Enantioselective Total Syntheses of Lyconadins A-E through a Palladium-Catalyzed Heck-Type Reaction

Jiayang Zhang; Yangtian Yan; Rong Hu; Ting Li; Wen-Ju Bai; Yang Yang

doi:10.1002/anie.201912948

Enantioselective Total Syntheses of Lyconadins A-E through a Palladium-Catalyzed Heck-Type Reaction

Angew Chem Int Ed Engl. 2020 Feb 10;59(7):2860-2866. doi: 10.1002/anie.201912948. Epub 2020 Jan 7.

Authors

Jiayang Zhang¹, Yangtian Yan¹, Rong Hu¹, Ting Li¹, Wen-Ju Bai², Yang Yang¹

Affiliations

¹ Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei, 430030, China.
² Department of Chemistry, Stanford University, Stanford, CA, 94305-5080, USA.

PMID: 31743549
DOI: 10.1002/anie.201912948

Abstract

A novel palladium-catalyzed Heck-type reaction of thiocarbamates has been designed to construct bridged seven-membered-ring systems that are otherwise challenging to prepare. Taking advantage of this newly developed method, enantioselective syntheses of lyconadins A-E (1-5), lycopecurine (6), and dehydrolycopecurine (7) have been realized in a divergent fashion. Our synthetic strategy also features an intramolecular cyclization of a N-chloroamine to forge the C6-N bond, a transannular Mannich-type reaction of a cyclic nitrone to stitch the C4 and C13 together, and a cyclocondensation to deliver the (dihydro-)pyridone motif.

Keywords: Heck-type reactions; alkaloids; natural products; total synthesis; transannular cyclization.

Publication types

Research Support, Non-U.S. Gov't