Synthesis Of Benzimidazo[2,1-α]isoquinoline And Seleno-benzo[b]azepines Compounds

N-heterocycles are important molecular backbones in medicinal chemistry and synthetic chemistry.Almost half of the top 200 drugs by sales contain N-heterocyclic molecular skeletons.The design and synthesis of N-heterocyclic molecular skeletons is a crucial part of medicinal chemistry.Therefore,the development of concise methods for the construction of Nheterocyclic molecular skeletons is an important topic in medicinal chemistry research.Structurally diverse tetracyclic benzimidazo[2,1-α]isoquinolines are important synthetic intermediates.They are also key molecular backbones for antidiabetic,antibacterial,and antitumor compounds and possess powerful biological properties.There are many previous methods to construct these polycyclic frameworks,but they mainly involve multi-step condensation reactions and harsher reaction conditions.Therefore,this thesis need to develop more concise routes for efficient access to these tetracyclic frameworks.In contrast,fluorinated organic molecules have a wide range of biological functions and have important applications in pharmaceuticals,materials and agriculture.Among the fluorinated groups,trifluoromethylthio group(SCF3)has attracted the attention of chemists because of its strong electron-absorbing effect,high lipophilicity and metabolic stability.Incorporation of trifluoromethylthio groups into drugs or lead compounds helps to improve their medicinal properties such as membrane permeability,absorption rate and stability.Thus,the development of simple and efficient synthetic strategies for the preparation of SCF3-substituted tetracyclic benzimidazo[2,1α]isoquinoline derivatives is a very valuable research topic.In the second chapter of this thesis,we investigated the trifluoromethylthiolation cyclization reaction of N-methylacrylyl 2arylbenzimidazole and the fluorinated reagent AgSCF3 to successfully construct 26 trifluoromethylthio-substituted tetracyclic benzimidazo[2,1-a]isoquinoline derivatives.Mechanistic studies showed that the reaction was initiated by the peroxide-induced generation of the SCF3 radical from AgSCF3.The gram-level reaction further extends the utility of this radical cyclization strategy.This thesis also explored the inhibitory effect of some products on escherichia coli DH5α through inhibition circle experiments.In Chapter 3 of this thesis,we also designed a diene substrate,N-(but-3-en-l-yl)-4methyl-N-(2-(1-phenylvinyl)phenyl)benzenesulfonamide,to achieve electrochemically driven chemoselective addition cyclization of the diene substrate with diselenides to give 31 important selenium-containing 8-membered benzo[b]azepine derivatives.In addition,the seleniumcontaining 8-membered azacyclic compounds underwent oxidative elimination in the presence of m-chloroperoxybenzoic acid(m-CPBA)or hydrogen peroxide(H2O2)to give the deselenated conjugated diene products.Through radical inhibition assays and cyclicvoltammetry measurements,this thesis propose a possible mechanism of radical cyclization.