Aqueous synthesis of nucleoside analogs via direct coupling of natural sugars and purines

Nucleosides are the most widespread and fundamental N-glycosides in biological processes. Despite their prevalence in nature and significance of their analogs in medicinal chemistry, conventional synthetic approaches rely on complicated upstream preparation including well-designed glycosyl donor and pre-silylated nitrogen-containing acceptor. Here we report a direct coupling strategy delivering purine glycoside by the N-glycosylation between natural sugar and purine in aqueous solution. The transformations are realized by one simple and concise step using a new imidazolinium chloride salt, with high chemo-, regio-, and stereo-selectivity. These findings greatly simplify access to various nucleoside analogs. Mechanistic studies suggest that sugar and purine are respectively activated by the imidazolinium cation and chlorine anion of the reagent.