Analytical Sciences, Award Lecture
AS-011
Chromatographic resolution of racemic compounds on optically active polymers as chiral stationary phases (KGF-SCS Senior Industrial Science Award Lecture 2016)
E. Francotte1
1 Novartis Institutes for Biomedical Research, WKL-122.P.25, CH-4002 Basel
The awareness of the importance of chirality on the biological activity of chiral drugs, fungicides, insecticides, hormones, or fragrances is now well established. Over the last 30 years it has led to a rapidly increasing demand for tools addressing this fundamental question and for methodologies dealing with the chemistry challenges associated to this molecular feature.

Among all developed tools, enantioselective chromatography using chiral stationary phases has become a key technology for the analysis and preparative separation of the enantiomers of racemic compounds. It is now the standard technique for determining the optical purity of chiral substances, replacing almost completely the classical methods such as optical rotation.

In this context, polysaccharide derivatives have emerged as remarkably powerful chiral materials for the purpose of separating stereoisomers by chromatography, showing an exceptional chiral recognition capability not only for analytical determination of optical purity but also for the preparative utilization of this technology to produce optically pure compounds from mg to ton scale. The approach has now become the standard everyday process to access the single pure stereoisomers of potential new chiral drugs in drug discovery. Moreover, with the invention and introduction of immobilized polysaccharide-based chiral stationary phases, we have been able to considerably improve and extend the applicability of enantioselective chromatography to a broad variety of chiral molecules [1-3]. The process is based on a photochemical reaction which leads to a cross-linking of the polysaccharide chains.
The new generation (immobilized) of polysaccharide-based stationary phases has been gradually introduced on the market since 2004 and these phases are now used worldwide as the state-of-the art materials in almost all research laboratories dealing with chiral molecules both in academia and industry, as well as in many development and production units.

The advance of enantioselective chromatography has undeniably permitted to develop technological opportunities which were not conceivable some years ago in the field of large scale separation of stereoisomers of chiral drugs. Furthermore, this development has also favored the advent of the multi-column and continuous separation technology such as simulated moving bed (SMB) chromatography in the pharmaceutical environment, and the resurgence of the packed supercritical fluid chromatography (SFC) technique in general.
[1] E. Francotte, D. Huynh, J. Pharm. Biomed. Anal. 2002, 27, 421.
[2] E. Francotte, T. Zhang, Patent, PCT Int. Appl. (1997), WO 9704011 .
[3] E. Francotte, Chimia. 2009, 63, 867.