bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measurement of the (R)‐ and (S)‐isomers of warfarin in patients undergoing anticoagulant therapy
Authors: McAleer Sarah D. , Chrystyn Henry , Foondun Aboo S. 
Published: January 2005

AbstractAn achiral/chiral high‐performance liquid chromatographic system for the analysis of total warfarin together with the (R)‐ and (S)‐enantiomers in clinical samples has been developed. The achiral analysis is achieved using a C8 column, which is coupled to a chiral stationary phase, α1‐acid glycoprotein (AGP), thereby allowing for analysis of warfarin isomers without interfering serum peaks. A 0.015 M phosphate buffer mobile phase with 15% v/v propan‐2‐ol (pH 7.0) was used on the C8/AGP system. UV analysis at 308 nm was used for quantitation of total warfarin on the C8 column and fluorescence (excitation 300 nm, emission 390 nm) detection was employed for isomer quantitation on the AGP. Retention time of total warfarin on the C8 column was 5.95 min, while that of the (S)‐ and (R)‐warfarin on the AGP column was 10.38 and 12.69 min, respectively. Peak resolution of the warfarin isomers was 1.64. All serum samples were subjected to solid‐phase extraction. Data from two patients in a single dose study indicate that a two‐compartmental model could represent the warfarin concentration—time data with enterohepatic circulation. In some patients studied during steady state therapy, concentrations of (S)‐warfarin were greater than (R)‐warfarin indicating that the clearance of the former is slower in these patients. © 1992 Wiley‐Liss, Inc.
Indirect chiral separation and analyses in human biological fluids of the stereoisomers of a thienothiopyran‐2‐sulfonamide (TRUSOPT), a novel carbonic anhydrase inhibitor with two chiral centers in the molecule
Authors: Matuszewski B. K. , Constanzer M. L. 
Published: January 2005

AbstractThe indirect chiral separation of the four stereoisomers (1)‐‐(4) of a novel carbonic anhydrase inhibitor with two chiral centers in the molecule is reported. The method is based on chemical derivatization of the secondary amino group of the inhibitor with chiral isocyanate, formation of diastereomeric urea derivatives, each with three chiral centers in the molecule, and their separation under nonchiral HPLC conditions. The attempts to separate racemic mixture (1)+(2) from its diastereomeric counterpart (3)+(4) under nonchiral conditions, and to separate enantiomers (1) and (2) directly on a chiral stationary phase (CSP) are also reported. The indirect method was utilized for the assessment of an in vivo inversion of configuration at either one or both chiral centers of the molecule of (1). Analyses of selected whole blood and urine samples from human subjects after multiple bilateral topical ocular dosing with (1) did not reveal the presence of any of the three possible stereoisomers (2)‐‐(4) of (1) indicating that the inversion of configuration at neither one nor two chiral centers of (1) occurs in vivo. © 1992 Wiley‐Liss, Inc.
Absolute configuration of (+)‐cis‐2,3‐dihydro‐2‐[(methylamino)methyl]‐1‐ [4‐(trifluoromethyl)phenoxy]‐1H‐indene hydrochloride, a chiral serotonin uptake inhibitor
Authors: Michals Dawn R. , Smith Howard E. 
Published: January 2005

AbstractThe absolute configuration of (+)‐cis‐2,3‐dihydro‐2[(methylamino)methyl]‐1‐[4‐(trifluoromethyl)pheno<y]‐1H‐indene hydrochloride, the more active enantiomer of a new serotonin inhibitor, was established as 1S,2S. This assignment was based on the application of the benzene sector and chirality rules to the interpretation of the inhibitor's circular dichroism spectrum and the spectra of other related chiral 1‐substituted 2,3‐dihydro‐1H‐indenes. © 1993 Wiley‐Liss, Inc.
Synthesis of (+)‐(R)‐ and (−)‐(S)‐5‐hydroxy‐2‐methyl‐2‐dipropylaminotetralin: Effects on rat hippocampal output of 5‐HT, 5‐HIAA, and DOPAC as determined by in vivo microdialysis
Authors: Höök Berit Backlund , Johansson Anette M. , Hjorth Stephan , Sundell Staffan , Hacksell Uli 
Published: January 2005

