bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unusual amino acids I: Asymmetric synthesis of furylalanine derivatives
Authors: Krause H.W. , Wilcke F.W. , Kreuzfeld H.‐J. , Döbler Ch. 
Published: January 2005

AbstractNonproteinogenic amino acids are valuable active compounds from their pharmacological and biochemical effects and also as novel building blocks for peptides. The preparation of furylalanine derivatives by asymmetric hydrogenation is described. Amino‐phosphine‐phosphinite‐rhodium complexes catalyzed the hydrogenation of the prochiral dehydroamino acid precursors in high rate and with enantioselectivities of 70—90% ee. Substrate‐catalyst ratios up to 2,000 can be used depending on the catalyst applied. The procedure turns out to be suitable for larger scale preparations.
Effective methods for enantioselective analysis of glycidol derivatives by liquid chromatography
Authors: Kennedy Joseph H. , Weigel Leland O. 
Published: January 2005

AbstractMethodology for determination of the enantiomeric purity of sixteen 2,3‐epoxy‐1‐propanols (glycidols) is delineated. Conversion of these epoxy alcohols and 1‐naphthyl isocyanate (NIC) into the 1‐naphthyl carbamates is catalyzed by dibutyltin diacetate. Enantiomers of these carbamates are resolved on a Chiralcel® OD column. Advantages of this method include mildness of reaction conditions, nonreliance on diastereomeric derivatization, and appendage of a UV‐absorbing chromophore to the analyte.
Enantio‐ and regioselectivity in the epoxide‐hydrolase‐catalyzed ring opening of simple aliphatic oxiranes: Part I: Monoalkylsubstituted oxiranes
Authors: Wistuba D. , Schurig V. 
Published: January 2005

AbstractThe in vitro conversion of chiral aliphatic monoalkylsubstituted oxiranes into 1,2‐diols catalyzed by epoxide hydrolase of rat liver microsomes occurs with substrate enantioselectivity and regioselectivity. Substrate enantioselectivity is generally low, and has the same sense, for methyloxirane, vinyloxirane, epichloro‐, and epibromohydrin. In the hydrolysis of t‐butyloxirane inhibitory effects are involved leading to a complex pattern of enantioselectivity. All investigated monosubstituted aliphatic oxiranes are hydrolyzed with high regioselectivity by nucleophilic attack of water at the unsubstituted ring carbon atom. The enantiomeric excess of the unreacted oxirane substrates and the diol metabolites formed were determined by complexation and inclusion gas chromatography. © 1992 Wiley‐Liss, Inc.
Chiral α‐substituted α‐aryloxy acetic acids: Synthesis, absolute configuration, chemical resolution, and direct separation by hplc
Authors: Bettoni G. , Ferorelli S. , Loiodice F. , Tangari N. , Tortorella V. , Gasparrini F. , Misiti D. , Villani C. 
Published: January 2005

AbstractSeveral α‐monoalkyl‐α‐aryloxyacetic acids have been synthesized and resolved into their optical antipodes; their absolute configuration was also established by chiroptical and chemical methods. The two enantiomers of a series of these compounds show opposite effects on skeletal muscle fibers chloride conductance. Therefore a HPLC procedure was developed for the direct determination of the optical purity of the antipodes before submitting them to biological tests. The chromatographic study was performed on DACH‐DNB chiral stationary phase which shows a remarkable enantioselectivity for the considered compounds as free acids, esters and amides under different conditions with essentially the same chiral mechanism of separation. © 1992 Wiley‐Liss, Inc.
Synthesis and pharmacological investigation of stereoisomeric muscarines
Authors: Amici Marco De , Dallanoce Clelia , Micheli Carlo De , Grana Enzo , Dondi Giuseppina , Ladinsky Herbert , Schiavi Giovannibattista , Zonta Franco 
Published: January 2005

