Selection, design and application of novel biocatalytic reactive crystallization concepts for the preparation of chiral beta-amino alcohols and alpha-amino acids

该子项目的主要目标是开发一种有效的生物催化反应和选择性结晶程序的组合，用于在制备规模上合成手性β-氨基醇和α-氨基酸。该项目建立在对目标化合物的基本物理化学性质的研究基础上，这些化合物将直接从反应水溶液中分离出来。同时，选择和使用合适的生物催化剂或其相应的制备物的决定与选择整合的反应途径相关，因为相应的反应条件对目标化合物的溶解度有影响。对于氨基酸，优选在选定的结晶条件下直接结晶，而对于氨基醇，需要合适的结晶剂以使这些通常为亲水性的产物以盐的形式结晶。过程控制将通过整合过程分析技术（PAT）的适当概念得到支持，包括用于实时监测、控制和优化综合生物催化-结晶过程的自动化液相色谱方法。在上述所有方法的组合中，该方法将被优化并按比例放大到中试装置意义上的制备规模。

The primary goal of this subproject is to develop an efficient combination of biocatalytic reactions and selective crystallization procedures for the synthesis of chiral beta-amino alcohols and alpha-amino acids on a preparative scale. The project builds on the investigation of the fundamental physicochemical properties of the target compounds, which are to be isolated directly from aqueous reaction solutions. In parallel, the decision on the selection and use of suitable biocatalysts or their corresponding preparations is relevant for the selection of the integrated reaction route, since the corresponding reaction conditions have an influence on the solubilities of the target compounds. For amino acids, direct crystallization under the selected crystallization conditions is preferred, whereas suitable crystallization agents are required for amino alcohols to crystallize these often hydrophilic products in the form of a salt. Process control will be supported by the integration of suitable concepts for process analytical technology (PAT) including automated liquid chromatographic methods for real-time monitoring, control and optimization of the integrated biocatalysis-crystallization process. In the combination of all the processes described above, the process is to be optimized and scaled up to preparative scale in the sense of a pilot plant.