Polypeptides have been widely employed to prepare a wide variety of the functional biomaterials for the use of drug delivery system (DDS) and tissue engineering, because of their excellent biocompatibility and biodegradability. One of the most efficient routes is the ring-opening polymerization of a-amino acid N-carboxyanhydrides (NCAs) to give polypeptides with well-defined structures involving molecular weights and terminal structures. However, the synthesis of NCAs usually requires highly toxic phosgene and its derivatives. Sensitive nature of NCAs to moisture and heat has also prevented the production and the utilization of NCAs in an industrial scale. We will present a facile and phosgene-free synthesis of polypeptide (alanine, methionine, lysine and tryptophan) by the polycondensation of N-phenoxycarbonyl-L-amino acid. The urethane derivative was synthesized by N-carbamylation of tetrabutylammonium salt with diphenyl carbonate as the alternative of phosgene (Figure 1(a)). Their polycondensation proceeded smoothly at 60 oC in N,N-dimethylacetamide (DMAc) in the presence of amines such as n-butylamine along with the elimination of phenol and CO2 (Figure 1(b)). The molecular weight of polypeptide was adjusted by varying feed ratio of urethane derivative and amine. The structural analysis with MALDI-TOF mass spectroscopy showed that n-butylamine was successfully incorporated into the chain end of the polypeptide. The employment of an amine-terminated poly(ethylene glycol) in place of n-butylamine permitted the successful synthesis of the corresponding diblock copolymers composed of polyether and polypeptide segments. 

Facile synthesis of polypeptide through polycondensation of activated urethane derivative of <i>a</i>-amino acid

248th National Meeting (2014)

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Facile synthesis of polypeptide through polycondensation of activated urethane derivative of a-amino acid