bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acid‐Catalyzed nucleophilic substitution and racemization of 3‐methoxy‐N‐desmethyldiazepam enantiomers in methanol
Authors: Yang Shen K. , Lu Xiang‐Lin 
Published: January 2005

AbstractpKa1 values of 3‐methoxy‐N‐desmethyldiazepam in acetonitrile and methanol containing various acid concentrations were determined by spectrophotometry to be 3.5 and 1.3, respectively. Temperature‐dependent racemization of enantiomeric 3‐methoxy‐N‐desmethyldiazepam in methanol containing 0.5 M H2SO4 was studied by circular dichroism spectropolorimetry and the racemization reactions were found to follow apparent first‐order kinetics. Thermodynamic parameters of the racemization reaction were found to be: Eact = 18.8 kcal/mol, and at 25°C: ΔH‡ = 18.3 kcal/mol, ΔS‡ = −14.8 entropy unit, and ΔG‡ = 22.7 kcal/mol, respectively. The racemization had an isotope effect (kH/kD) of 1.6 at 42°C. Based on the results of this report and those of earlier reports by other investigators, a nucleophilically solvated C3 carbocation intermediate resulting from either a P (plus) or an M (minus) conformation is proposed to be an intermediate and responsible for the stereoselective nucleophilic substitution and the subsequent racemization of 3‐methoxy‐N‐desmethyldiazepam enantiomers. © 1993 Wiley‐Liss, Inc.
New optically active 1,3‐oxathiolanes
Authors: Kraus Jean‐Louis , Attardo Giorgio 
Published: January 2005

Abstractcis‐ and trans‐5‐Ethoxy‐1,3‐oxathiolane‐2‐carboxylic acids were obtained in pure form. The cis isomer was resolved into its enantiomers through diastereoisomeric salt formation with enantiomerically pure α‐methylbenzylamine. Reduction of the salt followed by benzoylation led to 2‐benzoyloxymethyl‐5‐ethoxy‐2(R)‐5(S)‐1,3‐oxathiolane and 2‐benzoyloxymethyl‐5‐ethoxy‐2(S)‐5(R)‐1,3‐oxathiolane, useful intermediates in nucleoside chemistry. © 1993 Wiley‐Liss, Inc.
The so‐called “interconversion” of stereoisomeric drugs: An attempt at clarification
Authors: Testa Bernard , Carrupt Pierre‐Alain , Gal Joseph 
Published: January 2005

AbstractA variety of reactions can be categorized under the global concept of the “interconversion of stereoisomers.” Thus, racemization or epimerization can result from inversion of labile chiral centers. From the examples available, some predictive rules are suggested for a chiral center of the type R″R′RCH undergoing base‐catalyzed inversion and a provisional table of affecting groups is presented. Unimolecular inversion of nonsymmetrical, nonplanar ring systems can also result in racemization or epimerization, but no generalization can yet be offered. Beside these cases of nonenzymatic reactions, a limited variety of enzymatic reactions can operate to interconvert stereoisomers, the outcome rarely being a racemic mixture. An important aspect of stereoisomer interconversion is the time scale in which the phenomenon is observed. Thus, several reactions to nonezymatic racemization or epimerization are fast compared to the duration of action of the drug and therefore have pharmacological significance, while other are slower and are of pharmaceutical relevance only. © 1993 Wiley‐Liss, Inc.
Stereoselective protein binding of ketoprofen: Effect of albumin concentration and of the biological system
Authors: Dubois Nathalie , Lapicque Françloise , Abiteboul Michel , Netter Patrick 
Published: January 2005

