bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma protein binding of ketoprofen enantiomers in man: Method development and its application
Authors: Hayball P. J. , Nation R. L. , Bochner F. , Newton J. L. , Massy‐Westropp R. A. , Hamon D. P. G. 
Published: January 2005

AbstractThe protein binding of ketoprofen enantiomers was investigated in human plasma at physiological pH and temperature by ultrafiltration. 14C‐labelled (RS)‐ketoprofen was synthesized and purified by high‐performance liquid chromatography and utilized as a means of quantifying the unbound species. In vitro studies were conducted with plasma obtained from six healthy volunteers. The plasma was spiked with (R)‐ketoprofen alone, (S)‐ketoprofen alone, and (RS)‐ketoprofen in the enantiomeric concentration range of 1.0 to 19.0 μg/ml. The plasma protein binding of ketoprofen was nonenantioselective. At a racemic drug concentration of 2.0 μg/ml the mean (± SD) percentage unbound of (R)‐ketoprofen was 0.80 (± 0.15)%. The corresponding value for (S)‐ketoprofen, 0.78 (± 0.18)%, was not statistically different (P > 0.05). At this racemic drug concentration (2.0 μg/ml) the percentage unbound of each enantiomer was unaffected (P > 0.05) by the presence of the glucuronoconjugates of ketoprofen (10 μg/ml) in plasma. At clinically relevant concentrations, the plasma binding of ketoprofen did not exhibit enantioselectivity or concentration dependence nor was the binding of either enantiomer influenced by its optical antipode (P > 0.05).
Enantiomeric separation of 2‐(phenoxy)propionate derivatives by chiral high‐performance liquid chromatography
Authors: Lin Shu‐Ling , Chiou Aih‐Jing , Wu Shih‐Hsiung , Wang Kung‐Tsung 
Published: January 2005

Abstract2‐(Phenoxy)propionate derivatives were separated on three chiral columns, OD, OK, and chiral‐2 columns. The chlorine substitution in the phenyl ring and the alcohol moiety of the ester groups of the derivatives had great influence for separation on the OD and OK columns, but little effect on the chiral‐2 column.
Stereoselective effect of phenprocoumon enantiomers on the binding of benzodiazepines to human serum albumin
Authors: Fitos Ilona , Simonyi Miklós 
Published: January 2005

AbstractThe effect of phenprocoumon enantiomers on the stereoselective binding of 3‐substituted 1,4‐benzodiazepines to human serum albumin (HSA) was studied by chromatography on HSA‐Sepharose column. (S)‐Phenprocoumon exerts stereoselective allosteric interaction on the binding of benzodiazepines. The structural requirements of enhanced stereoselectivities are similar to those found previously with (S)‐warfarin.
Chirality evaluation in flavour and essential oil analysis
Authors: Mosandl Armin , Askari Christiane , Hener Uwe , Juchelka Dieter , Lehmann Detmar , Kreis Peter , Motz Christine , Palm Ursula , Schmarr Hans‐Georg 
Published: January 2005

AbstractThe simultaneous stereodifferentiation of all aromarelevant 4(5) alkylsubstituted γ(δ)‐lactones is described, using enantioselective multidimensional gas chromatography (MDG), and the column combination OV 1701/octakis(3‐O‐butyryl‐2,6‐di‐O‐pentyl)‐γ‐cyclodextrin. The method is applicated to the lactone flavour compounds of fruits, indicating the advance to the analytical differentiation between “natural” and “nature‐identical” aromas. Modified cyclodextrins are also proved to be powerful tools in the chirospecific CGC analysis of monoterpenoid constituents of essential oils. Optical purity control is discussed as an indicator for their natural origin.
Determination of the enantiomeric purity of (−−) 2‐(N‐propyl‐n‐2‐thienylethylamino)‐5‐hydroxytetralin (n‐0923) by chiral stationary phase HPLC
Authors: Witte Dirk T. , Franke Jan‐Piet , Swart Pieter J. , De Zeeuw Rokus A. 
Published: January 2005

