bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stereoselective analysis of ketorolac in human plasma by high‐performance liquid chromatography
Authors: Hayball Peter J. , Tamblyn Julie G. , Holden Yvonne , Wrobel Jan 
Published: January 2005

AbstractA high‐performance liquid chromatographic (HPLC) analytical method is described for the quantification of the (R)‐ and (S)‐enantiomers of ketorolac when present together in human plasma. The method involves derivatization with thionyl chloride/(S)‐1‐phenylethylamine and subsequent reversed‐phase chromatography of the diastereomeric (S)‐1‐phenylethylamides of (R)‐ and (S)‐ketorolac. The method is suitable for the analysis of large numbers of plasma samples and has been applied in this report to a pharmacokinetic study of ketorolac enantiomers upon intramuscular administration of racemic drug to a human subject. The limit of quantification for each enantiomer of ketorolac is 50 ng/ml (signal‐to‐noise ratio > 10). © 1993 Wiley‐Liss, Inc.
Asymmetric transformation of a racemic α‐(phthalimidooxy)arylacetic ester by a combination of preferential crystallization and simultaneous racemization
Authors: Murakami Kimihiro , Ohashi Masayuki , Matsunaga Atsuo , Yamamoto Ichiro , Nohira Hiroyuki 
Published: January 2005

AbstractAn asymmetric transformation of racemic t‐butyl 2‐(3,4‐O‐carbonyldioxy‐phenyl)‐2‐(phthalimidooxy)acetate [(RS)‐2b] into one of its optically active forms was carried out by a combination of preferential crystallization of a desired enantiomer and the simultaneous racemization of the antipode. (R)‐2b was easily racemized in diethylketone in the presence of a small amount of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU). Under the conditions for racemization, the asymmetric transformation was achieved successfully to give (S)‐2b with 84% optical purity in 80% yield. A potent antipseudomonal cephalosporin M‐14659 (1) was prepared from the pure (S)‐2b which was obtained by the recrystallization of the crude (S)‐2b. © 1993 Wiley‐Liss, Inc.
Theoretical study of enantiodifferentiation in solid state cyclodextrins
Authors: Lipkowitz Kenny B. , Green Karen M. , Yang Jia‐An , Pearl Greg , Peterson Michael A. 
Published: January 2005

AbstractA molecular mechanics investigation of R‐ vs. S‐phenylethanol, R‐ vs. S‐mandelic acid, R‐ vs. S‐flurbiprofen, and R‐ vs. S‐fenoprofen in their cyclodextrin crystal environments was undertaken. It was found that the dominant force responsible for guesthost complexation is the short‐range London force; the enantiodiscriminating forces tend to be very small and are generally, but not always, dominated by long‐range electrostatic contributions. Derivatized cyclodextrins are generally more enantiodiscriminating than native cyclodextrins, perhaps due to exterior rather than interior guest‐host binding. © 1993 Wiley‐Liss, Inc.
Racemization and hydrolysis of tropic acid alkaloids in the presence of cyclodextrins
Authors: Blaschke Gottfried , Lamparter Erich , Schlüter Jürgen 
Published: January 2005

AbstractBecause of the constantly increasing demand for optically pure drugs it is of great importance to elucidate factors affecting stereochemistry, in order to provide a stable formulation with a high chiral quality of the desired isomer. Therefore, the effects of cyclodextrins (CyDs) and their alkylated and hydroxyalkylated derivatives on racemization and hydrolysis of (−)‐(S)‐hyoscyamine and (−)‐(S)‐scopolamine were examined kinetically and spectroscopically (NMR). Direct methods, based on a chiral and achiral chromatographic phase system, were used to determine their degradation products and enantiomer composition during stability tests. All different CyDs, except α‐CyD, retarded racemization and hydrolysis. The inclusion of the drug substances in CyDs inhibits the attack of hydroxyl ions and/or water molecules and thus retards the racemization and hydrolysis. The racemization of the tropic acid alkaloids is dependent on the pH and temperature. NMR studies were used to evidence the formation of a soluble 1:1 complex in aqueous solution. © 1993 Wiley‐Liss, Inc.
Direct separation of cone‐shaped tri‐O‐alkylated chiral calix[4]arenes by enantioselective HPLC
Authors: Caccamese Salvatore , Pappalardo Sebastiano 
Published: January 2005

