Enantiomeric Separation and Molecular Modelling of Bioactive 4-Aryl-3,4-dihydropyrimidin-2(1H)-one Ester Derivatives on Teicoplanin-Based Chiral Stationary Phase
| Autor: | Isabella Bolognino, Antonio Carrieri, Rosa Purgatorio, Marco Catto, Rocco Caliandro, Benedetta Carrozzini, Benny Danilo Belviso, Maria Majellaro, Eddy Sotelo, Saverio Cellamare, Cosimo Damiano Altomare |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Separations, Vol 9, Iss 7, p 7 (2022) Separations 9 (2022). doi:10.3390/separations9010007 info:cnr-pdr/source/autori:Bolognino, Isabella; Carrieri, Antonio; Purgatorio, Rosa; Catto, Marco; Caliandro, Rocco; Carrozzini, Benedetta; Belviso, Benny Danilo; Majellaro, Maria; Sotelo, Eddy; Cellamare, Saverio; Altomare, Cosimo Damiano/titolo:Enantiomeric Separation and Molecular Modelling of Bioactive 4-Aryl-3,4-dihydropyrimidin-2(1H)-one Ester Derivatives on Teicoplanin-Based Chiral Stationary Phase/doi:10.3390%2Fseparations9010007/rivista:Separations/anno:2022/pagina_da:/pagina_a:/intervallo_pagine:/volume:9 Separations; Volume 9; Issue 1; Pages: 7 |
| ISSN: | 2297-8739 |
| DOI: | 10.3390/separations9010007 |
| Popis: | The enantiomeric separation of 15 racemic 4-aryl-3,4-dihydropyrimidin-2(1H)-one (DHP) alkoxycarbonyl esters, some of which proved to be highly active as A2B adenosine receptor antagonists, was carried out by HPLC on ChirobioticTM TAG, a chiral stationary phase (CSP) bearing teicoplanin aglycone (TAG) as the chiral selector. The racemic compounds were separated under polar organic (PO) conditions. Preliminarily, the same selectands were investigated on three different Pirkle-type CSPs in normal-phase (NP) conditions. A baseline separation was successfully obtained on TAG-based CSPs for the majority of compounds, some of which achieved high enantioselectivity ratios (α > 2) in contrast with the smaller α values (1–1.5) and the lack of baseline resolution observed with the Pirkle-type CSPs. In particular, the racemic tetrazole-fused DHP ester derivatives, namely compounds 8 and 9, were separated on TAG-based HPLC columns with noteworthy α values (8.8 and 6.0, respectively), demonstrating the potential of the method for preparative purposes. A competition experiment, carried out with a racemic analyte (6) by adding N-acetyl-d-alanine (NADA) to the mobile phase, suggested that H-bonding interactions involved in the recognition of the natural dipeptide ligand d-Ala-d-Ala into the TAG cleft should be critical for enantioselective recognition of 4-aryl DHPs by TAG. The X-ray crystal structure of TAG was elucidated at a 0.77 Å resolution, whereas the calculation of molecular descriptors of size, polar, and H-bond interactions, were complemented with molecular docking and molecular dynamics calculations, shedding light on repulsive (steric effects) and attractive (H-bond—polar and apolar) interactions between 4-aryl DHP selectands and TAG chiral selectors. |
| Databáze: | OpenAIRE |
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