Abstract
The development of optically active fluorinated synthetic building
blocks of general utility is a current goal of organofluorine
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.
Key words
fluoroamino acids - fluoropeptides - stereoselective
synthesis - γ-glutamyl hydrolase - fluorescence
enzyme assay
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