- Cellulose type chiral stationary phase based on reduced graphene oxide@silica gel for the enantiomer separation of chiral compounds
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The graphene oxide (GO) was covalently coupled to the surfaces of silica gel (SiO2) microspheres by amide bond to get the graphene oxide@silica gel (GO@SiO2). Then, the GO@SiO2 was reduced with hydrazine to the reduced graphene oxide@silica gel (rGO@SiO2), and the cellulose derivatives were physically coated on the surfaces of rGO@SiO2 to prepare a chiral stationary phase (CSP) for high performance liquid chromatography. Under the optimum experimental conditions, eight benzene-enriched enantiomers were separated completely, and the resolution of trans-stilbene oxide perfectly reached 4.83. Compared with the blank column of non-bonded rGO, the separation performance is better on the new CSP, which is due to the existence of rGO to produce special retention interaction with analytes, such as π-π stacking, hydrophobic effect, π-π electron-donor–acceptor interaction, and hydrogen bonding. Therefore, the obtained CSP shows special selectivity for benzene-enriched enantiomers, improves separation selectivity and efficiency, and rGO plays a synergistic effect with cellulose derivatives on enantioseparation.
- Li, Yuanyuan,Li, Qiang,Zhu, Nan,Gao, Zhuxian,Ma, Yulong
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p. 996 - 1004
(2018/07/29)
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- A chiral enantioseparation generic strategy for anti-Alzheimer and antifungal drugs by short end injection capillary electrophoresis using an experimental design approach
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The present study describes a generic strategy using capillary electrophoretic (CE) method for chiral enantioseparation of anti-Alzheimer drugs, namely, donepezil (DON), rivastigmine (RIV), and antifungal drugs, namely, ketoconazole (KET), Itraconazole (ITR), fluconazole (FLU), and sertaconazole (SRT) in which these drugs have different basic and acidic properties. Several modified cyclodextrins (CDs) were applied for enantioseparation of racemates such as highly sulfated α, γ CDs, hydroxyl propyl-β-CD, and Sulfobutyl ether-β-CD. The starting screening conditions consist of 50-mM phosphate-triethanolamine buffer at pH?2.5, an applied voltage of 15?kV, and a temperature of 25°C. The CE strategy implemented in the separation starts by screening prior to the optimization stage in which an experimental design is applied. The design of experiment (DOE) was based on a full factorial design of the crucial two factors (pH and %CD) at three levels, to make a total of nine (32) experiments with high, intermediate, and low values for both factors. Evaluation of the proposed strategy pointed out that best resolution was obtained at pH?2.5 for five racemates using low percentages of HS-γ-CD, while SBE-β-CD was the most successful chiral selector offering acceptable resolution for all the six racemates, with the best separation at low pH values and at higher %CD within 10-min runtime. Regression study showed that the linear model shows a significant lack of fit for all chiral selectors, anticipating that higher orders of the factors are most likely to be present in the equation with possible interactions.
- Abdel-Megied, Ahmed M.,Hanafi, Rasha S.,Aboul-Enein, Hassan Y.
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p. 165 - 176
(2017/11/27)
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- Chiral separation of four stereoisomers of ketoconazole drugs using capillary electrophoresis
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This work aimed to develop a chiral separation method of ketoconazole enantiomers using electrokinetic chromatography. The separation was achieved using heptakis (2, 3, 6- tri-O-methyl)-β-cyclodextrin (TMβCD), a commonly used chiral selector (CS), as it is relatively inexpensive and has a low UV absorbance in addition to an anionic surfactant, sodium dodecyl sulfate (SDS). The influence of TMβCD concentration, phosphate buffer concentration, SDS concentration, buffer pH, and applied voltage were investigated. The optimum conditions for chiral separation of ketoconazole was achieved using 10mM phosphate buffer at pH2.5 containing 20mM TMβCD, 5mM SDS, and 1.0% (v/v) methanol with an applied voltage of 25 kV at 25 °C with a 5-s injection time (hydrodynamic injection). The four ketoconazole stereoisomers were successfully resolved for the first time within 17 min (total analysis time was 28 min including capillary conditioning). The migration time precision of this method was examined to give repeatability and reproducibility with RSDs ≤5.80% (n =3) and RSDs ≤8.88% (n =9), respectively.
- Ibrahim, Wan Aini Wan,Arsad, Siti Rosilah,Maarof, Hasmerya,Sanagi, Mohd Marsin,Aboul-Enein, Hassan Y.
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p. 223 - 227
(2015/03/18)
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- Stereoselective Syntheses of Both Enantiomers of Ketoconazole from (R)- and (S)-Epichlorohydrin
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Stereoselective syntheses of both enantiomers of ketoconazole (1) from commercially available (R)- or (S)-epichlorohydrin has been developed.The key-step of syntheses involves the selective substitution of the methylene chlorine atom by benzoate on a mixture of (2S,4R)-14a and (2R,4R)-15a or of their enentiomers, followed by crystalization of the corresponding cis-benzoates, (2R,4R)-18 or (2S,4S)-18, from which (+)- or (-)-1 were obtained as described for (+/-)-1.The ee's of (+)- and (-)-ketocanazole were determined by HPLC on the CSP Chiracel OD-H.
- Camps, Pelayo,Farres, Xavier,Garcia, Luisa,Ginesta, Joan,Pascual, Jaume,et al.
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p. 1283 - 1294
(2007/10/03)
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- Stereoisomers of ketoconazole: Preparation and biological activity
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The four stereoisomers of the antifungal agent ketoconazole (1) were prepared and evaluated for their selectivity in inhibiting a number of cytochrome P-450 enzymes. Large differences in selectivity among the isomers were observed for inhibition of the cytochromes P-450 involved in steroid biosynthesis, whereas little differences was observed for inhibition of those associated with hepatic drug metabolism. The cis-(2S,4R) isomer 2 was the most effective against rat lanosterol 14α-demethylase, (2S,4R)-2 > (2R,4S)-4 >> (2R,4R)-3 = (2S,4S)-5, and progesterone 17α,20-lyase, (2S,4R)-2 >> (2S,4S)-5 > (2R,4R)-3 = (2R,4S)-4, whereas the cis-(2R,4S) isomer 4 was more effective against cholesterol 7α-hydroxylase, (2R,4S)-4 > (2S,4S)-5 > (2R,4R)-3 > (2S,4R)-2, and the trans-(2S,4S) isomer 5 was the most effective against aromatase, (2S,4R)-5 >> (2R,4R)-3 = (2R,4S)-4 > (2S,4R)-2. The cis- (2S,4R) and trans-(2R,4R) isomers 2 and 3 are equipotent in inhibiting corticoid 11β-hydroxylase and much more effective than their antipodes. Little selectivity was observed for inhibition of cholesterol side chain cleavage or xenobiotic hydroxylases. These data indicate that the affinity of azoles for cytochrome P-450 enzymes involved in steroid synthesis is highly dependent on the stereochemistry of the entire molecule, whereas binding to drug metabolizing enzymes is a less selective process.
- Rotstein,Kertesz,Walker,Swinney
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p. 2818 - 2825
(2007/10/02)
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