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Abstract
In this study, we present results obtained on the enantioseparation of some cationic compounds of pharmaceutical relevance, namely tetrahydro-ß-carboline and 1,2,3,4-tetrahydroisoquinoline analogs. In high-performance liquid chromatography, chiral stationary phases (CSPs) based on strong cation exchanger were employed using mixtures of methanol and acetonitrile or tetrahydrofuran as mobile phase systems with organic salt additives.Through the variation of the applied chromatographic conditions, the focus has been placed on the study of retention and enantioselectivity characteristics as well as elution order. Retention behavior of the studied analytes could be described by the stoichiometric displacement model related to the counter-ion effect of ammonium salts as mobile phase additives. For the thermodynamic characterization parameters, such as changes in standard enthalpy Δ(ΔH°), entropy Δ(ΔS°), and free energy Δ(ΔG°), were calculated on the basis of van't Hoff plots derived from the ln α vs. 1/T curves. In all cases, enthalpy-driven enantioseparations were observed with a slight, but consistent dependence of the calculated thermodynamic parameters on the eluent composition. Elution sequences of the studied compounds were determined in all cases. They were found to be opposite on the enantiomeric stationary phases and they were not affected by either the temperature or the eluent composition.
Highlights
Numerous alkaloids, containing tetrahydroisoquinoline (THIQ)and tetrahydro-β-carboline (THβC) core including their individual enantiomers, have important pharmacological activity
The compounds employed in this study are analogs of tetrahydro-ß-carboline and 1,2,3,4-tetrahydroisoquinoline
The calculated pKa values of secondary amino groups of analytes 1–6 are 9.16, 9.29, 9.30, 8.89, 9.04, and 9.06, respectively. (Calculations were performed with the Marvin Sketch v. 17.28 software, ChemAxon Ltd., Budapest.) The calculated pKa values of the amino group in the pyrrole moiety for analyte 1–3 were above 16, i.e., no protonation can be expected under the applied conditions
Summary
Tetrahydro-β-carboline (THβC) core including their individual enantiomers, have important pharmacological activity. Liensinine (Nelumbo nucifera) [4], saframycine A (Myxococcus xanthus) [5], and other synthetic THIQ analogs such as Zalypsis® [6], have promising pharmaceutical activities toward HIV or cancer. THβC alkaloids, originated from both natural and synthetic sources, have been investigated intensively in drug research. Vincristine, vinblastine [7], and reserpine [8] are used in the therapies of cancer or hypertension. Callophycine A (Callophycus oppositifolius) [9] has cytotoxic, harmicine (Kopsia Griffithii) [10] exhibits antinociceptive, and (+)-7-bromotypargine (Ancorina sp.) shows antimalarial activity [11], whereas Tadalafil (Cialis®) was successfully applied in the treatment of erectile dysfunction [12]. In the course of the synthesis and stereochemical characterization of these compounds, enantioselective chromatographic protocols have to be integrated as well
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