AbstractThe determination of the enantiomeric impurity, i.e., the percentage of (+) N−0437 (= N−0924) in several batches of (−−) N‐0437 (= N‐0923) by chiral HPLC is described. Enantiomeric impurities were calculated based on the peak areas of the two baseline separated enantiomers in the chromatogram. The enantiomeric impurities found in different batches ranged from 0.02% to 0.11%. Calibration curves of the two isomers of N‐0437 (Fig. 1,) were made twice to study the reproducibility and linearity of the method. The absorbance ratio, N‐0923/N‐0924, was found to be 1.02 with a relative standard deviation (RSD) of 9% over the whole concentration range used for the calibration curves.
Stereoselective biliary elimination of disopyramide and mono‐N‐desisopropyldisopyramide in humans
Authors: Corre Pascal Le , Malledant Yannick , Chevanne Francois , Sado Pierre , Verge Roger Le 
Published: January 2005

AbstractThe results of a previous pharmacokinetic study of disopyramide (DP) enantiomers in humans suggested that DP and/or mono‐N‐desisopropyldisopyramide (MND) may show stereoselective extrarenal elimination. Thus, the present study investigates the biliary elimination of DP and MND enantiomers in three patients who had undergone cholecystectomy for cholelithiasis. DP and MND enantiomers displayed biliary elimination. In both subjects, this elimination pathway showed the same characteristics: (1) biliary elimination of DP and MND was stereoselective, (2) the stereoselectivity was opposite to that observed for the metabolic and renal elimination pathways, i.e., the elimination of the (−)‐(R)‐enantiomer was higher than that of the (+)‐(S)‐enantiomer, and (3) biliary elimination of MND was higher than that of DP, for both enantiomers. Estimates of the relative contribution of the biliary clearance in the total clearance of DP and MND indicated that this elimination pathway was secondary, especially for DP. The biliary clearance (expressed as % of total clearance) was 1.9 to 4.0% for (−)‐(R)‐DP, 1.2 to 1.7% for (+)‐(S)‐DP, 7.8 to 22.9% for (−)‐(R)‐MND, and 5.2 to 10.5% for (+)‐(S)‐MND.
Optically‐Active compounds via biocatalytic methods
Authors: Sih Charles J. , Gu Qu‐ming , Holdgrün Xenia , Harris Keith 
Published: January 2005

AbstractDifferent approaches to improve the enantioselectivity of biocatalytic systems are presented. These methodologies have been successfully applied to the preparation of optically active dihydropyridine, calcium antagonists, and cis‐3‐hydroxy‐6‐acetoxy‐cyclohex‐1‐ene, a valuable chiral building block for natural products synthesis. The phenomenon of enantioselective inhibition is described and several new heterocyclic amines have been shown to be effective enantioselective inhibitors in the Candida lipase system.
Enzymatic resolutions of α‐ and β‐hydroxypropionic acid esters
Authors: Gruber‐Khadjawi M. , Hönig H. , Weber H. 
Published: January 2005

AbstractThe synthesis of some acyloxy‐methoxy‐cinnamic acid derivatives, azidohydroxy butanoates, and azidohydroxy butanedioates in enantiomerically pure form is presented. Racemic diastereomerically pure educts were prepared in few steps. These racemates are resolved with lipases from Candida cylindracea (CC) and Pseudomonas fluorescens (P).
Optical resolution of β‐lactams on 1‐phenylethylcarbamates of cellulose and amylose
Authors: Kaida Yuriko , Okamoto Yoshio 
Published: January 2005

AbstractOptical resolution of six β‐lactams was examined by HPLC using chiral stationary phases consisting of tris((R)‐, (RS)‐, and (S)‐1‐phenylethylcarbamate)s of cellulose and amylose. All β‐lactams were optically resolved at least by one of the carbamates. Amylose tris((S)‐1‐phenylethylcarbamate) showed high optical resolving abilities for some β‐lactams.
Enantioselective pharmacokinetics of ethotoin in humans following single oral doses of the racemate
Authors: Hooper Wayne D. , O'shea Nerida J. , Qing Mi Sui 
Published: January 2005

