Studies On The Synthesis Of Actinphyllic Aicd

Thrombotic disease caused by thrombus has always been the number one killer of human health.Studies have found that the formation of thrombus is closely related to the imbalance of fibrinolysis.One of the endogenous inhibitors to fibrinolysis is carboxypeptidase U(CPU).Carboxypeptidase is a thrombin-activatable fibrinolysis inhibitor(TAFIa)activated by thrombin.Its effect can indirectly inhibit the formation of plasmin and then affect the dissolution of plasmin.Therefore,finding an inhibitor with a high inhibitory effect on TAFIa is of great significance for the treatment of thrombosis.(-)-Actinophyllic Acid(1)is a monoterpene indole alkaloid isolated by Professor Carroll from the leaves of the oleander family Alstonia actinophylla in 2005.This compound has structures bearing azabicyclo [4.2.1] dodecane and azabicyclo [4.2.1] nonane and octahydropyrrole [1,2-a] azaazecin.In addition to the rare structural unit of indole alkaloids,it also has five consecutive chiral centers.Furthermore,(-)-Actinophyllic Acid(1)posesses a very high inhibitory effect on TAFIa,can effectively inhibit the activation of TAFIa,and has high potential to be developed as a new type of antithrombotic drug.Therefore,the research on the total synthesis of Actinophyllic Acid was carried out in this paper.This thesis is divided into the following three parts.The first part is an overview.The isolation,extraction,structure identification and activity research of Actinophyllic Acid were introduced,and the research on the total synthesis of Actinophyllic Acid in recent years was reviewed.The second part is the experimental part,which introduces the research on the synthesis of Actinophyllic Acid.The Suzuki reaction is used to introduce a carbon chain at the indole C-2 position,and the chiral tert-butyl sulfinamide is introduced at the indole C-3 position to establish the chiral center as well as to introduce introduce nitrogen atom.When the indole C-2 was introduced into the carbon chain,We also attempted other methods to introduce C-2 side chain in indole units,and found a relatively general method for the introduction of side chain via Michael addition.To a certain extent,the universality of this method is verified.The third part is the synthesis of related compounds and some important spectral data.