bluuebunny/crossref_metadata_2025_split huggingface dataset:
The direct determination of the enantiomers of ketorolac and parahydroxyketorolac in plasma and urine using enantioselective liquid chromatography on a human serum albumin‐based chiral stationary phase
Authors: Diaz‐Perez Maria J. , Chen John C. , Aubry Anne‐Francoise , Wainer Irving W. 
Published: January 2005

AbstractAn enantioselective assay has been developed for the determination of the enantiomers of ketorolac and its metabolite p‐hydroxyketorolac in plasma and urine. The analytical method utilizes a coupled achiral–chiral HPLC system where the initial separation of ketorolac from p‐hydroxyketorolac and matrix interferences was achieved on a C18‐stationary phase and the enantioselective separations of the two target solutes were accomplished on a human serum albumin‐based chiral stationary phase. The two columns were attached in sequence and the assay was carried out without the necessity of column‐switching techniques. The method has been validated for use in pharmacokinetic and metabolic studies and represents the initial report of the determination of ketorolac and p‐hydroxyketorolac enantiomers in urine. The results of the study indicate that after the administration of racemic ketorolac there was an enantioselective distribution of ketorolac enantiomers in plasma [(R)‐ketorolac: (S)‐ketorolac = 3.89 ± 0.93 (n = 6) and urine (R)‐ketorolac: (S)‐ketorolac = 1.26 ± 0.09 (n = 7)]. The mean ratio of the p‐hydroxyketorolac enantiomers was 1.77 ± 0.46 (n = 7). Both ketorolac and p‐hydroxyketorolac are glucuronized in the acyl carboxyl moiety and the results of this study indicate that this process is not enantiospecific. © 1994 Wiley‐Liss, Inc.
Preparation of milligrams of pure enantiomers using analytical‐scale high‐performance liquid chromatography
Authors: Liu Gaoyuan , Goodall David M. , Hunter Anna T. , Massey Peter R. 
Published: January 2005

AbstractPure enantiomers of an agrochemical process intermediate, (RS)‐1‐(4‐chlorophenyl)‐4,4‐dimethyl‐2‐(1H‐1,2,4‐triazol‐1‐yl)‐pentan‐3‐one (1), have been prepared on the milligram scale under overload chromatographic conditions on an analytical chiral column (250 × 4.6 mm i.d.). The effects of variation of temperature and mobile phase composition on retention factor, separation factor, and peak resolution have been investigated. Effects of flow rate, enantiomer ratio, sample concentration, and column load on productivity are also studied. Seven milligrams of the less retained (+)‐enantiomer and 5 mg of the (−)‐enantiomer were obtained from a single injection of 21 mg of (RS)‐1. © 1994 Wiley‐Liss, Inc.
Lack of stereoselectivity of the peroxisome proliferation induced by 2‐phenylpropionic acid: Evidence against a role for lipid disturbance in peroxisome proliferation
Authors: Ahmad Dzulkifly , Caldwell John 
Published: January 2005

AbstractThe significance of disturbances of lipid metabolism caused by xenobiotic acyl‐CoAs as possible causes of peroxisomal proliferation has been studied with the enantiomers of 2‐phenylpropionic acid (2‐PPA), the (R)‐enantiomer of which is converted to the acyl‐CoA in rats while its (S)‐antipode is not. rac‐2‐PPA (250 mg/kg/day ip × 3) was shown to be an hepatic peroxisomal proliferator in male Sprague–Dawley rats on the basis of increases in microsomal cytochrome P‐450 content and lauric acid hydroxylation and hepatic CN−‐insensitive palmitoyl‐CoA oxidation, a peroxisomal marker activity, while electron microscopy revealed a rise in the peroxisome/mitochondria ratio in hepatocytes. Further studies established the dose–response relationships for these biochemical changes. The (R)‐ and (S)‐enantiomers were administered at a dose of 50 mg/kg/day ip × 3 and both were peroxisome proliferators of very similar potency. The effects of 100 mg/kg/day ip × 3 of the racemate, a dose giving ca. 75% of maximal response, were essentially additive of those of 50 mg/kg/day ip × 3 of its two component isomers. The stereoselectivity of acyl‐CoA formation from the enantiomers of 2‐PPA was confirmed by their differential inhibition of microsomal palmitoyl‐CoA synthesis. Taken together, these data indicate that it is very unlikely that the acyl‐CoA of 2‐PPA plays any role in the peroxisomal proliferation which this compound causes in the rat. © 1994 Wiley‐Liss, Inc.
Investigation of the enantioselectivity and enantiomeric elution order of some piperidine‐2,6‐dione drugs on chiralcel OD column
Authors: Aboul‐Enein Hassan Y. , Serignese Vince 
Published: January 2005

