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  • Organic Chemistry  (15,506)
  • 1995-1999  (2,690)
  • 1980-1984  (3,406)
  • 1975-1979  (3,423)
  • 1970-1974  (3,415)
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  • 1
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 7 (1995), S. 1-9 
    ISSN: 0899-0042
    Keywords: acyl glucuronide ; enantiomer ; epimer ; diastereomer ; nonsteroidal antiinflammatory drug ; 2-arylpropionic acid ; systemic cycling ; reactivity ; hydrolysis ; covalent binding ; drug-protein adduct ; regioisomer ; aglycone ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 2
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 7 (1995), S. 23-27 
    ISSN: 0899-0042
    Keywords: felodipine ; retention model ; micellar mobile phases ; chiral resolution ; CHIRAL-AGP ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A retention model for the chiral separation of an uncharged solute, felodipine, on CHIRAL-AGP, using a micellar mobile phase is proposed. The model assumes the presence of two stereoselective sites and each enantiomer was found to interact with different sites. Addition of a chiral aliphatic alcohol, (+)-(S)-2-octanol, preferentially interacted with the binding site for (-)-(S)-felodipine. The monomeric form of the micellar agent (Tween® 20) competed with the enantiomers for the adsorption sites, and the formation of a 1:1 complex between the enantiomers and the micelles was assumed. The retention of the solutes was effectively controlled by adding small quantities (〈1.63 × 10-3 M) of the nonionic detergent Tween 20 to the mobile phase. Baseline separation was achieved by addition of 1.0 mM n-octylamine to the mobile phase; 8.14 × 10-4 M Tween 20 in phosphate buffer pH 7.0. The separation factor (α = 1.74) was unaffected by the detergent concentration in the presence of 1.0 mM n-octylamine. © 1995 Wiley-Liss, Inc.
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  • 3
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 7 (1995), S. 40-43 
    ISSN: 0899-0042
    Keywords: enantioselectivity ; pig liver esterase ; hydrolysis ; oxazepam ; chiral stationary phase HPLC ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A widely utilized pig liver esterase preparation has been found to be derived essentially exclusively from the cytosolic fraction of pig livers. Esterases in cytosol and microsomes prepared from a fresh pig liver hydrolyzed the S- and R-enantiomers of racemic oxazepam 3-acetate (rac-OXA) with specific activity ratios of approximately 2.3:1 and 1:62, respectively. Product formations were analyzed by chiral stationary phase high-performance liquid chromatography. The commercial pig liver esterase preparation showed greater activity toward S-OXA than did the esterases in the cytosolic fraction prepared from fresh pig liver. The results established that (i) esterases contained in microsomes and cytosol of pig liver have opposite enantioselectivity in the hydrolysis of rac-OXA and (ii) the commercial pig liver esterase preparation has a cytosolic origin. © 1995 Wiley-Liss, Inc.
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 7 (1995) 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 5
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 7 (1995), S. 62-68 
    ISSN: 0899-0042
    Keywords: chiral symmetry breaking ; chiral autocatalysis ; asymmetric crystallization ; origin of optical activity ; secondary nucleation ; stirred crystallization ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Chiral symmetry breaking can be realized in stirred crystallization of Na-ClO3. We present experimental and theoretical studies of the random distribution of crystal enantiomeric excess (cee) for various stirring and solvent evaporation rates. For a fixed solvent evaporation rate, as the stirring RPM is increased, the probability distribution of cee initially broadens and subsequently develops a sharp peak close to cee = 1. On further increase of stirring rate, the probability distribution once again broadens. This broad probability distribution becomes narrow, with a sharp peak near cee = 1, if the solvent evaporation rate is decreased. Thus we show some ways in which the probability distribution of cee can be controlled in stirred crystallization. In particular, our study shows that the stirring rate and the solvent evaporation rate can be adjusted to maximize crystal enantiomeric excess. © 1995 Wiley-Liss, Inc.
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  • 6
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 7 (1995), S. 82-89 
    ISSN: 0899-0042
    Keywords: CD ; conformational behaviour ; configuration ; helicity rules ; 2-aminotetralin ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The circular dichroism (CD) spectra of a series of oxygenated 2-(dipropylamino)tetralin derivatives are reported. On the basis of known absolute configurations and conformational preferences of the compounds, the validity of published correlations between the sign of the 1Lb Cotton effect and the three-dimensional structure was examined. Contrary to predictions, substitution in position 6 or 7 of the tetralin moiety did not change the sign of the 1Lb Cotton effect. An unexpected sign inversion was, however, observed in some of the compounds containing methyl substituents in the nonaromatic ring. The occurrence of this inversion was not correlated with a change in conformational behaviour and varied depending on the position and nature of the aromatic substituent. No correlations were obvious between the sign of the 1Lb Cotton effect and the absolute configuration and conformational preferences of the compounds. Therefore, at present, CD spectroscopy does not appear to be useful in assignments of the absolute configurations of 2-(dipropylamino)tetralin derivatives. © 1995 Wiley-Liss, Inc.
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  • 7
    ISSN: 0899-0042
    Keywords: conformational effect ; intramolecular ; allylic ; stereogenic ; steric ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The diastereofacial selectivity of both inter- and intramolecular Diels-Alder reactions with dienes having an allylic stereogenic center has been studied by varying the allylic oxygen protective group. Four different hydroxy protective groups were investigated including benzyl, t-butyldiphenylsilyl, triethylsilyl, and t-butyldimethylsilyl ethers. For intermolecular reactions, the benzyl ether derivative gave the highest sπ-facial selectivity through a transition state in which the allylic stereocenter favors the CH eclipsed conformation. For intramolecular cycloadditions, the t-butyldimethylsilyl group gave a slightly higher selectivity than the benzyl ether derivative through a transition state in which the allylic stereocenter favors the CO eclipsed conformation. The opposite diastereofacial selectivity observed for inter- and intramolecular reactions is explained by considering both steric and electronic effects. © 1995 Wiley-Liss, Inc.
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  • 8
    ISSN: 0899-0042
    Keywords: chiral 1,5-bisnitrogen ligands ; homogeneous asymmetric cyclopropanation ; copper(I) complexes ; enantioselectivity ; chiral gas chromatography ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Optically active enamines of 2-(2′-pyrido)acetophenone or 2-(2′-quinolino)acetophenone with (R)-1-phenylethylamine, (R)-1-(1-naphthyl)ethylamine, (R)-cyclohexylethylamine, and (R)-phenylglycinol were prepared and their copper(I) complexes used in the enantioselective cyclopropanation of styrene with ethyl- and menthyldiazoacetate. Enantioselectivities of up to 42% enantiomeric excess were obtained for cis/trans 2-phenylcyclopropan-1-carboxylic acid ethyl esters, as determined by gas-liquid chromatography (GLC) on chiral chromatographic columns. © 1995 Wiley-Liss, Inc.
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  • 9
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 7 (1995), S. 121-127 
    ISSN: 0899-0042
    Keywords: cyclic formyl-monoterpenes ; tricyclic formyl-sesquiterpenes ; homogeneous catalyst ; rhodium-phosphine catalyst ; platinum-phosphine-tin(II)chloride catalyst ; hydroformylation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The hydroformylation of (+)-(R)-limonene (1), (+)-(1R)-isolimonene (2), camphene (3), and (+)-β-cedrene (4) resulted in the regiospecific formation of the corresponding linear aldehyde in the presence of homogeneous platinum and, in some cases, rhodium catalysts. The epimeric composition could be influenced slightly by optically active catalysts formed with chiral bidentate phosphines. The relative configurations of newly formed stereogenic centers were analyzed by 1H and 13C NMR. The primarily formed aldehydes of (+)-8(15)-cedren-9-ol (5) and γ-gurjunene (6) underwent cyclization, giving a mixture of epimers of tetracyclic terpenes. Despite the moderate diastereoselection, the products are of practical importance due to their highly regioselective formation. © 1995 Wiley-Liss, Inc.
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  • 10
    ISSN: 0899-0042
    Keywords: biooxidation ; Pseudomonas putida 39/D ; absolute stereochemistry ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: 2(2-Bromoethyl)bromobenzene was subjected to microbial oxidation by the whole cells of Pseudomonas putida 39/D and JM109(pDTG601) yielding (3R,4S)-2-(2-bromoethyl)-bromocyclohexa-1,5-diene-3,4-diol. © 1995 Wiley-Liss, Inc.
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  • 11
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 7 (1995), S. 560-564 
    ISSN: 0899-0042
    Keywords: β-cyclodextrin ; β-cyclodextrin derivatives ; methyl-β-cyclodextrin ; hydrolysis ; 2-methoxy-2-phenylacetic acid-4-nitrophenylester ; methoxy mandelic acid esters ; chirality ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Assessing the reactivity of optical antipodes is of central importance in drug research. Using the model of 2-methoxy-2-phenylacetic acid-4-nitrophenylester (MPE), the rate of hydrolysis in the presence of β-cyclodextrin (CD), hydroxyethyl- and hydroxypropyl-β-CD, as well as methyl-β-CD is studied photometrically and by means of HPLC (Chiralcel-OD-R-column). Both β-CD and hydroxyalkylated-β-CD catalyze (-)-(R)-enantiomers to a larger extent than (+)-(S)-enantiomers, resulting in an enrichment of the latter. Methyl-β-CD stabilizes the ester trifold, thus abolishing chiral discrimination. © 1995 Wiley-Liss, Inc.
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  • 12
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 7 (1995), S. 605-609 
    ISSN: 0899-0042
    Keywords: aminosuccinyl peptides ; circular dichroism measurements ; II′ β-turns ; conformational equilibrium ; thermodynamics ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The conformational equilibrium of aminosuccinyl peptides between extended conformations and an intramolecularly hydrogen bonded type II′ β-turn conformation has been studied on the peptide Boc-L-Asu-Gly-L-Ala-OMe (Asu = aminosuccinyl residue) by means of temperature dependence of circular dichroism spectra.Owing to the peculiar chiroptical and conformational properties of the Asu residue, this technique proved to be very useful for deriving thermodynamic data for the above folding process. The value of ΔH0 (-6.6 kJ mol-1), obtained for the peptide studied in a chloroformacetonitrile mixture, shows that the lower energy of the folded conformer is primarily due to the characteristic intramolecular hydrogen bond of the β turns. © 1995 Wiley-Liss, Inc.
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  • 13
    ISSN: 0899-0042
    Keywords: domiodol ; mucolytic ; chiral synthesis ; D-mannitol ; lithium iodide ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The acid-catalyzed reaction of D-mannitol 4 with bromoacetaldehyde diethyl acetal followed by periodate cleavage of the corresponding diacetal 5 afforded (4S, 2R, S)-2-bromomethyl-4-hydroxymethyl-1,3-dioxolane 3c in good yields, from which the title compound 1 is obtained by displacement of the bromine with lithium iodide. © 1995 Wiley-Liss, Inc.
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  • 14
    Electronic Resource
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    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 7 (1995), S. 219-225 
    ISSN: 0899-0042
    Keywords: chiral separation ; cyclodextrins ; basic drugs ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The influence of the choice of type and/or concentration of cyclodextrin, other additives, the temperature surrounding the capillary, and buffer pH on the separation of some chiral basic drug substances in capillary zone electrophoresis has been evaluated. It was found that pH of the buffer and type and concentration of cyclodextrin had a major influence on the separation. © 1995 Wiley-Liss, Inc.
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  • 15
    ISSN: 0899-0042
    Keywords: chiral HPLC ; cellulose tris(3,5-dimethylphenyl carbamate) ; hydroperoxides ; enantiomers ; circular dichroism ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The analytical and preparative scale optical resolution of 1-cyclohexyl-1-phenylethyl hydroperoxide and 1,2,3,4-tetrahydro-1-napthyl hydroperoxide has been achieved by chiral HPLC on a cellulose tris(3,5-dimethylphenyl carbamate) stationary phase coated on silica gel. The method has been used to obtain several hundred milligrams of highly enriched enantiomers (%ee 〉98) which were characterized by [α]D and circular dichroism spectra, respectively. Configurational assignments were achieved for 1,2,3,4-tetrahydro-1-naphthyl hydroperoxide enantiomers. © 1995 Wiley-Liss, Inc.
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  • 16
    ISSN: 0899-0042
    Keywords: chirality ; cyclopyrrolone ; isomers ; racemization ; stability ; zopiclone ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: We investigated the degradation and racemization of zopiclone (ZOP) enantiomers in plasma and partially aqueous solutions (ethanol:phosphate buffer). Degradation and racemization increased with increasing pH and temperature. Degradation products were identified by means of mass spectrometry, which revealed hydrolysis of the carbamate function and opening of the pyrrolidone ring. In plasma, neither degradation nor racemization occurred after 6 months of storage at -20°C and subsequent extraction. © 1995 Wiley-Liss, Inc.
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  • 17
    Electronic Resource
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    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 6-10 
    ISSN: 0899-0042
    Keywords: enantiopure levodropropizine ; synthesis ; (R)-glycidol ; enantiomeric separation ; chiral HPLC ; enantiomeric enrichment ; binary melting point phase diagram ; crystal structure determination ; intermolecular hydrogen-bonding interactions ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Enantiopure levodropropizine can be synthesized in high yield by the direct nucleophilic addition of 1-phenylpiperazine to (R)-glycidol followed by recrystallization in absolute ethanol. A chiral HPLC method has been developed for the determination of its optical purity. The enantiomeric enrichment behavior of this compound in the recrystallization process is discussed according to its binary melting point phase diagram. Single crystal x-ray structural analysis shows the intermolecular hydrogen-bonding interactions between the hydroxyl and piperazinyl groups within the crystal lattice of levodropropizine. © 1996 Wiley-Liss, Inc.
