Brønsted Acid Mediated Aglycon Swapping Editing Reaction (ASER)

Abstract

Chemical synthesis of glycoconjugates is a formidable challenge due to the complex interplay of factors affecting glycoside formation. In Nature, glycosidases guide the precise stereo- and regio-selective swapping of aglycons by harnessing the spatial proximity of reactive partners. However, replicating this control in chemical synthesis has proven difficult. Here, we introduce the aglycon swapping editing reaction (ASER) as a novel approach to the glycan editing. Our design features a strategically cleavable trisaccharide yielding a nonreactive 1,6-anhydro sugar by extrusion of a highly electrophilic intermediate. Hence, produced intermediate is primed for nucleophilic attack enabling the formation of a diverse array of glycoconjugates such as O-, N-, S-, and C-glycosides. Our findings reveal ASER as a versatile way to access structurally varied glycoconjugates broadening the toolkit for glycan syntheses.