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.