Total Synthesis of Asperchalasines†A, D, E, and H.

ABSTRACT

The first total syntheses of the cytochalasan dimers asperchalasines A, D, E, and H have been accomplished. The key steps of the synthesis include a highly stereoselective intermolecular Diels-Alder reaction and a Horner-Wadsworth-Emmons macrocyclization to establish the key monomer aspochalasin B, and an intermolecular Diels-Alder reaction followed by a biomimetic oxidative heterodimerization by 5+2 cycloaddition to furnish asperchalasine A. The synthetic efforts provide insight into the biosynthetic pathway of cytochalasan dimers and enables the further study of their biological properties.