AbstractRacemic 5‐methoxy‐2‐methyl‐2‐dipropylaminotetralin (3) has been prepared by a short synthetic route, in which the N,N‐dipropyliminium perchlorate of 5‐methoxy‐2‐tetralone (4) is a key intermediate. Racemic 3 was resolved by crystallization of the corresponding diastereomeric di‐p‐toluoyltartrates. The enantiomeric excess (%ee) of the phenolic derivatives of (+)‐(R)‐ and (−)‐(S)‐3 [(+)‐(R)‐ and (−)‐(S)‐2] was determined by 1HNMR spectroscopic analysis of the corresponding diastereomeric (−)‐(R)‐1,1′‐binaphthyl‐2,2′‐diylphosphoric acid salts utilizing 13C satellites. X‐ray crystallography established the absolute configuration of (−)‐(S)‐2 · HCl. The enantiomers of 2 were tested for hippocampal output of 5‐hydroxytryptamine, 5‐hydroxyindoleacetic acid, and dihydroxyphenylacetic acid in rats by use of in vivo microdialysis. The (−)‐(S)‐enantiomer appeared to affect 5‐HT‐turnover, whereas (+)‐(R)‐2 was inactive. Results obtained provide support for the previously reported hypothesis that the inactivity of (−)‐(S)‐2 at central DA receptors is caused by the steric bulk of the C(2)‐methyl group. This makes it possible to define a “DA D2 receptor essential volume.” © 1993 Wiley‐Liss, Inc.
Stereoselectivity of the aliphatic hydroxylation of 6‐n‐propylchromone‐2‐carboxylic acid in rat and guinea pig
Authors: Darbyshire John F. , Caldwell John 
Published: January 2005

AbstractFollowing administration of 6‐n‐propylchromone‐2‐carboxylic acid (6‐n‐PCCA) (500 μmol/kg) to male rats, three metabolic products were detected and isolated from the 0–24 h urine. All were identified as resulting from oxidation exclusively along the 6‐n‐propyl moiety. Some 66% of the dose was excreted in the 0–24 h urine, 55% of which was 6‐PCCA, with 15% as (6‐1′‐hydroxypropyl)chromone‐2‐carboxylic acid (6‐1′‐HPCCA), 22% as 6‐(2′‐hydroxypropyl)chromone‐2‐carboxylic acid (6‐2′‐HPCCA), and 4% as (6‐3′‐carboxypropyl)chromone‐2‐carboxylic acid (6‐3′‐CPCCA). Derivatization of the methyl esters of the hydroxylated metabolities with S‐α‐methoxy‐α‐(trifuloromethyl)‐phenylacetyl chloride (Mosher's reagent) allowed the evaluation of urinary enantiomeric composition by HPLC and assignment of their absolute configurations by NMR. This was found to be 90:10 (R/S) for 6‐2′‐HPCCA, and 7:93 (R/S) for 6‐1′‐HPCCA. When rats were dosed with the racemic 1′‐ and 2‐hydroxy metabolites; no stereoselective metabolism or excretion was observed. Administration of 6‐n‐PCCA to male guinea pigs revealed that this species was unable to metabolise this compound. © 1993 Wiley‐Liss, Inc.
Chiral discrimination by albumin: A mechanistic study of liquid chromatographic optical resolution of nonaromatic carboxylic acids
Authors: Allenmark Stig 
Published: January 2005

