Convenient and Useful Synthesis of N-Carboxyanhydride Monomers through Selective Cyclization of Urethane Derivatives of alpha-Amino Acids

摘要

A new convenient synthesis of N-carboxyanhydrides (NCAs) of alpha-amino acids was achieved by selective cyclization of urethane derivatives of alpha-amino acids. The urethanes were readily synthesized via N-carbamoylation of alpha-amino acids by bis(4-nitrophenyl)carbonate quantitatively. These urethanes having 4-nitrophenoxy moiety were tolerant to air and moisture to allow their facile purification and storage. When the obtained urethanes were heated in 2-butanone at 60 degrees C, they underwent the selective cyclization via intramolecular nucleophilic attack of the carboxyl moiety to the urethane moiety with releasing 4-nitrophenol, leading to the successful formation of the corresponding NCAs. Addition of carboxylic acids remarkably stabilized the formed NCAs during the reaction, allowing their isolation in high yields.