Design Of Novel Metal-enzyme Catalysts And Their Applications For Dynamic Kinetic Resolution Of Chiral Amines

Enzyme and metal catalysis used to be considered as unconnected just like “two sides of amedal”.Chemoenzymatic dynamic kinetic resolution is an important application of metal complexes in cooperative catalysis with enzymes.Dynamic Kinetic resolution is a method for the separation and purification of optically active substances,which has been widely used in production of chiral compounds.In this thesis,the chiral amines were used as probes to study the design of metal-enzyme catalysts and their application of dynamic kinetic resolution.?1?Pd@NH₂-MIL-101 and CALB-CLEAs were used to study for dynamic kinetic resolution of amines.In this chapter,we synthesized the metal nanoparticles by reduction method and loaded them onto the support to prepare the metal hydrogenation catalyst?Pd@NH2-MIL-101?.Then,the metal catalyst was applied to one-pot DKR rac-1-phenethylamine reaction combined with cross-linked enzyme aggregates?CALB-CLEAs?.The yield and ee value of the optically pure product R-amide were more than 99% after 4 h of reaction without adding any additional base.In addition,in this chapter we demonstrate that mild microwave conditions can be applied to the DKR of an amine.The reaction time was reduced to 1 h,and excellent results were obtained in which both the yield and the ee value exceeded 99%.The catalyst system also has good universality for different substrates.The catalyst was maintained at a higher activity after repeated use for 9 times,confirming that the stability of the metal-enzyme catalyst is great.This recyclable combination of metal-enzyme co-catalysts also provides a preferred method for microwave industrial applications of DKR amines.?2?In order to achieve the industrialization of dynamic kinetic resolution,use the non-precious metals to instead of the precious metals is a future development trend,but the non-precious metals can cause the inactivate of enzymes has been an intractable problem.The separation of metal and enzyme active sites is the key to solving this problem.Aiming at this problem,a Yolk-Shell structure metal catalyst was prepared in this chapter,which can achieve the functional separation of metal and enzyme catalysts in different regions of core-shell materials.In order to further improve the enzyme activity,we developed a novel double-layered enzyme aggregates based on the traditional method.Both the inside and the outside of the enzyme aggregates can provide the active site of the resolution reaction,so the new enzyme catalyst further improving the immobilization rate of the CALB.We prepared the Yolk-Shell structure metal catalyst in combination with the double-layered enzyme aggregates for the one-pot DKR reaction of rac-1-phenethylamine.In the absence of any additional base,the conversion of the optically pure product R-amide was 99% after the reaction for 5 h,and the ee value and selectivity were both >99%.