Phosgene-free synthesis of polypeptides: Useful synthesis for hydrophobic polypeptides through polycondensation of activated urethane derivatives of -amino acids

We report a useful synthetic method of polypeptides using a series of urethane derivative of -amino acids (l-leucine, l-phenylalanine, l-valine, l-alanine, l-isoleucine, l-methionine), which are readily synthesized by N-carbamoylation of tetrabutylammonium salts of -amino acids with diphenyl carbonate. Heating these urethane derivatives in N,N-dimethylacetamide in the presence of n-butylamine successfully gave the corresponding polypeptides with well-defined structures through polycondensation with the elimination of phenol and CO2. The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry investigation showed that the resulting polypeptides had an n-BuNH2-incorporated initiating end and an amino group at propagating end. These results strongly indicated that primary amines served as an initiator in this polycondensation system. (c) 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3726-3731