- Absolute configuration of natural diastereoisomers of 6β- hydroxyhyoscyamine by vibrational circular dichroism
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The absolute configuration of the two natural diastereoisomers of 6β-hydroxyhyoscyamine has been determined using vibrational circular dichroism (VCD) spectroscopy. The predicted VCD and IR spectra of (3R,6R,2′S)-6β-hydroxyhyoscyamine (1) and (3S,6S,2′S)-6β- hydroxyhyoscyamine (2) were calculated using density functional theory (DFT) with the B3LYP functional and 6-31G(d) basis set and considering the eight lower energy conformations of each diastereoisomer. In both cases, the first four conformers showed the N-Me group in the syn orientation, permitting the formation of a hydrogen bond between the hydroxy group at the tropane ring and the tertiary nitrogen atom. In addition the eight conformers showed an intramolecular hydrogen bond between the hydroxy and carbonyl groups of the tropic ester moiety. The calculated IR spectra of both molecules showed good agreement with the experimental spectra, while comparison of the experimental and calculated VCD spectra showed that the absolute configuration of dextrorotatory 6β-hydroxyhyoscyamine is (3R,6R,2′S), while the levorotatory isomer is (3S,6S,2′S).
- Munoz, Marcelo A.,Munoz, Orlando,Joseph-Nathan, Pedro
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- RESOLUTION OF ENANTIOMERS BY HPLC ON CELLULOSE TRANS- AND CIS-TRIS(4-PHENYLAZOPHENYLCARBAMATE)
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Cellulose tris(4-phenylazophenylcarbamate) ( CPAPC ) having azobenzene pendant groups was adsorbed on silica gel to use as a chiral stationary phase for HPLC.Pure trans-CPAPC resolved many racemic compounds, whereas 70 percent cis-CPAPC showed very poor resolving power.
- Okamoto, Yoshio,Sakamoto, Hideaki,Hatada, Koichi,Irie, Masahiro
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- Tropic acid biosynthesis: The incorporation of (RS)-phenyl[2-18O,2-2H]lactate into littorine and hyoscyamine in Datura stramonium
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The incorporation of oxygen-18 from (RS)-phenyl-[2-18O,2-2H]lactate into the tropane alkaloids littorine 1 and hyoscyamine 2 in Datura stramonium reveals that up to 29% of the oxygen-18 is lost during the transformation of 1 to 2.
- Wong, Chi W.,Hamilton, John T. G.,O'Hagan, David,Robins, Richard J.
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- Strategy Approach for Direct Enantioseparation of Hyoscyamine Sulfate and Zopiclone on a Chiral αl-Acid Glycoprotein Column and Determination of Their Eutomers: Thermodynamic Study of Complexation
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Rapid and simple isocratic high-performance liquid chromatographic methods with UV detection were developed and validated for the direct resolution of racemic mixtures of hyoscyamine sulfate and zopiclone. The method involved the use of αl-acid glycoprotein (AGP) as chiral stationary phase. The stereochemical separation factor (Greek small letter alpha with tonos) and the stereochemical resolution factor (Rs) obtained were 1.29 and 1.60 for hyoscyamine sulfate and 1.47 and 2.45 for zopiclone, respectively. The method was used for determination of chiral switching (eutomer) isomers: S-hyoscyamine sulfate and eszopiclone. Several mobile phase parameters were investigated for controlling enantioselective retention and resolution on the chiral AGP column. The influence of mobile phase, concentration and type of uncharged organic modifier, ionic strength, and column temperature on enantioselectivity were studied. Calibration curves were linear in the ranges of 1-10 μg mL-1 and 0.5-5 μg mL-1 for S-hyoscyamine sulfate and eszopiclone, respectively. The method is specific and sensitive, with lower limits of detection and quantifications of 0.156, 0.515 and 0.106, 0.349 for S-hyoscyamine sulfate and eszopiclone, respectively. The method was used to identify quantitatively the enantiomers profile of the racemic mixtures of the studied drugs in their pharmaceutical preparations. Thermodynamic studies were performed to calculate the enthalpic ΔH and entropic ΔS terms. The results showed that enantiomer separation of the studied drugs were an enthalpic process.
- Zaazaa, Hala E.,Salama, Nahla N.,Abd El Halim, Lobna M.,Salem, Maissa Y.,Abd El Fattah, Laila E.
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- Comparison of three S-β-CDs with different degrees of substitution for the chiral separation of 12 drugs in capillary electrophoresis
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Three kinds of sulfated β-cyclodextrin (S-β-CD), including a single isomer, heptakis-6-sulfato-β-cyclodextrin (HS-β-CD), degree of substitution (DS) of 7, which was synthesized in our laboratory and another two commercialized randomly substituted mixtures, a sulfated β-cyclodextrin with DS of 7 to 11, as well as a highly sulfated-β-cyclodextrin with DS of 12 to 15, were used for the enantioresolution of 12 drugs (the β-blockers, phenethylamines, and anticholinergic agents) in capillary electrophoresis. The enantioseparation under varying concentrations of S-β-CD and background electrolyte pH were systematically investigated and compared. Based on the experimental results, the effect of the nature of S-β-CD and analyte structure on the enantioseparation is discussed.
- Wang, Zhaokun,Zhang, Qiongwen,Luo, Linda,Sun, Tiemin,Guo, Xingjie
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p. 558 - 565
(2017/08/26)
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- ALKOXY ARYL BETA2 ADRENERGIC RECEPTOR AGONISTS
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The invention provides novel β2 adrenergic receptor agonist compounds. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat diseases associated with β2 adrenergic receptor activity, and processes and intermediates useful for preparing such compounds.
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- Differential analgesic activity of the enantiomers of atropine derivatives does not correlate with their muscarinic subtype selectivity
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The enantiomers of several tropic and p-substituted tropic acid esters related to atropine obtained by esterification under non-racemizing conditions after resolution of the corresponding racemic acids [(+)- and (-)-18, (+)- and (-)-19] are reported. They were tested in vitro on muscarinic subtype receptors and in vivo for their analgesic activity on mice. As in the case of the lead compound, R-(+)-hyoscyamine, these substances show enantioselectivity in analgesic tests, the eutomers being the R-(+) or R-(+)-p-substituted tropic acid derivatives. However, this property, which is a consequence of increased central release of ACh, seems unrelated to muscarinic subtype selectivity insofar as the compounds are unable to discriminate muscarinic subtype receptors. A possible explanation of these results which does not involve subtype selectivity is proposed, based on the recently developed concept of inverse agonism.
- Dei,Bartolini,Bellucci,Ghelardini,Gualtieri,Manetti,Romanelli,Scapecchi,Teodori
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p. 595 - 605
(2007/10/03)
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- 7β-HYDROXYHYOSCYAMINE FROM DUBOISIA MYOPOROIDES-D. LEICHHARDTII HYBRID AND HYOSCYAMUS ALBUS
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A new tropane alkaloid, 7β-hydroxyhyoscyamine was isolated, together with 6β-hydroxyhyoscyamine, hyoscyamine, norhyoscyamine, scopolamine and tropine, from the leaves of Duboisia hybrid M-II-8-6 (crossbred between D. myoporoides and D. leichhardtii) and the hairy roots of Hyoscyamus albus.Key Word Index - Duboisia myoporoides; D. leichhardtii; Hyoscyamus albus; Solanaceae; Agrobacterium rhizogenes; tropane alkaloid; 7β-hydroxyhyoscyamine; 6β-hydroxyhyoscyamine.
- Ishimaru, Kanji,Shimomura, Koichiro
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p. 3507 - 3510
(2007/10/02)
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