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 (alpha-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.

Automated summary

The synthesis of C-nucleoside analogues through photoredox-catalyzed radical coupling allows for good functional group tolerance and site- and stereoselectivities, making it applicable for coupling various monosaccharides, disaccharides, and polysaccharides with nonfunctionalized heteroarenes. Biologically important molecules can be glycosylated directly through a C-C bond using this method, and the site- and stereoselectivities can be rationalized and predicted by density functional theory (DFT) calculations.