仿酶手性分子用于液-液两相手性萃取拆分氨基酸的研究

The chiral extractants so far developed for the liquid-liquid enantioselective extraction of amino acids is limited due to the low selectivity and narrow range of applicable substrates. In this proposal, inspired by the reaction mechanism of the natural enzyme - codecarboxylase with the amino acids, novel and highly enantioselective mimic enzyme chiral-extractants will be studied. The key ideas to prepare such chiral receptors would be mainly based on the cooperation of novel double helical chiral-centers and a unique group providing resonance-assistant hydrogen bond inside the mimic enzyme molecular. Meanwhile, the much more flexible structures of the chiral centers and the different substituent groups introduced in the receptors could be very helpful to the systematic study on the structure-activity relationship between mimic enzyme molecules and their performance in the resolution of chiral amino acids. These works would open new design strategies for the development of such mimic enzyme chiral-extractants. To reveal the effect of the different structures of the mimic-enzyme molecules on the enantioselectivity, stability of the final product and extraction-system efficiency, the reaction mechanism of the chiral receptors with the enantiomers of amino acids and the relationships between these receptors and the factors of the whole extraction system will be mainly studied. Our research works will not only lay a theoretical foundation for the development of novel high-performance mimic-enzyme chiral extractants, but also provide a practical approach to improve our amino acids industry. Thus, the research of this proposal would have both theoretical and practical applications.

项目针对现有手性萃取剂在用于液-液两相萃取拆分光学纯氨基酸领域所存在的选择性低、应用范围小等问题，以天然辅酶-磷酸吡哆醛对氨基酸的作用机制作为化学模拟对象，旨在研究新型的高效仿酶手性萃取剂。拟以双螺旋手性中心的协同作用、新型共振-辅助氢键供体基团的引入作为切入点，通过设计更加灵活的手性中心结构和不同取代基团等来对新型仿酶分子的性能与结构之间的关系进行系统的研究，制备高选择性、应用面宽的新型仿酶手性萃取剂，对仿酶分子的设计理念进行拓宽和创新。希望通过对所设计合成的仿酶分子在萃取过程中的反应机理、与萃取拆分系统内部各因素之间的作用规律等，揭示和总结其结构对选择性、产物稳定性以及系统效率的影响，为新型的高效仿酶萃取剂的发展奠定理论基础，而且该项目还可为提高我国氨基酸产业的水平提供切实可行的新途径，具有理论和实际的双重意义。

液-液两相手性萃取拆分（ELLE）是一类新型的光学纯氨基酸的不对称拆分方法，仿酶型手性萃取剂在该体系中表现出较高的反应活性和选择性。基于此，本项目主要研究了两类新型的仿酶型手性萃取剂的结构设计、合成、表征与应用研究，揭示新型仿酶型手性萃取剂的构效关系，研究其反应的历程和机理，以期为新型仿酶型手性萃取剂的设计合成奠定理论和实践基础。其中，所制备的双螺旋手性中心的仿酶手性萃取剂MECE-1实现了对10种天然氨基酸的高效手性拆分，产物ee%>97%；所制备的具有新型分子内共振-辅助氢键（RAHB）结构的MECE-2分子实现对7种天然氨基酸的高效手性拆分，选择性D/L=17~50。同时，本项目还进行了一定的拓展研究，一方面利用仿酶型手性萃取剂的重要中间体联二萘酚单羧酸衍生物BNA实现了对手性脂肪胺类化合物对映异构体的结晶分离，该方法反应速度快，收率和光学纯度高（ee%>99%），具有很强的实用性能；另一方面，将ELLE方法的体系和构建思想应用于光学纯氨基酸的不对称合成中，并积极探索各类新型的手性化合物的碳氢官能团化方法。项目执行期间发表SCI论文3篇，授权专利3项（成果转化2项），受邀会议报告1次，会议论文1篇。通过本项目的研究，即为新型仿酶型手性分子的发展奠定了良好的理论和实践基础，也为液-液两相萃取拆分方法的拓展研究和应用起到了推动作用。