AbstractThe synthesis of the eight stereoisomers of muscarine has been efficiently accomplished by utilizing the two enantiomers of lactic esters as starting material. The synthetic strategy is based on a SnCl4‐catalyzed addition of allyltrimethylsilane to O‐protected lactic aldehydes followed by an iodocyclization process. All the final derivatives possess an enantiomeric excess higher than 98%. The four pairs of enantiomers bound to M1, M2, and M3 muscarinic receptor subtypes in membranes from cerebral cortex, heart, and salivary glands, respectively, and recognized heterogeneous states of the receptors. Of the eight isomers, only natural muscarine (+)‐1 recognized three affinity states of the M2 receptor. The compound was also the only one to show selectivity in the binding study, demonstrating 37‐ to 44‐fold higher affinity for the M2 than for the M1 or M3 receptors. In addition, the compounds were tested in functional assays on isolated guinea pig atria (M2 receptors) and ileum (mixed population of M2 and M3 receptors) and their muscarinic potencies were determined. Among the eight isomers, again only (+)‐1 enantiomer was found to be very active on both tissues. Its potency was more than two orders of magnitude higher than that of its enantiomer (−)‐1 as well as the other six isomers. The eudismic ratios (E.R.) deduced from the two functional tests were 324 and 331. © 1992 Wiley‐Liss, Inc.
Stereoselective binding of etodolac to human serum albumin
Authors: Muller Noëlle , Lapicque Françoise , Monot Claudine , Payan Elisabeth , Dropsy Rémi , Netter Patrick 
Published: January 2005

AbstractThe protein binding of etodolac enantiomers was studied in vitro by equilibrium dialysis in human serum albumin (HSA) of various concentrations varying from 1 to 40 g/liter, by addition of each enantiomer at increasing concentrations. In the 1 g/liter solution, at the lowest drug levels, the (R)‐form is more bound than its antipode, the contrary being observed at the highest drug levels. For higher albumin concentrations, S was bound in a larger extent than R. Using the displacement of specific markers of HSA sites I and II, studied by spectrofluorimetry, it was suggested that R and S are both bound to site I, while only S is strongly bound to site II. © 1992 Wiley‐Liss, Inc.
Stereospecific gas chromatographic method for determination of methadone in serum
Authors: Kristensen K. , Angelo H.R. 
Published: January 2005

Abstractrac‐Methadone is used clinically for the chronic maintenance treatment of heroin addiction and for the relief of pain. As the pharmacological activity of methadone is due primarily to the (−)‐(R)‐enantiomer, stereospecific measurements of methadone serum concentrations in methadone‐treated patients are expected to be more relevant for clinical studies than earlier described total drug measurements. This study describes a stereospecific gas chromatographic (GC) method for the determination of methadone in serum. The extracted methadone was derivatizised with (−)‐menthyl chloroformate. The diastereometric derivatives were analysed by GC on a capillary column and detected with a nitrogen‐phosphorus detector. The resolution factor obtained for the methadone enantiomers was 1.1 with a relatively short time of analysis (30 min). By analysing the pure (−)‐(R)‐enantiomer, no racemization was seen during the analysis. The lower limit of quantitation was 75 nmol/1 for each enantiomer. Measurements of the ratio between (−)‐(R)‐ and (+)‐(S)‐methadone concentrations in serum from five methadone‐treated patients showed interindividual differences (range 0.5–1.1). The patient results correlated well with those from another GC method measuring total methadone.
Asymmetric synthesis polymerization of meso oxiranes and thiiranes
Authors: Spassky Nicolas , Momtaz Ardéchir , Kassamaly Asmina , Sepulchre Maurice 
Published: January 2005

