Enantiomer separation of imidazo-quinazoline-dione derivatives on quinine carbamate-based chiral stationary phase in normal phase mode

Krisztina Gyimesi-Forrás, Norbert M. Maier, József Kökösi, András Gergely, Wolfgang Lindner

Research output: Article

14 Citations (Scopus)

Abstract

The normal phase mode liquid chromatographic enantiomer separation capability of a quinine tert-butyl-carbamate-type chiral stationary phase (CSP) has been investigated for a set of polar [1,5-b]-quinazoline-1,5-dione derivatives. This class of chiral heterocycles is currently under development as potential α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and/or N-methyl-D-aspartic acid (NMDA) receptor antagonists. The effect of the nature and concentration of polar modifier, i.e., ethanol and isopropanol, in n-hexane-based mobile phases, as well as the substituent pattern of the phenyl ring attached to the quinazolone framework on retention factor, enantioselectivity, and resolution was investigated. The Soczewiński competitive adsorption model was used to describe the relationship between the retention and the binary mobile phase compositions. According to this model, linear plots of the logarithms of retention factor versus molar fractions of the polar modifiers were obtained over a wide concentration range (XB between 0.15 and 0.35). Addition of equimolar ethanol yields higher resolution than isopropanol, RS values ranging between 1.54 and 2.75, whereas the latter allows to achieve moderately increased enatioselectivity. The resolution was further improved by using a ternary mixture of n-hexane:methanol:isopropanol/85:5:10 (v/v). The most pronounced selectivity factor α and resolution RS values were obtained for the para-hydroxy substituted compound, indicating that chiral recognition is sensitive to steric and stereoelectronic factors. In the course of optimization, the temperature-dependence on the chiral separation was also investigated. It turned out that the enantiomer separation is predominantly enthalpically driven in normal phase mode.

Original languageEnglish
Pages (from-to)199-207
Number of pages9
JournalChirality
Volume21
Issue number1
DOIs
Publication statusPublished - márc. 2 2009

ASJC Scopus subject areas

  • Analytical Chemistry
  • Catalysis
  • Pharmacology
  • Drug Discovery
  • Spectroscopy
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Enantiomer separation of imidazo-quinazoline-dione derivatives on quinine carbamate-based chiral stationary phase in normal phase mode'. Together they form a unique fingerprint.

  • Cite this