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Alkene-alkyne coupling as a linchpin: an efficient and convergent synthesis of amphidinolide P
Barry M Trost1, Julien P N Papillon
1Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA. bmtrost@stanford.edu
Abstract:
A short and efficient synthesis of the cytotoxic macrolide amphidinolide P is described. A remarkably chemo- and regioselective ruthenium-catalyzed alkene-alkyne coupling allows for a convergent synthesis and demonstrates that both enynes and beta-lactones are suitable coupling partners. This work also features a novel strategy for the preparation of macrolactones via intramolecular transesterification of beta-lactones. The target structure was prepared in 15 steps for the longest linear sequence and 10% overall yield, 24 steps total.
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