Preparative enantiomeric separation of new selective CB₂ receptor agonists by liquid chromatography on polysaccharide‐based chiral stationary phases: Determination of enantiomeric purity and assignment of absolute stereochemistry by X‐ray structure analysis

Abstract

The development of high-performance liquid chromatography (HPLC) methods using derivatized amylose chiral stationary phases has permitted preparative enantioseparations of substituted 4-oxo-1,4-dihydroquinoline-3-carboxamide derivatives with satisfactory yields. These compounds constitute new potent selective agonists of the cannabinoid CB(2) receptor. Analytical enantioseparation methods using UV detection were validated to determine the enantiomeric purity of these compounds. Linear calibration curves in the range from 0.18 to 0.40 mM were obtained; repeatability, limits of detection (LOD), and quantification (LOQ) were determined: LOD varied, for the various solutes, from 0.5 to 1.2 μM. All the separated compounds were prepared with high enantiomeric purities superior to 99.3% Absolute configuration of the enantiomers was unequivocally established by single crystal X-ray diffraction method and correlated to the chiroptical properties of isolated enantiomers.

Chiral separation of quinolones by liquid chromatography and capillary electrophoresis

“…The collected fractions of the optical antipodes required further purification by column chromatography on silica gel. The yields of the preparative separations were not worse than 78% . Bach et al.…”

“…Stern et al. had reported chiral resolution of 4‐oxo‐1,4‐dihydroquinoline‐3‐carboxamide derivatives (for example, XVI) on amylose CSPs Chiralpak AD‐H, AD, and AS. The Chiralpak AD columns were found to separate better enantiomers of the quinolones in question.…”

“…The effects of the mobile phase composition (hexane/ethanol or 1‐propanol or 2‐propanol) and temperature on retention and enantioresolution were studied. The absolute configuration of the enantiomers was established by single crystal X‐ray diffraction method and correlated to the chiroptical properties of the resolved enantiomers . Analytical characteristics of the method were evaluated.…”