bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclodextrin derivatives in GC separation of racemic mixtures of volatiles: Part III
Authors: Bicchi Carlo , Artuffo Giuseppe , D'Amato Angela , Galli Anna , Galli Mario 
Published: January 2005

AbstractThe gas chromatographic performance of differently derivatized α‐, β‐, and γ‐cyclodextrins in the separation of racemic mixtures of volatiles is investigated. The performances of 2,3,6‐permethylated α‐, β‐, and γ;‐cyclodextrins and 2,6‐dimethyl‐3‐trifluoro‐acetyl α‐, β‐, and γ‐cyclodextrins mixed with different ratios of OV‐1701 or OV‐1701‐OH terminated were tested with racemates with widely differing structures. The influence of the percentage of cyclodextrins in polysiloxane, of film thickness of the stationary phase, of the length of the column, of column conditioning, and of the operating temperatures in the separations of different racemates has been evaluated.
Stereoselective disposition and tissue distribution of carvedilol enantiomers in rats
Authors: Fujimaki Masayoshi 
Published: January 2005

AbstractAfter intravenous bolus injection of rac‐carvedilol at 2 mg/kg to the rat, the (+)‐(R)‐ and (—)‐(S)‐enantiomer levels in the blood and tissues (liver, kidney, heart, muscle, spleen, and aorta) were measured by stereospecific HPLC assay. As compared with the (+)‐(R), the (—)‐(S) had a larger Vdss (3.32 vs. 2.21 liter/kg), MRT (33.4 vs. 25.6 min), and CLtot (96.1 vs. 83.8 ml/min/kg). AUC comparison after iv and po administration showed systemic bioavailability of the (—)‐(S) to be about half that of its antipode, explained by the fact that the free fraction of the (—)‐(S) in blood was 1.65‐fold greater than that of the (+)‐(R). Tissue‐to‐blood partition coefficient values for the (—)‐(S) were 1.6‐ to 2.1‐fold greater than those for the (+)‐(R) in all tissues, showing that the (—)‐(S) accumulates more extensively in the tissues. These results were consistent with the greater Vdss for the (—)‐(S) estimated from systemic blood data. The stereoselective tissue distribution of carvedilol enantiomers results from an enantiomeric difference in plasma protein binding rather than in tissue binding. © 1992 Wiley‐Liss, Inc.
Chiral hplc‐cd studies of the antituberculosis drug (+)‐ethambutol
Authors: Blessington B. , Beiraghi A. , Lo T.W. , Drake A. , Jonas G. 
Published: January 2005

AbstractLong standing errors in major pharmacopoeiae (BP,USP, and Eu.Ph.) concerning the absolute stereochemistry of the widely used antituberculosis drug (+)‐ethambutol have been clarified by unambiguous synthesis and chiral HPLC. on a Pirkle, covalent D‐phenylglycine column of perbenzoyl derivatives of each stereomer; the enantiomeric (−)‐(R,R) and (+)‐(S,S)‐ethambutols together with the optically inactive (meso)‐(R,S)‐ethambutol. This paper describes how circular dichroism (CD) alone and combined with HPLC is used to demonstrate this chiral separation and also to confirm the absolute stereochemistry of each stereomer of ethambutol and its synthetic precursor 2‐aminobutan‐1‐ol from studies of „exciton coupling.”︁ The strengths and weaknesses of these chiral techniques are discussed.
Effects of the stereochemical orientation of phenethylamines and imidazolines on α‐adrenergic receptor‐mediated dna synthesis in primary cultured rat hepatocytes
Authors: Esbenshade Timothy A. , Hamada Akihiko , Miller Duane D. , Feller Dennis R. 
Published: January 2005

