Dihydropyran ring conformations. I. Structures of 2-methoxy- and 2-hydroxy-2,4-dimethyl-3,4-dihydro-2H,5H-pyrano[3,2-c][1]benzopyran-5-ones

Valente, E.; Eggleston, Drake S.

doi:10.1107/s0108768191000423

Cited by 4 publications

(4 citation statements)

References 14 publications

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“…3A) arising from the 1 L a band of the 4-carboxy-5,6-dihydro-[ 1H ]-pyrano chromophore 13 . Since compound 1 assumes a distorted dihydropyran conformation 14 and the helicity rule is applicable in this case, the CE with shorter wavelength predicts the 1 S and 5 S configuration 15,16 . In addition, chemical shifts of compounds with the 1 β configuration generally appeared at approximately 94–96 ppm, while oleonin with the 1 α configuration showed a chemical shift of 105.7 ppm in CD 3 OD 17 .…”

Section: Resultsmentioning

confidence: 99%

Hydroxyoleoside-type seco-iridoids from Symplocos cochinchinensis and their insulin mimetic activity

Lee

Pham

et al. 2019

Sci Rep

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As part of an ongoing study of new insulin mimetic agents from medicinal plants, the 70% EtOH extract of Symplocos cochinchinensis was found to have a stimulatory effect on glucose uptake in 3T3-L1 adipocyte cells. The intensive targeted isolation of this active extract resulted in ten new hydroxyoleoside-type compounds conjugated with a phenolic acid and monoterpene (1–6 and 8–11), as well as four known compounds (7 and 12–14). The chemical structures of the new compounds were determined based on spectroscopic data analysis (1H and 13C NMR, HSQC, HMBC, NOESY and MS). The absolute configurations of the isolated compounds were determined by electronic circular dichroism (ECD) analysis of derivatives obtained after a series of reactions, such as those with dirhodium (ІІ) tetrakis (trifluoroacetate) and dimolybdenum (ІІ) tetraacetate. In vitro, compounds 3, 7 and 8 moderately increased the 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG) uptake level in differentiated 3T3-L1 adipocytes. For further studies, we evaluated their effects on the expression of glucose transporter-4 (GLUT4), its translocation, protein tyrosine phosphatase 1B (PTP1B) inhibition and expression of phosphorylated Akt. Our results strongly suggest that the traditional uses of this plant can be described as active constituents by hydroxyoleoside-type compounds.

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Section: Resultsmentioning

confidence: 99%

Hydroxyoleoside-type seco-iridoids from Symplocos cochinchinensis and their insulin mimetic activity

Lee

Pham

et al. 2019

Sci Rep

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“…[26] The crystal forms trap a conformation along this continuum evident from many structural studies. [15,24,26,58] The crystal structure of 4 is of the a-anomer In solution, the NMR signals for the cyclic hemiketal warfarin tautomers (1b, 1c) have been assigned by comparison with the methyl ketals (trans 4, cis 5). Spectra in CDCl 3 have been previously reported, but not in CD 3 OD, and incompletely in d 6 -DMSO (Table 1).…”

Section: Discussionmentioning

confidence: 99%

“…In d 6 -DMSO, the carbon signals for the seventeen carbons of both cyclic warfarin hemiketals (1b, 1c) have been reported more or less completely. [14,[24][25][26]33] Re-determined here, the complete assignments are given in Table S-2b where they are tabulated with their reference methyl ketals (4, 5). However, even though the minor open form 1a composes about 15% of the tautomeric mixture in this solvent, Obaseki & Porter (1987) reported that signal broadening had obscured all but four carbons.…”

Section: Discussionmentioning

confidence: 99%

“…[12][13][14] Additionally, many warfarin analogs and derivatives with similar co-reactive groups are also found in hemiketal forms by crystallography. [15][16][17][18][19][20][21][22][23][24] In solution, NMR and by UV-VIS spectroscopy has shown that warfarin exists in an equilibrium between the diastereomeric coumarin hemiketals and the intermediate coumarin open form (Scheme 1, 1a -c). [25][26][27][28][29] The question of the heterocycle tautomers, coumarin and chromone, has been studied over years, with spectroscopic assignments typically support the coumarin structure.…”

Section: Introductionmentioning

confidence: 99%

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Warfarin tautomers in solution: a structural, computational and thermodynamic study

Osborne,

Danielyan,

Hoang

et al. 2023

Preprint

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Variable temperature NMR spectroscopic measurements on (S)-warfarin [open-form: 3-(1’-phenyl-3’-oxobut-1’-yl)-4-hydroxycoumarin] in CDCl3, CD3OD and d6-DMSO generally showed tautomeric compositions in the order trans (2S,4S) coumarin hemiketal > cis (2R,4S) coumarin hemiketal > open (S) coumarin enol in slow dynamic equilibrium over temperature ranges rising modestly from ambient. A computational (DFT - M06-2X) examination of the lower energy tautomers including coumarin and chromone open and cyclic forms (gas phase, chloroform or DMSO fields) was consistent with the general solution compositions. The crystal and molecular structures for model compounds of the major solution tautomers are reported: (2S,4S)-warfarin methyl ketal [orthorhombic, P212121], (2R,4S)-warfarin methyl ketal [orthorhombic, P212121], (rac)-warfarin-4-methyl ether [monoclinic, P21/n], and the open chromone (S)-warfarin-2-methyl ether [monoclinic, P21, Z = 8]. A combination of direct integration and line-fitting methods were used to determine solution (S)-warfarin tautomer compositions. As temperatures were increased, the concentrations of the open coumarin form increased at the expense of the cyclic hemiketals. Equilibrium constants were used to determine the standard free-energy differences for the two open-cyclic equilibria (trans hemiketal open, open cis hemiketal, respectively) in three solvents: CDCl3 [+ 3.7(4), -2.8(6) kJ/mol], CD3OD [+ 7.6(16), -4.7(9) k/mol], d6-DMSO [+ 3.5(7), -1.1(2) kJ/mol]. Standard enthalpy and entropy differences were also determined from van’t Hoff analysis. Rates of the respective reactions were estimated from line-widths for the cyclic hemiketals and solution equilibrium compositions for each species. Eyring analysis gave ΔG‡, ΔH‡, and ΔS‡, respectively, for the forward and reverse reactions of coumarin trans hemiketal open-form and for the open-form cis hemiketal. Negative entropic contributions to the observed transition state energies were consistent with solvent or solute ordering in the prototropic reactions. Open-form NMR signals were broader than could be accounted for by the open-cyclic equilibria alone, increasingly so in polar and protic solvents and with rising temperatures. While a conformational equilibrium may operate, an increasingly faster intermediate dynamic equilibrium between open coumarin-chromone tautomers may be a more likely explanation.

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Dynamic Study of Cyclic-Open Tautomerism in a Warfarin Analog

Danielyan,

Zuniga,

Hoang

et al. 2023

J Chem Crystallogr

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Dihydropyran ring conformations. I. Structures of 2-methoxy- and 2-hydroxy-2,4-dimethyl-3,4-dihydro-2H,5H-pyrano[3,2-c][1]benzopyran-5-ones

Cited by 4 publications

References 14 publications

Hydroxyoleoside-type seco-iridoids from Symplocos cochinchinensis and their insulin mimetic activity

Hydroxyoleoside-type seco-iridoids from Symplocos cochinchinensis and their insulin mimetic activity

Warfarin tautomers in solution: a structural, computational and thermodynamic study

Dynamic Study of Cyclic-Open Tautomerism in a Warfarin Analog

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