Enantiomers enantiomer association

All enantioselective separation techniques are based on submitting the enantiomeric mixture to be resolved to a chiral environment. This environment is usually created by the presence of a chiral selector able to interact with both enantiomers of the mixture, albeit with different affinities. These differences in the enantiomer-selector association will finally result in the separation that is sought. 

FIGURE 4.18 Comportment of enantiomers in the presence of another chiral molecule. Only one enantiomer reacts with an enzyme. Enantiomers associate differently with another chiral molecule. 

The numerator in equation (22-26) represents the processes occurring in the mobile phase, while the denominator represents the processes occurring in the stationary phase. Such a situation can be realized by combining a chiral stationary phase in a push-pull mode with a chiral mobile phase of opposite con-hguration, where two enantiomers of the chiral selector are involved, one for the chiral stationary phase and the other for the chiral mobile phase. The most selective chiral chromatographic system should be encountered when one enantiomer binds to the immobilized chiral selector in the stationary phase, whereas the other enantiomer predominantly associates with the chiral mobile-phase additive [158]. The above treatment is applicable to all applications regarding the use of chiral mobile phases. 

The GRIND descriptors are insensitive to the chirality of the structures. This has the undesirable side effect of providing exactly the same description for the two enantiomers associated with any chiral center. Diastereomers might, on the contrary, produce different correlograms, due to the presence of differences in the internal geometry. 

In subsequent work it was found that the carboxylic acid form of 25 and 27 could be solubilized in chloroform-rf by the addition of triethylamine. Addition of Eu(fod)3 caused the reverse behavior from what had been observed with the ester forms of the CSA, as the enantiomer that associated more favorably with the CSA has the larger lanthanide-induced shifts. This observation was explained by assuming that the carboxylate form of the CSA is bound to the lanthanide ion to create the species [Ln(fod)3CSA] . The substrate then associated with the CSA in its lanthanide-bound form ° . ... 

Studies with the male antifertility agents 3-chloropropane-l,2-diol and 3-amino-l-chloropropane-2-ol have indicated that the antifertility activity in rat is due to the 5-enantiomers, whereas the i -enantiomers are associated with nephrotoxicity [160,161]. Metabolic studies indicated that a common metabolite was the causative agent, which was postulated to be (i )-3-chlorolactate. Administration of the enantiomers of 3-chlorolactate to rats resulted in elevated urinary excretion of oxalate, presumably formed via oxidation of the intermediate 3-chloropyruvate, a known inhibitor of renal... 

In contrast to the Chinese, the black population responds less to the same dose of propranolol, than the white population. Sowinski et al. [45] showed that both the systemic and oral clearances of both enantiomers of propranolol are substantially higher in blacks than in whites. This difference was mostly attributed to a higher intrinsic clearance of propranolol enantiomers, in association with a slightly lower (9%) hepatic blood flow in blacks. The limited available information on the effects of ethnicity on the pharmacokinetics of propranolol suggest that the racial differences in the effects of this drug cannot be attributed to the stereoselectivity in the pharmacokinetics of the drug. Rather, these differences may be due to pharmacodynamic differences among ethnic populations. 

In terpene products, terpenes exist as two enantiomers in different mixture ratios. Enantiomers are associated with characteristic odour (e.g. d-limonene in orange-oil). Odors ofterpenes are essential criteria in the classification ofterpenes. Some terpenes can be smelt in extremely low concentrations. ... 

Most of the CSs used in the aqueous phase of the CCC solvent system had been previously used in capillary electrophoresis (CE). Like CCC, CE does not involve a solid support and the CS-enantiomer association takes place in an aqueous or strongly polar environment. The information obtained in CE separations has been useful to further develop CCC methods for certain compounds and to elucidate the recognition mechanism of the selector. 

The Cahn-Ingold-Prelog (CIP) rules stand as the official way to specify chirahty of molecular structures [35, 36] (see also Section 2.8), but can we measure the chirality of a chiral molecule. Can one say that one structure is more chiral than another. These questions are associated in a chemist s mind with some of the experimentally observed properties of chiral compounds. For example, the racemic mixture of one pail of specific enantiomers may be more clearly separated in a given chiral chromatographic system than the racemic mixture of another compound. Or, the difference in pharmacological properties for a particular pair of enantiomers may be greater than for another pair. Or, one chiral compound may rotate the plane of polarized light more than another. Several theoretical quantitative measures of chirality have been developed and have been reviewed elsewhere [37-40]. 

A chiral axis is present in chiral biaryl derivatives. When bulky groups are located at the ortho positions of each aromatic ring in biphenyl, free rotation about the single bond connecting the two rings is inhibited because of torsional strain associated with twisting rotation about the central single bond. Interconversion of enantiomers is prevented (see Fig. 1.16). 

Chiral separations are concerned with separating molecules that can exist as nonsupetimposable mirror images. Examples of these types of molecules, called enantiomers or optical isomers are illustrated in Figure 1. Although chirahty is often associated with compounds containing a tetrahedral carbon with four different substituents, other atoms, such as phosphoms or sulfur, may also be chiral. In addition, molecules containing a center of asymmetry, such as hexahehcene, tetrasubstituted adamantanes, and substituted aHenes or molecules with hindered rotation, such as some 2,2 disubstituted binaphthyls, may also be chiral. Compounds exhibiting a center of asymmetry are called atropisomers. An extensive review of stereochemistry may be found under Pharmaceuticals, Chiral. 

An alternative model has been proposed in which the chiral mobile-phase additive is thought to modify the conventional, achiral stationary phase in situ thus, dynamically generating a chiral stationary phase. In this case, the enantioseparation is governed by the differences in the association between the enantiomers and the chiral selector in the stationary phase. 

Care should be exercised when attempting to interpret in vivo pharmacological data in terms of specific chemical—biological interactions for a series of asymmetric compounds, particularly when this interaction is the only parameter considered in the analysis (10). It is important to recognize that the observed difference in activity between optical antipodes is not simply a result of the association of the compound with an enzyme or receptor target. Enantiomers differ in absorption rates across membranes, especially where active transport mechanisms are involved (11). They bind with different affinities to plasma proteins (12) and undergo alternative metaboHc and detoxification processes (13). This ultimately leads to one enantiomer being more available to produce a therapeutic effect. 

Cromakalim (137) is a potassium channel activator commonly used as an antihypertensive agent (107). The rationale for the design of cromakalim is based on P-blockers such as propranolol (115) and atenolol (123). Conformational restriction of the propanolamine side chain as observed in the cromakalim chroman nucleus provides compounds with desired antihypertensive activity free of the side effects commonly associated with P-blockers. Enantiomerically pure cromakalim is produced by resolution of the diastereomeric (T)-a-meth5lben2ylcarbamate derivatives. X-ray crystallographic analysis of this diastereomer provides the absolute stereochemistry of cromakalim. Biological activity resides primarily in the (—)-(33, 4R)-enantiomer [94535-50-9] (137) (108). In spontaneously hypertensive rats, the (—)-(33, 4R)-enantiomer, at dosages of 0.3 mg/kg, lowers the systoHc pressure 47%, whereas the (+)-(3R,43)-enantiomer only decreases the systoHc pressure by 14% at a dose of 3.0 mg/kg. 

Next, examine the lowest-unoccupied molecular orbital (LUMO) for the cation. The components of the LUMO (its lobes ) identify locations where the cation might bond to a water molecule. How many lobes are associated with C 7 For each lobe, draw the alcohol that will be produced (show stereochemistry). How many alcohol enantiomers will form If more than one is expected, decide which wiU form more rapidly based on the relative sizes of the lobes. 

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