bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimation of the number of enantioselective sites of bovine serum albumin using frontal chromatography
Authors: Jacobson Stephen C. , Andersson Shalini , Allenmark Stig G. , Guiochon Georges 
Published: January 2005

AbstractOn a column with bovine serum albumin (BSA) immobilized covalently to silica, the adsorption isotherms of the enantiomers of mandelic acid, tryptophan, 2‐phenylbutyric acid, and N‐benzoylalanine are measured using a buffered mobile phase. Knowing the amount of BSA immobilized on the column (36 mg), the ratio of the number of enantiomer molecules needed to saturate the enantioselective retention mechanism to the number of BSA molecules is determined. The mean of the set of eight enantiomers is 0.28. These data confirm that at most one enantioselective site exists for each BSA molecule for the kind of enantiomers studied. © 1993 Wiley‐Liss, Inc.
Separation of the enantiomers of some racemic nonsteroidal aromatase inhibitors and barbiturates by capillary electrophoresis
Authors: Francotte Eric , Cherkaoui Samir , Faupel Michel 
Published: January 2005

AbstractHigh‐performance capillary electrophoresis (HPCE) and micellar electrokinetic capillary chromatography (MECC) were applied to the resolution of racemic nonsteroidal antiaromatase drugs and intermediates. Successful results were obtained in both modes using α‐cyclodextrin (α‐CD), β‐cyclodextrin (β‐CD), γ‐cyclodextrin (γ‐CD), or 2,6‐di‐O‐methyl‐β‐cyclodextrin (DM‐β‐CD) as chiral selectors. Depending on the structure of the solute, one of the cyclodextrins was generally better suited for resolution of the racemate. The basic solutes were analyzed under HPCE conditions, whereas the nonionizable compounds such as glutethimide (Doriden®) were analyzed in MECC mode. For the azole‐type antiaromatase Fadrozole, both HPCE and MECC modes could be used to achieve the separation of the enantiomers. The influence of experimental factors such as pH, the presence of organic modifier, temperature, the micelle concentration, and the concentration of the chiral selector is also discussed on the basis of the results obtained with some chiral barbiturates. The possibility of analyzing the enantiomers directly in plasma samples was also demonstrated. © 1993 Wiley‐Liss, Inc.
Commonly used chiral drugs: A survey
Authors: Millership Jeffrey S. , Fitzpatrick Anne 
Published: January 2005

AbstractInitial results of a comparative survey of commonly used chiral drugs are presented. The survey considered the differences between drugs used in 1982 with those in use in 1991. Two major conclusions were reached: the use of single isomer chiral drugs had increased from 31.1% in 1982 to 34.3% in 1991 and the proportion of synthetic single isomer chiral drugs available in 1991 was considerably greater than in 1982. © 1993 Wiley‐Liss, Inc.
Microbial metabolism of 2‐arylpropionic acids: Chiral inversion of ibuprofen and 2‐phenylpropionic acid
Authors: Hutt Andrew J. , Kooloobandi Azam , Hanlon Geoffrey W. 
Published: January 2005

AbstractThe metabolism of (R,S)‐ibuprofen has been investigated in 24 microbial cultures. Of these Cunninghamella elegans, Mucor hiemalis, and Verticillium lecanii catalyzed the oxidation of the drug to 2‐[4‐(2‐hydroxy‐2‐methylpropyl)phenyl]propionic acid, a known mammalian metabolite. The extent of metabolism was greatest with V. lecanii, with some 47% of the substrate being consumed over a 7‐day incubation period. Enantiomeric analysis indicated stereoselective metabolism of (R)‐ibuprofen, the enantiomeric composition of the residual substrate being R/S = 0.25. Following a preparative scale incubation of (R,S)‐ibuprofen with V. lecanii, in which the reaction was allowed to go to completion, the metabolite was found to be predominantly of the S‐configuration (S/R = 2.1), suggesting that chiral inversion of either the drug and/or the metabolite had taken place. Analysis of extracts following incubation of (R,S)‐, (R)‐, and (S)‐2‐phenylpropionic acid with V. lecanii, for 21 days, indicated that chiral inversion of the (R)‐enantiomer to its optical antipode had taken place. The results of these investigations indicate that microorganisms, in addition to mammals, are able to mediate the chiral inversion of 2‐arylpropionic acids. This observation may have implications for the preparation of optically pure 2‐arylpropionic acids. © 1993 Wiley‐Liss, Inc.
Stereoselective sulfate conjugation of isoproterenol in humans: Comparison of hepatic, intestinal, and platelet activity
Authors: Pesola Gene R. , Walle Thomas 
Published: January 2005

