Chiral separations CSPs

From the pioneering studies of Ito et al. [117], CCC has been mainly used for the separation and purification of natural products, where it has found a large number of applications [114, 116, 118, 119]. Moreover, the potential of this technique for preparative purposes can be also applied to chiral separations. The resolution of enantiomers can be simply envisaged by addition of a chiral selector to the stationary liquid phase. The mixture of enantiomers would come into contact with this liquid CSP, and enantiodiscrimination might be achieved. However, as yet few examples have been described in the literature. 

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). 

Enantiomeric separations have become increasingly important, especially in the pharmaceutical and agricultural industries as optical isomers often possess different biological properties. The analysis and preparation of a pure enantiomer usually involves its resolution from the antipode. Among all the chiral separation techniques, HPLC has proven to be the most convenient, reproducible and widely applicable method. Most of the HPLC methods employ a chiral selector as the chiral stationary phase (CSP). 

If some fields may be empty in the sublevels, all the fields in the main level are required for each entry. A new chiral separation record can be added in CHIRBASE solely if the authors correctly identify both sample and CSP. Since the beginning of the project, our policy has been to contact the authors of all publications containing incomplete, ambiguous or inconsistent data and to ask for additional information. Providing the separations with unique case numbers helps us considerably in this essential task, and also facilitates avoiding redundancies in the database. When chiral separations are reported for the second time in a new publication with exactly the same chromatographic conditions, this is stated in a footnote added in the field comments . In this field, miscellaneous information that cannot appear elsewhere are listed (detection limit, description of a reported chromatogram, racemization study, mobile phase limitations, etc.). 

The forms comprise several sections (REE, CSP, COND, SAMP, and DATA) which follow the ordered way chiral separations are planned in an organized laboratory. The user first puts in the section REP the full information related to a given reference. Then, in CSP, SAMP and COND he or she will enter all the columns, samples and operating conditions. The separations are actually created in the last windows DATA, where each sample will be connected to all the columns which have been used, and each column will be connected to all the tested conditions in front of these conditions are entered the experimental results of each separation. This hierarchical structure thus enables a rapid and easy registration of several chiral separations for a given compound. 

By clicking the appropriate buttons on the form, the user can combine molecular structure queries of sample, CSP and solvent, using operators AND, OR, NOT with data queries in one search. A query for the search of chiral separations of alpha-aromatic acids on any polysaccharide phases coated on silica gel providing an alpha value superior to 1.2 is shown in Eig. 4-4. 

Temperature can also be used to optimize enantioselectivity in SFC. The selectivity of most CSPs increases as temperature decreases. For this reason, most chiral separations in SFC are performed at ambient or subambient temperatures [50, 74]. Subambient temperatures are particularly useful for compounds having low conformational stability [75]. Stringham and Blackwell explored the concept of entropically driven separations [76]. As temperature increased, enantioselectivity decreased until the enantiomers co-eluted at the isoelution temperature. Further increases in temperature resulted in reversal of elution order of the enantiomers. The temperature limitations of the CSP should be considered before working at elevated temperatures. 

Fig. 4-4. The query menu form search of chiral separations of alpha-aromatic acids on any polysaccharide CSPs with a > 1.2.

FIGURE 14.4 Achiral separation (a) of rye grass extract containing 2-(2,4-diclorophenoxy) propionoic acid (2,4-DP) on a C18 column and subsequent chiral separation (b) of the heart-cut portion on a Chirobiotic T CSP. Reprinted from Schneiderheinze et al. (1999) with permission John Wiley Sons. 

In a recent study, chiral separations for pyrethroic acids, which are the chiral building blocks of synthetic pyrethroids and the primary metabolites of the acid part of these potent ester insecticides, have been developed [62], For example, a polar-organic mobile phase allowed the complete baseline resolution of all four stereoisomers of chrysanthemic acid (2,2-dimethyl-3-(2-methylprop-l-enyl)-cyclopropanecarboxylic acid) on a 0-9-(tcrt-butylcarbamoyl)quinine-based CSP(acjj = 1.20, oLtrans = 1-35, critical Rs = 3.03) (Figure 1,32a). This chiral acid is the precursor of pyrethroids like allethrin, phenothrin, resmethrin, and tetramethrin but not excreted as metabolite. The primary acid metabolite of these pyrethroids is chrysanthemum dicarboxylic acid (3-[(l )-2-carboxyprop-l-enyl]-2,2-dimethylcyclopropanecarboxylic acid) the stereoisomers of which could also be resolved with a reversed-phase eluent (acetonitrile— 30-mM ammonium acetate buffer 90 10, v/v pHa = 6.0) and employing an O-9-(2,6-diisopropylphenylcarbamoyl)quinine-based CSP ads = 1-09, atrans = 1-50,... 

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