Facile Synthesis of dl-4,4-Difluoroornithine, dl-4,4-Difluoroglutamine, and γ-dl-4,4-Difluoroglutamyl-Containing Peptides: Regiospecific Addition of Nucleophiles to N-Cbz-di-tert-butyl-dl-4,4-difluoroglutamate

Abstract

The reaction of several nucleophiles with N-Cbz-protected di-tert-butyl-dl-4,4-difluoroglutamate was investigated as an approach to the synthesis of various fluorinated amino acids and peptides. The γ-carboxyl group is highly activated by the two adjacent fluorine atoms, and nucleophilic reactions occurred exclusively at that carbonyl carbon. Further transformations of the reaction products resulted in the synthesis of dl-4,4-difluoroornithine, dl-4,4-difluoroglutamine, and γ-dl-4,4-difluoroglutamyl-containing dipeptides.