Polysaccharide Meets Polyoxazoline: Regio- and Stereodefined β-1,2-Linked Pseudo-polysaccharides via Controlled Cationic Ring-Opening Polymerization

Polysaccharides exhibit remarkable stereochemical and regiochemical complexity, yet their natural heterogeneity produces differences in composition and material behavior that are difficult to control or predict. Here, we report a synthetic approach that overcomes these challenges through the controlled, cationic ring-opening polymerization of glucosamine-derived 2-oxazoline monomers, affording a new class of well-defined pseudo-polysaccharides, wherein each saccharide subunit is 1,2-<i>N</i>-linked through a nitrogen containing a pendant acyl group. Under optimized conditions using a benzyl-protected monomer (OBn-GlcOx) and a methyl tosylate initiator, polymerization proceeds to full conversion within 3 h at 75 °C with linear molecular weight growth, first-order kinetics, and low dispersity (D̵ ≤ 1.2), consistent with a controlled polymerization mechanism. The resulting polymers exhibit complete β-1,2-regio- and stereoselectivity, narrow molecular-weight distributions, and retention of chain-end functionality that enables chain extension to form diblock copolymers with 2-methyl-2-oxazoline. Following quantitative deprotection, the resulting polymer is water-soluble and both protected and nonprotected versions display markedly enhanced resistance to ultrasonic, acidic, and thermal degradation as compared to chitosan (mass loss ≤63% vs 93% under harshest conditions). These findings establish a synthetic route to stereoregular, amide-linked pseudo-polysaccharides with tunable physicochemical properties, expanding the accessible design space for well-defined, carbohydrate-based materials.