Unichiral

Discrimination between the enantiomers of a racemic mixture is a complex task in analytical sciences. Because enantiomers differ only in their structural orientation, and not in their physico-chemical properties, separation can only be achieved within an environment which is unichiral. Unichiral means that a counterpart of the race-mate to be separated consists of a pure enantiomeric form, or shows at least enrichment in one isomeric form. Discrimination or separation can be performed by a wide variety of adsorption techniques, e.g. chromatography in different modes and electrophoresis. As explained above, the enantioseparation of a racemate requires a non-racemic counterpart, and this can be presented in three different ways ... 

As a unichiral template which is used as a stationary phase itself, or which is bonded to a solid support (silica particles or fused silica capillaries). 

As a unichiral additive which is mixed with the racemate of interest to form non-covalent diastereomeric complexes which can be distinguished by achiral techniques. 

As a unichiral group which reacts with the racemate to form diastereomeric molecules which can be separated by achiral adsorption processes. 

The educt, a racemate, is derivatized before the separation with an agent which might be achiral or unichiral (Fig. 7-1), and afterwards is passed through a chromatographic system which is equipped with a stationary phase. This stationary phase may also be achiral or unichiral in nature. 

Fig. 7-2. Type I Covalent derivatization with a unichiral reagent.

Type I Covalent Derivatization with a Unichiral Derivatizing Agent... 

This strategy is the one most commonly used for the analytical determination of ena-tiopurity. A given racemate is reacted with a unichiral derivatizing agent, and the resulting pair of diastereomers is separated on an achiral stationary phase, in most of the cases on a reversed-phase type (Fig. 7-2). 

Most of the reactions applied to amines can also be transferred to alcohols (Eig. 7-5). One large group of chiral alcohols are the (i-adrenoreceptor blockers, for which a variety of derivatization agents was developed. One highly versatile reagent for the separation of (i-blockers is A-[(2-isothiocyanato)cyclohexyl]3,5-dinitrobenzoyl-amide (DDITC) [11]. Alternatively, unichiral drugs such as (3-blockers or (S)-naproxen [12] may be used in a reciprocal approach to derivatize racemic amine compounds. 

While amino compounds can be derivatized with acids and acid chlorides, it is possible to separate racemic acids (vice versa) with unichiral amino compounds... 

Fig. 7-6). Two unichiral amides which have been known capable of this reaction are 1-phenylethylamine [15] and l-(l-naphthyl)ethylamine [16]. Marfey s reagent [N-a-(2,4-dinitro-5-fluorophenyl)-L-alaninamide] was introduced as a reagent to deriva-tize amino acids with cyclopentane, tetrahydroisoquinoline or tetraline structures [17]. Simple chiral alcohols such as 2-octanol can also be used to derivatize acids such as 2-chloro-3-phenylmethoxypropionic acid [18]. 

Separation of Amino Acid Enantiomers after Derivatization with Or/ho-Phthaldialdehyde (OPA) and a Unichiral Tliiol Compound... 

The mixture of free amino acids is reacted with OPA (Fig. 7-8) and a thiol compound. When an achiral thiol compound is used, a racemic isoindole derivative results. These derivatives from different amino acids can be used to enhance the sensitivity of fluorescence detection. Figure 7-9 shows the separation of 15 amino acids after derivatization with OPA and mercaptothiol the racemic amino acids may be separated on a reversed-phase column. If the thiol compound is unichiral, the amino acid enantiomers may be separated as the resultant diastereomeric isoindole compound in the same system. Figure 7-10 shows the separation of the same set of amino acids after derivatization with the unichiral thiol compound Wisobutyryl-L-cysteine (IBLC). 

Ferroelectric Macroscopic Racemate from Unichiral Mesogen... 

Along with the prediction and discovery of a macroscopic dipole in the SmC phase and the invention of ferroelectric liquid crystals in the SSFLC system, the discovery of antiferroelectric liquid crystals stands as a key milestone in chiral smectic LC science. Antiferroelectric switching (see below) was first reported for unichiral 4-[(l-methylheptyloxy)carbonyl]phenyl-4/-octyloxy-4-biphenyl carboxylate [MHPOBC, (3)],16 with structure and phase sequence... 

While the existence of the anticlinic minimum in conventional SmC materials has been suggested by experiments with DOBAMBC,17 by far the majority of tilted smectics only exhibit the synclinic structure of the SmC or SmC under normal conditions. When the mesogenic compound is unichiral (i.e., enantiomerically pure) or enantiomerically enriched, a macroscopic polarization with the same orientation in each layer is produced, as discussed above. In the SmCA phase of MHPOBC, however, the anticlinic structure is the global minimum structure, as shown at the bottom of Figure 8.9. In this case, given that the chirality of the molecules is fixed, the polarization must alternate... 

Figure 8.36 Structure and phase sequence of unichiral bent-cote mesogen (S,S)-KYOBOW is given.

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