Enantioselective Synthesis of (+)-Hippolide J and Reevaluation of Antifungal Activity

A synthesis of the reported antifungal agent (+)-hippolide J is presented. The rapid assembly of the natural product was enabled through implementation of an enantioselective isomerization/[2 + 2]-cycloaddition sequence. Due to the simplicity of the route, >100 mg of the natural product were prepared in a single pass. Anitfungal assays of hippolide J, however, confirmed that it showed no activity against several fungal strains, contrary to the isolation report.