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

Abstract

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.