4′-Selenonucleosides: Regio- and Stereoselective Synthesis of Novel Ribavirin and Acadesine Analogs as Anti-Hepatitis C Virus (HCV) Agents

Intrigued by the biological activity of 2′-C-methylribofuranosyl nucleosides, and ribavirin/acadesine, based on the bioisosteric rationale between oxygen and selenium, we herein report a design and synthesis of the 2′-C-methyl-4′-seleno-ribavirin and -acadesine as potential anti-HCV agents. The 2′-C-methyl 4′-selenoribavirin was synthesized in a regio- and stereoselective manner and completely characterized through 2D NMR and X-ray crystallography. While the 2′-C-methyl 4′-selenoacadesine has been efficiently synthesized by utilizing purine-ring opening/degradation procedure via nucleophilic cleavage of N3−C2 bond of a purine by ethylenediamine (EDA) as the key step.