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Direct Enantiomeric Resolution of Seventeen Racemic 1,4-Dihydropyridine-Based Hexahydroquinoline Derivatives by HPLC

1,4-Dihydropyridine (DHP) scaffold holds an outstanding position with its versatile pharmacological properties among all heterocyclic compounds. Although most of the commercially available DHPs are marketed as a racemic mixture, the chiral center at C-4 can lead to even opposite pharmacological acti...

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Autores principales: Sun, Jiayi, Gözde Gündüz, Miyase, Zhang, Junyuan, Yu, Jia, Guo, Xingjie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566779/
https://www.ncbi.nlm.nih.gov/pubmed/31121823
http://dx.doi.org/10.3390/ijms20102513
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author Sun, Jiayi
Gözde Gündüz, Miyase
Zhang, Junyuan
Yu, Jia
Guo, Xingjie
author_facet Sun, Jiayi
Gözde Gündüz, Miyase
Zhang, Junyuan
Yu, Jia
Guo, Xingjie
author_sort Sun, Jiayi
collection PubMed
description 1,4-Dihydropyridine (DHP) scaffold holds an outstanding position with its versatile pharmacological properties among all heterocyclic compounds. Although most of the commercially available DHPs are marketed as a racemic mixture, the chiral center at C-4 can lead to even opposite pharmacological activities between the enantiomers. In the present study, enantioseparation of seventeen DHP structural analogues, consisting of either pharmacologically active or newly synthesized derivatives, (M2-4, MD5, HM2, HM10, CE5, N11, N10, N7, M11, MC6-8, MC13, MD23, and 42IIP) by high-performance liquid chromatography was investigated using immobilized polysaccharide-based chiral stationary phase, Chiralpak IC column. Due to the solvent versatility of the covalently immobilized chiral stationary phase in enantiomer separation, multiple elution modes including standard normal phase, nonstandard mobile phase, and reversed phase were used to expand the possibility to find the optimum enantioselective conditions for the tested analytes. Under appropriate separation conditions, complete enantiomeric separation was obtained for nearly all compounds except MC6-8 and MC13 which contained two chiral centers. Additionally, the effects of the polar modifier, the additive, and column temperature on the chiral recognition were evaluated. The thermodynamic parameters calculated according to the linear van’t Hoff equation indicated that the chiral separations in this study were enthalpy-driven or entropy-driven. Some parameters of method validation such as linearity, limit of quantitation, and repeatability were also measured for all studied compounds to prove the reliability of the method.
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spelling pubmed-65667792019-06-17 Direct Enantiomeric Resolution of Seventeen Racemic 1,4-Dihydropyridine-Based Hexahydroquinoline Derivatives by HPLC Sun, Jiayi Gözde Gündüz, Miyase Zhang, Junyuan Yu, Jia Guo, Xingjie Int J Mol Sci Article 1,4-Dihydropyridine (DHP) scaffold holds an outstanding position with its versatile pharmacological properties among all heterocyclic compounds. Although most of the commercially available DHPs are marketed as a racemic mixture, the chiral center at C-4 can lead to even opposite pharmacological activities between the enantiomers. In the present study, enantioseparation of seventeen DHP structural analogues, consisting of either pharmacologically active or newly synthesized derivatives, (M2-4, MD5, HM2, HM10, CE5, N11, N10, N7, M11, MC6-8, MC13, MD23, and 42IIP) by high-performance liquid chromatography was investigated using immobilized polysaccharide-based chiral stationary phase, Chiralpak IC column. Due to the solvent versatility of the covalently immobilized chiral stationary phase in enantiomer separation, multiple elution modes including standard normal phase, nonstandard mobile phase, and reversed phase were used to expand the possibility to find the optimum enantioselective conditions for the tested analytes. Under appropriate separation conditions, complete enantiomeric separation was obtained for nearly all compounds except MC6-8 and MC13 which contained two chiral centers. Additionally, the effects of the polar modifier, the additive, and column temperature on the chiral recognition were evaluated. The thermodynamic parameters calculated according to the linear van’t Hoff equation indicated that the chiral separations in this study were enthalpy-driven or entropy-driven. Some parameters of method validation such as linearity, limit of quantitation, and repeatability were also measured for all studied compounds to prove the reliability of the method. MDPI 2019-05-22 /pmc/articles/PMC6566779/ /pubmed/31121823 http://dx.doi.org/10.3390/ijms20102513 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sun, Jiayi
Gözde Gündüz, Miyase
Zhang, Junyuan
Yu, Jia
Guo, Xingjie
Direct Enantiomeric Resolution of Seventeen Racemic 1,4-Dihydropyridine-Based Hexahydroquinoline Derivatives by HPLC
title Direct Enantiomeric Resolution of Seventeen Racemic 1,4-Dihydropyridine-Based Hexahydroquinoline Derivatives by HPLC
title_full Direct Enantiomeric Resolution of Seventeen Racemic 1,4-Dihydropyridine-Based Hexahydroquinoline Derivatives by HPLC
title_fullStr Direct Enantiomeric Resolution of Seventeen Racemic 1,4-Dihydropyridine-Based Hexahydroquinoline Derivatives by HPLC
title_full_unstemmed Direct Enantiomeric Resolution of Seventeen Racemic 1,4-Dihydropyridine-Based Hexahydroquinoline Derivatives by HPLC
title_short Direct Enantiomeric Resolution of Seventeen Racemic 1,4-Dihydropyridine-Based Hexahydroquinoline Derivatives by HPLC
title_sort direct enantiomeric resolution of seventeen racemic 1,4-dihydropyridine-based hexahydroquinoline derivatives by hplc
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566779/
https://www.ncbi.nlm.nih.gov/pubmed/31121823
http://dx.doi.org/10.3390/ijms20102513
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