AbstractEquilibrium dialysis was used to study in vitro the enantioselective binding of R, S, and racemic ketoprofen at physiological pH and temperature in human serum albumin (HSA) (1, 20, and 40 g/liter) and in plasma. The binding of enantiomers in a racemic mixture was studied to see the effect of each isomer on the other's interaction with the protein. The free fractions were determined by high‐performance liquid chromatography. The binding of ketoprofen enantiomers to albumin was enantioselective, depending on both drug and protein concentrations. Enantioselectivity was observed in plasma too but was the opposite of that in HSA at 40 g/liter. The percentage of each isomer unbound was higher in the racemic mixture than with the isomer alone. The displacement of probes specific for HSA sites I and II, studied by spectrofluorimetry, suggests that all three preparations of ketoprofen are bound mainly to site I and secondarily to site II. © 1993 Wiley‐Liss, Inc.
CHIRBASE, a graphical molecular database on the separation of enantiomers by liquid‐, supercritical fluid‐, and gas chromatography
Authors: Koppenhoefer Bernhard , Nothdurft Andreas , Pierrot‐Sanders Joanna , Piras Patrick , Popescu Cristina , Roussel Christian , Stiebler Matthias , Trettin Ulrich 
Published: January 2005

AbstractIn order to cope with the increasing number of publications on the separation of enantiomers by chromatography on a chiral stationary phase, the graphical molecular database CHIRBASE was created. In the present state, the database package covers information (structural, bibiographic, and chromatographic data) on liquid‐, supercritical fluid‐, and gas chromatography; other methods will follow. CHIRBASE, running on the MDL software Chembase®, meets the requirements of contemporary information management in the chemical and pharmaceutical industry. (Detailed information including a demo‐version of each part of CHIRBASE can be obtained from the authors on request.) © 1993 Wiley‐Liss, Inc.
Benzoylcellulose derivatives as chiral stationary phases for open tubular column chromatography
Authors: Francotte Eric , Grolimund Karl , Juvancz Zoltan 
Published: January 2005

AbstractThe application of cellulose‐based stationary phases for chiral separations has been extended to open tubular column chromatography. Efficient columns were obtained by coating the capillaries with mixtures of chiral cellulose materials and conventional achiral stationary phases for gas chromatography. In this study, various siloxane and polyethylene glycol polymers were used as achiral components and mixed with different substituted benzoylcellulose derivatives as chiral components. Systematic investigations were carried out to determine the optimal ratio for the components of the stationary phase. Depending on the chromatographic mode—gas chromatography (GC) or supercritical fluid chromatography (SFC)—the stationary phases were found to behave differently. The applicability of the technique was demonstrated by the resolution of various racemic compounds. © 1993 Wiley‐Liss, Inc.
Use of cyclodextrins as chiral selectors for direct resolution of the enantiomers of fluoxetine and its metabolite norfluoxetine by HPLC
Authors: Piperaki Stavroula , Parissi‐Poulou Maria 
Published: January 2005

AbstractThe goal of this work is to investigate the direct chromatographic separation of the enantiomers of fluoxetine and its active metabolite norfluoxetine. The liquid chromatographic retention behavior of these enantiomers on a β‐cyclodextrin bonded‐phase column was investigated with respect to mobile phase composition, pH, ionic strength, and solvent selectivity. Relationships were established between these factors and the three most important chromatographic parameters: retention time, resolution, and selectivity. Most of the evidence suggests that the unique selectivity of this column isdue to inclusion complex formation, which provides the physical basis for enantiomeric resolution. After these studies a set of optimum chromatographic conditions was chosen for the simultaneous separation/determination of a mixture of the four enantiomers using fluorescence detector. © 1993 Wiley‐Liss, Inc.
Optical resolution by crystalline inclusion formation using new lactic acid derived hosts
Authors: Weber Edwin , Wimmer Claus 
Published: January 2005

AbstractNew optically active host compounds for chiroselective crystalline inclusion formation derived from natural lactic acid are synthesized. They enable useful enantiomer separations of different chiral compounds via cocrystallization and sorption on preparative scale including various ketones, lactones, alcohols, sulfoxides, and methyloxiranes. In the cases of 3‐methylcyclohexanone, 4‐methyl‐δ‐valerolactone, and 2‐phenylpropanol, ees > 99% were obtained from one cocrystallization step using these hosts. © 1993 Wiley‐Liss, Inc.
Enantioselective epoxidation by an optically active hydroperoxide
Authors: Hamann Hans‐Jürgen , Höft Eugen , Chmielewski Marek , Maciejewski Sylvester 
Published: January 2005

