手性离子液体在药物萃取拆分中的性能及机理研究

Extraction enantioseparation has attracted attention for resolution of drug enantiomers not only in lab research but in industrial manufacturing. The enantio-selectivity is originated from chiral recognition which is based on host-guest chemistry. However, the chiral extraction is suffering the limited options of solvents of extraction system, the host extractants and the targeted guests. Meanwhile, the operational selectivity have to be improved further. In present work, a series of chiral ionic liquids based on natural amino acids will be designed and synthesized, with the structure systematically adjusting the physico-chemical properties including the polarity, the compatibility with molecular organic solvents, and the different solvation to medicine enantiomers. Synchrotron radiation based XAFS (X-ray Absorbtion Fine Structure) and vacuume UV spectroscopy and circular dichroism spectrums would be used to pursue the mechanism and structure-performance relationship of differential enantiomer solvation in chiral ionic liquids. The study will be carried out to confirm the primary influence factors for operational selectivity in extraction resolution. The picked out chiral ionic liquids would be not only used as chiral extractants for a series of chiral drugs of similar molecular-molecular interaction with these chiral ionic liquids, but as the possible solvent systems of high-speed countercurrent chromatography for chiral resolution application.

手性萃取适用于实验室分离分析研究、也适于工业规模生产，其手性选择性基于主客体化学的手性识别。本课题拟针对手性萃取中萃取体系两相溶剂选择范围比较单一、手性主体（即萃取剂）的可选择范围及适用对象比较受限、萃取操作选择性不够高的问题，设计、合成一系列手性离子液体，通过结构的改变来系统调控离子液体的粘度、极性、与有机溶剂的互溶性和对药物对映体差异性溶解的能力，运用同步辐射的X射线吸收光谱法、真空紫外和圆二色谱法研究手性离子液体差异性溶解对映体的机理；进行单级萃取实验研究确定影响萃取表观选择性的关键因素，筛选出兼具溶剂和手性萃取剂功能的离子液体，为建立萃取和反萃的串级实验工艺和流程、实现药物对映体的手性萃取拆分奠定基础，同时也为高速逆流色谱手性分离分析用溶剂系统的选择提供参考。