AbstractThe enantioselectivity and enantiomeric separation of five racemic piperidine‐2,6‐dione compounds, on the cellulose tris(3,5‐dimethylphenyl carbamate) chiral stationary phase Chiralcel OD‐CSP were investigated under the same chromatographic conditions. This class of drugs includes glutethimide, aminoglutethimide, cyclohexylaminoglutethimide, pyridoglutethimide, and phenglutarimide. The results revealed that chiral recognition and the binding sites of these drugs on the Chiralcel OD column are similar, regardless of the absolute configuration of the individual enantiomers. A possible chiral recognition mechanism(s) for this class of drugs and the CSP is presented. © 1994 Wiley‐Liss, Inc.
Absolute configuration and biological activity of mequitamium iodide enantiomers
Authors: Di Bugno Cristina , Dapporto Paolo , Giorgi Raffaello , Manzini Stefano , Paoli Paola , Subissi Alessandro , Arcamone Federico 
Published: January 2005

AbstractThe enantiomers of 1‐methyl‐3‐(10H‐phenothiazine‐10‐ylmethyl)‐1‐azoniabicyclo[2,2,2]octane iodide (1) were prepared by chiral chromatographic resolution of the precursor mequitazine (2). The (+)‐(S)‐enantiomer 1b is 10‐fold more potent than (−)‐(R)‐enantiomer 1a as a histamine antagonist, while the two enantiomers show the same antimuscarinic activity in vitro. The absolute configuration of the more active dextrorotatory isomer has been determined by X‐ray analysis. Conformational analysis and molecular modeling suggest that the (+)‐(S)‐enantiomer can adopt a conformation similar to that attributed to the receptor binding conformers of classical antihistamines. © 1994 Wiley‐Liss, Inc.
Preparation and configuration of racemic and optically active analgesic dialkylaminoalkylnaphthalenes
Authors: Ghislandi Victor , Azzolina Ornella , Collina Simona , Paroli Eugenio , Antonilli Letizia , Giuseppetti Giuseppe , Tadini Carla 
Published: January 2005

AbstractThe alkylaminoalkylnaphthalene 3 shows interesting opioid‐like analgesic properties, μ‐selective ligand competition, and enkephalin hydrolyzing enzyme inhibition. 3 possesses two chiral centers and can exist as two racemic pairs and four diastereomers. Since the binding of opioids with the receptor is stereoselective, it was important to have the two racemic pairs as well as the four diastereomers. In this paper the synthesis of the (1R,2R/1S,2S)‐ and (1R,2S/1S,2R)‐racemates and the (1R,2R)‐ and (1S,2S)‐enantiomers of the 1‐ethyl‐1‐hydroxy‐1‐[2‐(6‐hydroxynaphthyl)]‐2‐methyl‐3‐dimethylaminopropane 3 is considered and the determination of absolute configuration is described. The (1R,2R/1S,2S)‐3 and (1R,2S/1S,2R)‐3 racemates and the (1R,2R)‐3 and (1S,2S)‐3 enantiomers were prepared by reaction of the racemic and optically active 1‐dimethylamino‐2‐methylpentan‐3‐one 2, respectively, with the lithiation product obtained from 2‐bromo‐6‐tetrahydropyranyloxynaphthalene and acidic hydrolysis. The optical resolution of aminoketone 2 was carried out via fractional crystallization of salts (+)‐ and (−)‐dibenzoyltartrates. The configuration of the optically active compounds was determined by X‐ray analysis of a crystal of (+)‐(1R,2R)‐3 · HCl · H2O. Preliminary pharmachological tests showed that (+)‐(1R,2R)‐3 enantiomer is able to induce opioid‐like analgesia with a relative potency 2.5 times that of (1R,2R/1S,2S)‐3 and about 4 times that of morphine. © 1994 Wiley‐Liss, Inc.
Evidence of absorption rate dependency of ibuprofen inversion in the rat
Authors: Sattari Saeed , Jamali Fakhreddin 
Published: January 2005

