摘要:

AbstractThe stereoselective metabolism of the former sedative thalidomide and the metabolism of its analogue EM 12 were studied in vitro with liver homogenates. In our study we focused on hydroxylated nonhydrolyzed metabolites of thalidomide. An analytical HPLC method was developed to determine these metabolites directly. The investigations showed a highly stereoselective biotransformation of thalidomide. 5‐Hydroxy thalidomide was preferentially formed by (−)‐(S)‐thalidomide, whereas (+)‐(R)‐thalidomide was metabolized to two hitherto unknown compounds (Met A and B). Mass spectrometry of these metabolites Met A and B indicated that oxidation or hydroxylation took place in the glutarimide moiety. Biotransformation studies with the more stable thalidomide analogue EM 12 revealed four new metabolites (Met CF) whose quantities differed in the selected liver homogenate. © 1994 W

ISSN:0899-0042    

DOI:10.1002/chir.530060402

出版商:Wiley‐Liss, Inc.    

年代:1994

数据来源: WILEY

摘要:

AbstractThe separation and quantitation of coumarinic anticoagulant drug enantiomers were achieved by direct chiral capillary electrophoresis using complex maltooligosaccharide mixtures as stereoselective electrolyte modifiers. Chiral separations were characterized by a high selectivity and efficiency, enabling enantiomeric excess determinations. In addition, preliminary results indicate the applicability of the method for the determination of individual enantiomers in biological samples. So the method can be used to perform stereoselective pharmacokinetic studies. © 1994 Wiley‐Liss, I

ISSN:0899-0042    

DOI:10.1002/chir.530060403

出版商:Wiley‐Liss, Inc.    

年代:1994

数据来源: WILEY

摘要:

AbstractWhen a protein such as human serum albumin is added to the separation buffer in capillary electrophoresis, the mobility of solutes which bind to that protein may be altered. The change in mobility of the solute is a function both of the strength of the binding interaction, and the difference in mobility between the free solute and protein additive. By adding other ligands which themselves bind to the protein, the strength of the solute–protein binding may be modified, leading to a measurable change in the mobility of the solute. These effects are particularly striking for chiral compounds, where enantioselectivity may be completely lost on addition of a competitive ligand. Capillary electrophoresis with human serum ablumin as a buffer additive was used to separate the enantiomers of benzoin and three phenothiazine derivatives. A comparison of the binding of (S)‐benzoin to human serum albumin as determined by capillary electrophoresis and by ultrafiltration was made. A variety of other ligands were then added to the buffer along with the protein, and the effects on mobility and enantioselectivity were studied. The displacers included (R)‐ and (S)‐oxazepam hemisuccinate, (R)‐ and (S)‐warfarin, nitrazepam, phenylbutazone, and octanoic acid. From the results obtained, it seems that capillary electrophoresis may be a useful, rapid method to screen for drug–drug interactions. There are some advantages of using this technique to study protein–ligand interactions: Only very small amounts of ligand are needed (useful when dealing with metabolites); for chiral compounds, if protein binding is stereoselective, then the method is also stereoselective, so single enantiomers are not needed; finally, measurements are obtained in solution, without the need for immobilization of the protein. A disadvantage is that the ligand and protein must have significantly different electrophoretic mobilities. © 1994

ISSN:0899-0042    

DOI:10.1002/chir.530060404

出版商:Wiley‐Liss, Inc.    

年代:1994

数据来源: WILEY

摘要:

AbstractMolecular modelling of β‐cyclodextrin and optimisation of its potential energy suggests that a favoured conformation is that distorted from a symmetrical torus. The inclusion of water molecules into the torus cavity simulates the increased stability in an aqueous solvent. Complexes of β‐cyclodextrin with (R)‐ and (S)‐enantiomers of methylphenobarbitone have been modelled and energetically optimised by the application of molecular mechanics. The simulations suggests that the guest molecules adopt an orientation in which the phenyl ring is projected into the torus cavity, with in each case the plane of the ring parallel to a longer axis of the distorted torus and slightly displaced from the axis through the torus cavity. It is suggested that the asymmetry in the macrocyclic ring contributes to chiral recognition as a result of additional discriminatory binding to the barbiturate ring residue of each enantiomer, which occupy different 3D geometries. The enantiomers form complexes of different minimum potential energies. The resulting difference in complex stability can be related to the behaviour of β‐cyclodextrin, as a mobile phase additive in reverse‐phase HPLC to effect chiral separation ofrac‐medthylphenobarbitone during chromatography. © 199

ISSN:0899-0042    

DOI:10.1002/chir.530060405

出版商:Wiley‐Liss, Inc.    

年代:1994

数据来源: WILEY

摘要:

Abstract2,2,2‐Trifluoro‐(9‐anthryl)‐ethanol (TFAE) has been extensively used, in its pure enantiomeric forms, as a chiral solvating agent in nuclear magnetic resonance spectroscopy (NMR). It has also played an important role in the development of chiral stationary phases in liquid chromatography (LC). X‐ray crystallography of the enantiomeric and racemic crystals shows, in both cases, the formation of an intermolecular hydrogen bond between the OH and the π‐face of one of the rings of the anthracene aromatic system.1Few examples of such hydrogen bonding have been published previously, and those that have are not as clear cut as in this case. An explanation for the hydrogen bonding is sought using molecular modelling via the PM3 analytically derived molecular electrostatic potentials. Using NMR and dynamic lineshape analysis, the barrier to rotation about the aryl‐carbon bond is estimated, indicating the CCF3bond to be perpendicular to the anthracene axis in nonpolar solution. This conformation is identical to the conformation in the crystal. Evidence is also presented to support the formation of intermolecular π‐facial hydrogen bonding in TFAE solutions. It is thought that such hydrogen bonding may be implicated in chiral recognition using this compound.

