Solution conformations of the antimetabolite 9-beta-D-xylofuranosyladenine and its 8-bromo analogue.

An analysis has been made, with the aid of 1H NMR spectroscopy, of the solution conformation of the known antimetabolite, 9-beta-D-xylofuranosyladenine (xyloA), and of its 8-bromo analogue. For xyloA, the results point to a strong preference for the sugar ring of the conformation type N (C(3') endo), a relatively low population of the gauche-gauche rotamer of the exocyclic 5'-CH2OH, and a preference for the conformation anti about the glycosidic bond. For 8-bromo-xyloA, the preference for the type N conformation of the sugar ring is less marked, and the preferred conformation about the glycosidic bond is syn. The conformation of the sugar ring in the foregoing xylonucleosides consequently differs appreciably from that for the corresponding ribonucleosides, which adopt preferentially the type S (C(2')endo) and gauche-gauche conformations. Comparison with previously reported results for O'-methyl derivatives of xyloA points to the similarity in conformational properties of all of these. In contrast to arabinonucleosides with free 2' and 5' hydroxyls, the conformation of xyloA is relatively unaffected in strongly alkaline medium where the sugar hydroxyl(s) dissociate. Under these conditions, there is no formation of an intramolecular hydrogen bond such as might have been anticipated from X-ray diffraction studies in the solid state.