Stereoselective Formation of a Functionalized Dipeptide Isostere by Zinc Carbenoid-mediated Chain Extension
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.
Journal of Organic Chemistry
American Chemical Society
Digital Object Identifier (DOI)
Stereoselective Formation of a Functionalized Dipeptide Isostere by Zinc Carbenoid-mediated Chain Extension, Lin, W.; Theberge, C. R.; Henderson, T. J.; Zercher, C. K.; Jasinski, J. P., Butcher, R. J. J. Org. Chem. 2009, 74, 645-651. PMCID: PMC2680025
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