Cyclic Poly(α-peptoid)s by Lithium bis(trimethylsilyl)amide (LiHMDS)-Mediated Ring-Expansion Polymerization: Simple Access to Bioactive Backbones

Cyclic polymers display unique physicochemical and biological properties. However, their development is often limited by their challenging preparation. In this work, we present a simple route to cyclic poly(alpha-peptoids) from N-alkylated-N-carboxyanhydrides (NNCA) using LiHMDS promoted ring-expansion polymerization (REP) in DMF. This new method allows the unprecedented use of lysine-like monomers in REP to design bioactive macrocycles bearing pharmaceutical potential against Clostridioides difficile, a bacterium responsible for nosocomial infections.

Automated summary

This study presents a simple method for the synthesis of cyclic poly(alpha-peptoids) using LiHMDS promoted ring-expansion polymerization (REP) from N-alkylated-N-carboxyanhydrides (NNCA). The new method allows the use of lysine-like monomers in REP to design bioactive macrocycles with potential pharmaceutical applications against Clostridioides difficile. This novel approach offers a more efficient and straightforward route compared to traditional methods.