AbstractIn order to get further insight into the mechanism by which bovine serum albumin (BSA) discriminates between enantiomers of organic acids, some radioisotopically labeled, nonaromatic carboxylic acids were studied under varying mobile phase conditions. It was found for a series of N‐alkanoyl‐DL‐[3H]leucines that the D‐enantiomers were much more strongly retained and that the composition of the mobile phase could be adjusted to give very large (α > 20) enantiomeric separation factors. The elution order was consistent with what has been found earlier for other N‐acyl derivatives as well as for N‐arylcarbamoyl derivatives of simple aliphatic amino acids. A marked increase in the hydrophobic interaction of the D‐enantiomers with the chiral phase was found upon a lowering of the mobile phase strength, conditions under which the L‐form was only slightly influenced. These and other results are consistent with a chiral recognition model by which inclusion of the compound in a hydrophobic chiral cavity of BSA with simultaneous charge interaction is assumed to take place and whereby discrimination is determined by the steric bulk and orientation of the α‐substituent. © 1993 Wiley‐Liss, Inc.
HPLC separation of the enantiomers of nicotine and nicotine‐like compounds
Authors: Demetriou Demetrios , Rustemeier Klaus , Voncken Peter , Schepers Georg 
Published: January 2005

AbstractA sensitive and reproducible HPLC method utilizing a commercially available chiral α1‐acid glycoprotein (AGP) phase has been developed to separate and quantify the enantiomers of nicotine. The method is suitable for routine use as indicated by column life. The quantification of (R/S:0.05/99.95)‐nicotine or (R/S:99/1)‐nicotine was possible. In addition, the separation or at least partial separation of the enantiomers of nornicotine and nornicotine‐derived compounds was achieved. © 1993 Wiley‐Liss, Inc.
Dissymmetric calix[4]arenes: Optical resolution of some conformationally fixed derivatives
Authors: Pickard Simeon T. , Pirkle William H. , Tabatabai Moniralsadat , Vogt Walter , Böhmer Volker 
Published: January 2005

AbstractVarious possibilities to obtain intrinsically chiral calix[4]arenes are discussed. The enantiomers of three 1,3‐dietheresters and one monoether compound derived from dissymmetric calix[4]arenes with C4 symmetry were separated by HPLC using chiral stationary phases and characterized by their CD spectra. © 1993 Wiley‐Liss, Inc.
D‐amino acid levels in human physiological fluids
Authors: Armstrong Daniel W. , Gasper Mary , Lee Sun Haing , Zukowski Janusz , Ercal Nuran 
Published: January 2005

AbstractPlasma, urine, cerebrospinal fluid (CSF), and amniotic fluid were examined to determine whether free D‐amino acids were present and if so at what levels. It was found that D‐amino acids exist in all physiological fluids tested, but that their level varied, considerably. The lowest levels of D‐amino acids were usually found in amniotic fluid or CSF (almost always <1% of the corresponding L‐amino acid). The highest levels were found in urine (usually tenth percent to low percent levels). Pipecolic acid seemed to be different from the other amino acids tested in that it was excreted primarily as the D‐enantiomer (often >90%). Correspondingly high levels of D‐pipecolic acid were not found in plasma. Some of the trends found in this work seemed to be analogous to those found in a recent rodent study. © 1993 Wiley‐Liss, Inc.
Stereoselective and isozyme‐selective drug interactions
Authors: Gibaldi Milo 
Published: January 2005

AbstractA surprisingly large number of marketed drugs are racemic mixtures. The pharmacokinetic literature on racemic drugs contains a vast amount of information on drug–drug interactions derived from the measurement of total drug concentrations in plasma and urine. The appreciation of the role of stereochemistry in drug interactions with racemic warfarin resulted in a long‐overdue scientific rigor being applied to the study of drug interactions. It also compelled us to recognize that much of the literature was uninterpretable. A better understanding of oxidative metabolism, particularly the complexity of the cytochrome P‐450 family of enzymes, has also strengthened the scientific basis of drug interactions. We now recognize that investigators and clinicians must consider both stereoselectivity and isozyme selectivity in the study of drug interactions to understand the nature of the interaction so as to more effectively use new and potent drugs. © 1993 Wiley‐Liss, Inc.
Tissue distribution of bupivacaine enantiomers in sheep
Authors: Rutten Albert J. , Mather Laurence E. , McLean Colin F. , Nancarrow Craig 
Published: January 2005

