Model Study toward Total Synthesis of Mytilipin C

Synthetic studies on mytilipin C, belonging to the chlorosulfolipid (CSL) family, with a model substrate are described. Although the isolation and structure determination of mytilipin C were first reported by Ciminiello and Fattorusso in 2002, the originally proposed structure possibly needs revision because the originally proposed structure of mytilipin B, a similar natural product, was revised through excellent work by Carreira. Our synthetic study includes three unique reactions: (1) preparation of a labile alpha,ss-chlorinated Weinreb amide from an epoxide precursor, (2) nucleophilic addition of an acetylide to the resultant amide to give a labile alpha,ss-chlorinated ketone, and (3) effective formation of a highly functionalized acetylide from the corresponding iodoalkyne by treatment with Turbo Grignard reagent. The vicinal coupling constants between aand ss-protons of syn- and anti-alpha,ss-dichlorocarbonyl compounds show small and large values, respectively.