Concise Asymmetric Syntheses of Radicicol and Monocillin I

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• 作者：Robert M. Garbaccio ; Shawn J. Stachel ; Daniel K. Baeschlin ; and Samuel J. Danishefsky
• 刊名：Journal of the American Chemical Society
• 出版年：2001
• 出版时间：November 7, 2001
• 年：2001
• 卷：123
• 期：44
• 页码：10903 - 10908
• 全文大小：102K
• 年卷期：v.123,no.44(November 7, 2001)
• ISSN：1520-5126

文摘

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