bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stereochemistry of tissue distribution of racemic propranolol in the dog
Authors: Walle U. Kristina , Thibodeaux Harold , Privitera Philip J. , Walle Thomas 
Published: January 2005

AbstractOnly limited information is available on the stereochemistry of the in vivo distribution of β‐receptor‐blocking drugs. In this study we determined the levels of the propranolol enantiomers in plasma, cerebrospinal fluid (CSF) and central nervous system (CNS), and peripheral tissues in the dog following an intravenous dose of a deuterium‐labeled pseudoracemate. The appearance of the propranolol enantiomers in the CSF was rapid and nonstereoselective, with maximum concentrations reached at 15 min after dosing. The levels of the enantiomers in both CSF and plasma then declined in a parallel biphasic fashion, with a terminal t1/2 of about 125 min. Except for an early high CSF/plasma concentration ratio of 0.35, the CSF propranolol levels corresponded to the unbound concentration in plasma, CSF/plasma 0.20. All areas of the brain showed a similar uptake of propranolol, with a tissue concentration exceeding that in plasma about 10‐fold during the terminal phase of elimination. The uptake of propranolol by peripheral tissues varied widely, ranging from a 50‐fold accumulation by the lungs compared to plasma to no accumulation by adipose tissue. However, as for the CSF, there was no evidence of stereoselective uptake of propranolol by any CNS or peripheral tissue except for the liver. A significantly higher level of (+)‐ vs. (–)‐propranolol in liver tissue presumably was a reflection of stereoselective hepatic metabolism of (–)‐propranolol by this tissue. The slight stereoselectivity in plasma binding of propranolol known to exist in the dog had no significant influence on tissue or CSF distribution.
The determination of (−)‐(S)‐ and (+)‐(R)‐ ifosfamide in plasma using enantioselective gas chromatography: A validated assay for pharmacokinetic and clinical studies
Authors: Young Connie L. , Frank Hartmut , Stewart Cynthia R. , Wainer Irving W. 
Published: January 2005

AbstractAn enantioselective gas chromatographic method has been developed and validated for the determination of the plasma concentration of the enantiomers of the anticancer drug ifosfamide (IFF). In this approach, the IFF enantiomers are separated from the plasma matrix by solid phase extraction, chromatographically resolved by gas chromatography on a chiral stationary phase, and detected by mass selective detection using selective ion monitoring. The assay has been validated for routine clinical and pharmacokinetic use and has a limit of detection in plasma of 250 ng/ml of each isomer.
Chiral stationary phase high‐performance liquid chromatographic resolution and absolute configuration of enantiomeric benzo[a]pyrene diol‐epoxides and tetrols
Authors: Weems Henri B. , Yang Shen K. 
Published: January 2005

AbstractEnantiomers of diastereomeric benzo[a]pyrene (BP) diol‐epoxides, r‐7,t‐8‐dihydroxy‐t‐9,10‐epoxy‐7,8,9,10‐tetrahydro‐BP (BP 7,8‐diol‐anti‐9,10‐epoxide), r‐‐‐‐7,t‐8‐dihydroxy‐c‐9,10‐epoxy‐7,8,9,10‐tetrahydro‐BP (BP 7,8‐diol‐syn‐9,10‐epoxide), r‐9,t‐10‐dihydroxy‐t‐7,8‐epoxy‐7,8,9,10‐tetrahydro‐BP (BP 9,10‐diol‐antiy7,8‐epoxide), and several 7,8,9,10‐tetrahydroxy‐7,8,9,10‐tetrahydrobenzo[a]pyrenes (BP tetrols) were resolved by high‐performance liquid chromatography (HPLC) using columns packed with either (R)‐N‐(3,5‐dinitrobenzoyl)phenylglycine[(R)‐DNBPG] or (S)‐N‐(3,5‐dinitrobenzoyl)leucine [(S)‐DNBL], which is either ionically or covalently bonded to γ‐aminopropylsilanized silica. Resolution of enantiomers was confirmed by ultraviolet‐visible absorption and circular dichroism spectral analyses. Resolved enantiomers of BP diol‐epoxides were each hydrolyzed in acidic solution to a pair of diastereomeric tetrols which were separated by reversed‐phase HPLC. Absolute stereochemistries of enantiomeric diol‐epoxides were deduced by the absolute configuration of their hydrolysis products.
Interactions of chiral molecules with an (r)‐n‐(3,5‐dinitrobenzoyl) phenylglycine HPLC stationary phase
Authors: Berthod Alain , Jin Heng Liang , Stalcup Apryll M. , Armstrong Daniel W. 
Published: January 2005

