• Title/Summary/Keyword: 2'-Spirocarbocyclic nucleoside

Search Result 1, Processing Time 0.015 seconds

2'-Spirocyclopropyl-carbocyclic Nucleoside as a Novel Scaffold for Potent Anti-HCV Agents

  • Li, Hua;Yoo, Jin-Cheol;Hong, Joon-Hee
    • Bulletin of the Korean Chemical Society
    • /
    • v.32 no.4
    • /
    • pp.1146-1152
    • /
    • 2011
  • The discovery of 2'-spirocyclopropyl-ribocytidine (J. Med. Chem. 2010, 53, 8150-8160) as a potent inhibitor of RNA synthesis by NS5B ($IC_{50}=7.3{\mu}M$), the RNA polymerase encoded by hepatitis C Virus (HCV), has led to the synthesis and biological evaluation of several carbocyclic versions of 2'-spiropropyl-nucleosides. The cyclopentenol intermediate 7 was successfully constructed via ring-closing metathesis (RCM) from divinyl 6. Spirocyclopropanation of enone 8 was effected by using (2-chloroethyl)-dimethylsulfonium iodide and potassium tert-butoxide to form the desired intermediate 9. The synthesized nucleoside analogues 21-24 were assayed for their ability to inhibit HCV RNA replication in a subgenomic replicon Huh7 cell line. Among them, the cytosine nucleoside analogue 22 exhibited significant anti-HCV activity ($EC_{50}= 8.2{\mu}M$).