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  • 18
    Electronic Resource
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    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 24-29 
    ISSN: 0899-0042
    Keywords: CHO cells ; HeLa cells ; lipid peroxidation ; catalase ; D-amino acids ; L-amino acids ; toxicity ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: While the L-configuration of amino acids predominates in all known living systems, D-enantiomers of amino acids have been detected with highly sensitive chromatographic techniques in human physiological fluids. In the present study, the survival of Chinese hamster ovary cells (CHO) and HeLa cells was inhibited by exposure to high concentrations of some D- or L-amino acids. Inhibition of colony formation, though, was not necessarily observed to be chiral-dependent. Some L-amino acids (LAAS) were found to be toxic while other D-amino acids (DAAS) were innocuous in both cultures. This is contradictory to the previous observations that DAAS were generally considered to be harmful. Frequently it was implied, although not experimentally proven, that the LAAS were not toxic. One of the metabolites produced by oxidative deamination of D- or LAAS is hydrogen peroxide (H2O2), a reactive oxygen species (ROS) that is decomposed by catalase. Increased intracellular H2O2 can result in peroxidation of lipids. We measured catalase activity and the lipid peroxide levels (LPO) after incubating cells in either D- or LAAS. The amino acids (AAS) that were found to inhibit colony formation were found to be associated with higher levels of catalase activity and LPO. Therefore, we hypothesize that enhanced ROS generation may be, in part, responsible for the observed toxicity of some amino acids. © 1996 Wiley-Liss, Inc.
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  • 19
    Electronic Resource
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    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 35-38 
    ISSN: 0899-0042
    Keywords: ion channels ; receptors ; state-dependent interactions ; stereoselectivity ; local anesthetics ; 1,4-dihydropyridines ; Ca2+ channels ; Na+ channels ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Ion channels are pharmocologic receptors and as such exhibit stereoselective interactions with drugs. Ion channels are conformationally mobile transmembrane proteins existing in a number of open and closed states. Drug interactions with these different states may differ quantitatively and qualitatively. Stereoselectivity may not be a constant factor and may change according to channel state as determined by stimulus mode or experimental conditions. Selected examples are cited for Na+ and Ca2+ channels. © 1996 Wiley-Liss, Inc.
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  • 20
    Electronic Resource
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    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 39-48 
    ISSN: 0899-0042
    Keywords: α-pinene ; β-pinene ; camphene ; limonene ; borneol ; isoborneol ; succinite ; geochemistry ; stereochemistry ; pine resins ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Among the more prevalent chiral monoterpenoid compounds in conifers are α-pinene, β-pinene, and smaller amounts of camphene and limonene. The most prevalent chiral monoterpenoid compounds in fossilized resin (referred to as amber in this paper) appear to be borneol, isoborneol, and camphene. Most of these compounds have easily measured enantiomeric excesses. The borneol and isoborneol in some amber samples have pronounced enantiomeric excesses despite the fact that they are tens of millions of years old. The enantiomeric ratios of the monoterpenoids in different ambers vary tremendously and often are distinct. However, in any single amber sample, the stereochemistry (absolute configuration) of the excess monoterpenoid enantiomers appears to be identical. The camphene in amber may be a secondary reaction product formed over time, possibly from the dehydration of borneol. Although a compound's original stereochemistry can be preserved, it also may diminish with the number and type of chemical transformations over geological time. The monoterpene enantiomeric ratios in modern conifer resins vary tremendously. Future stereochemical studies are outlined that could provide the data necessary for more exact geochemical interpretations and possibly for obtaining pertinent paleobiological information. © 1996 Wiley-Liss, Inc.
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  • 21
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    Chirality 8 (1996), S. 77-83 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Excellent separations were achieved using a coated column to suppress electroosmotic flow and employing a countercurrent process between chiral selector and racemic solute. Using the macrocyclic antibiotic vancomycin as a chiral selector in capillary electrophoresis the resolution of nonsteroidal antiinflammatories and dansyl amino acids was achieved. Improvement in sensitivity due to the elimination of background absorbance and increased efficiency due to the removal of wall adsorption effects are both achieved using this technique. © 1996 Wiley-Liss. Inc.
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  • 22
    ISSN: 0899-0042
    Keywords: chiral purity ; pharmaceutical ; achiral ; cyclodextrin ; SBE cyclodextrin ; purity ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: In the past several years, capillary electrophoresis (CE) has generated considerable interest from pharmaceutical companies for control of both the chiral and achiral purity of bulk drugs and drug products. This paper evaluates the use of CE as: (1) a technique complementary to HPLC for the determination of peak homogeneity of a drug, (2) for determination of chiral purity, and (3) for determination of achiral purity. It would be greatly advantageous if CE could be used to determine both the chiral and achiral purity in a single assay. This investigation compares the results obtained for the separation of the enantiomers of duloxetine using several neutral cyclodextrins to those obtained using anionic cyclodextrins (sulfobutyl ether derivatives) as chiral selectors added to the separation buffer. In addition, it reports chiral separations obtained by using neutral cyclodextrins in a sulfonic acid-coated capillary column, which give a negatively charged capillary surface and electro-osmotic flow even in low pH buffers. The possible mechanism of separation is discussed. © 1996 Wiley-Liss, Inc.
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  • 23
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    Chirality 7 (1995), S. 311-325 
    ISSN: 0899-0042
    Keywords: enantiomers ; pharmaceuticals ; β-blockers ; chiral stationary phases ; Chiralcel ; Chiralpak ; liquid chromatography ; supercritical fluid chromatography ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: This paper presents a systematic comparison of liquid chromatography (LC) and supercritical fluid chromatography (SFC) for Chiralcel OD and Chiralpak AD chiral stationary phases (CSPs), performed using various chiral compounds having a known or potential pharmaceutical activity. The chiral recognition mechanisms involved in LC and SFC for the enantiomeric separation of β-blockers have been studied more particularly. As a general rule, it appears that the presence of polar functions, like primary or secondary hydroxyl or amine functions, may result in marked discrepancies in selectivity between LC and SFC. This result is peculiar to cellulose- and amylose-derived CSPs, for which the interactions involved in chiral recognition mechanism are not always well balanced, contrary to what happens for independent CSPs. In the case of chiral resolution of polar solutes or polymer-type CSPs, the analyst should try both the LC and SFC techniques to be able to choose the more stereoselective one. © 1995 Wiley-Liss, Inc.
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  • 24
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    Chirality 7 (1995), S. 349-352 
    ISSN: 0899-0042
    Keywords: development of chiral drugs ; regulatory affairs ; industrial opinion ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The purpose of this commentary is to provide information on the present status of the racemate/enantiomer debate in Japan and current industrial and regulatory attitudes to chiral drugs in Japan. It provides an update of our previous paper (Shindo and Caldwell, Chirality 3:91-93, 1991), and the interested reader is referred to this for background information. © 1995 Wiley-Liss, Inc.
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  • 25
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Investigations into the parameters affecting the enantiomeric separation of an intermediate in the synthesis of a drug targeted for cardiac arrhythmia is presented. The separation was achieved under subcritical fluid chromatography using CO2 modified with methanol and co-modifiers isopropyl amine and methylene chloride. The stationary phase was a cellulose based stationary phase manufactured under the trade name Chiracel OB. The results showed the addition of methylene chloride had a noticeable effect on resolution while the separation factor, α, remained constant. The co-modifier, isopropyl amine, did not considerably influence the resolution, or separation factor. Temperature studies were performed in order to establish the thermodynamic parameters of the interaction between the enantiomers and the stationary phase. Plots of In k′ vs. 1/T proved to be curved, while plots of In α vs. 1/T were linear. © 1996 Wiley-Liss, Inc.
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  • 26
    ISSN: 0899-0042
    Keywords: chiral ligand exchange chromatography ; chiral coating ; chiral discrimination ; chiral copper(II) complexes ; amino acids ; amino acid esters ; amino acid amides ; hydroxy acids ; dipeptides ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Copper(II) complexes of N2-octyl-(S)-phenylalaninamide (Noc-Phe-NH2), N2-dodecyl-(S)-phenylalaninamide (Ndo-Phe-NH2), and N2-octyl-(S)-norleucinamide (Noc-NLeu-NH2), dynamically adsorbed on a reversed-phase C18 column, were able to perform the direct enantiomeric separation of unmodified amino acids, amino acid amides and esters, hydroxy acids, and dipeptides by elution with aqueous or mixed aqueous-organic solutions containing copper(II) sulphate or acetate. The role played by several parameters in the separation procedure was examined with the copper(II) complex of Noc-Phe-NH2 [concentration of the copper(II) ion in the eluent, pH and eluent polarity, amount of adsorbed selector]. The separation was shown to occur entirely on the stationary phase. The mechanism of chiral discrimination is discussed in terms of the chromatographic parameters and of the structure of the copper(II) complexes in solution and in the solid state. The chiral stationary phase maintained its separation ability for about 3 months. However, the column could be easily restored by recovering the selector with methanol and repeating the loading procedure. © 1996 Wiley-Liss, Inc.
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  • 27
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    Chirality 8 (1996) 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 28
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    Chirality 8 (1996), S. 234-243 
    ISSN: 0899-0042
    Keywords: enantiomeric ; non-racemic mixtures ; binaphtol ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: It is shown that chromatography with achiral phases of non-racemic mixture of binaphthol can furnish fractions which differ in enantiomeric excess. The first fraction contains one pure enantiomer i.e., has an enantiomeric excess (ee %) close to 100% and the following fractions have an ee % close to 0% (racemic mixture). As a consequence, such chromatography may be used to enrich a non-racemic mixture of binaphthol in one enantiomer. In this paper a model is proposed allowing us to calculate with good accuracy the experimental elution curves. This simple model is capable of using only a few chromatographic experiments to predict the enantiomeric enrichment of a non-racemic mixture and to calculate precisely the retention time of each fraction. © 1996 Wiley-Liss, Inc.
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  • 29
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    Chirality 8 (1996), S. 249-257 
    ISSN: 0899-0042
    Keywords: chiral SubFC resolution ; analysis time ; column efficiency ; library of chiral columns ; selectivity ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A model is presented that predicts a defined relationship between chiral SubFC resolution and analysis time. This model is based upon ideal chromatographic behavior and requires column efficiency and selectivity to be independent of mobile phase modifier level and flow rate. The validity of these assumptions was found to be imperfect but acceptable for two model compounds on two commonly used chiral columns.A major implication of the model is that the maximum resolution obtainable with a particular column and mobile phase modifier may be predicted from one injection. The retention time required to obtain a desired resolution is also calculable. This information enables the practitioner to discern quickly the futility of method development efforts. Insufficient maximum resolution predicted from the first injection would require an increase in selectivity to achieve a useful separation. Selectivity may then be altered by temperature, modifier, or stationary phase. The increased column efficiency of SubFC at typical flow rates rescues separations that fail by HPLC, thus shrinking the practitioner's required library of chiral columns. This work demonstrates that SubFC also allows the practitioner to skim through that library very quickly. © 1996 Wiley-Liss, Inc.
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  • 30
    ISSN: 0899-0042
    Keywords: 5-aminovaleric acid (DAVA) ; 4-OH-DAVA ; 2-Me-4-OH-DAVA ; stereoisomers ; pharmacology ; GABAB antagonist ; GABAB receptor affinity ; X-ray analysis ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: We have previously shown that (R)-5-amino-4-hydroxyvaleric acid [(R)-4-OH-DAVA] and (S)-2-OH-DAVA bind to GABAB receptor sites and antagonize GABAB receptor-mediated function in a stereoselective manner. Furthermore, we have identified energy-minimized superimposable conformations of (R)-4-OH- and (S)-2-OH-DAVA which are assumed to reflect the receptor-active conformations of these compounds. This paper describes the in vitro enantiopharmacology of 5-amino-4-hydroxy-2-methylvaleric acid (2-Me-4-OH-DAVA). Whereas none of the four stereoisomers showed significant affinity for GABAA receptor sites or GABA uptake mechanisms in rat brain synaptic membranes, (2R,4R)-2-Me-4-OH-DAVA was shown to inhibit stereoselectively the binding of [3H]GABA to rat brain GABAB receptor sites (IC50 = 14 ± 4 μM). (2R,4R)-2-Me-4-OH-DAVA (Ki = 36 μM) and, with much lower potency, (2S,4R)-2-Me-4-OH-DAVA (Ki = 370 μM) stereoselectively antagonized GABAB receptor-mediated function in the isolated guinea pig ileum. The structure of the eutomer, (2R,4R)-2-Me-4-OH-DAVA, was established by an X-ray crystallographic analysis, and the solid-state conformation of (2R,4R)-2-Me-4-OH-DAVA was compared with the proposed receptor-active conformations of (R)-4-OH-DAVA and (S)-2-OH-DAVA. © 1995 Wiley-Liss, Inc.
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  • 31
    ISSN: 0899-0042
    Keywords: o-phthalaldehyde ; chiral ; amino acid ; amino alcohol ; thiol ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A high-performance liquid chromatography and molecular modelling study is presented for the diastereomeric adducts of a series of chiral thiol compounds and chiral amine compounds after reaction with o-phthalaldehyde (OPA). It is shown that the possibility of hydrogen bonds forming between the thiol and amino residues in the diastereomeric adducts is an important factor for obtaining good selectivity. The experimental elution orders were explained on the basis of the strength of the interaction between the polar groups of the thiol and amine constituents; it was found that the diastereomeric form having the largest distance between these groups always eluted first. Moreover, within a series of OPA derivatives, the differences between the Boltzmann weighted averages of the distances between the polar groups of the two diastereomers show a good correlation with the experimental selectivities. © 1995 Wiley-Liss, Inc.
