SYNTHESIS OF ANTIVIRAL AGENTS ACYCLIC NUCLEO-SIDES OF 4-SUBSTITUTED PYRROLO 2,3-d PYRIMIDINE

Naturally occurring nuclcosidcs of pyrrolo 2,3-d pyrimidine, tubercidin, sangivamycin and toyocamycin were known as antibiotics not only for their potent antitumor activity but also for their significant antiviral effects. However, none of them was developed to be a useful drug duc to their high toxicity. In order to reduce the toxicity of this kind of compounds and reveal the relationship between structure and biological activity, a series of acyclic analogues of tubercidin with varied 4-subtituted amino groups were synthesized. 4-chlor-pyrrolo (2,3-d) pyrimidin was used as starting material which reacted with 1,3-dibenzyloxy-glycerol-2-chloro-methylether by direct sodium salt glycosylation procedure provided thc key intermediate (Ⅸ). After hydrogenation, amination of compound Ⅸ gave the final free hydroxy products. All the cmopounds were tested in vitro against HSV-1 and Cox B6. Only three of them (Ⅸ₆, Ⅸ₇, Ⅸ₉) showed certain activities against Cox B6.