AbstractThe direct HPLC separation of eight inherently chiral atropisomeric calix[4]arenes has been achieved using Chiralcel OD phase. A rationale is given for the variation of the enantioselectivity as a function of the O‐alkyl or O‐aryl groups. In closely related structures hydrogen bond formation between the free hydroxyl of the analyte and the chiral phase plays an important role in the chiral recognition process. © 1993 Wiley‐Liss, Inc.
Chiral resolution of some antimalarial agents by sub‐ and supercritical fluid chromatography on an (S)‐naphthylurea stationary phase
Authors: Peytavin Gilles , Gimenez Françlois , Genissel Brigitte , Gillotin Catherine , Baillet Arlette , Wainer Irving W. , Farinotti Robert 
Published: January 2005

AbstractThe behavior of mefloquine, halofantrine, enpiroline, quinine, quinidine, chloroquine and primaquine is studied by subcritical fluid chromatography on a (S)‐naphthylurea column (250 mm × 4.6 mm ID) with a subcritical mobile phase composed of carbon dioxide, methanol and triethylamine (flow rate of 3 ml/min). Except for primaquine and chloroquine, each enantiomer was separated at a temperature between 40 and 60°C, and at a pressure below 15 MPa. A 98/2, v/v CO2/methanol 0.1% triethylamine mixture allowed the separation of halofantrine enantiomers while the enantiomers of the more polar metabolite (N‐desbutylhalofantrine) were separated with a 80–20 v/v mixture as used for mefloquine, enpiroline, quinine and quinidine. The influence of temperature, pressure and of the nature of the mobile phase is discussed. © 1993 Wiley‐Liss, Inc.
Determination of the enantiomeric purity of 5,6‐ and 6,7‐dihydroxy‐2‐aminotetralins by chiral HPLC
Authors: Castelnovo Pierfrancesco 
Published: January 2005

Abstract5,6‐ and 6,7‐Dihydroxy‐2‐aminotetralin (ADTN), racemic dopamine receptor agonists, were resolved into their enantiomers by a new chiral HPLC assay. The separation was performed on a Crownpack CR column, which contains an 18‐crown‐6‐type chiral crown ether as a chiral selector. The chiral recognition is based on the compiexation of the protonated primary amino group and the oxygen atoms inside the cavity of the crown ether. The amino group is attached to the chiral centre and therefore these compounds could be resolved. Mobile phase was perchloric acid pH 2.0 and the detection was UV at 200 nm. Resolution factors were 3.1 for 5,6‐ADTN and 1.1 for 6,7‐ADTN resulting in very low limits of quantitation (<0.1%) of the enantiomer present as impurity. Data on the validation of the assay and on the stability of the column are also reported. © 1993 Wiley‐Liss, Inc.
Direct resolution of enantiomers of basic imidazol‐2‐yl‐substituted alcohols by gas chromatography on chirasil‐val
Authors: Briody John M. , Keenan David , Nicholson Graeme J. , Koppenhoefer Bernhard 
Published: January 2005

AbstractThe direct resolution of enantiomers of a series of imidazol‐2‐yl‐substituted alcohols has been achieved by gas chromatography on a well‐deactivated fused‐silica capillary column, coated with L‐Chirasil‐Val as the chiral stationary phase. The separation of these basic compounds is accomplished without exaggerated peak tailing. Compared to simpler alcohols the resolution factors (α) observed are extraordinarily large. While the imidazolyl substituent may contribute to the mechanism of the chiral discrimination, the crucial interaction is assumed to be through the hydroxy group, based on the observation that the resolution factors for the corresponding O‐acetyl derivatives are markedly reduced. © 1993 Wiley‐Liss, Inc.
High‐Performance liquid chromatography (HPLC) chiral separations of guaifenesin, methocarbamol, and racemorphan
Authors: Demian Iulia 
Published: January 2005

