Recent trends and applications in liquid‐phase chromatography enantioseparation of atropisomers

Abstract

The term Atropisomerism defines a type of enantiomerism that arises from hindered rotation around an axis that makes two rotational isomers enantiomers. Atropisomeric compounds are present in nature, being important building blocks of many biologically active compounds. Atropisomers have been extensively studied in environmental and toxicological chemistry and, in particular, separating them has become a need in specific fields as organic synthesis and pharmaceutical research. High-performance LC has been fruitfully applied in this context, and despite HPLC separation on chiral stationary phase is considered as mature technology nowadays, in the last years several advancements and applications contributed to study compounds where axial chirality is of utmost importance. Moreover, dynamic chromatography has been exploited as a versatile tool for kinetic studies of systems with slow internal motion gaining essential information on their stereodynamic behavior. On this basis, current topics and trends in liquid-phase chromatography enantioseparation of atropisomers are presented herein with specific focus on new representative applications with HPLC, covering years 2010-2016. Some examples concerning supercritical fluid chromatography applications are also reported. This review aims to provide the reader with a modern overview of the field to highlight the renewed interest toward the chemistry of molecules with atropisomeric properties. A systematic compilation of all published literature has not been attempted.

Chiral Chalcogen Bond Donors Based on the 4,4′-Bipyridine Scaffold

“…Beer's group described a chiral selenium-containing receptor for enantiomeric discrimination of dicarboxylates [24]. Following previous studies on XB-based high performance liquid chromatography (HPLC) enantioseparations [31][32][33][34][35][36], our groups demonstrated that ChB can participate in the recognition process underlying the enantioseparation of sulfur-containing atropisomeric 4,4 -bipyridine 1 on a cellulose-based chiral stationary phase [37].…”

Recent studies of docking and molecular dynamics simulation for liquid‐phase enantioseparations

“…In the last years, our groups investigated the factors governing HPLC enantioseparation of atropisomeric halogenated 4,4’‐bipyridines on polysaccharide‐based CSPs . Following these studies, we have demonstrated the contribution of XB and chalcogen bonds (ChBs) for the enantiorecognition of analytes on CDMPC under NP elution conditions.…”

“…In the last decades, both LC and CE techniques have been successfully employed in enantioseparation science . Despite the huge number of papers published in these fields, the understanding of the stereoselective interaction process is still an open issue.…”

Colistin Sulfate Chiral Stationary Phase for the Enantioselective Separation of Pharmaceuticals Using Organic Polymer Monolithic Capillary Chromatography

“…To access enantiomerically pure compounds, enantioselective chromatographic techniques have been considered as the most feasible method compared to other more expensive and time-consuming approaches [4,5,6,7,8,9,10]. Among these techniques, High Performance Liquid Chromatography (HPLC) is the most widely used technique in enantiomer separation [11,12,13]. In HPLC, a chiral selector is required to form a Chiral Stationary Phase (CSP), the main driver for the chiral separation.…”