Epothilone derivatives and their synthesis and use

摘要

The invention relates to epothilone analog represented by the formula I wherein (i) R2 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 R2 is oxygen then "b" and "c" are both a single bond and "a" is a single bond; if R2 is absent then "b" and "c" are absent and "a" is a double bond; and if "a" is a double bond, then R2, "b" and "c" are absent; R3 is a radical selected from the group consisting of hydrogen; lower alkyl; -CH-CH2; -C≡CH; -CH2F; -CH2Cl; -CH2-OH; -CH2-O-(C1-C6-alkyl); and -CH2-S-(C1-C6-alkyl); R4 and R5 are independently selected from hydrogen, methyl or a protecting group; and R1 is as defined in the specification, or a salt of a compound of the 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.