AbstractThe hepatic α1‐adrenergic receptor mediates a variety of hepatic functions including respiration, glycogenolysis, gluconeogenesis, and growth. We have utilized a rat primary hepatocyte culture system to show that the α1‐adrenergic receptor can be activated in a stereoselective manner by a series of phenethylamines and catecholimidazolines resulting in the stimulation of DNA synthesis as determined by [3H]thymidine incorporation. The phenethylamines adhered to the Easson–Stedman hypothesis with a rank order of potency of (–)‐(R)‐norepinephrine (NE) > (+)‐(S)‐NE > the desoxy analog dopamine (DA) for the stimulation of DNA synthesis. However, the 2‐substituted catecholimidazolines did not follow this trend and demonstrated an order of potency of the desoxy analog 3,4‐dihydroxybenzyl imidazoline (DHT) ≥ (–)‐(R)‐2‐(3,4,α‐trihydroxybenzyl)imidazoline (TBI) > (+)‐(S)‐TBI. 4‐Substituted catecholimidazolines were less potent as inducers of DNA synthesis than the corresponding 2‐substituted analogs with an order of potency of (+)‐(R)‐4‐(3,4‐dihydroxybenzyl)imidazoline (DBI) > (+, –)‐(R,S)‐DBI > (–)‐(S)‐DBI. When the β‐hydroxyl moiety of NE is replaced with an amino group as in 3,4‐dihydroxyphenylethylenediamine, the isomers are less active than the β‐hydroxylated analogs and also demonstrate no stereoselectivity for the stimulation of DNA synthesis. These results demonstrate that the hepatic α1‐adrenergic receptor can recognize various isomeric forms of these compounds and that hepatocellular growth can be modulated in a stereoselective manner by phenethylamines and imidazolines. © 1992 Wiley‐Liss, Inc.
An improved synthesis of the enantiomers of bm‐5 and their effects on the central in vivo release of acetylcholine
Authors: Nilsson Björn M. , De Boer Peter , Grol Cor. J. , Hacksell Uli 
Published: January 2005

AbstractRacemic N‐methyl‐N‐(1‐methyl‐4‐pyrrolidino‐2‐butynyl)acetamide (BM‐5), a putative postsynaptic agonist and presynaptic antagonist at muscarinic receptors, was resolved into the enantiomers by a new method suitable for large scale preparation. The method involves a chemoselective N‐debenzylation as the key step. The enantiomers of BM‐5 were obtained after six separate steps in 25% overall yield. The ability of the enantiomers to release acetylcholine was evaluated in vivo by use of brain dialysis. (R)‐BM‐5 was the more potent enantiomer in this assay. © 1992 Wiley‐Liss, Inc.
Absolute configuration and conformation of the pure opioid antagonist (+)‐2,9α‐dimethyl‐5‐(m‐hydroxyphenyl)morphan
Authors: Froimowitz Mark , Pangborn Walter , Cody Vivian 
Published: January 2005

Abstract(+)‐2,9α‐Dimethyl‐5‐(m‐hydroxyphenyl)morphan is the only phenylmorphan analog whose affinity for opioid K‐receptors is greater than its affinity for opioid κ‐receptors. Pharmacologically, the compound is a pure opioid antagonist devoid of agonist activity in in vivo assays of antinociception. The absolute configuration of the compound has been determined to be (1R,5S,9R) from an X‐ray crystallographic study of the chloride salt. Thus, the absolute configuration corresponds to that of the atypical opioid agonist (–)‐phenylmorphan while the weak atypical agonist (–)‐2,9α‐dimethyl‐5‐(m‐hydroxyphenyl)morphan corresponds to the potent morphine‐like (+)‐phenylmorphan. The preferred orientations of the phenyl ring for the two stereoisomers were determined using the molecular mechanics program MM2‐87 and found to vary from that of the two parent compounds. The atypical properties of the two 9α‐methyl analogs is consistent with an opioid ligand model which proposes that morphine‐like properties require a particular range of phenyl orientations. There was good agreement between the structure obtained from X‐ray crystallography and computed with the MM2‐87 program. © 1992 Wiley‐Liss, Inc.
Resolution and stability of oxazepam enantiomers
Authors: Yang Shen K. , Lu Xiang‐Lin 
Published: January 2005

