Enantioselective Total Synthesis of (+)- and (−)-Nigellamine A2

Jianwei Bian, Matthew Van Wingerden, and Joseph M. Ready*
Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038
J. Am. Chem. Soc., 2006, 128 (23), pp 7428–7429
DOI: 10.1021/ja061559n
Publication Date (Web): May 23, 2006
Copyright © 2006 American Chemical Society
*

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

, joseph.ready@utsouthwestern.edu

Abstract

Abstract Image

The nigellamine alkaloids are dolabellane diterpenes displaying potent lipid metabolism-promoting activity. Total synthesis of (+)- and (−)-nigellamine A2 has been accomplished. Absolute stereochemistry of synthetic nigellamine A2 was established through an intramolecular asymmetric allylic alkylation using a Pd(phosphinooxazoline) catalyst. Other notable transformations include a radical alkynylation, a diastereoselective Nozaki−Hiyama−Kishi cyclization, and a regio- and stereoselective catalytic epoxidation. On the basis of X-ray crystallographic analysis of an optically active intermediate, we have confirmed the assigned absolute stereochemistry of the natural product. Minor modifications of the synthetic sequence outlined here should provide access to the other nigellamine alkaloids.

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History

  • Published In Issue June 14, 2006
  • Received March 6, 2006

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