Enantioselective chromatographic analysis

Chiral monoterpenoids in plants-enantioselective chromatographic analysis, and their bioactivity... 

CHIRAL MONOTERPENOIDS IN PLANTS -ENANTIOSELECTIVE CHROMATOGRAPHIC ANALYSIS, AND THEIR BIOACTIVITY... 

Shellie R, Mondello L, Dugo G, Marriott P, Enantioselective gas chromatographic analysis of monoterpenes in essential oils of the family Myrtaceae, Flavour Fragr J 19 582-585, 2004. 

First success in enantioselective flavouring analysis was achieved by chromatographic separations of diastereomeric derivatives. In spite of limited sensitivity and frequently laborious work-up conditions, these methods revealed reliable insight into enantiomeric distribution of y(5) lactones and other chiral fruit flavouring compounds, as reviewed previously [55]. 

The four isomers of 45 showed identical IR, H-NMR, and 13C-NMR spectra. In addition, all of them were equally bioactive as the sex pheromone. Accordingly, their derivatization to 52 followed by HPLC analysis was the only way to distinguish the stereoisomers. Finally, the natural pheromone component was shown to be (6i , 19Jfi )-45 by its derivatization to 52 followed by HPLC analysis.35 Enantioselective HPLC or gas chromatography (GC) and chromatographic analysis after derivatization with Ohrui s reagent seems to be the most sensitive method for discrimination of stereoisomers. Thus, it may be concluded that structural analysis must, from time to time, be carried out by employing various kinds of different analytical methods. Otherwise, mistakes are likely to occur. 

An example of a catalytic, enantioselective [3 + 2] cycloaddition is the formation of 2 from MCP and methyl acrylate. The stereochemical information in these nickel(0)-catalyzed reactions is introduced by employing dilTerent phosphanes and phosphites with a (l/, 45) menthyl substituent as modifying ligand. Enantiomeric excesses of up to 36% have been reported, as determined by gas chromatographic analysis of the 3-methylenecyclopentanemethanol produced upon reduction of ester 2. 

Fig. 5.13. Enantioselective gas chromatographic analysis of trans-a-ionone in aroma extracts of different raspberry fruit juice concentrates (according to Werkhoff et al., 1990) a and b samples with nature identical aroma, c natural aroma...

The method frequently applied to determine ee values is the enantioselective gas chromatographic analysis of the aroma substance on a chiral phase, e. g., peralkylated cyclodextrins. This method was used, e. g., to test raspberry fruit juice concentrates for unauthorized aromatization with trans-a-ionone. The gas chromatograms of trans-a-ionone from two different samples are shown in Fig. 5.13. The low excesses of the R-enantiomer of ee = 8% (concentrate A) and ee = 24% (B) can probably be put down to the addition of synthetic trans-a-ionone racemate to the fruit juice concentrate because in the natural aroma (C), the ee value is 92.4%. 

ENANTIOSELECTIVE LIQUID CHROMATOGRAPHIC ANALYSIS OF AMINO ACIDS... 

As a matter of fact, the main advantage in comparison with HPLC is the reduction of solvent consumption, which is limited to the organic modifiers, and that will be nonexistent when no modifier is used. Usually, one of the drawbacks of HPLC applied at large scale is that the product must be recovered from dilute solution and the solvent recycled in order to make the process less expensive. In that sense, SFC can be advantageous because it requires fewer manipulations of the sample after the chromatographic process. This facilitates recovery of the products after the separation. Although SFC is usually superior to HPLC with respect to enantioselectivity, efficiency and time of analysis [136], its use is limited to compounds which are soluble in nonpolar solvents (carbon dioxide, CO,). This represents a major drawback, as many of the chemical and pharmaceutical products of interest are relatively polar. 

A. Berthod, W. Li, and D. W. Armstrong, Multiple Enantioselective Retention Mechanisms on Derivatized Cyclodextrin Gas Chromatographic Chiral Stationary Phases, Anal. Chem. 1992,64, 873 K. Bester, Chiral Analysis for Environmental Applications, Anal. Bioanal. Chem. 2003,... 

Levin, S. and Abu-Lafi, S. The Role of Enantioselective Liquid Chromatographic Separations Using Chiral Stationary Phases in Pharmaceutical Analysis , in Advances in Chromatography. 

Lanchote, V.L., Bonato, P.S., Cerqueira, P.M., Pereira, V.A., Cesarino, E.J. Enantioselective analysis of metoprolol in plasma using highperformance liquid chromatographic direct and indirect separations applications in pharmacokinetics. J. Chromatogr. B 738, 27-37 (2000)... 

In this context, enantioselective analysis and in particular chromatographic separation methods have gained a vital interest and central importance for the following reasons. 

Optimum chiral resolution without any racemization and reliable interpretation of chromatographic behaviour of enantiomers have to be considered as the first targets in enantioselective analysis (section 6.2.3.1.). Even if a universal recommendation on sample clean-up cannot be given, depending on the complexity of samples to be analyzed, preseparation procedures of highest efficiency are needed if a reliable stereodifferentiation should be achieved. 

Since in most cases only one enantiomer possesses a desired pharmacological activity, it is necessary to construct enantioselective sensors to improve the quality of analysis due to the high uncertainty obtained in chiral separation by chromatographic techniques.315 For this purpose, enantioselective amperometric biosensors and potentiometric, enantioselective membrane electrodes have been proposed.264 The selection of one sensor from among the electrochemical sensor categories for clinical analysis depends on the complexity of the matrix because the complexity of different biological fluids is not the same. For example, for the determination of T3 and T4 thyroid hormones an amperometric biosensor and two immunosensors have been proposed. The immu-nosensors are more suitable (uncertainty has the minimum value) for direct determination of T3 and T4 thyroid hormones in thyroid than are amperometric biosensors. For the analysis of the same hormones in pharmaceutical products, the uncertainty values are comparable. 

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