bluuebunny/crossref_metadata_2025_split huggingface dataset:
Substituent effects in the enantioselective reduction of acetophenones with nabh4 in the presence of β‐cyclodextrin
Authors: Deratani André , Renard Estelle 
Published: January 2005

AbstractThe effect of substituent groups on asymmetric induction by β‐cyclodextrin (β‐CD) was investigated in the reduction of a series of o‐, m‐, and p‐substituted acetophenones (X = H, Br, Cl, CH3, NO2, OCH3) with aqueous NaBH4. The inclusion of the ketones studied in β‐CD led to water‐insoluble compounds so that the reaction proceeded in the solid state. The substitutions resulted generally in higher enantioselectivities than that obtained for acetophenone indicating stronger host—guest interactions. Acetophenone and its m‐ and p‐derivatives gave preponderantly the (−)‐alcohol while the prevailing enantiomer was the (+)‐alcohol in the case of the o‐derivatives. The enantioface selectivity was found to be mainly governed by steric demands imposed by the size and the shape of the β‐CD cavity in the case of the o‐substituted acetophenones and by hydrophobic interactions in the case of the m‐derivatives. A more complicated situation arose from the asymmetic reduction of p‐derivatives where a combination of these factors with hydrogen bonding of the carbonyl group to the hydroxyls of β‐CD are responsible for the enantioselectivity. © 1994 Wiley‐Liss, Inc.
Circular dichroism studies of the self‐association of amphotericin B
Authors: Brittain Harry G. 
Published: January 2005

AbstractCircular dichroism (CD) spectroscopy has been used to evaluate the ability of 21 different solvents to influence the aggregation state of amphotericin B. Using the relative donor/acceptor tendencies known for each solvent system, it was possible to deduce information as to the factors which goven the self‐association of amphotericin B. It was concluded that in the absence of strong solvent interaction, amphotericin B prefers to self‐associate into oligomeric species. This intrinsic driving force can be overcome through the use of solvents which function as strong electron pair donors, probably forming specific solvent—solute species. © 1994 Wiley‐Liss, Inc.
Stereospecific determination, chiral inversion in vitro and pharmacokinetics in humans of the enantiomers of thalidomide
Authors: Eriksson Tommy , Bjöurkman Sven , Roth Bodil , Fyge Årsa , Höuglund Peter 
Published: January 2005

AbstractThe purposes of this work were (1) to develop a high performance liquid chromatographic (HPLC) assay for the enantiomers of thalidomide in blood, (2) to study their inversion and degradation in human blood, and (3) to study the pharmacokinetics of (+)‐(R)‐ and (−)‐(S)‐thalidomide after oral administration of the separate enantiomers or of the racemate to healthy male volunteers. The enantiomers of thalidomide were determined by direct resolution on a tribenzoyl cellulose column. Mean rate constants of chiral inversion of (+)‐(R)‐thalidomide and (−)‐(S)‐thalidomide in blood at 37°C were 0.30 and 0.31 h−1, respectively. Rate constants of degradation were 0.17 and 0.18 h−1. There was rapid interconversion in vivo in humans, the (+)‐(R)‐enantiomer predominating at equilibrium. The pharmacokinetics of (+)‐(R)‐ and (−)‐(S)‐thalidomide could be characterized by means of two one‐compartment models connected by rate constants for chiral inversion. Mean rate constants for in vivo inversion were 0.17 h−1 (R to S) and 0.12 h−1 (S to R) and for elimination 0.079 h−1 (R) and 0.24 h−1 (S), i.e., a considerably faster rate of elimination of the (−)‐(S)‐enantiomer. Putative differences in therapeutic or adverse effects between (+)‐(R)‐ and (−)‐(S)‐thalidomide would to a large extent be abolished by rapid interconversion in vivo. © 1995 Wiley‐Liss, Inc.
Macromolecular ionophores. 1. Chiral recognition properties of poly[(1→6)‐2,5‐anhydro‐D‐glucitol] toward racemic amino acid ester
Authors: Kakuchi Toyoji , Satoh Toshifumi , Umeda Satoshi , Mata Junji , Yokota Kazuaki 
Published: January 2005

