Determination of enantiomeric form

More recently, the chiral phosphonate 85 has been used as a CDA with chiral amines to form diastereomeric phosphonic amides (86)79 which are analyzed by 31P-NMR spectroscopy for the determination of enantiomeric ratios. The reagent is readily prepared from (5)-2-butanol and phosphorous trichloride, and all a-amino acids and amines thus far examined react quantitatively in a few hours at room temperature in aqueous ethanol79. 

As a result, the CD of a chiral molecule can in principle be used to determine its enantiomeric form, referred to as its Absolute Configuration (AC). Since the discovery of CD by Cotton [1], the determination of the ACs of chiral compounds has been the predominant application of CD spectroscopy. 

Quinine is an optically pure derivatizing reagent that forms a diastereomeric mixture of salts whose 13c NMR spectrum would be expected to show individual peaks for the diastereomers present. A 13c NMR of the salt formed from 1 equivalent of quinine and 1 equivalent of racemic acid (V) revealed two peaks for the carbon atom 3 to the carbonyl group. The NMR (25.2 MHz) of the salt of the partially resolved acid (Figure 1) indicates that the ratio of diastereomers is approximately three to one (optical purity 75%). As is seen in the expansion, overlap of peaks precludes precise determination of enantiomeric composition, but a more powerful instrument should completely resolve the two peaks. We are currently investigating the generality of this procedure. 

In traditional analytical chemistry the determination of enantiomeric purity is sometimes carried out by capillary electrophoresis (CE) in which the electrolyte contains chiral selectors such as cyclodextrin (CD) derivatives [54], Unfortunately the conventional form of this analytical technique allows only a few dozen ee determinations per day. However, as a consequence of the analytical demands arising from the Human Genome Project, CE has been revolutionized in recent years so that efficient techniques for instrumental miniaturization are now available, making ultra-high-through-put analysis of biomolecules possible for the first time [55]. Two different approaches have emerged, namely capillary array electrophoresis (CAE) [55a - e] and CE on microchips (also called CAE on chips) [55f - m[. Both techniques can be used to carry out... 

The two forms of capillary array electrophoresis are emerging as powerful methods for the determination of enantiomeric purity of chiral compounds in a truly high-through-put manner. Various modifications are possible, for example, detection systems based on UV/Vis, MS, or electrical conductivity. Moreover, chiral selectors in the CE electrolyte are not even necessary if the mixture of enantiomers is first converted into diastereo-mers, for example, using chiral fluorescent-active derivatization agents [51,57]. 

A review appeared on the practice and theory of enantioselective CGC with optically active selectors, e.g. 3-(perfluorobutyryl)-(17 )-camphorate residues forming complexes on a functionalized polysiloxane stationary phase (e.g. Chirasil, 65) SEC operates at temperatures lower than those of CGC, thus allowing better resolution, especially of thermally unstable enantiomers (e.g. those based on restricted free rotation, as is the case of dimethyl l,l -binaphthyl-2,2 -dicarboxylate, 66 ). Various analytical problems were addressed, such as determination of enantiomeric excess, assignment of absolute configuration, the elusive separation of protio- and deuterio-substituted enantiomers and the semipreparative separation of enantiomers. The following chromatographic parameters are related to the chemical and thermodynamic properties enclosed in parentheses of the enantiomeric system (i) peak retention (chemoselectivity, —AG), (ii) peak separation... 

In addition, OPEN is an efficient chiral solvating agent for determination of the enantiomeric excess in the H NMR analysis of various chiral mono- and dicarboxylic acids including a-arylpropanoic and a-halo carboxylic acids. The chemical-shift non-equivalence (S A) in certain diastereomeric complexes is greater than 0.05 ppm. A DPEN/Pd(II) complex can be used for determination of enantiomeric excess of the non-protected chiral amino acids by H and C NMR analysis. For example, Pd[(S,S)-dpen](D20)2 and racemic alanine with a base forms the square-planar complex (eq 14). The 5 A of H-NMR resonance in the diastereomeric complexes in D2O is 0.056 ppm, while this complex hardly dissolves in D2O. 

