Total Synthesis of seco-Plakortolide E and (-)-ent-Plakortolide I: Absolute Configurational Revision of Natural Plakortolide I

A first total synthesis of (-)-ent-plakortolide I and seco-plakortolide E was accomplished from (S)-2-methylglycidol. The relevant key reactions involve a diastereoselective Mukaiyama aldol reaction, a regioselective hydroperoxysilylation, and elaboration of the 1,2-dioxane ring by intramolecular Michael addition of a hydroperoxide group to a butenolide. This synthesis allowed the revision of the absolute configuration of plakortolide I and structural revision of plakortolide E.