Use for chiral separation

Preparative chromatography has been used for chiral separations for years, but examples of multi-kg separations (and hence larger ones) were rare until recently. The development of SMB techniques (both hardware and simulation software) has made major breakthroughs in this field. The ability of SMB as a development tool has allowed the pharmaceutical manufacturer to obtain kilo grams quantities of enantiopure drug substances as well benefit from the economics of large-scale production. 

Transition metal coupling polymerization has also been used to synthesize optically active polymers with stable main-chain chirality such as polymers 33, 34, 35, and 36 by using optically active monomers.29-31 These polymers are useful for chiral separation and asymmetric catalysis. For example, polymers 33 and 34 have been used as polymeric chiral catalysts for asymmetric catalysis. Due... 

Proteins have also been successfully used for chiral separations in CE. One of the characteristics of proteins is their isoprotic point, pi. The protein will mainly be charged positively if pHpI. Therefore, the pH of the BGE is a very important parameter for the optimization of the separations. As with charged-CD derivatives, it is possible to separate both charged and uncharged chiral species with... 

K Kano, K Minami, K Horiguchi, T Ishihana, M Kodera. Ability of noncyclic oligosccharides to form molecular complexes and its use for chiral separation by capillary zone electrophoresis. J Chromatogr A 694 307-313, 1995. 

The mobile phases used for chiral separations on CSPs differ depending on the type of column and range from normal-phase systems containing high amounts of nonpolar solvent (e.g., hexane) to... 

Finally, libraries aimed to chiral resolution of racemates will be covered here in particular, the use of chiral stationary phases (CSPs) has recently been reported for the identification of materials to be used for chiral separation of racemates by HPLC. The group of Frechet reported the selection of two macroporous poly methacrylate-supported 4-aryl-1,4-dihydropyrimidines (DHPs) as CSPs for the separation of amino acid, anti-inflammatory drugs, and DHP racemates from an 140-member discrete DHP library (214,215) as well as a deconvolutive approach for the identification of the best selector phase from a 36-member pool library of macroporous polymethacrylate-grafted amino acid anilides (216,217). Welch and co-workers (218,219) reported the selection of the best CSP for the separation of a racemic amino acid amide from a 50-member discrete dipeptide iV-3,5-dinitrobenzoyl amide hbrary and the follow-up, focused 71-member library (220). Wang and Li (221) reported the synthesis and the Circular Dichroism- (CD) based screening of a 16-member library of CSPs for the HPLC resolution of a leucine ester. Welch et al. recentiy reviewed the field of combinatorial libraries for the discovery of novel CSPs (222). Dyer et al. (223) reported an automated synthetic and screening procedure based on Differential Scanning Calorimetry (DSC) for the selection of chiral diastereomeric salts to resolve racemic mixtures by crystallization. Clark Still rejxrrted another example which is discussed in detail in Section 9.5.4. 

Direct separation of enantiomers may be performed on cellulose the use of microcrystalline cellulose is especially widely used. An other stationary phase is the microcrystalline triacetylcellulose, which is stable when using alcoholic and phenolic mobile phases however, it is unstable when glacial acetic acid and ketones are used. Optically active poly(meth)acrylate may be bound to the silica gel. and these stationary phases are widely used under the names of CHIRALPLATE or CHIR . Beta cyclodextrin can also be covalently bound to silica, and also reversed-phase plates may be used for chiral separation when the mobile phase consists of beta-cyclodextrin. 

Chiral columns are packed with stereo-specific sorbents for the separation of stereoisomers in the sample.27 Many chiral columns operate in hydrophilic interaction mode (e.g., Pirkle-type) whereas others are used in reversed-phase mode (proteins, macrocyclic antibiotics, polysaccharides, etc.). The use of these columns is critical in the development of chiral drugs. Most chiral columns are quite expensive and many older chiral columns have low efficiencies and limited lifetimes. Examples of chiral separations are shown in Chapter 6. Alternately, convention columns can also be used for chiral separations using a chiral selector in the mobile phase.27... 

There are a large number of possible derivatives that can be prepared and almost every one will probably possess some unique property that will enhance the separation of certain enantiomeric pairs. The examples given in figure 8.18 are those selected by the chiral stationary phase manufacturer ASTEC as those more broadly useful for chiral separations. Other stationary phase manufacturers may well select other types of derivatives for optimal use. 

Kempe, M. Mosbach, K. Molecular imprinting used for chiral separations. J Chromatogr. A 1995, 694, 3-13. 

Analogous to liquid chromatography, CCC can be used for chiral separation by dissolving the chiral selector in the liquid stationary phase. The method has some advantages over liquid chromatography in that the amount of the chiral selector in the column can be much greater (since it is dissolved in the stationary phase) and the same column may be used for various kinds of chiral separations simply by changing the chiral selector in the stationary phase. 

Partition chromatographic mechanisms operate on cellulose thin layers even if adsorption effects cannot be excluded (for separation of substance classes, see Table 2). Celluloses are naturally occurring chiral adsorbents and can be used for chiral separation of optically active amino acids and dipeptides. 

Alkaloids have been used for chiral separations from a long time ago. In 1853, Pasteur achieved the resolution of isomers of tartaric acid by precipitation of their salts with cinchona alkaloids (Figure 18), which are still perhaps the most popular chiral building blocks for preparation of chiral catalysts and reactants. However, the receptor properties of these compounds and some of their simple derivatives in solution were studied only recently. 

These materials are composed of small chiral imits that are regularly repeated along the polymeric chain, hence the density of active sites capable of chiral recognition is very high, and this results in a high loading capacity. MicrocrystaUine cellulose triacetate and cellulose tribenzoate have, in some instances, been used for chiral separations as neat, non-coated particles. However, they are inconvenient to pack, are of limited chemical stability, and show low efficiency. 

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