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Schlagwörter:
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Zusammenfassung:
The large discrepancies in the physiological impact of a pair of molecules, that can be discriminated by its mirror symmetry only, are widely known not only after the commercialisation of the molecule Thalidomide (Contergan®, Grünenthal/Germany). Initiated by a claim by the American Food and Drug Administration (FDA) a so-called 'chiral switch' took place in the chemical, pharmaceutical and biotechnological branches. It aims on the exclusive formulation of products, which contain only the desired enantiomer, the active mirror image. Due to the very similar nature of the molecules, the claim remains very demanding and requires usually an extensive screening of suitable methods for each new molecule. Within the thesis in hand new powerful chiral purification methods were developed, which allow a certain degree of generalisation and the simplified access to single enantiomers.
Within the first part of the tripartite thesis, a systematic analysis of complex liquid/solid and solid/solid phase equilibria was performed, whose understanding provides the foundation for chiral separations. Therefore, the system of the chiral malic acid, which exhibits partial solid solutions, was investigated exemplarily in different solvents. The experimental determination of tie lines was accompanied by time-resolved X-ray powder determination of the corresponding solid phases. The obtained data on the prevailing phase equilibria allowed estimating the degree of success of crystallisation-based separations of this and conceptionally similar systems.
The second part or the thesis is concerned with the extension and application of both, correlative and entirely predictive thermodynamic models for a number of chiral systems in order to obtain relevant key properties of phase equilibria necessary for the design of chiral separations. Significant potential was found, which often allowed the estimation and design of chiral separation processes based on rather limited experimental data. The developed short-cut model and a more detailed model allowed tailoring a characteristic thermodynamic property, which was considered the key element for a new and more effective crystallisation process. The latter was validated using different chiral systems in the following part of the thesis.
The last part compares synergetic couplings of chiral separation processes. Hereby, selected combinations of continuous multi-column chromatography and selective crystallisation were evaluated for two chiral systems on a theoretical and experimental basis and both, on lab-scale and on a pilot-plant-scale. Optimisation of selected couples processes revealed significant increases in productivities compared to the individual separation processes. It was shown, that the combination of a newly developed 2-step crystallisation process and a chromatographic pre-enrichment step with internal recycling of fractions leads to additional improvements in productivities. This process variation outperforms other coupled processes state-of-the-art in terms of robustness and productivity.
© Shaker Verlag 2012
