Asymmetric Synthesis Of Chiral 3,3'-dihydrofuran Spirooxindoles Catalyzed By Dinuclear Zinc Cooperative Catalyst

Oxygen heterocycle spirooxindoles have good biological activities,such as antibacterial,antiviral,anti-tuberculosis,anti-cancer,anti-HIV and anti-malarial biological traits with extensive application in fields such as drug synthesis and biopharmaceutical research.They have drawn much attention from scientists.Good antimicrobial activity is indicated in the use of racemic N-CH3 dihydrofuran spirooxindole derivatives to deal with pathogenic strains in vitro.Moreover,most of its antibacterial properties are superior to the standard antibiotic ampicillin,such as MIC(minimum inhibitory concentration),MBC(minimum bactericidal concentration)and IC50(inhibitory concentration).This thesis describes a new bimetallic cooperative catalytic asymmetric three-component reaction of ?-hydroxy ketones,isatins and malononitile,which involves a domino Knoevenagel/Michael/Pinner/isomerization sequence.The optimal reaction condition is achieved by screening the reaction conditions(catalyst,solvent,temperature,material ratio and additives).A series of new chiral 3,3'-dihydrofuran spirooxindoles are obtained in excellent enantioselectivities(up to 99% ee)and yields(up to 99%)under the optimal reaction conditions.Moreover,this protocol can proceed on a gram-scale synthesis without any loss in reactivity and stereoselectivity.And a possible mechanism of the reaction is proposed.