Synthesis and Characterization of Regioselectively Functionalized Mono-Sulfated and -Phosphorylated Anionic Poly-Amido-Saccharides

Polysaccharides are abundant in nature andemployed in various biomedical applications ranging from scaffoldsfor tissue engineering to carriers for drug delivery systems.However,drawbackssuchastediousisolationprotocols,contamination, batch-to-batch consistency, and lack of composi-tional control with regards to stereo- and regioselectivity impedethe development and utility of polysaccharides, and thus mimeticsare highly sought after. We report a synthetic strategy toregioselectively functionalize poly-amido-saccharides with sulfateor phosphate groups using post-polymerization modificationreactions. Orthogonally protected beta-lactam monomers, synthesized from D-glucal, undergo anionic ring-opening polymerizationto yield polymers with degrees of polymerization of 12, 25, and 50. Regioselective deprotection followed by functionalization andglobal deprotection affords the sulfated and phosphorylated poly-amido-saccharides. The resulting anionic polymers are watersoluble and non-cytotoxic and adopt helical conformations. This new methodology provides access to otherwise inaccessiblefunctional polysaccharide mimetics for biomedical applications

Automated summary

Polysaccharides play an important role in biomedical applications, but their preparation faces challenges. This study presents a synthetic strategy to regioselectively functionalize polysaccharides using post-polymerization modification reactions. This new method provides a new approach for obtaining functional polysaccharide mimetics for biomedical applications.