AbstractForty different chiral molecules were studied by liquid chromatography with a Pirkle‐type, (R)‐N‐(3,5‐dinitrobenzoyl) phenylglycine (DNBPG), chiral stationary phase column. The dramatic effect of a small molecular change on chiral recognition was demonstrated using DL‐amino acid derivatives. The inductive effect on chiral recognition was also studied using trifluoro‐, trichloro‐, dichloro‐, monochloroacetyl, and acetyl derivatives of four different chiral amines. The study of the enantiomer separation of 11 different crown ethers of 2,2′‐binaphthyldiyl showed that the rigidity of the chiral center can be an additional parameter in chiral recognition for the DNBPG phase but not for a β‐cyclodextrin bonded chiral phase. It is apparent from this study that steric effects, inductive effects, and molecular rigidity play important roles in chiral recognition with DNBPG chiral stationary phases.
Resolution of derivatized acids and amines on JTB‐X: A new urea bonded chiral stationary phase
Authors: Kakodkar Sunil V. , Zief Morris 
Published: January 2005

AbstractA new urea‐bonded chiral stationary phase has been developed in our laboratory. This bonded phase has been shown to resolve N‐terminal substituted amino acids and the carboxyl derivatized anti‐inflammatory drugs. Typical α‐value for dinitrobenzoyl phenylglycine was 1.7. Values for derivatized ibuprofen, naproxen, and fenoprofen were 2, 1.84, and 1.6, respectively. Further application of these studies to biologically active compounds such as peptides and drugs is in progress.
Enantioselective hydrolysis of oxazepam 3‐acetate by esterases in human and rat liver microsomes and rat brain s9 fraction
Authors: Yang Shen K. , Liu Kan , Guengerich F. Peter 
Published: January 2005

AbstractRates of hydrolysis of racemic and enantiomeric oxazepam 3‐acetates (OXA) by esterases in human and rat liver microsomes and rat brain S9 fraction were compared. When rac‐OXA was the substrate, esterases in human and rat liver microsomes were highly enantioselective toward (R)‐OXA. In contrast, esterases in rat brain S9 fraction were highly enantioselective toward (S)‐OXA. Hydrolysis rates of rac‐OXA were highly dependent on the amount of esterases used. At 0.05 mg protein equivalent of esterases and 150 nmol of rac‐OXA per ml of incubation mixture, the (R)‐OXA was hydrolyzed 3.6‐fold and 18.5‐fold faster than (S)‐OXA by rat and human liver microsomes, respectively. The specific activities (nmol of OXA hydrolyzed/mg microsomal protein/min) of liver microsomes in the hydrolysis of enantiomerically pure (R)‐OXA were approximately 120 (rat) and 1,980 (human), and in the hydrolysis of enantiomerically pure (S)‐OXA were 4 (rat) and 7 (human), respectively. In the incubation of rac‐OXA with rat brain S9 fraction, (S)‐OXA was hydrolyzed ∼6‐fold faster than (R)‐OXA. Results also indicated an enantiomeric interaction in the hydrolysis of rac‐OXA by esterases in rat and human liver microsomes; the presence of (R)‐OXA stimulated the hydrolysis of (S)‐OXA, whereas the presence of (S)‐OXA inhibited the hydrolysis of (R)‐OXA. In rat brain S9 fraction, the presence of (R)‐OXA inhibited the hydrolysis of (S)‐OXA, whereas the presence of (S)‐OXA appeared to have stimulated the hydrolysis of (R)‐OXA.
Investigation of the chiral recognition by “Brush‐Type” phases in liquid chromatography using crystal structure analyses of diastereomeric 1:1 complexes of a π‐donor and a π‐acceptor derivative of leucine
Authors: Däppen R. , Rihs Grety , Mayer Carl W. 
Published: January 2005

