Hierarchical Self‐Assembly of Amphiphilic β‐C‐Glycosylbarbiturates into Multiresponsive Alginate‐Like Supramolecular Hydrogel Fibers and Vesicle Hydrogel

Ordered molecular self‐assembly of glycoamphiphiles has been regarded as an attractive, practical and bottom‐up approach to obtain stable, structurally well‐defined, and functional mimics of natural polysaccharides. This study describes a versatile and rational design of carbohydrate‐based hydrogelators through N,N’‐substituted barbituric acid‐mediated Knoevenagel condensation onto unprotected carbohydrates in water. Amphiphilic N‐substituted β‐C‐maltosylbarbiturates self‐assembled into pH‐ and calcium‐triggered alginate‐like supramolecular hydrogel fibers with a multistimuli responsiveness to temperature, pH and competitive metal chelating agent. In addition, amphiphilic N,N’‐disubstituted β‐C‐maltosylbarbiturates formed vesicle gels in pure water that were scarcely observed for glyco‐hydrogelators. Finally, barbituric acid worked as a multitasking group allowing chemoselective ligation onto reducing‐end carbohydrates, structural diversity, stimuli‐sensitiveness, and supramolecular interactions by hydrogen bonding. Barbituric acid‐mediated Knoevenagel condensation on unprotected carbohydrates enabled the molecular design of amphiphilic β‐C‐glycosyl barbiturates as hydrogelators. The single‐tailed glycoamphiphiles self‐assembled into alginate‐like multistimuli‐triggered and responsive supramolecular hydrogel fibers. While, the double‐tailed glycoamphiphiles led to vesicle hydrogels. Barbituric acid proves to be an efficient and versatile chemical toolbox for the access and design of glycoconjugates.