Enantiomerization of chiral 2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c][1,2,4]benzothiadiazine 5,5-dioxide by stopped-flow multidimensional HPLC☆

Cannazza, Giuseppe; Carrozzo, Marina M.; Braghiroli, Daniela; Parenti, Carlo

doi:10.1016/j.jchromb.2008.05.009

Cited by 19 publications

(24 citation statements)

References 32 publications

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“…Among different commercial available chiral stationary phases (CSP), cellulose 3,5‐dimethylphenylcarbamate (Chiracel OD‐RH) was chosen, because it was previously employed successfully for the enantioseparation of chiral benzothiadiazine‐type compounds 4, 29, 30, 32–34…”

Section: Resultsmentioning

confidence: 99%

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Determination of kinetic parameters of enantiomerization of benzothiadiazines by DCXplorer

et al. 2010

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Benzothiadiazines differently substituted at the sulfonamidic nitrogen atom, at the stereogenic carbon atom and at the anilinic nitrogen atom have been synthesized and fully characterized. Enantioseparation of these compounds has revealed rapid on-column enantiomerization. The recently developed software DCXplorer has been successfully applied to calculate enantiomerization kinetic parameters. Enantiomerization barriers of 3-phenyl substituted benzothiadiazines, calculated in this work, have indicated a higher enantiomerization rate suggesting that the aromatic substituent exerts a strong effect on the enantiomerization process. Methyl substitution on N(2) position led to higher free energy barriers of enantiomerization, suggesting negative influence of methyl in the N(2) position on enantiomerization kinetics. However, methylation on N(4) position increases the enantiomerization rates significantly. The results obtained have been employed to postulate an enantiomerization mechanism for chiral benzothiadiazine type compounds.

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Section: Resultsmentioning

confidence: 99%

“…As we have demonstrated that some chiral 3,4‐dihydro‐1,2,4‐benzothiadiazine 1,1‐dioxide type compounds undergo rapid enantiomerization during enantioseparation in reverse phase conditions,29, 30 DCXplorer has been applied to calculate enantiomerization rate constants of synthesized benzothiadiazines 1 – 12 here (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Determination of kinetic parameters of enantiomerization of benzothiadiazines by DCXplorer

et al. 2010

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“…This column is Samples were injected for 2 s, and separated using a constant current of 90 mA in 0.1 M phosphate buffer, pH 7.3. heated up to a predefined temperature for a defined time period, then cooled down, and the de novo enantiomeric ratio determined by separation on a third column. Recently, Cannazza et al [149] have applied this to HPLC (sfMDHPLC). By the sfCE, atropisomeric compounds 30 and 31 were separated and enantiomerized using permethylated b-cyclodextrin as chiral selector [142,143].…”

Section: Atropisomersmentioning

confidence: 99%

Investigation of the stereodynamics of molecules and catalyzed reactions by CE

Trapp

2010

Electrophoresis

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The investigation of the molecular dynamics of stereoisomers and the study of the kinetics of reactions, in particular of catalyzed reactions, is of fundamental interest in chemistry, biochemistry, and medicine. Understanding how to control the transition state of a reaction allows for a directed design of new catalysts and benign processes. The integration of reactions and capillary or microchip-based electrophoretic separations is highly attractive to perform on-column derivatizations or enzymatic on-column digests of peptides and proteins for further characterization. The present review article focuses on the recent advances to study the stereodynamics of molecules and reaction kinetics of catalyzed processes by means of CE. Models and algorithms to evaluate interconversion profiles obtained by electrophoretic separation techniques are discussed with respect to the challenging demands of high separation efficiencies typical for electrophoretic techniques. Models used for evaluation are based on iterative computer simulation algorithms using the theoretical plate model or stochastic model of chromatography, empirical calculation methods, derived from equations used in chemical engineering, namely Damköhler analysis, and direct access with the approximation function and more recently with the unified equation, which can be applied to all kinds of first-order reactions taking place during a chromatographic or a electrophoretic separation. Furthermore, areas of applications are presented and discussed to give a guideline for using dynamic CE and on-column reaction electrophoresis to study kinetics of reactions and dynamic processes.

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“…The interconversion barrier of the diaziridine units is typically greater than 80 kJ mol −1 ,25, 27, 28 which allows studying the stereodynamics by dynamic enantioselective chromatographic techniques 21, 29–41. Advantages are the necessity of only minute amounts of racemates, the possibility to simultaneously determine interconversion rate constants,42 and the superior precision to estimate activation parameters over broad temperature ranges.…”

Section: Introductionmentioning

confidence: 99%

Stereodynamics of tetramezine

Kamuf

Trapp

2010

Chirality

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The antidepressant drug tetramezine [1,2-bis-(3,3-dimethyldiaziridin-1-yl)ethane] consists of two bridged diaziridine moieties with four stereogenic nitrogen centers, which are stereolabile and, therefore, are prone to interconversion. The adjacent substituents at the nitrogen atoms of the diaziridines moieties exist only in an antiperiplanar conformation, which results in a coupled interconversion. Therefore, three stereoisomers exist (meso form and two enantiomeric forms), which epimerize when the diaziridine moieties are regarded as stereogenic units due to the coupled interconversion. Here, we have investigated the epimerization between the meso and enantiomeric forms by dynamic gas chromatography. Temperature-dependent measurements were performed, and reaction rate constants were determined using the unified equation of chromatography implemented in the software DCXplorer. The activation barriers of the epimerization were found to be ΔG(≠) = 100.7 kJ mol(-1) at 25°C and ΔG(≠) = 104.5 kJ mol(-1) at 37°C, respectively. The activation enthalpy and entropy were determined to be ΔH(≠) = 70.3 ± 0.4 kJ mol(-1) and ΔS(≠) = -102 ± 2 J mol(-1) K(-1) .

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Enantiomerization of chiral 2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c][1,2,4]benzothiadiazine 5,5-dioxide by stopped-flow multidimensional HPLC☆

Cited by 19 publications

References 32 publications

Determination of kinetic parameters of enantiomerization of benzothiadiazines by DCXplorer

Determination of kinetic parameters of enantiomerization of benzothiadiazines by DCXplorer

Investigation of the stereodynamics of molecules and catalyzed reactions by CE

Stereodynamics of tetramezine

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