Chromatography in Enantiomeric Separations

Chromatography is very commonly used in production processes of bio-pharmaceutical compounds. Chromatography is particularly effective in breaking the symmetry of racemic mixtures and in obtaining enantiomeric enrichment thanks to the availability of efficient and stable chiral stationary phases. The presence of impurities and foreign species beside the two enantiomers to be separated may dramatically enhance or hinder chromatographic resolution. It is also worth noting that chromatography and crystallization can be conveniently combined to exploit their complementarities, i.e. the capacity of chromatography to break the symmetry of a racemate and the capacity of crystallization to achieve high enantiomeric enrichment from a partially enriched solution.
In the case of chromatography, impurities, which may be unconverted reactants, byproducts or additives, e.g. catalysts, might be co-eluting with the target enantiomers or not depending on their chemical nature. In either case, advanced separation strategies based on batch chromatography, either isocratic or gradient, and on multicolumn chromatography, e.g. Simulated Moving Bed, have to be investigated. Proper protocols to screen stationary phases and mobile phase compositions to identify optimal conditions for the target separation have to be devised.

This work is part of European Union Framework Program 7 project INTENANT

INTegrated synthesis and purification of single ENANTiomers (INTENANT)

Several industries have an increasing interest in improving their access to pure single
enantiomers of biologically active substances. The latter often form the basis for valued added products relevant for, among others, the pharmaceutical, cosmetic, and food industries.
Up to now there exist two generally rivalling concepts for producing pure enantiomers. One approach is based on developing and applying enantioselective synthesis techniques, which often consist of a large number of reaction steps. Alternatively, simple non-selective synthesis can be applied in combination with advanced downstream separation techniques and recycling strategies. These two competing approaches have been up to now hardly combined and considered in a holistic way.
It is the goal of the proposed project to combine the available chemical and physical methods to effectively and efficiently produce single enantiomers at high purity. For this a strong consortium of academic and industrial experts in various fields of synthesis and separation technologies will work together on several well selected model systems as well as industrially relevant components. Based on case studies performed, main outcome of the project will be innovative, shorter, cheaper and widely applicable pathways for the production of pure
enantiomers, which will be brought into industrial practice and enhance the competitiveness of European industry.

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