Supercritical fluid chromatographic chiral separation of potential P2RX7 antagonists containing one, two and three chiral centers - Archive ouverte HAL
Journal Articles Journal of Chromatography Open Year : 2024

Supercritical fluid chromatographic chiral separation of potential P2RX7 antagonists containing one, two and three chiral centers

Abstract

Chiral compounds with multiple chiral centers Small-scale preparative separation A B S T R A C T

Eleven polysaccharide-based chiral stationary phases were screened to separate stereoisomers of six lactam derivatives by supercritical fluid chromatography (SFC). Those molecules are antagonists of the P2×7 receptor with potential anti-inflammatory activity. They present a mixture of either two enantiomers, or four or eight stereoisomers depending on the number of chiral centers in their structure. The effect of chiral stationary phase, either amylose-or cellulose-based, coated or immobilized, chlorinated or non-chlorinated, on retention and selectivity of those compounds was studied. The effect of the co-solvent nature (methanol, ethanol, propan-2-ol and acetonitrile) and percentage (15 to 40 %), temperature (20 to 45 • C) and backpressure (8 to 20 MPa) on the enantioseparation and retention of 1-(2-chlorobenzyl)-5-((4-methoxyphenyl)amino)pyrrolidin-2-one (compound 4) was thoroughly studied. Thus, optimal conditions were defined for each derivative in order to implement the preparative separation of the whole series, except of 1-((3,4-dimethoxyphenyl)(phenyl)methyl)-5-oxo-N-(1phenylethyl)pyrrolidine-2-carboxamide) (compound 6) for which none of the eleven columns could resolve the eight stereoisomers. The small-scale preparative separation of the enantiomers of the most promising derivative, i.e. 3-acetyl-1-(4-chlorophenyl)-N-(2,4-dichlorobenzyl)-5-oxopyrrolidine-2-carboxamide (compound 2), is presented.

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hal-04723076 , version 1 (06-10-2024)

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Naomi Knavs, Andreea Zubaş, Georgiana Apostol, Christophe Furman, Adrian Sorin Nica, et al.. Supercritical fluid chromatographic chiral separation of potential P2RX7 antagonists containing one, two and three chiral centers. Journal of Chromatography Open, 2024, 5, pp.100129. ⟨10.1016/j.jcoa.2024.100129⟩. ⟨hal-04723076⟩
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