This proposal addresses a concise synthetic route to the recently isolated cytotoxic polycyclic alkaloids, communesins A and B. The title compounds share a number of structural motifs with a vanity of biologically active natural products, including chaetocin, quadrigemine C, kapakahine B, and ervafolene. Nonetheless, the specific array of functionality of the communesins is unique. A synthetic strategy is proposed that will address the construction of two adjacent chiral quaternary centers flanked by animals. Recent advances in the intramolecular Heck reaction will be built upon to prepare the constrained core of the communesins. Experiments meant to address control over regiochemistry and stereochemistry during the Heck reactions will be conducted. Development of these methods should have further application in the synthesis of the related natural products, and other therapeutically important targets.