AbstractIbuprofen (IB) is a chiral 2‐arylpropionic acid derivative used as a nonsteroidal antiinflammatory drug (NSAID). It undergoes substantial R to S chiral inversion in humans and rats. In addition to systemic inversion, presystemic chiral inversion has been suggested for IB in humans but only after administration of formulations with slow absorption rates. In search for a suitable animal model, the absorption rate dependency of the extent of inversion was examined in male Sprague–Dawley rats given 20 mg/kg of racemic IB in aqueous solution (Tmax, 0.6 h), suspension (Tmax, 1 h) or as sustained release granules (Tmax, 2.3 h). In addition, (R)‐IB (5 mg/liter) was incubated in the presence of everted rat gut segments in an organ bath at 37°. After sustained release granules, the S:R AUC ratios (7.3 ± 1.5) were significantly higher than suspension (3.6 ± 1.1) and solution (3.5 ± 0.2). Accordingly, AUCS and AUCR, as percent of the total AUC (S + R), significantly increased and decreased, respectively, after administration of the sustained released granules as compared with the solution and suspension. A significant positive linear correlation was found between the S:R AUC ratios and the corresponding Tmax for (R)‐IB (r = 0.82). In vitro, (R)‐IB was inverted by everted jejunum (12.2 ± 1.6%), ileum (14.2 ± 2.0%), and colon (4.4 ± 0.6%) segments. IB was also glucuronidated in the presence of the intestinal segments. Therefore, similar to earlier observations made in humans, in the rat, the S:R AUC ratio was positively and significantly correlated with the absorption rate from the dosage form. Rat small intestine was capable of inverting and conjugating (R)‐IB. Hence, rat is a suitable model for studying the chiral inversion of IB. © 1994 Wiley‐Liss, Inc.
Stereoselective pharmacokinetics of methadone in beagle dogs
Authors: Schmidt Norbert , Brune Kay , Williams Kenneth M. , Geisslinger Gerd 
Published: January 2005

AbstractThe pharmacokinetics of methadone were studied in beagle dogs (n = 4) following intravenous administration of the racemate (0.5 mg/kg) and of the individual (R)‐(0.25 mg/kg) and (S)‐enantiomers (0.25 mg/kg) using a stereospecific HPLC assay. There was no significant difference between the pharmacokinetic parameters of (R)‐methadone and (S)‐methadone following administration of the individual enantiomers. Stereoselective differences were evident following administration of the racemate (P values for differences in AUC and CL were 0.001 and 0.046, respectively) and the clearance of the (S)‐enantiomer was increased when administered as part of the racemate (316 ± 81 vs 487 ± 128 ml/min, P = 0.04). The data suggest that stereoselective disposition including potential enantiomer–enantiomer interactions should be considered in pharmacokinetic–pharmacodynamic studies of (R,S)‐methadone. © 1994 Wiley‐Liss, Inc.
Enantiomerization of 2,2′‐diisopropylbiphenyl during chiral inclusion gas chromatography: Determination of the rotational energy barrier by computer simulation of dynamic chromatographic elution profiles
Authors: Jung Martin , Fluck Markus , Schurig Volker 
Published: January 2005

