Synthesis Of Prohematoxylin A And Its Derivatives

Protosappanin A,which is an effective component of Caesalpinia sappan L that is a traditional medicine plant,has antitumor and immunosuppressive effects.Protosappanin A is restricted in the scientific research and the clinical application because of its extraction workload and low yield.On the other hand,the structure of protosappanin A is a dibenzo eight-membered heterocyclic compound with multiple hydroxyls.Synthesis of protosappanin A is quite difficult,the total chemical synthesis work have not been reported in literature.In this paper,different synthetic routes of the protosappanin A were designed.Through the research and analysis,a better synthesis scheme was finally determined.The scheme is that a phenolic compounds as raw material was successfully prepared protosappanin A and its derivatives by bromide,condensation reaction,Suzuki coupling,intramolecular Friedel-Crafts acylation,carbonyl addition,reduction,Tiffeneau--Demjanov rearrangement and deprotection.In the process of synthesis,methylated protosappanin A and benzylated protosappanin A,as protosappanin A with protective group,were obtained.They were deprotected to prepare protosappanin A and 3-methoxy protosappanin A,respectively.14 kinds of derivatives of protosappanin A were synthesized by the synthesis scheme.Antitumor activity and structure-activity relationship of the protosappanin A and its derivativesthe were researched and evaluated.The results showed that protosappanin A and 3-methoxy protosappanin A have good antitumor effect on human hepatoma HegP2 cells,in which 3-methoxy protosappanin A was superior to protosappanin A.Key reaction steps of the synthesis scheme include Suzuki coupling,intramolecular Friedel-Crafts acylation,and carbonyl addition and deprotection.The best approaches of these key steps were optimized.Structures of all products and intermediates were confirmed by 1H NMR and 13C NMR.