Chiral components, identification

For identification of chiral components, optical rotatory dispersion (ORD) or circular dichroism (CD) techniques may be used. With the appropriate column, HPLC may be used most effectively for chiral compound identification. 

Dynamic combinatorial chemistry (DCC) is marvelously effective at discovering receptors for a broad array of analytes. The nature of the internal competition experiment ensures (normally) that the most effective binder for the analyte of interest is amplified for subsequent identification and characterization. In the context of a host-guest assembly, the issue of stereochemistry can be manifested in a number of scenarios. These include various permutations of chiral or achiral guests, along with achiral, enan-tiopure, or racemic dynamic library components. 

Capillary gas chromatography (GC) using modified cyclodextrins as chiral stationary phases is the preferred method for the separation of volatile enantiomers. Fused-silica capillary columns coated with several alkyl or aryl a-cyclo-dextrin, -cyclodextrin and y-cyclodextrin derivatives are suitable to separate most of the volatile chiral compounds. Multidimensional GC (MDGC)-mass spectrometry (MS) allows the separation of essential oil components on an achiral normal phase column and through heart-cutting techniques, the separated components are led to a chiral column for enantiomeric separation. The mass detector ensures the correct identification of the separated components [73]. Preparative chiral GC is suitable for the isolation of enantiomers [5, 73]. 

NMR is also a non-destructive technique, and a small number of sequential applications have been published. Wilson and co-workers [147] used HPLC-DAD-NMR-MS to characterize plant extracts. Hanson and co-workers [148] used a similar approach to examine another plant extract of pharmaceutical interest. In both cases, the complementary nature of the data provided quantitation of both major and minor constituents and aided in the structural identification of several of the minor components, including chiral isomers. Lommen et al. [149] describe a similarly configured system. The DAD and MS outputs were used to detect peaks, which were then transferred for NMR. They examined glycosides found in apple peel. They identified six quercetin glycosides and two phloretin glycosides, with the NMR data providing the definitive conformational data to differentiate the isomers. 

During the last years, a number of articles have been published by Casanova and coworkers (e.g., Bradesi et al. (1996) and references cited therein). In addition, papers dealing with computer-aided identification of individual components of essential oils after C-NMR measurements (e.g., Tomi et al., 1995), and investigations of chiral oil constituents by means of a chiral lanthanide shift reagent by carbon-13 NMR spectroscopy have been published (Ristorcelli et al., 1997). 

In 2011, Jacobsen et al. [38] reported a dual catalyst system consisting of a chiral primary amine thiourea and an achiral thiourea that promoted an intramolecular variant of the oxidopyrylium-based [5-1-2] cycloaddition reaction with high enanti-oselectivity (Scheme 43.25). Initially, poor enantioselectivity (21% ee) was obtained in the presence of catalyst 119. Subsequent studies showed that the addition of an achiral thiourea catalyst 120 dramatically improved the reaction enantioselectivily (67% ee, entry 2, Table 43.1). Further optimization led to the identification of 121, which bears a 2,6-diphenylanilide component, as the most enantioselective ami-nothiourea catalyst (88% ee, entry 3, Table 43.1). A clear and dramatic cooperative effect between the optimal catalysts was supported by a series of experiments. With optimal catalytic conditions, valuable tricyclic stractures were obtained in moderate to good yields and with high enantioselectivities (up to 95% ee) (Scheme 43.25). 

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