Synthesis And Activity Of Antitumor Indole Alkaloids Calothrixin A And B And Their Derivatives

Objective: Natural products play an vital role in the pharmaceutical field.Modern medicines such as penicillin,morphine and paclitaxel,which are used for the treatment of bacterial infections,pain,and cancer obviously.These products are abundant in several sources,and can be obtained from animal plants and microorganisms.The anti-inflammatory and anti-cancer activity of calothrixins is also prominent,but these compounds are mainly derived from cells of Calothrix strains and have complicated procedures and low yields.Due to its excellent anticancer activity and unique framework structure,its synthesis has not been stopped at home and abroad.At present,there are more than ten reports of its total synthesis at home and abroad.We have reviewed most of the research reports on the total synthesis of calothrixins and established the synthetic strategy of calothrixins.Methods: It was designed to synthesize calothrixin B via heck reaction/introduction of Alkene and reductive amination to formation of protecting group,cyclization,deprotection,hydrolysis and a series of reactions from 2-iodoaniline.The key is indole-to-carbazole transformations in one-pot.C-C bonds and 2 rings are created in a single step via a indole-to-carbazole transformation triggered by Pd(II)-catalyzed direct C-3alkenylation of indole.Results: We have succeeded in synthesizing 16 compounds of calothrixin B and its derivatives,and tested the activity of some compounds.Based on this,we optimized the synthesis conditions to increase the yield of some compounds.Conclusion: A rapid construction of carbazolones and its application for synthesis of calothrixin B and give intermediate derivatives,demonstrating the versatility of the route,using oxygen as the oxidant at key steps,not only reduces costs but also is more environmentally friendly.