Collective Total Synthesis of Ergot Alkaloids

Ergot alkaloids represent a class of bioactive natural products that contain a tetrahydrobenzo[cd]indole structural unit. We report a structural unit-oriented collective total synthesis of nine tetracyclic ergot alkaloids. Among them, isopenniclavine and roquefortine A were synthesized for the first time. Key transformations of our strategy are a vinylogous arylation to establish the C10-C11 bond, an intramolecular diastereoselective vinylogous Mannich reaction to construct the critical tricyclic ergoline core along with two vicinal chiral stereocenters at C5 and C10, and a consecutive Mannich cyclization/reductive N-methylation to build the D ring.