Organic Chemistry

Collective Total Synthesis of Mavacuran Alkaloids via an Intermo-lecular 1,4-Addition Approach



We report a synthetic endeavor towards the highly strained pentacyclic caged framework of the mavacuran alkaloids which culminated with the concise total synthesis of C-fluorocurine, C-profluorocurine, C-mavacurine, normavacurine, 16-epi-pleiocarpamine and taberdivarine H. We designed an original strategy which involves a late stage construction of the D ring via a Michael addition of a vinylic nucleophile to a 2-indolyl acrylate moiety. While the intramolecular Michael addition did not succeed, we were able to perform a diastereoselective unusual intermolecular 1,4-addition of a functionalized vinyl lithium reagent onto a readily accessible Michael acceptor. Final cyclization was achieved via nucleophilic substitution into an ammo-nium intermediate. The first total syntheses of C-profluorocurine and C-fluorocurine were finalized via respectively the dihy-droxylation of C-mavacurine and a pinacol rearrangement.


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