Click-Inspired Functionalization of Glycans: Rational Design and Efficient Synthesis of C3-OH Specific Derivatives

As pivotal functional biomolecules, carbohydrates acquire diverse biological recognition capabilities through structural modifications that fine-tune their interactions with biological systems.Glycan derivatives bearing C3-position modifications have emerged as a focal point in glycochemistry research due to their distinctive physiological and pharmacological activities.This study implemented a modular design strategy to construct multifunctional C3-glycoside scaffolds by synergistically integrating biologically oriented bonding patterns.Three complementary functional motifs-ester linkages (for controlled degradation), perfluoroaryl groups (for hydrophobicity enhancement), and site-specific nucleophilic aromatic substitution (SNAr)-were strategically incorporated to confer multi-responsive potential.For the synthesis process, we established a highly efficient reaction protocol.Under standard reaction conditions, cesium carbonate was employed as the base, and a tetrahydrofuran (THF)/dimethyl sulfoxide (DMSO) (V/V, 51) mixed solvent system was utilized.Remarkably, the reactions could be completed within as little as 20 s at room temperature, achieving yields exceeding 90%.This rapid and efficient reaction exhibits remarkable versatility and broad substrate tolerance.Taking this reaction as the standard condition, we successfully constructed the efficient synthesis of over 30 related C3-glycan derivatives, demonstrating the robustness and scalability of our developed method.This green synthesis protocol, characterized by mild reaction conditions and a rapid process, represents a significant advancement in achieving efficient C3-site derivatization.Furthermore, we pioneered preliminary investigations on the luminescent signal responses mediated by carbohydrate-lectin recognition interactions using the synthesized C3-modified glycoconjugates, laying groundwork for advanced glycan-based biosensing platforms.