Enantiomeric separation of thiourea derivatives of naringenin on amylose and cellulose polymeric chromatographic chiral columns.

Due to a great demand for amylose and cellulose polymeric chromatographic chiral columns, the enantiomeric separation of thiourea derivatives of naringenin was achieved on the different amylose (Chiralpak-IB) and cellulose chiral (Chiralcel-OJ and Chiralcel-OD-3R) columns with varied chromatographic conditions. The isocratic mobile phases used were ethanol and methanol, where ethanol/hexane and methanol/hexane were used as gradient mode and were prepared in volume/volume relation. The separation and resolution factors for all the enantiomers were in the range of 1.25 to 3.47 and 0.48 to 1.75, respectively. The enantiomeric resolution was obtained within 12 min making fast separation. The docking studies confirmed the chiral recognition mechanisms with binding affinities in the range of -4.7 to -5.7 kcal/mol. The reported compounds have good anticoagulant activities and may be used as anticoagulants in the future. Besides, chiral separation is fast and is useful for enantiomeric separation in any laboratory in the world.

Enantioseparation and antioxidant activity of novel diarylpyrazoline derivatives.

Three chiral pyrazoline derivatives were synthesized by a flavanone ring-opening reaction followed by cyclocondensation with hydrazine hydrate to give better yields. Their enantiomeric resolution was achieved using polysaccharide chiral stationary phase columns consisting of cellulose (Chiralcel®OD-RH, Chiralcel®OZ-3) and amylose (Chiralpak®IA) by high-performance liquid chromatography. The separation was affected by the nature and concentration of the alcohol modifiers in the mobile phase. Taking 5-methoxy-2-(3-phenyl-4,5-dihydro-1H-pyrazol-5-yl)phenol (3a) as an example, the best separation was obtained by using the Chiralpak®IA column, with a separation factor α = 1.24 and Rs = 5.66 within an analysis time of <30 min. The diarylpyrazolines showed good antioxidant activity, studied by the DPPH method.

Synthesis and chiral separation of atropisomers of 4,5-Di methyl ∆4 N-phenyl N-aryl imidazoline-2-thione derivatives.

Synthesis of three chiral 4,5-Di methyl ∆4 N-phenyl N-aryl imidazole-2-thione derivatives was obtained by the condensation reaction of thiourea derivatives with α-hydroxy ketone. The structure of these compounds has been characterized by using spectroscopic methods (UV, IR, 1 H NMR, and 13 C NMR). The 4,5-Di methyl ∆4 N-phenyl N-aryl imidazole-2-thiones display a chiral axis around the N-C bond linking between the nitrogen of the heterocyclic framework and the carbon of the aryl group. Screening on chiral analysis of the atropisomers of these derivatives was performed by high-performance liquid chromatography method on seven chiral selectors based on polysaccharides consisting of amylose and cellulose, namely, Chiralpak®AD, Chiralcel® OD, Chiralcel® OD-H, Chiralcel® OJ, Chiralcel® OD-3R, Chiralcel® OZ-3, and Chiralpak® AS-3R. The impact of ortho-substituent in the resolution of 4,5-Di methyl ∆4 N-phenyl N-aryl imidazole-2-thione derivatives was also studied in this work.

Synthesis, enantioseparation, and absolute configuration assignment of iminoflavans by chiral high-performance liquid chromatography combined with online chiroptical detection.

Four racemic iminoflavan derivatives were synthesized by simple condensation at C-4 position of flavanone. All new compounds were characterized by using ultraviolet-visible, infrared, and nuclear magnetic resonance spectroscopic techniques. A chiral chromatographic analysis of racemic mixtures was performed by direct chiral high-performance liquid chromatography using Chiralcel® OD-H as chiral stationary phase, and online-coupled with electronic circular dichroism detector. The correlation of experimental electronic circular dichroism traces with quantum chemical electronic circular dichroism calculations run with time-dependent density functional theory made it possible to elucidate the absolute configuration for each enantiomer, and to establish the elution order.

Development of stability indicating HPLC method for the separation and validation of enantiomers of miconazole.

A selective and sensitive stability indicting HPLC method was developed for the analysis of enantiomers of miconazole. For this purpose, six different polysaccharide-based chiral columns were evaluated. Optimization was performed using several polar organic and alcohol-hydrocarbon mobile phases. As a result of optimization studies, the analysis was carried out using Lux Cellulose-3, methanol as a mobile phase at a flow rate of 1 mL·min-1 , and the detection wavelength was arranged to 230 nm. Developed method has been fully validated according to International Council on Harmonization guidelines. Method was found linear in the concentration range of 1 to 200 µg·mL-1 . Coefficient of determination (R2 ) was calculated as 0.9996, intraday precision of the method was found with the RSD% of 0.56, and the recovery of the method was calculated close to 100%. Furthermore, some other validation parameters like specificity, selectivity, LOD, and LOQ were also investigated. Stability indicating capability of this method was shown by forced degradation studies, and the run time for each analysis was less than 6 minutes. As a result, simple, fast, reliable HPLC method was developed for the separation and determination of the enantiomers of miconazole. Applicability of the developed method was shown with the application of marketed pharmaceutical preparations.

