Photocatalytic Glycosylation Reaction Using Pyridinium, Phosphonium Ions and 9-Fluorenyl Glycosyl Donors

The critical role that carbohydrates and their conjugates play in biological interactions is of interest in medicinal research, making the chemical synthesis of these molecules essential.¹ The complexity of carbohydrates, due to their configuration, connectivity, and composition, makes the chemical synthesis lengthy and complicated.¹ All these factors make synthesizing the stereoselective oligosaccharide a significant challenge. 

Here, we report the development of direct photochemical glycosylation methods without the need for any external reagent, promoter, or catalysts, thus condensing the system to its essentials: a glycosyl donor, a glycosyl acceptor, and solvent. This strategy employs a light-activated leaving group based on phosphonium ions and a 9-aryl-9-fluorene stable glycosyl donor system to generate a glycosyl cation. The positively charged intermediates undergo a nucleophilic substitution reaction with the glycosyl acceptor to form a glycosidic bond between two pyranose sugars. The reaction mechanism of the photoactivation of these glycosyl donors takes place through a fast SN2-like mechanism. Irradiation of glycosyl pyridinium derivatives, glycosyl phosphonium derivatives, and 9-fluorene glycosyl donor at 300 nm in dichloromethane and in the presence of methanol as nucleophile yields methoxy glucopyranoside. The technology developed here has a shorter reaction time than standard photo-stimulated glycosylation, and thus could be applied for more practical uses for large-scale production.

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