AbstractThe asymmetric synthesis polymerization or “enantiogenic” polymerization of some meso oxiranes, cis‐dimethyloxirane (cis‐DMO) and cyclohexene oxide (CHO), and thiiranes, cis‐dimethylthiirane (cis‐DMT) and cyclohexene sulfide (CHS), initiated with different chiral systems was examined. Strong differences in behaviour were observed between oxiranes and thiiranes depending on the initiator used. The initiators based on ZnEt2 or CdMe2 and a chiral diol give optically active polymers from meso thiiranes but fail to induce an asymmetric polymer synthesis with meso oxiranes. A new chiral initiator based on ZnEt2 and (1S,2R)‐ephedrine allowed us to prepare optically active poly CHOs, which can be fractionated into fractions exhibiting opposite optical activities. © 1992 Wiley‐Liss, Inc.
High enantiofacial selectivity in the OsO4 dihydroxylation of e‐stilbene with a chiral biphenyl diamine catalyst
Authors: Haubenstock Howard , Subasinghe Kamani 
Published: January 2005

AbstractThe chiral biphenyl‐containing diamine 1 complexed with OsO4 oxidized trans‐stilbene at –80°C to (+)‐(1R;2R)‐1,2‐diphenyl‐1,2‐ethanediol in high enantiomeric excess. On the other hand, (R)‐ or (S)‐2,2'‐bis(dimethylamino)‐6,6'‐dimethylbiphenyl proved to be ineffective in promoting oxidation. © 1992 Wiley‐Liss, Inc.
Separation of enantiomeric amines and acids using chiral ion‐pair chromatography on porous graphitic carbon
Authors: Karlsson A. , Pettersson C. 
Published: January 2005

AbstractThe application of porous graphitic carbon as adsorbing phase for direct separation of enantiomeric acids and amines using chiral ion‐pair chromatography is described. The enantiomeric amines were separated as diastereomeric ion pairs with N‐benzyloxycarbonylglycyl‐L‐proline, N‐benzyloxycarbonylglycylglycyl‐L‐proline, or captopril as the chiral counterion. High enantioselectivities were obtained for amines having a hydrogen bonding function in the vicinity of the asymmetrical carbon atom. Quinine was the chiral counterion used to separate the enantiomeric acids. The strongly UV‐absorbing quinine improved detection of solutes having low UV‐absorbing properties, e.g., (R,S)‐2‐chloropropionic acid, by “indirect detection.” Retention and stereoselectivity of enanticmeric acids were regulated by the quinine concentration and by the addition of carboxylic acids as well as polar modifiers, e.g., methanol and 2‐propanol, to the mobile phase. © 1992 Wiley‐Liss, Inc.
Pulmonary inversion of 2‐arylpropionic acids: Influence of protein binding
Authors: Hall S.D. , Hassanzadeh‐Khayyat M. , Knadler M.P. , Mayer P.R. 
Published: January 2005

AbstractThe possible contribution of pulmonary metabolism to the putative first‐pass metabolism of 2‐arylpropionic acid nonsteroidal antiinflammatory drugs has not been documented. Isolated perfused rabbit lungs, perfused with 4.5% bovine serum albumin or 5% dextran, were used to study the pulmonary elimination of (R)‐ and rac‐ibuprofen, fenoprofen, and flurbiprofen. In the absence of protein binding, ibuprofen was metabolized via inversion and other pathways, whereas fenoprofen metabolism was essentially restricted to inversion of the (R)‐enantiomer; fraction inverted (± SE) was 0.37 ± 0.05 for (R)‐ibuprofen and 0.85 ± 0.03 for (R)‐fenoprofen. In the presence of protein, neither ibuprofen nor fenoprofen was metabolized. Flurbiprofen did not undergo pulmonary elimination under any condition studied. This study illustrates that even though a tissue is capable of metabolism, particularly inversion of 2‐arylpropionics, the quantitative importance of such elimination pathways may be minimal in the presence of the high degree of protein binding that is characteristic of these drugs. © 1992 Wiley‐Liss, Inc.
Stoichiometry of interaction between soluble (—)‐dopa melanin and enantiomers of ephedrine by NMR spectroscopy
Authors: Salazar‐Bookaman M.M. , Fowble J.W. , Patil P.N. 
Published: January 2005

