N-Heterocyclic Carbene-Catalyzed Random Copolymerization of N-Carboxyanhydrides of α-Amino Acids.

Synthetic polypeptides prepared from N-carboxyanhydrides (NCAs) of α-amino acids are useful for elucidating the relationship between the primary structure of natural peptides and their immunogenicity. In this study, complex copolypeptide sequences were prepared using a recently developed technique; specifically, the random copolymerization of l-alanine NCA with NCAs of l-glutamic acid 5-benzylester (Bn-Glu NCA), S-benzyl-cysteine (Bn-Cys NCA), O-benzyl-l-serine (Bn-Ser NCA), and l-phenylalanine (Phe NCA) was performed using N-heterocyclic carbene (NHC) catalysts. The NHC-initiated Ala NCA/Bn-Glu NCA and Ala NCA/Bn-Cys NCA copolymerization reactions achieved 90% conversion within 30 min. The reactivity ratio values estimated using the Kelen and Tudos method show that poly(Bn-Glu-co-Ala) and poly(Bn-Cys-co-Ala) have random repeating units with rich alternating sequences, whereas poly(Bn-Ser-co-Ala) and poly(Phe-co-Ala) contain a larger proportion of Ala-repeating units than Bn-Ser and Phe in random placement.