AbstractA solvent mixture containing dioxane, acetonitrile, and hexane was found to be suitable as a mobile phase to resolve oxazepam enantiomers by chiral stationary phase high performance liquid chromatography using covalent Pirkle columns. The resolved oxazepam enantiomers in this solvent mixture had a racemization half‐life greater than 3 days at 23°C. When desiccated at 0°C as dried residue, OX enantiomers were stable for at least 50 days with less than 2% racemization. The conditions which stabilized OX enantiomers significantly facilitated the determination of racemization half‐lives of OX enantiomers in a variety of aqueous and nonaqueous solvents and at different temperatures. © 1992 Wiley‐Liss, Inc.
Enantioselectivity in the induction of peroxisome proliferation by 2‐ethylhexanoic acid
Authors: Macherey Anne Christine , Grégoire Stéphane , Tainturier Gérard , Lhuguenot Jean Claude 
Published: January 2005

AbstractThe stereoselectivity of the peroxisome proliferation potency of 2‐ethylhexanoic acid (2‐EHA), a metabolite of the plasticizer di‐(2‐ethylhexyl) adipate, was investigated in vitro. The enantiomers of 2‐EHA were prepared via the semipreparative HPLC resolution of their diastereoisomeric (+)‐(R)‐1‐phenylethylamine derivatives and the subsequent hydrolytic cleavage. Monolayers of hepatocytes were incubated 3 days with solutions of (—)‐(R), (+)‐(S), and (±)‐2‐EHA. The peroxisome proliferation potency was measured by means of determination of the peroxisomal palmitoyl coenzyme A oxidation. The theoretical induction component due to each enantiomer were calculated from the experimental data considering the enantiomeric purities of the acids. The (+)‐(S)‐enantiomer was found to be the most potent inducer, e.g., the eutomer, while the (—)‐(R) was the distomer. The eudismic ratio was about 1.6 and the racemic mixture exhibited an intermediary potency. These results, obtained in vitro in conditions avoiding confounding factors such as pharmacokinetics, suggest that the peroxisome proliferation induced by 2‐ethylhexanoic acid is a stereoselective phenomenon. © 1992 Wiley‐Liss, Inc.
Discrimination in resolving systems: Ephedrine‐mandelic acid
Authors: Valente Edward J. , Zubkowski Jeffrey , Eggleston Drake S. 
Published: January 2005

AbstractResolution of mandelic acid with (—)‐(1R,2S)‐ephedrine in water and ethanol produces intermediate diastereomeric salts with greatly disparate solubilities and melting points. Single crystal X‐ray analysis of the less (L) and more (M) soluble (—)‐ephedrinium mandelates (I, II) shows crystal structures which are isosteric, each crystallizing in the monoclinic system, space group C2. Protonated ephedrines occupy the same relative positions in the L‐ and M‐salts, and mandelates are in the same general locations. Hydrogen bonds link alternating protonated ephedrine nitrogens and mandelate carboxylate oxygens in each salt forming columns of ions. The helical H‐bonded chain winds down the crystallographic 2‐fold screw axis. Additional H‐bonds form between 2‐fold related mandelates in the L‐salt. Mixed crystals, containing both mandelate isomers, (2R)‐ and (2S)‐mandelates, are obtained from the resolving system partly depleted of the L‐salt. A specimen with nearly equal amounts of the mandelates (III) is also isosteric with the commensurate structures. I (294K), L‐salt: a = 18.160(7), b = 6.538(2), c = 13.898(4) Å, β = 92.02(3)°, V = 1649.1(9) Å3; IIa (294K), M‐salt: a = 17.978(11), b = 7.164(4), c = 13.574(6)Å, β = 96.41(4)°, V = 1737.3(16) Å3; IIb (223K), M‐salt: a = 17.805(8), b = 7.115(2), c = 13.50(5) Å, β = 96.89(3)°, V = 1697.9(15) Å3; III (294K), mixed‐salt: a = 18.184(22), b = 6.792(7), c = 13.808(19) Å, β = 93.74(10)°, V = 1701.7(35) Å3. © 1992 Wiley‐Liss, Inc.
Rats with portacaval shunt as a potential experimental pharmacokinetic model for liver cirrhosis: Application to carvedilol stereopharmacokinetics
Authors: Stahl Elke , Baumgartner Ulrich , Henke Dorit , Schölmerich Jürgen , Mutschler Ernst , Spahn‐Langguth Hildegard 
Published: January 2005