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  • 32
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    Chirality 7 (1995) 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 33
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    Chirality 7 (1995), S. 575-579 
    ISSN: 0899-0042
    Keywords: rac-2-[4-(1,3-dihydro-1-oxo-2H-isoindol-2-yl)-phenyl]-butyric acid ; enantiomeric purity ; differential scanning calorimetry ; optical rotation, circular dichroism ; RP-HPLC ; 1H-NMR spectroscopy ; IR spectroscopy ; X-ray powder diffraction ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The binary phase diagram of the enantiomers of indobufen, 1 (Ibustrin), an antithrombotic drug, has been investigated by differential scanning calorimetry (DSC); 1 is a racemic compound (racemate) with melting point lower than that of the enantiomers. Its thermal behaviour (DSC) has been examined and is discussed in comparison with other physical methods (IR spectroscopy and X-ray powder diffraction). Absolute configuration has been assigned to the enantiomers by 1H-NMR correlations. © 1995 Wiley-Liss, Inc.
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  • 34
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    Chirality 7 (1995), S. 580-585 
    ISSN: 0899-0042
    Keywords: asymmetric dihydroxylation ; enantiomeric excesses ; polymerization ; chiral separation ; optically active diols ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A new insoluble polymer containing a Cinchona alkaloid derivative has been synthesized and used as chiral ligand in the heterogeneous enantioselective dihydroxylation of olefins. It is shown that the enantioselectivity of the optically active diols obtained from both aliphatic and aromatic substrates is always comparable to that observed in the homogeneous phase under the same reaction conditions. A method for evaluating the enantiomeric excesses of the optically active products is also described. © 1995 Wiley-Liss, Inc.
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  • 35
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    Chirality 7 (1995), S. 598-604 
    ISSN: 0899-0042
    Keywords: hydroxychloroquine ; metabolites ; enantiomers ; disposition ; distribution ; stereoselectivity ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Racemic hydroxychloroquine-sulfate (HCQ-sulfate) was administered to rats orally. Groups of 9 male and 9 female rats received doses of 0, 8, 16, or 24 mg/kg/day for 6 weeks, followed by a reduction of the higher doses to 8 mg/kg/day for the duration of the study. Whole blood samples were collected at 0, 3, 6, 8, and 10 weeks, and eleven tissues were harvested after the tenth week. The concentrations and enantiomer ratios of the parent drug and three metabolites, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ), were determined. The highest concentration of HCQ was found in the intestinal smooth muscle, and the lowest in the brain and adipose tissue. The highest concentrations of the metabolites were found in the liver, adrenals, and lung tissue.The metabolism of HCQ in the rats was found to be stereoselective with R/S 〉 1 for the drug and 〈 1 for the metabolites. Gender-specific differences in the proportions of the drug and its metabolites and their enantiomers in blood and tissue were found. Varying dosages appeared to have only a temporary influence on blood concentrations and not to effect the enantiomer ratios in blood. Only a limited number of tissues exhibited significant differences between dose groups. There were no observed differences in enantiomer ratios among the blood collection times. © 1995 Wiley-Liss, Inc.
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  • 36
    ISSN: 0899-0042
    Keywords: oxprenolol ; propranolol ; verapamil ; enantiomers ; inflammation ; endotoxin ; protein binding ; pharmacokinetics ; species ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The influence of endotoxin-induced inflammation was studied on the pharmacokinetics of the enantiomers of the racemic drugs oxprenolol, propranolol, and verapamil in rabbits and dogs. Enantioselective pharmacokinetics were seen for oxprenolol and propranolol in the rabbit and for propranolol and verapamil in the dog. In the dog, the enantioselective differences in plasma concentrations are due to differences in both protein binding and metabolism, whereas in the rabbit the differences are due solely to differences in metabolism. In both species endotoxin treatment increases the plasma concentrations of the enantiomers of the three drugs; both protein binding and metabolism are influenced. In rabbits and in dogs, the influence of endotoxin on the disposition of the three drugs is less enantioselective than was previously observed in the rat. © 1995 Wiley-Liss, Inc.
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  • 37
    ISSN: 0899-0042
    Keywords: enantiomeric separation ; Chiralcel OD-R ; Chiralcel OJ-R ; reversed-phase HPLC ; proton pump inhibitor ; pantoprazole ; omeprazole ; lansoprazole ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A direct, isocratic, and simple reversed-phase HPLC method was described for the separation of enantiomers of the proton pump inhibitor, rac-pantoprazole (PAN) using cellulose-based chiral stationary phases (Chiralcel OD-R and Chiralcel OJ-R). Some structurally related chiral benzimidazole sulfoxides, rac-omeprazole (OME) and raclansoprazole (LAN), were also studied. Chiralcel OJ-R was successful in the resolution of enantiomers of rac-PAN and rac-OME, while Chiralcel OD-R was most suitable for resolving the enantiomers of rac-LAN. Highest enantioselectivity to rac-PAN and rac-OME was achieved on Chiralcel OJ-R by using acetonitrile as an organic modifier, whereas methanol afforded better resolution of rac-LAN on Chiralcel OD-R than acetonitrile. Increases in buffer concentration and column temperature decreased retention and did not improve the resolution of the enantiomers on both columns. Using a mixture of 50 mM sodium perchlorate solution and acetonitrile as a mobile phase at a flow rate of 0.5 ml/min, maximum separation factors of 1.26 and 1.13 were obtained for the enantiomers of rac-PAN and rac-OME using a Chiralcel OJ-R column, while maximum separation factor of 1.16 was obtained for the enantiomers of rac-LAN using a Chiralcel OD-R column. © 1995 Wiley-Liss, Inc.
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  • 38
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    Chirality 7 (1995), S. 541-546 
    ISSN: 0899-0042
    Keywords: chiral liquid chromatography ; chromatographic resolution ; cyclic sulfoximides ; reaction stereochemistry ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Three endocyclic sulfoximides of the 1-aryl- and 1-alkyl-3-oxo-benzo[d]-isothia (IV)-azole 1-oxide type (1-substituent = 2′-carboxyphenyl, 2′-carbethoxyphenyl, and octyl, respectively) were found to be well resolved on a chiral phase derived from bovine serum albumin (BSA). Selectivities (α) of 1.74, 1.12, and 1.44, respectively, were obtained. The retention behaviour of 1-octyl-3-oxo-benzo[d]isothia(IV)-azole 1-oxide was further investigated in some detail as a function of the mobile phase composition and the elution order was established from optically active material obtained from the enantiopure sulfoxide precursor. An enantiomeric excess of 85.4% was obtained in the cyclocondensation reaction of the octyl-substituted sulfoxide precursor with hydrazoic acid to the corresponding endocyclic sulfoximide. © 1995 Wiley-Liss, Inc.
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  • 39
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
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  • 40
    ISSN: 0899-0042
    Keywords: β-blockers, bevantolol, NC-1400, epichlorohydrin, absolute configuration, enantiomer, chiral cellulose column, direct separation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Synthesis of (-)-bevantolol hydrochloride from 3,4-dimethoxyphenethylamine and (S)-(+)-m-tolyl glycidyl ether derived from (R)-(-)-epichlorohydrin established the absolute configuration of the (+) and (-) enantiomer as R and S, respectively. The purity of the enantiomers was determines using a chiral cellulose column (CHIRALCEL OD®) which allowed direct separation of the enantiomers. A separation factor (α) of 4.20 and a resolution factor (Rs) of 9.21 were obtained. © 1995 Wiley-Liss, Inc.
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  • 41
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    Chirality 7 (1995), S. 567-571 
    ISSN: 0899-0042
    Keywords: enantiomer separation ; chromatographic resolution ; peak integration ; peak size ratio ; calibration curve ; determination of optical purity ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The chromatographic quantitation of very low amounts of an enantiomer in the presence of its antipode can be an extraordinary challenge. If resolution of the peaks is not complete even at extreme mass ratios an integrator will yield inaccurate results due to geometric effects. A given resolution can be adequate for peaks of similar size but result in severe overlap if one of the signals is markedly smaller. If tailing occurs, which is more the rule than the exception, the problem is especially severe for last eluted small peaks. Additional obstacles are detector nonlinearity and other sources of unsatisfactory calibration curves, overloading phenomena, and the possible lack of standards of highest optical purity. These problems have been studied by computer simulations and the liquid chromatographic separation of (R,S)-phenylethyl naphthoic acid amide on a chiral stationary phase. © 1995 Wiley-Liss, Inc.
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  • 42
    ISSN: 0899-0042
    Keywords: axially chiral biphenyl ; rotational energy barrier ; enantiomeric separation ; high-performance liquid chromatography ; triacetylcellulose ; deracemization ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The enantiomers of rac-2,2′-diiodobiphenyl were separated by liquid chromatography on microcrystalline triacetylcellulose. The conformational lability, a large separation factor α, and a suitable capacity factor k′(+) of this biphenyl allowed us to convert the racemate into 90% of enantiomerically pure (-)-2,2′-diiodobiphenyl and 10% of pure (+)-2,2′-diiodobiphenyl, respectively, by a series of in situ racemization-elution cycles. The much better retained (+)-enantiomer was racemized on the chromatographic column at 50°C after the less retained (-)-enantiomer has already been eluted at 8°C. © 1995 Wiley-Liss, Inc.
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  • 43
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    Chirality 7 (1995), S. 586-597 
    ISSN: 0899-0042
    Keywords: PK/PD modelling ; ketoprofen ; enantiomers ; calves ; NSAIDs ; chirality ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The pharmacokinetics (PK) and pharmacodynamics (PD) of (S)- and (R)- ketoprofen (KTP) enantiomers were studied in calves after intravenous administration of each enantiomer at a dose of 1.5 mg/kg. Pharmacodynamic properties were evaluated using a model of acute inflammation, comprising subcutaneously implanted tissue cages stimulated by intracaveal injection of carrageenan.Chiral inversion of (R)-KTP to the (S)-antipode occurred. The R:S ratio in plasma was 33:15 min after administration, decreasing to 1:1 at 8 h. The calculated extent of inversion was 31 ± 7%. The R:S ratio in inflammatory exudate was of the order 3:1 at all the sampling times and the ratio in transudate was approximately 2:1 for 6 h, declining to 1:1 at 30 h. Only (S)-KTP was detected in biological fluids after administration of this enantiomer. Elimination half-life was longer for the (S) (2.19 h) than the (R)-enantiomer (1.30 h) and volume of distribution was also somewhat higher for the (S)-enantiomer. Body clearance values were 0.119 1/kg/h for (S)-KTP and 0.151 1/kg/h for the (R)-antipode. For (R)-KTP effects obtained were considered as a hybrid, since they potentially reflect the actions of both enantiomers. Concentrations of LTB4 and the cytokines interleukin-1, interleukin-6, and tumor necrosis factor alpha, in exudate were not significantly affected by either (R)- or (S)-KTP treatments. Inhibition of ex vivo thromboxane B2 (TxB2) synthesis, exudate prostaglandin E2 (PGE2) synthesis, β-glucuronidase release (β-glu), and bradykinin-induced skin swelling was significant in both treated groups. PK/PD modelling was applied to the (S)-KTP treatment only. EC50 values for inhibition of serum TxB2, exudate PGE2 and β-glu and BK-induced swelling were 0.047, 0.042, 0.101, and 0.038 μg/ml, respectively. It is concluded that the low EC50 values for inhibition of TxB2 and PGE2 by (S)-KTP are likely to explain the effects produced by (R)-KTP administration, since concentrations of (S)-KTP in exudate of these calves following chiral inversion were at least 5 times higher than the EC50 at all sampling times. The data for β-glu and bradykinin-induced swelling inhibition indicate possible inhibitory actions of (R)-KTP as well as (S)-KTP. © 1995 Wiley-Liss, Inc.
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  • 44
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    Chirality 7 (1995), S. 632-635 
    ISSN: 0899-0042
    Keywords: chiral inversion ; deconvolution ; 2-arylpropionates ; ibuprofen ; linear systems analysis ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: An alternative method based on linear systems analysis is presented for the analysis of concentration-time data for the enantiomers of the 2-arylpropionic acids. This approach uses deconvolution to estimate the rate and extent of chiral inversion with respect to time, assuming linear pharmacokinetics and time invariance, without the need for complicated modelling procedures. Application to data for the chiral inversion of ibuprofen in the rat indicates that this approach provides a valid alternative to previous procedures for the analysis of chiral inversion data. © 1995 Wiley-Liss, Inc.
