Enantiomeric composition

Benzodiazepine enantiomers have also been resolved on the Chiralcel OD CSP. Wang et al. utilized this CSP to determine the enantiomeric composition of camazepam and its metabolites [59]. SFC provided improved resolution of the compounds of interest in a shorter period of time than LC. Phinney et al. demonstrated the separation of a series of achiral and chiral benzodiazepines. An amino column was coupled in series with the Chiralcel OD CSP to achieve the desired separation [41]. 

The enantiomeric compositions of the titanium reagents are monitored easily by the reaction with enantiomerically pure chiral aldehydes, such as 2-(fer/-butyldimethylsilyloxy)propanal104. Here, the ratio of diastereomeric products reflects the ratio of enantiomers of the reagent, although a small error arises from double stereodifferentiation95 104. 

The stannanes (-)-ent-12 and ( + )-ent- 3 (R = CH3) are obtained with >80% ee from the alkenyllithium (-)-sparteine complex105,107a (Section 1.3.3.3.1.1.). Hence, their titanium(IV) chloride mediated carbonyl additions are accompanied by chirality transfer and enantioface selection of opposite sense. This was demonstrated for the reaction with (5)-2-benzyloxy-propanal107b the d.r. (88 12) roughly reflects the enantiomeric composition of the stannanes. 

Partial photochemical decomposition of racemic alkyl aryl sulphoxides in the presence of chiral amines as sensitizers gave non-decomposed sulphoxides in optically active form with optical purity of about 3%339. The report340 on the use of cholesteric liquid crystalline reaction media to change the enantiomeric composition of racemic sulphoxides at high temperatures could not be reproduced341. 

A kinetic resolution depends on the fact that the two enantiomers of a racemic substrate react at different rates with the enzyme. The process is outlined in Figure 6.1, assuming that the (S) substrate is the fast-reacting enantiomer (ks > ka) and Kic = 0-In ideal cases, only one enantiomer is consumed and the reaction ceases at 50% conversion. In most cases, both enantiomers are transformed and the enantiomeric composition ofthe product and the remaining starting material varies with the extent... 

In an asymmetric synthesis, the enantiomeric composition of the product remains constant as the reaction proceeds. In practice, ho vever, many enzymatic desymmetrizations undergo a subsequent kinetic resolution as illustrated in Figure 6.5. For instance, hydrolysis of a prochiral diacetate first gives the chiral monoalcohol monoester, but this product is also a substrate for the hydrolase, resulting in the production of... 

Sutherland JB, PP Fu, SK Yang, LS von Tungeln, RP Casillas, SA Crow, CE Cerniglia (1993) Enantiomeric composition of the fran -dihydrodiols produced from phenanthrene by fungi. Appl Environ Microbiol 59 2145-2149. 

Ekgorg-Ott, K.H., Taylor, A., Armstrong, D.W. (1997). Varietal differences in the total and enantiomeric composition of theanine in tea. J. Agric. Food. Chem. 45, 353-363. 

Kullman, J.P., Chen, X., Armstrong, D.W. (1999). Evaluation of the enantiomeric composition of amino acids in tobacco. Chirality 11, 669-673. 

Each entry is an average of data obtained from two separate experiments using different microsomal preparations. Enantiomeric composition was determined by CD spectral data (18) and by CSP- HPLC (19,20). 

Figure 3. Mechanism of microsomal EH-catalyzed hydration of the K-region epoxide enantiomers of BA, BaP, and DMBA. The percentages of the trans-addition product by water for each enantiomeric epoxide are indicated. The enantiomeric composition of the dihydrodiol enantiomers formed from the hydration of DMBA 5S,6R-epoxide was determined using 1 mg protein equivalent of liver microsomes from pheno-barbital-treated rats per ml of incubation mixture and this hydration reaction is highly dependent on the concentration of the microsomal EH (49). The epoxide enantiomer formed predominantly from the respective parent hydrocarbon by liver microsomes from 3-methylcho-lanthrene-treated rats is shown in the box.

Table II. Enantiomeric Composition of the 3,4- and 5,6-Dihydrodiols Formed in the Metabolism of BA and DMBA by Liver Microsomes from Rats of the Sprague-Dawley Strain...

BA 3,4-dihydrodiol metabolites were isolated by a reversed-phase HPLC using a Vydac C18 column (Chiu et al., unpublished results). DMBA dihydrodiol metabolites were isolated as described (42). The enantiomeric composition was determined either by CD spectral data or by CSP-HPLC (7.19.20). 

For a number of the systems, comparisons were made between the effects of enantiomeric composition in the monolayer and corresponding melting-point-composition curves for the crystals. All of the latter gave clear evidence of racemic compound formation in the crystals, and this type of pattern was repeated in the monolayer properties. 

The use of diazaphospholidines as chiral derivatizing agents for the determination of the enantiomeric composition of choro- or bromohydrins has been reported. Thus, 31P NMR spectra of a range of diastereomeric derivatives have been described to show a systematic deshielding from 0.2 to 12.9 ppm of isomers 48 compared to isomers 49 <2000TA1273>. 

Since the separated enantiomers of a dissymmetric compound must crystallize in a different space group than does the racemic mixture, it should not be unanticipated that quantitative XRPD would be useful in the determination of enantiomeric composition. For instance, the differing XRPD characteristics of (S)-(+)-ibuprofen relative to the (-RS)-racemate have been exploited to develop a sound method for the determination of the enantiomeric purity of ibuprofen samples [53]. 

An alternative approach is provided by NMR spectroscopy. Separate NMR signals can be in principle obtained for stable or short-lived diastereomeric derivatives of the enantiomeric mixtures, the intensities of which are correlated with the enantiomeric composition and their relative stereochemistry to the absolute configuration. For this reason, great effort has been continually devoted to the development of new chiral auxiliaries for NMR spectroscopy. The majority of these are dedicated to the chiral assay of molecules having polar functional groups. 

On the basis of the results above it can be concluded that, at least for the allenes investigated, the complete separation of the two allene absorptions can be achieved both by varying the molar ratio and by lowering the temperature, and hence the enantiomeric composition can be accurately determined by comparing the areas of the two absorptions by integration. 

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