摘要:

AbstractGlutathione (GSH) conjugation of the chiral compound 2‐bromo‐3‐phenylpropionic acid (BPP) was studied in vitro and in the rat in vivo. GSH conjugation of BPP, catalyzed by a mixture of glutathione‐S‐transferases (GST's) from rat liver cytosol in vitro, was stereoselective: at a substrate concentration of 250 μM, (R)‐BPP was more rapidly conjugated than (S)‐BPP (R/S‐ratio = 2.6). The blood elimination kinetics of the separate BPP enantiomers and the biliary excretion kinetics of the corresponding GSH conjugates were studied in the rat in vivo after administration of (R)‐ or (S)‐BPP at a dose level of 50 μmol/kg. Elimination of (R)‐BPP from blood was faster than that of (S)‐BPP: half lives were 9 ± 2 min for (R)‐BPP and 13 ± 1 min for (S)‐BPP. The biliary excretion rate of the GSH conjugate of (R)‐BPP declined monoexponentially, while that of the GSH conjugate of (S)‐BPP displayed a biphasic profile. Half lives of excretion were 13 ± 1 for the GSH conjugate of (R)‐BPP, and 11 ± 2 for the GSH conjugate of (S)‐BPP (second phase). The first phase in the biliary excretion of the GSH conjugate of (S)‐BPP could not be attributed to capacity limitation of biliary transport carriers as higher excretion rates were attained upon administration of higher doses (100 and 200 μmol/kg) of ((S)‐BPP). The blood elimination profiles of (R)‐ and (S)‐BPP differed greatly from the biliary excretion profiles of the corresponding GSH conjugates. This suggests that the kinetics of BPP conjugate excretion are determined by other processes th

ISSN:0899-0042    

DOI:10.1002/chir.530040702

出版商:Alan R. Liss, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractThe ability of two enantiomeric fluoro‐analogues ofD‐myo‐inositol 1,4,5‐trisphosphate [Ins(1,4,5)P3] to mobilize intracellular Ca2+stores in SH‐SY5Y neuroblastoma cells has been investigated. (—)‐D‐2,2‐difluoro‐2‐deoxy‐myo‐Ins(1,4,5)P3[D‐2,2‐F2‐Ins(1,4,5)P3] was a full agonist [EC500.21 μM] and slightly less potent thanD‐Ins(1,4,5)P3[EC500.13 μM]. (+)‐L‐2,2‐F2Ins(1,4,5)P3was a very poor agonist, confirming the stereospecificity of the Ins(1,4,5)P3receptor.D‐2,2‐F2‐Ins(1,4,5)P3mobilized Ca2+with broadly similar kinetics to Ins(1,4,5)P3and was a substrate for Ins(1,4,5)P33‐kinase inhibiting Ins(1,4,5)P3phosphorylation (apparentKi= 10.2 μM) but was recognised less well than Ins(1,4,5)P3.L‐2,2‐F2‐Ins(1,4,5)P3was a potent competitive inhibitor of 3‐kinase (Ki= 11.9 μM). WhereasD‐2,2‐F2‐Ins(1,4,5)P3was a good substrate for Ins(1,4,5)P35‐phosphatase,L‐2,2‐F2Ins(1,4,5)P3

ISSN:0899-0042    

DOI:10.1002/chir.530040703

出版商:Alan R. Liss, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractSynthetic soluble (—)‐dopa melanin was prepared in deuteriated buffer, pH 8, by autooxidation of the precursor. At 6 mMof the precursor, the incorporation was over 90%. The changes in the line width measurements of N‐CH3protons 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

ISSN:0899-0042    

DOI:10.1002/chir.530040704

出版商:Alan R. Liss, Inc.    

年代:1992

数据来源: WILEY

摘要:

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, fromAspergillus oryzaeand fromBacillus subtilis. The enantioselective hydrolysis of the methyl esters of theN‐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. subtilisprotease yielded better results thanA. oryzaeprotease. 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, theL‐enantiomers were preferentially hydrolyzed as in the lipase‐catalyzed enantioselective hydrolysis reported previously. © 1992 Wiley

ISSN:0899-0042    

DOI:10.1002/chir.530040705

出版商:Alan R. Liss, Inc.    

年代:1992

数据来源: WILEY

摘要:

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‐med

ISSN:0899-0042    

DOI:10.1002/chir.530040706

出版商:Alan R. Liss, Inc.    

年代:1992

数据来源: WILEY

摘要:

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 ≥

ISSN:0899-0042    

DOI:10.1002/chir.530040707

出版商:Alan R. Liss, Inc.    

年代:1992

数据来源: WILEY

摘要:

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‐L

ISSN:0899-0042    

DOI:10.1002/chir.530040708

出版商:Alan R. Liss, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractAn overall view on some new chiral stationary phases based on (trans)‐1,2‐diaminocyclohexane is illustrated. The selected chiral moiety, derivatized with different aroyl groups, has been linked to a silica matrix in order to give chiral stationary phases (CSPs) enabling them to be used efficiently in the normal and reverse phase, both for analytical and preparative purposes. In addition new polymeric CSPs have been prepared by using the same selector, suitably modified, as monomer. The new chiral stationary phases have been characterised by physicochemical methods and used for the resolution of various racemic compounds classes such as α‐aryloxyacetic acids, alcohols, sulfoxides, selenoxides, phosphinates, tertiaryphosphine oxides, benzodiazepines etc. without prederivatization or as amines, amino acids, amino alcohols, nonsteroidal antiinflammatory agents in a derivatized form. The separated solutes structural variety suggests that multiple interaction sites are involved in the recognition process: some thermodynamic data relative to the CSPs—selectands interactions are also illustrated. © 1992 Wiley

ISSN:0899-0042    

DOI:10.1002/chir.530040709

出版商:Alan R. Liss, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractApplication of cellulose‐based chiral stationary phases was extended to open tubular columns. These chiral materials were mixed with achiral matrix stationary phases. Compromises were found among the polarity and the ratio of achiral matrix polymers against the content of the chiral cellulose derivative in order to optimize the resolution of the investigated racemates. In GC, the high efficiency feature of open tubular columns allows fast analysis, however, compounds which express strong H‐bond interaction with cellulose derivatives elute with a bad peak shape. The application of these stationary phases for open tubular SFC was more successful, because the solvation power of the mobile phase can compensate the strong interaction between the solute and the cellulose derivative. Immobilization of the stationary phases were achieved for SFC purposes. © 1992 Wiley‐Lis

ISSN:0899-0042    

DOI:10.1002/chir.530040710

出版商:Alan R. Liss, Inc.    

年代:1992

数据来源: WILEY

ISSN:0899-0042    

DOI:10.1002/chir.530040711

出版商:Alan R. Liss, Inc.    

年代:1992

数据来源: WILEY