Study Of Three-component Reaction For The Construction Of Bisindoles Based On Active Zwitterion

Bisindole alkaloids widely appear in active natural products, especially the sea creatures, multistep and tough conditions are involved in the methods for synthesizing this series of compounds. This dissertation successfully completed highly efficient construction of this class of molecules’ skeleton by the usage of Three-component Reaction Methodology our group developed.This dissertation mainly consists of two parts of the research:Part Ⅰ, Highly diastereoselective synthesis of mix-bisindole derivatives via Three-component Reaction of trapping of active zwitterionic intermediate with ethyl glyoxylate. Part Ⅱ, Exploring the construction of chiral bisindole skeleton structure, to achieve the synthesis of bisindole alkaloids Gliocladin C. To be specific, We empoly ethyl glyoxylate to trap active zwitterionic intermediate generated by indole and carbenoid which were formed via decomposion of diazo by Rh2(OAc)4, to highly diastereoselective achieve mix-bisindole products. Then, in view of the reaction, we do preliminary asymmetric catalysis research. The quinine- and thiourea alkaloids-catalyzed asymmetric aldol reactions gave the desired product with 79% ee as a single diastereoisomer. The developed method was used in the synthesis of bisindole alkaloids Gliocladin C, but put forwards some feasible studies and explorations.Finally, these compounds were subjected to HCT116 cells for preliminary biological active test, and fortunately, some of them had good inhibitory to human colon cancer cells.