A Facile Synthesis Of Tris(indolyl)Propanes Of Indoles To α,β-Unsaturated Imines

Scientific research found that indoles and their derivatives widely exist in nature,many structures of natural compounds contain indole ring, such as the oil of natural flowers,jasmine, neroli, daffodils, wallflowers and so on. Some indole derivatives closely related to the life activities, so the indole compounds are very extensive in the pharmaceutical field and in the organic synthesis and chemistry of drugs field. Indoles and their derivatives are often used as a reactant or target molecules in the design of a variety of chemical reactions. The precious study of indole compounds emphasized on the synthesis of mono-substituted and disubstituted indole compounds which have a good biological activity, but triindole compounds have not yet been fully researched as the difficult of synthesis and high cost. In this paper, we carried out the research for simple and efficient synthesis of tri-indole compounds.First, we choose α, β-unsaturated imine and indole and its derivatives as the reaction substrates. At the first step, we synthesized the different types of α, β-unsaturated imide, and then make them react with indoles and their derivatives through the Friedel-Crafts reaction.After the optimization and screening of a series of reaction conditions such as reaction solvent,reaction temperature, etc., we finally obtained an optimal and efficient reaction condition.Unsaturated imides and indole derivatives react in the condition of catalytic amount phosphonic acid as catalyst by the Friedel- Crafts reaction. As the results, we successfully got15 compounds of triindole compounds with high yields above 80%.Furthermore, we selected compounds 4a, 4c, 4d and 4e and tested their biologicalactivity. The results showed that they have certain growth inhibition on human lung cancer cells, human prostate cancer cells, human pancreatic cancer cells and human hepatoma cells.IC50 values ranging from 9.9 to 17.3 μM, especially compound 4e on human pancreatic cancer cells(CFPACA-1) is lowest. Its IC50 value was 9.9 μM. These results indicated that triindoles is an important biologically active substances.This thesis, triindole compounds with biological activity were successfully synthesized. These results will provide a wider range of application and in-depth study for indole derivatives. It will be important scientific value for triindole anti-cancer drugs.