Stereoselective formation of a functionalized dipeptide isostere by zinc carbenoid-mediated chain extension.

Academic Article


  • 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 alpha-unsubstituted gamma-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 alpha-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.
  • Authors

  • Lin, Weimin
  • Theberge, Cory R
  • Henderson, Timothy J
  • Zercher, Charles
  • Jasinski, Jerry
  • Butcher, Ray J
  • Status

    Publication Date

  • January 16, 2009
  • Published In


  • Biomimetic Materials
  • Catalysis
  • Catalytic Domain
  • Dipeptides
  • Organometallic Compounds
  • Serine Endopeptidases
  • Stereoisomerism
  • Digital Object Identifier (doi)

    Start Page

  • 645
  • End Page

  • 651
  • Volume

  • 74
  • Issue

  • 2