AbstractThe chiral recognition property of poly[(1→6)‐2,5‐anhydro‐3,4‐di‐O‐alkyl‐D‐glucitol] (1) toward racemic RCH (CO2CH3)NH3+ · PF6− (2 · HPF6) has been studied using a transport system involving an aqueous source and receiving phases separated by a chloroform phase containing 1. Transport rates for aromatic guests 2a (R = Ph) and 2b (R = CH2Ph) were faster than those for aliphatic guests, 2c (R = CH(CH3)2) and 2d (R = CH2CH(CH3)2), using the polymer substituted with methyl groups (1a). The enantiomeric excess (e.e.) was 10.9% for 2a as a maximum value and decreased in the order of 2a > 2c > 2b = 2d. When the transport of 2a · HPF6 was carried out using the polymers with 3,4‐di‐O‐methyl (1a), ethyl (1b), allyl (1c), and pentyl (1d) groups, the e.e. was 22.0% for 1d as a maximum value and increased in the order of 1a < 1b < 1c < 1d. The formation of a complex between 1a and 2a · HPF6 was confirmed by 1H and 13C NMR spectral measurements. © 1995 Wiley‐Liss, Inc.
Resolution and determination of enantiomeric purity of the enantiomers of felodipine using chiral‐AGP® as stationary phase
Authors: Karlsson Anders , Pettersson Karin , Hernqvist Kerstin 
Published: January 2005

AbstractA direct chiral chromatographic reversed phase method for the determination of the enantiomers of felodipine is described. The influence of charged and uncharged modifiers as well as the effect of the mobile phase pH on the enantiomeric resolution is discussed. A high mobile phase pH and the addition of 2‐propanol as organic modifier gave the highest separation factor (α = 1.3). The high mobile phase pH (pH = 7.6) is outside the recommended pH limit of silica based columns but was necessary to achieve baseline resolution of (R)‐ and (S)‐felodipine. Improvement of column efficiency by increasing column temperature was utilized for optimization of the enantiomeric resolution (Rs = 1.7). The enantiomers of felodipine and three related compounds were separated within 15 min. The enantiomeric purity of (R)‐ and (S)‐felodipine in injections and (R)‐felodipine in bulk substance was higher than 99.5% and no racemization was observed after storage at accelerated conditions. A poor Chiral‐AGP® column used for a long period was restored using a simple wash step together with repacking the top of the chromatographic column. © 1995 Wiley‐Liss, Inc.
Resolution by chiral hplc of the stable free radical perchlorotriphenylmethyl: Thermodynamic and chiroptical properties
Authors: Irurre José , Santamaría Jesüs , González‐rego M. Concepción 
Published: January 2005

AbstractThe perchlorotriphenylmethyl radical (PTM) shows enantiomerism due to restricted internal rotations. Several chiral stationary phases have been tested in different conditions for the resolution of PTM by HPLC. Only poly(triphenylmethyl methacrylate) provided sufficient resolution for carrying out a micropreparative scale separation. Racemization of (+)‐ and (−)‐PTM was monitored polarimetrically as a function of time. The process was found to follow strict first‐order kinetics. The value of ΔG#303.8 = 23.6 Kcal · mol−1 agrees with that determined previously by HPLC with the stopped flux technique (Crespo, Doctoral Thesis, CETS Institut Químic de Sarrià, 1991). Following the helicity rules in the circular dichroism spectrum, (+)‐PTM can be assumed to have (P) configuration and (−)‐PTM (M) configuration. © 1995 Wiley‐Liss, Inc.
Myocardial uptake kinetics of tocainide enantiomers in the isolated perfused rabbit heart
Authors: Christensen Ellen Bech , Hansen Steen Honoré , Rasmussen Søren Nørgaard 
Published: January 2005

AbstractThe extent of myocardial accumulation of tocainide, administered as single enantiomers and as well as racemate, was determined in the isolated, spontaneous beating rabbit heart. The heart was retrogradely perfused at a constant rate and fractions of the perfusate were collected during and after infusion. Kinetic parameters for myocardial accumulation and disposition of tocainide were indirectly determined from drug concentration/time course in the outflow perfusate. No stereoselectivity in myocardial accumulation was observed. A two compartment model with mean half‐lives for distribution and elimination of 0.60 and 3.78 min, respectively, was fitted to the accumulation and disposition data. At steady‐state, tocainide enantiomers were accumulated about three times in the myocardium relative to the perfusion liquid. © 1995 Wiley‐Liss, Inc.
Preparative scale enantioseparation of 1‐cyclohexyl‐1‐phenylethyl hydroperoxide and 1,2,3,4‐tetrahydro‐1‐naphthyl hydroperoxide on a modified cellulose stationary phase
Authors: Wagner Jürgen , Hamann Hans‐Jürgen , Döpke Werner , Kunath Annamarie , Höft Eugen 
Published: January 2005

