Synthesis Of9-Substituted-6-Alkylamino-2-Alkylthio Purines And Their Anti-Platelet Aggregation Activity

Purine derivatives are widely exists in nature. They not only play a keyrole in the life of genetic and metabolic processes, but also have some goodbiological activities in the field of anti-virus, anti-tumor and anti-plateletaggregation. So purine derivatives have been the focus of attention.2-amino-6-chloropurine (1) as the starting material was treated with2-bromoethyl acetate to yield9-acetoxy-ethyl-2-amino-6-chloropurine (2).Compound2was diazotized and reacted with disulfides to afford9-acetoxyethyl-2-alkythio-6-chloropurine (3). A new series of9-acetoxyethyl-6-alkylamino-2-alkylthio purine (4) were acquired by aminolysis reaction ofcompounds3. And deprotection of acetyl4c in Bouveault-Blanc reactionswith sodium furnished5. Phosphorylation of5afforded the phosphoric acidintermediates dibenzyl2-(6-alkylamino-2-propylthio-9H-purin-9-yl)ethylphosphate (6). Finally,2-(6-alkylamino-2-propylthio-9H-purin-9-yl)ethyl dihydrogen phosphate (7) were afforded by bromotrimethylsilane withcompounds6. The structures of title compound and some intermediates weredetermined by IR,¹H NMR,¹³C NMR and HRMS. Meanwhile, theanti-platelet aggregation rates of compounds4and5were measured.