Phosgene‐Free Synthesis of Poly(l‐cysteine) Containing Styrene Moiety as a Reactive Function

A novel approach toward the synthesis of N-carboxyanhydride precursor available for postpolymerization modification has been developed through a phosgene-free method offering a safer and green way to obtain peptide monomers under exceptionally mild reaction conditions. The homo and co-polypeptide bearing a reactive styrene moiety are prepared through the polycondensation of N-phenoxycarbonyl derivative of 4-vinylbenzyl-L-cysteine (NPC-Cys(VBn)) with the elimination of phenol and CO2 while varying the feed ratio to the primary amine initiator to give the corresponding polypeptides without any degradation of styrene moieties. The postpolymerization modification of styrene moiety is carried out by a radical addition or thiol-ene (photo) click reaction using 1,4-bis(3-mercaptobutylyloxy) butane, leading to the formation of a cross-linked polypeptide. The prepolymerization modification of NPC-Cys(VBn) by a click reaction with benzyl mercaptan as a model compound also demonstrates the side-chain functionalization to make a new monomer for polypeptide synthesis.