AbstractThe analytical and preparative scale optical resolution of 1‐cyclohexyl‐1‐phenylethyl hydroperoxide and 1,2,3,4‐tetrahydro‐1‐napthyl hydroperoxide has been achieved by chiral HPLC on a cellulose tris(3,5‐dimethylphenyl carbamate) stationary phase coated on silica gel. The method has been used to obtain several hundred milligrams of highly enriched enantiomers (%ee >98) which were characterized by [α]D and circular dichroism spectra, respectively. Configurational assignments were achieved for 1,2,3,4‐tetrahydro‐1‐naphthyl hydroperoxide enantiomers. © 1995 Wiley‐Liss, Inc.
A new class of network‐polymeric chiral stationary phases
Authors: Allenmark Stig G. , Andersson Shalini , Möller Per , Sanchez Domingo 
Published: January 2005

AbstractA strategy based on the use of homo bi‐ and multifunctional building blocks for the synthesis of a new class of network‐polymeric chiral stationary phases has been evaluated. The key steps comprise acylation of N,N′‐diallyl‐L‐tartardiamide (DATD) and reaction with a multifunctional hydrosilane, yielding a network polymer incorporating the bifunctional C2‐symmetric chiral selector. Covalent bonding to a functionalized silica takes place during the latter process. Many of these chiral sorbents show interesting enantioselective properties toward a wide variety of racemic solutes under normal‐phase (hexane‐based) conditions. The retention is mainly caused by the hydrogen‐bonding ability of the analyte, which is regulated by mobile phase additives like alcohol or ether cosolvents. The most interesting chiral stationary phases, in terms of broad enantioselectivity, were obtained from O,O′‐diaryol‐DATD‐derivatives, particularly those containing the 3,5‐dimethylbenzoyl and the 4‐(tert‐butyl)benzoyl moieties. Since high column efficiencies can be obtained with these chiral sorbents, an α‐value of ca. 1.2 is usually sufficient to produce baseline separation. A large number of neutral as well as acidic or basic drug racemates are resolved without derivatization. © 1995 Wiley‐Liss, Inc.
Stereochemical aspects of the hydration of trans‐anethole epoxide in the rat
Authors: Ishida Takashi , Bounds Stephen V. J. , Caldwell John 
Published: January 2005

AbstractRacemic trans‐anethole epoxide [1‐(4′‐methoxyphenyl)‐propane‐1,2‐oxide] was incubated with water, buffers, and rat liver microsomes and cytosol and the stereochemistry of the diols produced was determined by HPLC as their dicamphanyl esters. The diol metabolites were isolated by HPLC from the urine of rats administered [1′‐14C] trans‐anethole and their stereochemistry determined after derivatization to their camphanyl esters. The stereochemical course of the metabolism of trans‐anethole by rat liver microsomes and cytosol is discussed. © 1995 Wiley‐Liss, Inc.
Stereoselective and species‐dependent kinetics of reboxetine in mouse and rat
Authors: Benedetti Margherita Strolin , Frigerio Enrico , Tocchetti Paola , Brianceschi Giannantonio , Castelli Maria Grazia , Pellizzoni Cinzia , Dostert Philippe 
Published: January 2005

AbstractReboxetine, (RS)‐2‐[(RS)‐α‐(2‐ethoxyphenoxy)benzyl]morpholine methanesulphonate, is a racemic compound and consists of a mixture of the (R,R)‐ and (S,S)‐enantiomers. In this study, brain and plasma levels of both enantiomers were determined in mice and rats after oral administration of reboxetine at doses (1.1 mg/kg, mouse; 20 mg/kg, rat) twice the respective ED50 values in the antireserpine test. Plasma and brain concentrations of each enantiomer were measured up to 6 h postdosing using an HPLC method with fluorimetric detection after derivatization with a chiral agent (FLEC). In mice and rats, brain and plasma levels of the (R,R)‐enantiomer were always higher than those of the (S,S)‐enantiomer. After normalization for dose, the mean AUC0‐tz values of both the (R,R)‐ and (S,S)‐enantiomers in mouse brain were about 23 and 32 times higher than in rat brain, respectively. In plasma, the corrected mean AUC0‐tz values were about 5 (R,R) and 10 (S,S) times higher in mice than in rats. These results provide evidence for the higher bioavailability and/or lower clearance of both enantiomers in mice than in rats, and for a higher penetration of both enantiomers into mouse brain compared to rat brain. © 1995 Wiley‐Liss, Inc.
Does solute stereochemistry influence percutaneous penetration?
Authors: Heard Charles M. , Brain Keith R. 
Published: January 2005

