EPOTHILONE DERIVATIVES AND THEIR SYNTHESIS AND USE

摘要

The invention relates to epothilone analog represented by formula (I) wherein (i) R>2< is absent or oxygen; "a" can be either a single or double bond; "b" can be either absent or a single bond; and "c" can be either absent or a single bond, with the proviso that if R>2< is oxygen then "b" and "c" are both a single bond and "a" is a single bond; if R>2< is absent then "b" and "c" are absent and "a" is a double bond; and if "a" is a double bond, then R>2<, "b" and "c" are absent; R>3< is a radical selected from the group consisting of hydrogen; lower alkyl; -CH=CH>2<; -CCH; -CH>222<-OH; -CH>2<-O-(C>1<-C>6<-alkyl); and -CH>2<-S-(C>1<-C>6<-alkyl); R>4< and R>5< are independently selected from hydrogen, methyl or a protecting group; and R>1< is as defined in the specification, or a salt of a compound of formula (I) where a salt-forming group is present. A further aspect of the invention is related to the synthesis of epothilone E. These compounds have inter alia microtubuli depolymerisation inhibiting activity and are e.g. useful against proliferative diseases.