Synthesis Of Indoles Alkaloids Skeleton Compounds From Marine Natural Products

Marine indole alkaloids have attracted much attention in the field of drug development due to their various pharmacological activities.However,it is difficult,expensive and timeconsuming to isolate bioactive compounds from natural sources,so chemists have focused on organic synthesis pathways that can more efficiently provide large quantities of such compounds.How to develop a more efficient,economic and green strategy to synthesize the dominant heterocyclic indole rings framework compounds has become a hot research topic for chemists.Meanwhile,as an interesting heterocyclic pharmacophore,the 1,2,3-triazole framework with antibacterial,anticancer,antiviral,anticonvulsant and other biological activities has attracted much attention in drug development and has been used for the synthesis of a variety of bioactive molecules.Encouraged by these findings,chemists selectively bound the active part of 1,2,3-triazole to the indole skeleton as a link between the two active pharmacological parts,and prepared a large number of triazole-containing indole compounds with a wide range of biological activities.However,many total synthesis of indoles alkaloid derivatives usually requires preactivated substrates using strong acids or strong bases,and their application in pharmaceutical industry is limited due to the various reaction steps.In view of the above studies,and considering the great potential of indole and triazole frameworks in the field of drug development in recent years,the research direction of this topic is to develop a more efficient,economic and green strategy for the preparation of potentially bioactive indole heterocyclic compounds containing triazoles.In response to the call of green chemistry,this project prepared azidyl indole through free radical series azidation-cyclization reaction promoted by organic selenium,and then introduced triazole ring into the indole nucleus under mild click reaction conditions to prepare the required products.The strategy effectively avoids the pre activate the substrate reaction conditions demanding various reaction steps such as faults and through a novel azide reaction method obtained azide indole,then use the economic available copper catalyst as cyclization reaction catalyst will azide indole with higher yield ground into the required product.Finally,the antibacterial activities of some final products containing representative substitutions were studied in vitro.Compound 4e,4j,4b,4a,4d,4k,4o,4l showed good inhibitory effect on Bacillus subtilis,and compound 4o,4c also showed good inhibitory effect on Escherichia coli.