AbstractBy computer simulation of experimental dynamic gas chromatographic elution profiles, the rotational energy barrier ΔG= of racemic 2,2′‐diisopropylbiphenyl has been determined as 114.6–115.0 kJ/mol (75–100°C). These data are in good agreement with a value that was determined previously by measuring the racemization kinetics of an enriched sample. This indicates that there is no measurable catalytic or inhibitory effect of the stationary phase. © 1994 Wiley‐Liss, Inc.
Determination of the enantiomers of mianserin, desmethylmianserin, and 8‐hydroxymianserin in the plasma and urine of mianserin‐treated patients
Authors: Eap Chin B. , Powell Kerry , Campus‐Souche Donatella , Monney Christian , Baettig Dominique , Taeschner Walter , Baumann Pierre 
Published: January 2005

AbstractAn HPLC method is presented which allows the measurement in the same run of the enantiomers of mianserin, desmethylmianserin, and 8‐hydroxymianserin in plasma and urine of mianserin‐treated patients. Limits of quantitation for the (S)‐ and (R)‐ enantiomers of mianserin and desmethylmianserin were 4 and 2.5 ng/ml, respectively, in plasma, and for the (S)‐ and (R)‐enantiomers of mianserin, desmethylmianserin, and 8‐hydroxymianserin 5, 2.5, and 5 ng/ml, respectively, in urine. The measured ratios of (S)‐mianserin/(R)‐mianserin and (S)‐desmethylmianserin/(R)‐desmethylmianserin in the plasmas of 10 mianserin‐treated patients, all extensive metabolizers of debrisoquine as determined by CYP2D6 genotyping, varied, respectively, from 1.0 to 4.06 and from 0.19 to 0.64. As the enantiomers of mianserin differ in their pharmacological profile, these results could partially explain why, until now, no consistent relationship has been established between the therapeutic response and total [(S) + (R)] plasma levels of this antidepressant. © 1994 Wiley‐Liss, Inc.
In vitro inhibition of aromatase by the enantiomers of aminoglutethimide and analogs
Authors: Ogbunude Patrick O.J. , Aboul‐Enein Hassan Y. 
Published: January 2005

AbstractThe in vitro aromatase activity in microsomal fractions from rat ovary and its inhibition by enantiomers of aminoglutethimide (AG), rogletimide (RG), and cyclohexylaminoglutethimide (ChAG) were studied by analysing the [3H]H2O released when [1β‐3H]androstenedione was converted to estrone. Maximum velocity (Vmax) and the Michaelis‐Menten constant (Km) of the microsomal aromatase enzyme were 17.40 ± 0.45 pmol/ml/mg protein/min and 1.02 ± 0.06 μM, respectively. The IC50s for the enantiomers were similar for (+)‐R‐AG and (−)‐R‐ChAG (0.86 ± 0.06 and 0.89 ± 0.15 μM, respectively). (+)S‐ChA'G was most potent with IC50 of 0.075 ± 0.003 μM. The IC50s for (−)‐S‐AG, (+)‐R‐RG, and (−)‐S‐RG were in the same range (23.15 ± 2.74, 24.58 ± 2.46, and 24.43 ± 2.20 μM, respectively). © 1994 Wiley‐Liss, Inc.
Direct determination of the enantiomeric purity of (R)‐ and (S)‐2‐hydroxy‐4‐phenylbutyric acid
Authors: Chilmonczyk Zdzisław , Ksycińska Hanna , Kruszewska Hanna , Cybulski Jacek 
Published: January 2005

AbstractThe determination of enantiomeric purity of (R)‐ and (S)‐2‐hydroxy‐4‐phenylbutyric acid by chiral HPLC is described. Good resolution has been obtained on covalently bonded L‐hydroxyproline saturated with Cu(II) ions. The method makes possible the determination of enantiomeric purity in media containing growing cells. © 1994 Wiley‐Liss, Inc.
Optically active analogues of ebastine: Synthesis and effect of chirality on their antihistaminic and antimuscarinic activity
Authors: Zhang Ming‐Qiang , Walczynski Krzysztof , Ter Laak Anton M. , Timmerman Henk 
Published: January 2005

