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 methyl (R)-3-hydroxy-2-methylpropionate. The synthesis is highly convergent by coupling the three fragments C1-C6 (fragment D), C7-C10 (fragment C), and C11-C21 (fragment B). Key steps are two stereoselective Wittig type olefinations to generate the 12,13- and 16,17-double bonds, an enantioselective Mukaiyama aldol addition to synthesize fragment D, and a sulfone anion allyl iodide alkylation to connect fragments B and C. Finally fragment D was attached to the B + C fragment via aldol addition.
Mulzer
J
J
Institut fuer Organische Chemie, Universitaet Wien,Waehringerstrasse 38, A-1090 Wien, Austria.
Mantoulidis
A
A
Ohler
E
E
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis*; D034261:Epothilones; D004852:Epoxy Compounds / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D013844:Thiazoles / Q000138:chemical synthesis*
D000972:Antineoplastic Agents, Phytogenic; D034261:Epothilones; D004852:Epoxy Compounds; D007202:Indicators and Reagents; D013844:Thiazoles; C114026:desoxyepothilone B