AbstractSynthetic soluble (—)‐dopa melanin was prepared in deuteriated buffer, pH 8, by autooxidation of the precursor. At 6 mM of the precursor, the incorporation was over 90%. The changes in the line width measurements of N‐CH3 protons of enantiomers of ephedrine in the soluble melanin were quantified by NMR spectroscopy. The dissociation constants of (—)‐1R,2S‐ephedrine, (+)‐1S,2R‐ephedrine, (—)‐1R,2R‐ψ‐ephedrine, and (+)‐1S,2S‐ψ‐ephedrine were 11.7, 4.20, 3.60, and 4.80 mM, respectively. Since the concentration of (—)‐dopa was known and since the conversion of (—)‐dopa to indole units of melanin was considered as 1:1, the stoichiometry of the interaction between the drug and the indole unit was calculated. Based on the dissociation constants of the enantiomers, it appears that up to four molecules of (—)‐ephedrine can interact with one indole unit of the melanin, while such a ratio for other isomers appear to be 2:1. The preference by indole units of melanin is stereoselective. © 1992 Wiley‐Liss, Inc.
Optical resolution of unusual amino acids using microbial proteases
Authors: Miyazawa Toshifumi , Iwanaga Hitoshi , Yamada Takashi , Kuwata Shigeru 
Published: January 2005

AbstractWe have developed novel enzymatic methods for the optical resolution of unusual amino acids. In this work, we tried two microbial proteases, available inexpensively in a crude state, from Aspergillus oryzae and from Bacillus subtilis. The enantioselective hydrolysis of the methyl esters of the N‐benzyloxycarbonyl (Z) derivatives of a number of amino acids, both aliphatic and aromatic, was examined using these microbial proteases. The enantiomeric purities of the resolved Z‐amino acids were determined accurately by methods based on the reversed‐phase HPLC separation of diastereomeric derivatives or the HPLC separation of enantiomeric derivatives on chiral stationary phases. In general, B. subtilis protease yielded better results than A. oryzae protease. Using the former protease, the amino acids bearing aliphatic side chains were resolved with good to excellent enantioselectivities and reasonable hydrolysis rates. The speed of hydrolysis was reduced significantly when the length of the side chain was longer than 5 carbon atoms. Phenylalanine, halogenated phenylalanines, and phenylalanine homologs were also resolved, generally with high enantiomeric purities, though the hydrolysis rates were not always reasonably fast. In all the cases examined, the L‐enantiomers were preferentially hydrolyzed as in the lipase‐catalyzed enantioselective hydrolysis reported previously. © 1992 Wiley‐Liss, Inc.
Resolution and adrenergic activities of the optical isomers of 4‐[1‐(1‐Naphthyl)ethyl]‐1H‐imidazole
Authors: Hong Seoung S. , Romstedt Karl J. , Feller Dennis R. , Hsu Fu‐Lian , George Clifford , Cupps Thomas L. , Lyon Robert A. , Miller Duane D. 
Published: January 2005

AbstractRecently we synthesized a naphthalene analog of medetomidine, 4‐[1‐(1‐naphthyl)ethyl]‐1H‐imidazole hydrochloride (1), and found it to be highly potent in adrenergic systems. The separation of optical isomers of this naphthalene analog was achieved by using the isomers of tartaric acid. The optical purities of the isomers were determined by HPLC using a chiral column. Using X‐ray analysis the (+)‐isomer was determined to have the S absolute configuration. It has been reported that the (+)‐isomer of medetomidine (2) is the most potent enantiomer on α2‐adrenergic receptors. There were both qualitative and quantitative differences in biological activities of the optical isomers of 1 in α1‐ and α2‐adrenergic receptor systems of guinea pig ileum and human platelets. (+)‐(S)‐1, but not (—)‐(R)‐1 was a selective agonist of α2‐mediated responses in ileum whereas (—)‐(R)‐1 was more potent than (+)‐(S)‐1 as an inhibitor of α2‐mediated platelet aggregation. © 1992 Wiley‐Liss, Inc.
Improved resolution of (±)‐trans‐2'‐hydroxy‐5,9‐dimethyl‐6,7‐benzomorphans
Authors: Wetzel Joseph R. , Grego John D. , Mallamo John P. 
Published: January 2005

