Synthesis of polypeptides from activated urethane derivatives of α-amino acids

A series of activated urethane-type derivatives of alpha-amino acids were synthesized and applied to polypeptide synthesis. The urethane used herein, N-(4-nitrophenoxycarbonyl)-alpha-amino acids 1, were synthesized by N-carbamoylation of gamma-benzyl-L-glutamate, beta-benzyl-L-aspartate, L-leucine, L-phenylalanine, and L-proline, with 4-nitrophenyl chloroformate. When 1 was dissolved in N,N-dimethylacetamide (DMAc) and heated at 60 degrees C, it was smoothly converted into the corresponding polypeptides with releasing 4-nitrophenol and carbon dioxide. Spectroscopic analyses of the obtained polypeptides revealed that they were comparable with the authentic polypeptides synthesized by the ring-opening polymerizations of amino acid N-carbox-yanhydrides (NCAs). Besides the successful polycondensations of a series of 1, their polycondensations of 1a and other 1 were also successfully carried out to obtain the corresponding statistic copolypeptides. (C) 2008 Wiley Periodicals, Inc.