by
Saul Martinez-Montero;
Susana Fernandez;
Yogesh S. Sanghvi;
Emmanuel A. Theodorakis;
Mervi Detorio;
Tamara Mcbrayer;
Tony Whitaker;
Raymond F Schinazi;
Vicente Gotor;
Miguel Ferrero
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 = 36.9 μM) in this series. None of the compounds synthesized in this study demonstrated anti-HCV activity.