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