Enantioseparations in Achiral Environments and Chromatographic Systems

Abstract

Since the very first resolution of racemic tartaric acid by Pasteur, the importance of resolution and methodology has been on a path of continuous understanding and expansion. The science and chemistry of achieving such targets has changed a lot. The advent of chromatography changed the direction by involving synthetic, semisynthetic, or naturally occurring chiral materials for a direct approach to resolution, where rapid and reversible association occurs to form diastereomers with different stabilities and partition coefficients responsible for overall enantioseparation. It has now reached a stage where the separation of excess enantiomers from nonracemic mixtures has been achieved in a totally achiral environment, which does not appear to be in line with the prevalent concepts of basic stereochemistry. Caution should be exercised when enantiomerically enriched mixtures – obtained by enantioselective synthesis – are chromatographed for purification in preparative organic synthesis.

Bioassay, determination and separation of enantiomers of atenolol by direct and indirect approaches using liquid chromatography: A review

“…These examples are by all means different than the literature on enantioseparation of nonracemic mixtures (that is basically enantiomeric enrichment), under achiral phases and the concept involved therein (Martens & Bhushan, ).…”

“…Photograph of an actual chromatogram showing resolution of (RS)-Atl; from left to right: Line 1, [(R):(S), 1:99], lower spot for (S)isomer and upper spot for (R)-isomer; line 2, S)-isomer. Mobile phase: CH 3 CN-CH 3 OH-CH 2 Cl 2 -H 2 O (6:3:3:1.5, v/v); solvent front, 8 cm; temperature: 25 ± 2°C; detection, iodine vapor; development time, 10 min enantiomeric enrichment), under achiral phases and the concept involved therein(Martens & Bhushan, 2016).…”

Recommended Tests for the Self-Disproportionation of Enantiomers (SDE) to Ensure Accurate Reporting of the Stereochemical Outcome of Enantioselective Reactions

“…While the SDE is unavoidable, its effect on the accuracy of the data reporting can be mitigated by simple SDE tests, which may reveal the SDE magnitude as a function of the physicochemical conditions, as well as the range of possible error for the data under the given conditions. We believe that overall knowledge of the nature and manifestation of the SDE phenomenon has come of age and the time is right for the introduction of mandatory SDE tests to be part of the supporting documentation and a cultured practice of research chemistry, as it is clearly necessary [ 45 , 46 , 47 ]. In this article, we provide a short overview of the SDE phenomenon, cite key examples of extraordinary cases, and suggest simple generic SDE tests via achiral chromatography and sublimation, to be performed as an integral part of the experimental work submitted for publication when the work concerns scalemic samples that arise from enantioselective reactions or as a result of natural products isolation.…”

Enantiospecific equilibrium adsorption and chemistry of d‐/l‐proline mixtures on chiral and achiral Cu surfaces

“…This necessitates the development of enantioselective chemical processes. In recent years, much research has focused on the adsorption and reaction of chiral molecules on chiral surfaces relevant to applications in the fields of heterogeneous catalysis, 3,4 chromatographic separation of enantiomers, [5][6][7] supramolecular self-assembled systems 8,9 and materials such as liquid crystals 10 and sensors. 11,12 Specifically, the interaction of natural amino acids (all but one of which are chiral) with surfaces has been studied in recent years because amino acids serve as model systems for understanding the interactions of large biomolecules, such as proteins, with surfaces.…”