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  • 45
    ISSN: 0899-0042
    Keywords: diastereomeric salts ; molecular recognition ; hydrogen bonding ; polymorphism ; thermal analysis ; crystallography ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Binary diastereomeric (-) (1R,2S)-ephedrine salts of various mandelic acids obtained from 95% ethanol show considerable differences in solubility. Structures and some properties of the less-soluble (L) and more-soluble (M) solid phases of (-)-ephedrine with unsubstituted mandelic acid, 2-, 3-, and 4-monosubstituted halo (F, Cl, Br) mandelic acids, and 3- and 4-methylmandelic acids have been determined. Salts were found to be binary, without solvent of crystallization, and composed of double-layered arrays of alternating anions and cations linked by H-bonds normal to the layers. H-bonding links charged donors and acceptors usually along a crystallographic 2-fold screw axis. A striking discrimination is evident in that the (2R)-mandelate salts typically display a compact four-atom chain as the H-bonding repeating unit [+N - H…O( - C- - O)…H-N′, C21(4)] while the (2S)-mandelate salts adopt a more dimensionally variable six-atom chain repeating unit [+N - H…O - C- - O…H - N′, C22(6)]. Two distinct packing schemes display the shorter H-bonding chain of the (2R)-mandelates which always occurs with ephedrinium ions in the fully extended conformation. Slightly greater packing efficiency and H-bonding energies of the (2R)-mandelate salts correlates with increased fusion points, lower solubilities (95% ethanol), and higher heats of fusion relative to the phase adopted by their diastereoisomers. In contrast, (2S)-mandelate salts exhibit considerably more structural variability involving all three major ephedrinium conformations, and at least four distinct packing motifs. Mandelates with larger 3′-substituents (Cl, Br, methyl) show similar property discriminations, but these occur with an opposing trend, that is, between phases in which the less-soluble salts contain (2S)-mandelates. Salts with 2-bromomandelate do not show property disparities and their structures are dissimilar to the other phases. © 1995 Wiley-Liss, Inc.
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  • 46
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    Chirality 8 (1996), S. 11-17 
    ISSN: 0899-0042
    Keywords: thalidomide enantiomers ; mobile phase additive ; stereoselective analysis ; high-performance liquid chromatography ; chiral separation ; β-cyclodextrin ; inclusion complex ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: R- and S-Thalidomide were resolved by reversed-phase HPLC on a C-18 column with β-cyclodextrin in the mobile phase. As the concentration of β-cyclodextrin was increased stepwise from 0 to 20 mM, enantiomeric resolution increased and retention times decreased significantly. The influence of different organic modifiers in the mobile phase were evaluated, and ethanol, among others, proved to be effective. Equilibrium constants for the formation of β-cyclodextrin inclusion complexes of R- and S-thalidomide in EtOH-buffer (5:95) were calculated to be 64 and 76 M-1, respectively. © 1996 Wiley-Liss, Inc.
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  • 47
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    Chirality 8 (1996) 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
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  • 48
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    Chirality 8 (1996), S. 58-66 
    ISSN: 0899-0042
    Keywords: molecular mechanics ; HPLC ; chiral separation ; methylphenobarbitone ; hexobarbitone ; ibuprofen ; mandelic acid ; ephedrine ; pseudoephedrine ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: β-Cyclodextrin and its derivatives have been utilised to effect chiral separation in HPLC and CZE, both as stationary phases and mobile phase additives. The basis of the method is assumed to depend upon the formation of inclusion complexes of differing stabilities between enantiomeric analytes and the cyclodextrin, resulting in a differential dynamic distribution between chromatographic phases. In this study, force field calculations have been employed to model the inclusion complexes of enantiomeric brompheniramine, ephedrine, pseudoephedrine, ibuprofen, mandelic acid, methylphenobarbitone, and hexobarbitone with β-cyclodextrin. The resulting values for Δ(ΔH), the difference in enthalpy of complex formation between enantiomeric pairs has been compared with literature chromatographic data to explain the ability of the systems to achieve enantiomeric separations. © 1996 Wiley-Liss, Inc.
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  • 49
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    Chirality 9 (1997), S. 10-12 
    ISSN: 0899-0042
    Keywords: piperidine-2,6-dione ; chiral recognition ; enantioselectivity ; elution order ; cellulose based chiral stationary phase ; reversed phase mode ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A newly developed reversed phase cellulose tris(4-methyl benzoate) known as Chiralcel OJ-R was used to investigate the chiral recognition and enantiomeric separation of eight racemic piperidine-2,6-dione compounds - namely, aminoglutethimide and its major metabolite acetylaminoglutethimide, glutethimide, cyclohexylamino-glutethimide, pyridoglutethimide, thalidomide, phenglutarimide, and 3-phenylacetyl-amino-2,6-piperidinedione (antineoplaston A-10). Chiral separation of these compounds was achieved under varying ratios of the mobile phase, except for phenglutarimide and 3-phenylacetylamino-2,6-piperidinedione, for which separation was unsuccessful. Possible chiral recognition mechanisms are also presented. Chirality 9:10-12, 1997. © 1997 Wiley-Liss, Inc.
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  • 50
    ISSN: 0899-0042
    Keywords: proton pump inhibitor ; pantoprazole ; stereoselective pharmacokinetics ; genetic polymorphism ; human ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Pantoprazole (PAN) is a proton pump inhibitor that is administered as a racemic mixture. The pharmacokinetics of PAN enantiomers were investigated in extensive metabolizers (EMs) and apparent poor metabolizers (PMs) of PAN who received a single 40, 60, or 80 mg oral dose of racemic PAN as enteric-coated formulation. In the EMs, the serum concentrations of (-)-PAN were slightly higher than those of (+)-PAN at each dose level. The (+)/(-) ratios for the area under the concentration-time curve (AUC) and the half-life were 0.58-0.89 and 0.62-0.88, respectively. In the PMs, the serum concentrations of both enantiomers were much higher than those in the EMs at each dose level and significant differences in pharmacokinetics of (+)- and (-)-PAN were observed. The half-lives for (+)-PAN were 2.67-3.77 times longer than those for (-)-PAN. The AUCs for (+)-PAN were 2.65-3.45 times greater than those for (-)-PAN. Therefore, the metabolism of (+)-PAN is impaired to a greater extent than (-)-PAN in the PMs, which resulted in the stereoselective disposition of PAN in the PMs. It has been suggested that the EMs and the PMs of PAN could be differentiated by determining the (+)/(-) enantiomer ratio in serum at one time point, possibly 2-6 h after oral dosing, because the (+)/(-) enantiomer ratios in the PMs were opposite those in the EM subjects. Chirality 9:17-21, 1997 © 1997 Wiley-Liss, Inc.
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  • 51
    ISSN: 0899-0042
    Keywords: optical resolution ; conglomerate ; preferential crystallization ; optically active 2-amino-3-chloropropanoic acid ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The racemic structures of (RS)-2-amino-3-chloropropanoic acid [(RS)-ACP] and (RS)-2-amino-3-chloropropanoic acid hydrochloride [(RS-ACP·HCl] were examined to obtain (R)- and (S)-ACP via optical resolution by preferential crystallization. The melting point, infrared spectrum, solubility, and ternary solubility diagram suggested that (RS)-ACP·HCl exists as a conglomerate and that (RS)-ACP forms a racemic compound. Optical resolution by preferential crystallization of (RS)-ACP·HCl was successfully achieved to yield (R)- and (S)-ACP·HCl. Optically pure (R)- and (S)-ACP were obtained from the purified (R)-and (S)-ACP·HCl, respectively. © 1996 Wiley-Liss, Inc.
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  • 52
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    Chirality 8 (1996), S. 207-213 
    ISSN: 0899-0042
    Keywords: CS-670 ; anti-inflammatory drug ; stereoselective metabolism GC-MS ; diastereomer HPLC ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: CS-670, a novel nonsteroidal anti-inflammatory drug, is a racemic prodrug. Plasma concentrations and urinary excretion of CS-670 and its metabolites were determined in experimental subjects after oral administration at a single 120 mg dose. CS-670 and four metabolites, the saturated ketone (M-A), unsaturated-alcohol (M-B), cis-alcohol (M-C), and trans-alcohol (M-D), were quantitated by GC-MS. The major metabolites in human plasma were M-B, M-C, and M-D and their terminal half-lives (t½) were 0.9, 2.6, and 1.2 h, respectively. The total recovery in the urine was 26% of the dose, but unchanged CS-670 accounted for less than 2% over a 48 h period. In addition, the absolute configurations of the metabolites were examined by HPLC after derivatization with chiral reagents. It was found that the configuration of the propionic acid moiety of the metabolites, M-B, M-C, and M-D, in human plasma, was rapidly inverted from (-)-(R) to the (+)-(S) configuration in stereoselective biotransformation. Furthermore, the configurations of the 1′- and 2′-carbons of M-C and M-D, were found to be (1′R,2′S) and (1′R,2′S), respectively. These results show that CS-670 is readily biotransformed by chiral inversion of the 2-arylpropionic acid moiety and stereoselective reduction of the α, β-unsaturated ketone moiety in humans. © 1996 Wiley-Liss, Inc.
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  • 53
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    Chirality 8 (1996), S. 356-356 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 54
    ISSN: 0899-0042
    Keywords: NSAIDs ; esterification ; resolution ; Candida antarctica lipase ; Mucor miehei lipase ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The resolution of rac-suprofen (1) catalysed by lipase in organic solvents was investigated. Direct esterification of rac-1 with methanol in dichorometane catalysed by Novozym® 435 furnished the pharmacologically active (+)-(S)-suprofen as unreacted product with excellent enantiomeric excess. The same procedure in toluene using Mucor miehei lipase adsorbed in Celite as catalyst afforded (-)-(R)-suprofen with good optical purity. © 1996 Wiley-Liss, Inc.
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  • 55
    ISSN: 0899-0042
    Keywords: diols ; hydroperoxides ; absolute configuration ; exciton coupling ; circular dichroism ; enantiomeric separation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Allylic hydroperoxides are a class of compounds of versatile synthetic utility. Optically active diastereomeric hydroperoxy homoallylic alcohols and their corresponding diols are easily available through horseradish peroxidase (HRP)-catalyzed kinetic resolution of racemic hydroperoxides. Here we describe the assignment of the absolute configuration of the optically active products and substrates obtained after HRP-catalysis by the circular dichroism exciton chirality method. Moreover, the analytical-scale separation of the enantiomers based on multidimensional gas chromatography on chiral columns is presented. Since the enantiomeric elution order on the ciral columns was constituted, the absolute stereochemistry of optically active allylic diols can easily be deduced by their retention times on β-cyclodextrins. Chirality 9:69-74, 1997. © 1997 Wiley-Liss, Inc.
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  • 56
    ISSN: 0899-0042
    Keywords: enantioseparation ; HPLC ; cyclodextrin ; phenylcarbamate ; chiral stationary phase ; optical resolution ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: New dichloro-, dimethyl-, and chloromethylphenylcarbamate derivatives of cyclodextrins (CDs) were prepared and their enantiomeric recognition abilities were evaluated as chiral stationary phases (CSPs) in normal phase high-performance liquid chromatography (HPLC). The effects of the type of cyclodextrins, the nature and position of the substituents on the phenyl ring, binding mode and spacer on the chiral recognition were studied in detail. No marked change of chiral recognition abilities was established by reversing the binding side of CDs (i.e., by the narrower [primary] opening of the cone-shaped CD to silica gel with the wider [secondary] opening sides). This result indirectly proves the previously drawn conclusion about the minor role of inclusion phenomena in chiral recognition in this case. Nevertheless, chiral recognition of these CSPs toward some compounds critically depends on the type of CDs used. All CD derivatives described in this study show rather low enantiomeric resolving abilities compared with corresponding polysaccharide (cellulose and amylose) derivatives, although very high enantioselectivity of separation was observed for a few compounds, such as racemic flavanone and cyclopropanedicarboxilic acid dianilide. © 1996 Wiley-Liss, Inc.
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  • 57
    ISSN: 0899-0042
    Keywords: rac-propranolol ; enantiomers ; drug intoxication ; cardiovascular function ; respiratory function ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The contribution of the individual enantiomers ([+]-[R]- and [-]-[S]-propranolol) to rac-propranolol intoxication was studied in anaesthetized, spontaneously breathing (SB) rats and artificially ventilated (AV) rats and rabbits. In the SB rat, propranolol (30 mg.kg-1.h-1 i.v.) decreased heart rate and mean arterial blood pressure and caused hypoventilation, serious hypoxaemia, respiratory acidosis, and death by respiratory arrest. Survival time (ST) in the (+)-(R)-propranolol group (ST 91 ± 5 min) was significantly longer than in the rac-propranolol group (ST 68 ± 6 min). In AV rats and rabbits toxic doses of rac-, (-)-(S)- and (+)-(R)-propranolol, 30 mg.kg-1.h-1 and 15 mg.kg-1.h-1 i.v., respectively, induced comparable effects on haemodynamic variables as in the SB rat. Artificial ventilation lengthened ST by a factor of three to four in rats. In the AV rat, ST's were not significantly different between the rac-, (-)-(S)- and (+)-(R)-propranolol groups. In the rabbit, as in the SB rat, ST in the (+)-(R)-propranolol group was significantly longer than ST's in the rac- and (-)-(S)-propranolol groups. The acute respiratory acidosis in SB rats and the prolonged ST in AV rats suggest that respiratory failure is the primary and cardiovascular failure the secondary cause of death in propranolol intoxication. The potentiation of the toxic effect of the enantiomers observed after dosing the racemate instead of the pure enantiomers could not be explained by a stereoselective difference in plasma propanolol concentration. © 1996 Wiley-Liss, Inc.
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  • 58
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    Chirality 8 (1996) 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 59
    ISSN: 0899-0042
    Keywords: enantiomers ; HPLC ; DNS-animo acids ; fluorescence quenching ; ligand-exchange mechanism ; adsorption ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The copper(II) complexes of two new diastereomeric ligands, N2-(R)- and N2-(S)-2′-hydroxypropyl-(S)-phenylalaninamide [(R, S)-1 and (S, S)-1], have been used as additives to the eluent in high-performance liquid chromatography (HPLC) reversed phase for the chiral separation of DNS-amino acids. The aim was that of comparing the separation process obtained by the chiral eluent with that obtained by an analogous bonded stationary phase containing (S)-phenylalaninamide, previously studied [CSP-(S)-Phe-NH2]. The affinity of the ternary complexes for the C18 column was determined by adsorption experiments in HPLC. It was shown that the two systems (chiral eluent, chiral stationary phase) work according to different mechanisms. Ternary complex formation in solution was studied by fluorescence spectroscopy. It was shown that chiral separation with the Cu(II) complexes added to the eluent was determined by the relative affinities of the ternary complexes for the column-stationary phase rather than by their stabilities in solution. With CSP-(S)-Phe-NH2 the separation is accounted for by the relative stabilities of the ternary complexes, which depends mainly on the “allowed” geometry of the complex and on the steric repulsion of the amino acid side chain with the spacer. © 1996 Wiley-Liss, Inc.
