Concise syntheses and HCV NS5B polymerase inhibition of (2′ R )-3 and (2′ S )-2′-ethynyluridine-10 and related nucleosides

摘要

Graphical abstract Display Omitted Abstract (2′ R )-Ethynyl uridine 3 , and its (2′ S )-diastereomer 10 , are synthesised in a divergent fashion from the inexpensive parent nucleoside. Both nucleoside analogues are obtained from a total of 5 simple synthetic steps and 3 trivial column chromatography purifications. To evaluate their effectiveness against HCV NS5B polymerase, the nucleosides were converted to their respective 5′-O-triphosphates. Subsequently, this lead to the discovery of the 2′-β-ethynyl 18 and -propynyl 20 nucleotides having significantly improved potency over Sofosbuvir triphosphate 24 .