AbstractThe stratum corneum, the rate‐limiting barrier to percutaneous penetration, is made up of several components, principally keratin and ceramides. These are potential sources of chiral discrimination that could result in differential diffusion rates, dependent upon the stereochemistry of the solute. Although binding to keratin can occur it is not a stereoselective process [percent binding to solubilised epidermal keratin: (R)‐propranolol 7.9 ± 1.7, (S)‐propranolol 8.3 ± 2.0]. On the other hand, studies with ceramide monolayers produced qualitative evidence of dose‐dependent stereoselective interaction when the pure diastereomers of ephedrine were present in the aqueous subphase which suggested that differences in diffusion rates might occur in skin. However, the differences in permeation rates in vitro for these diastereomers through human skin were not statistically different [(+)‐(1S, 2R)‐ephedrine 119.1 ± 2.6 μg/cm2, (‐)‐(1R,2S)‐ephedrine 107.0 ± 3.9 μg/cm2, 12 h]. Time averaging, involving contributions from binding to all lipid headgroups present in the intercellular channels, may obscure specific differential interactions. Further, any stereospecific interaction may be subtle and readily overwhelmed if diffusant concentration is greater than the capacity of the skin to differentiate between stereoisomers. Evidence for intrinsic stereoselectivity in skin permeation has therefore yet to be obtained. © 1995 Wiley‐Liss, Inc.
Stereoselectivity of the carbonyl reduction of dolasetron in rats, dogs, and humans
Authors: Dow James , Berg Christiane 
Published: January 2005

AbstractThe initial step in the metabolism of dolasetron or MDL 73, 147EF [(2α,6α,8α,9aβ)‐octahydro‐3‐oxo‐2,6‐methano‐2H‐quinolizin‐8‐yl 1H‐indol‐3‐carboxylate, monomethanesulfonate] is the reduction of the prochiral carbonyl group to give a chiral secondary alcohol “reduced dolasetron.” An HPLC method, using a chiral column to separate reduced dolasetron enantiomers, has been developed and used to measure enantiomers in urine of rats, dogs, and humans after dolasetron administration. In all cases, the reduction was enantioselective for the (+)‐(R)‐enantiomer, although the dog showed lower stereoselectivity, especially after iv administration. An approximate enantiomeric ratio (+/−) of 90:10 was found in rat and human urine. The contribution of further metabolism to this enantiomeric ratio was considered small as preliminary studies showed that oxidation of the enantiomeric alcohols by human liver microsomes demonstrated only minor stereoselectivity. Further evidence for the role of stereoselective reduction in man was obtained from in vitro studies, where dolasetron was incubated with human whole blood. The enantiomeric composition of reduced dolasetron formed in human whole blood was the same as that found in human urine after administration of dolasetron. Enantioselectivity was not due to differences in the absorption, distribution, metabolism, or excretion of enantiomers, as iv or oral administration of rac‐reduced dolasetron to rats and dogs lead to the recovery, in urine, of essentially the same enantiomeric composition as the dose administered. It is fortuitous that the (+)‐(R)‐enantiomer is predominantly formed by carbonyl reductase, as it is the more active compound. © 1995 Wiley‐Liss, Inc.
Development of chiral drugs in Japan: An update on regulatory and industrial opinion
Authors: Shindo Hideyo , Caldwell John 
Published: January 2005

AbstractThe purpose of this commentary is to provide information on the present status of the racemate/enantiomer debate in Japan and current industrial and regulatory attitudes to chiral drugs in Japan. It provides an update of our previous paper (Shindo and Caldwell, Chirality 3:91–93, 1991), and the interested reader is referred to this for background information. © 1995 Wiley‐Liss, Inc.
A conformational analysis of mono and dialkyl ethers of 2,2′‐dihydroxy‐1,1′‐binaphthalene by circular dichroism spectroscopy and cholesteric induction in nematic liquid crystals
Authors: Rosini Carlo , Rosati Ivana , Spada Gian Piero 
Published: January 2005

AbstractThe coupling of the analysis of the absorption and circular dichroism (CD) spectra with that of the cholesteric mesophases induced in nematic liquid crystals indicated some interesting conformational features of bridged and nonbridged mono‐ and dialkylethers of optically active 2,2′‐dihydroxy‐1,1′‐binaphthalene. Bridged derivatives are characterized by relatively small dihedral angles. Simple monoalkyl ethers are characterized by larger dihedral angles but they all assume an s‐cis conformation, owing to the existence of intramolecular hydrogen bonds. Nonbridged dialkylethers prefer even larger dihedral angles and, depending on the bulkiness of the alkyl groups, the s‐trans conformation can be found. Interestingly, the conformation of dialkylethers is strongly dependent on the structure of the liquid crystal solvent, because the intramolecular hydrogen bond is not possible there. © 1995 Wiley‐Liss, Inc.
A new method for enantiomer enrichment: Distillation to separate the free and complexed enantiomers after partial salt formation
Authors: Kozma Dávid , Madarász Zoltán , Ács Mária , Fogassy Elemér 
Published: January 2005

