bluuebunny/crossref_metadata_2025_split huggingface dataset:
Species variability in the stereoselective N‐oxidation of pargyline
Authors: Hadley Mark R. , Švajdlenka Emil , Damani Lyaquatali A. , Oldham Harriet G. , Tribe Jeanette , Camilleri Patrick , Hutt Andrew J. 
Published: January 2005

AbstractThe monoamine oxidase inhibitor pargyline (N‐benzyl‐N‐methyl‐2‐propynylamine) is known to undergo extensive in vitro microsomal N‐oxidation, thought to be mediated predominantly by the flavin‐containing monooxygenase (FMO) enzyme system. Formation of the pargyline N‐oxide (PNO) metabolite creates a chiral nitrogen centre and thus asymmetric oxidation is possible. This study describes a reverse‐phase high‐performance liquid chromatographic (HPLC) method for the quantitation of PNO and a chiral‐phase HPLC method for the determination of the enantiomeric ratio of PNO. In vitro microsomal N‐oxidation of pargyline was found to be highly steroselective in a number of species, with the (+)‐enantiomer being formed preferentially. This metabolic transformation was stereospecific when purified porcine hepatic FMO was used as the enzyme source. © 1994 Wiley‐Liss, Inc.
Chiral assay methods for lifibrol and metabolites in plasma and the observation of unidirectional chiral inversion following administration of the enantiomers to dogs
Authors: Walters Rodney R. , Hsu Chang‐Yuan L. 
Published: January 2005

AbstractLifibrol, a new drug for the treatment of hypercholesterolemia, contains a stereogenic center bearing a secondary alcohol group. A normal‐phase achiral–chiral HPLC separation of the enantiomers of lifibrol and two of its metabolites was developed and validated for quantitation in dog plasma. A silica and a Chiralcel OD‐H column were operated in series and all six enantiomeric components and internal standard were directly separated. An initial solid‐phase extraction (phenyl) clean‐up step and a column‐switching step to eliminate late‐eluting compounds were also utilized. The solid‐phase extraction step was automated using a robotic system. Assay development, validation, and application of the method to a bioavailability study of the racemate and enantiomers of lifibrol in dogs are described. The lower limit of quantitation was 0.0125 μg/ml for each enantiomer of lifibrol using 200 μl of dog plasma with UV detection (255 nm). In dog plasma following oral or intravenous administration of the racemate, the (R)/(S) ratio of the enantiomers of lifibrol was greater than one and increased with time. Following administration of the individual enantiomers, chiral inversion of the (S)‐enantiomer but not the (R)‐enantiomer was observed. © 1994 Wiley‐Liss, Inc.
Input rate‐dependent stereoselective pharmacokinetics: Effect of pulsatile oral input
Authors: Mehvar Reza 
Published: January 2005

AbstractComputer simulation was used to test the effects of pulsatile oral input on the stereoselectivity in the area under the blood concentration–time curves (AUCs) of the enantiomers of racemic drugs. The effects of input rate determinants, namely, dose, dosage interval, and formulation on the stereoselectivity were investigated under both steady‐state and nonsteady‐state conditions. Simulations were carried out for drugs undergoing Michaelis–Menten hepatic metabolism with different enantiomeric maximum velocity (Vmax) or constant (Km) values. With pulsatile input, the enantiomeric AUC ratios of both types of drugs were dependent on all the determinants of input rate. However, in most cases, the direction of input rate‐dependent changes in the enantiomeric AUC ratios for drugs with different enantiomeric Vmax was opposite of that for drugs with different enantiomeric Km. The direction and magnitude of changes in the enantiomeric AUC ratios were also dependent on the selected dose, dosage interval, and formulation. Further, different conclusions could be reached based on the nonsteady‐state and steady‐state data. Additional simulations were then performed to test the effects of input rate‐dependent stereoselective pharmacokinetics on the bioequivalence of chiral drugs with nonlinear metabolism. These simulations suggested that bioequivalence studies based on the racemic drug measurement may result in erroneous conclusions for the individual enantiomers. The results of this study may be used as a tool for the design of experiments to test the input rate dependence of stereoselective pharmacokinetics and bioequivalence of racemic drugs in animals and humans. © 1994 Wiley‐Liss, Inc.
(R,R)‐N,N′‐Dimethylcyclohexyl‐1,2‐diazaseleno‐phospholidine as a chiral derivatizing agent for the evaluation of chiral alcohols
Authors: House Karen L. , O'Connor Megan J. , Silks Louis A. , Dunlap R. Bruce , Odom Jerome D. 
Published: January 2005

