Enantioseparation of Benzoxazolinone Aminoalcohols and Their Aminoketone Precursors, Potential Adrenergic Ligands, by Analytical and Preparative Liquid Chromatography on Amylose Chiral Stationary Phases and Characterization of the Enantiomers

摘要

To obtain milligram amounts of the enantiomers of benzoxazolinone derivatives to be tested for binding to adrenergic sites, analytical HPLC methods using derivatized amylose chiral stationary phases were developed for the direct enantioseparation of benzoxazolinone aminoalcohols and their aminoketone precursors, derivatives with one or two chirals centers. The separations were made using normal phase methodology with a mobile phase of n-hexane-alcohol (ethanol, 1-propanol, or 2-propanol) in various proportions, and silica-based amylose (tris-3, 5-dimethylphenylcarbamate) Chiralpak AD and (tris-(S)-1-phenylethylcarbamate) Chiralpak AS columns. The effects of concentration of various aliphatic alcohols in the mobile phase were studied. The best separation was achieved on Chiralpak AS, so preparative HPLC was set up with this chiral stationary phase using a mobile phase consisting of n-hexane-alcohol using isocratic conditions and multiple repetitive injections. Physicochemicals properties of enantiomers were reported The effect of structural features of the solutes on discrimination between the enantiomers was examined. Limit of detection (LD) and Emit of quantification (LQ) were determined using both ultra-violet (UV) and evaporative light-scattering detection (ELSD). Chirality 21:769-776, 2009.