Enantiomeric Separation of New Chiral Azole Compounds

Abstract

Twelve new azole compounds were synthesized through an ene reaction involving methylidene heterocycles and phenylmaleimide, producing four oxazoles, five thiazoles, and one pyridine derivative, and ethyl glyoxylate for an oxazole and a thiazole compound. The twelve azoles have a stereogenic center in their structure. Hence, a method to separate the enantiomeric pairs, must be provided if any further study of chemical and pharmacological importance of these compounds is to be accomplished. Six chiral stationary phases were assayed: four were based on macrocyclic glycopeptide selectors and two on linear carbohydrates, i.e., derivatized maltodextrin and amylose. The enantiomers of the entire set of new chiral azole compounds were separated using three different mobile phase elution modes: normal phase, polar organic, and reversed phase. The most effective chiral stationary phase was the MaltoShell column, which was able to separate ten of the twelve compounds in one elution mode or another. Structural similarities in the newly synthesized oxazoles provided some insights into possible chiral recognition mechanisms.

Chiral Separation of Econazole by High Performance Liquid Chromatography Method using Cyclodextrin as Chiral Column

“…The quantification limit test results of the first and second enantiomeric peaks are 11.029 and 5.995 mg/L, respectively. This value is in accordance with research by Kenari et al, (2021) which separated the econazole enantiomer with a beta-cyclodextrin-based column with LOD values of 1.6 mg/L and LOQ 5.3 mg/L, respectively combined with ionic liquids based on L-glutamic acid and Llysine. The smaller the detection limit and the quantification limit, the better and more sensitive the method will be in detecting an analyte.…”

“…The developed method will save analytical time so that it will be more efficient compared to the previously available methods. The need for short analytical methods has always been a priority in the development of analytical methods because these methods will be used for routine analysis purposes with relatively big sample sizes of various pharmaceutical formulations (Kenari et al, 2021).…”

An overview of chiral separations of pharmaceutically active substances by HPLC (2018–2020)

“…Chiralpak IA column showed the best resolution and peak shapes along with a shorter retention time [ 68 ]. This column was the only one which was able to separate all new chiral azoles in another comparative study with several polysaccharide-based columns with various CSs [ 69 ]. The same column demonstrated good enantioselectivity in the analysis of seven process-related impurities of celecoxib as well as for enantiomers of sterubin, a potential neuroprotector extracted from Eriodictyon californicum plant [ 70 , 71 ].…”

Enantioselective Liquid Chromatographic Separations Using Macrocyclic Glycopeptide-Based Chiral Selectors

“…In the case of macrocyclic glycopeptide selectors, high enantiomeric selectivity was obtained for acidic pesticides using TeicoShell CSP, while the NicoShell and VancoShell CSPs were efficient in the chiral separation of pesticides with amine functionalities. Enantiomeric separation of twelve new chiral azole compounds was investigated with six different CSPs, four of them possessing macrocyclic glycopeptide selector (NicoShell, TagShell, TeicoShell, VancoShell, AZYP, LLC, Arlington, TX, USA) [ 82 ]. Regarding mobile phase composition, the application of RP mode resulted in better enantiomeric separations of azole compounds on macrocyclic glycopeptide CSPs than using NP or PO conditions.…”