Simultaneous microbatch screening of enantiorecognition on solid chiral selectors using selected mixtures of test‐racemates: a case study on cellulose tris(α‐phenylpropionate) with configurational diversity

Abstract

An improved methodology for microbatch screening in the liquid-solid enantioselective adsorption of racemates by solid chiral selector is presented and illustrated by the evaluation of a series of six cellulose tris(alpha-phenylpropionate) presenting a configurational diversity and cellulose tris (4-methylbenzoate). Analyses were performed on 5 mg scale of chiral selector and 150 microL of supernatant containing a mixture of three test-racemates. Fifteen test-racemates were chosen according to their molecular diversity using a hierarchical clustering approach for seven selected three-dimensional molecular properties. The 15 racemates were sorted in five test mixtures composed of three racemates each according to the following constraints: each triplet of test-racemates can be analyzed without peak overlap on a commercially available chiral stationary phase (CSP). The designed five groups of three racemates may be used for the evaluation of other chiral selectors in view of the preparation of CSPs. This methodology improves the throughput of the evaluation and could be automated.

Enantiorecognition on solid chiral selectors using microbatch technology: an example of limitation in case of strong association in the racemate

“…The vessels were sonicated for 10 min and kept at 10°C for 2 h. Then, 20 µL of the supernatant were injected onto the Chiralcel OD-H to determine the enantiomeric excesses and the initial racemic solution was also injected. Comparison between the areas of the peaks in the two chromatograms, taking into account the internal standard, allowed the determination of the enantiomer adsorption on the chiral selector and the enantioselectivity (Roussel et al, 2001). In this first evaluation, the two enantiomers had significant adsorptions, around 25% on CS1, 15% on CS2, 45% on CS3 and 40% on CS4, and enantioselectivity could be determined.…”

“…In the last few years, we and others have developed microbatch methodologies to evaluate the application field of new chiral selectors or to select commercially available chiral stationary phases (CSPs) (Wolf et al, 1993;Nakano et al, 1998Nakano et al, , 2001Welch et al, 1999Welch et al, , 2001Welch et al, , 2002Roussel et al, 2000Roussel et al, , 2001Bluhm et al, 2000;Tobler et al, 2000;Wang et al, 2000;Xu et al, 2001). The so-called microbatch method for the evaluation of solid chiral selectors as potential CSP involves the enantioselective partition of a racemate between the solid chiral support and an achiral solvent.…”

“…We have already applied microbatch technology to evaluate some new polysaccharide CSPs developed in our group. We revised the microbatch method by adding an internal standard, a compound which is not adsorbed on the chiral selector and which allows a more accurate evaluation of the absolute enantioselective adsorptions (Roussel et al, 2001).…”

Optical Purifications via Self‐Disproportionation of Enantiomers by Achiral Chromatography: Case Study of a Series of α‐CF3‐containing Secondary Alcohols

“…5,8,[26][27][28][29][30][31][32][33][34][35] Similar to the phenomenon of nonlinear effects in asymmetric catalysis, 27,28 the origin of the SDE under the conditions of achiral chromatography is the dynamic formation of homo-or heterochiral high-order species which have different chromatographic behaviour as compared with monomers or other low-order species. 5,8,[26][27][28][29][30][31][32][33][34][35] Similar to the phenomenon of nonlinear effects in asymmetric catalysis, 27,28 the origin of the SDE under the conditions of achiral chromatography is the dynamic formation of homo-or heterochiral high-order species which have different chromatographic behaviour as compared with monomers or other low-order species.…”

Self-disproportionation of enantiomers (SDE) of chiral sulfur-containing compounds via achiral chromatography

“…It is worth mentioning that the results of experiments are supported by theoretical modelling of chromatographic behaviour of non-racemic compounds under various conditions of achiral chromatography. [43][44][45][46][47][48][49][50] The results of these experimental studies and theoretical calculations allow the formulation of the concept of the SDE-phoric groups as a structural element responsible for the occurrence of the SDE during achiral chromatography. [51][52][53][54][55][56][57][58][59][60][61] Considering the structure of the SDE-phoric moieties one can expect interesting properties for a chiral sulfinyl grouping or a chiral thioamide residue.…”