Total Synthesis of Ipomoeassin F and Its Analogs for Biomedical Research

As a unique family of resin glycosides, ipomoeassins exhibit exceptionally high potency against cancer cell growth with a novel unknown mode of action. This account describes the development of a more efficient synthetic route for scalable assembly of ipomoeassin F, a flagship congener of the family. The new synthesis highlights a series of highly regioselective transformations, including α configuration-controlled allyloxycarbonylation of a glucose diol, TBS silylation of a fucose triol, and stereospecific β glycosylation of a fucose diol. Immediately after the completion of the synthesis, we also embarked on systematic exploration of structure–activity relationship for ipomoeassin F and acquired a great amount of firsthand information on its pharmacophore. The new knowledge on organic synthesis and medicinal chemistry studies will expand applications of the ipomoeassins to more areas of biomedical research in the future.