AbstractEnantioselective epoxidation of prochiral allylic alcohols with optically active 4,6‐di‐O‐acetyl‐2,3‐dideoxy‐α‐D‐threo‐hex‐2‐enopyranosyl hydroperoxide in the presence of Ti(O‐i‐Pr)4 gives chiral epoxy alcohols with moderate enantiomeric excess. © 1993 Wiley‐Liss, Inc.
Chiral discrimination and antipicornavirus activity of 6‐oxazolinylisoflavan
Authors: Quaglia M. Giovanna , Desideri Nicoletta , Bossù Elena , Sestili Isabella , Tomao Paola , Conti Cinzia , Orsi Nicola 
Published: January 2005

AbstractRacemic 6‐oxazolinylisoflavan, a highly effective inhibitor of rhinovirus serotype 1B in vitro, was resolved by high‐performance liquid chromatography on a chiral stationary phase in order to study the activity of the enantiomers against picornaviruses. The absolute configuration of the two isomers was determined by circular dichroism curves. The antipicornavirus activity of each isomer, separately collected, was evaluated in vitro against human rhinovirus serotype 1B, enterovirus 71, echovirus 6, coxsackievirus B4, and poliovirus type 2 by means of the plaque reduction assay. Both enantiomers were inhibitors of picornavirus replication with the degree of their activity depending on virus and isomer tested. © 1993 Wiley‐Liss, Inc.
Racemization of chlorthalidone in the presence of liposomes
Authors: Lamparter Erich , Blaschke Gottfried , Schlüter Jürgen 
Published: January 2005

AbstractThe extent of racemization of (+)‐chlorthalidone as a function of pH is examined. The minimum of the log K/pH curve is pH 3. The reaction mechanism of inversion is postulated to involve a carbenium cation over the entire pH range and a ring opening reaction in the alkaline range. The influence of liposomes on the inversion rate is also studied, retardation of the racemization rate being observed with increasing liposome concentration. A model of drug distribution between liposome phase and aqueous phase based on the Nernst distribution principle is presented and reaction kinetic aspects are considered. © 1993 Wiley‐Liss, Inc.
Chirality of the γ‐lactones formed by Fusarium poae INRA 45
Authors: Latrasse Alain , Guichard Elisabeth , Piffaut Catherine , Fournier Nicole , Dufosse Laurent 
Published: January 2005

AbstractA filamentous fungus, Fusarium poae INRA 45, was grown in two liquid Czapek‐type media (a Czapek medium, and a yeast extract plus casaminoacids‐enriched Czapek medium). Eight γ‐lactones, i.e., γ‐penta‐, γ‐octa‐, γ‐nona‐, γ‐deca‐, and γ‐dodecalactone, (6Z)‐γ‐ and (6E)‐γ‐dodecenolactones, and a di‐unsaturated γ‐dodecalactone, were tentatively, or conclusively, identified by capillary gas chromatography (GC) and coupled GC‐MS, in the volatile fractions of the cultures. Kinetics of the formation of γ‐decalactone, (6Z)‐γ‐ and (6E)‐γ‐dodecenolactones, (three major lactones), and γ‐dodecalactone (a minor lactone) were quantitatively studied by computerized GC integration. Variations of the (R/S) ratios of the lactone enantiomers were quantitatively studied by computerized multidimensional gas chromatography (MDGC) integration. The levels of the lactones were superior in the enriched Czapek‐type medium to those of the Czapek medium, but the compositions of these media did not influence significantly the (R/S) ratios of these lactones. Formation of the enantiomers is discussed in terms of metabolism of potential precursors. © 1993 Wiley‐Liss, Inc.
Chirality of amino acids of microorganisms used in food biotechnology
Authors: Brückner Hans , Becker Dieter , Lüpke Michael 
Published: January 2005

