Stereolabile chiral compounds: analysis by dynamic chromatography and stopped-flow methods

Abstract

Enantiomerization and diastereomerization reactions of chiral compounds play a major role in all aspects of chemistry spanning a wide bridge from drug development to supramolecular chemistry. Traditionally, these reactions are studied by variable-temperature NMR spectroscopy and chiroptical methods such as polarimetry. However, powerful complimentary methods based on chromatography and electrophoresis have been developed and applied to a variety of stereolabile chiral compounds. This tutorial review explains the principles, applications, and limitations of dynamic chromatography and chromatographic and electrophoretic stopped-flow analysis for the investigation of isomerization reactions of chiral compounds.

Serendipitous discovery of a pH-dependant atropisomer bond rotation: Toward a write-protectable chiral molecular switch?☆

“…The chromatographic separation of slowly interconverting atropisomers is a popular subject within the field of chiral chromatography, with molecules from diverse structural classes having been studied using a variety of chromatographic techniques [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. We herein report the serendipitous discovery of an unusual interconverting atropisomer system, 1, where a strong influence of pH on carboxamide bond rotation is observed.…”

Enantiomerization of chiral 2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c][1,2,4]benzothiadiazine 5,5-dioxide by stopped-flow multidimensional HPLC☆

“…Rate constants and free energy barriers of enantiomerization of configurationally labile chiral compounds have been calculated by means of dynamic NMR (DNMR) [28][29][30], chirooptical methods [31,32], dynamic gas chromatography (DGC) [33], dynamic high-performance liquid chromatography (DHPLC) [26], dynamic capillary electrophoresis (DCE) [34].…”

A novel software tool for high throughput measurements of interconversion barriers: DCXplorer☆

“…Furthermore no special analytical equipment is necessary. For the evaluation ଝ This paper is part of the Special Issue 'Enantioseparations', dedicated to W. of elution profiles obtained by dynamic chromatography or electrophoresis sophisticated methods have been developed in the past for the relatively fast and precise determination of reaction rate constants [4][5][6][7][8][9][10][11][12][13][14][15][16]. Despite these efforts, there is still a need for improvement in the evaluation process of dynamic elution profiles [17], because using iterative computer simulations, especially for large datasets is computationally expensive and direct calculation with the approximation function [18][19][20] is only possible for the investigation of enantiomerization processes of racemic mixtures.…”