AbstractThe stereochemistry of sulfate conjugation of isoproterenol (ISO) was examined with human liver, intestine, and platelets as the phenolsulfotransferase (PST) enzyme source and PAP35S as the cosubstrate. With the hepatic cytosol, two distinct sulfation reactions were identified, a high affinity reaction (Km 5 to 50 μM) and a low affinity reaction (Km 360 to 2,900 μM). The efficiency of sulfation (Vmax/Km) for both reactions was 5‐fold higher for (+)‐ than for (−)‐ISO. When the hepatic PSTs were resolved by ionexchange chromatography, it could be shown that the high affinity reaction was catalyzed by the monoamine (M) form and the low affinity reaction by the phenol (P) form of PST. Only the high affinity (M form) sulfation was detected in the jejunal cytosol with a Vmax/Km value 6.1‐fold higher for (+)‐ than for (−)‐ISO. Finally the platelet, as a potentially useful model tissue, also demonstrated only the high affinity M form reaction with a Vmax/Km value 5.7‐fold higher for (+)‐ than for (−)‐ISO. In summary, this study has shown that sulfation of ISO by PSTs in various human tissues is stereoselective and favors the inactive (+)‐enantiomer over the active (−)‐enantiomer by about 5‐fold, a finding which should be considered in the therapeutic use of chiral drugs cleared by sulfate conjugation. © 1993 Wiley‐Liss, Inc.
The temperature dependence of steady‐state kinetics: What can be learned about pig liver esterase stereospecificity?
Authors: Van Gelderen Hans , Mayer Joachim M. , Cellamare Saverio , Testa Bernard 
Published: January 2005

AbstractThe steady‐state kinetic parameters for pig liver carboxylesterase (PLE)‐catalyzed hydrolysis of the prochiral substrate dimethyl phenylmalonate (DMPM) (product enantioselectivity) and the separate enantiomers of three chiral 2‐phenylpropionic acid esters (substrate enantioselectivity) were measured at seven temperatures between 288 K and 312 K. Arrhenius plots of turnover numbers against the reciprocal of experimental temperatures yielded enthalpies and entropies of activation at enzyme saturation. (+)‐(S)‐methyl‐2‐phenylpropionate, (+)‐(S)‐4‐nitrophenyl 2‐phenylpropionate, and both enantiomers of phenyl 2‐phenylpropionate showed very similar activation enthalpies and entropies (approximately 50 kJ mol−1 and −50 J mol−1 K−1, respectively), but differences were observed for (−)‐(R)‐methyl 2‐phenylpropionate and (−)‐(R)‐4‐nitrophenyl 2‐phenylpropionate. Whereas the entropies of activation of all 2‐phenylpropionates were negative, positive entropies of activation were measured in the formation of monomethyl phenylmalonate enantiomers from DMPM. Enthalpy–entropy compensation analysis of the data indicates a common mechanism of PLE substrate and product enantiospecificity in the reactions studied here. © 1994 Wiley‐Liss, Inc.
Challenges and frustrations in the separation and analysis of chiral agrochemicals
Authors: Massey Peter R. , Tandy Michael J. 
Published: January 2005

AbstractThe development of chiral HPLC methods and isolation techniques within Zeneca Agrochemicals (formerly ICI Agrochemicals) is reviewed. The use of low temperature to improve chiral separations has been successfully applied to production analysis, but although useful for some compounds it is regrettably not a universal panacea for all poor separations. The need to isolate small quantities of individual enantiomers from new compounds for research evaluation has led us to devise a more universal and cheap chiral stationary phase (CSP) for Preparative‐LC. Joint academic research produced a CSP based on tartaric acid which was made commercially available and it was gratifying to find it was the only phase able to resolve a novel insecticide. However, as new CSPs emerged almost every month, our attention turned to using a universal chiral detector for analysis, rather than via separation of individual enantiomers. Diode laser‐based polarimeters offered the opportunity of cheap, sensitive chiroptical detectors for HPLC and the ability to move away from chiral columns in both research and production analysis. Jointly sponsored research with a university has successfully explored the versatility of chiroptical detectors in agrochemical and food analysis. Comparison of chiral SFC with chiral HPLC and an extensive evaluation of established and research agrochemicals on a wide range of commercial CSPs have led to a revised method development strategy. Current work with high load displacement chiral chromatography will be described as a potential means of isolating pure enantiomers from racemates. © 1994 Wiley‐Liss, Inc.
Isomeric‐Activity ratios of trimetoquinol enantiomers on β‐adrenergic receptor subtypes: Functional and biochemical studies
Authors: Fraundorfer Paul F. , Lezama Edwin J. , Salazar‐Bookaman M. Margarita , Fertel Richard H. , Miller Duane D. , Feller Dennis R. 
Published: January 2005