AbstractPreviously, a diazaphospholidine has been synthesized and evaluated as a chiral derivatizing reagent for the determination of the optical purity of chiral alcohols via 31P NMR spectroscopy (Alexakis et al., J. Org. Chem. 57:1224–1237, 1992). Our laboratory is interested in the advantageous and practical applications of 77Se NMR spectroscopic studies in many facets of chemistry and biochemistry. To this end we have used this diazaphospholidine as a starting point and have investigated chiral alcohols coupled to an optically pure diazaselenophospholidine. The diastereomers formed were then evaluated by 77Se NMR spectroscopy, and these results were compared to the 31P NMR results published by Alexakis and co‐workers. It was found that addition of the Se atom produced diastereomers that were air stable and, in many cases, the individual diastereomers could be distinguished by 77Se NMR spectroscopy. Preliminary results indicate that the 77Se nucleus is somewhat more sensitive to remotely disposed chiral centers than is the 31P nucleus. Furthermore, because of their stability, these compounds do not readily decompose and can, therefore, be studied by a variety of chromatographic and spectroscopic techniques. © 1994 Wiley‐Liss, Inc.
π‐Facial hydrogen bonding in the chiral resolving agent 2,2,2‐trifluoro‐1‐(9‐anthryl)‐ethanol and its racemic modification
Authors: Webb Michael L. , Rzepa Henry S. 
Published: January 2005

Abstract2,2,2‐Trifluoro‐(9‐anthryl)‐ethanol (TFAE) has been extensively used, in its pure enantiomeric forms, as a chiral solvating agent in nuclear magnetic resonance spectroscopy (NMR). It has also played an important role in the development of chiral stationary phases in liquid chromatography (LC). X‐ray crystallography of the enantiomeric and racemic crystals shows, in both cases, the formation of an intermolecular hydrogen bond between the OH and the π‐face of one of the rings of the anthracene aromatic system.1 Few examples of such hydrogen bonding have been published previously, and those that have are not as clear cut as in this case. An explanation for the hydrogen bonding is sought using molecular modelling via the PM3 analytically derived molecular electrostatic potentials. Using NMR and dynamic lineshape analysis, the barrier to rotation about the aryl‐carbon bond is estimated, indicating the CCF3 bond to be perpendicular to the anthracene axis in nonpolar solution. This conformation is identical to the conformation in the crystal. Evidence is also presented to support the formation of intermolecular π‐facial hydrogen bonding in TFAE solutions. It is thought that such hydrogen bonding may be implicated in chiral recognition using this compound. © 1994 Wiley‐Liss, Inc.
Effects of alkyl substituents on chiral separation of N‐arylthiazolin‐2‐(thi)‐one atropisomers on tris (p‐methylbenzoyl)cellulose beads and cellulose triacetate: Lipophilicity aspects
Authors: Roussel Christian , Popescu Cristina 
Published: January 2005

AbstractThe determination of lipophilicity of the title compounds allowed treatment of the data for chiral separation (capacity factors) on CTA and CTPB according to these parameters. A linear correlation between In k′(+) and log k′w was found on both CTA and CTPB, as far as the substituents are situated in the plane of the aryl ring or the heterocycle. This correlation with a nonchiral descriptor allows treatment of capacity factors for (−)‐enantiomers as deviations from the lipophilicity line or derived parallels. It results in a clear description of the molecular area affecting enantioselectivity. Application to larger alkyl derivatives shows that the effect of the substituent should be treated on a basis of attractive effect in the case of CTA and on the basis of attractive and repulsive effects for CTPB. © 1994 Wiley‐Liss, Inc.
Use of a new pirkle‐type chiral stationary phase in analytical and preparative subcritical fluid chromatography of pharmaceutical compounds
Authors: Blum Andrew M. , Lynam Kenneth G. , Nicolas Edgar C. 
Published: January 2005

AbstractGood results have been obtained with use of the new bonded chiral stationary phase Whelk‐O 1 in analytical and preparative subcritical fluid chromatography. A wide variety of enantiomeric pairs of compounds with different functional groups that are of pharmaceutical and biological interest have been resolved. This Pirkle‐concept CSP appears to be more rugged than cellulosic phases (e.g., Chiralcel) with regards to solvents and pressure. In comparing the usefulness of the column for SFC versus HPLC chiral analysis, we have observed a clear superiority of SFC in terms of higher speed and efficiency of analysis, and faster method development. This is consistent with our experience with Chiralcel CSPs. With the Whelk‐O 1 we have shown that the effects of temperature and modifier on SFC separations are similar to what has been reported for most other CSPs. We also observed a unique selectivity advantage of SFC for verapamil. We had good success with using a 1‐in. diameter column packed with Whelk‐O 1 to perform preparative SFC separations of a number of enantiomeric mixtures. The advantages of preparative SFC over preparative HPLC will be discussed. The feasibility of preparative SFC is dependent on how well we meet the practical challenges such as sample introduction issues, special hardware requirements due to the high pressure, and fraction collection issues. © 1994 Wiley‐Liss, Inc.
New technique in optical resolutions
Authors: Ács Mária , Mravik András , Fogassy Elemér , Böcskei Zsolt 
Published: January 2005