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  • 60
    ISSN: 0899-0042
    Keywords: rac-amlodipine ; amlodipine ; liquid chromatography ; chiral ; charged cyclodextrin ; optimisation ; central composite design ; mobile phase additive ; experimental design ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A negatively charged derivative of β-cyclodextrin, sulphobutyl ether-β-cyclodextrin (SBE-β-CD), was examined as a chiral mobile phase additive in reversed-phase high-performance liquid chromatography for the enantiomeric resolution of the calcium channel blocker rac-amlodipine. Theoretical and practical aspects are discussed for setting up a central composite design applicable to any analytical method. These include the correct location of factor points for maintaining orthogonality within the design and the augmentation of centrepoint experiments to allow a larger factor space by increasing the distance of axial star points. Optimised separation was achieved using a reverse-phase column with eluent comprising: acetonitrile (ACN) - potassium dihydrogen phosphate (pH 3.93) containing 2.66 mM SBE-bgr;-CD (26.5:73.5% v/v) at a flow rate of 1.0 ml/min. This yielded a Kaiser peak separation index, Pi = 0.96, at tR2 = 52 min with satisfactory reproducibility, relative standard deviation values: tR1, 0.39%; tR2, 0.47% (n = 5). These experimental results were in excellent agreement with those predicted by the SAS software package for a chromatographic response function model. Multiple regression analysis in four dimensions, with three response models based on Rs, Pi, and a function of Pi, produced response surfaces which revealed zones of optimum robustness and illustrated the interactions involved between the key chromatographic factors. Putative proposals for a mechanism involving the interaction of each of the positively charged enantiomers with the negatively charged cyclodextrin are also discussed. These examine the possibility of ion-pairing and inclusion phenomena to account for the excellent resolution observed. © 1996 Wiley-Liss, Inc.
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  • 61
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    Chirality 8 (1996), S. 503-510 
    ISSN: 0899-0042
    Keywords: enantioseparations ; carrageenans ; sulfated polysaccharides ; beta blockers ; tryptophan and derivatives ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Lambda-carrageenan, a linear high molecular weight sulfated polysaccharide, has been employed as a chiral selector in capillary electrophoresis for the separation of enantiomers of weakly basic pharmaceutical compounds. The racemic compounds that were enantioresolved included propranolol, pindolol, tryptophanol, laudanosine and laudanosoline. In addition, the diastereomeric pair of cinchonine and cinchonidine were also resolved. Method conditions such as buffer pH, electrolyte concentration, column temperature, and chiral selector concentration were found to be important for improvement of enantioselectivity. © 1996 Wiley-Liss, Inc.
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  • 62
    ISSN: 0899-0042
    Keywords: stereoisomer separation ; cyclodextrin ; pesticide ; capillary electrophoresis ; high-performance liquid chromatography ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Micellar electrokinetic capillary chromatography (MECC) and high-performance liquid chromatography (HPLC) were used for the separation of stereoisomers of the lipophilic uncharged pyrethroids cypermethrin, alphamethrin, permethrin, and fenpropathrin. Different kinds of cyclodextrin (β-cyclodextrin, hydroxypropyl-β-cyclodextrin, dimethyl-β-cyclodextrin, and γ-cyclodextrin), surfactants (sodium dodecyl sulphate [SDS] and cetyltrimethylammonium bromide [CTAB]), and cations of background electrolyte (sodium, ammonium, TRIS, and Ammediol) were tested. Optimized conditions (background electrolyte: 50 mmol/l sodium phosphate, pH ≈ 2.5, 150 mmol/l SDS, 150 mg/ml γ-cyclodextrin) allowed the separation of alphamethrin, the eight cypermethrin stereoisomers being eluted in seven peaks and the separation of two enantiomers of fenpropathrin with resolution Rs = 10 and with n ≃ 500,000 theoretical plates. Different experimental conditions, e.g., mobile phase composition, temperature, injected amount, and flow rate, were also optimized in HPLC experiments. The optimal conditions (stationary phase: ChiraDex, 5 μm; mobile phase: 150 mmol triethylamine/l with H2SO4 in water (pH = 3.5) with methanol or acetonitrile; flow rate: 0.8 or 0.6 ml/min; temperature: ambient or 30°, 20°, or 10°C; experimental conditions were modified according to the type of analysis) allow chiral discrimination of alphamethrin enantiomers and analysis of permethrin stereoisomers. MECC offers higher efficiency and shorter analysis time than HPLC, but under tested conditions it was shown that the methods complement each other. Chirality 9:162-166, 1997. © 1997 Wiley-Liss, Inc.
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  • 63
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    Chirality 9 (1997), S. 191-197 
    ISSN: 0899-0042
    Keywords: TADDOL ; titanium complexes ; chiral Lewis acid ; polymer-supported ; polystyrene-divinylbenzene ; enantioselective ; Diels-Alder ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The synthesis of the first polymer-supported TADDOL is reported. Its efficiency as chiral ligand of Ti(IV) was studied in the Diels-Alder cycloaddition of cyclopentadiene to 3-crotonoyl-1,3-oxazolidin-2-one, and was superior to that observed for its homogeneous equivalent. (4R,5R)-α,α,α′,α′-2-pentaphenyl-4,5-dimethanol-1,3-dioxolane. Recycling of the heterogeneous Ti(IV)-TADDOLate was also studied, being the most suitable method for the repreparation of the catalyst from the ligand after use. Chirality 9:191-197, 1997. © 1997 Wiley-Liss, Inc.
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  • 64
    ISSN: 0899-0042
    Keywords: rac-doxazosin ; doxazosin ; liquid chromatography ; chiral ; carboxymethyl-β-cyclodextrin ; optimisation ; central composite design ; mobile phase additive ; experimental design ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The chromatographic resolution of rac-doxazosin using reversed-phase high performance liquid chromatography (HPLC) with the chargeable chiral mobile phase additive, carboxymethyl-β-cyclodextrin (CM-β-CD), is described. The effects of different modifiers (acetonitrile, methanol and tetrahydrofuran), pH, temperature, and cyclodextrin concentration were investigated to (a) assess the key chromatographic parameters for subsequent chemometric optimisation, and (b) explore the enantioselective mechanism. Assuming a 1:1 complex between each doxazosin enantiomer and CM-β-CD, studies of the relationship between the capacity factors (k′) and functions of CM-β-CD concentration indicate that the mechanisms for retention and chiral selectivity are comparable with those proposed earlier by Sybilska et al.1 Stability constants (KG) calculated for rac-doxazosin complexed with CM-β-CD (647 ± 55 and 594 ± 45 M-1 for each enantiomer respectively) are significantly larger than those calculated for the barbiturates complexed with β-CD (ca. 101-108 M-1).1 Investigations on pH indicate an ionic or ion-pair interaction between the anionic CM-β-CD and the cationic doxazosin enantiomers.A central composite design was used to optimise the key chromatographic parameters: pH, methanol (v/v) and CM/β-CD concentration. The Kaiser peak separation index, Pi, was used for the response function. The predicted response for this chiral separation has been compared with that observed experimentally and samples of the four-dimensional response surface have been assessed for their value in showing robustness. Chirality 9:184-190, 1997. © 1997 Wiley-Liss, Inc.
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  • 65
    ISSN: 0899-0042
    Keywords: 1H NMR β-cyclodextrin ; heptakis(2,3-di-O-acetyl)β-cyclodextrin ; heptakis(6-O-acetyl)β-cyclodextrin ; ephedrine derivatives ; job technique ; ROESY ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: NMR spectroxcopy has been used to compare the interaction of ephedrine and N-methylephedrine with β-cyclodextrin, heptakis(2,3-di-O-acetyl)β-cyclodextrin, heptakis(6-O-acetyl)β-cyclodextrin. The stoichiometry of the complexes formed between all three cyclodextrins and N-methylephedrine was found to be 1:1 by UV spectroscopy by means of the Job technique. NMR spectra of the single enantiomers of ephedrine and N-methylephedrine in the presence of all three cyclodextrins gave information about the parts of the ligands which interact differently with the host molecules and may be responsible for the chiral discrimination. To quantify the complex stabilities, binding constants were calculated from the changes in the chemical shifts of the ligand signals upon complexation. Analyses of the coupling constants of both species showed that no significant conformational change occurs upon complexation. ROESY spectra of these optical isomers with all three cyclodextrins provided detailed information about the geometry of the complexes. Different intermolecular cross-peaks between the individual isomers of ephedrine and N-Methylephedrine were found for native β-cyclodextrin and its 2,3-diacetylated derivative but not for 6-acetyl cyclodextrin. Analyses of the intramolecular cross-signals of the ligands confirmed that no significant conformational change occurs upon complexation. Chirality 9:211-219, 1997. © 1997 Wiley-Liss, Inc.
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  • 66
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    Chirality 9 (1997), S. 233-237 
    ISSN: 0899-0042
    Keywords: non-covalent molecular imprinting ; Scatchard plot ; batch rebinding ; site specificity ; boc-amino acids ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A potential problem associated with molecularly imprinted polymer (MIP) sorbents is that of cross-reactivity. In this study three MIPs (imprinted with Boc-L-phenylalanine, Boc-L-alanine, Boc-L-glutamic acid) plus a non-imprinted control were prepared and examined for their ability to bind differentially the enantiomers of boc-protected phenylalanine in an effort to quantify cross-reactivity and to develop a predictive model. Batch rebinding studies showed a degree of predictability for a number of MIP-ligand pairs, but other combinations showed unexpectedly high levels of cross-reactivity. Despite the general acceptance of heterogeneity of MIP binding sites, many previous studies report linear Scatchard plots, which is indicative of binding site homogeneity. The data from this study produced curves, clearly demonstrating heterogeneity. The theoretical and practical implications of this heterogeneity are discussed. Chirality 9:233-237, 1997. © 1997 Wiley-Liss, Inc.
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  • 67
    ISSN: 0899-0042
    Keywords: 1,2-diacetoxycyclohexanes ; 1,3-diacetoxycyclohexanes ; 2,3-diacetoxynorbornanes ; 2,7-diacetoxynorbornane ; enantioselective hydrolysis ; biocatalyst ; cultured plant cells ; Marchantia polymorpha ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Very high enantioselectivities were observed in the hydrolysis of racemic 1,2- and 1,3-diacetoxycyclohexanes and their derivatives by cultured cells of Marchantia polymorpha in suspension. Asymmetry was also induced in the hydrolyses of meso-1,2- and 1,3-diacetates to the corresponding monoacetates. These findings indicate that these cultured cells hydrolyze the acetoxyl groups enantioselectively at the stereogenic center of R-configuration. Chirality 9:250-253, 1997. © 1997 Wiley-Liss, Inc.
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  • 68
    ISSN: 0899-0042
    Keywords: microbial chiral inversion ; 2-phenylpropionic acid ; kinetic isotope effect ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Previous investigations have described the development of nongrowing suspension of Verticillium lecanii as a microbial model of the mammalian chiral inversion of the 2-arylpropionic acids (2-APAs). Mechanistic studies in mammals have shown that inversion involves loss of the α-methine proton but retention of the original atoms at the β-methyl position, and a mechanism has been proposed involving enzymatic epimerisation of acyl-CoA thioester derivatives of the substrate. Inversion of the 2-APAs by V. lecanii exhibits extensive intersubstrate variation in the presence, rate, extent, and direction of inversion, which are different from those observed in mammalian systems, possibly indicating differences in the mechanism of inversion between mammalian and microbial cells. This study involved the investigation of proton/deuterium exchange by 1H-nuclear magnetic resonance following incubation of deuterated derivatives of 2-phenylpropionic acid (2-PPA), a model compound, in cell suspensions of V. lecanii and incubation of undeuterated 2-PPA in cell suspensions containing D2O. The results indicated that the inversion of 2-PPA by V. lecanii also involved exchange of the α-methine proton but complete retention on the original atoms at the β-methyl position. No kinetic deuterium isotope effect was observed, indicating that loss of the α-methine proton is not the rate-limiting step of the inversion process. This suggests that the observed differences between microbial and mammalian systems probably involve the stereoselective acyl-CoA thioester formation step and not the subsequent epimerisation of the resultant diastereomers. Chirality 9:254-260, 1997. © 1997 Wiley-Liss, Inc.
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  • 69
    ISSN: 0899-0042
    Keywords: enantioselective transport ; single two-phase liquid-liquid extraction ; N-protected α-amino acid derivatives ; quinine carbamate-type chiral selectors ; chiral anion-exchange carrier ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Two-phase liquid-liquid extraction experiments were undertaken to study the enantioselective transport of the chiral N-protected α-amino acid derivatives from an aqueous buffer solution into an organic phase employing highly lipophilic carbamoylated quinine as chiral selector and phase transfer carrier, respectively. The chiral separation, derived from enantioselective ion-pair formation and differential solubility in the aqueous and organic phases of diastereomeric associates thus formed has been shown to be primarily dependent on the structure of the selectand, the nature of the organic solvent, the molar ratio of a given chiral selector to selectand in the two phases, and the pH of the aqueous phase. Extracted enantiomers were recovered by back-extraction using a relatively polar acidic medium in which the selector is barely insoluble. Thus, the enantiomeric purity of N-(3,5-dinitrobenzoyl)-leucine exceeded 95% enantiomeric excess with 70% overall yield with a single extraction and back-extraction step. Chirality 9:268-273, 1997. © 1997 Wiley-Liss, Inc.
