Total synthesis of palmyrolide A and its 5,7-epi isomers

Abstract

Stereoselective total synthesis of palmyrolide A, a 15-membered neuroactive macrolide, was described by adopting a synthetic strategy developed for the proposed structures, and its 5,7-epi isomers. The strategy was designed in such a way that the set of stereoisomers, which were needed for establishing the absolute configuration of palmyrolide A, could be obtained from one time operation. The diastereoselective hydrogenation of exo-methylene-γ-butyrolactone to α-methyl-γ-butyrolactone, Yamaguchi esterfication, and intramolecular dehydrative cyclization to form trans-enamide were the key steps involved in the synthesis.