Enantiomers distribution

Enantiomer distribution constant (EDC). Estimates in CDClj-rich layer in the partitioning of an equivalent of racemic host (H) and optically pure L-valine as guest (G) and their complexes between two liquid phases composed of RCO,D(H). CDC1 and 020"... 

Since the early times of stereochemistry, the phenomena related to chirality ( dis-symetrie moleculaire, as originally stated by Pasteur) have been treated or referred to as enantiomericaUy pure compounds. For a long time the measurement of specific rotations has been the only tool to evaluate the enantiomer distribution of an enantioimpure sample hence the expressions optical purity and optical antipodes. The usefulness of chiral assistance (natural products, circularly polarized light, etc.) for the preparation of optically active compounds, by either resolution or asymmetric synthesis, has been recognized by Pasteur, Le Bel, and van t Hoff. The first chiral auxiliaries selected for asymmetric synthesis were alkaloids such as quinine or some terpenes. Natural products with several asymmetric centers are usually enantiopure or close to 100% ee. With the necessity to devise new routes to enantiopure compounds, many simple or complex auxiliaries have been prepared from natural products or from resolved materials. Often the authors tried to get the highest enantiomeric excess values possible for the chiral auxiliaries before using them for asymmetric reactions. When a chiral reagent or catalyst could not be prepared enantiomericaUy pure, the enantiomeric excess (ee) of the product was assumed to be a minimum value or was corrected by the ee of the chiral auxiliary. The experimental data measured by polarimetry or spectroscopic methods are conveniently expressed by enantiomeric excess and enantiomeric... 

The term enantiomer distribution" expresses the difference (%) of the numbers of respective enantiomers [e.g., S (%) — R (%)] existing in the system. Since C(2) of 8 is highly susceptible to racemization, 8 exists as a racemate in natural. The enantiomer distribution of racemate should be 0, because a racemate consists of equal amounts of (R)- and (S)-isomers. 

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. 

This relationship shows that there is a linear correlation between the enantiomeric excess of the product of an asymmetric synthesis and the enantiomeric excess of the chiral auxiliary. As pointed out in Ref. 10, such a simple relationship does not exist if enantiomeric ratios (er) are used to describe the enantiomer distributions. It was classically Eq. (14), or the equivalent Eq. (1), which was implicitly used to extrapolate the enantiomeric excess of the product (ee0) prepared under the influence of enantiopure chiral auxiliary. 

The yeast strain used for fermentation had no impact on the enantiomer distribution of these volatile thiols. 3SHA is generally considered to be formed by esterification of 3SH by yeast during alcoholic fermentation. The esterase or lipase involved probably acetylates 3SH with a certain enantioselectivity. In contrast, the enantiomer distribution of 3SH in wine made from botrytized grapes (Botrytis cinerea) is 25 75 in favor of the S form, which has also been found in botrytized must (Thibon et al. 2007,2008a). 

U. Hener, P. Kreis and A. Mosandl. Chiral compounds of essential oils IV. Enantiomer distribution of a-pinene, jl-pinene and fimonene in essential oils and extracts Part 2 Perfumes and cosmetics. Flaw Fragr. J., 5, 201-204 (1990). 

High resolution H- and C-NMR of polypropylene and of ethylene-propylene copolymers as well as determination of enantiomers distribution in polymers from racemic a-olefins demonstrated that the catalytic complex is responsible for the isotactic enchainment. This implies the chiral (racemic)structure of the catalyst which at present seems to be adequately proved as discussed in the two following sections. 

Scott and Beesley [2] measured the corrected retention volumes of the enantiomers of 4-benzyl-2-oxazolidinone employing hexane/ethanol mixtures as the mobile phase and correlated the corrected retention volume of each isomer to the reciprocal of the volume fraction of ethanol. The results they obtained at 25°C are shown in Figure 8. It is seen that the correlation is excellent and was equally so for four other temperatures that were examined. From the same experiments carried out at different absolute temperatures (T) and at different volume fractions of ethanol (c), the effect of temperature and mobile composition was identified using the equation for the free energy of distribution and the reciprocal relationship between the solvent composition and retention. 

The enantioselectivity a is defined as the distribution ratio of one single enantiomer over the two chiral phases and has been determined experimentally for a variety of compounds (Table 5-1). It has been known from work by Prelog [66, 67] that tartaric acid derivatives show selectivities towards a-hydroxyamines and amino acids. However, from Table 5-1 it is obvious that tartaric acid derivatives show selectivity for many other compounds, including various amino bases (e.g. mirtazapine (10)) and acids (e.g. ibuprofen (11)). The use of other chiral selectors (e.g. PLA)... 

