2-deoxy-beta-D-erythro-pentofuranose: Hydroxymethyl group conformation andsubstituent effects on molecular structure, ring geometry, and NMR spin-spin coupling constants from quantum chemical calculations

The effect of hydroxymethyl conformation (gg, gt, and tg rotamers about the C4-C5 bond) on the conformational energies and structural parameters (bond lengths, bond angles, bond torsions) of the 10 envelope forms of the biolo gically relevant aldopentofuranose, 2-deoxy-beta -D-erythro-pentofuranose ( 2-deoxy-D-ribofuranose) 2, has been investigated by ab initio molecular orb ital calculations at the HF/6-31G* level of theory. C4-C5 bond rotation ind uces significant changes in the conformational energy profile of 2 (2gt and 2tg exhibit one global energy minimum, whereas 2gg exhibits two nearly equ ivalent energy minima), and structural changes, especially those in bond le ngths, are consistent with predictions based on previously reported vicinal , 1,3- and 1,4-oxygen lone pair effects. HF/6-31G*-optimized envelope geome tries of 2gg were re-optimized using density functional theory (DFT, B3LYP/ 6-31G*), and the resulting structures were used in DFT calculations of NMR spin-spin coupling constants involving C-13 (i.e., J(CH) and J(CC) over one , two, and three bonds) in 2gg according to methods described previously. T he computed J-couplings were compared to those reported previously in 2gt t o assess the effect of C4-C5 bond rotation on scalar couplings within the f uranose ring and hydroxymethyl side chain. The results confirm prior predic tions of correlations between (2)J(CH), (3)J(CH), (2)J(CC) and (3)J(CC), an d ring conformation, and verify the usefulness of a concerted application o f these couplings (both their magnitudes and signs) in assigning preferred ring and C4-C5 bond conformations in aldopentofuranosyl rings. The new calc ulated J-couplings in 2gg have particular relevance to related J-couplings in DNA (and RNA indirectly), where the gg rotamer, rather than the gr rotam er, is observed in most native structures. The effects of two additional st ructural perturbations on 2 were also studied, namely, deoxygenation at C5 (yielding 2,5-dideoxy beta -D-erythro-pentofuranose 4) and methyl glycosida tion at O1 (yielding methyl 2-deoxy-beta -D-erythro-pentofuranoside 5) at t he HF/6-31G* level. The conformational energy profile of 4 resembles that f ound for 2,or, not 2gg, indicating that 4 is an inappropriate structural mi mic of the furanose ring in DNA. Glycosidation failed to induce differentia l stabilization of ring conformations containing an axial C1-O1 bond (anome ric effect), contrary to experimental data. The latter discrepancy indicate s that either the magnitude of this differential stabilization depends on r ing configuration or that solvent effects, which are neglected in these cal culations, play a role in promoting this stabilization.