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Synthesis, Evaluation Of Anti-HIV-1 And Anti-HCV Activity Of Novel 2',3'-dideoxy-2',2'-difluoro-4'-azanucleosides.

Saúl Martínez-Montero, S. Fernández, Y. Sanghvi, E. Theodorakis, Mervi A. Detorio, Tamara R. Mcbrayer, T. Whitaker, R. Schinazi, V. Gotor, M. Ferrero
Published 2012 · Chemistry, Medicine

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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 of N(7) and N(9) regioisomers and their structures were identified based on NOESY and HMBC spectral data. Among the 4'-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 (EC(50)=36.9μM) in this series. None of the compounds synthesized in this study demonstrated anti-HCV activity.
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