Chiral compounds analysis

A large amount of fuel and environmentally based analysis is focused on the determination of aliphatic and aromatic content. These types of species are often notoriously difficult to deconvolute by mass spectrometric means, and resolution at the isomeric level is almost only possible by using chromatographic methods. Similarly, the areas of organohalogen and flavours/fragrance analysis are dominated by a need to often quantify chiral compounds, which in the same way as aliphatic... 

Derivatization of a racemic compound with an achiral group may play an important role in the analysis of a chiral compound (Fig. 7-15). In the case of substances with low or no UV-activity, the compounds can be rendered detectable by introducing an UV-absorbing or fluorescent group. If the racemate itself shows selectivity on a chiral stationary phase (CSP), this method can be applied to reduce the limit of detection. Examples have been reported in the literature, especially for the derivatization of amino acids which are difficult to detect using UV detection. Different derivatization strategies can be applied (Fig. 7-16). 

Method development remains the most challenging aspect of chiral chromatographic analysis, and the need for rapid method development is particularly acute in the pharmaceutical industry. To complicate matters, even structurally similar compounds may not be resolved under the same chromatographic conditions, or even on the same CSP. Rapid column equilibration in SFC speeds the column screening process, and automated systems accommodating multiple CSPs and modifiers now permit unattended method optimization in SFC [36]. Because more compounds are likely to be resolved with a single set of parameters in SFC than in LC, the analyst stands a greater chance of success on the first try in SFC [37]. The increased resolution obtained in SFC may also reduce the number of columns that must be evaluated to achieve the desired separation. 

The development of a single enantiomer as a new active substance should be described in the same manner as for any other new chemical entity. Studies should be carried out with the single enantiomer, but if development began with the race-mate then these studies may also be taken into account. Chiral conversion should be considered early on so that enantiospecific bioanalytical methods may be developed. These methods should be described in chemistry and pharmacy part of the dossier. If the opposite enantiomer is formed in vivo, then it should be evaluated in the same way as other metabolites. For endogenous human chiral compounds, enantiospecific analysis may not be necessary. The enantiomeric purity of the active ingredient used in preclinical and clinical studies should be stated. 

The catalyst testing was carried out in a gas phase downflow stainless steel tubular reactor with on-line gas analysis using a Model 5890 Hewlett-Packard gas chromatograph (GC) equipped with heated in-line automated Valeo sampling valves and a CP-sD 5 or CP-sil 13 capillary WCOT colunm. GC/MS analyses of condensable products, especially with respect to O-isotopic distribution, was also carried out using a CP-sil 13 capillary column. For analysis of chiral compounds, a Chirasil-CD capillary fused silica column was employed. 

From the hair-pencils of butterflies in Danainae and Ithomiinae (Papilion-oidea Nymphalidae), a wider variety of pyrrolizines (la-d, and 6a-d) have been identified than from Arctiidae moths. These compounds are biosynthesized from pyrrolizidine alkaloids, which are included in host plants fed by the larvae and protect them from the attacks of other herbivores [122]. In addition to novel lactones (7, 8a, and 8b) derived from an acid part of the alkaloids, many volatiles of more than 100 compounds (aromatics, terpenoids, hydrocarbons, and others) constitute scent bouquets of the male butterflies [123]. For example, the hair-pencil of Idea leuconoe (Danainae) which is distributed in South-East Asia contained 16 compounds (6b, 8a, 8b, 9, and others), and a mixture of the major volatiles applied to a butterfly dummy elicited an abdomen-curling acceptance posture in the females as a crude extract of the male hair-pencils did [ 124]. A chiral GC analysis revealed the absolute config-... 

As also shown in Scheme 4, when rac-20, prepared from simple alkylation of the corresponding allylic alcohol with allylbromide, is treated with 2 mol% la and the reaction mixture is then treated with 10 mol% (R)-3b and five equivalents of EtMgCI at 70°C, (S)-21 and (3S,4k)-22 are obtained in >99% ee and 41% and 47% yield after silica gel chromatography,respectively (chiral GLC analysis) [5b]. Thus, from simple starting materials and in a single vessel, compounds of excellent optical purity can be obtained efficiently (88% yield). As before, the racemic dihydrofuran intermediate need not be isolated. 

CE has been applied extensively for the separation of chiral compounds in chemical and pharmaceutical analysis.First chiral separations were reported by Gozel et al. who separated the enantiomers of some dansylated amino acids by using diastereomeric complex formation with Cu " -aspartame. Later, Tran et al. demonstrated that such a separation was also possible by derivatization of amino acids with L-Marfey s reagent. Nishi et al. were able to separate some chiral pharmaceutical compounds by using bile salts as chiral selectors and as micellar surfactants. However, it was not until Fanali first showed the utilization of cyclodextrins as chiral selectors that a boom in the number of applications was noted. Cyclodextrins are added to the buffer electrolyte and a chiral recognition may... 

