Other CSPs

Although about 20 polysaccharide-based CSPs have been commercialized and much work on enantioresolution has been carried out on these phases, it remains very difficult to predict the best CSP for the chiral resolution of a particular compound. It has been observed that most of the resolved racemic compounds contain aromatic rings or groups such as carbonyl, sulfinyl, nitro, amino, and benzoyl. However, some reports have been published on the chiral resolution of nonaromatic racemates on polysaccharide CSPs [61]. As in the case of other CSPs, polysaccharide-based CSPs do not require a certain combination of functional groups. However, only one group can afford a satisfactory separation. Presumably some chiral space (e.g., a concavity or ravine existing on a polysaccharide derivative) could enable such a separation [62],... 

As in the case of other CSPs, the chiral resolution is effected by the structure of the solute. The chiral resolution of amino acids may be considered as the best example for this study. The work of Fukushima et al. [20] (i.e., the chiral resolution of amino acids) indicated the different behavior of the chiral resolution on (i8 )-/V-3,5-dinitrobcnzoyl-l -naphthylglycine CSP. Altomare etal. [142] studied the chiral resolution of a series of 3-phenyl-4-(l-adamantyl)-5-A-phcnyl-A2-1,2,4-oxadiazolines on A,Af,-(3,5-dinitrobenzoyl)-l(7 ),2( )-diaminocyclohcxanc CSP. The effect of the influence of aromatic ring substituents on enantioselectivity was studied by traditional linear free-energy-related equations and comparative molecular field analysis methods. The authors reported that an increase in retention was favored by the re-basicity and the hydrophilicity of the solutes. In... 

As in case of other CSPs, the chiral resolution is also effected on protein phases by the structures of the racemic compounds. Allenmark and co-workers [23] resolved several sulfoxides on the BSA-based CSP. These sulfoxides contain different structures with various groups such as methyl, methoxy, and acetate. We analyzed the results of this study and, generally, it was found that the separation factor decreased by introducing larger groups in the sulfoxides. This behavior may be the result of a steric effect the author did not consider in the discussion... 

As in the case of other CSPs, the chiral resolution on these CSPs is also affected by a change in the structures of the racemic compounds. The different selectiv-ities of amino acids on these CSPs may be considerd as the best example. The effect of structures of the racemates on the chiral resolution may be understood from the work carried out by Shieh et al. [71]. The authors studied the chiral resolution of amino acids as their Schiff s bases. These racemates differ slightly in their structure and the substituent, such as alkyl groups, hence showed different values of enantioselectivities. The values of retention and separation factors decreased by introducing bulky groups in the racemates. Aboul-Enein and Ali [70] observed the lower values of retention factors of miconazole in comparison to econazole and sulconazole. The authors explained this sort of behavior on the basis of the steric effect exerted by the extra chlorine atom in miconazole molecule. 

The most popular and commonly used chiral stationary phases (CSPs) are polysaccharides, cyclodextrins, macrocyclic glycopeptide antibiotics, Pirkle types, proteins, ligand exchangers, and crown ether based. The art of the chiral resolution on these CSPs has been discussed in detail in Chapters 2-8, respectively. Apart from these CSPs, the chiral resolutions of some racemic compounds have also been reported on other CSPs containing different chiral molecules and polymers. These other types of CSP are based on the use of chiral molecules such as alkaloids, amides, amines, acids, and synthetic polymers. These CSPs have proved to be very useful for the chiral resolutions due to some specific requirements. Moreover, the chiral resolution can be predicted on the CSPs obtained by the molecular imprinted techniques. The chiral resolution on these miscellaneous CSPs using liquid chromatography is discussed in this chapter. 

In the phasmid Eurycantha calcarata, a CSP has been isolated from the cellular layer underlying the cuticle (Marchese el ah, 2000). In the cockroach Periplaneta americana, the CSP plO is expressed in legs and antennae (Nomura et al., 1992 Kitabayashi et al., 1998 Picimbon et al., 2001), and other CSPs have been detected in tissues including legs, brain and cerci (Picimbon and Leal, 1999 unpublished). 

