Total syntheses of epothilones B and D

Total syntheses of the microtubule stabilizing antitumor drugs epothilone B and D are described, starting from optically pure (S)-malic acid and methy l (R)-3-hydroxy-2-methylpropionate. The synthesis is highly convergent by c oupling the three fragments C1-C6 (fragment D), C7-C10 (fragment C), and C1 1-C21 (fragment B). Key steps are two stereoselective Wittig type olefinati ons to generate the 12,13- and 16,17-double bonds, an enantioselective Muka iyama aldol addition to synthesize fragment D, and a sulfone anion allyl io dide alkylation to connect fragments B and C. Finally fragment D was attach ed to the B + C fragment via aldol addition.