Pirkle-CSPs

Pirkle CSPs have been used for LC separations of the enantiomers of alcohols, sulfoxides, bi-(3-naphthols, (3-hydroxysulfides, heterocycles such as hydantoins, succinimides, and agents related to propranolol. These phases have also been used in SFC for the separation of phosphine oxide enantiomers.40... 

LC on Pirkle CSP Direct method Reproducibility problems around 0.5%... 

Figure 14 shows the enantiomer separation of trans-stilbene oxide (2) (Fig. 13) on the Pirkle CSP Whelk-0 1. The two enantiomers induce opposite rotations of plane-polarized light the achiral meso form of trans-stilbene oxide elutes between the two enantiomers and shows no signal under polarimetiric detection. 

If a number of chiral recognition models have been proposed today, early models of the chiral recognition mechanism in chiral HPLC derive from the evolution of the first Pirkle CSP based on the use of a chiral solvating agent [22] followed by spectroscopic investigations [23]. 

With regard to the resolution of enantiomers, some applications can be found with modified silica gel supports. Thus, a Pirkle-type CSP was used for the separation of 200 mg of a racemic benzodiazepinone [75]. Also tris-(3,5-dimethylphenyl)carba-mate of cellulose coated on silica [91, 92] was applied successfully to the resolution of the enantiomers of 2-phenoxypropionic acid and to oxprenolol, alprenolol, propranolol among other basic drugs. However, the low efficiency of this technique and the relative high price of the CSPs limits its use to the resolution of milligram range of sample. 

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]. 

Examples with other Pirkle-type CSPs have also been described [139, 140]. In relation to polysaccharides coated onto silica gel, they have shown long-term stability in this operation mode [141, 142], and thus are also potentially good chiral selectors for preparative SFC [21]. In that context, the separation of racemic gliben-clamide analogues (7, Fig. 1-3) on cellulose- and amylose-derived CSPs was described [143]. 

Small chiral molecules. These CSPs were introduced by Pirkle about two decades ago [31, 32]. The original brush -phases included selectors that contained a chiral amino acid moiety carrying aromatic 7t-electron acceptor or tt-electron donor functionality attached to porous silica beads. In addition to the amino acids, a large variety of other chiral scaffolds such as 1,2-disubstituted cyclohexanes [33] and cinchona alkaloids [34] have also been used for the preparation of various brush CSPs. 

This technique has been used to track conceivable enantiophores of the Whelk-0 1 CSP ((3R,4S)-4-(3,5-dinitrobenzamido)-3-[3-(dimethylsilyloxy)propyl ]-l,2,3,4-tetrahydrophenanthrene) which was prepared in 1992 by Pirkle and Welch [22]. As seen in Fig. 4-7, a Whelk enantiophore should contain two ore more of the following molecular properties ... 

To demonstrate the excellent correlation (r- = 0.99) between the luminance of the images and molecular diversity, we plotted the luminance values of the map versus the mean similarity values of data sets (Fig. 4-13). From this plot, a scoring scheme for the classification of CSPs from specific to broad application range can be well established Crownpak CR > Pirkle DNBPG > Whelk > Chiralpak AD > Chiralcel OD. 

Whelk-0 1 and Pirkle DNBPG have appreciable differences in terms of application range. This is not surprising since Pirkle DNBPG often requires a prior derivatization of solutes to achieve a separation. This also confirms the atypical character of Whelk-0 1 compared to other Pirkle-like CSPs. 

Utilization of intelligent systems in chiral chromatography starts with an original project called CHIRULE developed by Stauffer and Dessy [36], who combined similarity searching and an expert system application for CSP prediction. This issue has recently been reconsidered by Bryant and co-workers with the first development of an expert system for the choice of Pirkle-type CSPs [37]. 

An example for this approach is the immobilization of (5 )-(-)-a-A-(2-naph-thyl)leucine, a 7t-donating group on silica. This chiral selector exhibits excellent recognition for 3,5-dinitrobenzoyl (DNB)- and 3,5-dintroanilido (DNAn)-deriva-tives. Amines and alcohols can be derivatized with DNB- or DNAn-chloride to the esters or carbamates and separated on the CSP, as shown by Pirkle for a wide variety of compounds [27]. 

The Novasep team in 1994, successfully resolved 2 kg of racemic binaphthol per day on a Pirkle-Type 3,5-DNBPG CSP (Merck KGaA, Germany) using a Licosep 8-200 SMB system (Summary report on the BRITE-EURAM project BRE2-CT92-0337). 

The brush-type (Pirkle-type) CSPs have been used predominantly under normal phase conditions in LC. The chiral selector typically incorporates tt-acidic and/or n-basic functionality, and the chiral interactions between the analyte and the CSP include dipole-dipole interactions, n-n interactions, hydrogen bonding, and steric hindrance. The concept of reciprocity has been used to facilitate the rational design of chiral selectors having the desired selectivity [45]. 

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