Synthesis, evaluation of anti-HIV-1 and anti-HCV activity of novel 2â€2,3â€2-dideoxy-2â€2,2â€2-difluoro-4â€2-azanucleosides
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چکیده
A series of 20 ,30-dideoxy-20,20-difluoro-40-azanucleosides of both pyrimidine and purine nucleobases were synthesized in an efficient manner starting from commercially available L-pyroglutamic acid via glycosylation of difluorinated pyrrolidine derivative 15. Several 40-azanucleosides were prepared as a separable mixture of aand b-anomers. The 6-chloropurine analogue was obtained as a mixture of N and N regioisomers and their structures were identified based on NOESY and HMBC spectral data. Among the 40-azanucleosides tested as HIV-1 inhibitors in primary human lymphocytes, four compounds showed modest activity and the 5-fluorouracil analogue (18d) was found to be the most active compound (EC50 = 36.9 lM) in this series. None of the compounds synthesized in this study demonstrated antiHCV activity. 2012 Elsevier Ltd. All rights reserved.
منابع مشابه
Synthesis, evaluation of anti-HIV-1 and anti-HCV activity of novel 2',3'-dideoxy-2',2'-difluoro-4'-azanucleosides.
A series of 2',3'-dideoxy-2',2'-difluoro-4'-azanucleosides of both pyrimidine and purine nucleobases were synthesized in an efficient manner starting from commercially available L-pyroglutamic acid via glycosylation of difluorinated pyrrolidine derivative 15. Several 4'-azanucleosides were prepared as a separable mixture of α- and β-anomers. The 6-chloropurine analogue was obtained as a mixture...
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