SYNTHESIS AND ANTI-HEPATITIS-B VIRUS ACTIVITY OF 9-(2-DEOXY-2-FLUORO-BETA-L-ARABINOFURANOSYL)PURINE NUCLEOSIDES

Since the discovery of 2'-fluoro-5-methyl-beta-L-arabinofuranosyluraci l (L-FMAU) as a potent anti-HBV and anti-EBV agent, we have studied th e structure-activity relationships of -deoxy-2'-fluoro-beta-L-arabinof uranosylpyrimidine nucleosides as anti-REV agents. Therefore it is rat ional to extend this study to the purine nucleosides. Thus, O-benzoyl- 2-deoxy-2-fluoro-beta-L-arabinofuranosyl bromide (Ii), which was prepa red from L-xylose via a multistep procedure, was coupled with several purines by the sodium salt method. From this general synthesis, 10 pur ine nucleosides containing the 2-deoxy-2-fluoro-beta-L-arabinofuranosy l moiety have been obtained. The anti-HBV activity and toxicity of the synthesized nucleosides were evaluated in HepG2 2.2.15 cells. among t hem, the adenine (10) and hypoxanthine (15) derivatives exhibit good i n vitro anti-HBV activity (EC50 = 1.5 and 8 mu M, respectively) withou t significant toxicity up to 200 mu M.