AbstractHPLC chiral separations on silica gel coated with derivatized cellulose stationary phases are described. Most examples make use of the Chiralcel OD column from Daicel, Inc. With a judiciously chosen mobile phase, baseline separations of the enantiomers can be achieved. If those separations are used as a base for enantiomeric purity determination, detectable limits of 0.1% of the minor enantiomer are routinely accessible. Examples are given concerning separations of guaifenesin, methocarbamol, and racemorphan. © 1993 Wiley‐Liss, Inc.
Helical stereochemistry and chiral apple halves. 2. La coupe du roi via double helical complexation using oligo(bipyridine) strands and Cu(I)/Ag(I)
Authors: Glaser Robert 
Published: January 2005

AbstractOligo(bipyridine) strands and Cu(I)/Ag(I) form duplexes having a 21‐screw coincidental with a C2‐axis. A segment containing a complete turn of the duplex can be considered to be a coupe du roi ensemble of two homochiral strands. Moreover, for D2d symmetry monocationic Cu(I) complexes of bipyridine trimers and pentamers, addition of the requisite Cu(I) cations is a true chemical example of la coupe du roi. In this reaction, an achiral monocationic complex is converted into a multiple‐cationic duplex of two homochiral and homotopic 21‐helical halves. The chirality of the resulting duplex is a function of the particular set of bipyridine enantiotopic faces which are used for binding the additional cations. © 1993 Wiley‐Liss, Inc.
Feasibility of chiral discrimination using X‐ray anomalous scattering
Authors: Grochowski Jacek , Serda Pawel 
Published: January 2005

AbstractThe paper discusses several feasibility prediction criteria with particular emphasis on light atom molecules. For several examples of refined absolute structures, feasibility predictions are calculated and compared with a posteriori calculated values of the Bijvoet ratio. An extension of the Pathasarathy table of the expected value of the Bijvoet ratio is given for parameter ranges corresponding to light anomalous scatters. Practical conclusions are drawn for absolute structure determination of compounds containing oxygen or nitrogen as anomalous scatterers. © 1993 Wiley‐Liss, Inc.
Stereoselectivity in β‐cyclodextrin complexation of 1,4‐dihydropyridine derivatives
Authors: Ferčej‐Temeljotov Darja , Kmet Matevž , Kocjan Darko , Kotnik Sonja , Resman Aleksander , Urleb Uroš , Verhnjak Katarina , Zver Igor , Žmitek Janko 
Published: January 2005

AbstractStructure–interaction relationships, stereoselectivity, and solubility enhancement in inclusion compexation of β‐cyclodextrins (CDs) with some racemic and enantiomerically pure 1,4‐dihydropyridine derivatives (DHPs) were investigated. 1:1 and 1:2 (mole ratio) complexes were prepared and characterized by X‐ray powder diffraction, differential scanning calorimetry (DSC), MS‐FAB spectrometry,1H‐NMR spectroscopy, water and phase solubility. The solubility studies have revealed different complexation equilibria for optically pure DHP enantiomers, and corresponding racemic mixtures in water solutions. By means of1H‐NMR chemical shift measurements, the inclusion of aromatic fragments of racemic and enantiomerically pure DHP molecules within the cavities of different CDs was elucidated. Considerable stereoselectivity in complexation interactions was observed. The results indicate the potential use of cyclodextrins as chiral selectors for enantiomeric resolution of 1,4‐DHP calcium antagonists. © 1993 Wiley‐Liss, Inc.
Development of the enzyme‐catalysed Baeyer–Villiger reaction as a useful technique in organic synthesis
Authors: Roberts Stanley M. , Willetts Andrew J. 
Published: January 2005