AbstractA new method is described for the enrichment of enantiomeric mixtures having an enantiomeric ratio other than 1:1. The method is based on partial salt formation of the enantiomeric mixture with an achiral substance followed by the distillation of the free enantiomer. The distillate has a different enantiomeric composition than the starting mixture. The method was performed on enantiomeric mixtures of α‐phenylethylamine using four different dicarboxilic acids. © 1995 Wiley‐Liss, Inc.
Circular dichroism of ketoprofen complexed to serum albumins: Conformational selection by the protein: A novel optical purity determination technique
Authors: Zandomeneghi Maurizio 
Published: January 2005

AbstractComplexation of 2‐(3′‐benzoylphenyl)propionic acid (ketoprofen), 1, to bovine serum albumin (BSA) results in an intense negative circular dichroism in the ketonic n → π* band of the benzoylphenyl moiety. This high CD contrasts with the weak CD of 1‐enantiomers dissolved in common solvents. Furthermore, a number of chiral and achiral molecules containing the benzophenone moiety are easily complexed to BSA: all these complexes show an intense CD at the same transition. To account for the observed CD intensities of the above molecules, it appears that BSA complexation markedly shifts the equilibrium between strongly asymmetric, antipodic conformers. Dissymmetry of these conformers is connected to the instability of a structure with phenyl rings coplanar to the carbonyl chromophore, as also indicated by molecular mechanics calculations. The magnification of the Cotton effects of the 1‐antipodes, due to the protein, can be used to measure the optical purity of 1‐samples with excellent precision. In contrast with BSA, human SA is unable to recognize the chirality of 1‐antipodes; oleic acid cocomplexation modifies this fact as well as other features of the binding. © 1995 Wiley‐Liss, Inc.
Determination of the enantiomeric purity of dihydroxy‐ and dimethoxy‐2‐aminotetralins by high‐performance capillary electrophoresis with cyclodextrins as chiral selector
Authors: Castelnovo Pierfrancesco , Albanesi Carlo 
Published: January 2005

AbstractA chiral separation of 5,6‐ and 6,7‐dihydroxy‐2‐aminotetralin and of the corresponding dimethoxy analogues can be achieved by high‐performance capillary electrophoresis using cyclodextrins as chiral selector. The selectivity of a number of native and derivatized cyclodextrins was screened and hydroxylalkyl‐β‐cyclodextrins turned out to be the most effective. Optimization of hydroxyethylcyclodextrin and hydroxypropylcyclodextrin concentration for each compound led to baseline separation (resolution factors from 1.7 to 2.3) resulting in a detection limit of 0.1% for the enantiomer present as impurity. Modifiers of the electroendosmotic flow, such as hydroxypropylcellulose and hexadecyltrimethylammoniun bromide, must be added to the background electrolyte to obtain such results. © 1995 Wiley‐Liss, Inc.
Accuracy in the chromatographic determination of extreme enantiomeric ratios: A critical reflection
Authors: Meyer Veronika R. 
Published: January 2005

AbstractThe chromatographic quantitation of very low amounts of an enantiomer in the presence of its antipode can be an extraordinary challenge. If resolution of the peaks is not complete even at extreme mass ratios an integrator will yield inaccurate results due to geometric effects. A given resolution can be adequate for peaks of similar size but result in severe overlap if one of the signals is markedly smaller. If tailing occurs, which is more the rule than the exception, the problem is especially severe for last eluted small peaks. Additional obstacles are detector nonlinearity and other sources of unsatisfactory calibration curves, overloading phenomena, and the possible lack of standards of highest optical purity. These problems have been studied by computer simulations and the liquid chromatographic separation of (R,S)‐phenylethyl naphthoic acid amide on a chiral stationary phase. © 1995 Wiley‐Liss, Inc.
Synthesis of optically active diols using an efficient polymer bound cinchona alkaloid derivative
Authors: Petri Antonella , Pini Dario , Rapaccini Silvia , Salvadori Piero 
Published: January 2005

AbstractA new insoluble polymer containing a Cinchona alkaloid derivative has been synthesized and used as chiral ligand in the heterogeneous enantioselective dihydroxylation of olefins. It is shown that the enantioselectivity of the optically active diols obtained from both aliphatic and aromatic substrates is always comparable to that observed in the homogeneous phase under the same reaction conditions. A method for evaluating the enantiomeric excesses of the optically active products is also described. © 1995 Wiley‐Liss, Inc.