Photoredox-Catalyzed Stereoselective Synthesis of C-Nucleoside Analogues from Glycosyl Bromides and Heteroarenes

C-nucleosides, analogues of nucleosides by replacing a C–N glycosidic bond with a C–C bond, are potential anticancer or antiviral agents. Synthesis of C-nucleoside analogues enabled by photoredox-catalyzed radical coupling of glycosyl bromides with nonfunctionalized heteroarenes has been described. This strategy features readily available starting materials, mild conditions, good functional group tolerance, and site- and stereoselectivities (α-configuration). A variety of monosaccharides (d-lyxose, d-ribose, l-arabinose, d-glucose, d-mannose, d-glucuronide, and d-fucose), disaccharides (lactose, melibiose, and maltose), and polysaccharide (maltriose) can couple with a series of nonfunctionalized heteroarenes, such as purine, benzothiazole, thiazolopyridine, benzoxazole, benzimidazole, imidazopyridine, and phenanthridine. Biologically important molecules, such as theophylline, famciclovir, ribufuranoside, and adenine, can be glycosylated directly through a C–C bond using this method. Site- and stereoselectivities can be rationalized and predicted by density functional theory (DFT) calculations.