Total Synthesis And Antibacterial Activity Of Caulerpin

Caulerpin,a bis-indole alkaloid from the marine algal Caulerpa sp.It had been proved that caulerpin showed many activities and part of them gave good results such as promotion of plant growth?anti-tumor?anti-inflammation etc.Because of the limited content of this compound in marine algal,it is difficult to obtain it in large quantities,which limits its further research and development.Thus we have to find a synthetic method to solve the bottleneck problem of subsequent research and development.This article divides into two parts:one is the total synthesis of caulerpin and the other is the antimicrobial activity research of caulerpin and its intermediates.In the first part,a five-step synthesis method was designed through an inverse synthesis analysis method.Indolin-2-one was used as a starting material,we designed to complete the total synthesis of caulerpin through the Vilsmeier-Haack reaction,protection of the indole-N and substitution of dimethyl malonate etc.In order to improving the product yield of caulerpin,we had to find out the optimization conditions in the processes and finally reached 13%yield.All the compound structures were characterized by means of ¹H-NMR,¹³C-NMR and ESI-HRMS.In the second part,we studied the antibacterial activity of caulerpin and its intermediates through CCK-8 antibacterial activity assay,apoptosis assay,ROS level and mitochondrial membrane potential detection.With the concentration increasing,it was found that caulerpin could promote the generation of cellular ROS for the cause of the apoptosis of Staphylococcus aureus and Candida albicans.Additionally,the intermediate P2 inhibited the growth and proliferation of E.coli by decreasing the mitochondrial membrane potential.