Polyacrylamide CSPs

Cross-linked, optically active polyacrylamides and polymefhacrylamides constitute another class of polymeric CSPs. These CSPs were introduced by Blaschke and coworkers about 30 years ago and their usefulness for preparative applications had already been demonstrated before the 1980s [46]. However, the gel structure of these cross-linked polymers prevents utilization at high pressure, and only moderate throughput could be obtained. Improvement in the mechanical performances of these CSPs was achieved by polymerization of the acrylic monomer on the surface of silica gel, yielding a grafted polymer [47, 48]. 

The preparative separations reported in the literature have been carried out using (S)-phenylalanine ethyl ester (a), (S)-l-cyclohexylethylamine (b) and menthyl amine (c) [49] as the chiral selector (Fig. 6.6). 

Both modes, normal and reversed, have been applied for preparative separations on the silica grafted polyacrylamide CSPs. The feasibility of achieving preparative separations on this last CSP has been demonstrated [48, 50, 51]. 

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The type of CSPs used have to fulfil the same requirements (resistance, loadabil-ity) as do classical chiral HPLC separations at preparative level [99], although different particle size silica supports are sometimes needed [10]. Again, to date the polysaccharide-derived CSPs have been the most studied in SMB systems, and a large number of racemic compounds have been successfully resolved in this way [95-98, 100-108]. Nevertheless, some applications can also be found with CSPs derived from polyacrylamides [11], Pirkle-type chiral selectors [10] and cyclodextrin derivatives [109]. A system to evaporate the collected fractions and to recover and recycle solvent is sometimes coupled to the SMB. In this context the application of the technique to gas can be advantageous in some cases because this part of the process can be omitted [109]. 

Other polyacrylamides and polymethacrylamides (4, 5)55 56 have been prepared and their chiral recognition abilities as CSPs have been evaluated. Chiral stationary phase 5 shows high recognition for several drugs. 

Blaschke et al. [54—56] synthesized polyacrylamide and polymethacrylamide containing chiral side chains. In order to make CSPs, these polymers were bonded to silica gel chemically [54-56]. The CSP obtained by /V-acrylol-(.S)-phenylalanine ethyl ester was commercialized by Merck Chemical Company by the trade name ChiraSpher. The racemic compounds resolved are those capable of forming hydrogen-bondings (i.e., amides, imides, carboxylic acids, and alcohols). It has been reported that nonpolar solvents like benzene and toluene individually or their mixtures were the best mobile phases. In addition to these CSPs, other amide CSPs were prepared and tested for the chiral resolution [57,58]. 

LI.2 Synthetic polymeric type CSPs. With the aim of mimicking nature and naturally occurring biopolymeric SOs like polysaccharides or proteins, researchers have developed several approaches for the preparation of new types of synthetic macromolec-ular SOs. These new polymeric SOs may be divided into (a) SOs synthesized from achiral monomers including helical polyacrylates and molecular imprint type CSPs and (b) SOs synthesized from chiral monomers including polyacrylamides and network polymers based on tartaric acid diamides. 

Such polyacrylamide type CSPs are best operated under normal-phase conditions (usually u-hexane with a polar modifier like alcohols, dioxane, THF, etc.). The spectrum of applicability includes a wide variety of drug substances with hydrogen donor-acceptor and aromatic groups. Other groups also prepared CSPs from chiral (meth)acrylamide monomers with various chiral amino components. An extensive review on this topic was published by Kinkel 47j. 

A CSP consists of a chiral selector, which either alone constitutes the stationary phase or which has been immobilised to a solid phase. The chiral selector is a low molecular weight compound or a polymer, either synthetic or natural. A broad range of CSPs has been developed. Examples of CSPs that have been used successfully include polysaccharides, such as cellulose and its derivatives [6] and cyclodex-trins [7], and proteins, e.g. bovine serum albumin, aj-acid glycoprotein, cellulase, trypsin and a-chymotrypsin [8]. Several different synthetic polymers have also proven to be useful CSPs, for example the Blaschke-type CSPs (polyacrylamides and polymethacrylamides) [9] and the Pirkle-type CSPs [10]. 

According to their chemical structures, CSPs can be divided into three different groups. A multitude of chiral stationary phases is derived from (modified) natural or synthetic polymers, e.g., the polysaccharides, proteins or polyacrylamides. A second type of selectors is based on large chiral ring systems, such as cyclo-dextrins, macTocycKc antibiotics, and crown ethers. The last group comprises moleailes of small and medium size, such as amino acids and their derivatives, alkaloids, and fuUy synthetic selectors. 

Once the problem of immobilization has been solved, polysaccharide-derived CSPs (Figure 54.4) are probably the best adapted materials because of their loadability and broad application domain. Also, polymeric CSPs (Figure 54.10), such as polyacrylamides 17-19 and polytartardia-mides 20,21 have an interesting high loadability. Nevertheless, on certain occasions, this property is sacrificed while gaining in stability. This is the case for brush-type stationary phases (Figure 54.8) in which chemical durability and... 

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