Chiral molecules enantioseparation

For these reasons large chiral molecules (SAs) which often possess more than one deriva-tizable functional group will most likely be problematic in the course of developing an indirect enantioseparation method. 

The heart of any enantioseparation by liquid chromatography is a chiral column packed with a CSP or rarely a chiral selector immobilized on the wall of a capillary. A CSP consists of a chiral selector and an inert carrier. Both constituents are equally important for the separation performance. The chromatographic literature reports several himdreds of chiral compoimds applied as chiral LC selectors. A more or less complete overview of all materials applied as chiral selectors is impossible within the framework of this short chapter. In principle, any chiral compound possessing the ability to interact noncovalently with chiral molecules has the potential to be used as chiral selector in liquid chromatography. A chiral selector has to meet a set of characteristics that depend on the goal of the separation as well as the mode and technique used. The advantages and bottlenecks of the major classes of commercially available CSPs are summarized in Table 4.1. 

Beautiful models of chiral molecule-selector association are particularly useful in crystallography and GC. In LC, they may well explain a particular enantioseparation but often have no predictive ability because, so far, models ignored critical solvent effects in a particular interaction. 

It was found that the CIL, (/ )-A/,A/,N-trimethyl-2-aminobutanol-bis (trifluo-romethanesulfonyl)imide (5), was a good chiral selector that can be used in HPLC for enantioseparation of compounds such as alcohol, amine, and amino acids. The presence of this CIL in the mobile phase led to the enantioseparation of 2,2 -diamino-l,r-binaphthalene (Fig. 2B) [76]. Clearly, these limited studies using CILs in HPLC suggest that more CILs with multiple functional groups need to be explored for enantioseparation of various chiral molecules in HPLC. 

As mentioned, a chiral environment is required to induce differences between enantiomers. In chromatography, a chiral molecule, the so-called chiral selector (CS), is responsible for producing this environment. The mechanism of enantioseparation involves the formation of transient diastereomeric adsorbates between CS and enantiomers, which are based on weak noncovalent interactions. Differences in stability for the two adsorbates CS/enantiomer determine separation ... 

As discussed earlier, the concepts of chiral chromatography can be divided into two groups, the indirect and the direct mode. The indirect technique is based on the formation of covalently bonded diastereomers using an optically pure chiral derivatizing agent (CDA) and reacting it with the pair of enantiomers of the chiral analyte. The method of direct enantioseparation relies on the formation of reversible quasi diastereomeric transient molecule associates between the chiral selector, e.g., i /t)-SO, and the enantiomers of the chiral selectands, [R,S)-SAs [(Ry SA + (S)-SA] (Scheme 1). 

In addition to the classification of liquid chromatographic enantioseparation methods by technical description, these methods could further be classified according to the chemical structure of the diverse CSPs. The chiral selector moiety varies from large molecules, based on natural or synthetic polymers in which the chirality may be based on chiral subunits (monomers) or intrinsically on the total structure (e.g., helicity or chiral cavity), to low molecular weight molecules which are irreversibly and/or covalently bound to a rigid hard matrix, most often silica gel. 

In contrast to the various CSPs mentioned so far, but still based on covalently or at least very strongly adsorbed chiral selectors (from macromolecules to small molecules) to, usually, a silica surface, the principle of dynamically coating an achiral premodified silica to CSPs via chiral mobile phase additives (CMPA) has successfully been adapted for enantioseparation. The so-called reverse phase LC systems have predominantly been used, however, ion-pairing methods using nonaqueous mobile phases are also possible. 

For a quite long period of time, chiral ligand-exchange chromatography (CLEC) has been the standard method for the enantioseparation of free amino acids. Meanwhile, other methods became available for these target molecules, such as teicoplanin or chiral crown-ether-based CSPs. However, for the enantioseparation of aliphatic a-hydroxy carboxylic acids, it is still one of the most efficient methods. 

The functions of bioniolecules, bioactive molecules, ferroelectronic crystalline liquids, organic nonlinear optical molecules and so on often arise from their chirality. This means that the development of methods for obtaining enantiopure compounds is very important. Many methods have been reported for obtaining enantiopure compounds and these can be roughly classified into two categories, enantioseparation and asymmetric synthesis. Each category is further classified into physical, chemical, and biological methods. 

CyDs offer several advantages as chiral selectors for CE. The most important is that these macrocydic molecules possess a quite universal chiral recognition ability for many different dasses of organic compounds. In addition, CyDs are water soluble, transparent in the UV range, relatively inexpensive, and nontoxic. All of these contribute significantly to the status of CyDs as one of the most useful chiral selectors in CE. Free hydroxyl groups on the outer rim of CyDs offers various derivatiza-tion possibilities for introduction of nonionic and ionic groups into the structure of CyDs. Several CyD derivatives developed to be used in enantioseparations are presented in Chapter 2. 

Owing to some unique properties, cyclodextrins have been successfidly established as very useful chiral selectors in all instrumental analytical enantioseparation techniques. Further studies are required for a better understanding of the fine mechanisms of enantioselective recognition of these wonderful macrocydic molecules as well as for evaluation of their potential for preparative scale enantioseparations. 

Separation of enantiomers in CE significantly differs from true electrophoretic separations that are based on the difference in charge-to-mass (size) ratio between the analyte molecules. These peculiarities need to be considered when looking at the differences between enantioseparations with uncharged and charged chiral selectors... 

The use of a high-molecular-mass surfactant (HMMS) or polymerized surfactant has been recently investigated as a pseudo-stationary phase in MEKC. Because a HMMS forms a micelle with one molecule, enhanced stability and rigidity of the micelle can be obtained. Also, it is expected that the micellar size is controlled easier than with a conventional low-molecular-mass surfactant (EMMS). The first report on enantiomer separation by MEKC using a chiral HMMS appeared in 1994, where poly(sodium N-undecylenyl-L-valinate) [poly(L-SUV)] was used as a chiral micelle and binaphthol and laudano-sine were enantioseparated. The optical resolution of 3,5-dinitrobenzoylated amino acid isopropyl esters by MEKC with poly(sodium (lO-undecenoyl)-L-valinate) as well as with SDVal, SDAla, and SDThr was also reported. 

Bile salts are chiral rigid molecules. They serve as important building blocks in the synthesis of both cyclic and acyclic hosts." " Natural bile acids are employed for enantioseparation of racemates of various classes of organic compounds by enantioselective inclusion complex-ation in the solid state." " " Crystals of bile acids contain... 

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