A Second-Generation Synthesis of the C1−C28 Portion of the Altohyrtins (Spongistatins)

Jed L. Hubbs and Clayton H. Heathcock*
Contribution from the Center for New Directions in Organic Synthesis, Department of Chemistry, University of California, Berkeley, California 94720
J. Am. Chem. Soc., 2003, 125 (42), pp 12836–12843
DOI: 10.1021/ja030316h
Publication Date (Web): September 27, 2003
Copyright © 2003 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.

, heathcock@cchem.berkeley.edu

Abstract

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A practical second-generation synthesis of an advanced intermediate in our total synthesis of altohyrtin C (spongistatin 2) has been developed. A new approach to the C1−C15 (AB) portion features a vinyllithium addition to an aldehyde followed by a palladium-catalyzed allylic reduction to install the troublesome C13−C15 segment. Our general approach to the C16−C28 (CD) spiroketal has been retained, but some improvements have been made. Most notably, the kinetically controlled CD-spiroketalization reaction now proceeds in high yield with excellent diastereoselection. This new strategy uses the anti-aldol coupling used in our first-generation synthesis to join AB and CD fragments. A total of 9.6 g of intermediate 57 has been produced using this improved route.

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History

  • Published In Issue October 22, 2003
  • Received May 27, 2003

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