AbstractAs an experimental model for reduced liver function rats with surgical portacaval shunts (pcs) may be used. Carvedilol, a nonselective β‐adrenoceptor antagonist with vasodilating activity, is extensively metabolised by phase I as well as phase II pathways. In order to study the stereoselective pharmacokinetics of carvedilol in liver disease, pcs and control rats were given rac‐carvedilol intravenously and p.o. The carvedilol enantiomers and their conjugates were assayed in plasma, urine, and bile. Carvedilol was highly bound to plasma proteins; binding was reduced by pcs. In all groups, the plasma concentrations of (R)‐carvedilol exceeded those of (S)‐carvedilol significantly. In comparison to the control group the plasma concentrations of both enantiomers increased after pcs, while the difference between the stereoisomers decreased. The total clearance decreased proportionally to the decrease in liver weight (30%). Both the apparent oral clearance, as well as its stereoselectivity were reduced, by up to 90 and 43%, respectively. The biliary clearance of the parent drug after i.v. dosage increased in rats with pcs due to the reduced hepatic metabolism. © 1993 Wiley‐Liss, Inc.
The effects of (±)‐, (+)‐, and (−)‐atenolol, sotalol, and amosulalol on the rat left atria and portal vein
Authors: Doggrell Sheila A. 
Published: January 2005

AbstractThe effects of (±)‐, (+)‐, and (−)‐atenolol, sotalol, and amosulalol alone on the rat left atria and portal vein and on the respective β1‐ and β2‐adrenoceptor‐mediated responses to isoprenaline have been determined. (±)‐Atenolol at 10−6 M had no effect whereas high concentrations of (+)‐ and (−)‐sotalol, 10−5–10−4 M, and (±)‐, (+)‐, and (−)‐amosulalol depressed the response of the rat left atria to cardiac stimulation which indicates membrane stabilizing activity. None of the drugs tested had any effect alone on the rat portal vein. The order of potency as antagonists was (±)‐amosulalol > (±)‐atenolol > (±)‐sotalol at β1‐adrenoceptors and (±)‐amosulalol > (±)‐sotalol > (±)‐atenolol at β2‐adrenoceptors. (±)‐Atenolol and (±)‐amosulalol are β1‐selective whereas (±)‐sotalol is β2‐selective. For each of the racemic β‐blockers, the β1‐ and β2‐adrenoceptor blocking activity was predominantly due to the (−)‐enantiomer. © 1993 Wiley‐Liss, Inc.
Ciliotoxicity of intranasal formulations: Menthol enantiomers
Authors: Su Xiang‐Yao , Po Alain Li Wan , Millership Jeffrey S. 
Published: January 2005

AbstractIt is shown, using in vitro measurements of beat frequency of rat tracheal cilia, that (+)‐(1S, 2R, 5S)‐menthol and (−)−(1R, 2S, 5R)−menthol have equipotent ciliotoxicities despite the fact that inhalation of menthol vapours from the crystals of the pure enantiomers show clearly that the (−)−(1R, 2S, 5R)‐menthol produces a more potent cooling sensation. Differential scanning calorimetry demonstrates the formation of a racemic compound when equimolar amounts of the two enantiomers are admixed. © 1993 Wiley‐Liss, Inc.
Diastereomeric phosphonate ester adducts of chymotrypsin: 31P‐NMR measurements
Authors: Kovach Ildiko M. , McKay Linda , Velde David Vander 
Published: January 2005