Abstract(R,S)‐N‐Acetyl‐leucine‐2‐naphthylamide can be resolved into its enantiomers on a (S)‐DNBLeucine chiral stationary phase. The mechanism of this separation was investigated using as model complexes the 1:1 S,S‐ and the 1:1 R,S‐cocrystals of the above naphthylamide and N‐3,5‐dinitrobenzoylleucinemethylamide, a soluble analogue of the stationary phase. The observed enantiomeric elution order can be rationalized from their X‐ray data.
Enantiomeric resolution of DNS‐amino acids by ligand exchange chromatography: Comparison of different chiral amino acid amides as additives to the mobile phase
Authors: Girelli A. M. , Sinibaldi M. 
Published: January 2005

AbstractA study developing enantiomeric separations by metal chelate additives to the mobile phase in reversed‐phase liquid chromatography is reported. In particular the use of Cu(II) complexes of L‐prolinamide (L‐ProNH2) and L‐valinamide (L‐ValNH2) is examined and discussed. Interestingly, for a series of DNS‐amino acids these selectors show higher enantioselectivity than that obtained with the corresponding nonderivatized amino acid–Cu(II) complexes.
A vivid model illustrating chiral recognition induced by achiral structures
Authors: Davankov Vadim A. , Meyer Veronika R. , Rais Maya 
Published: January 2005

AbstractIf diastereomeric complexes are adsorbed on a surface or if they include a molecule of solvent, two points of attractive interaction between the chiral species of the complex can be sufficient for mutual chiral recognition of these species. In special cases even one single point of interaction is sufficient. This extension of the three‐point contact rule of Dalgliesh, first observed in chiral ligand‐exchange chromatogrphy, can be demonstrated by using hands.
Studies on the stereoselective effects of a novel 5‐HT2 receptor antagonist on contractile responses of rat aorta
Authors: Mikkelsen Erich O. , Nielsen Tove J. , Nyborg Niels C. B. 
Published: January 2005

AbstractThe effect of the enantiomers of a novel 5‐HT2 receptor antagonist, (±)‐(1R,3S)‐1‐[2‐[4‐[3‐(p‐fluorophenyl)‐1‐indanyl]‐piperazinyl]ethyl]–2‐imidazolidinone, was studied on serotonin (5‐HT), noradrenaline (NA), potassium (K+), and calcium (Ca2+)‐induced contractions in isolated rat thoracic aorta. The enantiomers shifted the 5‐HT, NA, K+, and Ca2+ concentration–response curves to the right in a concentration‐dependent manner and depressed the maximal contractile responses. The (+)‐enantiomer was a far more potent inhibitor of 5‐HT‐induced contractions than the (−)‐enantiomer. The (+)‐enantiomer and phentolamine, both at 10−6 M, had equal inhibitory effects on NA‐evoked contractions. The (+)‐enantiomer was again more potent in inhibiting NA‐induced contractions than the (−)‐enantiomer. Both enantiomers had an equieffective inhibitory effect on K+ and Ca2+‐induced contractions. The results show that the 5‐HT and α‐adrenoceptor antagonism of the two enantiomers is stereoselective, the (+)‐enantiomer being more potent than the (−)‐enantiomer. In contrast the enantiomers had equal, nonstereoselective inhibitory effects on K+ and Ca2+‐evoked contractions.
High‐Performance liquid chromatographic resolution of oxamniquine enantiomers: Application to in vitro metabolism studies
Authors: Noctor Terence A. G. , Fell Anthony F. , Kaye Barry 
Published: January 2005