AbstractTrimetoquinol [1‐(3′,4′,5′‐trimethoxybenzyl)‐6,7‐dihydroxy‐1,2,3,4‐tetrahydroisoquinoline, TMQ] exists as two enantiomers, and the (−)‐(S)‐isomer is a potent β‐adrenergic receptor (β‐AR) agonist. Experiments were conducted to examine the functional and biochemical potencies of the (S)‐ and (R)‐enantiomers of TMQ for interaction with β‐AR subtypes in tissues, membrane fractions, and cell systems. The isomeric‐activity ratios (IARs) of the TMQ isomers [(S)‐isomer ≫ (R)‐isomer] for stimulation of β1‐ and β2‐AR of guinea pig right atria and trachea were 224 and 1585, respectively; these IARs were similar to those observed on atypical β‐AR systems of rat distal colon (575), rat brown adipocytes (398), but differed from that of rat esophageal smooth muscle (2884) in the presence of pindolol. In the absence of pindolol, the potencies for the TMQ enantiomers were slightly increased; however, the IARs remained unchanged in rat distal colon, rat brown adipocytes, and rat esophageal smooth muscle. Similarly, radioligand binding studies demonstrated that the TMQ isomer β‐AR affinities were stereoselective for the (−)‐(S)‐isomer in membranes of guinea pig left ventricle (β1) and lung (β2) giving IARs of 115 and 389, respectively; and in E. coli expressing human β1‐ and β2‐AR giving IARs of 661 and 724, respectively. Corresponding IARs of receptor affinities and stimulation of cAMP accumulation in Chinese hamster ovary cells expressing human β2‐AR and rat β3‐AR were 331 and 282, and 118 and 4678, respectively. These results indicate that the (−)‐(S)‐isomer of TMQ exhibits high affinity, and is a potent and highly stereoselective agonist for each β‐AR subtype, that the isomers generally fail to differentiate between the β‐AR subtypes, and that, based upon differences in IAR within β3‐AR containing systems, subtypes of atypical β (or β3)‐AR may exist in adipose tissue and smooth muscle. © 1994 Wiley‐Liss, Inc.
Asymmetric metabolic N‐oxidation of N‐ethyl‐N‐methylaniline by purified flavin‐containing monooxygenase
Authors: Hadley Mark R. , Oldham Harriet G. , Damani Lyaquatali A. , Hutt Andrew J. 
Published: January 2005

AbstractThe prochiral tertiary amine N‐ethyl‐N‐methylaniline (EMA) is known to be metabolically N‐oxygenated in vitro with microsomal preparations. This biotransformation is thought to be mediated predominantly by the flavin‐containing monooxygenase (FMO) enzyme system. Microsomal N‐oxygenation of EMA is known to be stereoselective and varies between species. In order to further characterise this metabolic transformation, we have examined the in vitro metabolism of EMA using purified porcine hepatic FMO. Following incubation of EMA with purified FMO, EMA N‐oxide, the only metabolite detected, was found to be produced stereoselectively [ratio (−)‐(S):(+)‐(R), ca. 4:1]. The enantiomeric ratio of the N‐oxide product did not change markedly with respect to time, enzyme or substrate concentration. Determination of the kinetics of formation of the N‐oxide indicated a single affinity for the prochiral substrate with differential rates of formation of the enantiomers. The extent of EMA N‐oxide formation was shown to be affected by activators and inhibitors of FMO and pH, but its stereoselectively was unaltered. © 1994 Wiley‐Liss, Inc.
Chiral HPLC with carbohydrate carbamates: Influence of support structure on enantioselectivity
Authors: Grieb Sally J. , Matlin Stephen A. , Phillips Joseph G. , Belenguer Ana M. , Ritchie Harald J. 
Published: January 2005

AbstractThe effect of particle size and pore size of the aminopropylated silica support for cellulose tris(phenylcarbamate) and tris(3,5‐dimethylphenylcarbamate) chiral HPLC phases was investigated. It was necessary to reduce phase loading below 20% w/w as pore size and particle size were reduced, but high efficiency columns could be prepared at a 15% w/w loading on 5 and 2.5 μm supports with 120‐Å‐diameter pores. The 2.5 μm phase permits the use of relatively high flow rates and very efficient enantioselective separations of a range of chiral compounds could be achieved in less than 3 min. © 1994 Wiley‐Liss, Inc.
Determination of the absolute configuration of secondary alcohols with Horeau's method including enantioselective gas chromatography
Authors: König Wilfried A. , Gehrcke Bärbel , Weseloh Gerald 
Published: January 2005

