Preparative chiral separations

As in analytical chiral LC, Daicel derivatised polysaccharide CSPs are the most frequently used materials in preparative scale chiral separations. Recently CSPs have been prepared in which derivatised polysaccharides have been covalently bonded to the solid support rather than coated on as in the Diacel materials. The rationale for this is that it is advisable to reduce the chance of the chiral selector leeching off the column in trace amounts to contaminate samples of chiral dmgs isolated by production scale LC. However, the extent to which the Daicel coated CSPs are now used in production scale chiral LC would tend to suggest that such a problem, if it exists, is not a very significant risk. 

The most discernible recent trends in preparative chiral resolution have been the increasing use of supercritical fluid chromatography (SFC) and simulated moving bed (SMB) chromatography, and the fact that Daicel through its US and European Chiral Technologies subsidiaries have offered these as a custom service has played a role in this. 

The logical conclusion of these recent trends in preparative chiral chromatography ought to be that the next step would be to carry out SFC in an SMB system. Unfortunately it seems that the technological difficulties would almost certainly outweigh any potential benefits (personal communication [CIO]). 

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Although some applications for preparative-scale separations have already been reported [132] and the first commercial systems are being developed [137, 138], examples in the field of the resolution of enantiomers are still rare. The first preparative chiral separation published was performed with a CSP derived from (S -N-(3,5-dinitrobenzoyl)tyrosine covalently bonded to y-mercaptopropyl silica gel [21]. A productivity of 510 mg/h with an enantiomeric excess higher than 95% was achieved for 6 (Fig. 1-3). 

In the next section, a few illustrative examples of the use of ChiraLig for the analytical and three-stage preparative chiral separations involving amines and amino acids are presented and discussed. 

Electrophoretic ally Driven Preparative Chiral Separations using Cyclodextrins... 

Enantiomeric separations have proven to be one of the most successful applications of packed column SEC. Despite initial reluctance, many analysts now use SEC routinely for both analytical and preparative chiral separations. Additional studies of chiral recognition in SEC and continued improvements in instrumentation will ensure a prominent role for SEC in chiral separations methodology in the future. 

Electrophoretically-driven Preparative Chiral Separations using... 

Kennedy, J.H., Sharp, V.S., Williams, J.D. Development of preparative chiral separations using an intelligent chiral resolution system. J. Liq. Chrom. Rel. Techn. 2003, 26, 529-543. 

As a result of certain drawbacks attached to coated silica gel CSPs, they could not be used for preparative separations. However, the literature provides some reports on the preparative chiral separations on the bonded CSPs. The bonded CSPs are suitable for use at a preparative scale but the yield is very poor due to poor loading capacities. Davankov et al. [73] packed a column with 300 g of the L-hydroxyproline-type resin and used the chiral separation at a preparative scale. 

Before starting a preparative chiral separation it is essential to identify a chiral stationary phase (CSP) exhibiting good chiral recognition ability. This is usually done with an analytical column because it is less substance- and time-consuming. A stationary phase mostly composed of silica gel with only a few chiral elements will be rapidly overloaded. In this event, even if the phase exhibits useful properties for analytical purposes, it will not be appropriate for preparative applications this is the case for protein-based phases [102, 103], Most chiral stationary phases have relatively low saturation capacity, so the enantiomer separations are usually done under strongly nonlinear conditions [103], Accordingly, the accurate determination of the adsorption isotherms of the two enantiomers on a CSP is of fundamental importance to allow computer-assisted optimization to scale up the process. 

The accurate determination of the adsorption isotherm parameters of the two enantiomers on a CSP is of fundamental importance to do computer-assisted optimization to scale up the process. Such determinations are usually done with an analytical column and the most traditional method to determine the parameters and saturation capacity is by frontal analysis (see section 3.4.2). The aim of paper III was to investigate the adsorption behavior and the chiral capacity of the newly developed Kromasil CHI-TBB column using a typical model compound. Many of the previous studies from the group have been made on low-capacity protein columns which has revealed interesting information about the separation mechanism [103, 110, 111], For this reason a column really aimed for preparative chiral separations was chosen for investigation [134], As solute the enantiomers of 2-phenylbutyric acid was chosen. 

E. R. Erancotte, Preparative chiral separations by chromatography a powerful approach for the isolation of optically pure compounds, in Proceedings of the ChiralEurope 96 Symposium (Strasbourg), Spring Innovations Dd., Stockport SK7 IBA(UK), 1996, pp. 89-95. 

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