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

Series of Boc- and Cbz-NCAs (2), and of N,N-bis(alkoxycarbonyl) amino acid fluorides U(2)AAFs (3) have been prepared by activation of N,N-bis-Boc- and N-Cbz,N-Boc-alpha-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 alpha-H is shown by the considerable racemization of Boc(2)Phe-OSu (8) in the presence of base, and by the formation of a Dakin-West type product 11 from the dipeptide Boc(2)Phe-Leu-OBn.