Synthesis of N_ɛ-protected-L-lysine and γ-benzyl-L-glutamate N-carboxyanhydrides (NCA) by carbamoylation and nitrosation

Summary.

This paper reports on an original process to synthesize N-carboxyanhydrides, which consists of nitrosating N-carbamoylamino acids with a NO/O₂ gas mixture in acetonitrile. The synthesis of several N-carbamoylamino acids of L-lysine was described using potassium cyanate in water. The latter were then nitrosated to yield the corresponding NCA with more or less efficiency. Indeed, the NCA carrying an acid-sensitive protecting group led to a partial deprotection to give the L-lysine NCA salt. The NCA of N_ɛ-trifluoroacetyl-L-lysine, N_ɛ-benzyloxycarbonyl-L-lysine and γ-benzyl-L-glutamate were successfully synthesized with satisfactory yields. Their polymerizability was compared to that of the N_ɛ-trifluoroacetyl-L-lysine NCA initiated by n-hexylamine in N,N-dimethylformamide. It also showed that this new process of NCA synthesis could be applied to the synthesis of polypeptides and more generally to the protein chemistry.