Chiral separation of novel iminonaringenin derivatives.

A series of 4-iminonaringenin derivatives 2-6 have been prepared in good overall yields from a condensation reaction between naringenin and primary amines. The structures of all products were confirmed by ultraviolet, infrared, proton nuclear magnetic resonance, and carbon-13 nuclear magnetic resonance spectroscopic techniques. These derivatives were analyzed by high-performance liquid chromatography using polysaccharide-based chiral stationary phases, namely, Chiralpak IB and Chiralcel OD, using various mobile phases. 2-Propanol showed a high enantioselectivity for naringin and its derivatives using achiral column containing immobilized polysaccharides (Chiralpak IB).

Screening Approach for Chiral Separation of ß-Aminoketones by HPLC on Various Polysaccharide-Based Chiral Stationary Phases.

Nine ß-aminoketones were synthesized via Mannich reaction when benzaldehyde was condensed with some primary amines and acetophenone. The purified compounds were identified by using spectroscopic methods. The enantiomeric separation of these derivatives was carried out by high-performance liquid chromatography (HPLC) using several coated and immobilized polysaccharide stationary phases, namely, Chiralcel(®) OD-H, Chiralcel(®) OD, Chiralcel(®) OJ, Chiralpak(®) AD, Chiralpak(®) IA, and Chiralpak(®) IB using different mobile phases composed of n-hexane and alcohol mixed in various ratios or pure ethanol or isopropanol. The retention behavior and selectivity of these chiral stationary phases were examined in isocratic normal phase mode. The results indicate that cellulose derivatives have higher enantioselectivity than amylose derivatives for the separation of racemic ß-amino ketones.

A comparison of chiral resolution of antifungal agents on different polysaccharide chiral columns under various mobile phase modes: Application in the biological samples.

The current article describes the chiral separation of tioconazole, miconazole, isoconazole, sertaconazole and terconazole, with Lux i-Cellulose 5 and Lux i-Amylose-1 chiral columns under organic polar, normal and reversed mobile phases modes. The mobile phase flow rate was 1 mL/min with 230 nm detection at 25 ± 1 °C temperature. The polar organic mobile phases offered certain advantages for separation such as short analysis time, order of elution, high plate numbers and favorable signal to noise ratio. The values of k, α and Rs were ranged from 0.6 to 7.87, 1.10 to 1.62 and 0.37 to 5.72 in polar organic, 0.15 to 43.86, 1.02 to 2.01 and 0.36 to 8.03 in normal, and 0.34 to 15.99, 1.03 to 1.40 and 0.59 to 4.18 in reversed phases modes, respectively. The reported methods were applied in urine samples and the results were satisfactory. The reported methods were applied to the analysis of urine samples.

Synthesis and Chiral Separation of Some 4-thioflavones.

A thionation reaction was performed on some chiral flavanones using Lawesson's reagent (LR) and leads to the formation of new chiral thiocarbonyl flavanes. LR in this thionation reaction with Hesperetin and Naringenin gives new flavan-4-thiones with yields ranged between 41 and 52%. Based on the Wittig reaction principle, LR is currently the most widely used reagent for this type of reaction. Enantiomeric separation by high-performance liquid chromatography methods was then set-up using three different polysaccharide-based chiral stationary phases (CSPs). Chiral separations were successfully accomplished with high resolution (1.22 ≤ Rs ≤ 5.23). The chiral discrimination mechanism(s) between the analytes under study, mobile phase, and the CSPs were discussed.

Pharmacological studies on aqueous extract of Launaea arborescens from southwest Algeria.

ETHNOPHARMACOLOGICAL RELEVANCE: Launaea arborescens, its vernacular name is Mol-albina belonging to asteracaea family origin of the southwest of Algeria. This plant is used in folk medicines to treat gastroenteritis, diabetes, child aliment and other diseases; it is taken macerated or boiled. AIM: This study aims to evaluate the anti-inflammation an analgesic activity of the aqueous extract of Launaea arborescens (AqELA) and its pathway of action. METHODS: the investigation of anti-inflammatory and analgesic effects were done using formalin test, acetic acid test. For mechanism investigation, it was used hot plate test to induce opioid receptors, a histamine and serotonin test to induce edema paw, finally, for the TRPV1 receptor, it was used the capsaicin test. RESULTS: The aqueous extract of Launaea arborescens showed a significant inhibition of abdominal writhing test 95% and 100% inhibition of licking paw using acid acetic test and formalin test respectively (EC: 47 mg/kg and 104 mg/kg). The analgesic effect of the aqueous extract of Launaea arborescens showed inhibition of sensation of pain after 120 min compared to morphine effect. The aqueous extract of Launaea arborescens reduced paw volume after 180 min and 120 min for histamine and serotonin respectively with dose-dependent. Concerning of TRPV1 receptors, the inhibition was showed at doses 100 mg and 300 mg. CONCLUSION: Our results contribute towards validation of the traditional use of Launaea arborescens for inflammation ailment.