AbstractThe reaction of optically active secondary alcohols with excess of racemic 2‐phenylbutyric acid anhydride in pyridine proceeds at different rates to the diastereoisomeric esters (kinetic partial resolution). According to Horeau the (unknown) absolute configuration of the alcohol can be derived from the optical rotation of the remaining excess of 2‐phenylbutyric acid in the reaction mixture. Measuring the optical rotation may be very difficult in cases of small absolute rotation values and may be inaccurate due to the necessity to completely remove all chiral impurities. The application of Horeau's method is greatly facilitated by gas chromatographic determination of the enantiomeric ratio of the remaining 2‐phenylbutyric acid after methylation using a short capillary column with heptakis(2,6‐di‐O‐methyl‐3‐O‐pentyl)‐β‐cyclodextrin as a chiral stationary phase. Baseline resolution of the enantiomers is achieved after approximately 10 min of retention time. Due to the high selectivity of capillary gas chromatography the probability of impurities in the mixture to interfere with the measurement of the enantiomeric ratio is extremely low. © 1994 Wiley‐Liss, Inc.
Inversion of chiral α‐methylbenzylamine
Authors: Johansen Cecilie , Fiksdahl Anne 
Published: January 2005

AbstractMore effective use of optical resolution processes can be obtained by increasing the overall yields after development of methods for inversion of the chiral centre of the unwanted isomer. The configuration of some optically active amines can be inverted in a three‐step synthesis via the N,N‐ditosylimides and a subsequent nucleophilic substitution by the azide ion. The azide product is reduced by hydrogenolysis. Low stereoselectivity caused by racemization to some extent was at first observed for the inversion of the benzylic substrate, (S)‐α‐methylbenzylamine (5a). However, modified reaction conditions allowed increased stereoselectivity, a more rapid and almost complete inversion of this substate as well. © 1994 Wiley‐Liss, Inc.
Acid‐catalyzed stereoselective heteronucleophilic substitution and racemization of 3‐O‐methyloxazepam and 3‐O‐ethyloxazepam
Authors: Yang Shen K. 
Published: January 2005

AbstractEnantiomers of 3‐O‐methyloxazepam (MeOX) and 3‐O‐ethyloxazepam (EtOX) were resolved by chiral stationary phase high‐performance liquid chromatography (CSP‐HPLC). Reaction kinetics and deuterium isotope effects of acid‐catalyzed racemization of enantiomeric MeOX in ethanol and enantiomeric EtOX in methanol were studied by spectropolarimetry. The acid‐catalyzed heteronucleophilic substitution reactions of racemic MeOX in ethanol and racemic EtOX in methanol were studied by reversed‐phase HPLC. Thermodynamic parameters involved in the reactions were obtained by temperature‐dependent reaction rates. The effects of solvent's dielectric constant on the heteronucleophilic substitution reactions were also determined. A nucleophilically solvated and transient C3 carbocation intermediate resulting from an N4‐protonated enantiomer, derived from a 1,4‐benzodiazcpine either in M (minus) or P (plus) conformation, is proposed to be an intermediate and responsible for the acid‐catalyzed stereoselective nucleophilic substitution and the resulting racemization. © 1994 Wiley‐Liss, Inc.
The rabbit liver microsomal biotransformation of 1,1‐dialkylethylenes: Enantioface selection of epoxidation and enantioselectivity of epoxide hydrolysis
Authors: Bellucci Giuseppe , Chiappe Cinzia , Cordoni Antonio , Marioni Franco 
Published: January 2005

AbstractThe rabbit liver microsomal biotransformation of α‐methylstyrene (1a), 2‐methyl‐1‐hexene (1b), 2,4,4‐trimethyl‐1‐pentene (1c), and 2,3,3‐trimethyl‐1‐butene (1d) has been investigated with the aim at establishing the enantioface selection of the cytochrome P‐450‐promoted epoxidation of the double bond and the enantioselectivity of microsomal epoxide hydrolase (mEH)‐catalyzed hydrolysis of the resulting epoxides. GLC on a Chiraldex G‐TA (ASTEC) column was used to determine the enantiomeric composition of the products. The epoxides 2 first produced in incubations carried out in the presence of an NADPH regenerating system were not detected, being rapidly hydrolyzed by mEH to diols 3. The enantiomeric composition of the latter showed that no enantioface selection occurred in the epoxidation of 1c and 1d, and a very low (8%) ee of the (R)‐epoxide was formed from 1b. Incubation of racemic epoxides 2b–d with the microsomal fraction showed that the mEH‐catalyzed hydrolysis of 2c and 2d was practically nonenantioselective, while that of 2b exhibited a selectivity E = 4.9 favoring the hydrolysis of the (S)‐enantiomer. A comparison of these results with those previously obtained for linear and branched chain alkyl monosubstituted oxiranes shows that the introduction of the second alkyl substituent suppresses the selectivity of the mEH reaction of the latter and reverses that of the former substrates. © 1994 Wiley‐Liss, Inc.
Direct enantiomeric resolution of ibuprofen and flurbiprofen by packed column SFC
Authors: Wilson William H. 
Published: January 2005