AbstractA series of optically active analogues of the H1‐antihistamine ebastine, with chiral center(s) at the benzhydryl and/or phenylbutyl part of the molecule, have been synthesized. Their in vitro antihistaminic and antimuscarinic activities were investigated, along with a molecular modelling study. It was found that introduction of the benzhydryl chiral center yielded significant stereoselectivity for both antihistaminic and antimuscarinic activities. The steric preferences of the benzhydryl chiral center for antihistaminic and antimuscarinic actions were mirror images of each other. The (−)‐isomer of 4‐methylebastine (6d) showed more than 10‐fold higher in vitro antihistaminic potency than ebastine. Meanwhile the selectivity of 6d for histamine H1‐receptors was also increased by more than 20 times in comparison with ebastine. The chirality at the phenylbutyl part of the molecule does not significantly alter the antihistaminic or antimuscarinic activity of the compounds although the (S)‐isomers showed slightly but unanimously higher antihistaminic activity than the (R)‐isomers. These results have been discussed with existing stereoselectivity data of antihistamines and an asymmetric pharmacophore model for H1‐antagonists has been described. © 1994 Wiley‐Liss, Inc.
Successive optical resolution by replacing crystallization of DL‐threonine
Authors: Shiraiwa Tadashi , Miyazaki Hideya , Kurokawa Hidemoto 
Published: January 2005

AbstractDL‐Threonine [DL‐Thr; (2RS,3SR)‐2‐amino‐3‐hydroxybutanoic acid] was optically resolved by replacing crystallization using L‐serine (L‐Ser) and 4‐hydroxy‐L‐proline (L‐Hyp) as optically active cosolutes. D‐Thr was allowed to crystallize preferentially from racemic aqueous solutions in the presence of these L‐α‐amino acids. The optical resolution of DL‐Thr was more successfully achieved by using L‐Ser, whose structure is more similar to that of DL‐Thr than L‐Hyp, and successively gave D‐ and L‐Thr of 87—92% optical purities. The D‐ and L‐Thr obtained were then recrystallized from water to give optically pure D‐ and L‐Thr. © 1994 Wiley‐Liss, Inc.
Analysis of warfarin enantiomers: Chromatographic separation of six stereoisomeric esters prepared from (−)‐(1S,2R,4R)‐endo‐1,4,5,6,7,7‐hexachlorobicyclo[2.2.1]hept‐5‐ene‐2‐ carboxylic acid
Authors: Duke Colin C. , Carter Stephen R. , Hambley Trevor W. , Holder Gerald M. , Cutler David J. 
Published: January 2005

AbstractReaction of rac‐warfarin, (−)‐(1S,2R,4R)‐endo‐1,4,5,6,7,7‐hexachlorobicyclo[2.2.1]hept‐5‐ene‐2‐ carboxylic acid [(−)‐HCA] and carbodiimide reagents gave two noncyclic ketonic diastereoisomeric derivatives whereas rac‐warfarin and (−)‐HCA acid chloride with 4‐(dimethylamino)pyridine gave four cyclic hemiketal diastereoisomeric ester derivatives. The structure and stereochemistry of diastereoisomeric esters prepared from warfarin and p‐chlorowarfarin were determined from 1H‐ and 13C‐NMR spectra, mass spectra, and hydrolysis to warfarin and p‐chlorowarfarin enantiomers. The structure and stereochemistry of one of the cyclic hemiketal diastereoisomeric derivatives of warfarin are supported by an X‐ray crystallographic determination. Mechanisms for the formation of all products are proposed. © 1994 Wiley‐Liss, Inc.
Synthesis and enantiomeric purity determination of chiral 3‐benzylglycidol, a key synthon for hiv protease inhibitors
Authors: Shum Wilfred P. , Chen Jian , Cannarsa Michael J. 
Published: January 2005

AbstractThe detailed synthesis of (2R,3R)‐3‐benzylglycidol by the Sharpless asymmetric epoxidation route is described. The enantiomeric purity determination of this compound is complicated by the presence of small quantities of the diastereometric (2R,3S)‐3‐benzylglycidol from the asymmetric epoxidation of the cis‐allylic alcohol, and the unreacted allylic alcohols that are not removed in the product isolation steps. We have developed a direct chiral HPLC method that can resolve all these components for the precise determination of enantiomeric excesses of chiral 3‐benzylglycidols. © 1994 Wiley‐Liss, Inc.
K‐Opioid activity of the four stereoisomers of the peripherally selective κ‐agonists, EMD 60 400 and emd 61 753
Authors: Gottschlich Rudolf , Krug Michael , Barber Andrew , Devant Ralf M. 
Published: January 2005

