Exploiting orthogonally reactive functionality: synthesis and stereochemical assignment of (-)-ushikulide A.

In spite of the tremendous advances in modern spectroscopic methods, organic synthesis continues to play a pivotal role in elucidating the full structures of complex natural products. This method has the advantage that, even in the absence of a firm structural assignment, a combination of logic and spectroscopic comparison can arrive at the correct structure. Herein, we report execution of this strategy with respect to ushikulide A, a newly isolated and previously stereochemically undefined member of the oligomycin-rutamycin family. To maximize synthetic efficiency, we envisioned chemoselective manipulation of orthogonally reactive functional groups, notably alkenes and alkynes as surrogates for certain carbonyl and hydroxyl functionalities. This approach has the dual effect of minimizing the number of steps and protecting groups required for our synthetic route. This strategy culminated in the efficient synthesis and stereochemical assignment of ushikulide A.