Abstractrac‐Bupivacaine HCl was infused intravenously to constant arterial blood drug concentrations in sheep using a regimen of 4 mg/min for 15 min followed by 1 mg/min to 24 h. At 24 h, arterial blood was sampled, the animal was killed with a bolus of KCl solution, then rapidly dissected and samples were obtained from heart, brain, lung, kidney, liver, muscle, fat, gut, and rumen. Tissue:blood distribution coefficients for (+)‐(R)‐bupivacaine exceeded those of (−)‐(S)‐bupivacaine (P < 0.05) for heart, brain, lung, fat, gut, and rumen by an overall mean of 43%. Blood:plasma distribution coefficients of (−)‐(S)‐bupivacaine exceeded those of (+)‐(R)‐bupivacaine by a mean of 29% and this offset the tissue:blood distribution coefficients so that the previously significant enantioselective differences disappeared. It is concluded that although enantioselectivity of bupivacame distribution is shown by the measured tissue:blood distribution coefficients, it is not shown when tissue:plasma water distribution coefficients are calculated, suggesting that there is no intrinsic difference between the bupivacaine enantiomers in tissue affinity. Sheep given fatal intravenous bolus doses of rac‐bupivacaine had significantly greater concentrations of (+)‐(R)‐bupivacaine than (−)‐(S)‐bupivacaine in brain (P = 0.028) and ventricle (P = 0.036); these could augment the greater myocardial toxicity of this enantiomer found in vitro. © 1993 Wiley‐Liss, Inc.
Enantioselectivity of esterases in human brain
Authors: Yang Shen K. , Huang Amy , Huang Jin‐Ding 
Published: January 2005

AbstractSubcellular fractions of three human brain specimens were found to contain esterase activities which hydrolyzed racemic oxazepam 3‐acetate (rac‐OXA). All three human brain preparations were highly selective toward the S‐enantiomer of rac‐OXA. © 1993 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
Chiral discrimination in nonracemic mixtures of methanephosphonic acid, N,N′‐bis(1‐phenylethyl)diamides
Authors: Ouryupin Andrei B. , Kadyko Mikhail I. , Petrovskii Pavel V. , Fedin Erlen I. 
Published: January 2005

AbstractEnantiomeric (S,S)‐ and (R,R)‐bis(1‐phenylethyl)diamidomethylphosphonates, the phosphorus atom being prochiral, have been synthesized, starting from the methanephosphonic acid dichloride and corresponding chiral amines. The splitting observed in the 31P‐NMR spectra of their nonracemic mixtures may be accounted for the self‐discrimination of chiral species. This effect can be very useful for enantiomeric analysis of amines based on coupling reactions with methanephosphonic acid dichloride. © 1994 Wiley‐Liss, Inc.
Enantioselective separations using capillary electrophoresis
Authors: Rogan Manus M. , Altria Kevin D. , Goodall David M. 
Published: January 2005

AbstractThe preconditions are outlined for enantioselective separations in capillary electrophoresis (CE) with chiral selectors as additives to the background electrolyte. Free solution capillary electrophoresis conditions are characterised by a single solution phase. Chiral separations are reviewed by selector type (chiral ligand exchange, cyclodextrins, crown ethers, glycoproteins) with the extensive studies on cyclodextrins grouped into sections on amino acids, pharmaceuticals, and speciality chemicals, optimisation, biological fluids, and quantitative aspects. In micellar electrokinetic capillary chromatography, enantioselective discrimination occurs by partition in a two‐phase system, with a chiral micellar phase as selector. Optimum separation conditions can be readily predicted for a given selector–selectand combination, and absolute values of binding constants determined by CE. Advantages of CE in comparison with HPLC using a chiral stationary phase include robust, rapid assays and the use of small volumes of aqueous solutions; disadvantages include less favourable detection limits. © 1994 Wiley‐Liss, Inc.
HPLC with carbohydrate carbamate chiral phases: Influence of chiral phase structure on enantioselectivity
Authors: Matlin Stephen A. , Tiritan M. Elizabeth , Crawford Andrew J. , Cass Quezia B. , Boyd Derek R. 
Published: January 2005

