Total Synthesis and Configurational Validation of (+)-Phorbaside A

The configurational assignment of the cytotoxic marine macrolide phorbaside A has been verified by the stereodefined synthesis of the proposed structure 1 and its (18S,19R)-diastereomer 3, followed by correlation using circular dichroism spectroscopy. This first total synthesis, which proceeds in 8.2% yield over 23 steps, features two 1,4-syn boron aldol reactions, a Sonogashira coupling, and an alpha-glycosylation to append the L-evalose sugar moiety.