AbstractRacemic ethotoin (1000 mg) was administered orally as a single dose to six healthy adult volunteers. Blood samples were collected at appropriate times for 120 h following the dose. Ethotoin was quantified enantioselectively in plasma using a novel chiral column HPLC procedure. One of the enantiomers of the chiral metabolite, 5‐phenylhydantoin, was also quantified in the HPLC method. The Cmax and AUC0—∞ values for (+)‐(S)‐ethotoin were significantly greater than those for (—)‐(R)‐ethotoin (ratio of mean AUC0—∞ values 0.88), but the elimination half‐lives of the isomers were virtually identical [12.35 ± 5.15 h for (—)‐(R)‐thotoin; 12.28 ± 5.34 h for (+)‐(S)‐ethotoin]. Parameters derived from AUC0—∞ (Cl0/F and Varea/F) also differed slightly between the isomers. The data were interpreted as indicating a small difference in the absorption of the two isomers; it seemed unlikely, in terms of the identical elimination rates, that their metabolic profiles would differ greatly. The 5‐phenyl‐hydantoin was eliminated with a significantly longer half‐life (18.69 ± 6.11 h) than that of ethotoin. Enantioselectivity in the pharmacokinetics of ethotoin is therefore a minor issue. © 1992 Wiley‐Liss, Inc.
Liquid chromatographic separation of chiral diarylcarbinols
Authors: Caccamese Salvatore , Maccagnano Maria Grazia 
Published: January 2005

AbstractThe direct HPLC separation of three chiral carbinols of general formula Mesityl‐CH(OH)‐Aryl has been achieved using Pirkle (R)‐DNBPG ionic or covalent columns and, for Aryl = o‐tolyl, on a Chiralpak OP(+) phase. It is apparent that steric hindrance and hydrogen bonding play important roles in chiral recognition. Two compounds structurally very similar but lacking the hydroxyl group were not resolved in their enantiomeric pairs. © 1992 Wiley‐Liss, Inc.
Structural characteristics of cyclodextrins in the solid state
Authors: Lipkowitz Kenny B. , Green Karen , Yang Jia‐An 
Published: January 2005

AbstractA comparison of α‐, β and γ‐cyclodextrins in the solid state is made. Monomeric features analyzed include orientations of primary hydroxyl groups and pyran ring pucker. Macromolecular features examined include planarity of the oligomer, tilting of pyran rings, and, deviation from Cn symmetry where n = number of monomers. The mean values and standard deviations of these shape descriptors are given for cyclodextrins with and without guests embedded in their interiors. Molecular mechanics calculations using the MM2, AMBER, and CHARMM force fields show that most solid state cyclodextrins are trapped in high‐energy conformations relative to the most stable forms found in this study. © 1992 Wiley‐Liss, Inc.
Spontaneous racemization of chlorthalidone: kinetics and activation parameters
Authors: Severin Gregory 
Published: January 2005

AbstractThe enantiomers of chlorthalidone (CTD) and a minor, achiral dehydration product, δ2‐CTD, are shown to exist in dynamic equilibrium in aqueous media through a carbonium ion intermediate. The barrier to inversion at carbon is low for an uncatalyzed system: ΔG‡ = 21.6 kcal/mol. This behavior extends to other 3‐hydroxy‐3‐phenylphthalimidines (HPPs), with formation of the analogous Δ2‐HPP blocked by alkyl substitution at the 2‐nitrogen. © 1992 Wiley‐Liss, Inc.
Enzymes in stereoselective pharmacokinetics of endogenous substances
Authors: Marzo A. , Cardace G. , Arrigoni Martelli E. 
Published: January 2005

AbstractThe use of enzymes to assay individual components of the L‐carnitine family in pharmaceuticals, foodstuffs, and biological fluids with various forms of detection is reviewed. The most useful enzyme in the assay of compounds of the L‐carnitine family is carnitine acetyl transferase (CAT), which catalyses the reversible interconversion of L‐carnitine and its short‐chain acyl esters. CAT can be used in one or more coupled reactions combined with U.V., or radiolabelled detection, or combined with HPLC, allowing, enantioselective, structurally specific, and, in the case of radiolabelled tracing, highly sensitive assays to be carried out. When compared with chromatographic separation of enantiomers or diastereoisomers, enantioselective enzyme mediated assays may be cheaper, more sensitive, and simpler, but they do not allow the nonpreferred isomer to be assayed. Consequently, they are appropriate for the specific assay of endogenous enantiomeric substrates of the enzyme concerned, in biological samples. The analysis of the other enantiomer in raw materials or in pharmaceuticals must be more properly approached by enantioselective chromatographic methods.
Direct enantiomeric separation of β‐blockers on ChyRoSine‐a by supercritical fluid chromatography: Supercritical carbon dioxide as transient in situ derivatizing agent
Authors: Siret L. , Bargmann N. , Tambuté A. , Caude M. 
Published: January 2005

