Bioinspired Glycosylpyridinium Donors for Mild and Stereoselective Glycosylation

High Resolution Image Download MS PowerPoint Slide Despite substantial progress in glycosyl donor design, the development of mild and stereoselective glycosylation methods remains a central challenge in carbohydrate chemistry. Inspired by the native enzymatic ADP-ribosylation process, in which NAD + serves as the glycosyl donor and nicotinamide acts as the leaving group, we developed a pyridinium-based glycosyl donor that chemically mimics this biological transformation. The donor enables the α-selective formation of O -, S -, and N -glycosides under mild activation conditions. Mechanistic studies indicate that the product configuration is independent of that of the donor and is instead governed by thermodynamic control, favoring formation of the α-configured product. Modification of the protecting groups on the donor allows selective access to β-configured products. This pyridinium donor is fully orthogonal to conventional donors, such as glycosyl thioglycosides and o -alkynylbenzoates, enabling iterative assembly of complex oligosaccharides. This bioinspired platform provides a versatile and complementary approach for the stereoselective construction of both α-and β-glycosidic linkages.