Total Synthesis of Pestalotioprolide E and Structural Revision of Pestalotioprolide F.

A short and convergent strategy for the first asymmetric total synthesis of cytotoxic macrolides pestalotioprolides E and F has been developed. The key features of this synthesis include Takai olefination, Sonogashira coupling, Ni-assisted partial hydrogenation of alkyne, modified Steglich reaction to generate the ester moiety, and intramolecular Horner-Wadsworth-Emmons (HWE) olefination to complete the macrocycle. This synthetic study revised the proposed structure of pesralotioprolide F.