Total Synthesis of Voratin C: Formation of the [6,5]-Spiroketal Core through Acid-Mediated Epoxide Cascade Opening

An enantioselective total synthesis of voratin C is reported. Key steps include a ketalization through an epoxide-opening cascade to construct the spiroketal core. An enriched Sharpless dihydroxylation, followed by a stereospecific diol-to-epoxide conversion, furnished the key epoxide intermediate. The carbon skeleton of the natural product was assembled in a cross-olefin metathesis between a vinylpyridine and a C10-C18 alkene fragment. The C3 stereocenter was established via an enantioselective Cu-mediated conjugate reduction of an acrylonitrile.