Synthesis of Quinoline-Based New Chiral Derivatizing Reagents and its use in the Derivatization and Enantioseparation of Few Structurally Similar β-Blockers using Liquid Chromatography and Structural Optimization using DFT

Abstract

In this work, quinoline based new chiral derivatizing reagent was synthesized by introducing chiral amino acid (L-proline) in the molecule. Synthesized chiral derivatizing reagent was characterized by spectroscopic techniques (1H NMR, FT-IR, HRMS and CHNS analysis) and used in the synthesis of diastereomer of chosen β-blockers. The RP-HPLC system was used to separate synthesized diastereomers (indirect approach of enantioseparation). Acetonitrile and buffer solution was used as mobile phase for analysis. The effect of varying concentrations and pH of mobile phase was optimized for the separation of diastereomers. The density functional theory calculations were also carried out to develop the lowest energy-minimize optimized diastereomer structures and to design separation mechanisms and elution orders. The retention factor (k), selectivity factor (α), resolution factor (RS), the limit of detection (0.192 ng mL–1) and the limit of quantification (0.576 ng mL–1) were calculated in the context of the method’s validation in accordance with ICH guidelines.