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1. |
Metabolism of halazepam by rat liver microsomes: Stereoselective formation andn‐dealkylation of 3‐hydroxyhalazepam |
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Chirality,
Volume 2,
Issue 1,
1990,
Page 1-9
Xiang‐Lin Lu,
Shen K. Yang,
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摘要:
AbstractMetabolism of halazepam [7‐chloro‐1,3‐dihydro‐5‐phenyl‐1‐(2,2,2‐trifluoroethyl)‐2H‐1,4‐benzodi epin‐2‐one, HZ] was studied by incubation with liver microsomes prepared from untreated, phenobarbital (PB)‐treated, and 3‐methylcholanthrene (3MC)‐treated male Sprague–Dawley rats. Metabolites of HZ were separated by normal‐phase HPLC. Relative rates of HZ metabolism by liver microsomes prepared from untreated and treated rats were PB‐treated ≫ untreated>3MC‐treated at low concentration of microsomal enzymes (0.25 mg protein per ml of incubation mixture) and PB‐treated ≫ 3MC‐treated ≈ untreated at high concentration of microsomal enzymes (2 mg protein per ml of incubation mixture). The relative amounts of major metabolites were found to be 3‐hydroxy‐HZ (3‐OH‐HZ)>N‐desalkylhalazepam (NDZ, also known asN‐desmethyldiazepam and nordiazepam) ≫ oxazepam (OX) for all three rat liver microsomal preparations and the distribution of metabolites was independent of microsomal enzyme concentrations. Enantiomers of 3‐OH‐HZ were resolved by HPLC on a Chiralcel OC column (cellulose trisphenylcarbamate coated on silica gel, particle size 10 μm). 3‐OH‐HZ enantiomeres have racemization half‐lives of ∼ 150 min in pH 4,7.5, and 10 aqueous solutions. 3‐OH‐HZ formed in the metabolism of HZ by liver microsomes prepared from untreated and treated rats were found to have 3R/3S enantiomer rations of 37/63 (untreated), 55/45 (PB‐treated), and 36/64 (3MC‐treated), respectively.N‐dealkylation of 3‐OH‐HZ by liver microsomes from PB‐treated rats was substrate enantioselective; the 3R‐enantiomer wasN‐dealkylated faster than 3S‐enantiomer. The results indicated that the stereoselective C3‐hydroxylation of HZ is dependent on the cytochromesP‐450 present in the rat liver microsomal preparations; pro‐R in liver microso
ISSN:0899-0042
DOI:10.1002/chir.530020102
出版商:Alan R. Liss, Inc.
年代:1990
数据来源: WILEY
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2. |
Stereoselective interaction of an azole antifungal agent with its target, lanosterol 14α‐demethylase (cytochromep‐45014dm): A model study with stereoisomers of triadimenol and purified cytochromep‐45014dmfrom yeast |
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Chirality,
Volume 2,
Issue 1,
1990,
Page 10-15
Yuzo Yoshida,
Yuri Aoyama,
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摘要:
AbstractThe effect of the four triadimenol stereoisomers on the purified yeast lanosterol 14α‐demethylase (cytochromeP‐45014DM), the primary target of azole antifungal agents, was studied. (1S,2R)‐Triadimenol was the most potent demethylase inhibitor and bound quantitatively to the enzyme below 0.05 μM. This isomer also interfered with the chemical reduction of cytochromeP‐45014DMand the binding of CO to the cytochrome. The other isomers showed a lower inhibitory effect on the enzyme, and the order of activity was (1R,2R)>(1R,2S) ≧ (1S,2S). Based on these findings and the reported preferred conformations for the triadimenol stereoisomers (Anderson, N.H. et al., Pestic. Sci. 15:310–316, 1984), it is predicted that orientation of the hydrophobictert‐butyl andp‐chlorophenyl groups relative to the azole nitrogen is important to fit the antifungal agent in the active site o
ISSN:0899-0042
DOI:10.1002/chir.530020103
出版商:Alan R. Liss, Inc.
