Enantiomer ratio

Another possibility of constructing a chiral membrane system is to prepare a solution of the chiral selector which is retained between two porous membranes, acting as an enantioselective liquid carrier for the transport of one of the enantiomers from the feed solution of the racemate to the receiving side (Fig. 1-5). This system is often referred to as membrane-assisted separation. The selector should not be soluble in the solvent used for the elution of the enantiomers, whose transport is driven by a gradient in concentration or pH between the feed and receiving phases. As a drawback common to all these systems, it should be mentioned that the transport of one enantiomer usually decreases when the enantiomer ratio in the permeate diminishes. Nevertheless, this can be overcome by designing a system where two opposite selectors are used to transport the two enantiomers of a racemic solution simultaneously, as it was already applied in W-tube experiments [171]. 

In general, high selectivities can be obtained in liquid membrane systems. However, one disadvantage of this technique is that the enantiomer ratio in the permeate decreases rapidly when the feed stream is depleted in one enantiomer. Racemization of the feed would be an approach to tackle this problem or, alternatively, using a system containing the two opposite selectors, so that the feed stream remains virtually racemic [21]. Another potential drawback of supported enantioselective liquid membranes is the application on an industrial scale. Often a complex multistage process is required in order to achieve the desired purity of the product. This leads to a relatively complicated flow scheme and expensive process equipment for large-scale separations. 

To demonstrate the potential of the process in obtaining both enantiomers at a high purity, experiments were performed using racemic norephedrine as the compound to be separated. Two columns of seven small membrane modules were used. The enantiomer ratios in the outflows during start-up are shown in Fig. 5-15. It can be concluded that the system reaches equilibrium within approximately 24 h, and that both enantiomers are recovered at 99.3-99.8 % purity. 

Fig. 5-15. Enantiomer ratio in the outflow versus time for the separation of raeemie norephedrine.

Finally, the data in Table 8-6 show the elution of the lead column. The eluent is H,0. The driving force for the elution in this case is the lack of C10 present to act as an anion in the binding of the ammonium perchlorate salt pair. The D-enantiomer versus L-enantiomer ratio in the elution is slightly greater than 6 1, as expected by the inherent selectivity of the ligand. For this separation system, LiClO is then added back to the eluent and the eluent is sent on as load to the next purification stage. 

In practise, if using one of these reagents to follow the course of a chiral separation, it is essential to determine whether resolution is possible, by performing a test experiment either on a sample of racemate, or at least a sample known to contain significant quantities of both enantiomers. Once useable resolution has been established, the technique can be used to monitor solutions of unknown enantiomer ratios with reasonable accuracy, down to normal NMR detection limits. 

Brunner et al. attached chiral branches to non-chiral catalytically active sites. With the aim to influence the enantioselectivity of transition metal catalyzed reactions they synthesized several dendritically enlarged diphosphines such as 81 [101] (Fig. 29). In situ prepared catalysts from [Rh(cod)Cl]2and81 have been tested in the hydrogenation of (a)-N-acetamidocinnamic acid. After 20 hours at 20 bar H2-pressure (Rh/substrate ratio 1 50) the desired product was obtained with an enantiomer ratio of 51 49. 

In another reaction dendritic pyridine derivatives such as 82 or 83 were tested as co-catalysts for enantioselective cyclopropanation of styrene with ethyl diazoacetate [102]. Using catalyst 82, enantiomer ratios of up to 55 45 were obtained. However, with catalyst 83 bearing larger branches yields and selectivities did not increase. The relatively low selectivities were rationalized by the presence of a large number of different conformations that this non-rigid system may adopt. 

It was recently reported that. >97% of BaP 4,5-epoxide metabolically formed from the metabolism of BaP in a reconstituted enzyme system containing purified cytochrome P-450c (P-448) is the 4S,5R enantiomer (24). The epoxide was determined by formation, separation and quantification of the diastereomeric trans-addition products of glutathione. Recently a BaP 4,5-epoxide was isolated from a metabolite mixture obtained from the metabolism of BaP by liver microsomes from 3-methylcholanthrene-treated Sprague-Dawley rats in the presence of the epoxide hydrolase inhibitor 3,3,3-trichloropropylene oxide, and was found to contain a 4S,5R/4R,5S enantiomer ratio of 94 6 (Chiu et. al., unpublished results). However, the content of the 4S,5R enantiomer was <60% when liver microsomes from untreated and phenobarbital-treated rats were used as the enzyme sources. Because BaP 4R,5S-epoxide is also hydrated predominantly to 4R,5R-dihydro-... 

BA trans-3.4-dihvdrodiol cannot be separated from BA trans-8.9-dihydrodiol in several HPLC conditions (27-29). Quantification of BA trana-3,4-dihydrodiol by HPLC can only be accomplished after converting the 3,4-dihydrodiol to its diacetate (25.26). The BA trans-3.4-dihydrodiol formed in BA metabolism by liver microsomes from pheno-barbital-treated rats was determined to have a 3R,4R/3S,4S enantiomer ratio of 69 31 (30). Recently we have determined the optical purity of the BA trans-3.4-dihvdrodiol formed in the metabolism of BA by three liver microsomes prepared from untreated rats and rats that had been pretreated with an enzyme inducer. As shown in Table II, cytochrome P-450 isozymes contained in liver microsomes from 3-methylcholanthrene- or phenobarbital-treated rats had similar stereoselectivity toward the 3,4-double bond of BA. BA trans-3.4-dihydrodiol is formed via the 3,4-epoxide intermediate (31). 

