Stereoselective Formation of a Functionalized Dipeptide Isostere by Zinc Carbenoid-Mediated Chain Extension

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• 作者：Weimin Lin ; Cory R. Theberge ; Timothy J. Henderson ; Charles K. Zercher ; Jerry Jasinski ; Ray. J. Butcher
• 刊名：Journal of Organic Chemistry
• 出版年：2009
• 出版时间：January 16, 2009
• 年：2009
• 卷：74
• 期：2
• 页码：645-651
• 全文大小：290K
• 年卷期：v.74,no.2(January 16, 2009)
• ISSN：1520-6904

文摘

The application of a zinc carbenoid-mediated chain-extension reaction to a functionalized peptide isostere is reported. The cleavage site of human CVM protease was utilized as a target for testing the synthetic methodology. The utility of this chain-extension reaction is demonstrated in the preparation of an amino acid-derived α-unsubstituted γ-keto ester, which is incorporated into a framework that mimics a tetrapeptide. The identification of a suitable protecting group strategy facilitated the application of a tandem reaction for the incorporation of an α-side chain, and the use of an oxazolidinone auxiliary provided excellent diastereocontrol in a tandem chain-extension−aldol reaction. Stereoselectivity of the tandem chain-extension−aldol reaction was determined through application of a CAN-mediated oxidative cleavage reaction.