An enantioselective synthesis of natural anticancer macrolide pladienolide B is described. The synthetic highlights include Sharpless asymmetric epoxidation, ring closing metathesis (RCM), Ireland-Claisen rearrangement, Shi epoxidation, and Pd-catalyzed Stille coupling as key steps. The synthetic route also allowed the synthesis of the truncated analogues (41a-d) of pladienolide B.
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