Enantioselective Formal Total Synthesis of (+)-Aspergillide C

Abstract

An enantioselective formal total synthesis of the cytotoxic macrolide (+)-aspergillide C has been accomplished from (S)-(-)-glyceraldehyde acetonide and the Danishefsky-Kitahara diene. Strategic transformations include a hetero Diels-Alder reaction, Ferrier-type addition, and palladium-catalyzed oxidative lactonization to set key stereocenters within the dihydropyran core, followed by fragment coupling via (E)-selective Julia-Kocienski olefination.