AbstractAn efficient resolution of (±)‐trans‐2'‐hydroxy‐5,9‐dimethyl‐6,7‐benzomorphan has been developed employing (—)‐(R)‐ and (+)‐(S)‐O‐acetylmandelic acids. Measurement of optical rotations on the resolved bases, NMR analyses of diastereomeric urea derivatives, as well as gas chromatographic analyses of diastereomeric amide derivatives indicate a net improvement over previous resolution methodology and an enantiomeric excess ≥ 99%. © 1992 Wiley‐Liss, Inc.
Enantioselective pharmacodynamics of the nonsteroidal antiinflammatory drug ketoprofen: In vitro inhibition of human platelet cyclooxygenase activity
Authors: Hayball Peter J. , Nation Roger L. , Bochner Felix 
Published: January 2005

AbstractThe pharmacological activity of ketoprofen enantiomers was investigated in humans by an in vitro method. The antiplatelet effect of ketoprofen was assessed by measuring the inhibition of platelet thromboxane B2 (TXB2) generation during the controlled clotting of whole blood obtained from each of four healthy volunteers. Ketoprofen was added separately to whole blood as a range of concentrations of (1) predominantly (S)‐ketoprofen, (2) racemic ketoprofen, and (3) predominantly (R)‐ketoprofen. (S)‐Ketoprofen was found to be solely active at inhibiting human platelet TXB2 production; (R)‐ketoprofen was devoid of such activity and did not modify the potency of its optical antipode. A relationship between the percentage inhibition of TXB2 generation and the unbound concentration of (S)‐ketoprofen in serum was modelled according to a sigmoidal Emax equation. The mean (±SD) serum unbound concentration of (S)‐ketoprofen required to inhibit platelet TXB2 generation by 50% (EC50) was 0.320 (±0.062) ng/ml. This value for ketoprofen is considerably lower than previously reported values for (S)‐ibuprofen and (S)‐naproxen. © 1992 Wiley‐Liss, Inc.
Direct coupled column separation and determination of the diastereomeric glucuronides of almokalant, a new class III antiarrhythmic drug, in human urine
Authors: Stefansson Morgan , Hoffmann Kurt‐Jürgen 
Published: January 2005

AbstractA reversed‐phase coupled column separation (CCS) system for the analysis of two diastereomeric glucuronides of almokalant, a new class III antiarrhythmic drug, in human urine is described. After direct injection of urine samples (50 μl) the glucuronides were isolated by complex formation on a terbium(III) loaded strong cation exchanger at alkaline pH. The solutes were eluted from the precolumn by an acidic mobile phase, enriched and separated on Hypercarb (porous graphitic carbon) as analytical column with 0.1 M acetic acid pH 2.8 and 30% acetonitrile as mobile phase. The calibration graph was linear (r2 = 0.9999) and the detection limits were in the low picomole (UV) or femtomole (fluorescence) range. Optimization of the analytical column revealed that elution order and selectivity for the glucuronides were dependent on the buffer agent and temperature used. By appropriate choice of mobile phase conditions all four diastereomers could be separated. © 1992 Wiley‐Liss, Inc.
Influence of uncharged mobile phase additives, pH, and structure differences on retention and enantioselectivity of chiral hexa‐ and octa‐hydrobenzo(g) quinolines on an ovomucoid glycoprotein column
Authors: Küsters Ernst , Spöundlin Christoph , Redey Stephan , Widmer Armin 
Published: January 2005

