Stereospecific synthesis of unnatural β-L-enantiomers of 2-chloroadenine pentofuranonucleoside derivatives

Abstract

2′,3′-Dideoxy- (1), 2′,3′-unsaturated- (2), 2′,3′-dideoxy-3′-fluoro- (3), 3′-azido-2′,3′-dideoxy- (4) and 2′-deoxy- (5) β-L-ribofuranonucleosides of 2-chloroadenine have been synthesised and their antiviral properties examined. All these derivatives were stereospecifically prepared by glycosylation of 2,6-dichloropurine with a suitable peracylated L-xylo-furanose (6). Treatment of the resulting protected β-L-nucleoside with methanolic ammonia followed by appropriate chemical modifications gave the 2-chloro-9-(2-deoxy-β-L-threo-pentofuranosyl)adenine 11. Its 5′-O-benzoyl derivative 12 was then converted to nucleosides 1 and 2 via radical deoxygenation reaction or base-promoted β-elimination of the corresponding mesyl ester. Additionally, compounds 3–5 were obtained from 12 either by reaction with (diethylamino)sulfur trifluoride or via Mitsunobu reactions using diphenylphosphoryl azide or benzoic acid as incoming nucleophiles. The prepared compounds were tested for their activity against HIV and HBV viruses, but they did not show significant antiviral activity nor cytotoxicity.