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

Abstract

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.