Enantiomerization barrier of 1-[2-(2-methyl-2-methoxycarbonylacetamido) benzenesulfonyl]-1h-pyrrole studied by enantioselective dynamic HPLC, classical off column technique and computational approach

Many commonly used drugs are chiral compounds. As known, drugs’ enantiomers are certainly characterized by identical physicochemical properties, but can differ in their pharmacokinetics, pharmacodynamics and toxicity. In connection with this, interest in chiral analysis and evaluation of stereolability of biologically active compounds has grown significantly in recent years. In this work, the stereochemical analysis of the chiral heterocyclic compound 1-[2-(2-methyl-2-methoxycarbonylacetamido) benzenesulfonyl]-1h-pyrrole [1] was carried out through the aid of two different analytical approaches: 1) kinetic batchwise studies monitored by enantioselective HPLC (eHPLC) technique; 2) kinetic on-column studies monitored by Dynamic enantioselective High Performance Liquid Chromatography (D-eHPLC). The chromatographic analyses were carried out by the commercially available Chiralcel OJ column. The study also covered the effects arising from the modification of the mobile phase, with variations concerning kind and polarity of the employed solvents, as well as the transition from normal to reverse phase, in presence or not of organic modifiers, such as triethylamine (TEA) and trifluoroacetic acid (TFA). All the resulting dynamic chromatograms were analysed by means of the home-made computer program Auto-DHPLC-y2k. Analysis of the obtained experimental data made it possible to achieve kinetic and thermodynamic information relevant to the enantiomerization/racemization process of the heterocyclic compound under consideration. [2,3] Finally, as the conclusive step of the investigation, the possible mechanisms responsible for the observed enantioisomerizations have been inquired by computational study.