Synthesis and antiviral activity evaluation of 3′-fluoro-3′-deoxyribonucleosides: broad-spectrum antiviral activity of 3′-fluoro-3′-deoxyadenosine

Abstract Five 3′-fluorinated ribonucleosides were prepared and evaluated for their inhibitory properties against different viruses. The synthesis of these compounds was achieved by treatment of 2′,5′-di- O -tritylated nucleoside analogues possessing a xylo -configuration with diethylaminosulfur trifluoride, followed by deprotection. 3′-Fluoro-3′-deoxyadenosine was active against a broad range of viruses, encompassing both DNA viruses [pox (vaccinia)], single-stranded (+) RNA viruses [picorna (polio, Coxsackie B), toga (sindbis, Semliki Forest)] and double-stranded RNA viruses (reo). In its antiviral activity spectrum 3′-fluoro-3′-deoxyadenosine clearly differed from those adenosine analogues that are known as inhibitors of S -adenosylhomocysteine hydrolase. 3′-Fluoro-3′-deoxyadenosine also proved effective in vivo, in inhibiting tail lesion formation in mice inoculated intravenously with vaccinia virus.