Article

Total Synthesis of (+)-Lysergic Acid

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China
J. Org. Chem., 2013, 78 (21), pp 10885–10893
DOI: 10.1021/jo4018777
Publication Date (Web): October 10, 2013
Copyright © 2013 American Chemical Society

Abstract

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We report the enantioselective total synthesis of (+)-lysergic acid using two different strategies, which featured three metal-catalyzed reactions for the construction of the BCD three rings, involving Pd-catalyzed indole synthesis for the construction of the B ring, a ring-closing metathesis reaction for the formation of the D ring, and an intramolecular Heck reaction to forge the C ring. In synthetic strategy I, the synthesis was achieved in 20 steps following the ring construction sequence of BDC. In synthetic strategy II, the synthetic route was shortened to only 12 steps by following the ring construction sequence of DBC and using a 4-chlorotryptophan derivative for the intramolecular Heck reaction. Moreover, we also discussed an unsuccessful synthetic strategy.

1H and 13C NMR spectra for all new compounds. This material is available free of charge via the Internet at http://pubs.acs.org.

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Received 23 August 2013
Published online 10 October 2013
Published in print 1 November 2013
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