In contrast to the metabolism of BA and BaP, the 5,6-dihydrodiols formed in the metabolism of DMBA by liver microsomes from untreated, phenobarbital-treated, and 3-methylcholanthrene-treated rats are found to have 5R,6R/5S,6S enantiomer ratios of 11 89, 6 94, and 5 95, respectively (7.49 and Table II). The enantiomeric contents of the dihydrodiols were determined by a CSP-HPLC method (7.43). The 5,6-epoxide formed in the metabolism of DMBA by liver microsomes from 3MC-treated rats was found to contain predominantly (>97%) the 5R,6S-enantiomer which is converted by microsomal epoxide hydrolase-catalyzed hydration predominantly (>95%) at the R-center (C-5 position, see Figure 3) to yield the 5S,6S-dihydrodiol (49). In the metabolism of 12-methyl-BA, the 5S,6S-dihydrodiol was also found to be the major enantiomer formed (50) and this stereoselective reaction is similar to the reactions catalyzed by rat liver microsomes prepared with different enzyme inducers (unpublished results). Labeling studies using molecular oxygen-18 indicate that 5R,68-epoxide is the precursor of the 5S,6S-dihydrodiol formed in the metabolism of 12-methyl-BA (51). 

The phase transitions of cholesteryl nonanoate have been studied with a new apparatus for thermal analytical microscopy. The enantiomer ratio of some chiral sulphoxides can be changed from racemic to a modest preference for one enantiomeric form by dissolution in a cholesteryl ester in its liquid-crystalline ( cholesteric ) state. 5,6-Epoxycholestan-3-yl p-nitrobenzoates exhibit liquid-crystal properties, but 5,6-diols and dibromides are inactive. ... 

Anthonsen, H.W., Hoff, B.H. and Anthonsen, T. (1996) Calculation of enantiomer ratio and equilibrium constants in biocatalytic ping-pong bi-bi resolutions. Tetrahedron ... 

Because ee and op values are not suited for mathematical formulae, it is much simpler and clearer if enantiomer ratios are used, Up to around 1980 it was the custom, as assessed from older textbooks and reviews, to define enantiomeric and optical purity by fractions and use terms enantiomeric and optical yield for the percentage values as described earlier. 

One way method to enantioface differentiation proceeds via a chiral catalyst (+)-3 and gives an enantiomer ratio of 11 1. 

I 13 Dynamic Resolution of Chiral Amine Pharmaceuticals Turning Waste Isomers into Useful Product Table 13.3 Enantiomer ratios at different stages of the (IS, 4S)-sertraline mandelate process. 

Sublimation. Such effects can also be seen in solid-gas interphase. Scheme 30 shows the consequences of fractional sublimation of partially resolved L-mandelic acid (47). The optical purity could be enhanced or reduced, depending on the optical purity of the starting material. Since the eutectic point of mandelic acid is obtained with about a 75 25 enantiomer ratio, such a mixture is more readily sublimed than the racemate or conglomerate. Scheme 30 gives other examples of optical enrichment by sublimation. Phenyl 1-phenyl-1-propyl sulfide in 6% ee affords the sublimed compound in 74% ee, but the residue is... 

Food scientists are interested in the enantiomer distribution of chiral food odorants because enantiomers may have different odors and odor intensities. Determination of enantiomer ratios and their sensory properties can provide information about origin of food aromas and the perceived variations in the taste of foods. These data can be collected only when the enantiomers are separated using enantiose-lective high-resolution gas chromatography, which is the leading method for stereodifferentiation of chiral food odorants. 

More recently, enantiomer ratios have been used as evidence of adulteration in natural foods and essential oils. If the enantiomer distribution of achiral component of a natural food does not agree with that of a questionable sample, then adulteration can be suspected. Chiral GC analysis alone may not provide adequate evidence of adulteration, so it is often used in conjunction with other instrumental methods to completely authenticate the source of a natural food. These methods include isotope ratio mass spectrometry (IRMS), which determines an overall 13C/12C ratio (Mosandl, 1995), and site-specific natural isotope fractionation measured by nuclear magnetic resonance spectroscopy (SNIF-NMR), which determines a 2H/ H ratio at different sites in a molecule (Martin et al 1993), which have largely replaced more traditional analytical methods using GC, GC-MS, and HPLC. 

Values for the enantiomer ratio found in natural products can range from 0% to 100%. If the enantiomeric purity is 100%, care must be taken to determine which isomer is present by comparison of retention times with a known standard. Samples from different geographic or growing regions may show some variation in the ratio of a specific compound, while others will not deviate from a known value. 

Knowledge of enantiomer ratios, particularly for compounds that occur naturally with 100% of one enantiomer, can form the basis of an authenticity determination (Kreis and Mosandl, 1992 Mosandl and Juchelka, 1997). In such analyses, deviations from known enantiomer ratios of authentic samples can indicate adulteration of the sample, where synthetic materials have been added, or the sample has been distilled although it was labeled as a natural product. 

The trans .cis (or E/Z) ratios of cyclopropane products are higher than those obtained with styrene, and the diastereomer ratio or enantiomer ratio for the trans( ) isomer is generally >90 10. Although these reactions are usually performed with 1.0 mol % of catalyst, Evans has optimized the cyclopropanation of isobutylene to a 0.25 mol scale [40], by using only 0.1 mol % of catalyst, and obtained a 91 % yield of the (S)-cyclopropane enantiomer whose enantiopurity... 

Table 7 Enantiomer Ratios of selected hepta and octachlorobornane congeners in air, open lake and tributary waters, and sediments in Lake Superior [91]. Parlar numbers for each congener are shown in parentheses...

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