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971.
The contamination of drug residues, including chiral ones, is not acceptable in earth's ecosystem. The dynamicity of enantiomers of thalidomide and its derivatives (3‐methyl thalidomide, 3‐ethyl thalidomide, and 3‐butyl thalidomide) was ascertained at supramolecular level in water‐sediment system using solid phase extraction (SPE) and stereoselective HPLC. Enantiomeric separation of these drugs was carried out on Ceramosphere RU‐2 (25 cm × 0.46 cm, particle size 50 μm) chiral column using pure ethanol (1.0 ml/min) as eluent at 230 nm detection. Retention times, capacity, separation, and resolution factors of the enantiomers of these drugs were in the range of 20.0–36.0, 2.08–3.93, 1.35–1.57, and 1.0–2.0 min, respectively. Percentage recoveries of the enantiomers in SPE were in the range of 90.0 to 95.0 in water‐sediment system. Langmuir and Freundlich model were best fitted for dynamic equilibrium concentrations at different experimental parameters. Thalidomide and its derivatives follow first‐order kinetics at dynamic equilibrium. The rate constants of chiral interconversions were 0.390 and 0.385 days?1 for S‐ and R‐enantiomers, respectively. The uptake of thalidomide by sediment is quite good and of endothermic nature indicating good self‐purification capacity of the nature for such toxic species. Chirality, 2010. © 2009 Wiley‐Liss, Inc. 相似文献
972.
G. Bettoni S. Ferorelli F. Loiodice N. Tangari V. Tortorella F. Gasparrini D. Misiti C. Villani 《Chirality》1992,4(3):193-203
Several α-monoalkyl-α-aryloxyacetic acids have been synthesized and resolved into their optical antipodes; their absolute configuration was also established by chiroptical and chemical methods. The two enantiomers of a series of these compounds show opposite effects on skeletal muscle fibers chloride conductance. Therefore a HPLC procedure was developed for the direct determination of the optical purity of the antipodes before submitting them to biological tests. The chromatographic study was performed on DACH-DNB chiral stationary phase which shows a remarkable enantioselectivity for the considered compounds as free acids, esters and amides under different conditions with essentially the same chiral mechanism of separation. © 1992 Wiley-Liss, Inc. 相似文献
973.
Stacy L. Gelhaus A. Clementina Mesaros Ian A. Blair 《Journal of visualized experiments : JoVE》2011,(57)
The metabolism of fatty acids, such as arachidonic acid (AA) and linoleic acid (LA), results in the formation of oxidized bioactive lipids, including numerous stereoisomers1,2. These metabolites can be formed from free or esterified fatty acids. Many of these oxidized metabolites have biological activity and have been implicated in various diseases including cardiovascular and neurodegenerative diseases, asthma, and cancer3-7. Oxidized bioactive lipids can be formed enzymatically or by reactive oxygen species (ROS). Enzymes that metabolize fatty acids include cyclooxygenase (COX), lipoxygenase (LO), and cytochromes P450 (CYPs)1,8. Enzymatic metabolism results in enantioselective formation whereas ROS oxidation results in the racemic formation of products.While this protocol focuses primarily on the analysis of AA- and some LA-derived bioactive metabolites; it could be easily applied to metabolites of other fatty acids. Bioactive lipids are extracted from cell lysate or media using liquid-liquid (l-l) extraction. At the beginning of the l-l extraction process, stable isotope internal standards are added to account for errors during sample preparation. Stable isotope dilution (SID) also accounts for any differences, such as ion suppression, that metabolites may experience during the mass spectrometry (MS) analysis9. After the extraction, derivatization with an electron capture (EC) reagent, pentafluorylbenzyl bromide (PFB) is employed to increase detection sensitivity10,11. Multiple reaction monitoring (MRM) is used to increase the selectivity of the MS analysis. Before MS analysis, lipids are separated using chiral normal phase high performance liquid chromatography (HPLC). The HPLC conditions are optimized to separate the enantiomers and various stereoisomers of the monitored lipids12. This specific LC-MS method monitors prostaglandins (PGs), isoprostanes (isoPs), hydroxyeicosatetraenoic acids (HETEs), hydroxyoctadecadienoic acids (HODEs), oxoeicosatetraenoic acids (oxoETEs) and oxooctadecadienoic acids (oxoODEs); however, the HPLC and MS parameters can be optimized to include any fatty acid metabolites13.Most of the currently available bioanalytical methods do not take into account the separate quantification of enantiomers. This is extremely important when trying to deduce whether or not the metabolites were formed enzymatically or by ROS. Additionally, the ratios of the enantiomers may provide evidence for a specific enzymatic pathway of formation. The use of SID allows for accurate quantification of metabolites and accounts for any sample loss during preparation as well as the differences experienced during ionization. Using the PFB electron capture reagent increases the sensitivity of detection by two orders of magnitude over conventional APCI methods. Overall, this method, SID-LC-EC-atmospheric pressure chemical ionization APCI-MRM/MS, is one of the most sensitive, selective, and accurate methods of quantification for bioactive lipids. 相似文献
974.