AbstractBacteria of the genera Acetobacter, Bifidobacterium, Brevibacterium, Lactobacillus, Micrococcus, Propionibacterium, and Streptococcus, which are used as so‐called starter cultures for the large‐scale production of fermented foods and beverages in food biotechnology, have been investigated for the chirality of their amino acids (AA) by gas chromatography (GC). Bacteria were grown in complex media, centrifuged, and washed with 0.85% aqueous NaCl. Aliquots were totally hydrolyzed (6 M HCl, 110°C, 18 h), or extracted with 70% aqueous ethanol in order to isolated free AA. The AA were adsorbed on Dowex WX 8 cation‐exchanger, eluted with 4 M ammonia and converted into their N(O)‐trifluoroacetyl(TFA) 2‐propyl esters or TFA methyl esters. The AA derivatives were investigated by capillary GC using the chiral stationary phases Chirasil‐L‐Val, Chirasil‐D‐Val, and Lipodex E. Besides L‐AA, in all bacteria D‐amino acids (D‐AA) were detected; those in the highest relative amounts were D‐Ala and D‐Asp (occurring in all bacteria) and, in several cases, D‐Glu. Lower, but significant amounts of other D‐AA such as D‐Ser, D‐Pro, D‐Val, D‐Thr, D‐Ile, D‐Leu, D‐Met, D‐Phe, D‐Tyr, D‐Orn, and D‐Lys were also detected in certain bacteria. These findings explain the origin of D‐AA found in all fermented foods and drinks produced with the aid of bacterial starter cultures. © 1993 Wiley‐Liss, Inc.
Enantioselective gallopamil protein binding
Authors: Gross Annette S. , Eser Claudia , Mikus Gerd , Eichelbaum Michel 
Published: January 2005

AbstractThe protein binding of the enantiomers of gallopamil has been investigated in solutions of human serum albumin, α1‐acid glycoprotein and serum. Over the range of concentrations attained after oral gallopamil administration, the binding of both enantiomers to albumin, α1‐acid glycoprotein, and serum proteins was independent of gallopamil concentration. The binding to both human serum albumin (40 g/liter) [range of fraction bound (fb) R: 0.624 to 0.699; S: 0.502 to 0.605] and α1‐acid glycoprotein (0.5 g/liter) (range of fb R: 0.530 to 0.718; S: 0.502 to 0.620) was stereoselective, favoring the (R)‐enantiomer (predialysis gallopamil concentrations 2.5 to 10,000 ng/ml). When the enantiomers (predialysis gallopamil concentration 10 ng/ml) were studied separately in drug‐free serum samples from six healthy volunteers the fraction of (S)‐gallopamil bound (fb: 0.943 ± 0.016) was lower (P < 0.05) than that of (R)‐gallopamil (fb: 0.960 ± 0.010). The serum protein binding of both (R)‐ and (S)‐gallopamil was unaffected by their optical antipodes (fb R: 0.963 ± 0.011; S: 0.948 ± 0.015) indicating that at therapeutic concentrations a protein binding enantiomer–enantiomer interaction does not occur. The protein binding of (R)‐ and (S)‐gallopamil ex vivo 2 h after single dose oral administration of 50 mg pseudoracemic gallopamil (fb R: 0.960 ± 0.010: predialysis [R] 6.9 to 35.3 ng/ml; S: 0.943 ± 0.016: predialysis [S] 9.5 to 30.7 ng/ml) was comparable to that observed in vitro in drug‐free serum. Gallopamil metabolites formed during first‐pass following oral administration, therefore, do not influence the protein binding of (R)‐ or (S)‐gallopamil. © 1993 Wiley‐Liss, Inc.
Stereoselectivity of biliary excretion of 2‐arylpropionates in rats
Authors: Menzel Sabine , Beck Winfried S. , Brune Kay , Geisslinger Gerd 
Published: January 2005

