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Enantiomer separation of imidazo‐quinazoline‐dione derivatives on quinine carbamate‐based chiral stationary phase in normal phase mode
Author(s) -
GyimesiForrás Krisztina,
Maier Norbert M.,
Kökösi József,
Gergely András,
Lindner Wolfgang
Publication year - 2009
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.20640
Subject(s) - chemistry , enantiomer , chiral column chromatography , isoxazole , resolution (logic) , substituent , chiral resolution , carbamate , capacity factor , selectivity , chirality (physics) , phase (matter) , stereochemistry , chromatography , organic chemistry , nambu–jona lasinio model , chiral symmetry breaking , physics , quantum mechanics , artificial intelligence , quark , computer science , catalysis
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 ( X B between 0.15 and 0.35). Addition of equimolar ethanol yields higher resolution than isopropanol, R S 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 R S 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. Chirality, 2009. © 2008 Wiley‐Liss, Inc.