《Chirality》2017,29(6):247-256
The enantioresolution and determination of the enantiomeric purity of 32 new xanthone derivatives, synthesized in enantiomerically pure form, were investigated on (S ,S )‐Whelk‐O1 chiral stationary phase (CSP). Enantioselectivity and resolution (α and RS) with values ranging from 1.41–6.25 and from 1.29–17.20, respectively, were achieved. The elution was in polar organic mode with acetonitrile/methanol (50:50 v/v ) as mobile phase and, generally, the (R )‐enantiomer was the first to elute. The enantiomeric excess (ee ) for all synthesized xanthone derivatives was higher than 99%. All the enantiomeric pairs were enantioseparated, even those without an aromatic moiety linked to the stereogenic center. Computational studies for molecular docking were carried out to perform a qualitative analysis of the enantioresolution and to explore the chiral recognition mechanisms. The in silico results were consistent with the chromatographic parameters and elution orders. The interactions between the CSP and the xanthone derivatives involved in the chromatographic enantioseparation were elucidated. 相似文献
975.
A concise synthetic route to a novel class of conformationally rigid 3 ′,4 ′-cis-fused bicyclic nucleoside derivatives has been developed. The synthetic strategy and approach involves initial synthesis of a key [5,5]-bicyclic 6-aminofurofuran-2-one scaffold, employing an L-serine derived aminobutenolide as a strategically functionalized chiral template. Subsequent utilization of the carbonyl functionality of the above bicyclic lactone toward nucleobase incorporation, and linking of the resident amine functionality with appropriately protected amino acids completed the syntheses of the target bicyclic nucleoside-amino acid conjugates. Following the above route, and utilizing a combination of easily available nucleobases (4) and amino acids (4) as the two diversity elements, combinatorial synthesis of a 16-member demonstration library of the title amino acid-linked nucleosides has been accomplished. 相似文献
976.
Five optically active urea derivatives ( 1 ‐ 5 ) were used as NMR solvating agents for analysis of the optical purity of different 2‐arylpropanoic acids commonly used as nonsteroidal anti‐inflammatory drugs. These novel chiral solvating agents were more efficient at discriminating the respective enantiomers of targets than the chiral solvating agents known so far, without the need to add a base for achieving the signal splitting. The advantages and limits of the use of these novel chiral solvating agents were studied. 相似文献
977.
《Chirality》2017,29(10):579-588
An interesting mode of chromatography for preparation of pure enantiomers from pure samples is the method of stacked injection as a pseudocontinuous procedure. Maximum throughput and minimal production costs can be achieved by the use of total chiral column length in this mode of chromatography. To maximize sample loading, often touching bands of the two enantiomers is automatically achieved. Conventional equations show direct correlation between touching‐band loadability and the selectivity factor of two enantiomers. The important question for one who wants to obtain the highest throughput is “How to optimize different factors including selectivity, resolution, run time, and loading of the sample in order to save time without missing the touching‐band resolution?” To answer this question, tramadol and propranolol were separated on cellulose 3,5‐dimethyl phenyl carbamate, as two pure racemic mixtures with low and high solubilities in mobile phase, respectively. The mobile phase composition consisted of n‐hexane solvent with alcohol modifier and diethylamine as the additive. A response surface methodology based on central composite design was used to optimize separation factors against the main responses. According to the stacked injection properties, two processes were investigated for maximizing throughput: one with a poorly soluble and another with a highly soluble racemic mixture. For each case, different optimization possibilities were inspected. It was revealed that resolution is a crucial response for separations of this kind. Peak area and run time are two critical parameters in optimization of stacked injection for binary mixtures which have low solubility in the mobile phase. 相似文献
978.
Gaspar Diaz‐Muoz Izabel Luzia Miranda Sulen Karine Sartori Daniele Cristina de Rezende Marisa Alves Nogueira Diaz 《Chirality》2019,31(10):776-812
This review article describes the use of some of the most popular chiral auxiliaries in the asymmetric synthesis of biologically active compounds. Chiral auxiliaries derived from naturally occurring compounds, such as amino acids, carbohydrates, and terpenes, are considered essential tools for the construction of highly complex molecules. We highlight the auxiliaries of Evans, Corey, Yamada, Enders, Oppolzer, and Kunz, which led to remarkable progress in asymmetric synthesis in the last decades and continue to bring advances until the present day. 相似文献
979.
《Biocatalysis and Biotransformation》2013,31(1-4):313-320
Fluorine-containing β-diketones (la-d) were reduced by free bakers' yeast (FBY) and immobilized baker yeast (IMBY) in water, to give optically-active fluorinated β-hydroxyketones (2a-d). It was found that the reaction is highly regioselective, and that the stereochemistry of the reduction is controlled by the R substituent. 相似文献
980.
An algorithm is employed to retrieve the differential bond polarizabilities of the C‐C bonds from the Raman optical activity (ROA) spectrum of (?)α‐pinene. (?)α‐pinene possesses two asymmetric centers (carbon atoms) and a local mirror symmetry. These differential bond polarizabilities show the characteristics of the asymmetry around the asymmetric carbons with respect to the mirror reflection. This analysis is accompanied along with the ROA mode signatures and the calculated β(G ')2 and β(A)2which show the ROA coupling mechanisms involving the electric/magnetic dipoles and the electric dipole/quadrupole, respectively. Chirality 25:600–605, 2013. © 2013 Wiley Periodicals, Inc. 相似文献