Total synthesis of (+)-18-epi-latrunculol A: development of a synthetic route.

Abstract

The evolution of an enantioselective total synthesis of (+)-18-epi-latrunculol A, a congener of the marine-sponge-derived latrunculins A and B, is reported. Key steps include a late-stage Mitsunobu macrolactonization to construct the 16-membered macrolactone, a mild Carreira alkynylation to unite the northern and southern hemispheres, a diastereoselective, acid-mediated δ-hydroxy enone cyclization/equilibration sequence, and a functional-group-tolerant cross-metathesis to access the enone cyclization precursor.