Kinetics of racemization of enantiopure N-imidazole derivatives, aromatase inhibitors:: studies in organic, aqueous, and biomimetic media

被引：10

作者：

Danel, Cecile ^{[1
]}

Foulon, Catherine ^{[1
]}

Goossens, Jean-Francois ^{[1
]}

Bonte, Jean-Paul ^{[1
]}

Vaccher, Claude ^{[1
]}

机构：

[1] Univ Lille 2, Fac Sci Pharmaceut & Biol, Chim Analyt Lab, EA 4034, F-59006 Lille, France

来源：

TETRAHEDRON-ASYMMETRY | 2006年 / 17卷 / 16期

关键词：

D O I：

10.1016/j.tetasy.2006.08.014

中图分类号：

O61 [无机化学];

学科分类号：

070301 ; 081704 ;

摘要：

The configurational stability of N-imidazole derivatives, aromatase inhibitors, was investigated under organic, aqueous, and biomimetic media, by studying the effect of organic solvent, pH, and temperature. Validated chiral HPLC or CD-EKC methods allowed us to quantify the presence of both enantiomers. The rate constants, half-lives, and apparent free energy barriers of the racemization phenomenon were determined using a mathematical model of this first-order reaction. The presence of triethylamine (2000 equiv) at high temperature (70 degrees C) induces the fastest racemization with a t(1/2rac) less than 7 h. This result can be related to the lability of benzylic proton in these strongly basic conditions. Biomimetic media (the presence of bovine serum albumin in a pH 7.4 buffer at 37.4 degrees C) do not seem to preserve the initial configuration of each enantiomer. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：2317 / 2321

页数：5

共 23 条

[1] Resolution of the enantiomers of tetrahydrozoline by chiral HPLC. The racemization of the enantiomers via an imine-enamine tautomerism [J].

Caccamese, S ;

Principato, G .

TETRAHEDRON-ASYMMETRY, 1998, 9 (16) :2939-2945

[2] Validation of chiral electrokinetic chromatography methods using highly sulfated cyclodextrins: Determination of enantiomeric purity of aromatase inhibitors [J].

Danel, C ;

Foulon, C ;

Goossens, JF ;

Bonte, JP ;

Vaccher, C .

CHROMATOGRAPHIA, 2006, 63 (7-8) :353-358

[3] Enantiomeric resolution of new aromatase inhibitors by liquid chromatography on cellulose chiral stationary phases [J].

Danel, C ;

Foulon, C ;

Park, C ;

Yous, S ;

Bonte, JP ;

Vaccher, C .

JOURNAL OF SEPARATION SCIENCE, 2005, 28 (05) :428-434

[4] Chiral resolution of the enantiomers of new aromatase inhibitors by liquid chromatography on amylose stationary phases [J].

Danel, C ;

Foulon, C ;

Park, C ;

Yous, S ;

Bonte, JP ;

Vaccher, C .

CHROMATOGRAPHIA, 2004, 59 (3-4) :181-188

[5] Preparative enantiomeric separation of new aromatase inhibitors by HPLC on polysaccharide-based chiral stationary phases: Determination of enantiomeric purity and assignment of absolute stereochemistry by X-ray structure analysis [J].

Danel, C ;

Foulon, C ;

Guelzim, A ;

Park, CH ;

Bonte, JP ;

Vaccher, C .

CHIRALITY, 2005, 17 (09) :600-607

[6]

DANEL C, 2003, THESIS U LILLE 2

[7] NMR studies of chiral recognition mechanisms:: interaction of enantiomers of N-imidazole derivatives with cyclodextrin hosts.: Correlation with the CD-EKC studies [J].

Danel, Cécile ;

Azaroual, Nathalie ;

Foulon, Catherine ;

Goossens, Jean-François ;

Vermeersch, Gaston ;

Bonte, Jean-Paul ;

Vaccher, Claude .

TETRAHEDRON-ASYMMETRY, 2006, 17 (06) :975-983

[8] Controlled racemization of optically active organic compounds: Prospects for asymmetric transformation [J].

Ebbers, EJ ;

Ariaans, GJA ;

Houbiers, JPM ;

Bruggink, A ;

Zwanenburg, B .

TETRAHEDRON, 1997, 53 (28) :9417-9476

[9] AROMATASE INHIBITORS - SYNTHESIS, BIOLOGICAL-ACTIVITY, AND BINDING MODE OF AZOLE-TYPE COMPOUNDS [J].

FURET, P ;

BATZL, C ;

BHATNAGAR, A ;

FRANCOTTE, E ;

RIHS, G ;

LANG, M .

JOURNAL OF MEDICINAL CHEMISTRY, 1993, 36 (10) :1393-1400

[10] Pharmaceutical and biomedical applications of enantioseparations using liquid chromatographic techniques [J].

Haginaka, J .

JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 2002, 27 (3-4) :357-372

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