AbstractPacked column SFC is used to resolve the enantiomers of two nonsteroidal antiinflammatories. A Chiralpak AD column is used with a binary mobile phase of carbon dioxide/methanol to achieve resolution. The effects of composition, pressure, temperature, and flow on ibuprofen enantiomer separation are examined. In this instance, temperature affords the greatest change in resolution followed by pressure and composition. Baseline resolution of ibuprofen is achieved in less than 7 min and fluibiprofen is baseline resolved in less than 4 min. © 1994 Wiley‐Liss, Inc.
Evaluation of free D‐glutamate in processed foods
Authors: Rundlett Kimber L. , Armstrong Daniel W. 
Published: January 2005

AbstractMonosodium glutamate (MSG) is added to many processed foods at significant levels for flavor enhancement. It is also naturally occurring at high levels in some foods. The enantiomeric composition of free glutamate in foods was examined and all foods analyzed were found to contain D‐glutamate. The relative percent of D‐glutamate in the food products studied depended on the origin of the glutamate. Foods to which MSG was added by the manufacturer had a high total level of MSG but a lower relative percentage of the D‐enantiomer (usually less than 0.8%). In comparison, fermented foods tend to have high relative levels of D‐glutamate but a lower total amount of the amino acid. The relative percent of D‐glutamate in nonfermented foods containing no added MSG was also found to be low compared to fermented products. In some cases the percent D‐glutamate could be related to the relative amounts of other food ingredients such as cheese. © 1994 Wiley‐Liss, Inc.
Determination of amphetamine and methamphetamine enantiomers by chiral derivatization and gas chromatography–mass spectrometry as a test case for an automated sample preparation system
Authors: Sievert Hans‐Jürgen P. 
Published: January 2005

AbstractAn automated sample preparation system has been applied to the chiral analysis of amphetamine and methamphetamine using derivatization with trifluoracetyl‐L‐prolyl chloride (L‐TPC) and subsequent separation on a gas chromatography–mass spectrometry (GC‐MS) system. Tasks automated were the dilution of standards and the off‐line preparation of the diastereoisomer derivatives. Chromatographic performance, sensitivity, and reproducibility of the automated procedure were compared to the equivalent values obtained with two existing assays methods which employ manual derivatiation, either on‐column or off‐line. Chromatographic performance was unaffected by the derivatization procedure and sensitivity was better for both automated and manual off‐line derivatization. Qualitative reproducibility as based on enantiomeric composition was equivalent for all three approaches, while quantitative reproducibility as based on peak areas was best for the automated procedure. Considering the fact that the diastereoisomer derivatives are unstable over time, automated sample preparation with “just‐in‐time” derivatization can increase the overall precision of the analytical method. The procedures described here are general enough in nature that they could be applied to other chiral or even achiral analytes. © 1994 Wiley‐Liss, Inc.
Base‐catalyzed racemization of 3‐O‐acyloxazepam
Authors: Yang Shen K. , Bao Ziping 
Published: January 2005

AbstractEnantiomers of 3‐O‐acyloxazepam (oxazepam 3‐acetate; OXA) underwent base‐catalyzed hydrolysis and racemization. Kinetics of reaction products formed from an OXA enantiomer in buffered and unbuffered alkaline solutions were analyzed by chiral stationary phase high‐performance liquid chromatography. Racemization occurred with varying rates in aqueous solutions with pH ranging from 7.5 to 14. Racemization mechanism was studied by the dependence of rates of hydrolysis and racemization on temperature and pH. Mass spectral analysis of racemization products derived from an OXA enantiomer in a deuterated solvent indicated that racemization was accompanied by a proton exchange with the solvent. The results indicated that a base‐catalyzed keto‐enol tautomerism between the C2‐carbonyl group and the C3 carbon was responsible for the observed racemization. © 1994 Wiley‐Liss, Inc.This article is a US Goverment work and, as such, is in the public domain in the United States of America.