Synthesis and biological evaluation of novel 2',3',4'-triply branched carbocyclic nucleosides as potential antiviral agents.
Novel 2',3',4'-triply branched carbocyclic nucleosides were synthesized in this study. The introduction of two methyl groups in the 2'- and 3'-position was accomplished by a Horner-Wadsworth-Emmons reaction and isopropenyl magnesium bromide addition, respectively. The construction of the required 4'-quaternary carbon was carried out using a [3,3]-sigmatropic rearrangement. Bis-vinyls were successfully cyclized using a Grubbs' catalyst II. The natural bases (adenine, cytosine) were efficiently coupled using a Pd(0) catalyst. The antiviral activities of the synthesized compounds were evaluated against HIV-1, HSV-1, HSV-2 and HCMV. Compound 30 displayed moderate anti-HCMV activity (EC50 = 30.1 microg/mL), without exhibiting any cytotoxicity at up to 100 microM.
Ko
Ok Hyun
OH
College of Pharmacy, Chosun University, Kwangju 501-759, Republic of Korea.
Hong
Joon Hee
JH
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001555:Benzene Derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D009705:Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D010948:Viral Plaque Assay; D014780:Viruses / Q000187:drug effects
D000998:Antiviral Agents; D001555:Benzene Derivatives; D009705:Nucleosides