The structural and conformational features of the "anomeric" DL-trans- and DL-cis-5-(3-hydroxytetrahydrofuran-2-yl)uracils (3a, 4a) and five similar analogues were studied in order to determine their applicability as models of beta- and alpha-pseudouridine. The 270-MHz proton NMR spectra were measured for all analogues to define their ring geometries in solution and to estimate the solution population of model N, S conformers in a two-state dynamic equilibrium treatment. Two sets of calculations were employed to evaluate the relative contributions of these states to the observed vicinal coupling constants related to the C(3')-C(4') fragment. In the first, similar geometries were assumed for each pair of conformers, while in the second, limited to 3, the geometries were those derived from X-ray crystallographic data; both gave comparable results. The cis analogues 4a and 4b are excellent conformational models for alpha-pseudouridine. In the trans series (3a-c), the equilibrium is weighted toward the N conformer (approximately 80%), differing from that found in beta-pseudouridine for which each model conformer is equally populated. Possible implications of the conformational effects upon the pairing properties of pseudouridine in tRNA are discussed.
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