2'(beta)-Hydroxyethylated adenosine is a potent and selective inhibitor of hepatitis C virus (HCV) replication targeting the RNA-dependent RNA polymerase of HCV, NS5B. The synthesis and anti-HCV evaluation of carbodine analogues are described. The cyclopentene intermediate 10 was successfully made via sequential Johnson-Claisen orthoester rearrangement and ring-closing metathesis. Coupling of bases via a Pd(0) catalyst, selective dihydroxylation, and desilylation yielded the target carbodine analogues. Cytosine analogue 17 weakly inhibited the replication of the HCV replicon in Hua-7 cells by 50% at 21.1 muM.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1080/15257770903362248 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Synthesis of novel 4'α-trifluoromethyl-2'β-C-methyl-carbodine analogs as anti-hepatitis C virus agents.
Nucleosides Nucleotides Nucleic Acids
July 2015
a BK21 Project Team, College of Pharmacy , Chosun University, Kwangju , Republic of Korea.
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.
View Article and Find Full Text PDFSynthesis of cyclopentanyl carbocyclic 5-fluorocytosine ((-)-5-fluorocarbodine) using a facially selective hydrogenation approach.
J Org Chem
January 2013
Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Veterans Affairs Medical Center, Decatur, Georgia 30033, USA.
An efficient synthetic route to biologically relevant (-)-5-fluorocarbodine 6 was developed. Direct coupling of N(6)-protected 5-fluorouracil 15 with cyclopentenyl intermediate 13, followed by formation of a macrocycle between the base and the carbocyclic sugar moiety, via ring-closing metathesis, allowed for a facial selective hydrogenation of the sugar double bond to give, exclusively, the desired 4'-β stereoisomer.
View Article and Find Full Text PDF(-)-Carbodine: enantiomeric synthesis and in vitro antiviral activity against various strains of influenza virus including H5N1 (avian influenza) and novel 2009 H1N1 (swine flu).
Bioorg Med Chem Lett
April 2010
The University of Georgia College of Pharmacy, Athens, GA 30602, USA.
Enantiomerically pure cyclopentyl cytosine [(-)-carbodine 1] was synthesized from d-ribose and evaluated for its anti-influenza activity in vitro in comparison to the (+)-carbodine, (+/-)-carbodine and ribavirin. (-)-Carbodine 1 exhibited potent antiviral activity against various strains of influenza A and B viruses.
View Article and Find Full Text PDFSynthesis and anti-HCV evaluation of 4'(alpha)-ethyl and 2'(beta)-methyl-carbodine analogues.
Nucleosides Nucleotides Nucleic Acids
September 2009
BK21-Project Team, College of Pharmacy, Chosun University, Kwangju, Republic of Korea.
Novel 4'(alpha)-ethyl-2'(beta)-methyl carbocyclic nucleoside analogues have been prepared and evaluated for inhibition of hepatitis C virus (HCV) RNA replication in cell culture. The construction of cyclopentene intermediate 12 beta was successfully made via sequential Johnson-Claisen orthoester rearrangement and ring-closing metathesis (RCM) starting from Weinreb amide 5. Selective dihydroxylation and desilylation gave the target carbodine analogues.
View Article and Find Full Text PDFSynthesis and in vitro activity evaluation of 2',3'-C-dimethyl carbocyclic nucleoside analogues as potential anti-HCV agents.
Nucleosides Nucleotides Nucleic Acids
August 2009
BK21-Project Team, College of Pharmacy, Chosun University, Kwangju, Republic of Korea.
The first synthetic route of novel 2'(beta),3'(beta)-C-dimethyl carbodine analogues is described. The key intermediate cyclopentenyl alcohol 11(beta) prepared from Weinreb amide 4 via ring-closing metathesis (RCM) and vicinal dihydroxylation. Coupling of 12 with nucleosidic bases via the Pd(0) catalyzed reaction followed by stereoselective dihydoxylation and deprotection afforded the target carbocyclic nucleoside analogues.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!