AbstractA method is described for the HPLC analysis of oxamniquine enantiomers in liver fraction incubates, using a second‐generation α1‐acid glycoprotein‐based column (Chiral‐AGP). Oxamniquine is extracted from the incubation media by liquid–liquid extraction, using diethyl ether. The dried residue is redissolved in eluent, filtered, then injected directly onto the analytical column. The extraction method affords recoveries of oxamniquine of approximately 93%, at concentrations up to 525 μg/ml, with an average relative standard deviation of 5.9%. The limit of detection of the method (to give an SNR = 2 at 246 nm) is 0.3 ng on‐column for the first eluting, laevorotatory enantiomer and 2.3 ng for the dextrorotatory isomer. The method allowed study of the depletion of oxamniquine enantiomers in liver postimicrosomal incubates. In the rat, a turnover of 21.9% was observed, with no apparent enantioselectivity. Similar observations were made for a mouse liver subcellular fraction incubation. The absence of enantioselectivity in this biotransformation may be attributable to the low substrate specificity of the oxidase or dehydrogenase enzymes involved.
Enantiomers of 11‐hydroxy‐10‐methylaporphine having opposing pharmacological effects at 5‐HT1A receptors
Authors: Cannon Joseph G. , Moe Scott T. , Long John Paul 
Published: January 2005

AbstractThe two enantiomers of the title compound have been prepared by different synthetic routes. Both bind strongly to 5‐HT1A receptors from rat forebrain membrane tissue. However, in a guinea pig ileum preparation, the (R)‐enantiomer exhibits properties consistent with its being an agonist, whereas the (S)‐enantiomer shows no agonist effect, but it blocks the actions of the (R)‐enantiomer and of 8‐hydroxy‐2‐di‐n‐propylaminotetralin (8‐OH‐DPAT), a 5‐HT1A agonist. These data are presented as a rare example of enantiomers which demonstrate opposite pharmacological effects at the same receptor.
Direct measurement of enantiomeric ratios of enzymatic resolution by chiral high‐performance liquid chromatography
Authors: Wu Shih‐Hsiung , Lai Su‐Yuan , Lin Shu‐Ling , Chu Fei‐Ya , Wang Kung‐Tsung 
Published: January 2005

Abstract(R)‐ and (S)‐Methyl 2‐(phenoxy)propionate and their acids could be separated simultaneously by a Chiralcel OD or OK column, while (R)‐ and (S)‐methyl 2‐(4‐chlorophenoxy)propionate and their acids were separated concurrently only by an OK column. This is a novel and facile way to measure the enantiomeric excesses of the remaining substrate and product in the reaction of enzymatic resolution; enantiomeric ratios could then be calculated.
In vitro hydrolysis of RR,SS‐threo‐methylphenidate by blood esterases—differential and enantioselective interspecies variability
Authors: Srinivas N. R. , Hubbard J. W. , McKay G. , Hawes E. M. , Midha K. K. 
Published: January 2005

AbstractEnantioselective in vitro hydrolysis of methylphenidate (MPH) by the blood esterases of seven mammalian species is reported. The species included rats, rabbits, dogs, cattle, horses, monkeys, and humans. In vitro incubations up to 8 h were carried out in plasma, red blood cells, and whole blood of the various species. Enantioselective differences were evident among the different species on comparison of the data obtained from the three biological fluids. The esterases present in plasma appeared to show greater activity in the hydrolysis of MPH in all species where comparison with the other two biofluids was possible. Only in the case of humans did esterases present in plasma and red blood cells demonstrate opposite enantioselectivity in the hydrolysis of MPH. Thus after 8 h incubation, the RR‐MPH/SS‐MPH ratios in plasma and red blood cells were 0.31 and 1.16, respectively.
Separating enantiomers by HPLC on silica dynamically coated with a chiral stationary phase of permethylated β‐cyclodextrin
Authors: Pawlowska Maria 
Published: January 2005

AbstractThe paper demonstrates that the technique of solvent generated liquid‐‐solid chromatography can be used to create normal phase systems for chiral separations. The chiral adsorption layer was generated by pumping a binary hexane:ethanol eluent containing a small fraction of permethylated β‐cyclodextrin through a column packed with microparticulate silica. This technique leads to columns with good time stability and reproducibility. The possibility of generating normal phase systems with permethylated β‐cyclodextrin as chiral component via the mobile phase broadens the range of phase system which can be used to separate enantiomers by HPLC.
A method for the quantitative enantioselective HPLC analysis of ethambutol and its stereoisomers
Authors: Blessington B. , Beiraghi A. 
Published: January 2005

