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.
The development of high-performance liquid chromatography methods on polysaccharide-based stationary phases (cellulose or amylose derivatives) has permitted preparative enantioseparations of various 6-[1(imidazol-1-yl)-1-phenylmethyl]-3-methyl-1,3-benzoxazol-2(3H)-one and 6-[1(imidazol-1-yl)-1-phenylmethyl]-3-methyl-1,3-benzothiazol-2(3H)-one, aromatase inhibitors, with satisfactory yields. Analytical enantioseparation methods using both UV and evaporative light-scattering detection (ELSD) were validated to determine the enantiomeric purity of these compounds. Using UV detection, linear calibration curves in the range from 4 x 10(-6) to 4.8 x 10(-4) M range were obtained; repeatability, limits of detection (LD), and quantification (LQ) were determined: LD varied, for the various solutes, from 1 to 80 microg/l and from 2.05 to 10.05 mg/l with UV detection and ELSD, respectively. Single-crystal X-ray analysis was successful in determining the absolute configuration of the individual enantiomers. The relationship between retention order and absolute configuration of the enantiomers was established.
Danel
Cecile
C
Laboratoire de Chimie Analytique, EA 1043, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Lille 2, France.
Foulon
Catherine
C
Guelzim
Abdelhalim
A
Park
Chang Ha
CH
Bonte
Jean-Paul
JP
Vaccher
Claude
C
D047072:Aromatase Inhibitors / Q000737:chemistry* / Q000302:isolation & purification*; D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D015394:Molecular Structure; D011134:Polysaccharides / Q000737:chemistry*; D013237:Stereoisomerism; D013256:Steroids / Q000737:chemistry
D047072:Aromatase Inhibitors; D011134:Polysaccharides; D013256:Steroids