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  • 70
    ISSN: 0899-0042
    Keywords: Xenopus oocytes ; stereochemistry ; chiral chromatography ; chiral benzodiazepines ; enantioselective modulation of GABAA receptor ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Xenopus laevis oocytes injected with Poly(A)+-RNA isolated from neuronal tissue express membrane proteins peculiar to the origin of mRNA. The translation of gamma aminobutyric acid type A (GABAA) receptors has been shown by dose/ response behavior of GABA and the reversible blockade of the GABA-induced current by picrotoxin. This current was analyzed quantitatively under two electrode voltage-clamp conditions. This methodology has been applied for the first time to study the functional properties of the receptor as a function of the stereochemistry of the ligands. The (+)-S and (-)-R enantiomers of a water-soluble benzodiazepine derivative, 7-chloro-1,3-dihydro-3-hemisuccinyloxy-5-phenyl-1,4-benzodiazepin-2-one (OXHEM), obtained by preparative high performance liquid chromatographic (HPLC) resolution on chiral stationary phase, act as agonists in the in vitro modulation of the chloride channel. The (+)-S-OXHEM enantiomer was the more active. Chirality 9:286-290, 1997. © 1997 Wiley-Liss, Inc.
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  • 71
    ISSN: 0899-0042
    Keywords: capillary electrophoresis ; high-performance frontal analysis ; propranolol ; verapamil ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The function of sialic acid groups at the terminal of sugar chains of human α1-acid glycoprotein (AGP) was investigated with respect to chiral discrimination between optical isomers of basic drugs, using high-performance capillary electrophoresis/frontal analysis (HPCE/FA), a novel analytical method developed for the determination of unbound drug concentration with ultramicrosample volume (100-200 nl). Native human AGP and desialylated AGP were used as test proteins, and propranolol (PRO) and verapamil (VER) were used as model drugs. The unbound concentration of (S)-VER was 1.31 times higher than that of (R)-VER in native AGP solution. This selectivity was not affected by desialylation. Further, enzymatic elimination of galactose residues, which neighbored sialic acid groups, did not change the binding of either isomer of VER. On the other hand, the unbound concentration of (R)-PRO was 1.27 times higher than that of (S)-PRO in native AGP solution. Desialylation caused the unbound concentration of (S)-PRO to rise to the same level of (R)-PRO, resulting in loss of enantioselectivity. Thus, it follows that sialic acid groups of AGP, as a whole, are not responsible for chiral recognition between enantiomers of VER but are involved in enantioselectivity toward the isomers of PRO. Chirality 9:291-296, 1997. © 1997 Wiley-Liss, Inc.
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  • 72
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    Chirality 9 (1997), S. 303-306 
    ISSN: 0899-0042
    Keywords: reboxetine ; enantiomers ; dog ; pharmacokinetics ; HPLC determination ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Reboxetine, (RS)-2-[(RS)-α-(2-ethoxyphenoxy)benzyl]morpholine methanesulphonate, is a racemic compound and consists of a mixture of the (R,R)- and (S,S)-enantiomers. The pharmacokinetics of reboxetine enantiomers were determined in a crossover study in three male beagle dogs. Each animal received the following oral treatments, separated by 1-week washout period: 10 mg/kg reboxetine, 5 mg/kg (R,R)- and 5 mg/kg (S,S)-. Plasma and urinary levels of the reboxetine enantiomers were monitored up to 48 h post-dosing using an enantiospecific HPLC method with fluorimetric detection (LOQ: 1.1 ng/ml in plasma and 5 ng/ml in urine for each enantiomer). After reboxetine administration mean tmax was about 1 h for both enantiomers. Cmax and AUC were about 1.5 times higher for the (R,R)- than for the (S,S)-enantiomer, mean values ± SD being 704 ± 330 and 427 ± 175 ng/ml for Cmax and 2,876 ± 1,354 and 1,998 ± 848 ng.h/ml for AUC, respectively. No differences between the (R,R)- and (S,S)-enantiomers were observed in t½ (3.9 h). Total recovery of the two enantiomers in urine was similar, the Ae (0-48 h) being 1.3 ± 0.7 and 1.1 ± 0.7% of the enantiomer dose for the (R,R)- and the (S,S)-enantiomers, respectively. No marked differences in the main plasma pharmacokinetic parameters were found for either enantiomer on administration of the single enantiomers or reboxetine. No chiral inversion was observed after administration of the separate enantiomers, as already observed in humans. Chirality 9:303-306, 1997. © 1997 Wiley-Liss, Inc.
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  • 73
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    Chirality 9 (1997), S. 307-312 
    ISSN: 0899-0042
    Keywords: stereoselective release ; stereoselective dissolution ; propranolol ; enantiomers ; cellulose derivatives ; tablet matrices ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The dissolution characteristics of propranolol enantiomers from tablet formulations containing cellulose, or one of eight cellulose derivatives, were determined under a range of conditions. The derivatives examined were: cellulose tris(phenylcarbamate) (1), cellulose tris(2,3-dichlorophenylcarbamate) (2), cellulose tris 2,4-dichlorophenylcarbamate (3), cellulose tris(2,6-dichlorophenylcarbamate) (4), cellulose tris(2,3-dimethylphenylcarbamate) (5), cellulose tris(3,4-dichlorophenylcarbamate) (6), cellulose tris (3,5-dichlorophenylcarbamate) (7), cellulose tris(3,5-dimethylphenylcarbamate) (8). In water at 25°C, the release rates of (-)R-propranolol were generally greater than those of (-)-S-propranolol, although these differences were not always statistically significant; only compounds 5 and 8 demonstrated significant enantioselectivity. Using compound 8 in further experiments, statistically significant stereoselective dissolution of propranolol HCl was observed in buffer pH 7.4 at 25°C (intrinsic dissolution rates: 0.41 ± 0.01 mgcm2min-1 for R-propranolol and 0.30 ± 0.02 mgcm2min-1 for S-propranolol; P = 0.003). The cumulative amounts of enantiomers released at every time point were also found to be statistically significant (mean ratio R:S 1.25 ± 0.05). The observed low stereoselectivity of 8 with propranolol base was probably attributable to low solubility in pH 7.4 buffer, although stereoselective release did increase with time. This suggested that there is a relationship between stereoselectivity and contact time in an aqueous environment. Results also suggested that increased temperature may affect the release process as well as stereoselective interactions of 8 with individual enantiomers. To conclude, differential release of rac-propranolol from cellulose derivative matrices has been demonstrated, which supports the principle of stereoselective retardation as a potential means of stereoselective drug delivery for solid dosage forms. Chirality 9:307-312, 1997. © 1997 Wiley-Liss, Inc.
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  • 74
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    Chirality 9 (1997), S. 317-319 
    ISSN: 0899-0042
    Keywords: NSAID metabolism ; rat liver microsomes ; metabolic pathway ; He-Ne laser ; (+)-(R)-1-phenylethylamides ; HPLC separation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: This paper reports in vitro studies on the metabolic inversion of flurbiprofen (FL), an arylpropionic acid antiinflammatory agent (2-APA). The inversion was studied with both rac-FL and R-FL, by incubation with rat hepatic microsomes, in the presence of either CoASH and ATP or NADPH. The two isomers of the drug were separated as their (+)-(R)-1-phenylethylamides by direct phase high-performance liquid chromatography on a silica gel column with an achiral mobile phase. The inversion was more pronounced in the presence of CoASH and ATP for both the racemate and the R-isomer, which supports the key role of CoA thioesters in the metabolic inversion of profens. The inversion observed in the presence of NADPH suggests that, when the incubation is run with hepatic microsomes, a CYP450-mediated pathway is also active. In order to get more insight into the CYP450-mediated inversion pathway, we studied the effect of irradiating microsomes with a low dose of He-Ne laser radiation (0.2 J). Such irradiation caused a significant increase in inversion at all times studied and normalized the anomalous value of inversion observed at 15 min in his pathway. Chirality 9:317-319, 1997. © 1997 Wiley-Liss, Inc.
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  • 75
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    Chirality 9 (1997), S. 329-334 
    ISSN: 0899-0042
    Keywords: atenolol ; enantiomers ; liquid chromatography ; cellobiohydrolase I ; chiral CBH ; coupled-columns ; cellobiose ; peak compression ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Two different enantioselective chiral chromatographic methods were developed and validated to investigate the disposition of the β1-receptor antagonist atenolol in blood and in brain extracellular fluid of rats (tissue dialysates). System A for the plasma samples was a one-column chromatographic system with a Chiral CBH column with an aqueous buffer as mobile phase into which cellobiose was added for selective regulation of the retention of the internal standard, (S)-metoprolol. The plasma samples were analysed after a simple extraction procedure. The limit of quantitation was 0.2 μg/ml for the atenolol enantiomers. The repeatability of the medium concentration quality control plasma sample (6.0 μg rac-atenolol/ml) was 11-18% for the enantiomers. The dynamic linear range of the plasma samples was 0.5-20 μg/ml. For system B, since atenolol is an extremely hydrophilic drug, the tissue dialysate sample required a much more sensitive system as compared to the plasma samples. A coupled column system was used for peak compression of the enantiomers in the eluate after the separation on the Chiral CBH column, hence increasing the detection sensitivity. The limit of quantification was 0.045 μg/ml for the atenolol enantiomers in artificial CSF. The repeatability of the medium concentration quality control samples (0.1 and 4.0 μg rac-atenolol/ml in artificial CSF and Hepes Ringer, respectively) was 2.8-9.3% for the two enantiomers. The dynamic linear range of the brain samples was 0.05-1.0 and 0.5-20 μg/ml in artificial CSF and Hepes Ringer, respectively. Chirality 9:329-334, 1997. © 1997 Wiley-Liss, Inc.
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  • 76
    ISSN: 0899-0042
    Keywords: enantioseparation ; chiral stationary phase ; HPLC ; amylose phenylcarbamate ; chiral discrimination ; resolution ; enantiomer ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Four 4-halogen-substituted phenylcarbamate derivatives of amylose were prepared and their chiral recognition abilities as chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC) were evaluated and compared with those of the corresponding cellulose derivatives. The amylose derivatives with fluoro, chloro, bromo, or iodo group at the four-position on the phenyl group were found to show higher chiral resolving ability than the corresponding cellulose derivatives. Among four amylose derivatives 4-fluoro- and 4-chlorophenylcarbamates showed an excellent chiral recognition ability. Especially, amylose tris(4-chlorophenylcarbamate) resolved (±)-1,2,2,2-tetraphenylethanol with a very high α value (α = 8.29). In order to obtain useful information concerning the chiral recognition mechanism of this resolution, we also performed enantioseparation of a variety of analogous racemic alcohols, and found that both the hydroxy and bulky triphenylmethyl groups of the racemate are essential for the effective chiral recognition. Chirality 9:63-68, 1997. © 1997 Wiley-Liss, Inc.
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  • 77
    ISSN: 0899-0042
    Keywords: stereoselective synthesis ; carboxyibuprofen diastereoisomers ; circular dichroism ; chiral LC separation ; ibuprofen ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The chromatographic resolution of the four stereoisomers of carboxyibuprofen, a major metabolite of ibuprofen in man, was achieved using a Chiralpak AD chiral stationary phase (CSP) (J.T. Baker, Milton, Keynes, UK). The elution order of the stereoisomers was determined to be 2′S,2R; 2′R,2R; 2′R,2S; 2′S,2S by a combination of stereoselective synthesis of diastereoisomeric mixtures and analysis of the two diastereoisomers isolated from human urine following the administration of (S)-ibuprofen. The individual stereoisomers were isolated by semipreparative chiral phase chromatography and characterized by circular dichroism spectroscopy. Chirality 9:75-87, 1997. © 1997 Wiley-Liss, Inc.
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  • 78
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: In the article listed above, the caption for Figure 5 should read as“Ionspray mass spectra of the negatively charged [DPB-CHF 1024] (A) and [DPB-CHF 1024 urea derivative] (B) complexes. The m/z values referred to the normal masses of ions.” rather than “Collision-activated dissociation spectrum of….”.The authors apologize for the error.
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  • 79
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    Chirality 9 (1997), S. 103-103 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: No abstract.
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  • 80
    ISSN: 0899-0042
    Keywords: capillary electrophoresis ; HPLC, α-phosphonosulfonic acid ; enantiomers, β-cyclodextrin ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The enantiomers of α-phosphonosulfonic acids were completely resolved by capillary electrophoresis using β-cyclodextrin as a chiral selector in a borate electrolyte and HPLC using a chiral AGP column. The methods were used to quantitate the R-enantiomer present as an impurity in the S-enantiomer, a potential cardiovascular drug candiate. Chirality 9:104-108, 1997. © 1997 Wiley-Liss, Inc.
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  • 81
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    Chirality 9 (1997), S. 122-125 
    ISSN: 0899-0042
    Keywords: enantiomeric excess determination ; polarimetry ; HPLC ; enantiomers ; solvent effects ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Investigations into the parameters affecting the sensitivity of polarimetric detectors for the determination of enantiomeric excess by achiral HPLC are presented. The results obtained showed that the specific optical rotation of an analyte was highly sensitive to the methanol content of the mobile phase. The purpose of this short communication is to demonstrate that “off-line” optical rotation measurements are a necessary part of the method development process for successful use of polarimetric detectors. Chirality 9:122-125, 1997, © 1997 Wiley-Liss, Inc.
