, an ester, an anhydride, a halide, an azide or a carbonate to form a compound of formula (V) where R.sub.4 is selected from the group consisting of formyl, branched or unbranched aralkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, alkyloxycarbonyl, aryloxycarbonyl, aralkyloxycarbonyl, alkylsulfonyl, arylsulfonyl and aralkylsulfonyl, and where R.sub.4 is optionally substituted by least one halogen;(D) oxidatively cyclizing the compound of formula (V) from step (B) or step (C) to form a compound of formula (VI): ##STR19## (E) stereoselectively reducing the compound of formula (VI) to form at least one compound of formula (I): ##STR20## wherein the ratio of compound (VI) to solvent in the stereoselective reduction is less than about 200:1 and where one of Y.sub.1 or Y.sub.2 is hydrogen and the other is hydroxyl.