In the elucidation of retention mechanisms, an advantage of using enantiomers as templates is that nonspecific binding, which affects both enantiomers equally, cancels out. Therefore the separation factor (a) uniquely reflects the contribution to binding from the enantioselectively imprinted sites. As an additional comparison the retention on the imprinted phase is compared with the retention on a nonimprinted reference phase. The efficiency of the separations is routinely characterized by estimating a number of theoretical plates (N), a resolution factor (R ) and a peak asymmetry factor (A ) [19]. These quantities are affected by the quality of the packing and mass transfer limitations, as well as of the amount and distribution of the binding sites. 

The method described above is applicable to a wide range of samples for the determination of amino acids in different matrices. For example, the amino acid composition and distribution of single enantiomers has been determined in protein hydrolysates, orange juice (Fig. 7-11), yogurt and seawater [23]. 

It was apparent that the FDA recognized the ability of the pharmaceutical industry to develop chiral assays. With the advent of chiral stationary phases (CSPs) in the early 1980s [8, 9], the tools required to resolve enantiomers were entrenched, thus enabling the researcher the ability to quantify, characterize, and identify stereoisomers. Given these tools, the researcher can assess the pharmacology or toxicology and pharmacokinetic properties of enantiopure drugs for potential interconversion, absorption, distribution, and excretion of the individual enantiomers. 

Table 11-4. Distribution of piperoxan enantiomers in CFFE vials.

Fig. 11-6. Histograms showing the distribution of piperoxan enantiomers in the absenee (a) and pre-senee (b) of sulfated eyelodextrin in eontinuous free flow eleetrophoresis.

The applicant should provide justification for using the racemate. Where the interconversion of the enantiomers in vivo is more rapid than the distribution and elimination rates, then use of the racemate is justified. In cases where there is no such interconversion or it is slow, then differential pharmacological effects and fate of the enantiomers may be apparent. Use of the racemate may also be justified if any toxicity is associated with the pharmacological action and the therapeutic index is the same for both isomers. For preclinical assessment, pharmacodynamic, pharmacokinetic (using enantiospecific analytical methods) and appropriate toxicological studies of the individual enantiomers and the racemate will be needed. Clinical studies on human pharmacodynamics and tolerance, human pharmacokinetics and pharma-cotherapeutics will be required for the racemate and for the enantiomers as appropriate. 

This forward-backward asymmetry of the photoelectron distribution, expected when a randomly oriented sample of molecular enantiomers is ionized by circularly polarized light, is central to our discussion. The photoelectron angular... 

While it is clear that a direct measurement of the angular distribution, Eq. (4), with a given hehcity of hght should be capable of yielding the h angular parameter, it is often more convenient to examine the dichroism, or difference, obtained with opposite helicities of the light (or, possibly, of the enantiomer). From Eq. (4) and the antisymmetry property Eq. (6) one obtains an expression for the PECD ... 

A single image recorded for a fixed enantiomer and fixed circular polarization state in principle carries the full information sought consisting, after inversion, of the parameters and the radial distribution function n r). After... 

In accordance with the predictions that can be made on the basis of just the electric dipole approximation (see Section III.A) the observed dichroism is equal, but of opposite sign for the two enantiomers. This could be seen also in the valence shell ionization results for glycidol presented in Fig. 2. The added significance here is that a contribution to the angular distribution by higher order... 

The precision of the data is not such as to allow non-dipole interactions to be definitively ruled out, and more detailed study of this topic by careful measurement of the full angular distribution, as opposed to detection at a single angle, will be required to provide a complete probe. In the meantime a clear observation that enantiomer PECD curves have a mirror-image relationship... 

The experimental work described in this chapter clearly demonstrates that chiral asymmetries in the forward-backward distribution of photoelectrons emitted from randomly oriented enantiomers when ionized with circularly polarized light can be spectacularly large (to borrow and apply a superlative from previous accounts of an unprecedented chiral asymmetry)—on the order of 20%. The theory discussed here, as implemented in two computational methods, is fully capable of predicting this and being applied to develop an understanding of a phenomenon that at times displays some counterintuitive properties. Doing so is very much an ongoing quest. 

Kcurentjes et al. (1996) have also reported the separation of racemic mixtures. Two liquids are made oppositely chiral by the addition of R- or S-enantiomers of a chiral selector, respectively. These liquids are miscible, but are kept separated by a non-miscible liquid contained in a porous membrane. These authors have used different types of hollow-fibre modules and optimization of shell-side flow distribution was carried out. The liquid membrane should be permeable to the enantiomers to be separated but non-permeable to the chiral selector molecules. Separation of racemic mixtures like norephedrine, ephedrine, phenyl glycine, salbutanol, etc. was attempted and both enantiomers of 99.3 to 99.8% purity were realized. 

In which R/S is the required product purity and aR and as are the distribution ratios of the R- and -enantiomers over the two chiral liquids, respectively (by definition aR = l/as). NTU is the number of transfer units required for the separation. From the data given in Table 5-1 it can be concluded that enantioselectivities typically are in the range between 1.05 and 1.20. According to Equation (4), the number... 

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