Synthesis and antiviral activities of novel 2', 4'- or 3', 4'-doubly branched carbocyclic nucleosides as potential antiviral agents.
In this study, a series of 2', 4-' or 3', 4'-doubly branched carbocyclic nucleosides (11, 12, 19, and 20) were synthesized from simple acyclic ketone derivatives as starting materials. The installation of the 4'-quaternary carbon needed was carried out using a [3, 3]-sigmatropic rearrangement. In addition, the introduction of a methyl group in the 2'- or 3'-position was accomplished by either Grignard reaction or Horner-Wadsworth-Emmons reaction with triethyl-2-phosphonopropionate, respectively. Bis-vinyl was successfully cyclized using a Grubbs' catalyst II. The natural bases (adenine, cytosine) were coupled efficiently using a Pd(0) catalyst. Although all the synthesized compounds were assayed against several viruses, only the cytosine analogue showed moderate antiviral activity against the human cytomegalovirus.
Oh
Chang Hyun
CH
Medicinal Chemistry Research Center, Korea Institute of Science and Technology, Seoul, Republic of Korea.
Hong
Joon Hee
JH
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D009705:Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology*; D014780:Viruses / Q000187:drug effects*
D000998:Antiviral Agents; D007202:Indicators and Reagents; D009705:Nucleosides; D006152:Cyclic GMP