The main applications of enantiomeric separation by GC concern precise determination of enantiomeric composition of chiral research chemicals, drugs, intermediates, metabolites, pesticides, flavors and fragrances, etc. CHIRBASE, a database of chiral compounds, provides comprehensive structural, experimental, and bibliographic information on successful and unsuccessful chiral separations, and rule sets for each CSP and information about the processes of chiral separations. According to CHIRBASE, an appropriate CSP is available for almost every racemic mixture of compounds ranging form apolar to polar. Some 22,000 separations of enantiomers, involving 5,500 basic chiral compounds and documented in 2,200 publications, have been achieved by GC. This method is particularly suitable for volatile compounds such as inhalation anesthetic agents, e.g., enflurane, isoflurane, desflurane, and racemic a-ionone. 

Terrein (21), a metabolite of the mold Aspergillus terrei/5, was first isolated by Raistrick and Smith in 1935 [29]. Its correct structure was established independently by Grove [30] and by Barton and Miller [31]. The latter authors degraded (+)-21 to a derivative of (+)-tartaric acid and in this way determined the trans-configuration of the diol moiety. Barton and Hulshof [33] also described the synthesis of racemic isoterrein 22 which has a czs-diol unit. The structures of enantiomeric forms of 21 and 22 are shown below. 

The enantiomers of camphorcarboxylic and sulfonic acids are used for resolution of enantiomers from racemic chiral amines and alcohols via diastereomeric salts and esters, respectively. Europium(III)- and praseodymium(III)-chelates of hydroxy-methylenecamphor derivatives are suitable chiral shift reagents for the determination of enantiomeric purity by integration of NMR spectra, because they exchange ligands with enantiomeric substrates such as alcohols and amines, thus forming diastereomeric chelates characterized by different spectra. 

The properties of CD multimodel inclusion complexes were correctly reproduced by MM2 calculations. This method allows us to correctly determine the differences in the complexation of enantiomeric forms. Special care should be taken when selecting the molecules to model, and while analyzing the final geometries and interactions. ... 

As many biologically important analytes do not exhibit efficient detection properties (UV or visible light absorption, fluorescence, or electrochemical activity), their detection limits are relatively low. For example, drugs with chiral centers exist naturally in racemic mixtures that are optically inactive due to the nearly equal proportion of the enantiomers. The determination of enantiomeric purity is of paramount importance in the pharmaceutical industry as each enantiomer may have different therapeutic characteristics. Currently, a method that offers multiple advantages for chiral separations is by converting enantiomers to diastereomers by precolumn derivatization with a pure fluorescent enantiomer. For instance, propranolol existing in racemic form may be analyzed by precolumn derivatization with (+ )-l-(9-fluorenyl)ethyl chloroformate. Well correlated calibration plots were found up to 400pmol and a reproducibility of <2% for each derivative. 

H H non-bonded interactions are of great importance in organic compoimds, and thus it was of interest to attempt to investigate H H non-bonded potential functions via the determination of a steric isotope effect in the configurational inversion of an unsubstituted biaryl. In view of the extensive work of Harris and her co-workers in the 1,1 -binaphthyl series (see, for example, Badar et al., 1965 Cooke and Harris, 1963), and since the parent compound is one of the simplest hydrocarbons that may be obtained in enantiomeric forms, the determination of the isotope effect in the inversion of l,l -binaphthyl-2,2 -d2 (9) was... 

Studies focused on the determination of SAR have revealed that the different enantiomeric form of catechins apparently affects their antibacterial activity. Bais et al. [101] found that (-i-)-catechin inhibited soil-borne bacteria of the species Xanthomonas campestris, R fluorescens, and Erwinia caro-... 

Miscellaneous Reactions of Phosphines.- The role of chiral phosphines as ligands in the catalysis of reactions leading to the formation of chiral products has been reviewed.1111 A procedure for the determination of the enantiomeric excess in chiral phosphines has been developed, based on 13C n.m.r. studies of the diastereoisomeric complexes formed by phosphines with the chiral pinenyl nickel bromide complex. 111 Studies of the sulphonation of triphenylphosphine and of chiral arylphosphines have been reported in attempts to prepare water soluble ligands which aid... 

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