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  • 82
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    Chirality 9 (1997), S. 113-121 
    ISSN: 0899-0042
    Keywords: 1,3,5-triazine ; chiral discrimination ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: 2-Hexylamino-4-[(S)-1-(1-naphthyl)ethylamino]-6-L-valyl-L-valyl-L-valine isopropylester-1,3,5-triazine (1), a molecule characterized by two different chiral selectors, and 2-hexylamino-4,6-bis-L-valyl-L-valyl-L-valine isopropylester-1,3,5-triazine (2) and 2-ethoxy-4-hexylamino-6-[(S)-1-(1-naphthyl) ethylamino]-1,3,5-triazine (3), systems in which a single kind of chiral selector is present, have been prepared. The enantiodiscriminating ability in solution of the three compounds toward the N-3,5-dinitrobenzoyl derivatives of 1-phenylethylamine (4) or valine methylester (5) has been investigated by 1H nuclear magnetic resonance (NMR) spectroscopy: 1 shows an improved versatility, relative to 2 and 3, as a chiral solvating agent for NMR spectroscopy. On the basis of the indications obtained, the usefulness of 2-chloro-4-[(S)-1-(1-naphthyl)ethylamino]-6-L-val-L-val-L-valine isopropylester-1,3,5-triazine (1a), a direct precursor of 1, as chiral solvating agent for the determination by NMR of the enantiomeric compositions of derivatives of amines, amino alcohols, amino acids, and carboxyl acids bearing a 3,5-dinitrophenyl moiety, has been demonstrated. Chirality 9:113-121, 1997. © 1997 Wiley-Liss, Inc.
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  • 83
    ISSN: 0899-0042
    Keywords: anti-ischemic agent ; gerbil ; enantiomeric resolution ; column switching ; chiral crown ether ; HPLC ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A sensitive and selective high performance liquid chromatographic method using an automated column switching technique for the determination of FCE 28833 enantiomers in gerbil plasma was developed. After solid-liquid extraction using a Supelcosil C18 cartridge FCE 28833 was eluted on a clean-up column (Spherisorb CN) and the enantiomers were separated using an analytical chiral column (Crownpack CR(+)). The mobile phase (15% methanol in HClO4 1 mM) was directed through the columns at a flow rate of 1 ml/min and the fraction eluted between 13 and 40 min was transferred from the clean-up column into the analytical column. FCE 28833 enantiomers were monitored at 257 nm. The limit of quantitation of the method was 20 ng/ml plasma for both enantiomers and proved to be linear, precise, and accurate for the assay of both enantiomers in the 20-6,000 ng/ml concentration range. No interference from the blank gerbil plasma sample was observed. The suitability of the method was assessed using plasma samples obtained from male gerbils treated with a single oral dose (400 mg/kg) of FCE 28833. Chirality 9:133-138, 1997. © 1997 Wiley-Liss, Inc.
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  • 84
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    Chirality 9 (1997), S. 139-144 
    ISSN: 0899-0042
    Keywords: thin-layer chromatography ; propranolol ; bupranolol ; enantiomers ; cellulose derivatives ; chiral stationary phase ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Cellulose triphenylcarbamate derivatives have been used as stationary phases for resolution of the enantiomers of the β-blockers propranolol and bupranolol by TLC. The derivatives examined were: cellulose trisphenylacarbamate (1), cellulose tris(2,3-dichlorophenyl carbamate) (2), cellulose tris(2,4-dichlorophenyl carbamate) (3), cellulose tris(2,6-dichlorophenyl carbamate) (4), cellulose tris (2,3-dimethylphenyl carbamate) (5), cellulose tris(3,4-dichlorophenyl carbamate) (6), cellulose tris(3,5-dichlorophenyl carbamate) (7), and cellulose tris(3,5-dimethylphenyl carbamate) (8). A variety of mobile phases were used to achieve useful separations and the effects of solvent polarity are also discussed. The best resolution of rac-propranolol was obtained on CSP 8 (RfR = 0.26, RfS = 0.06, α = 4.33) in mobile phase hexane:propan-2-ol (80:20 v/v). The best resolution of rac-bupranolol was obtained on CSP 5 (RfR = 0.29, RfS = 0.09, α = 3.22) in mobile phase hexane:propan-2-ol (80:20 v/v). These results demonstrated the potential of cellulose triphenylcarbamates as chiral stationary phases in TLC and indicate that this is potentially a useful method for the direct, simple, and rapid (within 30 min) resolution of racemates in the analytical control of enantiomeric purity. Physical aspects such as problems in cracking of the CSP, adhesion to plate, and interference of spot detection due to triphenylcarbamate chromphores are also discussed, along with the method employed to overcome them. Chirality 9:139-144, 1997. © 1997 Wiley-Liss, Inc.
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  • 85
    ISSN: 0899-0042
    Keywords: chiral separation ; β-cyclodextrin derivatives ; capillary electrophoresis ; vicinal diols ; borate complexation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Capillary electrophoretic enantioseparation of compounds containing vicinal diol groups have been investigated using different β-cyclodextrin (CD) derivatives and borate as a background electrolyte. Both native β-CD and several β-CD derivatives are examined. Chiral recognition is attributed to both enantioselective inclusion of the analyte into the chiral cavity of the CD and complexation with borate. The influence of concentration of the chiral selector, pH, and organic modifiers on the resolution was studied. Four diols were baseline separated. Chirality 9:153-156, 1997. © 1997 Wiley-Liss, Inc.
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  • 86
    ISSN: 0899-0042
    Keywords: chromatographic resolution ; enantiomers ; sulfoximide ; sulfoximine ; sulfoxide ; hydrogen bonding ; DATD-based CSP ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Two O,O′-diaroyl derivatives of an N,N′-diallyl-L-tartardiamide-based CSP, 3,5-dimethylbenzoyl (CSP I) and 4-tert-butylbenzoyl (CSP II), have been investigated and compared with respect to retention behaviour and resolving capabilities of a series of endocyclic sulfoximides of the 1-R-3-oxo-benzo[d]-isothia (IV)-azole 1-oxide type (R = methyl, octyl, 2′-carboxyphenyl, and 2′-carbethoxyphenyl) and their corresponding sulfoxide precursors. For the sulfoximides, selectivities of 1.44, 1.27, 1.28, and 1.20, respectively, were found on CSP II when eluted with 15% 2-propanol in hexane. Both the sulfoximide compounds and their sulfoxide precursors are well resolved by CSPs I and II. The retention was larger on the former phase, indicating that the molecular skeletons of the analytes studied interact, through hydrogen bonding, more strongly with CSP I than CSP II. Chirality 9:167-172, 1997. © 1997 Wiley-Liss, Inc.
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  • 87
    ISSN: 0899-0042
    Keywords: chiral high-performance liquid chromatography ; polysaccharides ; structure-retention relationships ; amides ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A series of enantiomeric amides have been chromatographed on three amylose-based chiral stationary phases (CSPs): amylose tris(3,5-dimethylphenylcarbamate) (AD-CSP), amylose tris (S-phenylethylcarbamate) (AS-CSP), and amylose tris(R-phenylethyl-carbamate) (AR-CSP). The relative retentions and enantioselectives of the solutes on the three CSPs were compared and basic structure-retention relationships developed to describe the chromatographic results. The data indicate that for these solutes the observed elution order was a function of the chirality of the amylose backbone, while the magnitude of the enantioselective separations was affected by the chirality of the carbamate side chain. Chirality 9:173-177, 1997. © 1997 Wiley-Liss, Inc.
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  • 88
    ISSN: 0899-0042
    Keywords: chiral recognition mechanisms ; quantitative structure ; enantioselective retention relationships ; chiral chromatography ; enantioselective separations ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A series of 12 chiral arylcarboxylic acids were chromatographed on an immobilized human serum albumin chiral stationary phase (HSA-CSP). The effects of solute structure on chromatographic retentions and enantioselective separations were examined by linear regression analysis and the construction of quantitative structure-enantioselective retention relationships. Competitive displacement studies were also conducted using R-ibuprofen as the displacing agent. The results indicate that the enantioselective retention of the solutes takes place at the indole-benzodiazepine site (site II) on the HSA molecule and that chiral recognition is affected by the hydrophobicity and steric volume of the solutes. The displacement studies also identified a cooperative allosteric interaction induced by the binding of R-ibuprofen to site II. Chirality 9:178-183, 1997. © 1997 Wiley-Liss, Inc.
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  • 89
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    Chirality 9 (1997), S. 198-202 
    ISSN: 0899-0042
    Keywords: oligopeptide ; amino acid N-carboxyanhydride ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: This article describes improvements in the Juliá asymmetric epoxidation reaction. The oligopeptides needed for the study were synthesised from N-carboxyanhydrides (NCAs) employing various initiators, such as water, 1,3-diaminopropane (DAP), and cross-linked aminomethylpolystyrene (CLAMPS) 1. Chirality 9:198-202, 1997. © 1997 Wiley-Liss, Inc.
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  • 90
    ISSN: 0899-0042
    Keywords: chiral selectors ; natural product derived hosts ; optically active hosts ; clathrate hosts ; bulky diols ; inclusion compounds ; host-guest complexes ; chiroselective cocrystallization ; crystal packing analysis ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: New chiral host molecules 1 and 2 involving a bulky terpenoid unit and aromatic ethyne spacer groups were synthesized using Pd-catalyzed cross-coupling reactions of (+)-2α-ethynyl-2β-hydroxybornane (4) or (+)-2α-ethynyl-2β-hydroxyfenchane (5) with 9,10-dibromoanthracene. Host compounds 1 and 2 from crystalline inclusions with 1-methoxy-2-propanol (3) in 1:1 and 1:2 stoichiometry, respectively. In the case of 1, complete enantiomer resolution (ee 〉 99%) of 3 is effected in one cocrystallization step. However, constitutional isomer 2 failed in the enantiomer separation of 3, which might be explained due to the different crystal lattice buildup of these cocrystals. Chirality 9:203-210, 1997. © 1997 Wiley-Liss, Inc.
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  • 91
    ISSN: 0899-0042
    Keywords: quartz crystal microbalance ; electronic nose ; fragrance ; odour ; detection ; chemical sensor ; cyclodextrin ; chiral discrimination ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Quartz crystal microbalances (QCMB) have been constructed using 10 MHz AT cut quartz crystals coated with heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin, heptakis(6-O-methyl-2,3-di-O-pentyl)-β-cyclodextrin, and octakis(6-O-methyl-2,3-di-O-pentyl)-γ-cyclodextrin as 50% and 20% (w/w) solutions in OV1701. The reduction in frequency seen on exposure of each coated QCMB to pure enantiomeric forms of α- and β-pinene and cis- and trans-pinane show that statistically significant (P = 0.05, n = 7) differences are observed between the enantiomeric pairs. The apparent preferential binding shown by the QCMB for enanciomers of α- and β-pinene and cis- and trans-pinane have been compared with the elution order observed on the corresponding gas chromatographic stationary phase. The magnitude of the observed separation factor (calculated as the ratio of the OV1701 normalised frequency shift) is seen to be dependent upon the chiral stationary phase concentration. These results indicate that on-line determination of enantiomeric excess and concentration of certain monoterpenes is possible at room temperature using QCMB in conjunction with chiral gas chromatographic stationary phases. Chirality 9:225-232, 1997. © 1997 Wiley-Liss, Inc.
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  • 92
    ISSN: 0899-0042
    Keywords: racemic compound crystal ; mixed crystal of (+) and (-) enantiomers ; enantiomeric enrichment in solution ; reversal of chirality ; X-ray powder diffraction ; chiral sulfonium sulfonate ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A new example of a racemate showing unusual enantiomeric resolution phenomenon, in which simple recrystallization of the racemate leads to remarkable enantiomeric enrichment of either enantiomer up to 100% ee in the mother liquor, has been found. This compound is (±)-[2-[4-(3-ethoxy-2-hydroxypropoxy)phenylcarbamoyl]-ethyl]dimethylsulfonium p-nitrobenzenesulfonate [EtOCH2CH(OH)CH2OC6H4NHCOCH2CH2SMe2+O2NC6H4SO3-] [(±)-SN]. By repeating recrystallization of (±)-SN and the resulting deposited crystals successively and collecting the resulting enantiomerically enriched mother liquors with the same chirality sense, highly efficient enantiomeric resolution of the racemate into its separate enantiomers has been accomplished. The relationship between the occurrence of this enantiomeric resolution phenomenon and the crystal properties has been investigated with respect to SN and its aryl- and alkylsulfonate derivatives. The mode of enantiomeric resolution of (±)-SN was similar to that of para-substituted benzenesulfonate derivatives (±)-ST (4-MeC6H4SO3-) and (±)-SC (4-ClC6H4SO3-) previously reported, whereas the unsubstituted derivative (±)-SB (C6H5SO3-) and alkysulfonate derivatives (±)-SO (n-C8H17SO3-) and (±)-SM (CH3SO3-) did not show such an enantiomeric resolution phenomenon. The crystalline form of the former racemates that underwent the enantiomeric resolution was racemic compounds, while the latter were mixed crystals (solid solutions) composed of the respective optical antipodes. Chirality 9:220-224, 1997. © 1997 Wiley-Liss, Inc.
