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1. |
A comparison of LC and SFC for cellulose‐ and amylose‐derived chiral stationary phases |
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Chirality,
Volume 7,
Issue 5,
1995,
Page 311-325
Nathalie Bargmann‐Leyder,
André Tambuté,
Marcel Caude,
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摘要:
AbstractThis paper presents a systematic comparison of liquid chromatography (LC) and supercritical fluid chromatography (SFC) for Chiralcel OD and Chiralpak AD chiral stationary phases (CSPs), performed using various chiral compounds having a known or potential pharmaceutical activity. The chiral recognition mechanisms involved in LC and SFC for the enantiomeric separation of β‐blockers have been studied more particularly. As a general rule, it appears that the presence of polar functions, like primary or secondary hydroxyl or amine functions, may result in marked discrepancies in selectivity between LC and SFC. This result is peculiar to cellulose‐ and amylose‐derived CSPs, for which the interactions involved in chiral recognition mechanism are not always well balanced, contrary to what happens for independent CSPs. In the case of chiral resolution of polar solutes or polymer‐type CSPs, the analyst should try both the LC and SFC techniques to be able to choose the more stereoselective one. © 1995 Wiley
ISSN:0899-0042
DOI:10.1002/chir.530070502
出版商:Alan R. Liss, Inc.
年代:1995
数据来源: WILEY
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2. |
NMR investigations of the enantiomeric excess effects in solutions with weak intermolecular association |
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Chirality,
Volume 7,
Issue 5,
1995,
Page 326-330
Erlen I. Fedin,
Vadim A. Davankov,
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摘要:
AbstractThe main features of statistically controlled associate diasteromerism (SCAD) in solution as measured by nuclear magnetic resonance (NMR) are discussed. In an achiral solvent, (R)‐ and (S)‐enantiomers can demonstrate distinct NMR signals, with the intensity ratio equal to the concentration ratio. The previous theory of SCADA (anisochronism of nuclear magnetic moments caused by SCAD) is supplemented by treatment of enantiomeric excess phenomena in relation with the hypothesis that a sample consists totally of short‐living diastereomeric dimers which are involved in fast (on the NMR time scale) exchange by enantiomers. Thermodynamic parameters of SCAD as well as limits for enantioselectivity phenomena are estimated. © 1995 Wiley‐L
ISSN:0899-0042
DOI:10.1002/chir.530070503
出版商:Alan R. Liss, Inc.
年代:1995
数据来源: WILEY
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3. |
Chiral separation of unmodified α‐hydroxy acids by ligand exchange HPLC using chiral copper(II) complexes of (S)‐phenylalaninamide as additives to the eluent |
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Chirality,
Volume 7,
Issue 5,
1995,
Page 331-336
Gianni Galaverna,
Francesco Pantò,
Arnaldo Dossena,
Rosangela Marchelli,
Franca Bigi,
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摘要:
AbstractCopper(II) complexes of (S)‐phenylalaninamide have been successfully used for the direct enantiomeric separation of unmodified (R,S)‐α‐hydroxy acids in reversed phase high‐performance liquid chromatography (RP‐HPLC). The effect of various parameters (pH, eluent polarity, selector concentration) on enantioselectivity is discussed. Evidence is provided that a mechanism of ligand exchange is actually occurring during the chromatographic separation. The method is very convenient and easy to use, and the chiral selector is commercially available and can be recovered at the end of the analysis. A conventional achiral RP‐ODS‐2 column is used and no pretreatment of the samples is required. This method allows the accurate determination of the enantiomeric excess of α‐hydroxy acids in synthetic and biological samples. © 19
ISSN:0899-0042
DOI:10.1002/chir.530070504
出版商:Alan R. Liss, Inc.
年代:1995
数据来源: WILEY
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4. |
A serious problem with computer processing of stereochemistry in chemical structure files: The need for standardisation |
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Chirality,
Volume 7,
Issue 5,
1995,
Page 337-341
Bernard Blessington,
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摘要:
AbstractMany computer programmes exist for drawing and modelling small and large molecules. Small molecules related to the antitubercular drug ethambutol are discussed. Some specific software problems, with stereochemical representations, are illustrated. Incompatibility of molecular structure files produced by different programmes and different hardware are shown. The need for a standardised file format is stressed. © 1995 Wiley‐Liss, I
ISSN:0899-0042
DOI:10.1002/chir.530070505
出版商:Alan R. Liss, Inc.
年代:1995
数据来源: WILEY
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5. |
Stereoselectivity of the carbonyl reduction of dolasetron in rats, dogs, and humans |
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Chirality,
Volume 7,
Issue 5,
1995,
Page 342-348
James Dow,
Christiane Berg,
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摘要:
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 m
ISSN:0899-0042
DOI:10.1002/chir.530070506
出版商:Alan R. Liss, Inc.
年代:1995
数据来源: WILEY
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6. |
Development of chiral drugs in Japan: An update on regulatory and industrial opinion |
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Chirality,
Volume 7,
Issue 5,
1995,
Page 349-352
Hideyo Shindo,
John Caldwell,
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摘要:
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,Chirality3:91–93, 1991), and the interested reader is referred to this for background information. © 1995 Wiley‐Liss,
ISSN:0899-0042
DOI:10.1002/chir.530070507
出版商:Alan R. Liss, Inc.
