Trifluoromethylation on a Nucleoside Sugar Scaffold: Design and Synthesis of 6′-Trifluoromethylcyclopentenyl-purine and -pyrimidine Nucleosides

Based on the promising biological activity of 6′-fluorocyclopentenyl-cytosine and -adenine, we report the design and synthesis of 6′-trifluoromethylcyclopentenyl-pyrimidine and -purine as potential antiviral agents. The introduction of a trifluoromethyl (CF3) group onto a sugar scaffold has been achieved using methyl fluorosulfonyldifluoroacetate (Chen’s reagent) as a key step. The resulting trifluoromethylated sugar intermediate provides an efficient pathway for synthesizing various nucleoside analogues, facilitating the expansion of structure–activity relationship studies for neplanocin A analogues.