Application of 2,6-diazidopurine derivatives in the synthesis of thiopurine nucleosides

2,6-Diazidopurine derivatives undergo double azide–alkyne 1,3-dipolar cycloaddition (CuAAC) reactions to give 2,6-bis-(triazolyl)purine analogs, which undergo selective nucleophilic aromatic substitution with various thiols at C(6). This synthetic sequence produces nucleoside analogs with 6-alkyl/arylthio-2-(4-alkyl/aryl-1H-1,2,3-triazol-1-yl)purine bases. In contrast, glycosylated 2,6-diazidopurines exhibit reasonable C(2) selectivity in nucleophilic aromatic substitution with thiols. This permits the synthesis of 2-alkylthio-6-azido-purine derivatives, which after CuAAC provide the corresponding 2-alkylthio-6-triazolyl-purine analogs. The latter are also susceptible to nucleophilic aromatic substitution with amines at C(6). The above mentioned compounds are useful molecular platforms in terms of medicinal chemistry.