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The general objective of this work is to develop a high performance technology of preparative chromatographic separations of optical isomers.

Optical isomers (enantiomers) are those molecules which are not superimposable on their mirror images. They differ from each other only in the way their atoms are oriented in space, however, the practical effects are differences in biological activity. Thus in drug action individual enantiomers may have different potencies, toxicities, transport mechanisms and metabolic routes.

Among the industrial methods for enantiomer separation (chiral separation), chromatography is almost non-existent while this technique is well established on an analytical scale. The project will develop methods for the preparation of chiral stationary phases, having desirable and predictable chromatographic properties. The most successful materials will be scaled-up for further testing in a new chromatographic process - the simulated moving bed. If successful, this will generate a technology with a wide range of applications in large-scale chiral chromatography of drugs, pesticides, food additives and other biologically active compounds.
A number of new chiral stationary phases have been developed, which are able to solve a lot of chiral separations at the analytical scale. Although they are generally considered as purely analytical tools, a protein and a cyclodextrin based CSPs have been tested in the scope of preparative enantioseparations. The results are positive, and show that these phases could be used in a SMB for specific chiral applications.

Difficult separations of synthetic stereoisomers and enantiomers are achieved by an automated industrial high performance SMB on different silicas (classical or chiral). A few kg/day of a feed is processed, yielding highly purified products (> 99%) with a recovery ratio superior to 98%. The separation is optimized thanks to the numerical simulation.

The possibility to consider preparative chromatography (in the simulated moving bed mode) as a real production tool for performing optical isomers separation is thus completely proven.

Contrary to classical separations, which are performed on very efficient packings (normal and reversed phase silica), it must be pointed out that chiral separations are performed on polymer gels and monomer- or polymer-coated silica, which are in general much less efficient than classical silica packings. This means that the comparison between elution and SMB is more favourable to the latter process in these cases, because the high number of plates required by elution chromatography in order to reach a good resolution implies a low flow-rate, hence a low productivity.

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