A General Approach to Stereoregular Pseudo-Polysaccharides: Cationic Ring-Opening Polymerization of Monosaccharide Cyclic Thionocarbonates

Polysaccharide synthesis via chemical polymerization offers an efficient, facile, and cost-effective route to natural and mimetic polysaccharides with diverse biological and material properties. However, current polymerization-based approaches are largely restricted to low molecular weights (<50 kg/mol) and moderate stereoselectivity unlike their naturally derived counterparts where molecular weight is a key determinant of properties and function. Here, we report a robust strategy for constructing thiocarbonate-linked pseudo-polysaccharides via cationic ring-opening polymerization of readily accessible monosaccharide cyclic thionocarbonates. This polymerization proceeds with high reactivity and exclusive stereospecificity, affording pseudo-polysaccharides of high molecular weight (>500 kg/mol) across a variety of monosaccharide repeating units. Incorporation of a chain transfer agent (CTA) enables living polymerization, yielding polymers with predictable chain lengths and defined chain ends. Upon deprotection and sulfation, the resulting pseudo-polysaccharides exhibit strong fibroblast growth factor 2 (FGF2) binding and anticoagulant activity comparable to that of heparin, underscoring their potential as bioactive mimetics of biologically significant natural polysaccharides.