Structural Revision of (+)-Uprolide F Diacetate Confirmed by Asymmetric Total Synthesis

A new structure for the cytotoxic cembranolide uprolide F diacetate (UFD) was proposed, and an enantioselective total synthesis was accomplished to confirm that our revised structure correctly represented the natural UFD and its absolute configuration. Our synthesis features a late-stage, highly efficient, and diastereoselective Nozaki-Hiyama-Kishi macrocyclization (95% yield) and an unexpected reagent-controlled reversible translactonization, which, being the first example within the cembranolide family, might have biogenetic implications and be of great importance to synthetic studies of the α-methylene-γ-lactone-bearing cembranolides.