Total Synthesis Of (-)-?-KAINIC ACID Via Asymmetric Enyne Cycloisomerization And Mn(?)-catalyzed Asymmetric Hydrogenation Of Ketones

This thesis aims at researching the total synthesis of natural product?-?-?-kainic acid,and the design,synthesis of chiral ligands and their applications asymmetric catalysis.Kainoid amino acid is an unique category of amino acid with fascinating structure,in which kainic acid is the most representative natural product.Most natural products in kainoid amino acid family possess excellent bioactivities.Therefore,they are widely used in pharmaceutical research field.However,up to now,there is no straightforward and practical synthetic route which can produce this type of natural products in large quantity.In order to develop a simpler and more practical synthetic route,we took?-?-kainic acid as prime target and utilized asymmetric Zhang enyne cycloisomerization as our main synthetic strategy,which is an quite effective way to enantioselectively construct five-membered rings.After extensive research,we successfully developed a straightforward synthetic route with the application of Zhang enyne cycloisomerization.Our new-developed synthetic route has high possibility in producing?-?-kainic acid in large scale.Consequently,we lay the foundation for further study toward total synthesis of other natural products in kainoid amino acid family.Traditional asymmetric homogeneous hydrogenation catalysts are using precious metals ruthenium,rhodium,iridium and so on.Considering the limited on earth,the research and development of cheap metal catalyst instead of precious metals is a significant work.In the past two years,researches on cheap metal iron,cobalt,manganese began to increase.This chapter mainly described the designing and synthesis of a new PNNP tetra-dentate ligand,and then it was applied to the coordination with the iron and manganese metal precursor to get the complexes.The complexes were used in asymmetric hydrogenation of ketones,and the manganese catalyst was able to catalyze the ketone hydrogenation under mild conditions?45?,40 bar H₂?.Through the modificaiton of PNNP ligand,a tridentate PNN ligand was prepared,and the preliminary experimental results were similar to the tetra-dentate ligand.