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.