Synthesis Of Natural Active Bisindole And Its Analogs

The known indole alkaloids have demonstrated diverse biological activities,such as anticancer,antibacterial,antiviral,treatment of hypertension.A number of indole alkaloids have been developed into drugs for the treatment of diseases.For example,vinblastine and vincristine and its derivatives,separated from apocynaceae plant Catharanthus roseus,exhibit good antitumor effect.Especially the sulfate of vincristine,as a first-line anticancer drugs has been widely used in the treatment of leukemia and other cancers.Therefore,the further studies on indole alkaloids are still deserved.This thesis describes our studies on the synthesis of indole alkaloids.The thesis is divided into the following three chapters.First,the general methods for the synthesis of indolo [3,2-a] carbazole were introduced and we developed a simple and biomimetic synthetic strategy for indolo[3,2-a]carbazoles.A series of indolo[3,2-a]carbazoles were synthesized via a biomimetic transamination/aromatic cyclisation/decarboxylation sequence from 2,3'-biindolyl which synthesised of tryptophan derivatives and indoles.It provides a new idea for the further study of indolo [3,2-a] carbazole alkaloids.Second,based on the biomimetic synthetic strategy,using indolo[3,2-a]carbazole as molecular template,a series of indolo[3,2-a]carbazole derivatives were designed and synthesized by introducting pharmacophore.The results of a preliminary evaluation on their antitumor activity indicated that some compounds had modest to good antitumor activity for Hel?K562-1?WM9-1?MDA231?TK6?DP17-1?PC3.Third,the general methods for the synthesis of rutaecarpine were introduced and we developed a simple synthetic strategy for rutaecarpine.It was synthesized via amidization reaction/introduction of cyano in high chemical selectivity/aromatic cyclisation sequence from tryptamine and 2-fluorobenzoic acid.Then we synthesized eight analogs,confirming this method feasible.