AbstractThe present paper illustrates the development of an advanced technique in optical resolution. Both of the amphetamine enantiomers can be obtained by a two‐step distillation in nearly quantitative yield without any loss of the resolving agent. It is proved that the second‐order interactions (H‐bond) are sufficient for separation of enantiomers by distillation. © 1994 Wiley‐Liss, Inc.
Distribution of the enantiomers of hydroxychloroquine and its metabolites in ocular tissues of the rabbit after oral administration of racemic‐hydroxychloroquine
Authors: Wainer Irving W. , Chen John C. , Parenteau Heli , Abdullah Sami , Ducharme Julie , Fieger Hiltrude , Iredale Joanna 
Published: January 2005

AbstractThe disposition of the enantiomers of hydroxychloroquine (HCQ) and its major metabolites in ocular tissues of rabbits has been studied. Both albino, New Zealand White (NZW), and pigmented animals were administered daily oral doses of rac‐HCQ, (S)‐HCQ or (R)‐HCQ (20 mg/kg) over 1, 6, or 8 day periods or for 8 days followed by a 7‐day washout period. At the end of the study periods, plasma and whole blood samples were collected and the rabbits were sacrificed. The eyes were collected, the aqueous humor removed with a syringe, and the eyes separated into the cornea, lens, vitreous body, iris, choroid‐retina, sclera, and conjunctiva. The concentrations of (R)‐HCQ, (S)‐HCQ, and their respective metabolites were determined using a validated enantioselective liquid chromatographic assay. The data from these studies indicate that HCQ accumulated in both pigmented and nonpigmented ocular tissues. In the pigmented tissues, HCQ and its metabolites were bound to melanin and the binding was not enantiospecific. In the nonpigmented tissues and in the iris and retina‐choroid of the NZW rabbits, the accumulation appeared to be the result of a reversible and enantioselective binding of HCQ and its metabolites to an unidentified biopolymer present in these ocular tissues. © 1994 Wiley‐liss, Inc.
Pharmacokinetics and pharmacodynamics of hydroxychloroquine enantiomers in patients with rheumatoid arthritis receiving multiple doses of racemate
Authors: Tett Susan E. , McLachlan Andrew J. , Cutler David J. , Day Richard O. 
Published: January 2005

AbstractHydroxychloroquine, a slow acting antirheumatic drug, is administered as the racemic mixture. Blood concentrations of the two enantiomers of hydroxychloroquine were measured in two studies, one study of eight patients, in whom blood and urine concentrations were measured during the first 6 months of therapy with rac‐hydroxychloroquine, and one of 43 patients who had received rac‐hydroxychloroquine therapy for at least 6 months. In the latter study rheumatoid disease activity was also measured. The pharmacokinetics of hydroxychloroquine were found to be enantioselective. The concentrations of (−)‐(R)‐hydroxychloroquine were higher than those of the (+)‐(S)‐antipode in all patients at all time points, although the ratios of the two enantiomers did display a two to three fold variability between patients. Both total and renal clearance were greater for the (+)‐(S)‐enantiomer. From the observational, cross‐sectional study design used, it was not possible to differentiate concentration–effect relationships of the two enantiomers. The 11‐fold range of drug concentrations swamped any effect of variability between patients in enantiomer proportions. Blood concentrations of both enantiomers were significantly higher in groups of patients with less active disease. © 1994 Wiley‐Liss, Inc.
Disposition and absorption of hydroxychloroquine enantiomers following a single dose of the racemate
Authors: McLachlan Andrew J. , Tett Susan E. , Cutler David J. , Day Richard O. 
Published: January 2005