年代:1990
数据来源: WILEY
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3. |
Preparation of chiral building blocks and auxiliaries by chromatography on cellulose triacetate (CTA I): Indications for the presence of multiple interaction sites in CTA I |
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Chirality,
Volume 2,
Issue 1,
1990,
Page 16-31
Eric Francotte,
Romain M. Wolf,
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摘要:
AbstractDue to the increasing demand for optically active compounds, the development of methods supplying optically pure isomers is intensively progressing. Among these methods the chromatographic resolution on chiral stationary phases is very promising, although only a limited number of preparative applications have been reported so far. In this work, we demonstrate that especially cellulose triacetate I (CTA I) as a chiral phase presents a number of advantages for this purpose. The broad applicability and the high loading capacity of CTA I are particularly important features for preparative chromatography. Nevertheless, slight structural modifications of the racemates to be resolved can often strongly improve the resolution. This strategy has been applied to numerous practical problems and is illustrated in this work taking as examples some chiral building blocks and auxiliaries. Moreover, a systematic investigation of the influence of a substituent in thepara‐position of the phenyl ring for different series of aromatic compounds led to the conclusion that a large number of different interaction sites must be present in the chiral environment of CTA
ISSN:0899-0042
DOI:10.1002/chir.530020104
出版商:Alan R. Liss, Inc.
年代:1990
数据来源: WILEY
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4. |
The stereochemical resolution of the enantiomers of aspartame on an immobilized α‐chymotrypsin hplc chiral stationary phase: The effect of mobile‐phase composition and enzyme activity |
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Chirality,
Volume 2,
Issue 1,
1990,
Page 32-37
Philippe Jadaud,
Irving W. Wainer,
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摘要:
AbstractThe enantioselective and diastereoselective resolutions of the stereoisomers of Nα‐aspartyl‐phenylalanine 1‐methyl ester (APME) have been accomplished on an HPLC chiral stationary phase based upon α‐chymotrypsin (the ACHT‐CSP) with observed enantioselectivities (α1) for the DL‐/LD‐enantiomers of as high as 29.17 and for the DD‐/LL‐enantiomers of as high as 28.97. In addition, the effect on the chromatographic retention of the APME stereoisomers of the activity of the ACHT and the composition of the mobile phase—structure of the anionic component, molarity, and pH—have been studied. The results of this study suggest that the aspartyl moiety and/or the aspartyl‐phenylalanine amide linkage play key roles in the observed enantioselectivity; the APME stereoisomers containing L‐phenylalanine, i.e., DL‐ and LL‐APME, bind at a different site in the ACHT molecule (the L‐Phe site) than the APME stereoisomers containing D‐phenylalanine (the D‐Phe site); and the observed enantioselectivity is a measure of the difference in the binding affinities at the two sites rather than the consequence of di
ISSN:0899-0042
DOI:10.1002/chir.530020105
出版商:Alan R. Liss, Inc.
年代:1990
数据来源: WILEY
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5. |
Interactions of chiral molecules with an (r)‐n‐(3,5‐dinitrobenzoyl) phenylglycine HPLC stationary phase |
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Chirality,
Volume 2,
Issue 1,
1990,
Page 38-42
Alain Berthod,
Heng Liang Jin,
Apryll M. Stalcup,
Daniel W. Armstrong,
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摘要:
AbstractForty different chiral molecules were studied by liquid chromatography with a Pirkle‐type, (R)‐N‐(3,5‐dinitrobenzoyl) phenylglycine (DNBPG), chiral stationary phase column. The dramatic effect of a small molecular change on chiral recognition was demonstrated using DL‐amino acid derivatives. The inductive effect on chiral recognition was also studied using trifluoro‐, trichloro‐, dichloro‐, monochloroacetyl, and acetyl derivatives of four different chiral amines. The study of the enantiomer separation of 11 different crown ethers of 2,2′‐binaphthyldiyl showed that the rigidity of the chiral center can be an additional parameter in chiral recognition for the DNBPG phase but not for a β‐cyclodextrin bonded chiral phase. It is apparent from this study that steric effects, inductive effects, and molecular rigidity play important roles in chiral recognition with DNBPG ch
ISSN:0899-0042
DOI:10.1002/chir.530020106
出版商:Alan R. Liss, Inc.
