DFT-GIAO(1)H NMR chemical shifts prediction for the spectral assignment and conformational analysis of the anticholinergic drugs (-)-scopolamine and (-)-hyoscyamine
Copyright (c) 2010 John Wiley & Sons, Ltd.
| Veröffentlicht in: | Magnetic resonance in chemistry : MRC. - 1985. - 48(2010), 6 vom: 21. Juni, Seite 458-63 |
|---|---|
| 1. Verfasser: | |
| Weitere Verfasser: | |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2010
|
| Zugriff auf das übergeordnete Werk: | Magnetic resonance in chemistry : MRC |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Cholinergic Antagonists Atropine 7C0697DR9I Scopolamine DL48G20X8X |
| Zusammenfassung: | Copyright (c) 2010 John Wiley & Sons, Ltd. The relatively large chemical shift differences observed in the (1)H NMR spectra of the anticholinergic drugs (-)-scopolamine 1 and (-)-hyoscyamine 2 measured in CDCl(3) are explained using a combination of systematic/molecular mechanics force field (MMFF) conformational searches and gas-phase density functional theory (DFT) single point calculations, geometry optimizations and chemical shift calculations within the gauge including/invariant atomic orbital (GIAO) approximation. These calculations show that both molecules prefer a compact conformation in which the phenyl ring of the tropic ester is positioned under the tropane bicycle, clearly suggesting that the chemical shift differences are produced by the anisotropic effect of the aromatic ring. As the calculations fairly well predict these experimental differences, diastereotopic NMR signal assignments for the two studied molecules are proposed. In addition, a cursory inspection of the published (1)H and (13)C NMR spectra of different forms of 1 and 2 in solution reveals that most of them show these diastereotopic chemical shift differences, strongly suggesting a preference for the compact conformation quite independent of the organic or aqueous nature of the solvent |
|---|---|
| Beschreibung: | Date Completed 13.09.2010 Date Revised 01.12.2018 published: Print Citation Status MEDLINE |
| ISSN: | 1097-458X |
| DOI: | 10.1002/mrc.2601 |