| Abstract
| - The effect of hydroxymethyl conformation (gg, gt, and tg rotamers about the C4−C5 bond) on theconformational energies and structural parameters (bond lengths, bond angles, bond torsions) of the 10 envelopeforms of the biologically relevant aldopentofuranose, 2-deoxy-β-d-erythro-pentofuranose (2-deoxy-d-ribofuranose) 2, has been investigated by ab initio molecular orbital calculations at the HF/6-31G* level of theory.C4−C5 bond rotation induces significant changes in the conformational energy profile of 2 (2gt and 2tg exhibitone global energy minimum, whereas 2gg exhibits two nearly equivalent energy minima), and structural changes,especially those in bond lengths, are consistent with predictions based on previously reported vicinal, 1,3- and1,4-oxygen lone pair effects. HF/6-31G*-optimized envelope geometries of 2gg were re-optimized using densityfunctional theory (DFT, B3LYP/6-31G*), and the resulting structures were used in DFT calculations of NMRspin−spin coupling constants involving 13C (i.e., JCH and JCC over one, two, and three bonds) in 2gg accordingto methods described previously. The computed J-couplings were compared to those reported previously in2gt to assess the effect of C4−C5 bond rotation on scalar couplings within the furanose ring and hydroxymethylside chain. The results confirm prior predictions of correlations between 2JCH, 3JCH, 2JCC and 3JCC, and ringconformation, and verify the usefulness of a concerted application of these couplings (both their magnitudesand signs) in assigning preferred ring and C4−C5 bond conformations in aldopentofuranosyl rings. The newcalculated J-couplings in 2gg have particular relevance to related J-couplings in DNA (and RNA indirectly),where the gg rotamer, rather than the gt rotamer, is observed in most native structures. The effects of twoadditional structural perturbations on 2 were also studied, namely, deoxygenation at C5 (yielding 2,5-dideoxy-β-d-erythro-pentofuranose 4) and methyl glycosidation at O1 (yielding methyl 2-deoxy-β-d-erythro-pentofuranoside 5) at the HF/6-31G* level. The conformational energy profile of 4 resembles that found for2gt, not 2gg, indicating that 4 is an inappropriate structural mimic of the furanose ring in DNA. Glycosidationfailed to induce differential stabilization of ring conformations containing an axial C1−O1 bond (anomericeffect), contrary to experimental data. The latter discrepancy indicates that either the magnitude of this differentialstabilization depends on ring configuration or that solvent effects, which are neglected in these calculations,play a role in promoting this stabilization.
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