AbstractA rapid, quantitative, enantioselective HPLC method, using N,N′‐dibenzylethylenediamine as internal standard, for the analysis of the three stereoisomers of the antituberculosis drug ethambutol and 2‐aminobutan‐1‐ol is described. The derivatisation and chromatographic procedures and their reproducibility, durability, and sensitivity are discussed. Application to assays of raw material, tablet content, and synthetic reactions are illustrated. The method involves perbenzoylation, in pyridine, followed by direct HPLC on a “Pirkle covalent bonded column” containing a 3,5‐dinitrobenzoyl‐D‐phenylglycine as chiral stationary phase (CSP) using hexane/IPA as mobile phase and detection at 230 nm.
Synthesis and effects on peripheral thyroid hormone conversion of (R)‐4‐hydroxypropranolol, a main metabolite of (R)‐propranolol
Authors: Buchinger Wolfgang , Eber Otto , Uray Georg , Lind Peter , Lindner Wolfgang 
Published: January 2005

AbstractThe inhibiting effect of (R,S)‐propranolol on peripheral T4/T3 conversion can be related to the (R)‐isomer. The intention of this study is to clarify if (R)‐4‐hydroxypropranolol, a main metabolite of (R)‐propranolol, develops the same or even a stronger effect on peripheral thyroxine metabolism as the parent drug. (R)‐4‐hydroxypropranolol was synthesized via (R)‐4‐methoxypropranolol and their optical purity was checked chromatographically. Twenty patients suffering from hyperthyroidism were divided into five groups and treated with (R)‐4‐hydroxypropranolol · HCl in dosages from 12 to 75 mg per day in a placebo controlled study over a period of 5 days. The serum hormone levels and resting pulse rate were measured. No significant changes of thyroid parameter could be observed but a significant decrease of resting pulse rate under treatment with 75 mg (R)‐4‐hydroxypropranolol occurred. It could be concluded that (R)‐4‐hydroxypropranolol possesses negative chronotropic effects but develops no changes in thyroid hormone metabolism in hyperthyroid patients.
Fast liquid chromatography for the resolution of chiral compounds
Authors: Perrin Scott R. 
Published: January 2005

AbstractA Pirkle‐concept chiral stationary phase (CSP) derived from N‐(1‐naphthyl)leucine was evaluated for developing methods to reduce analysis times and investigating techniques in the rapid screening of a variety of chiral compounds over a given chiral selector. The effects of reduced column lengths and elevated temperatures were studied to shorten analysis times.
N,N‐dimethylcarbamyl derivatives of oxazepam
Authors: Yang Shen K. , Lu Xiang‐Lin 
Published: January 2005

AbstractThree N,N‐dimethylcarbamyl derivatives of oxazepam {1‐(N,N‐dimethylcarbamyl)oxazepam, 3‐O‐(N,N‐dimethylcarbamyl)oxazepam, and 1,3‐O‐bis(N,N‐dimethylcarbamyl)oxazepam} and a 3‐O‐acyl‐1‐(N,N‐dimethylcarbamyl)‐oxazepam were synthesized from either oxazepam or demoxepam. Enantiomeric pairs of these derivatives and of camazepam were resolved by high‐performance liquid chromatography on at least two of three commercially available chiral stationary phase columns employed. Absolute configurations of resolved enantiomers were established by comparing their circular dichroism spectra to those of enantiomeric oxazepams with known absolute stereochemistry. Similar to those of oxazepam, enantiomers of 1‐(N,N‐dimethylcarbamyl)oxazepam undergo rapid racemization (t½ 1.9 min at 23°C and 0.9 min at 37°C) in an aqueous solution at pH 7.5. The (R)‐enantiomer of rac‐3‐O‐acyl‐1‐(N,N‐dimethylcarbamyl)oxazepam was hydrolyzed ∼4.6‐fold faster than the (S)‐enantiomer by esterases in rat liver microsomes, whereas the (S)‐enantiomer was hydrolyzed ∼43‐fold faster than the (R)‐enantiomer by esterases in rat brain S9 fraction.
Chirality of reverse micelles
Authors: Colombo Luca M. , Thomas Richard M. , Luisi P. L. 
Published: January 2005

