Kristall- und Molekülstruktur von 1-Hyoscyaminhydrobromid

Kussäther, E.; Hasse, J.

doi:10.1107/s0567740872007174

Cited by 25 publications

(9 citation statements)

References 2 publications

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“…This particular disposition was later corroborated by 2D NOESY experiments as cross peaks between aromatic and H‐6/H‐7 signals in 1 were detected 13. In addition, a single crystal X‐ray study of the sesquihydrate of 1 17 afforded this compact conformation similar to the one proposed by Feeney et al , and an equivalent result was obtained for the hydrobromide of 2 when crystallized from an aqueous solution 18. Nevertheless, an anhydrous conformational pseudopolymorph of 1 HBr with an ‘ extended ’ conformation, where the phenyl group in the tropic acid moiety is anti to the tropane ring, can also be obtained by recrystallization from ethanol/acetone 19…”

Section: Introductionsupporting

confidence: 70%

DFT‐GIAO¹H NMR chemical shifts prediction for the spectral assignment and conformational analysis of the anticholinergic drugs (−)‐scopolamine and (−)‐hyoscyamine

Muñoz

Joseph‐Nathan

2010

Magnetic Reson in Chemistry

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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.

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Section: Introductionsupporting

confidence: 70%

DFT‐GIAO¹H NMR chemical shifts prediction for the spectral assignment and conformational analysis of the anticholinergic drugs (−)‐scopolamine and (−)‐hyoscyamine

Muñoz

Joseph‐Nathan

2010

Magnetic Reson in Chemistry

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“…The equation for best plane B through 0(2,3), and C(9,lO) was: 6.27(4)X + 4.50(16)Y -6.76(11)2 = 5.27 (13). The equation for best plane C throughC (12)(13)(14)(15)(16)(17) was: 2.37(3)X + 8.02(3)Y + 12.73(9)2 = 10.967 (17). 1 Also here, there is an ambiguity as to the atom descriptor for the ortho carbon [C( 13) us.…”

Section: Resultsmentioning

confidence: 99%

Solid-state stereochemistry of anhydrous (–)-scopolamine hydrobromide

Glaser¹,

Charland²,

Michel³

1989

J. Chem. Soc., Perkin Trans. 2

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The solid-state structure of anhydrous (Nr,C,-S) -( -)-scopolamine hydrobromide [ ( -)-hyoscine], an acetylcholine antagonist, has been determined by single crystal X-ray diffraction analysis. ( -) -Scopolamine hydrobromide [an hydrous form] gives crystals belonging to the orthorhombic P2,2,2, space group, and at 298 K: a = 7.348(1), b = 10.482(1), c = 22.867(1) 8, V = 1 761.26(1) A3, Z = 4, R ( F ) = 0.053, and R,(F) = 0.049. The (S)-absolute configuration was determined from the effects of anomalous dispersion of the bromide atom. The N-methyl group exists in an axial configuration similar to that previously described for the hemihydrate. However, in the anhydrous form the tropate residue exhibits a different conformation from that noted for the hemihydrate. The tropate ester moiety in (Nr,C,-S)-( -) -scopolamine hydrobromide [anhydrous form] and (Ns,C,-S) -Nbutylhyoscinium bromide both exhibit very similar crystalline-state conformations, while that in

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“…The 24 substances considered were: (-)-S-hyoscyamine hydrobromide (12,13); (-)-S-hyoscine hydrobromide (14); (-)--S-hyoscine-N-oxide hydrobromide (15) …”

Section: Appendixmentioning

confidence: 99%

Anticholinergic substances: A single consistent conformation

Pauling

Datta

1980

Proc. Natl. Acad. Sci. U.S.A.

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An interactive computer-graphics analysis of 24 antagonists of acetylcholine at peripheral autonomic postganglionic (muscarinic) nervous junctions and at similar junctions in the central nervous system, the crystal structures of which are known, has led to the determination of a single, consistent, energetically favorable conformation for all 24 substances, although their observed crystal structure conformations vary widely. The absolute configuration and the single, consistent (ideal) conformation of the chemical groups required for maximum anticholinergic activity are described quantitatively.

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Kristall- und Molekülstruktur von 1-Hyoscyaminhydrobromid

Cited by 25 publications

References 2 publications

DFT‐GIAO¹H NMR chemical shifts prediction for the spectral assignment and conformational analysis of the anticholinergic drugs (−)‐scopolamine and (−)‐hyoscyamine

DFT‐GIAO¹H NMR chemical shifts prediction for the spectral assignment and conformational analysis of the anticholinergic drugs (−)‐scopolamine and (−)‐hyoscyamine

Solid-state stereochemistry of anhydrous (–)-scopolamine hydrobromide

Anticholinergic substances: A single consistent conformation

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Kristall- und Molekülstruktur von 1-Hyoscyaminhydrobromid

Cited by 25 publications

References 2 publications

DFT‐GIAO1H NMR chemical shifts prediction for the spectral assignment and conformational analysis of the anticholinergic drugs (−)‐scopolamine and (−)‐hyoscyamine

DFT‐GIAO1H NMR chemical shifts prediction for the spectral assignment and conformational analysis of the anticholinergic drugs (−)‐scopolamine and (−)‐hyoscyamine

Solid-state stereochemistry of anhydrous (–)-scopolamine hydrobromide

Anticholinergic substances: A single consistent conformation

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DFT‐GIAO¹H NMR chemical shifts prediction for the spectral assignment and conformational analysis of the anticholinergic drugs (−)‐scopolamine and (−)‐hyoscyamine

DFT‐GIAO¹H NMR chemical shifts prediction for the spectral assignment and conformational analysis of the anticholinergic drugs (−)‐scopolamine and (−)‐hyoscyamine