Design,Synthesis And Antitumor Activity Evaluation Of Berberine Derivatives And Rh(Ⅲ)-Catalyzed Synthesis Of 3-acyl Indoles

In this paper,basing on the lead compound A1 screened from the berberine compound library of our research group,about 20 novel berberine derivatives were designed and synthesized by using the traditional pharmacochemical design theory and modern organic synthesis technology.In the pharmacological activity evaluation,it was found that most of the compounds exhibited better inhibitory activity than berberine on the proliferation of HCT-116 cells.The highest inhibition rate was over 70%.The IC50 values of HCT-116,PC-9 and MCF-7 cell lines were further tested.It was found that the IC50 values of five compounds(A10,All,A12,A13 and A22)against the three cell lines were between 1 and 10 uM,which were broad-spectrum anti-tumor active compounds.We also summarized the preliminary structure-activity relationships of these berberine derivatives,which will pave the way for futher structural optimization and chemical biology to find targets.In this paper,the synthetic methodology of 3-acylindole skeleton with pharmacological activities,were also studied.In this study,we attempted to develop a more efficient and convenient method for the synthesis of 3-acylindole.Herein,a common organic material,a-Cl ketone,was firstly designed as a single-carbon synthon and participated in Rh(Ⅲ)-catalyzed C-H activation and tandem cyclization of N-phenylamidine to construct 3-acylindole one step by step.This synthetic strategy is characterized by high efficiency,mild conditions,high regioselectivity and wide applicability of substrates.It has been successfully applied to the construction of natural product skeleton and the rapid synthesis of anti-inflammatory drug Pravadoline.