3-Methylxanthosine : Synthesis and Acidic Hydrolysis of the Glycosyl Bond

Abstract

An improved synthesis of 3, 9-dimethylxanthine (2a) was achieved via the reaction of 1-methyl-5-(methylamino)-imidazole-4-carboxamide (3a) with EtOCOCl in acetate buffer (pH 5) followed by treatment with aqueous NaOH. This method was successfully applied to the synthesis of 3-methylxanthosine (2b), whose N-glycosidic bond proved to be remarkably sensitive to acidic hydrolysis : 2b underwent hydrolysis at a rate more than 1000 times faster than that of xanthosine (10) in 1.0N aqueous HCl at 25°C.