AbstractFour chiral analogues of the surfactant Aerosol‐OT (AOT) have been synthesized and characterized. All of them form reverse micelles in apolar solvents in the w0 range 0–30 (w0 = [water]/[tenside]). Reverse micellar solutions have been investigated by UV absorption and circular dichroism spectroscopies with the aim of clarifying whether the formation of the macromolecular micellar structure induces the appearance of new chromophoric bands or perturbs the existing ones. Methanolic solutions of the surfactants, in which no micellar aggregates are formed, were taken as references. One of the products 1(S),1′(S)‐dimethylbisheptylsulphosuccinate sodium salt (MH‐AOT) was capable of forming reverse micelles of relatively high water content (w0 up to 40) and this process was accompanied by a specific increase in the intensity of the circular dichroism band associated with the ester absorbance of the molecule. As no concomitant changes were seen in the UV absorbance spectrum, it was concluded that this observation reflected conformational events occurring within the surfactant rather than chromophoric perturbation. These results are qualitatively similar to those found recently for lecithin reverse micelles which, however, form gels at sufficiently high water contents. The chiroptical properties of these supramolecular aggregates are compared with those of covalent macromolecular systems such as polypeptides.
Control of asymmetric induction in the organometallic synthesis of 3‐methyl‐(E)‐4‐hexen‐2‐one
Authors: Bartik T. , Markó L. , Gerdes I. , Heimbach P. , Knott W. , Schulte H.‐G. 
Published: January 2005

AbstractBis(μ‐methyl‐1,3‐dimethyl‐η3‐allylnickel) reacts in the presence of phosphorus(III) ligands (phosphines, phosphites) with CO to give 3‐methyl‐(E)‐4‐hexen‐2‐one. Systematic experiments were performed using chiral ligands containing menthyl or menthoxy groups and different achiral groups on the P atom to determine the influence of ligand structure and concentration on the direction and extent of chiral induction in this ketone synthesis. It could be shown that reversion of enantioselectivity can be obtained not only by the obvious method of reversing the absolute configuration of the ligand (“parity control”) but also by modifying the nonchiral substituents of the phosphorus ligand (“complementarity control”). The synthesis, physical, and spectroscopic properties of several new menthyl phosphines and phosphites are reported.
A highly enantioselective rhodium catalyst for the hydrogenation of aliphatic α‐keto esters
Authors: Spindler Felix , Pittelkow Ulrich , Blaser Hans‐Ulrich 
Published: January 2005

AbstractThe enantioselective hydrogenation of several α‐keto acid derivatives with rhodium diphosphine catalysts has been investigated using a random screening approach. The neutral rhodium catalyst prepared in situ from bis(2,5‐norbornadiene rhodium chloride) and NORPHOS has been found to be an excellent catalyst for preparing aliphatic α‐hydroxy esters in high optical purities. The reaction parameters for the hydrogenation of ethyl 2‐oxo‐4‐phenyl‐butyrate, an intermediate for the ACE inhibitor Benazepril, were optimized and the best optical yields obtained were 96%.
Steric hindrance influence on the enantiorecognition ability of tyrosine‐derived chiral stationary phases
Authors: Siret L. , Tambuté A. , Bégos A. , Rouden J. , Caude M. 
Published: January 2005

AbstractFour chiral stationary phases (CSPs) derived from N‐(3,5‐dinitrobenzoyl)tyrosine have been synthesized. They differ by the substituent nature (methyl, ethyl, isopropyl, tert‐butyl) of the aliphatic amide function. The enantiorecognition ability of these CSPs was evaluated with 10 racemates. For the majority of them, the stereoselectivity increases with the steric hindrance of the substituent. The chiral selector enantiomeric separation on the resulting CSPs has evidenced a reversal of elution order only for CS 4 on CSP 4 (tert‐butyl substituent), suggesting a change in its conformation.