ORGN 857

The Mediterranean sponge Reniera sarai is a rich source of structurally unique alkaloids. The most remarkable of these, sarains A–C, were isolated by Cimino and coworkers in 1986 and fully characterized three years later. Soon after the isolation of sarains A–C, their unprecedented, intricate structures stimulated synthetic efforts in many laboratories worldwide. In this presentation, we will describe the first total synthesis of sarain A. Key steps in the synthesis include a diastereoselective Michael reaction to form the C7'– C3'–C4' stereocenters, a stereoselective enoxysilane/N-sulfonyliminium ion cyclization to assemble the diazatricycloundecane core and form the C3 quaternary-carbon stereocenter, and a late-stage intramolecular Stille coupling to construct the unsaturated macrocyclic ring of the natural product.