AbstractThe disposition of hydroxychloroquine enantiomers has been investigated in nine patients with rheumatoid arthritis following administration of a single dose of the racemate. Blood concentrations of (−)‐(R)‐hydroxychloroquine exceed those of (+)‐(S)‐hydroxychloroquine following both an oral and intravenous dose of the racemate. Maximum blood concentrations of (−)‐(R)‐hydroxychloroquine were higher than (+)‐(S) ‐hydroxychloroquine after oral dosing (121 ± 56 and 99 ± 42 ng/ml, respectively, P = 0.009). The time to maximum concentration and the absorption half‐life, calculated using deconvolution techniques, were similar for both enantiomers. The fractions of the dose of each enantiomer absorbed were similar, 0.74 and 0.77 for (−)‐(R)‐ and (+)‐(S)‐hydroxychloroquine, respectively (P = 0.77). The data suggest that absorption of hydroxychloroquine is not enantioselective. The stereoselective disposition of hydroxychloroquine appears to be due to enantioselective metabolism and renal clearance, rather than stereoselectivity in absorption and distribution. © 1994 Wiley‐Liss, Inc.
Stereoisomeric flavour compounds LXVIII. 2‐, 3‐, and 4‐Alkyl‐branched acids, part 2: Chirospecific analysis and sensory evaluation
Authors: Karl Volker , Gutser Jutta , Dietrich Armin , Maas Birgit , Mosandl Armin 
Published: January 2005

AbstractEnantioselective GC analysis of 4‐ethyloctanoic and 4‐methylheptanoic acid, using heptakis(2,3‐di‐O‐methyl‐6‐O‐tert‐butyldimethylsilyl)‐β‐cyclodextrin as the chiral stationary phase, is described and the sensory properties of several 4‐alkyl‐branched acids, using gas chromatography‐olfactometry (GC‐O) equipment and octakis(2,3‐di‐O‐methyl‐6‐tert‐butyldimethylsilyl)‐γ‐cyclodextrin as the stationary phase, are evaluated. The chirospecific analysis of various 2‐, 3‐, and 4‐alkyl‐branched acids from commercially available Roman chamomile (Chamaemelum nobile (L.) Allioni), Parmesan cheese, and subcutaneous mutton adipose tissue, using either GC‐GC (MDGC) or GC‐MS analytical methods, is described. © 1994 Wiley‐Liss, Inc.
Separation of the optical isomers of a new 1,4‐dihydropyridine calcium channel blocker (LF 2.0254) by liquid and supercritical fluid chromatography
Authors: Siret Laurent , Macaudiere Pierre , Bargmann‐Leyder Nathalie , Tambute André , Caude Marcel , Gougeon Émile 
Published: January 2005

AbstractThe four optical isomers of a new calcium channel blocker LF 2.0254 (developed by Laboratoires Fournier) are resolved by chromatography using chiral stationary phases. Two methods are proposed: the first one involving two chiral stationary phases [(S)‐N‐(2‐naphthyl)alanine, a Pirkle type CSP and Chiralcel OJ, a cellulose derived CSP] in the liquid chromatographic mode, the second one involving a single CSP (Chiralcel OJ) in the supercritical fluid chromatographic mode. © 1994 Wiley‐Liss, Inc.
Pronase in amino acid technology: Optical resolution of nonproteinogenic α‐amino acids
Authors: Pugniere Martine , Domergue Nicole , Castro Bertrand , Inserm Aldo Previero 
Published: January 2005

AbstractWe describe a practical method to produce pure enantiomers of non‐proteinogenic α‐amino acids by pronase‐catalyzed hydrolysis of their methyl esters. Each of the two pure enantiomers was obtained in high yield, while the reaction conditions were optimized with a view to large scale production. Part of this work was devoted to conceiving an analytical procedure especially designed to monitor the steric course of enzymatic reactions. © 1994 Wiley‐Liss, Inc.
A preliminary pharmacokinetic study of the enantiomers of the terfenadine acid metabolite in humans
Authors: Surapaneni Sekhar , Khalil Shoukry K. W. 
Published: January 2005

AbstractA stereoselective and sensitive achiral/chiral method for the determination of terfenadine acid metabolite in human plasma was developed. The metabolite was separated and quantitated using an achiral chromatographic procedure with a cyano column. The mobile phase was 1 mM sodium acetate buffer (pH 4.0) and acetonitrile (25:75% v/v) at a flow rate of 2 ml/min, at ambient temperature. The stereospecific resolution was accomplished using a chiral‐AGP column and a mobile phase consisting of sodium acetate (0.01 M): methanol (98.7:1.3% v/v), and 20 mM di‐n‐butylamine at a flow rate of 1.2 ml/min. The column temperature was maintained at 32°C. The eluent was monitored at 230 nm (excitation) and 300 nm (emission) with a cut‐off filter at 270 nm. This assay was used for a pharmacokinetic study in five subjects after administration of a single dose of 60 mg of terfenadine. The t½ values of the two enantiomers were similar, but the AUC values of the (+)‐enantiomer were 2.05–2.35 times higher than those of (−)‐enantiomer. © 1994 Wiley‐Liss, Inc.
Direct resolution of ergot alkaloid enantiomers on a novel chiral silica‐based stationary phase
Authors: Flieger Miroslav , Sinibaldi Massimo , Cvak Ladislav , Castellani Loredana 
Published: January 2005

