Design, Synthesis And Application Of β-carboline Derivatives

Cancer morbidity and mortality present an up-going rate in our country at recent20years.And also cancer appears more and more frequent among young people.<2012China CancerRegistration Annual News>, published by National Cancer Registration Centre, says that6peopleare diagnosed as cancer every minute and one die of cancer in every7to8. Cancer has alreadybecome the “top killer” in human and threatens human life and health. Therefore, researches onanti-cancer medicine have long-term been a focus. Appearance of Cancer Molecular TargetedDrug can be called a great revolution in21century’s cancer therapy area.Latest research shows that β-carboline alkaloid can obviously restrain the proliferation activityof cancer cell and has significant function of restraining cancer new vessels. Based on Oleg S.Radchenko’s synthesis route in1997, this thesis improves the route and synthesis method,compounding a series of β-carboline derivant and proceeding relative biological activity testanalysis.(1) Taking5-methyl tryptamine and different phenylacetic acid substituendum as raw material,and dicyclohexyl carbodiimide as dehydrant at room temperature, acidamid is synthesized throughN-Hydroxy succinimide activation method one-pot method. Taking phosphorus oxychloride asdehydrant, dihydro-β-carboline is synthesized through Bischler-Napieralski method dehydratingamid to cycle. Taking active manganese dioxide as oxidative dehydrogenation reagent, a series ofβ-carboline derivative can be synthesized through the oxidization and aromatization of dihydro-β-carboline. The substituend o-bromine β-carboline is cyclized under220℃. Then through anionexchange, fascaplysin derivant is finally synthesized. The total recovery is around25%.(2) We discusse the effect of different methods and conditions to the synthesis of amid finalrecovery; studies the effect of different solvents to Bischler-Napieralski’s synthesis of dihydro-β-carboline; investigates active manganese dioxide from different methods, effects to oxidativedehydrogenation reaction of dihydro-β-carboline. Besides, it probes into the effect of potassiumpermanganate to the methy of β-carboline, when the methyl of β-carboline oxidiz to carboxylicacid under different solvent, temperature and dosage of oxidant.(3) We proceed a series of biological activity tests to β-carboline derivant and fascaplysinderivant, especially to1-(2-bromine-benzene formyl)-6-methyl-β-carboline and Me-fascaplysin.Results show that they have good restraint function to human colon cancer cell HT-29and Caco-2. While planar β-carboline’s biological activity is a bit higher than nonplanar β-carboline, anddifferences also exist in their cancer cell cycle control.