The synthesis of (2S)-4,4-difluoroglutamyl γ-peptides based on Garner's aldehyde and fluoro-reformatsky chemistry

David W. Konas, Jessica J. Pankuch, James K. Coward

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The development of optically active fluorinated synthetic building blocks of general utility is a current goal of organo-fluorine chemists. The serine-derived Garner aldehyde was converted to a general 4,4-difluoroamino acid building block via fluoro-Reformatsky reaction with ethyl bromodifluoroacetate. The utility of this building block was demonstrated by the synthesis of derivatives of (2S)-4,4-difluoroglutamine, (2S)-4,4-difluoroglutamic acid, and its incorporation into a fluorophore-containing isopeptide 2 designed as a mechanistic probe of γ-glutamyl hydrolase. Compound 2 proved to be a substrate for γ-glutamyl hydrolase and was hydrolyzed at a rate significantly slower than the corresponding non-fluorinated analog.

Original languageEnglish
Pages (from-to)2616-2626
Number of pages11
JournalSynthesis
Issue number17
DOIs
StatePublished - 1 Jan 2002

Keywords

  • Fluorescence enzyme assay
  • Fluoroamino acids
  • Fluoropeptides
  • Stereoselective synthesis
  • γ-glutamyl hydrolase

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