Convenient synthesis of poly(γ‐benzyl‐L‐glutamate) from activated urethane derivatives of γ‐benzyl‐L‐glutamate

Abstract

Abstract A series of activated urethane‐type derivatives of γ‐benzyl‐ L ‐glutamate were synthesized, and their potential as monomers for polypeptide synthesis was investigated. The derivatives of the focus of this work were a series of N ‐aryloxycarbonyl‐γ‐benzyl‐ L ‐glutamate 1 , of which aryl groups were phenyl, 4‐chlorophenyl, and 4‐nitrophenyl. These urethanes 1 were reactive in polar solvents such as dimethylsulfoxide, N , N ‐dimethylformamide (DMF), and N , N ‐dimethylacetamide (DMAc), and were efficiently converted into poly(γ‐benzyl‐ L ‐glutamate) (poly(BLG)) under mild conditions; at 60 °C without addition of any catalyst. Among the three urethanes, that having 4‐nitrophenoxycarbonyl group 1c was the most reactive to give poly(BLG) efficiently, as was expected from the highly electron deficient nature of the nitrophenoxycarbonyl group. On the other hand, the urethane 1a having phenoxycarbonyl group was also efficiently converted into poly(BLG), in spite of the intrinsically less electrophilicity of the phenoxycarbonyl group. In addition, the successful formation of poly(BLG) by the reaction of 1a favored its diluted concentration (0.1 M) much more than 2.0 M, the optimum initial concentration for 1c . 1 H NMR spectroscopic analyses of the reactions in situ revealed that the predominant pathway from 1 to poly(BLG) involved the intramolecular cyclization of 1 into the corresponding N ‐carboxyanhydride, with release of phenol and its successive ring‐opening polymerization with release of carbon dioxide. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2649–2657, 2008