AbstractThe enantiomeric resolution of six closely related hexa‐ and octa‐hydrobenzo(g) quinoline racemates by HPLC on an ovomucoid column (Ultron ES‐OVM) is described. First, the influence of uncharged mobile phase additives (with different hydrogen bonding properties) and pH on retention and enantioselectivity is investigated. It is shown that an optimum pH of around 6 for the given separations is much more important than the choice of modifier. Second, the influence on enantioselectivity of small differences in molecular structure is examined. In one case a large difference is obtained for diastereomeric racemates depending on the cis‐ or trans‐configuration of the quinoline skeleton. Higher flexibility of the solute seen in the cis enantiomers seems to improve enantioselectivity. © 1993 Wiley‐Liss, Inc.
Influence of the route of administration on the pharmacokinetics of pirprofen enantiomers in the rat
Authors: Brocks Dion R. , Liang William T.C. , Jamali Fakhreddin 
Published: January 2005

AbstractThe pharmacokinetics of the enantiomers of the non‐steroidal anti‐inflammatory drug pirprofen were studied in male Sprague‐Dawley rats after oral and intravenous (iv) doses of the racemate. No significant differences were detected between the enantiomers after oral or iv dosing in t½, Vd, or ∑Xu. However, the R:S area under the plasma concentration (AUC) ratio after oral doses (0.92 ± 0.13) was slightly but significantly lower than after matching iv doses (1.05 ± 0.036). The absolute bioavailability of the active S‐enantiomer (78.5%) after oral doses was higher than the inactive R‐enantiomer (69.3%). The plasma protein binding of both enantiomers was saturable over a fivefold range of plasma concentrations. At higher plasma concentrations, the S‐enantiomer was less bound than the R‐enantiomer. In an in vitro experiment using everted rat jejunum, no chiral inversion was discernible. The dependency of the AUC ratio of the enantiomers on the route of administration may be due to stereoselective first‐pass metabolism. © 1993 Wiley‐Liss, Inc.
Enantioselective determination of hydroxychloroquine and its major metabolites in urine and the observation of a reversal in the (+)/(−)‐hydroxychloroquine ratio
Authors: Fieger Hiltrud , Iredale Joanna , Wainer Irving W. 
Published: January 2005

AbstractA sequential achiral‐chiral high‐performance liquid chromatographic system has been developed for the quantitation in urine of the enantiomers of hydroxychloroquine (HCQ), and of its 3 major metabolites, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ). HCQ and its metabolites were separated and quantified on a cyano‐bonded phase, and the enantiomeric ratios were determined using a Chiral‐AGP chiral stationary phase. The assay validation and application of this method to a preliminary study in a human volunteer are presented. In this subject, the initial 0‐4 h urine contained the 2 HCQ enantiomers in a ratio of (+)‐HCQ:(−)‐HCQ of 3:2; by the 2,064 h of the study, this ratio had reversed to (+)‐HCQ:(−)‐HCQ of 3:7. © 1993 Wiley‐Liss, Inc.
Influence of specific albumin ligand markers used as modifiers on the separation of benzodiazepine enantiomers by chiral liquid chromatography on a human serum albumin column
Authors: Chosson Elizabeth , Uzan Serge , Gimenez Françclois , Wainer Irving W. , Farinotti Robert 
Published: January 2005

AbstractSpecific ligand markers for the various binding sites of human serum albumin (HSA) have been described in the literature. Some of these markers (medium chain fatty acids, warfarin, digoxin, and bilirubin) were used as mobile phase modifiers. Using a high performance liquid chromatographic (HPLC) column containing HSA as stationary phase, their influence was investigated on the separation in this phase of the enantiomers of three benzodiazepines (temazepam, oxazepam, and lorazepam). Displacement effects were observed with medium chain fatty acids. This influence was proportional to the chain length and to the concentration of acid. Allosteric cooperative effects were noted with digoxin for the three benzodiazepines. Both displacement and cooperative effects were observed with warfarin. Stereoselectivity was decreased for temazepam and oxazepam and increased for lorazepam. © 1993 Wiley‐Liss, Inc.