AbstractGeneration of diastereomeric phosphonate ester adducts of chymotrypsin was evidenced for the first time by 31P NMR and spectrophotometric kinetic measurements. 31P NMR signals were recorded for 4‐nitrophenyl 2‐propyl methylphosphonate (IMN) at 32.2 ppm and for its hydrolysis product at 26.3 ppm downfield from phosphoric acid. The inhibition of α‐chymotrypsin at pH > 8.0 by the faster reacting enantiomer of IMN or 2‐propyl methylphosphonochloridate (IMCl), or other phosphonate ester analogs of these compounds, all caused a ∼6.0 ppm downfield shift of the 31P signal to the 39–40 ppm region. IMN, when applied below the stoichiometric amount of chymotrypsin, under the same conditions, generated two signals, at 39.0 and at 37.4 ppm. Scans accumulated in hourly intervals showed the decomposition of both diastereomers, with approximate half‐lives of 12 h at pH 8.0 and 22°C, into a species with a resonance at 35.5 ppm. The most likely reaction to account for the appearance of this new peak is the enzymic dealkylation of the isopropyl group from the covalently bound phosphonate ester. We base this conclusion mostly on the similarity of the upfield shift to the hydrolysis of phosphonate esters. Contrary to experience with phosphate ester adducts of serine proteases, no signal was detected higher than 25.0 ppm downfield from phosphoric acid for several phosphonate ester adducts of chymotrypsin and in no case did the resonance for the adduct shift further downfield in the course of the experiments. © 1993 Wiley‐Liss, Inc.
N‐Acetyl‐D and L‐esters of 5′‐AMP hydrolyze at different rates
Authors: Wickramasinghe Nalinie S. M. D. , Lacey James C. 
Published: January 2005

AbstractStudies of the properties of aminoacyl derivatives of 5′‐AMP are aimed at understanding the origin of the process of protein synthesis. Aminoacyl (2′,3′) esters of 5′‐AMP can serve as models of the 3′‐terminus of aminoacyl tRNA. We report here on the relative rates of hydrolysis of AC‐D‐ and L‐Phe AMP esters as a function of pH. At all pHs above 3, the rate constant of hydrolysis of the AC‐L‐Phe ester is 1.7 to 2.1 times that of AC‐D‐Phe ester. The D‐isomer seems partially protected from hydrolysis by a stronger association with the adenine ring of the 5′‐AMP. © 1993 Wiley‐Liss, Inc.
Direct high‐performance liquid chromatography (HPLC) separation of etodolac enantiomers using chiral stationary phases
Authors: Caccamese Salvatore 
Published: January 2005

AbstractThe enantiomers of the antiinflammatory drug Etodolac were separated without derivatization on Chiralcel OD and Pirkle (R)‐DNBPG columns. Enantiomeric purity can be determined in less than 10 min. Optimization of separation was evaluated using various concentrations of 2‐propanol (doped with TFA) in hexane as the mobile phase. © 1993 Wiley‐Liss, Inc.
Use of chiral β‐lactones for the synthesis of chiral LC phases
Authors: Lohmann Dieter , Däppen Richard 
Published: January 2005

AbstractChiral β‐lactones offer an easy and economic approach to novel chiral R‐ or S‐configurated LC phases. The preferred method for their preparation is based on conventional ready‐to‐use aminopropyl‐functionalized silicas, e.g., aminopropyl HPLC columns. The new stationary phases can be used for analytical and preparative separations and are particularly suitable for the resolution of rotatory and heterocyclic stereoisomers. Applications in the LC, SFC, and TLC mode are possible, including the use of β‐lactone‐based mobile phase additives in a “push–pull” combination. A large variety of organic solvents can be used as eluents. © 1993 Wiley‐Liss, Inc.
Resolution of 7‐chloro‐4(4′‐diethylamino‐1′methylbutyl)aminoquinoline (chloroquine) into its enantiomers
Authors: Craiga J. Cymerman , Ansari Aslam M. 
Published: January 2005

