Synthetic Studiesof Zoaramine: Construction of theTetracyclic Skeleton in High Oxidation State

We report herein the synthetic studies toward zoaramine, a member of the family of zoaramine-type marine natural products bearing a unique structure. The major synthetic challenge is the stereoselective construction of the congested tetracyclic [6–6–6–6] skeleton in a high oxidation state. Our key strategies are the following: (1) radical cyclization was designed to install the quaternary stereocenters at C-9, C-22, and C-12 as well as formation of the B and D rings; (2) selective oxidations were realized to introduce the functional groups at C-11 and C-24 by using O₂/<i>t</i>-BuOK-promoted hydroxylation and MeReO₃-catalyzed Rubottom oxidation. Our studies reveal a special reactivity and stereocontrol model in the specific chemical environments, which might benefit the related synthetic exploration of this family of natural alkaloids.