Convenient phosgene-free synthesis of polypeptides bearing reactive alkene moiety through polycondensation of activated urethane derivative of α-amino acid

• Published in: Polymer (Guilford) 2016-06, Vol.93, p.174-180
• Main Authors: Yamada, Shuhei, Goto, Mitsuaki, Endo, Takeshi
• Format: Article
• Language: English
• Subjects: Bearing; Carbon dioxide; Derivatives; Initiators; Olefins; Polycondensation; Polypeptide; Polypeptides; Radicals; Thiol-ene reaction; Urethane derivative; Urethanes
• ISSN: 0032-3861; 1873-2291
• DOI: 10.1016/j.polymer.2016.04.029

Polypeptides bearing a reactive alkene moiety, including poly-dl-allylglycine (PGly(allyl)) and poly-dl-pentenylglycine (PGly(pent)) have been prepared through the polycondensation of activated urethane derivatives, N-phenoxycarbonyl derivative of α-amino acids. These urethane derivatives of dl-allylglycine (NPC-Gly(allyl)) and dl-pentenylglycine (NPC-Gly(pent)), are prepared by the N-carbamylation of the onium salt of the corresponding α-amino acid with diphenyl carbonate. The polycondensation of urethane derivatives proceeds when heated at 60 °C in N,N-dimethylacetamide, using amines as initiators, along with the elimination of phenol and CO2, to give the corresponding polypeptides without any degradation of alkene moieties. Varying the feed ratio of the urethane derivative to the initiator gives a predictable molecular weight with a narrow polydispersity index. Post-polymerization modifications of the alkene moiety of polypeptide are achieved with a high efficiency through a typical radical thiol-ene addition using a range of thiol-containing compounds, indicating the broad scope of this method as a conjugation tool for functional molecules. [Display omitted] •Polycondensation of N-phenoxycarbonyl-α-amino acid gives alkene-bearing polypeptide with eliminating phenol and CO2.•The polycondensation proceeds to give well-defined polypeptides with respect to molecular weight and terminal structure.•Post-polymerization modifications of the alkene moiety of polypeptide are achieved by radical thiol-ene reaction.