Phosgene-free synthesis of polypeptides using activated urethane derivatives of α-amino acids: an efficient synthetic approach to hydrophilic polypeptides?

RSC Advances Pub Date: 2014-07-08 DOI: 10.1039/C4RA03315A

Abstract

A series of polypeptides have been synthesized from the corresponding N-phenoxycarbonyl derivatives of hydroxyl- or amino-functionalized α-amino acids such as L-serine, L-cysteine, L-threonine, L-tyrosine, L-glutamine, and L-asparagine. These derivatives are prepared by N-carbamylation of tetrabutylammonium salts of α-amino acids with diphenyl carbonate (DPC). The synthesis of polypeptides can be achieved by heating these N-phenoxycarbonyl derivatives at 60 °C in N,N-dimethylacetamide (DMAc) in the presence of n-butylamine through the polycondensation of the derivatives with accompanying elimination of phenol and CO2. The NMR and MALDI-TOF mass analyses of the resulting polypeptides revealed that n-butylamine was successfully incorporated into the chain end of the polypeptides. Molecular weights of the polypeptides were controlled by varying the feed ratio of the urethane derivatives to n-butylamine. 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.

Graphical abstract: Phosgene-free synthesis of polypeptides using activated urethane derivatives of α-amino acids: an efficient synthetic approach to hydrophilic polypeptides
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