The Synthesis of (2S)-4,4-Difluoroglutamyl Γ-Peptides Based On Garner's Aldehyde and Fluoro-Reformatsky Chemistry
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.
MSU Digital Commons Citation
Konas, David; Pankuch, Jessica J.; and Coward, James K., "The Synthesis of (2S)-4,4-Difluoroglutamyl Γ-Peptides Based On Garner's Aldehyde and Fluoro-Reformatsky Chemistry" (2002). Department of Chemistry and Biochemistry Faculty Scholarship and Creative Works. 320.