AbstractThe direct enantiomeric separation of a series of β‐blockers has been carried out on two chiral stationary phases (CSPs) derived from 3,5‐dinitrobenzoyl tyrosine: the commercially available ChyRoSine‐A and a recent improved version of this CSP.Using supercritical fluid chromatography (SFC), facile separations are achieved (1.1 <Rs <7) within short analysis times. The parameters affecting the enantioselectivity (temperature, pressure, mobile phase nature, solute structure) have been investigated. The optimal mobile phase consists in a mixture of carbon dioxide‐methanol‐propylamine at 25°C. The solute structure has a great influence on the enantioselectivity. For instance, both amine and hydroxyl protons are necessary for chiral discrimination to occur. Furthermore, the steroselectivity value is directly connected to the amine substituent steric bulkiness.Surprisingly, these solutes are poorly resolved using normal phase liquid chromatography (NPLC). Accordingly, the specific influence of carbon dioxide on the enantiomeric separation of 1,2‐amino‐alcohols has been investigated using various techniques such as nuclear magnetic resonance (NMR) or molecular modelisation. It has been shown that carbon dioxide acts as a complexing agent toward the amino‐alcohol by setting up of a bridge with the hydroxyl and the amine protons of the solute. In that way, the resulting complex possesses lower acido‐basic properties and a higher conformational rigidity, responsible for chiral discrimination.
Resolution of terfenadine enantiomers by β‐cyclodextrin chiral stationary phase high‐performance liquid chromatography
Authors: Weems Henri , Zamani Kaveh 
Published: January 2005

AbstractEnantiomers of terfenadine were resolved by high‐performance liquid chromatography (HPLC) using a chiral stationary phase (CSP) column packed with β‐cyclodextrin (β‐CD) covalently bound to silica. Separation was achieved in both the reverse phase and normal phase modes. Resolution of enantiomers was confirmed by ultraviolet‐visible absorption, circular dichroism, and mass spectral analysis.
A proposal for the representation of the stereochemistry of quadrivalent centers
Authors: Lin Shu‐Kun 
Published: January 2005

AbstractThe broken wedge, broken line, solid bar, and broken bar are either not reasonable or can be replaced by only one type of solid wedge in the stereochemical formulation. A convention based on a one‐wedge symbolization is proposed, where a or b is used instead of c, d, e, f, g, or h. © 1992 Wiley‐Liss, Inc.
Application of antibody‐mediated extraction for the stereoselective determination of the active metabolite of loxoprofen in human and rat plasma
Authors: Takasaki Wataru , Tanaka Yorihisa 
Published: January 2005

AbstractAntibody‐mediated extraction followed by chiral high‐performance liquid chromatography (HPLC) was applied to stereoselective determination in human and rat plasma of the active metabolite [(2S,1]R,2[S)‐trans‐alcohol] with three chiral centers of Loxoprofen, a 2‐arylpropionic acid antiinflammatory agent after oral administration. Antiserum against the (1'R,2'S)‐cyclopentanol moiety was obtained from a rabbit immunized with bovine serum albumin conjugate linked to the propionic acid moiety, in which another chiral center is located. Then, the immunoglobulin G purified by a protein A column was coupled to BrCN‐activated Sepharose 4B. Plasma samples were applied to the immobilized antibody column. After washing the column to remove unrequired stereoisomers, a mixture of two diastereomers whose configurations were 1'R,2'S in the cyclopentanol moiety was extracted with 95% methanol. The solvent was evaporated and the residue was derivatized with (+)‐(R)‐1‐(1‐naphthyl)ethylamine as a chiral reagent to separate the diastereomers by HPLC. This combined analytical method showed the stereoselective metabolism of Loxoprofen in human, that is, 64% of the total amount of four trans‐alcohol stereoisomers was in the 2S, 1'R,2'S form, which is the active metabolite. This phenomenon was also observed in rats given Loxoprofen and its (2S)‐ and (2R)‐isomers, and is explained by stereoselective ketone reduction of Loxoprofen to the (1'R,2'S)‐trans‐alcohol and inversion from 2R to 2S in the propionic acid moiety. Antibody‐mediated extraction should be a selective and simple clean‐up method for determining haptens with complicated structures, combined with an appropriate analytical method. © 1992 Wiley‐Liss, Inc.
Resolution of the enantiomers of drugs containing amino alcohol structure after derivatization with bromoacetic acid
Authors: Gübitz G. , Pierer B. , Wendelin W. 
Published: January 2005

