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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
Author(s) -
Danel Cecile,
Foulon Catherine,
Guelzim Abdelhalim,
Park Chang Ha,
Bonte JeanPaul,
Vaccher Claude
Publication year - 2005
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.20206
Subject(s) - chemistry , enantiomer , absolute configuration , high performance liquid chromatography , chromatography , detection limit , chirality (physics) , enantiomeric excess , repeatability , cellulose , chromatography detector , analytical chemistry (journal) , stereochemistry , enantioselective synthesis , organic chemistry , catalysis , chiral symmetry breaking , physics , quantum mechanics , nambu–jona lasinio model , quark
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(3 H )‐one and 6‐[1(imidazol‐1‐yl)‐1‐phenylmethyl]‐3‐methyl‐1,3‐benzothiazol‐2(3 H )‐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 × 10 −6 to 4.8 × 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 μg/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. © 2005 Wiley‐Liss, Inc. Chirality 17:600–607, 2005.