H-1-NMR STUDY OF THE SUGAR PUCKER OF 2',3'-DIDEOXYNUCLEOSIDES WITH ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) ACTIVITY

The sugar ring conformations of 2′,3′-dideoxyribosyladenine (ddA), 2′,3′-dideoxyribosylcytosine (ddC), 2′,3′-dideoxyribosylguanine (ddG), 2′,3′-dideoxyribosylhypoxanthine (ddI), 3′-azido-2′,3′-dideoxyribosylthymine (AZT), 3′-azido-2′,3′-dideoxyribosyluracil (AZU) and 3′-fluoro-2′,3′-dideoxyribosylthymine (FddT) have been investigated by 1H NMR spectroscopy. While the sugar ring in FddT exists almost totally in C2′-endo geometry, other nucleosides show equilibrium between sugar puckers of C3′-endo family (N-type) and C2′-endo family (S-type). For unsubstituted dideoxynucleosides C3′-endo conformer is favoured ({reversed tilde equals} 75%), where-as for AZT and AZU both the conformers have almost equal populations. Unlike X-ray diffraction studies, the NMR results do not support the suggestion that C3′-exo sugar puckers are desirable for the anti-HIV activity of these nucleosides. © 1991.