[摘要]：Studies leading to a total synthesis of epothilones B (I) and D (II) are described. The overall synthetic plan was based on late-stage fragment assembly of two segments representing C1-C9 and C10-C21 of the structure. The C1-C9 fragment was prepd. by elaboration of com. available (2R)-3-hydroxy-2-methylpropanoate at both ends of the three-carbon unit. Introduction of carbons 1-4 contg. the gem-di-Me unit was achieved in a convergent manner using a diastereoselective addn. of a stannane equiv. of a b-keto ester dianion. An enantioselective addn. of such a stannane equiv. for a b-keto ester dianion was also used to fashion one version of the C10-C21 subunit; however, the fragment assembly (using bimol. esterification followed by ring-closing metathesis) with this subunit failed. Therefore, fragment assembly was achieved using a Wittig reaction; this was followed by macrolactonization to close the macrocycle. The C10-C21 subunit needed for this approach was prepd. in an efficient manner using the Corey-Kim reaction as a key element. Other key reactions in the synthesis include a stereoselective SmI2 redn. of a b-hydroxy ketone and a crit. opening of a valerolactone with aniline which required extensive investigation.
