Enantiomeric resolution of new aromatase inhibitors by liquid chromatography on cellulose chiral stationary phases

J Sep Sci. 2005 Mar;28(5):428-34. doi: 10.1002/jssc.200401761.

Abstract

Analytical HPLC methods using derivatized cellulose chiral stationary phases were developed for the direct enantioseparation of substituted [1-(imidazo-1-yl)-1-phenylmethyl)]-benzothiazolinone and benzoxazolinone derivatives with one chiral center. Those analogues of fadrozole constitute new potent nonsteroidal inhibitors of aromatase (P450 arom). The separations were made using normal phase methodology with a mobile phase consisting of n-hexane-alcohol (ethanol, 1-propanol, or 2-propanol) in various proportions, and a silica-based cellulose tris-3,5-dimethylphenylcarbamate (Chiralcel OD-H), or tris-methylbenzoate (Chiralcel OJ). The effects of concentration of various aliphatic alcohols in the mobile phase were studied. A better separation was achieved on cellulose carbamate phase compared with the cellulose ester phase. The effects of structural features of the solutes along with the temperature of the column on the discrimination between the enantiomers were examined. Baseline separation (Rs > 1.5) was easily obtained in many cases.

MeSH terms

  • Aromatase Inhibitors / chemistry*
  • Aromatase Inhibitors / isolation & purification*
  • Cellulose / chemistry*
  • Chromatography, Liquid
  • Molecular Structure
  • Stereoisomerism
  • Temperature
  • Thermodynamics

Substances

  • Aromatase Inhibitors
  • Cellulose