AbstractThe current practices of using monooxygenase enzymes to perform regio‐ and stereoselective oxidation reactions in organic syntheses are reviewed. The isolation of a monooxygenase from Pseudomonas putida NCIMB 10007 and its use in the conversion of bicyclo[3.2.0]hept‐2‐en‐6‐one into two isomeric optically active lactones is described. The monooxygenase utilises NADH as cofactor and NADH‐recycling is accomplished using formate and formate dehydrogenase. As alternative methodology, it is shown that a secondary alcohol can be converted into a chiral lactone using a dehydrogenase and a monooxygenase working in tandem with in situ cofactor recycling. © 1993 Wiley‐Liss, Inc.
Chirality of azelastine and flezelastine: Investigation of their enantiomers
Authors: Fleischhauer Ilona , Kutscher Bernhard , Engel Jürgen , Achterrath‐Tuckermann Ute , Borbe Harald O. , Schmidt Jürgen , Szelenyi Istvan , Camuglia Giancarlo 
Published: January 2005

AbstractThe racemic phthalazinone derivatives azelastine and flezelastine were resolved via formation of diastereomeric salts and fractional crystallization thereof. The optical purity of the enantiomers was checked by HPLC. Pharmacological investigations in vitro and in vivo related to antiallergic/antiasthmatic activity revealed some stereospecific differences. However, chiral discrimination could not be observed with regard to overall activity of azelastine and flezelastine. © 1993 Wiley‐Liss, Inc.
Pharmacokinetics of the enantiomers of verapamil in the dog
Authors: Bai Stephen A. , Lankford Susan M. , Johnson Lynetta M. 
Published: January 2005

AbstractThe intravenous (0.5 mg/kg) and oral (5 mg/kg) dose kinetics of verapamil were studied in 6 dogs during steady‐state oral verapamil dosing (5 mg/kg every 8 h for 3 days). Racemic verapamil and norverapamil, a metabolite of verapamil, were quantitated in plasma by HPLC‐fluorescence detection. The verapamil peaks eluting off the column were collected and rechromatographed on an Ultron‐OVM column, which resolved the two verapamil enantiomers. After intravenous administration, the systemic clearance and apparent volume of distribution of (−)‐(S)‐verapamil were nearly twice that of the (+)‐(R)‐isomer. There was no difference in the elimination half‐lives between the two isomers. After oral administration, the oral clearance of (−)‐(S)‐verapamil was 20 times that of the (+)‐(R)‐isomer. The apparent bioavailability of (+)‐(R)‐verapamil was over 14 times that of (−)‐(S)‐verapamil. The plasma protein binding of the (+)‐(R)‐isomer was slightly higher by 5% than (−)‐(S)‐verapamil; however, this effect was not enough to account for the difference between the apparent volume of distribution of the enantiomers, indicating that the tissue binding of (−)‐(S)‐verapamil was greater than that of the (+)‐(R)‐isomer. This data on the disposition of the enantiomers of verapamil in the dog is similar to that reported for man and demonstrates that the dog may be an appropriate animal model for man in future studies on the disposition of the enantiomers of verapamil. © 1993 Wiley‐Liss, Inc.
Enantiomeric resolution of sulfoxides on a DACH‐DNB chiral stationary phase: A quantitative structure–enantioselective retention relationship (QSERR) study
Authors: Altomare Cosimo , Carotti Angelo , Cellamare Saverio , Fanelli Francesca , Gasparrini Francesco , Villani Claudio , Carrupt Pierre‐Alain , Testa Bernard 
Published: January 2005

