Synthesis of 6- <i>epi</i> -Hypersampsone R by a Desymmetrization Strategy

We report an approach to hypersampsone R that results in a 10-step synthesis of 6-<i>epi</i>-hypersampsone R, a polycyclic polyprenylated acylphloroglucinol (PPAP) possessing a rare bicyclo[3.3.1]nonane-2-8-dione core. This strategy includes a high-yielding and scalable synthesis of an achiral [3.3.1] bicyclic bis-enone that is further elaborated via bridgehead functionalization and desymmetrization. The synthesis is completed through a one-pot conjugate addition/acylation strategy to construct the final two carbon-carbon bonds. Overall, the general strategy of (i) core synthesis, (ii) desymmetrization, and (iii) functionalization outlined herein may provide a general platform for the synthesis of structurally related PPAPs.