AbstractThe enantioselective resolution of trans‐stilbene oxide and of 23 chiral sulfoxides was investigated on cellulose and amylose tris(arylcarbamate) stationary phases coated on aminopropylated 7 μm spherical silica with 500 Å diameter pores. Cellulose tris‐(3,5 dimethylphenylcarbamate) showed good resolving power for many of the sulfoxides and amylose tris‐(3,5 dimethoxyphenylcarbamate) showed advantages for the resolution of certain sulfoxides which were not separated on other phases. © 1994 Wiley‐Liss, Inc.
The origin of chirality in protein amino acids
Authors: Chela‐Flores Julian 
Published: January 2005

AbstractWe discuss the origin of the chirality of protein amino acids from the point of view of a phase transition from a racemic mixture into an optically pure state. We assume that Bose–Einstein condensation may act as an amplification mechanism. The original theory is due to Salam. We suggest a new role for the phase transition. Following Quack we distinguish parity violation of two kinds (de facto and de lege symmetry breaking). While the Salam phase transition corresponds to parity violation of the second kind (de lege), the phase transition we discuss in this work corresponds to parity violation of what we may call a third kind. This is suggested by recent experimental phenomena which correlate chiral symmetry breaking and pattern formation (spontaneous symmetry breaking that separates an initial racemic mixture into right‐ and left‐handed space domains by means of a substrate). Tentative comments are given on the eventual design of possible experiments that may test this new hypothesis. © 1994 Wiley‐Liss, Inc.
Racemisation of drug enantiomers by benzylic proton abstraction at physiological pH
Authors: Pepper Christopher , Smith H. John , Barrell Kevin J. , Nicholls Paul J. , Hewlins Michael J. E. 
Published: January 2005

AbstractThe enantiomers of the aromatase inhibitors 3‐(4‐aminophenyl)‐pyrrolidine‐2,5‐dione (WSP‐3, II), its N‐pentyl derivative (III), and the antifungal econazole (IV), all possessing a benzylic proton at the chiral centre, are rapidly racemised in vitro in phosphate buffer (0.01 M) at pH 7.4 and 23°C with t½ values of 7, 6, and 5 h respectively. In vivo studies in rats show that (+)‐econazole is racemised after intraperitoneal injection with t½ = 1.24h. The enantiomers of the antifungal 1‐[(benzofuran‐2‐yl)‐4‐chlorophenylmethyl] imidazole (V) were stable at pH 7.4, attributable to steric hindrance to carbanion formation in the racemisation step. © 1994 Wiley‐Liss, Inc.
Enantioselective disposition of oral amlodipine in healthy volunteers
Authors: Laufen Heinrich , Leitold Máagtyá Ags 
Published: January 2005

AbstractPlasma concentrations of (R)‐ and (S)‐amlodipine were measured after single oral administrations to 18 healthy volunteers of 20 mg amlodipine racemate. The contribution of the pharmacologically active (S)‐enantiomer to the concentrations of total amlodipine (sum of enantiomers) was significantly higher than that of the inactive (R)‐enantiomer, with mean values of 47% R to 53% S for the Cmax and 41% R to 59% S for the AUC (range between 24% R:76% S and 50% R:50% S). The oral clearance of the active (S)‐form was subject to much less intersubject variation (25% CV) than that of the inactive (R)‐form (52% CV). (R)‐Amlodipine was more rapidly eliminated from plasma than (S)‐amlodipine, with mean terminal half‐lives of 34.9 h (R) and 49.6 h (S). The terminal half‐lives of total amlodipine (mean 44.2 h) were strongly correlated with—and thus highly predictive for—the half‐lives of the (S)‐enantiomer. It is proposed that the observed enantioselectivity of oral amlodipine is due to differences in the systemic blood clearance of the enantiomers. © 1994 Wiley‐Liss, Inc.
A nuclear magnetic resonance study of the diastereoisomer complexes formed between a terguride derivative and naproxen
Authors: Castellani Loredana , Flieger Miroslav , Mannina Luisa , Sedmera Petr , Segre Anna Laura , Sinibaldi Massimo 
Published: January 2005

