Activation of N,N-bis(alkoxycarbonyl) amino acids. Synthesis of N-alkoxycarbonyl amino acid N-carboxyanhydrides and N,N-dialkoxycarbonyl amino acid fluorides, and the behavior of these amino acid derivatives

Article abstract of DOI:10.1016/S0040-4020(01)80689-X

Series of Boc- and Cbz-NCAs (2), and of N,N-bis(alkoxycarbonyl) amino acid fluorides U₂AAFs (3) have been prepared by activation of N,N-bis-Boc- and N-Cbz,N-Boc-α-amino acids (1) with the Vilsmeier reagent or cyanuric fluoride. The absence of epimerization of 2 and 3 during both their formation and their coupling under standard conditions of peptide synthesis had been demonstrated by optical purity Young's tests. In other activated derivatives of bis-urethane protected activated amino acids, the exchangeability of the α-H is shown by the considerable racemization of Boc₂Phe-OSu (8) in the presence of base, and by the formation of a Dakin-West type product 11 from the dipeptide Boc₂Phe-Leu-OBn.