Polysaccharide-based chiral stationary phases as efficient tools for diastereo- and enantioseparation of natural and synthetic Cinchona alkaloid analogs

Attila Bajtai,István Ilisz,Róbert Berkecz,Ferenc Fülöp,Wolfgang Lindner,Antal Péter

doi:10.1016/j.jpba.2020.113724

Abstract

In this study, we present results obtained on the diastereo- and enantioseparation of some basic natural and synthetic Cinchona alkaloid analogs by applying liquid chromatographic (LC) and subcritical fluid chromatographic (SFC) modalities on amylose and cellulose tris-(phenylcarbamate)-based stationary phases using n-hexane/alcohol/DEA or CO2/alcohol/DEA mobile phase systems. Seven chiral stationary phases in their immobilized form were employed to explore their stereoselectivity for a series of closely related group of analytes. The most important characteristics of LC and SFC systems were evaluated through the variation of the applied chromatographic conditions (e.g., the nature and content of the alcohol modifier, the concentration of additives, temperature). The columns Chiralpak IC and IG turned out to be the best in both LC and SFC modalities. Temperature-dependence study indicated enthalpy-controlled separation in most cases; however, separation controlled by entropy was also registered.

Highlights

Both natural and synthetic Cinchona alkaloids have a rather complex structural pattern with more than thirty representatives, among these quinine (QN), quinidine (QD), cinchonidine (CD), and cinchonine (CN) represent the main components [1]
In addition to the pharmaceutical relevance of the main alkaloids and derivatives thereof, they may serve as catalysts in stereo-directed organic synthesis [2], and as chiral selectors in the course of the development of chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC) [3]
The main objective of the present paper is to reveal some general tendencies of a set of prominent PS-CSPs (Fig. S1) for the diastereo- and enantioseparation of the set of chiral analytes (Table 1) under normal-phase mode (NP)-liquid chromatographic (LC) and supercritical fluid chromatography (SFC) conditions

Summary

Introduction

Both natural and synthetic Cinchona alkaloids have a rather complex structural pattern with more than thirty representatives, among these quinine (QN), quinidine (QD), cinchonidine (CD), and cinchonine (CN) represent the main components [1]. Capillary electrophoretic [5] and HPLC-based [1,6] methods have been described for the separation of the four major Cinchona alkaloids QN, QD, CD, and CN as well as dihydroquinine (DHQN) and dihydroquinidine (DHQD). Along this line, the quantitative determination of six major alkaloids implementing supercritical fluid chromatography (SFC) has recently been reported [7]

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Results

Conclusion