年代:1995
数据来源: WILEY
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7. |
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 |
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Chirality,
Volume 7,
Issue 5,
1995,
Page 353-358
Carlo Rosini,
Ivana Rosati,
Gian Piero Spada,
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摘要:
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‐cisconformation, 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‐transconformation 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
ISSN:0899-0042
DOI:10.1002/chir.530070508
出版商:Alan R. Liss, Inc.
年代:1995
数据来源: WILEY
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8. |
Comparative toxicity of (+)‐(R)‐ and (−)‐(S)‐1,2‐dibromo‐3‐chloropropane |
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Chirality,
Volume 7,
Issue 5,
1995,
Page 359-364
Samir A. Kouzi,
Erik J. Søderlund,
Erik Dybing,
John H. N. Meerman,
Sidney D. Nelson,
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摘要:
AbstractThe haloalkane 1,2‐dibromo‐3‐chloropropane (DBCP), an environmental pollutant that was widely used as a soil fumigant, is a carcinogen and a mutagen and displays target‐organ toxicity to the testes and the kidneys. Because little is known about effects of stereochemistry on the metabolism and toxicity of halogenated alkyl compounds and because DBCP, which has a chiral center at C‐2, may show enantioselectivity in its metabolism and/or toxicities, the optically pure enantiomers of DBCP were tested in vivo in rats for organ toxicity as well as for bacterial mutagenicity. Organ toxicity studies showed that (S)‐DBCP was slightly more renal toxic than (R)‐DBCP but was not significantly more toxic than the racemate, and that no significant differences were observed in the extents of testicular necrosis and atrophy caused by either enantiomer or the racemate. In contrast, (R)‐DBCP was more mutagenic than either (S)‐DBCP or the racemate toSalmonella typhimurium (S. typhimurium)strains TA 100 and TA104. However, there was little or no enantioselectivity in glutathioneS‐transferase (GST)‐catalyzed conjugation reactions of glutathione with DBCP based on the lack of selectivity in the rates of disappearance of the enantiomers of DBCP in the presence of glutathione (GSH) and GSTs as monitored by chiral gas chromatography (GC).
ISSN:0899-0042
DOI:10.1002/chir.530070509
出版商:Alan R. Liss, Inc.
年代:1995
数据来源: WILEY
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9. |
Substitution and racemization of 3‐hydroxy‐ and 3‐alkoxy‐1,4‐benzodiazepines in acidic aqueous solutions |
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Chirality,
Volume 7,
Issue 5,
1995,
Page 365-375
Shen K. Yang,
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摘要:
AbstractOxazepam (OX), 3‐O‐methyloxazepam, 3‐O‐ethyloxazepam, temazepam (TMZ), 3‐O‐methyltemazepam, and 3‐O‐ethyltemazepam underwent acid‐catalyzed nucleophilic substitution reaction (hydrolysis) in an acetonitrile–oxygen‐18 water mixture to form either OX or TMZ in which the 3‐hydroxyl group was either partially or fully labeled with an oxygen‐18 atom. The dependence of the hydrolysis rates on solvent composition, temperature, ionic strength, and in deuterated solvent was studied by reversed‐phase high‐performance liquid chromatography (HPLC). The rates of racemization of enantiomeric compounds in acidic aqueous solutions were studied by both spectropolarimetry and chiral stationary phase HPLC. In acetonitrile: 2.5MH2SO4(4:1, v/v) at 50°C, enantiomers of OX and TMZ underwent racemization at rates ≥40‐fold faster than the rates of hydrolysis. Enantiomeric 3‐O‐alkyl derivatives of OX and TMZ in acidic aqueous solutions did not themselves undergo racemization and it was their hydrolysis products (either OX or TMZ) that underwen
ISSN:0899-0042
DOI:10.1002/chir.530070510
出版商:Alan R. Liss, Inc.
年代:1995
数据来源: WILEY
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10. |
Enantioselectivity of aromatase inhibitors: Substituted 3‐(4‐aminophenyl)pyrrolidine‐2,5‐diones |
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Chirality,
Volume 7,
Issue 5,
1995,
Page 376-380
Christopher Pepper,
H. John Smith,
Paul J. Nicholls,
Kevin J. Barrell,
Massoud Ahmadi,
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摘要:
AbstractThe (+)‐, (−)‐, and (±)‐forms of 1‐ and 1,3‐substituted 3‐(4‐aminophenyl)pyrrolidine‐2,5‐dione have been examined as inhibitors of P450AROMand P450CSCC. The inhibitory potency for P450AROMresided in the (+)‐enantiomers of (1), (2), and (4) and the (−)‐enantiomers of (3) and (5). These findings have been accommodated within a molecular graphics‐derived model for binding of P450AROMinhibitors to the substrate binding site. Crystallography showed that (+)‐(2) has the (R)‐configuration. Spectral binding studies with human placental P450AROMshowed type II binding but although theKSvalues were in line with the IC50values for individual compounds there was no overall correlation betweenKSand IC50within the series. There was little difference in the inhibitory potency of the enantiomers and racemate of individual compounds toward
ISSN:0899-0042
DOI:10.1002/chir.530070511
出版商:Alan R. Liss, Inc.
年代:1995
数据来源: WILEY
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