AbstractEvidence is accumulating that 7‐chloro‐4‐[4‐diethylamino‐1‐methylbutyl] amino quinoline (chloroquine) displays considerable stereoselectivity in its metabolism, pharmacokinetics, macromolecular interactions, and biological activity. The availability of the enantiomers has been hampered by the failure of direct methods of resolution. We now describe a successful resolution in which the atropisomeric 1,1′‐binaphthyl‐2,2′‐diyl hydrogen phosphate is used in a 1:1 ratio to form stereoselectively the 2:1 diastereomeric salt from one enantiomer of the base, leaving the other in solution. By this means both enantiomers of chloroquine may be readily isolated. © 1993 Wiley‐Liss, Inc.
Enzymatic and chromatographic chiral discrimination of racemic (thio)glycidyl esters: Part II. Optical resolution of racemic (thio)glycidyl esters on modified cellulose chiral stationary phases
Authors: Wagner Jürgen , Offhauss Ulrike , Martin Arnim A. 
Published: January 2005

AbstractChiral chromatography on cellulose tris(3,5‐dimethylphenyl carbamate) (Chiralcel OD) and cellulose tribenzoate (Chiralcel OB) coated stationary phases has been successfully used for the optical resolution of rac‐(thio)glycidyl esters (acetate, propionate, butyrate). Glycidyl esters could sufficiently be resolved on the OD column whereas for the thio analogues baseline resolution is obtained on CSP OB using hexane/2‐propanol mobile phases. The separation factor (α) and resolution (RS) depend on column temperature, eluent composition, and flow rate, respectively. Best results were obtained for the butyrates and at low temperatures in general. © 1993 Wiley‐Liss, Inc.
Chiral recognition by 1H‐NMR, EPR, and ENDOR spectroscopy
Authors: Stegmann Hartmut B. , Mäurer Manfred , Höfler Ulrike , Scheffler Klaus , Hewgill Frank 
Published: January 2005

AbstractChiral recognition with magnetic methods requires the formation of diastereomers. Due to the variety of appropriate reactions, hydrogen bond formation, esterification, and acetalization as well as host–guest interactions were chosen for basic investigations. The results obtained indicate that in the case of diamagnetic compounds the chemical shifts and for paramagnetic compounds the β‐proton coupling constants are the most useful parameters. By combination of both pieces of information, assignment of the absolute configuration was achieved. © 1993 Wiley‐Liss, Inc.
Resolution of rac‐ketoprofen esters by enzymatic reactions in organic media
Authors: Palomer Albert , Cabré Marta , Ginesta Joan , Mauleón David , Carganico Germano 
Published: January 2005

AbstractEnzyme‐catalyzed reactions in organic media of rac‐ketoprofen esters with different nucleophiles such as alcohols, amines, and water have been studied. Among the parameters optimized are the enzyme, the activated substrate, and the solvent. With the enzymes used in this study the preferred substrate was the trifluoroethyl ester of rac‐ketoprofen (rac‐2), whose (R)‐enantiomer reacted preferentially. The enzyme of choice was the lipase M‐AP‐10 from Mucor miehei and best results were obtained with diisopropyl ether as solvent. Three different methods have been scaled‐up for the resolution of 75–150 g of substrate: transesterification with 1‐butanol (90% yield of (S)‐ketoprofen, 88% ee), transesterification with 2‐(2‐pyridyl)ethanol (94% yield, 92% ee), and hydrolysis in wet organic solvent (93% yield, 97% ee). Despite the comparable chemical and optical yields obtained with these three methods, the use of 2‐(2‐pyridyl)ethanol and the hydrolysis allowed a much easier work‐up and isolation of the desired (+)‐(S)‐ketoprofen. © 1993 Wiley‐Liss, Inc.
Preparative and analytical separation of the zopiclone enantiomers and determination of their affinity to the benzodiazepine receptor binding site
Authors: Blaschke Gottfried , Hempel Georg , Müller Walter E. 
Published: January 2005

AbstractWe report the preparative separation of rac‐zopiclone using malic acid as the resolving agent. Furthermore, two different methods for the analytical determination of zopiclone enantiomers by HPLC on chiral stationary phases are described. The benzodiazepine receptor binding of the isolated enantiomers was investigated. Half‐maximal inhibitory concentrations of (+)‐ and (−)‐zopiclone were 21 or 1,130 nmol/liter, respectively, indicating a more than 50 times higher affinity of the (+)‐enantiomer toward the receptor. © 1993 Wiley‐Liss, Inc.