A Transient Initiator for Polypeptoids Postpolymerization α‐Functionalization via Activation of a Thioester Group

Abstract

Here, a postpolymerization modification method for an α‐terminal functionalized poly‐(N‐methyl‐glycine), also known as polysarcosine, is introduced. 4‐(Methylthio)phenyl piperidine‐4‐carboxylate as an initiator for the ring‐opening polymerization of N‐methyl‐glycine‐N‐carboxyanhydride followed by oxidation of the thioester group to yield an α‐terminal reactive 4‐(methylsulfonyl)phenyl piperidine‐4‐carboxylate polymer is utilized. This represents an activated carboxylic acid terminus, allowing straightforward modification with nucleophiles under mild reaction conditions and provides the possibility to introduce a wide variety of nucleophiles as exemplified using small molecules, fluorescent dyes, and model proteins. The new initiator yielded polymers with well‐defined molar mass, low dispersity, and high end‐group fidelity, as observed by gel permeation chromatography, nuclear magnetic resonance spectroscopy, and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectroscopy. The introduced method can be of great interest for bioconjugation, but requires optimization, especially for protein conjugation.

Facile synthesis of N-phenoxycarbonyl amino acids by a two-phase reaction for direct polymerization

“…Polymer Chemistry have adopted this method. [22][23][24][25][26][27][28][29][30][31][32][33][34] One possible reason could be the challenging purification process of NPC monomers, which are prepared through the nucleophilic reaction of amino acids with diphenyl carbonate (DPC) or phenyl chloroformate (PCF) (Scheme 1b). Few NPC monomers, such as serine urethane derivatives, can be successfully purified through column chromatography or recrystallization, resulting in a high-yield product.…”