年代:1990
数据来源: WILEY
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6. |
Reversed‐Phase LC resolutions of chiral antiarrhythmic agents via derivatization with homochiral isothiocyanates |
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Chirality,
Volume 2,
Issue 1,
1990,
Page 43-51
Joseph Gal,
Sabine Meyer‐lehnert,
Daksha M. Desai,
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摘要:
AbstractThe search for new antiarrhythmic agents has been intense, because the established drugs for the treatment of cardiac arrhythmias are neither uniformly effective nor well‐tolerated. Among the recently introduced new anti‐arrhythmic agents are tocainide (TOC), mexiletine (MEX), flecainide (FLE), and propafenone (PRO). Each of these drugs is a chiral amine used clinically as the racemic mixture. We have examined the high‐performance liquid chromatographic chiral resolution of the above four drugs via derivatization with homochiral derivatizing agents (HDAs). The amino functionality of the drugs was reacted with four homochiral isothiocyanates, 2,3,4,6‐tetra‐O‐acetyl‐β‐D‐glucopyranosyl isothiocyanate (TAGIT), (R)‐α‐methylbenzyl isothiocyanate (RAMBI), (S)‐1‐(1‐naphthyl)ethyl isothiocyanate (SNEIT), and (R)‐1‐(2‐naphthyl)ethyl isothiocyanate (RBEIT). Complete separation of the two peaks (resolution factorR= 1.5) was achieved with all four HDAs for TOC, with TAGIT, RBEIT, and RAMBI for MEX, with TAGIT and SNEIT for PRO, and only with TAGIT for FLE. SNEIT was used to develop analytical procedures for the determination of the enantiomeric composition of TOC in human urine and blood serum. The four HDAs offer several advantages over many other HDAs and should be useful in studies of enantiose
ISSN:0899-0042
DOI:10.1002/chir.530020107
出版商:Alan R. Liss, Inc.
年代:1990
数据来源: WILEY
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7. |
Preparative resolutions of an α‐methyl carboxylic acid through selective transformations of readily epimerizable intermediates |
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Chirality,
Volume 2,
Issue 1,
1990,
Page 52-57
Kurt A. Josef,
Thomas E. D'Ambra,
David Rosi,
Richard E. Philion,
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摘要:
AbstractTwo preparations of the enantiomers of 2 are described. The first makes use of the chromatographic separation of the diastereomeric amides 6a and 6b. Standard hydrolysis of these amides caused racemization, so a milder sequence was developed which utilized carbonyldiimidazole and 1 equivalent of 1NLiOH. The second preparation involved classical resolution of 9 with (−)‐cinchonidine. Subsequent transformations of this substrate involved ester formation, Friedel–Crafts acylation, and ester hydrolysis, all without racemization. The most notable of these reactions was the use of EtAlCl2in the Friedel–Crafts step, which provided a mild acylation of 10. This second preparation affords a high yield, mild process for the potential preparation of kilogram quantities of (
ISSN:0899-0042
DOI:10.1002/chir.530020108
出版商:Alan R. Liss, Inc.
年代:1990
数据来源: WILEY
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8. |
Absolute configuration ofcis‐5,6‐dihydrodiol enantiomers derived from helical conformers of 1,12‐dimethylbenz[a]anthracene |
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Chirality,
Volume 2,
Issue 1,
1990,
Page 58-64
Shen K. Yang,
Mohammad Mushtaq,
Peter P. Fu,
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摘要:
Abstract1,12‐Dimethylbenz[α]anthracene (1,12‐DMBA)cis‐5,6‐dihydrodiol was synthesized by oxidation of 1,12‐DMBA with osmium tetroxide in pyridine in low yield (⩽3%) and was purified by sequential use of reversed‐phase and normal‐phase HPLC. Two pairs of 1,12‐DMBAcis‐5,6‐dihydrodiol enantiomers, derived from P (right‐handed helix) and M (left‐handed helix) conformers, were eluted as a single chromatographic peak on both reversed‐phase and normal‐phase HPLC. However, these four enantiomers were resolved by sequential use of two chiral stationary phase (CSP) HPLC columns. CSP (Pirkle type I) columns were packed with either (R)‐N‐(3,5‐dinitrobenzoyl)phenylglycine or (S)‐N‐(3,5‐dinitrobenzoyl)leucine, which is ionically bonded to γ‐aminopropylsilanized silica. Absolute configurations of enantiomers were determined by comparing their circular dichroism spectra with those of conformationally similarcis‐5,6‐dihydrodiol enantiomers of 4‐methylbenz[α]anthracene and 7,12‐dimethyl
ISSN:0899-0042
DOI:10.1002/chir.530020109
出版商:Alan R. Liss, Inc.
年代:1990
数据来源: WILEY
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9. |
Announcements |
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Chirality,
Volume 2,
Issue 1,
1990,
Page 65-66
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ISSN:0899-0042
DOI:10.1002/chir.530020110
出版商:Alan R. Liss, Inc.
年代:1990
数据来源: WILEY
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10. |
Masthead |
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Chirality,
Volume 2,
Issue 1,
1990,
Page -
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PDF (133KB)
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ISSN:0899-0042
DOI:10.1002/chir.530020101
出版商:Alan R. Liss, Inc.
年代:1990
数据来源: WILEY
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