AbstractThe separation of the enantiomers of drugs containing an amino alcohol structure like adrenergic drugs or β‐blockers is described. The compounds are resolved on chiral ligand‐exchange chromatography phases after derivatization with bromoacetic acid. © 1992 Wiley‐Liss, Inc.
Stereochemical studies of chiral h‐1 antagonists of histamine: The resolution, chiral analysis, and biological evaluation of four antipodal pairs
Authors: Casy A.F. , Drake A.F. , Ganellin C.R. , Mercer A.D. , Upton C. 
Published: January 2005

AbstractThe resolution of the H‐1 antihistamines chloropheniramine, dimethindene, carbinoxamine, and mebrophenhydramine is described. The optical purity of antipodal products is investigated by chiral HPLC (use of α1 ‐acid glycoprotein and β‐cyclodextrin columns) and NMR (spectra of β‐cyclodextrin inclusion complexes). Configurational relationships among the group are reviewed and assignments are confirmed and extended by circular dichroism evidence. Affinity constants of antipodal pairs for guinea pig ileum and cerebellum sites, determined by gut bath and binding experiments respectively, are reported together with some in vivo tests in man for central effects. Results are discussed in terms of configurational requirements for activity and variations in antipodal potency ratios within the group. © 1992 Wiley‐Liss, Inc.
Strategy combining chiral chromatography with β‐cyclodextrin and stereospecific enzyme reaction detection with hydroxysteroid dehydrogenases for resolving steroid epimers
Authors: Lam S. , Malikin G. 
Published: January 2005

AbstractSteroids are chiral molecules with multiple stereogenic centers. Studies of their intermediary metabolism often require analytical techniques to separate the isomers and determine their stereochemistry. Methods for resolving steroid stereoisomers by HPLC using β‐cyclodextrin in the mobile phase are reported. Even with the improved selectivity of cyclodextrin chromatography, not all isomers within a steroid series can be resolved. Additional specificity is achieved by reaction detection using postcolumn reactors containing hydroxysteroid dehydrogenases stereospecific for the configuration of the hydroxy functions of steroids. The enzymes catalyze the oxidation of hydroxysteroids and reduction of the coenzyme NAD to NADH. NADH, which is highly fluorescent, is detected at the nanogram levels. Isomers not separated by chromatography were effectively resolved by reaction detection with stereospecific enzymes. © 1992 Wiley‐Liss, Inc.
Preparative resolution of some 5,5‐hydantoin derivatives via formation of diastereoisomeric salts
Authors: Coquerel Gérard , Petit Marie‐Noëlle , Bouaziz Roger , Depernet Dominique 
Published: January 2005

AbstractSeveral preparative resolutions of 5,5‐disubstituted hydantoins have been achieved via fractional crystallization of diastereoisomeric salts. The process can be extended by making use of the difference between the variation of solubilities of the hydantoins and their salts with α‐methylbenzylamine as a function of the alkalinity of the medium. Optimization for each resolution procedure involves a refinement of the excess amount of base needed. © 1992 Wiley‐Liss, Inc.
Application of γ‐cyclodextrin to enantiomeric purity determination of a new 2‐amino‐tetralin derivative by 1H‐NMR spectroscopy
Authors: Redenti Enrico , Fronza Giovanni , Bovis Giovanni , Ventura Paolo 
Published: January 2005