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  • 93
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    Chirality 9 (1997), S. 243-249 
    ISSN: 0899-0042
    Keywords: chiral polymethine dyes ; circular dichroism ; helicity ; helicity rules ; cis-peak ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Synthesis, chiroptical properties, and quantum-mechanical calculations of the monomethine dye 3 and of the trimethine dyes 7 and 11 are reported. In 3 and 11, the chromophore is forced into a twisted all-Z-conformation by steric interaction of the end groups in the former and the presence of a t-butyl group in the mesoposition of the latter, which is manifest in the UV/Vis spectra not only in the reduced intensity of the longest wavelength absorption, but also in the occurrence, at shorter wavelength, of a “cis-peak.” Chiral substitution of the end groups serves as chiral anchor to discriminate between otherwise enantiomeric forms and makes them amenable to chiroptical investigation. The results are in agreement with theoretically calculated chiroptical data based on helically twisted cyanine chromophores. They support the contention that not only the sense of the helix, but also its length determines the sign of the associated Cotton effect. Chirality 9:243-249, 1997. © 1997 Wiley-Liss, Inc.
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  • 94
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    Chirality 9 (1997), S. 238-242 
    ISSN: 0899-0042
    Keywords: non-covalent molecular imprinting ; hydrogen bonding parameters ; solvent properties ; chiral separation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The aim of this study was to rationalise retention behaviour of a chiral solute on molecularly imprinted polymer (MIP) HPLC stationary phases in terms of variation of the mobile phase. It is generally held that the most important interaction governing the separation of enantiomers on such materials is H-bonding, and that retention times increase with decreasing H-bonding potential of the mobile phase. Previous studies have largely concerned mobile phases containing chloroform with acetic acid as a polar modifier. Boc-L-Phenylalanine (Boc-L-Phe-OH) MIPs were prepared, processed, and packed into HPLC columns, which were then used to investigate the retention characteristics of Boc-L-Phe-OH and Boc-D-Phe-OH with a range of mobile phases. The main observations were as follows: (1) in chloroform-based mobile phases there was generally a linear relationship between the H-bond donator factor of the polar modifier and capacity (K′). Results also indicated a hydrogen bond donor parameter value for a polar modifier at which retention became concentration independent; (2) For given values of K′L, K′D varied depending on the polar modifier, indicating that enantiomer resolution was solvent dependent; (3) Using mobile phases based on solvents of lower polarity/H-bonding potential than chloroform, substantial increases in K′ were observed, although enantioselectivity was greatly reduced. Chirality 9:238-242, 1997. © 1997 Wiley-Liss, Inc.
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  • 95
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    Chirality 9 (1997), S. 261-267 
    ISSN: 0899-0042
    Keywords: industrial scale ; phenylalanine ; enhancing enantioselectivity ; membrane solvent ; chiral extraction ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: We describe the use of emulsion liquid membrane technology to perform chiral separations on low molecular weight species. We have reviewed liquid membrane technology in the context of existing process scale chiral separations. We illustrate the potential of this new technique by presenting our results on the selective extraction of phenylalanine enantiomers, using copper (II) N-decyl-(L)-hydroxyproline as a chiral selector in an emulsion liquid membrane configuration. This is compared with an analogous batch solvent extraction system. Initial batch enantiomeric excesses of greater than 40% were observed with the emulsion liquid membrane system compared with around 25% for the solvent extraction system. It was also noted that the system is not limited by the equilibrium capacity constraints of the solvent extraction system. We have shown that kinetic chiral liquid membrane technology offers high productivity and flexibility compared with analogous process scale chiral technologies. Recent transfer of highly specific chiral reversed-phase high-performance liquid chromatographic chemistries have shown that “one-stop” enantiomeric excesses of commercial interest (〉95%) are achievable using kinetic chiral liquid membrane systems. Solvent and temperature selection strategies also have been outlined as means of increasing the enantioselectivity of existing liquid membrane extraction chemistries. Chirality 9:261-267, 1997. © 1997 Wiley-Liss, Inc.
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  • 96
    ISSN: 0899-0042
    Keywords: chiral HPLC ; resolution ; enantiomeric purity ; configurational assignment ; circular dichroism ; AMPA receptor affinity ; electrophysiology ; AMPA receptor agonism ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: We have previously shown that whereas (RS)-2-amino-3-(3-hydroxy-5-phenylisoxazol-4-yl)propionic acid (APPA) shows the characteristics of a partial agonist at (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors, (S)-APPA is a full AMPA receptor agonist and (R)-APPA a weak competitive AMPA receptor antagonist. This observation led us to introduce the new pharmacological concept, functional partial agonism. Recently we have shown that the 2-pyridyl analogue of APPA, (RS)-2-amino-3-[3-hydroxy-5-(2-pyridyl)isoxazol-4-yl]propionic acid (2-Py-AMPA), is a potent and apparently full AMPA receptor agonist, and this compound has now been resolved into (+)- and (-)-2-Py-AMPA (ee ≥ 99.0%) by chiral HPLC using a Chirobiotic T column. The absolute stereochemistry of the enantiomers of APPA has previously been established by X-ray analysis, and on the basis of comparative studies of the circular dichroism spectra of the enantiomers of APPA and 2-Py-AMPA, (+)- and (-)-2-Py-AMPA were assigned the (S)- and (R)-configuration, respectively. In a series of receptor binding studies, neither enantiomer of 2-Py-AMPA showed detectable affinity for kainic acid receptor sites or different sites at the N-methyl-D-aspartic acid (NMDA) receptor complex. (+)-(S)-2-Py-AMPA was an effective inhibitor of [3H]AMPA binding (IC50 = 0.19 ± 0.06 μM) and a potent AMPA receptor agonist in the rat cortical wedge preparation (EC50 = 4.5 ± 0.3 μM) comparable with AMPA (IC50 = 0.040 ± 0.01 μM; EC50 = 3.5 ± 0.2 μM), but much more potent than (+)-(S)-APPA (IC50 = 5.5 ± 2.2 μM; EC50 = 230 ± 12 μM). Like (-)-(R)-APPA (IC50 〉 100 μM), (-)-(R)-2-Py-AMPA (IC50 〉 100 μM) did not significantly affect [3H]AMPA binding, and both compounds were week AMPA receptor antagonists (Ki = 270 ± 50 and 290 ± 20 μM, respectively). Chirality 9:274-280, 1997. © 1997 Wiley-Liss, Inc.
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  • 97
    ISSN: 0899-0042
    Keywords: dexketoprofen ; enantiomer ; stereoselectivity ; brain ; cyclooxygenase ; rat ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Although it has been assumed that the effects of nonsteroidal antiinflammatory drugs (NSAIDs) are mainly the result of their action on local synthesis of prostaglandins, there is growing evidence to suggest that they may also exert a central analgesic action. Some authors have suggested that inhibition of prostaglandin synthesis in the brain could contribute to the analgesic action. The effect of dexketoprofen trometamol (tromethamine salt of the enantiomer (+)-S-ketoprofen) on prostaglandin synthesis was investigated in rat brain fragments and in cyclooxygenase preparations from rat brain microsomes. Effects of the (-)-R-enantiomer and the racemic mixture were also evaluated. Significant levels of prostaglandin F2α (PGF2α) were synthesized in rat brain fragments after 10 min of incubation at 37°C. Dexketoprofen was found to be a potent inhibitor of this PGF2α production in rat brain (IC50 = 6.2 nM), and it completely suppressed PGF2α production at 1 μM concentration. In addition, inhibition of PGF2α synthesis by dexketoprofen was highly stereoselective since the enantiomer (-)-R-ketoprofen was significantly less potent (IC50 = 294 nM); with this enantiomer, even at high concentrations such as 1 μM, less than 60% inhibition was achieved. These results correlated with those obtained in the study of racemic ketoprofen and its enantiomers on cyclooxygenase activity of rat brain microsomes, where dexketoprofen also inhibited enzymatic activity stereoselectively. IC50 values obtained for dexketoprofen, (-)-R-ketoprofen, and rac-ketoprofen were 3.5 μM, 45.3 μM, and 5.8 μM, respectively. The above results could be related to the potent analgesic effect of dexketoprofen observed in vivo, which was also stereoselective. Taken together, these findings suggest that prostaglandin synthesis inhibition in rat brain by dexketoprofen could be associated, at least in part, with the analgesic effect of this NSAID. Chirality 9:281-285, 1997. © 1997 Wiley-Liss, Inc.
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  • 98
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    Chirality 9 (1997), S. 313-316 
    ISSN: 0899-0042
    Keywords: ibuprofen ; topical administration ; chromatography ; skin metabolism ; percutaneous penetration ; chiral ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: In vitro experiments to investigate possible stereoselective aspects of the topical administration of ibuprofen have been conducted. Incubation of ibuprofen with rat skin homogenates in the presence of coenzyme A, ATP, and magnesium provided no evidence for the formation of ibuprofenyl coenzyme A (the initial intermediate in the metabolic inversion of [R]- to [S]-ibuprofen). Similar incubation studies gave no indication of a change in the enantiomeric ratios of ibuprofen over the time course of the experiments. Percutaneous penetration studies of ibuprofen gel through porcine skin indicated that the ibuprofen enantiomer levels in the reservoir solutions were consistent with racemic ibuprofen having traversed the skin with no metabolic inversion. These results suggest that, in the models studied, skin metabolism does not result in the chiral inversion of (R)- to (S)-ibuprofen and that the topical administration of ibuprofen will result in the delivery of 50% “isomeric ballast.” Chirality 9:313-316, 1997. © 1997 Wiley-Liss, Inc.
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  • 99
    ISSN: 0899-0042
    Keywords: anti-inflammatory drugs ; ibuprofen ; clinical pharmacokinetics ; bioinversion ; enantiomers ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The pharmacokinetics of ibuprofen enantiomers were investigated in a crossover study in which seven healthy male volunteers received single oral doses of 800 mg racemic ibuprofen as a soluble granular formulation (sachet) containing L-arginine (designated trade name: Spedifen®), 400 mg (-)R-ibuprofen arginine or 400 mg (+)S-ibuprofen arginine.Plasma levels of both enantiomers were monitored up to 480 minutes after drug intake using an enantioselective analytical method (HPLC with ultraviolet detection) with a quantitation limit of 0.25 mg/l.Substantial inter-subject variability in the evaluated pharmacokinetic parameters was observed in the present study. After (+)S-ibuprofen arginine, the following mean pharmacokinetic parameters ±SD were calculated for (+)S-ibuprofen: tmax 28.6 ± 28.4 min; Cmax 36.2 ± 7.7 mg/l; AUC 86.4 ± 14.9 mg · h/l; t½ 105.2 ± 20.4 min. After (-)R-ibuprofen arginine, the following mean pharmacokinetic parameters were calculated for (+)S-ibuprofen and (-)R-ibuprofen, respectively: tmax 90.0 ± 17.3 and 50.5 ± 20.5 min; Cmax 9.7 ± 3.0 and 35.3 ± 5.0 mg/l; AUC 47.0 ± 17.2 and 104.7 ± 27.7 mg · h/l; t½ 148.1 ± 63.6 and 97.7 ± 23.3 min. After racemic ibuprofen arginine, the following mean pharmacokinetic parameters were calculated for (+)S- and (-)R-ibuprofen, respectively: tmax 30.7 ± 29.1 and 22.9 ± 29.8 min.; Cmax 29.9 ± 5.6 and 25.6 ± 4.4 mg/l; AUC 105.1 ± 23.0 and 65.3 ± 15.0 mg · h/l; t½ 136.6 ± 20.7 and 128.6 ± 45.0 min. Tmax values of S(+)- and (-)R-ibuprofen after a single dose of 400 mg of each enantiomer did not differ significantly from the corresponding parameters obtained after a single dose of 800 mg of racemic ibuprofen arginine, indicating that the absorption rate of (-)R- and (+)S-ibuprofen is not different when the two enantiomers are administered alone or as a racemic compound. An average of 49.3 ± 9.0% of a dose of the (-)R-ibuprofen arginine was bioinverted into its antipode during the study period (480 minutes post-dosing). The percent bioinversion during the first 30 minutes after (-)R-ibuprofen arginine intake averaged 8.1 ± 3.9%. The mean AUC of (+)S-ibuprofen calculated after 800 mg racemic ibuprofen arginine (105.1 ± 23.0 mg · h/l) was lower than the mean AUC value obtained by summing the AUCs of (+)S-ibuprofen after administration of 400 mg (+)S-ibuprofen arginine and 400 mg (-)R-ibuprofen arginine (133.4 ± 26.6 mg · h/l).In conclusion, the administration of Spedifen® resulted in very rapid absorption of the (+)S-isomer (eutomer) with tmax values much lower than those observed for this isomer when conventional oral solid formulations such as capsules or tablets of racemic ibuprofen are administered. This characteristic is particularly favourable in those conditions in which a very rapid analgesic effect is required. Chirality 9:297-302, 1997. © 1997 Wiley-Liss, Inc.
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  • 100
    ISSN: 0899-0042
    Keywords: Saccharomyces cerevisiae ; asymmetric β-keto-ester reduction ; enzymatic kinetic resolution ; chiral 2-allyl-2-carboethoxy-cyclopentanol ; chiral high resolution gas chromatography ; chiral stationary phase ; β-cyclodextrin derivative ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The improvement of the biocatalytic reduction of 2-allyl-carboethoxy-cyclopentanone (2) to the corresponding cyclopentanol derivative (+)-(1R,2R)-(1) was accomplished employing baker's yeast in organic media. This chiral cyclopentanol derivative (1), analyzed by high resolution gas chromatography performed over β-cyclodextrin stationary phase, was obtained in 38% yield (〉99% e.e.). Chirality 9:321-324, 1997. © 1997 Wiley-Liss, Inc.
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