Enantiomeric resolution and simulation studies of four enantiomers of 5-bromo-3-ethyl-3-(4-nitrophenyl)-piperidine-2,6-dione on a Chiralpak IA column

Abstract

Enantiomeric resolution and simulation studies of four enantiomers of 5-bromo-3-ethyl-3-(4-nitrophenyl)-piperidine-2,6-dione on a Chiralpak IA column were presented. The mobile phase used was pure acetonitrile at 1.0 mL min⁻¹ flow rate. The detection wavelength and column temperature were 254 nm and 27 °C. The column used was a Chiralpak IA (250 × 4.6 mm; 5 μm). The values of retention factors were 2.40, 2.95, 5.00 and 7.45 for 3S,5S, 3R,5R, 3S,5R and 3R,5S stereomers. The values of the separation factors were 1.22, 1.69 and 1.49. The values of the resolution factors were 3.88, 7.04 and 8.22. The limits of detections and quantitation ranged from 1.0–3.5 and 11.1–35.6 μg mL⁻¹, respectively. The chiral recognition mechanism and elution order of the reported stereomers were determined by simulation studies. It was observed that hydrogen bonding and π–π interactions are the major forces for the chiral resolution. The described chiral method may be used for the enantiomeric resolution of the four stereomers of 5-bromo-3-ethyl-3-(4-nitrophenyl)-piperidine-2,6-dione in any unknown matrices.