Chromatographic enantioseparation of chiral xenobiotics and their metabolites is a versatile tool for process studies in marine and terrestrial ecosystems [235]. In 1994, three papers focused on the enantioselective determination of toxaphene components [120,236,237]. Buser and Muller found that technical toxaphene mixtures are not necessarily racemic [237]. This observation was supported after isolation of non-racemic B7-1453 from the product Melipax which had an excess of ca. 25% of the dextrorotary enantiomer [27, 238]. The enantioselective separation of toxaphene components is almost restricted to chiral stationary phases (CSPs) based on randomly derivatized ferf-butyldimethyl-silylated /1-cyclodextrin (commercially available from BGB Analytik, Adliswil, Switzerland). So far, only a few toxaphene components were enantioseparated on other CSPs [239, 240]. Some of these CSPs are not well defined as well, and for this reason a test mixture called CHIROTEST X was suggested for initial column testing [241],... 

One of the advantages of MIP CSPs, in comparison with other CSPs, is that the material is designed directly for a specific molecule or class of molecules and that the elution order of the enantiomers is therefore known. 

Type V CSPs are protein phases. Because of the well established chemo- and stereospecificity of enzymes, a large number of experimentalists have adapted proteins in one form or another as stationary phases for chiral separations. The intermolecular forces responsible for analyte binding to these biopolymers are the same as for most other CSPs but the size and complexity of proteins makes them difficult to study computationally. One would think that with approximately 400 entries in the Brookhaven Protein Databank to select from, separation scientists would have used one of these proteins as a chiral selector and then use those atomic coordinates to carry out molecular modeling studies. Only one example has appeared in the literature where information from the PDB has been used to serve as a beginning point for molecular modeling of a protein CSP. In all other examples the CSP is viewed as having an unknown structure and Quantitative Structure-Enantioselective Retention Relationships (QSERRs) have been carried out. 

Some rare examples of separation on other CSPs have been reported Sumipax OA 2000 (88JCS(P1)313), home made tyrosine phase (92CHI36) Ceramospher Ru-(I) (96H415), Chiralpak OP(+) (08111335) Chirex 3018 (05CHI559), and ULMO (10JC(A1217)1017). 

Using 20 y of 1-24 ACTH per animal the shortest delay in the effect was obtained after injection into the third ventrl ole Inasmuch as the symptomatology evoked using this route was more pronounced than after injection into the lateral ven triole or into the cistema magna (table 2), these results se n to suggest that the 8ite(s) of action of ACTH are closer to the third ventricle than to other CSP sites. 

The helical polytriphenylmethyl methacrylate was the first synthetic chiral polymer able to separate a very limited number of enantiomers [28]. Recently a fully synthetic chiral stationary phase based on polymerized diacryloyl derivative of fra s-l,2-diaminocyclohexane [either (R, R) or (S, S)] bonded to silica gel in the form of a very thin layer was proposed as a new LC CSP [29]. This CSP could not resolve many enantiomeric pairs. However, when it could resolve a racemate, it was shown that the amount that could be loaded was much larger than that on most other CSPs. It means that the number of active sites is large. Hydrogen bonds were found to be pivotal in the chiral recognition mechanism of this CSP. The enan-tioselectivity was adjusted by the methanol content in the organic mobile phase. Polysodium A-undecanoyl-L-leucyl-leucinate (poly-SULL) and —L-leucyl-valinate... 

It was found that polar enantiomers could be separated with CDs in nonaqueous polar medium (e.g., 99% acetonitrile with 1% methanol). In this situation, inclusion complexation is unlikely, the solvent molecules occupying the CD cavity. The chiral mechanism involves H-bonds with the spatially oriented hydroxyl groups at the rims of the cavity and other interactions with the numerous asymmetric carbons of the glucopyranose units [36]. Polar organic mobile phases were tried with other CSPs and greatly extended their usefulness enhancing the role of H-bond interactions that were screened by water molecules. 

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