AbstractTo examine the stereoselectivity of biliary excretion, the optically pure enantiomers of ketoprofen (KT), ibuprofen (IBU), and flurbiprofen (FLU) were intravenously administered to normal and bile duct‐cannulated rats at 10 mg/kg. The recovery of total KT in bile was significantly higher after administration of (S)‐KT than after (R)‐KT [90.1 ± 3.5% vs 68.8 ± 8.2%, n =3, P < 0.05]. In normal rats the terminal half‐life of (R)‐KT was significantly shorter than that of (S)‐KT after administration of (R)‐KT (2.2 ± 0.6 h vs 14.3 ± 4.9 h, n = 3, P < 0.05). The terminal half‐life of both enantiomers was significantly shorter in rats with continuous bile drainage as compared to normal rats. No significant differences in pharmacokinetic parameters could be found between both enantiomers in bile duct‐cannulated animals. The total amount of IBU in bile was slightly higher after administration of (S)‐IBU than after (R)‐IBU administration. The percentage of (R)‐IBU after (R)‐IBU administration, however, was very low [(R)‐IBU: 1.5 ± 0.9%, (S)‐IBU: 23.4 ± 5.8%]. In normal rats the clearance of (R)‐IBU was significantly higher as compared to (S)‐IBU. Differences in pharmacokinetic parameters between normal and bile duct‐cannulated rats were not statistically significant due to high interindividual variability. The total recovery of FLU, which was excreted in bile to a lower extent than either KT or IBU, also tended to be greater after S‐enantiomer administration. Only small amounts of (S)‐FLU could be recovered in bile after (R)‐FLU administration. The pharmacokinetic parameters did not differ significantly between (R)‐ and (S)‐FLU or between normal and bile duct‐cannulated rats due to its low inversion rate and low excretion via bile. © 1993 Wiley‐Liss, Inc.
Selective antibodies to propranolol enantiomers produced from a new conjugate
Authors: Sahui‐Gnassi Albertine , Pham‐Huy Chuong , Galons Herve , Warnet Jean‐Michel , Claude Jean‐Roger , Duc Huynh‐Thien 
Published: January 2005

AbstractA selective antibody to (S)‐propranolol enantiomer was produced in rabbits by immunization with a new conjugate of N‐aminopropylpropranolol‐albumin. A hapten was first prepared by condensing (S)‐propranolol or the racemate with 3‐bromopropylphthalimide followed by hydrazinolysis, and the resulting compound conjugated to serum albumin by means of a glutaraldehyde‐ or carbodiimide‐mediated reaction. Rabbits were immunized, and titres and specificity of antibodies were determined by ELISA. The antibodies obtained were tested with (S)‐, (R)‐, (R, S)‐propranolol, and other structural analogs. Selective (S)‐antibodies recognized (S)‐propranolol 20 times more avidly than (R)‐isomer while an antiserum against (R, S)‐propranolol recognized both (S)‐ and (R)‐isomers to about the same degree. ©1993 Wiley‐Liss, Inc.
Chiral‐recognition chromatography of β‐blockers on continuous polymer beds with immobilized cellulase as enantioselective protein
Authors: Mohammad Jamil , Li Yi‐Ming , El‐Ahmad Mostafa , Nakazato Ken'ichi , Pettersson Göouran , Hjertéean Stellan 
Published: January 2005

AbstractColumns prepared by coupling cellulase as a chiral selector to silica beads are very efficient for the separation of enantiomers. In this paper we show that continuous polymer beds compete favorably with silica beads as chromatographic supports for such separations. The chiral stationary phase is prepared either by entrapment in and simultaneous covalent linkage of ally1 cellulase to the continuous beds during their preparation or by covalent immobilization of cellulase on an epoxy‐activated continuous bed. Enantiomers of β‐blockers were separated rapidly and with high resolution. The enantiomers of practolol were thus baseline resolved within 45 sec. The recognition center–or at least part of it—coincides with the active center of the enzyme, since the enantiomers could not be separated in the presence of the competitive enzyme inhibitors cellobiose and D‐glucose and the separation was also impaired upon addition of the substrate carboxymethyl cellulose to the eluent. Similar observations have been reported for silica columns derivatized with cellulase. The capacity factor and the separation selectivity could be tuned by the pH and the concentration of the mobile phase, a phosphate buffer. No modifier was required, as is sometimes the case with silica‐based supports. The continuous beds give faster enantiomer separations than do columns of silica and are more pH‐stable and cost effective to prepare. © 1993 Wiley‐Liss, Inc.
Direct enantiospecific HPLC bioanalysis of (R,S)‐atenolol on a chiral stationary phase
Authors: Kofahl Birgit , Henke Dorit , Mutschler Ernst 
Published: January 2005