ISSN:0899-0042    

DOI:10.1002/chir.530060406

出版商:Wiley‐Liss, Inc.    

年代:1994

数据来源: WILEY

摘要:

AbstractThe determination of lipophilicity of the title compounds allowed treatment of the data for chiral separation (capacity factors) on CTA and CTPB according to these parameters. A linear correlation between Ink′(+) and logk′wwas found on both CTA and CTPB, as far as the substituents are situated in the plane of the aryl ring or the heterocycle. This correlation with a nonchiral descriptor allows treatment of capacity factors for (−)‐enantiomers as deviations from the lipophilicity line or derived parallels. It results in a clear description of the molecular area affecting enantioselectivity. Application to larger alkyl derivatives shows that the effect of the substituent should be treated on a basis of attractive effect in the case of CTA and on the basis of attractive and repulsive effects for CTPB. © 1994 Wiley

ISSN:0899-0042    

DOI:10.1002/chir.530060407

出版商:Wiley‐Liss, Inc.    

年代:1994

数据来源: WILEY

摘要:

AbstractA method is described for the synthesis and optical purity determination of (−)‐(R)‐ and (+)‐(S)‐econazole via the optically pure intermediates, (R)‐ and (S)‐imidazolylethanol, which are available by chromatographic resolution or by fractional crystallization of diastereomericO,O′‐disubstituted (R*;R*)‐ or (S*;S*)‐tartaric acid monoesters of the parent imidazolylethanol racemate. Furthermore, this method allows the chromatographic assignment of the absolute configuration of the chiral center of the imidazolylethanol enantiomers and consequently of econazole enantiomers. In addition, a direct liquid chromatographic enantioseparation method for the determination of the optical purity of (R)‐ and (S)‐econazole and other chiral imidazoles on a protein type CSP (OVM) is described and applied to confirm chromatographically the absolute configuration evaluation

ISSN:0899-0042    

DOI:10.1002/chir.530060408

出版商:Wiley‐Liss, Inc.    

年代:1994

数据来源: WILEY

摘要:

AbstractHighly sensitive and accurate HPLC methods were used for the determination of total amounts of proline, leucine and phenylalanine and their enantiomeric ratios in a variety of different honey samples. Significant amounts ofD‐leucine andD‐phenylalanine and relatively low concentrations ofD‐proline have been found in honeys of different botanical and geographical origins. It is suggested that the enantiomeric ratios of amino acids could be used to test for storage effects, age, and the quality of the processing of the honey. © 1994 Wiley‐L

ISSN:0899-0042    

DOI:10.1002/chir.530060409

出版商:Wiley‐Liss, Inc.    

年代:1994

数据来源: WILEY

摘要:

AbstractMonosodium glutamate (MSG) is added to many processed foods at significant levels for flavor enhancement. It is also naturally occurring at high levels in some foods. The enantiomeric composition of free glutamate in foods was examined and all foods analyzed were found to containD‐glutamate. The relative percent ofD‐glutamate in the food products studied depended on the origin of the glutamate. Foods to which MSG was added by the manufacturer had a high total level of MSG but a lower relative percentage of theD‐enantiomer (usually less than 0.8%). In comparison, fermented foods tend to have high relative levels ofD‐glutamate but a lower total amount of the amino acid. The relative percent ofD‐glutamate in nonfermented foods containing no added MSG was also found to be low compared to fermented products. In some cases the percentD‐glutamate could be related to the relative amounts of other food ingredients such as cheese. © 1994 Wil

ISSN:0899-0042    

DOI:10.1002/chir.530060410

出版商:Wiley‐Liss, Inc.    

年代:1994

数据来源: WILEY

摘要:

AbstractAn enantioselective assay has been developed for the determination of the enantiomers of ketorolac and its metabolitep‐hydroxyketorolac in plasma and urine. The analytical method utilizes a coupled achiral–chiral HPLC system where the initial separation of ketorolac fromp‐hydroxyketorolac and matrix interferences was achieved on a C18‐stationary phase and the enantioselective separations of the two target solutes were accomplished on a human serum albumin‐based chiral stationary phase. The two columns were attached in sequence and the assay was carried out without the necessity of column‐switching techniques. The method has been validated for use in pharmacokinetic and metabolic studies and represents the initial report of the determination of ketorolac andp‐hydroxyketorolac enantiomers in urine. The results of the study indicate that after the administration of racemic ketorolac there was an enantioselective distribution of ketorolac enantiomers in plasma [(R)‐ketorolac: (S)‐ketorolac = 3.89 ± 0.93 (n= 6) and urine (R)‐ketorolac: (S)‐ketorolac = 1.26 ± 0.09 (n= 7)]. The mean ratio of thep‐hydroxyketorolac enantiomers was 1.77 ± 0.46 (n= 7). Both ketorolac andp‐hydroxyketorolac are glucuronized in the acyl carboxyl moiety and the results of this study indicate that this process is not enantiospec

ISSN:0899-0042    

DOI:10.1002/chir.530060411

出版商:Wiley‐Liss, Inc.    

年代:1994

数据来源: WILEY