SYNTHESIS AND ANTIVIRAL ACTIVITY OF 6-CHLOROPURINE ARABINOSIDE AND ITS 2'-DEOXY-2'-FLUORO DERIVATIVE

6-Chloropurine arabinoside (3a) was obtained by treatment of the 2'-O- acetylated congener (2) with ammonia in methanol. The 3',5'-di-O-trity lated riboside (6) was allowed to react with diethylaminosulfur triflu oride (DAST) in the presence of pyridine to give the 2'-deoxy-2'-fluor oarabinoside (7), from which 9-(2-deoxy-2-fluoro-beta-D-arabinofuranos yl)purine (3b) was obtained. The antiviral effects of 3a and 3b were a ssayed against several DNA and RNA viruses. Only 3a displayed potent a ctivity against varicella-zoster virus (VZV). This antiviral activity was dependent on phosphorylation by the VZV-induced thymidine kinase ( TK). Compound 3a showed moderate activity against other DNA viruses, h erpes simplex type 1 (HSV-1) and type 2 (HSV-2), and vaccinia virus. T hey were equally active against TK- and TK+ strains of HSV-I, which su ggests that the HSV-I-encoded TK does not play a role in the anti-HSV- l activity. No activity was noted with any of the compounds against va rious RNA viruses, including human immunodeficiency virus, at subtoxic concentrations.