Abstractγ‐Cyclodextrin was used to perform chiral discrimination of (±)‐5,6‐diisobutyroyl‐2‐methylaminotetralin hydrochloride by 1H‐NMR; the 95% enantiomeric excess of the (–)‐isomer was determined successfully. © 1992 Wiley‐Liss, Inc.
Glutathione conjugation and pharmacokinetics of 2‐bromo‐3‐phenylpropionic acid in vitro and in the rat in vivo
Authors: Wilco Snel C.A. , Mahadevan Sivi , Polhuijs Martine , Mulder Gerard J. 
Published: January 2005

AbstractGlutathione (GSH) conjugation of the chiral compound 2‐bromo‐3‐phenylpropionic acid (BPP) was studied in vitro and in the rat in vivo. GSH conjugation of BPP, catalyzed by a mixture of glutathione‐S‐transferases (GST's) from rat liver cytosol in vitro, was stereoselective: at a substrate concentration of 250 μM, (R)‐BPP was more rapidly conjugated than (S)‐BPP (R/S‐ratio = 2.6). The blood elimination kinetics of the separate BPP enantiomers and the biliary excretion kinetics of the corresponding GSH conjugates were studied in the rat in vivo after administration of (R)‐ or (S)‐BPP at a dose level of 50 μmol/kg. Elimination of (R)‐BPP from blood was faster than that of (S)‐BPP: half lives were 9 ± 2 min for (R)‐BPP and 13 ± 1 min for (S)‐BPP. The biliary excretion rate of the GSH conjugate of (R)‐BPP declined monoexponentially, while that of the GSH conjugate of (S)‐BPP displayed a biphasic profile. Half lives of excretion were 13 ± 1 for the GSH conjugate of (R)‐BPP, and 11 ± 2 for the GSH conjugate of (S)‐BPP (second phase). The first phase in the biliary excretion of the GSH conjugate of (S)‐BPP could not be attributed to capacity limitation of biliary transport carriers as higher excretion rates were attained upon administration of higher doses (100 and 200 μmol/kg) of ((S)‐BPP). The blood elimination profiles of (R)‐ and (S)‐BPP differed greatly from the biliary excretion profiles of the corresponding GSH conjugates. This suggests that the kinetics of BPP conjugate excretion are determined by other processes than hepatic GSH conjugation. © 1992 Wiley‐Liss, Inc.
Synthetic D‐ and L‐enantiomers of 2,2‐difluoro‐2‐deoxy‐myo‐inositol 1,4,5‐trisphosphate interact differently with myo‐inositol 1,4,5‐trisphosphate binding proteins: Identification of a potent small molecule 3‐kinase inhibitor
Authors: Safrany Stephen T. , Sawyer Deborah A. , Nahorski Stefan R. , Potter Barry V.L. 
Published: January 2005

AbstractThe ability of two enantiomeric fluoro‐analogues of D‐myo‐inositol 1,4,5‐trisphosphate [Ins(1,4,5)P3] to mobilize intracellular Ca2+ stores in SH‐SY5Y neuroblastoma cells has been investigated. (—)‐D‐2,2‐difluoro‐2‐deoxy‐myo‐Ins(1,4,5)P3 [D‐2,2‐F2‐Ins(1,4,5)P3] was a full agonist [EC50 0.21 μM] and slightly less potent than D‐Ins(1,4,5)P3 [EC50 0.13 μM]. (+)‐L‐2,2‐F2Ins(1,4,5)P3 was a very poor agonist, confirming the stereospecificity of the Ins(1,4,5)P3 receptor. D‐2,2‐F2‐Ins(1,4,5)P3 mobilized Ca2+ with broadly similar kinetics to Ins(1,4,5)P3 and was a substrate for Ins(1,4,5)P3 3‐kinase inhibiting Ins(1,4,5)P3 phosphorylation (apparent Ki = 10.2 μM) but was recognised less well than Ins(1,4,5)P3. L‐2,2‐F2‐Ins(1,4,5)P3 was a potent competitive inhibitor of 3‐kinase (Ki = 11.9 μM). Whereas D‐2,2‐F2‐Ins(1,4,5)P3 was a good substrate for Ins(1,4,5)P3 5‐phosphatase, L‐2,2‐F2Ins(1,4,5)P3 was a relatively potent inhibitor (Ki = 19.0 μM). © 1992 Wiley‐Liss, Inc.