AbstractA new covalently‐bonded, silica‐based stationary phase, using as the chiral selector the 1‐(3‐aminopropyl) derivative of (+)‐(5R,8S,10R)‐terguride, has been developed to resolve optically active isomers by HPLC. Good resolution of structurally related racemic ergot alkaloids were obtained using water‐methanol mixtures as the eluent. Analysis of the influence of the type and concentration of the organic modifier, and the pH of the buffer in the mobile phase allowed the enantioseparation of these compounds to be optimized. Determination of the optical purity of a lisuride‐containig drug is reported. © 1994 Wiley‐Liss, Inc.
Semipreparative enantiomeric separation of a series of putative melatonin receptor agents using tri‐acetylcellulose as chiral stationary phase
Authors: Jansen Johanna M. , Copinga Swier , Gruppen Gert , Isaksson Roland , Witte Dirk T. , Grol Cor J. 
Published: January 2005

AbstractIn order to obtain milligram amounts of the enantiomers of a series of compounds to be tested for binding to the melatonin binding site, a system for semipreparative enantiomeric separation was set up using tri‐acetylcellulose as the chiral stationary phase. Interactions of this class of compounds with tri‐acetylcellulose were examined on an analytical scale with a series of 20 compounds. Apparently, both steric and electrostatic interactions determine retention behavior on tri‐acetylcellulose. Semipreparative separations were carried out for a subset of seven compounds. The purity of the first eluting enantiomer usually was around 99%, whereas the purity of the second eluting enantiomer was slightly less. The system described is easy to use and has the major advantage that a series of compounds can be separated with one technique. The purities obtained are sufficient for a first screen of their affinity. © 1994 Wiley‐Liss, Inc.
Investigations into the chirality of the metabolic sulfoxidation of cimetidine
Authors: Kuzel Ryta A. , Bhasin Satvinder K. , Oldham Harriet G. , Damani Lyaquatali A. , Murphy Jo , Camilleri Patrick , Hutt Andrew J. 
Published: January 2005

AbstractThe individual enantiomers of cimetidine sulfoxide were resolved by preparative chromatography using a Chiralcel OC stationary phase and were characterized by the determination of optical rotation and circular dichroism spectra. Cimetidine sulfoxide was isolated from the urine of two healthy male volunteers following oral administration of cimetidine (400 mg). Urine was collected every 2 h for 12 h postdosing, after which time HPLC analysis indicated negligible recovery of the drug as the sulfoxide. Some 7% of the dose was recovered as cimetidine sulfoxide over this period. The enantiomeric composition of cimetidine sulfoxide was determined by sequential achiral—chiral chromatography using the OC phase. Over the collection period the enantiomeric ratio was found to be constant in all samples at (+/−) of 71 ± 2.5:29 ± 2.5. The enantiomeric composition of cimetidine sulfoxide was also determined in rat urine (24 h) following the administration of cimetidine (30 mg/kg po) to male Wistar rats (n = 7). The enantiomeric ratio in this case was found to be (+/−) 57 ± 2.3:43 ± 2.3. These preliminary data indicate that sulfoxidation of cimetidine is stereoselective with respect to the (+)‐enantiomer and that species variation in enantiomeric composition occurs. © 1994 Wiley‐Liss, Inc.
Enantioselective esterification of 2‐methylbutyric acid catalyzed via lipase immobilized in microemulsion‐based organogels
Authors: Uemasu Isamu , Hinze Willie L. 
Published: January 2005

AbstractChromobacterium viscosum lipase (c.v. lipase) was immobilized in microemulsion‐based órganogels and successfully utilized for the enantioselective esterification of (+/−)‐2‐methylbutynic acid to preferentially form ethyl‐(+)‐2‐methylbutyrate. The reaction time course and enantioselectivity obtained with the organogel—lipase system was compared and contrasted to that achieved in a reversed micellar solution system that contained lipase solubilized in its inner water core as well as that in which powdered lipases were directly dispersed in an organic solvent. The unique properties and potential benefits of the organogel system are discussed. © 1994 Wiley‐Liss, Inc.