Purine acyclic nucleosides. Unambiguous synthesis of acyclovir via a furazano[3,4-d]pyrimidine

Acyclovir was synthesized in five steps from 7-formamido-5-methylthiofurazano3,4-d]pyrimidine 2 . Alkylation of 2 with 2-(benzoyloxy)ethoxymethyl chloride, followed by reductive cleavage of the furazan ring gave 9-2-(benzoyloxy)ethoxy]methyl]-2-(methylthio)adenine 5 . Hydrolysis of the 6-amino group of 5 , followed by amination of 7 with ammonia gave 9-(2-hydroxyethoxy)methyl]guanine ( 1 , acyclovir).