AbstractThe interaction mechanism of a variety of racemic alkyl aryl sulfoxides with a π‐acid HPLC stationary phase containing N,N′‐(3,5‐dinitrobenzoyl)‐trans‐1,2‐diaminocyclohexane chiral selector was investigated by means of quantum‐chemical calculations (MNDO), partial least squares (PLS) analysis, and 3D comparative molecular field analysis (CoMFA). Quantitative structure–enantioselective retention relationships (QSERR), were derived which have yielded significant insights into physicochemical properties primarily responsible for chiral recognition. The increase in retention (k′) is favored especially by the analyte π‐basic character, accounted for by the sum of the electrophilic superdelocalizabilities of all aromatic carbon atoms (SPhHOMO), and to minor extent by the H‐bond basicity of the sulfoxide oxygen and the hydrophilicity of solutes. In contrast, the separation factor (α) varied mainly with the steric properties of the substituents and with polar and electrostatic properties of the sulfoxide group. A 3D‐QSERR analysis using CoMFA methodology has provided a more complete description of factors responsible for chiral recognition and has proven to be a useful tool to examine differences in noncovalent fields (both the electrostatic and the steric) mostly associated with variations of enantioselectivity. © 1993 Wiley‐Liss, Inc.
Comparison between cellulose and amylose tris(3,5‐dimethylphenylcarbamate) chiral stationary phases for enantiomeric separation of 17 amidotetralins
Authors: Witte Dirk T. , Bruggeman Frank J. , Franke Jan Piet , Copinga Swier , Jansen Johanna M. , De Zeeuw Rokus A. 
Published: January 2005

AbstractDirect enantiomeric separations of 17 chiral amidotetralins by means of high performance liquid chromatography were performed on stationary phases composed of tris(3,5‐dimethylphenylcarbamate) derivatives of cellulose and amylose, coated on silica gel. The enantiomers of 15 out of 17 amidotetralins were resolved with a resolution of more than 1.5 by at least one of the chiral stationary phases. The stationary phases showed complementary results with regard to the separation of the amidotetralins, that is, pairs that did not separate on the cellulose‐type column were well separated on the amylose‐type column, and vice versa. There was no significant correlation between the chromatographic properties of the chiral stationary phases. © 1993 Wiley‐Liss, Inc.
Enantiomeric conformers of the opioid agonist ketobemidone HCl in the crystal state
Authors: Froimowitz Mark , Cody Vivian 
Published: January 2005

AbstractA crystal of the potent opioid agonist ketobemidone [1‐methyl‐4‐(3‐hydroxyphenyl)‐4‐propionylpiperidine] HCl was analyzed by X‐ray crystallography. The crystal was monoclinic, space group P21/n with four molecules in the unit cell. In agreement with MM2 calculations (J. Med. Chem. 25:1127–1133, 1982), the crystal contains mirror image conformers in which the phenyl ring is equatorial to the piperidine ring. The conformers are enantiomers since they are not superimposable. One conformer is predicted to be responsible for the typical morphine‐like activity of the compound since it closely matches the preferred conformer of the morphine‐like (+)‐phenylmorphan whereas the other conformer resembles the preferred conformers of (+)‐β‐prodine and (−)‐phenylmorphan which have atypical opioid properties and/or structure–activity relationships. The importance of considering the conformational enantiomers of a nonchiral receptor ligand in centrosymmetric crystal structures is emphasized. © 1993 Wiley‐Liss, Inc.
Resolution of enantiomers by HPLC on tris(4‐alkoxyphenylcarbamate)s of cellulose and amylose
Authors: Okamoto Yoshio , Ohashi Toshiaki , Kaida Yuriko , Yashima Eiji 
Published: January 2005

AbstractTen phenylcarbamate derivatives of cellulose and amylose having alkoxy groups such as ethoxy, isopropoxy, and isobutoxy at 4‐position, and methyl groups at 3‐ and 5‐positions and methoxy group at 4‐position were synthesized and their chiral recognition abilities as stationary phases for high‐performance liquid chromatography were investigated and compared to those with tris(4‐methoxyphenylcarbamate)s of cellulose and amylose. In 4‐alkoxy derivatives of cellulose, chiral recognition ability increased as the bulkiness of 4‐alkoxy groups increased. 4‐Isopropoxy and 4‐isobutoxy derivatives showed high chiral recognition. On the other hand, chiral discrimination of amylose 4‐alkoxy derivatives scarcely depended on the bulkiness of the alkoxy group, and 4‐methoxy and 4‐isopropoxy derivatives showed high chiral recognition. 3,5‐Dimethyl‐4‐methoxyphenylcarbamates of cellulose and amylose possessed higher chiral recognition ability than the corresponding 4‐methoxy derivatives. © 1993 Wiley‐Liss, Inc.
Enantiomeric LC separation of calcium antagonists on protein‐based chiral stationary phases
Authors: De Lorenzi Ersilia , Fell Anthony F. , Holmes Alan L. , Caccialanza Gabriele , Massolini Gabriella , Gandini Carlo , Kitsos Mikes , Ponci Carolina 
Published: January 2005