Our previous work showed that alachlor, a compound that is structurally similar to metolachlor, could be separated from its acidic metabolites using a C-18 SPE cartridge (12). However, this procedure does not allow the separation of the OXA and the ESA. Thus, different adsorption mechanisms and solvent systems will be explored to separate the analytes into three fractions metolachlor, OXA, and ESA. This procedure is depicted in Figure 4 [not included in excerpt]. The SPE procedure will be necessary to avoid overlapping of the eight isomers of each compound in the chiral chromatographic analysis. 

The progress toward enantiomerically pnre drngs makes the selective and rapid analysis of enantiomers an important issue, both for chiral parity determinations and for enantioselective bioanalysis. Chankvetadze et al. [198] performed enantioseparations within an analysis time of 1 min for each of two chiral compounds (1,2,2,2-tetraphenylethanol and 2,2 -dihydroxy-6,6 -dimethylbiphenyl) by nsing a homemade capillary column containing monolithic silica modified with amylose tris(3,5-dimethylphenylcarbamate) (Figure 17.10). 

At present (2007), lOOC is carrying out some ring tests in order to verify the accordance of the two methods of elution. Separation on the basis of unsaturation can be improved by modifying the stationary phase by Ag-F ions, as the dimension of Ag+ ion is suitable to interfere with n bonds. Christie [10-12] adopted this technique to carry out structural analysis of TAGs. TAGs were hydrolyzed by Grignard reaction, then the stereoisomers 1,2 and 1,3-diacylglyreols were transformed into diasteroisomers by derivatization with a chiral compound, and were separated on normal-phase (NP)-HPLC. 

The direct gas-chromatographic method is especially suited as an analytical tool for enantiomer analysis when no sample derivatization is required. In the absence of diastereomeric effects between enantiomers ( EE-effect )25, the chiral compound may be investigated in situ, i.e., without isolation and purification using a minute amount of sample, e.g., by head-space analysis with 10 9 g using flame ionization detector (FID) or 1 (F 11 g using selected ion monitoring (GLC-MSSIM). 

The combination of enantio-MDGC with high-resolution MS or mass-selective detectors, both used in full scan or (at least) in the multiple ion monitoring (MIM) mode is currently the most potent analytical tool in enantioselective analysis of chiral compounds from complex mixtures. 

Enantio-cGC, however, fails in the case of non-chiral compounds, such as 1,8-cineol. In this special case 1,8-cineol may be attributed to high-level Melaleuca varieties or to the fraudulent addition of Eucalyptus oil. In order to get reliable results, enantio-MDGC-MS analysis and/or IRMS measurements (as far as possible) are necessary. 

This unit describes those methods that can differentiate between enantiomers found in foods that contribute to their taste and aroma. These compounds are volatile odorants that are most easily analyzed using enantioselective high resolution-gas chromatography (HRGC). Other methods exist for the separation and analysis of chiral compounds, which include optical methods, liquid and planar chromatography, and electrophoresis, but for food volatiles, gas chromatography has evolved to the point where it is now the cornerstone for the most comprehensive analysis of volatile compounds. 

The requirements for analyzing food odorants are demanding. The system must have a sensitivity of a few parts per billion or less, and be capable of handling highly volatile compounds. Although many methods exist for the analysis of chiral compounds, gas chromatography is the only viable method for analyzing food odorants because many are present in amounts too low for detection by most analyti-... 

Restek Corporation. 1997. A Guide to the Analysis of Chiral Compounds by GC. www.restekcorp.com/chiral/chiral.htm. 

D. Bartschat, D. Lehmann, A. Dietrich, A. Mosandl and R. Kaiser, Chiral compounds of essential oils. XIX. 4-methyl-5 decanolide chirospecific analysis, structure and properties of the stereoisomers , Phytochem. Anal. 6 130-134 (1995). 

Sensors for the detection of enantiomers are of great interest, as so far the on-line monitoring of production processes and medical diagnostics using standard chemical analytical methods is not possible. Quite often only one enantiomer of a chiral compound is actually a bioactive therapeutic. Therefore a proper analysis of the final product is essential. Currently, this involves separation techniques like liquid chromatography, GC and capillary electrophoresis, and determination of enantiomeric purity with circular dichro-ism and specific rotation. These are all off-line procedures and therefore no real-time analysis can be performed. Sensing devices for the distinction of different enantiomers would be a much cheaper, faster and easier-to-use alternative for this task, amenable to automation. 

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