title: Synthesis of novel 4'α-trifluoromethyl-2'β-C-methyl-carbodine analogs as anti-hepatitis C virus agents.
abstract: Novel 4 'α-trifluoromethyl-2 'β-methyl carbocyclic nucleoside analogs have been prepared and evaluated for inhibition of hepatitis C virus (HCV) RNA replication in cell cultures. Construction of cyclopentene intermediate 10a was achieved via sequential Johnson-Claisen orthoester rearrangement and ring-closing metathesis starting from the α-trifluoromethyl-α,β-unsaturated ester 5. Stereoselective dihydroxylation and desilylation yielded the target carbodine analogs. The synthesized nucleoside analogs mentioned above (18 and 19) were assayed for their ability to inhibit HCV RNA replication in a subgenomic replicon Huh7 cell line (LucNeo#2). However, the synthesized nucleosides showed neither significant antiviral activity nor toxicity up to 50 μM.
authors.affiliation: a BK21 Project Team, College of Pharmacy , Chosun University , Kwangju , Republic of Korea.
authors.forename: Seyeon
authors.initials: S
authors.lastname: Kim
authors.forename: Eunae
authors.initials: E
authors.lastname: Kim
authors.forename: Joon Hee
authors.initials: JH
authors.lastname: Hong
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis*; D045744:Cell Line, Tumor; D003517:Cyclopentanes / Q000737:chemistry; D003562:Cytidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D004952:Esters; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry; D012367:RNA, Viral / Q000737:chemistry; D017361:Viral Nonstructural Proteins / Q000737:chemistry; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D003517:Cyclopentanes; D004952:Esters; D009705:Nucleosides; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C016327:cyclopentanol; D003562:Cytidine; C033357:carbodine
keywords: Anti-HCV agent; branched carbocyclic nucleoside; carbodine