Total synthesis of epothilone A.
[reaction: see text]Epothilones A (1) and B (2) are potent antitumor natural products with a Taxol-like mechanism of action. A total synthesis of epothilone A (1) is reported, which utilized chiral silane-based bond construction methodology to introduce the key C-6 and C-7 stereocenters of fragment 4. The C-15 stereocenter of fragment 5 was established by a lipase-mediated kinetic resolution. The fragments were assembled with a Suzuki coupling reaction and an aldol condensation and cyclized with a Yamaguchi-type macrolactonization reaction.
Zhu
B
B
Department of Chemistry and the Center for Streamlined Synthesis, Metcalf Center for Science and Engineering, Boston University, Massachusetts 02215, USA.
Panek
J S
JS
D000447:Aldehydes; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D034261:Epothilones; D004852:Epoxy Compounds / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D013844:Thiazoles / Q000138:chemical synthesis*
D000447:Aldehydes; D000970:Antineoplastic Agents; D034261:Epothilones; D004852:Epoxy Compounds; D007202:Indicators and Reagents; D013844:Thiazoles; C093787:epothilone A