Liquid Chromatographic Enantioseparation of Some Fluoroquinoline Drugs Using Several Polysaccharide-Based Chiral Stationary Phases.

The enantioseparation of three fluoroquinoline antibacterial drugs, namely, flumequine, ofloxacin and lomefloxacin using high-performance liquid chromatography was optimized on seven polysaccharide-derived chiral stationary phases, namely, Chiralpak® IB, chiralpak® IA, Chiralpak® AD, Chiralcel® OJ, Chiralcel® OD, Chiralcel® OD-H and Chiralcel® OZ-3 and applying different mobile phases in isocratic mode is described. The role of addition of organic additives was also investigated. A baseline separation of flumequine, ofloxacin and lomefloxacin enantiomers was achieved. Parameters influencing enantioseparation including mobile phase, organic additive and chemical nature of the chiral selector found to be highly influencing on the enantiomeric separation were investigated. Chiral recognition mechanism(s) are also presented.

Liquid Chromatographic Chiral Separation of Acenocoumarol and Its Hemiketal Form.

Acenocoumarol, an anticoagulant drug, was separated successfully using polysaccharide-based chiral stationary phases columns namely Cellulose Chiralpak® IB and Chiralcel® OD, using various normal mobile phases by high-performance liquid chromatography. However, the appearance of four well separated peaks confirmed the presence of the hemiketal form of 4-hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]-2H-chromen-2-one.

Liquid Chromatographic Separation of Novel 4-Amino-Flavanes Series Diastereomers on a Polysaccharide-Type Chiral Stationary Phase.

Two broad approaches for the syntheses of a series of 4-aminoflavanes are used in this study, and they have been prepared in 30-99% overall yields using the reductive condensation of flavanone with primary amine, as a key step. By this methodology, the formyl derivatives of several secondary amines were obtained in good to excellent yields. The structures of all new products have been confirmed by spectral experiences (IR, 1H NMR and 13C NMR). However, the present non-stereoselective synthesis results in a mixture of 2-7: diastereomers, which differ from the configuration of the flavanone atom asymmetric center. Since each diastereomer may have different biological activity and pharmacokinetic profile, analytical methods have to be developed for their separation. The 4-aminoflavanes diastereomers were separated using polysaccharide chiral stationary phases columns consisting of cellulose (Chiralcel® OD-H and Chiralcel®OJ) by high-performance liquid chromatography; the separation was affected by the nature and concentration of the alcohol modifiers in the mobile phase. Separations were carried out under normal phase mode on the Chiralcel®OJ column. This method can properly separate the two diastereoisomers (Rs > 2) within an analysis time of <50 min.

New flavonoids from bioactive extract of Algerian medicinal plant Launeae arborescens.

OBJECTIVE: To investigate the butanol fraction of the water/acetone extract and isolate of the new flavonoids from Launeae arboescens. METHODS: The compounds were isolated by liquid chromatographic methods and their structures were identified by using spectroscopic analysis. RESULTS: THE ISOLATED COMPOUNDS WERE IDENTIFIED AS: 7-O-[α-rhamnopyranosyl 4',5,6-Trihydroxy flavone 1,4',5'-Di-Methoxy 7-(5″-Me Hexan)1-oyl flavanone 2, 3″-isopropyl pyrano [1″:7,4″:6] 3',4',5',5-Tetrahydroxy flavanone 3,5,4',5'-Tri-Hydroxy 7-(3″-Me butan) -yl flavanone 4, 5,7-Dihydroxy-2',4',5' -trimethoxy-isoflavanone 5,5,6,7,4'-tetrahydroxy flavonol 6,7-O-[α-rhamnopyranosyl-(1->6)-ß-glucopyranosyl]- 4',5,7-tri-hydroxy-flavanone 7,7-O-[α-rhamnopyranosyl-(1->6)-ß-glucopyranosyl] 3',5-Dihydroxy 4'-Methoxy flavanone 8. CONCLUSIONS: The presence of different types of bioactive flavonoids in Launeae arboescens extract can explain the large ethnopharmacological uses and the potential activity of this medicinal plant.

Chiral separation of hesperidin and naringin and its analysis in a butanol extract of Launeae arborescens.

Two flavanone glycosides were isolated from the aerial part of Launeae arborescens (Asteraceae), which were identified as hesperidin and naringin. They are the most abundant flavonoids in the edible parts of many species of citrus fruits. In this study, we were interested in the chiral separation and determination of the diastereomerisation barriers of hesperidin and naringin by HPLC methods. The chiral separation HPLC screening of diastereomers of hesperidin and naringin by HPLC methods was accomplished in the normal-phase mode using 11 chiral stationary phases and various n-hexane/alcohol mobile phases. The rate constants and activation energy of diastereomerisation (DeltaG#) of flavanones, naringin and hesperidin were determined, respectively, on Chiralpak IC and Chiralpak IA. The analysis of flavanones isolated in butanol extracts of Launeae arborescens were confirmed by HPLC on Chiralpak IC.