Concise Asymmetric Syntheses of Radicicol and Monocillin I

Robert M. Garbaccio, Shawn J. Stachel, Daniel K. Baeschlin, and Samuel J. Danishefsky*
Contribution from The Laboratory for Bioorganic Chemistry, The Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10021
J. Am. Chem. Soc., 2001, 123 (44), pp 10903–10908
DOI: 10.1021/ja011364+
Publication Date (Web): October 10, 2001
Copyright © 2001 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.

Abstract

Radicicol (1) exhibits potent anticancer properties in vitro, which are likely to be mediated through its high affinity (20 nM) for the molecular chaperone Hsp90. Recently, we reported the results of a synthetic program targeting radicicol (1) and monocillin I (2), highlighted by the application of ring-closing metathesis to macrolide formation. These efforts resulted in a highly convergent synthesis of radicicol dimethyl ether but failed in the removal of the two aryl methyl ethers. Simple exchange of these methyl ethers with more labile functionalities disabled a key esterification in the initial route. Through extended experimentation, a successful route to both natural products was secured, along with some intriguing results that emphasize the implications of this design on a broad range of fused benzoaliphatic targets, including analogues of these natural products.

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History

  • Published In Issue November 07, 2001
  • Received June 4, 2001

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