Cyclic Poly(α-peptoid)s by Lithium bis(trimethylsilyl)amide (LiHMDS)-Mediated Ring-Expansion Polymerization

Pedro Salas-Ambrosio (1) , Antoine Tronnet (2, 3) , Marc Since (4) , Sandra Bourgeade-Delmas (5) , Jean-Luc Stigliani (2) , Amelie Vax (1) , Sébastien Lecommandoux (1) , Bruno Dupuy (3) , Pierre Verhaeghe (2) , Colin Bonduelle (1)

1 Team 3 LCPO : Polymer Self-Assembly & Life Sciences
2 LCC - Laboratoire de chimie de coordination
3 PBA (U-Pasteur_6) - Pathogénèse des Bactéries Anaérobies / Pathogenesis of Bacterial Anaerobes
4 CERMN - Centre d'Etudes et de Recherche sur le Médicament de Normandie
5 PHARMA-DEV - Pharmacochimie et Biologie pour le Développement

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(α-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.

Mots clés: Macrocyclic polypeptoids; Clostridioides difficile; Ring expansion polymerization (REP)

Domaines: Polymères; Chimie thérapeutique

Pedro Salas-Ambrosio, Antoine Tronnet, Marc Since, Sandra Bourgeade-Delmas, Jean-Luc Stigliani, et al.. Cyclic Poly(α-peptoid)s by Lithium bis(trimethylsilyl)amide (LiHMDS)-Mediated Ring-Expansion Polymerization: Simple Access to Bioactive Backbones. Journal of the American Chemical Society, 2021, 143 (10), pp.3697-3702. ⟨10.1021/jacs.0c13231⟩. ⟨hal-03173586⟩