AbstractThe simultaneous determination of the enantiomers of the β1‐selective adrenergic antagonist atenolol in human plasma and urine is described. After an alkaline preextraction atenolol is extracted from biological material at pH 12.3 using dichloromethane/propan‐2‐ol. The separation of the underivatized enantiomers is achieved by high‐performance liquid chromatography on a chiral stationary phase (Chiralcel OD, cellulose tris‐3, 5‐dimethylphenylcarbamate, coated on silica gel) with fluorimetric detection. (−)‐(S)‐Pindolol is used as an internal standard. The detection limits of 5 ng/ml enantiomer in plasma and 50 ng/ml enantiomer in urine are sufficient for pharmacokinetic studies after therapeutic doses. © 1993 Wiley‐Liss, Inc.
Rac‐Flurbiprofen is more ulcerogenic than its (S)‐enantiomer
Authors: Wechter William J. , Bigornia Annette E. , Murray E. David , Levine Barry H. , Young James W. 
Published: January 2005

AbstractThe most common, and sometimes life‐threatening, side‐effects associated with the human use of the analgesic, nonsteroidal antiinflammatory drugs (NSAIDs) are gastrointestinal. These include gastritis, ulceration, and severe bleeding. The aryl propionic acid class of NSAIDs are among the most widely used of these drugs in the world, including rac‐ibuprofen, rac‐flurbiprofen, and rac‐ketoprofen. Marketed as racemates, it was assumed that the “inactive” (R)‐enantiomers, having no cyclooxygenase inhibiting effect, also had no toxic effect. In a 30‐day dose response study of (S)‐, (R)‐, and rac‐flurbiprofen given daily over a range of doses the (R)‐isomer alone proved to be without apparent gastrointestinal (GI) toxicity. On the other hand the racemate proved to be 2 to 4 times as ulcerogenic in enantiomerically equivalent doses as the (S)‐enantiomer. These results have significant clinical implications. © 1993 Wiley‐Liss, Inc.
Stereoselective HPLC bioanalysis of atenolol enantiomers in plasma: Application to a comparative human pharmacokinetic study
Authors: Egginger Gabriele , Lindner Wolfgang , Kahr Sabine , Stoschitzky Kurt 
Published: January 2005

AbstractAn enantioselective HPLC bioassay has been developed relying on extraction of (R)‐ and (S)‐atenolol from alkalinized plasma or serum (pH > 12) into dichloromethane containing 5% (v/v) 1‐butanol followed by an achiral derivatization of the drug with phosgene leading to (R)‐ and (S)‐oxazolidine‐2‐one derivatives. Under these conditions there was quantitative conversion of the acetamido group to the corresponding nitrile. These stable derivatives were separated on a (R,R)‐diaminocylohexane‐dinitrobenzoyl chiral stationary phase [(R,R)‐DACH‐DNB] using dichloromethane/methanol 98/2 as mobile phase. Determination limits of 0.5 ng for (R)‐ and 0.6 ng for (S)‐atenolol could be achieved using fluorimetric detection. The assay was applied to a human pharmacokinetic study which was performed in a randomized cross‐over, double‐blind fashion in 12 healthy volunteers, administering single oral doses of 100 mg (R,S)‐, 50 mg (R)‐, and 50 mg (S)‐atenolol AUC0–24 and Cmax values of (R)‐atenolol were slightly but significant higher than those of (S)‐atenolol. The R/S ratios were 1.09 for AUC(R)/AUC(S) and 1.03 for Cmax (R)/Cmax(S) (P < 0.01) respectively after administration of the racemic drug. However, there were no differences between AUC, Cmax, and t½ values of each enantiomer, whether they were administered as single enantiometers or in the form of its racemic mixture. © 1993 Wiley‐Liss, Inc.