Collective Total Synthesis of Ergot Alkaloids
Fuye Wang1, Botao Bao1, Li Yang1
1Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Key Laboratory of Research and Development for Natural Products, Yunnan Characteristic Plant Extraction Laboratory, School of Pharmacy, Yunnan University, Kunming, Yunnan 650500, P. R. China.
Abstract:
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.
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