Conformational studies on 2',3'-unsaturated pentopyranosyl nucleosides by H-1 NMR spectroscopy. Impact of pi->sigma* interactions on the axial preference of the purine versus pyrimidine nucleobase

Polak, M;Doboszewski, B;Herdewijn, P.;Plavec, J
(1997) Journal of the American chemical society — Vol. 119, n° 41, p. 9782-9792 (1997)

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  • Polak, M
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  • Doboszewski, B
    Author
  • Herdewijn, P.
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  • Plavec, J
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Abstract
A variable-temperature H-1 NMR study on beta- and alpha-D-glycero-pent-2'-enopyranosyl nucleosides 1-10 has shown that the constituent pyranosyl moiety is involved in a rapid two-state H-6(5) reversible arrow E-5/S-5(4) conformational equilibrium. The results of the conformational analysis of (3)J(HH) coupling constants were compared with the trends of X-ray crystallography and ab initio calculations, which support the two-state dynamic equilibrium and suggest hat the equilibrium is affected by the nature of the heterocyclic aglycon. The beta nucleosides 1-5 adopt predominantly (approximately 95% in purine and 80% in pyrimidine nucleosides at 298 K) the conformation that is intermediate between the E-5 and S-5(4) canonical forms, where both the nucleobase and 4'-OH are in the axial orientation. The pyranosyl moiety of alpha-purine nucleosides 6 and 7 is involved in an unbiased two-state conformational equilibrium. On the other hand, the alpha-pyrimidine nucleosides 8-10 show a conformational bias of ca. 75% toward E-5 canonical form. The van't Hoff type analysis of the changes in the conformational equilibrium with temperature afforded thermodynamic data on H-6(5) reversible arrow E-5/S-5(4) conformational equilibrium in 1-10. The comparative analysis of Delta H degrees has shown that H-6(5) reversible arrow E-5/S-5(4) conformational equilibrium in 1-10 is driven by the fine tuning of O6'-Cl'-N1/9 anomeric effect, the gauche effect of the [O6'-C5'-C4'-O4'] fragment, the interaction between pi-system of the C2'-C3' bond with the heterocyclic aglycon and 4'-OH in the allylic position, and the intrinsic steric effect. Dissection of the individual contributions to the drive of conformational equilibrium of 1-10 has shown that the relative strength of pi(-->) sigma*(Cl'-N1/9) interactions in purine vs pyrimidine nucleobases increases in the following order: cytosine < uracil < thymine < adenine < ganine.
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Polak, M., Doboszewski, B., Herdewijn, P., & Plavec, J. (1997). Conformational studies on 2′,3′-unsaturated pentopyranosyl nucleosides by H-1 NMR spectroscopy. Impact of pi->sigma* interactions on the axial preference of the purine versus pyrimidine nucleobase. Journal of the American chemical society, 119(41), 9782-9792. https://doi.org/10.1021/ja963683k (Original work published 1997)