Comparison of enhanced fluidity liquid chromatography with liquid chromatography for enantioseparation of selected γ-lactam derivatives

Abstract

The present paper describes the study of eight racemic γ-lactam derivatives with the goal of comparing three modes of liquid chromatography which are the reversed-phase mode, the normal-phase mode and the polar organic solvent chromatography mode with super/subcritical fluid chromatography and enhanced fluidity liquid chromatography in extreme conditions i.e. when the CO2 percentage is practically zero. For this study two CPSs were chosen. Chiralcel OD-H was used in HPLC conditions and Chiralcel OD-H and Lux Cellulose-2 were used in SFC conditions. It is reported in this work that the introduction of chlorine substituent on polysaccharide-based selectors contributes to an improved enantioselectivity in supercritical fluid chromatography (SFC) compared to the electron-donating substituted phenyl carbamate column, allowing the complete separation of seven analytes out of the eight.The effect of enhanced fluidity liquid chromatography conditions, described as an intermediate mode between HPLC and SFC is also explored. In this case, the composition of the mobile phase starting at 80% CO2 was replaced with almost 100% ethanol at the end, this assay achieving further extension of the polarity range of the mobile phase in a single run and successfully enabling the simultaneous analysis and separation of the racemates. Under a mobile phase constituted of 99% ethanol, the resolution values of the γ-lactam derivatives on Lux Cellulose-2 CSP, were comprised between 1.91 and 3.44. High values of flowrates, ranging from 4 mL/min to 10 mL/min were also evaluated for some analytes on the highly retentive Lux Cellulose-2 CSP, leading to resolution equal to 6.24 for compound 6 and 4.64 for compound 8.

Keywords

• Antibacterial compounds
• Cellulose tris(3‑chloro-4-methylphenylcarbamate)
• Cellulose tris(3,5-dimethylphenylcarbamate)
• Elevated percentage of co-solvent
• Flowrate