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


Correspondence to: T. Endo (Email:


We report a useful synthetic method of polypeptides using a series of urethane derivative of α-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 α-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. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3726–3731