Abstract1H NMR (600 MHz) measurements of chemical shift changes were made in acidified (DCI) CD3OD/D2O 1:9 v/v equimolar solutions of (S)‐ and (R,S)‐6‐methoxy‐α‐methyl‐2‐naphthaleneacetic acid (naproxen) in the presence of 1‐(3‐aminopropyl)‐(5R,8S,10R)‐terguride (AMP‐TER). The most significant bonding interactions concurring to the formation of diastereoisomer complexes are seen as chemical shifts in proximity to the positively charged nitrogen N(6)‐CH3 and of H(12), H(13), H(14) protons of the ergoline skeleton, both the adducts having an electrostatic term and different π–π stabilizing interactions. Chemical shift data exclude any contribution of the aminopropyl chain to the chiral recognition mechanism. These findings provide an experimental basis for the enantiodiscriminative process accounting for the observed chromatographic resolutions of arylcarboxylic acids on chiral stationary phases derived from AMP‐TER. © 1994 Wiley‐Liss, Inc.
Kinetic resolution of esters of amino acids in t‐butanol containing 5% water catalyzed by a stable industrial alkaline protease
Authors: Chen Shui‐Tein , Huang Wen‐Hong , Wang Kung‐Tsung 
Published: January 2005

AbstractWe developed a procedure for the resolution of esters of amino acids in 95% t‐butanol, followed by saponification of the unreacted esters to afford both enantiomers with high yield and optical purity. The hydrolysis, catalyzed by alkaline protease, was conducted in a mixture of t‐butanol (95%) and water (5%) at 25°C, with a pH controlled at pH 8.5 by the addition of NaOH (2 M). The hydrolyzed L‐amino acid, which was insoluble under these conditions, precipitated during the course of hydrolysis. After separation of the precipitate, the pH of the filtrate was adjusted to 11.5 to saponify the unreacted ester. The D‐antipode precipitated at pH 6.2–6.5. Both optically pure antipodes were obtained with high enantiomeric excesses and yields by simple filtration. © 1994 Wiley‐Liss, Inc.
Assignment of absolute configuration to an improved enantioselective naproxen selector
Authors: Pirkle William H. , Welch Christopher J. , Wilson Scott R. 
Published: January 2005

AbstractAssignment of absolute configuration to a recently developed chiral selector useful in the separation of the underivatized enantiomers of naproxen and other nonsteroidal anti‐inflammatory drugs (NSAIDs) is described. Circular dichroism, 1H NMR, and X‐ray diffraction have been used to confirm the original assignment which was based solely upon elution orders from HPLC chiral stationary phases. All of these techniques agree in the assignment of the (S,S) absolute configuration to the enantiomer of the chiral selector which associates preferentially with (S)‐naproxen. © 1994 Wiley‐Liss, Inc.
Simultaneous monitoring of the enantiomeric purities of both substrate and product in the enzymatic resolution of (R,S)‐2‐acetoxy‐3‐bromopropyl para‐toluenesulfonate by HPLC chiral column chromatography
Authors: Yin Grace F.S. , Chang Y. G. , Kiang C. M. , Chen G. M. 
Published: January 2005

AbstractThe enantiomeric purities of both substrate, 2‐acetoxy‐3‐bromopropyl para‐toluenesulfonate (I), and product, 2‐hydroxy‐3‐bromopropyl p‐toluenesulfonate (II) were examined in one analysis. The enzymatic resolution was conducted by Amano lipase AK and the enantiomeric excess as well as the conversion rate were monitored by HPLC analysis utilizing a Chiralcel OD column. After 7 h of reaction, HPLC results indicated that the enantiomeric purities of both substrate (I) and product (II) were greater than 95% and the conversion rate was around 55%. © 1995 Wiley‐Liss, Inc.
Protein binding investigation by difference circular dichroism: Native and acetylated human serum albumins
Authors: Bertucci Carlo , Viegi Alessandro , Ascoli Giorgio , Salvadori Piero 
Published: January 2005

AbstractA modified albumin was prepared by selective reaction of Lys199 with acetyl salicylic acid. Protein binding investigation was carried out on native and modified proteins by difference circular dichroism (ΔCD). Acetylation of Lys199 reduces significantly the effects of the interaction between drugs in the stereoselective HSA binding at specific binding areas. © 1995 Wiley‐Liss, Inc.