Cinchona chiral stationary phase

CINCHONA ALKALOID-BASED CHIRAL STATIONARY PHASES... 

Examines chiral stationary phases containing cinchona alkaloid-derived materials... 

Lammerhofer, M., Tobler, E., Zarbl, E., Lindner, W., Svec, E, and Frechet, J. M. J. (2003). Macroporous monolithic chiral stationary phases for capillary electrochromatography new chiral monomer derived from cinchona alkaloid with enhanced enantioselectivity. Electrophoresis 24, 2986-2999. 

Rosini, C., Altemura, P., Pini, D., Bertucci, C., Zullino, G., and Salvadori, P. (1985) Cinchona alkaloids for preparing new, easily accessible chiral stationary phases, J. Chromatogr. 348, 79-87. 

The cinchona alkaloid-based stationary phases are chiral stationary phases where quinine/ quinidine are chemically bonded to a silica gel matrix. The interaction between the selectand and selector is based on charge transfer n-n interactions as well as ion pairing with the selector. They operate under aqueous-organic mobile phases or mixtures of organic solvents such as hexane-alcohols. 

Pioneering attempts at using cinchona alkaloids as a platform for chiral stationary phase preparation have been reported as early as in the mid-1950s by Grubhofer and Schleith [52]. The chiral anion exchange polymeric materials were prepared by immobilization of quinine (and other cinchona alkaloids) via the 9-hydroxyl group or quinuclidine nitrogen to a polymer support. However, this resulted in very low selectivities of these phases toward racemic mandelic acid as a test analyte. Results of the early studies have been reviewed in detail by Davankov [53]. 

A special subclass of brush-type chiral stationary phases are the ion-exchange CSPs developed by Lammerhofer and Lindner (1996). By introducing an additional ionic moiety, a strong interaction between the selector and the selectand can be achieved. The first commercial available phases are based on the Cinchona alkaloids Quinine and Quinidine with an additional weak anion-exchange function offering good separation possibilities for chiral acids. A strong dependence of the capacity from the counter ion of the mobile phase could be demonstrated by Arnell (2009). 

Cinchona alkaloids comprising quinine, quinidine, cinchonidine, and cinchonine as the major members constitute a unique class of quinoline alkaloids with tremendous impact on human civilization. The odyssey of Cinchona alkaloids began with the discovery of their antimalarial properties followed by the very successful application in stereochemistry and in asymmetric synthesis. Currently, the portfolio of applications of Cinchona alkaloids is much broader, involving chiral stationary phases for enantioselective chromatography, novel biological activities, and several useful transformation converting them into other modular and chiral building blocks, such as, for example, quincorine or quincoridine. Current pressure on a more intense exploration of sustainable products and easy access to diverse molecular architectures make Cinchona alkaloids of primary importance for synthetic catalytic and medicinal chemistry. 

Cinchona-Alkaloid-Bonded Chiral Stationary Phase 144... 

Czerwenka C, Lammerhofer M, Lindner W (2003) Structure-enantioselectivity relationships for the study of chiral recognition in peptide enantiomer separation on cinchona alkaloid-based chiral stationary phases by HPLC influence of the N-tenninal protecting group. J Sep Sci 26 1499-1508... 

Alkaloids, for example, quinine, are widely applied as catalytic reagents in chiral organic syntheses and also in the production of HPLC stationary phases for chiral separations. Cinchona alkaloids also induce the enantioselection of chiral fluoro-compounds analyzed by FNMR spectroscopy [32]. (-)-Brucine and (-)-berberine mixed with silica gel were used for preparation of thin-layer plates to resolve racemic amino acids. Other optically active pure enantiomers of natural compounds are applied for impregnation of TLC plates (-l-)-tartaric acid, L-aspartic acid [33]. (—)-Menthol is used for preparation of diastereomeric derivatives in indirect enantiomeric separation of, for example, 2- and 3-hydroxy acids [34]. 

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