AbstractThree chiral calcium antagonist drugs, bepridil and two dihydropyridine derivatives (nicardipine and REC 15/2375), have been successfully separated within short retention times using either the α1‐acid glycoprotein chiral stationary phase (Chiral AGP) or the ovomucoid column (Ultron ES‐OVM). Aqueous buffer at defined pH is modified by the addition of an organic component (propan‐2‐ol, acetonitrile, ethanol) in order to modulate the retention properties of each system. The influence of pH and percentage of organic modifier on retention, selectivity, resolution, and column performance are discussed for bepridil analyzed on Chiral AGP and for the two dihydropyridines (nicardipine and REC 15/2375) analyzed on Ultron ES‐OVM stationary phases. © 1993 Wiley‐Liss, Inc.
Comparison of the potencies of (+)‐ and (−)‐2‐ethylhexanoic acid in causing peroxisome proliferation and related biological effects in mouse liver
Authors: Sundberg Carola , Wachtmeister Carl‐Axel , Lundgren Bo , DePierre Joseph W. 
Published: January 2005

AbstractMale C57BL/6 mice were exposed to 1% (w/w) (+)‐ or (−)‐2‐ethylhexanoic acid or an equimolar mixture of these enantiomers in their diet for 4 or 10 days. A significant increase in liver weight and a 2‐ to 3‐fold increase in the protein content of the mitochondrial fraction were seen in all cases. Peroxisomal palmitoyl‐CoA oxidation was increased 2‐ to 3.5‐fold after 4 days of treatment and 4‐ to 5‐fold after 10 days, while the corresponding increases in peroxisomal lauroyl‐CoA oxidase activity were 2‐ to 3‐fold and 9‐ to 12‐fold, respectively. Peroxisomal catalase activity was unchanged, whereas the microsomal and cytosolic activities were increased 2‐ to 3‐fold and 6‐ to 16‐fold, respectively. These treatments also induced microsomal ω‐hydroxylation of lauric acid 7‐fold and soluble epoxide hydrolase activity in the mitochondrial and cytosolic fractions, as well as microsomal epoxide hydrolase activity about 50–100%. The only significant differences observed between the effects of (+)‐2‐ethylhexanoic acid and its (−)‐enantiomer were on peroxisomal palmitoyl‐CoA oxidation and lauroyl‐CoA oxidase activity after 4 days of treatment. In both these cases the (+)‐enantiomer resulted in increases which were 50–75% greater than those seen with the (−)‐form. © 1994 Wiley‐Liss, Inc.
(Z)‐1,1‐dichloro‐2‐(4‐benzyloxyphenyl)‐2,3‐bis(4‐methoxyphenyl)cyclopropane: The synthesis and enantiomeric separation of an antitumor agent
Authors: Meyer Karen L. , Magarian Robert A. 
Published: January 2005

Abstract(Z)‐1,1‐Dichloro‐2‐(4‐benzyloxyphenyl)‐2,3‐bis(4‐methoxyphenyl)cyclopropane (5), a potential antitumor agent designed to treat breast cancer, was prepared in three steps. A stereospecific palladium‐catalyzed cross coupling reaction which provided the intermediate (Z)‐triaryl alkene 4 was a crucial step in the synthesis. Makosza phase transfer reaction on 4 gave the enantiomeric (Z)‐dichlorocyclopropane derivatives 5 which were resolved by semipreparative HPLC on a chiral stationary phase consisting of amylose tris‐3,5‐dimethylphenyl carbamate coated on silica gel. © 1994 Wiley‐Liss, Inc.