Cyclodextrin-based CSPs

Macaudiere et al. first reported the enantiomeric separation of racemic phosphine oxides and amides on native cyclodextrin-based CSPs under subcritical conditions [53]. The separations obtained were indicative of inclusion complexation. When the CO,-methanol eluent used in SFC was replaced with hexane-ethanol in LC, reduced selectivity was observed. The authors proposed that the smaller size of the CO, molecule made it less likely than hexane to compete with the analyte for the cyclodextrin cavity. 

An understanding of the recognition of chirality at a molecular level has become of interest in many fields of chemistry and biology. In the past decade, many attempts to clarify the mechanism of chiral recognition on CSPs for liquid chromatography have been made by means of chromatography, NMR spectroscopy,199 202 X-ray analysis, and computational methods.203 - 206 The successful studies have been mostly carried out for the small-molecule CSPs, especially cyclodextrin-based CSPs and Pirkle-type (brush-type) CSPs. In contrast, only a few mechanistic studies on chiral discrimination at the molecular... 

The PO mode is a specific elution condition in HPLC enantiomer separation, which has received remarkable popularity especially for macrocyclic antibiotics CSPs and cyclodextrin-based CSPs. It is also applicable and often preferred over RP and NP modes for the separation of chiral acids on the cinchonan carbamate-type CSPs. The beneficial characteristics of the PO mode may arise from (i) the offset of nonspecific hydrophobic interactions, (ii) the faster elution speed, (iii) sometimes enhanced enan-tioselectivities, (iv) favorable peak shapes due to improved diffusive mass transfer in the intraparticulate pores, and last but not least, (v) less stress to the column, which may extend the column lifetime. Hence, it is rational to start separation attempts with such elution conditions. Typical eluents are composed of methanol, acetonitrile (ACN), or methanol-acetonitrile mixtures and to account for the ion-exchange retention mechanism the addition of a competitor acid that acts also as counterion (e.g., 0.5-2% glacial acetic acid or 0.1% formic acid) is required. A good choice for initial tests turned out to be a mobile phase being composed of methanol-glacial acetic acid-ammonium acetate (98 2 0.5 v/v/w). 

Another study focused on aryl-substituted P-lactams, using the same set of teicoplanin-based CSPs and variable-temperature conditions [99]. Tricyclic P-lactams were investigated by the same group of authors, together with some bicyclic P-amino acids, on five different commercially available glycopeptides CSPs, namely ristocetin A, TE, TAG, vancomycin, and VAG, and on a new dimethylphenyl carbamate-derivatized 5-cyclodextrin-based CSP. The chromatographic results, achieved with different methods, were compared in systematic examinations [170]. 

TABLE 5 Examples of Separations Obtained on Cyclodextrin-based CSP... 

Figure 3.5 Measurement of the chiral purity of commercially available Jacobson s catalyst using a cyclodextrin-based CSP. (a) Lower trace / ,/ -enantiomer product upper trace / ,/ -enantiomer product artificially enriched with S -enantiomer and (b) lower trace S. S -enantiomer product upper trace S. S -enantiomer product artificially enriched with / ,/ -enantiomer. (Conditions CYCLOBOND 1 2000RSP 25 cm X 0.46 cm i.d. mobile phase acetonitrile triethylamine glacial acetic acid [1000 0.5 2.5, v/v] flow rate 1 ml/min temperature ambient detection UV at 240 nm sample preparation 1 mg/ml in acetonitrile injection volume 10 fxl). Reprinted from [19], copyright 1998, with permission of Wiley-Liss, Inc., a subsidiary of John Wiley and Sons, Inc.

FIGURE 3 The chemical structures of some cyclodextrin-based CSPs. 

Cyclodextrin-based CSPs are among the most popular materials used for the chiral resolution of racemic compounds. These CSPs have a wide range of applications because they can be used successfully in all three mobile phase modes normal, reversed, and polar organic. There are numerous examples of chiral separations on CDs and CSPs based on their derivatives. Some of the important chiral separations are discussed herein. 

In 1978, Harada et al. [17] used polymerized CD with gel support for the chiral resolution of mandelic acid and its derivatives. Later Zsadon et al. [18-21] used cyclodextrin-based CSPs for the chiral resolution of indole alkaloids, with aqueous buffers as the mobile phases. Today CD-based CSPs have a good reputation. In separate studies, Fujimura [22] and Kawaguchi [23] and their colleagues resolved the enantiomers of aromatic compounds in the reversed-phase mode. Armstrong et al. [29,30,33,34,41,44 46,48,54-63] carried out extensive and remarkable work on the chiral resolution of various racemic compounds using CD-based CSPs. 

TABLE 3 Enantiomeric Resolution of Some Racemic Compounds on Cyclodextrin-Based CSPs... 

Cyclodextrin-based CSPs have several modes of operation they can be used either in the (i) normal-phase mode, (ii) polar-organic phase mode, or (iii) reversed-phase mode. 

Enantioseparations in SEC have been reported for several CSPs. including native and derivatized cyclodextrin-based CSPs [427-432. Pirkle-concept CSPs [77,336-338,347,348,363,365,433,434], polysaccharide type CSPs [137.435-438], macrocyclic antibiotic type CSPs [436], and others. 

Cyclodextrin-based CSPs have been used for the chiral resolution of some pollutants. Schurig et al. [9, 10], Konig et al. [11] and Hardt etal.[ 2 used CD-based CSPs for the chiral separation of PCBs. Mannscreck etal. [13] resolved PCBs on triacetylcellulose CSP. Ludwig etal. [14] used the Chiral AGP column for the enantiomeric analysis of 2-(2,4-dichlorophenoxy)propionic acid (dichlorprop) and its degradation products in a marine microbial community. The authors used a... 

Abstract Development of chiral separations has been essential to the drug discovery and development process. The solubility requirements for a number of methods and/or the mobile phase requirements for application of certain detection systems have opened up many opportunities for cyclodextrin-based CSPs for liquid... 

A combination of acidic and basic additives is used for the separation of primary amines in the polar organic mode. Table 1 lists the chromatographic data obtained using different combinations of acidic and basic additives. The optimized additive composition is 0.3/0.2 (% v/v) acetic acid/triethylamine in pure methanol, which happens to be the recommended buffer for the polar organic mobile phase separation on cyclodextrin-based CSPs [40,41]. 

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