AbstractThe four stereoisomers of the two peripherally selective κ‐opioid agonists EMD 60 400 and EMD 61 753 were synthesized, tested for stereoisomeric purity, and examined for affinity to the κ opioid receptor. The relationships between the configuration of these molecules and their biological activity are discussed. © 1994 Wiley‐Liss, Inc.
Retention model for the resolved enantiomers of felodipine on chiral‐AGP using micellar mobile phases
Authors: Haupt Dan , Pettersson Curt , Westerlund Douglas 
Published: January 2005

AbstractA 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.
Stereoselectivity in acid‐catalyzed heteronucleophilic substitution of enantiomeric 3‐O‐methyloxazepam and 3‐O‐ethyloxazepam
Authors: Yang Shen K. 
Published: January 2005

AbstractKinetics of acid‐catalyzed heteronucleophilic substitution and racemization of enantiomeric MeOX in ethanol and enantiomeric EtOX in methanol were studied by quenching reaction products at various times by neutralization. Enantiomeric contents of remaining substrate and reaction product were determined by chiral stationary phase high‐performance liquid chromatography. The experimental procedure allowed the determination of the stereoselectivity (i.e., the enantiomeric ratio of a substitution product formed from an enantiomerically pure substrate) involved in the heteronucleophilic substitution reactions. The stereoselectivity was found to vary between 58:42 and 87:13, depending on the acid concentration, substrate, solvent, and temperature. The enantiomeric purity of remaining substrates was identical to that of the starting substrate, indicating that the enantiomeric substrates did not undergo a ring‐opening reaction. The results provided additional evidence supporting the mechanism proposed earlier in acid‐catalyzed stereoselective heteronucleophilic and homonucleophilic substitutions and the resulting racemization of enantiomeric 3‐alkoxy‐1,4‐benzodiazepines in alcoholic solvents. © 1995 Wiley‐Liss, Inc.
Structural features affecting chiral resolution of cannabimimetic enantiomers by amylose 3,5‐dimethylphenylcarbamate chiral stationary phase
Authors: Levin Shulamit , Sterin Marina , Abu‐lafi Saleh 
Published: January 2005

AbstractThe effect of structural features of six pairs of enantiomers of cannabimimetic compounds on their chromatographic resolution on an amylose tris(3,5‐dimethylphenylcarbamate) chiral stationary phase was studied using various compositions of n‐hexane with 2‐propanol and ethanol. Structural analysis by molecular mechanics was also performed to verify that the 3D conformation within this family of compounds was preserved with substitution. The homologous enantiomeric pairs showed better resolution when there was an additional OH group near the chiral centers (position 7 on the cannabinoid structure). Better resolution was observed also for the enantiomeric pair that had the smaller alkyl side chain. These differences indicated that the additional OH group contributed to a better discrimination of the enantiomers by the chiral sites of the stationary phase and that the bulkier alkyl side chain reduced it. The chromatographic resolution of two enantiomeric pairs of nonclassical cannabinoids HU‐249 and HU‐250, HU‐255 and HU‐256, was compared both in ethanol and 2‐propanol. Both enantiomeric pairs showed relatively high resolution and selectivity, but the rigid benzofuran analogs (HU‐249 and HU‐250) exhibited better resolution using 2‐propanol, in spite of the flexibility of the open chain analog (HU‐255 and HU‐256) and its additional OH group. The elution order of all the cannabinoids was (+)/(−) using both solvents. Unusual solvent effects were displayed by one enantiomeric pair, Δ6‐THC, which was resolved easily using 2‐propanol, but whose elution order reversed with 1% ethanol in the mobile phase. Partial separation was obtained at 5% ethanol [elution order (+)/(−)] and full separation was obtained at 0.5% ethanol [elution order (−)/(+)]. © 1995 Wiley‐Liss, Inc.