The Synthesis Of 2-phenylbenzo[b]furan Derivatives And Study On Anti-tumor Activity

The derivatives of 2-phenylbenzo[b]furan are fundamental building blocks of many natural products and pharmaceutical molecules with biological activities.Many2-phenylbenzo[b]furan compounds separated from botany are selective adenosine A1 receptor antagonists,antioxidants,anti-free radicals,immunosuppressors and they have good activities such as antitumor,antiviral and antibacterial.Because the derivatives of 2-phenylbenzo[b]furan are few in nature and they are difficult to be separated and purified,it is of great significance to synthesize the derivatives of2-phenylbenzo[b]furan in a high efficient and green way to study their pharmacological effects and develop drug leading compounds.The contents of this paper are divided into three parts:1.Using 2-iodophenol and phenylacetylene as substrates to build a model reaction on the synthesis of 2-phenylbenzo[b]furan in pure water and screening catalyst or catalytic system,and then studying the influences of other reaction conditions such as catalysts,co-catalysts,temperature,time and bases.The optimized conditions that we confirmed are: 0.5 mmol 2-iodophenol,0.6 mmol phenylacetylene,1mol % catalyst,2 mol % Cu I,4 mol % PPh3,1.5 mmol NEt3,2 m L H2 O,80 ℃,4 h,air condition.Evaluating the applicability of the catalytic system for the synthesis of 2-phenylbenzo[b]furan derivatives under the optimized conditions.2.Using the synthesized 2-(4-bromo-phenyl)-benzofuran and 4-methoxyphenylboronic acid as substrates to build a Suzuki coupling reaction catalyzed by palladium compounds,and then studying the influences of reaction conditions such as catalysts,solvents,bases,temperature and time.The optimized conditions that we confirmed are: 0.05 mmol 2-(4-bromo-phenyl)-benzofuran,0.08 mmol4-methoxyphenylboronic acid,0.1 mmol K2CO3,3 mol % catalyst,6 m L H2O+Et OH(V/V=1:1),80 ℃,4 h,air condition.Synthesizing a series of new2-phenylbenzo[b]furan derivatives under the optimized conditions.3.Detecting the anti-tumor activity of new 2-phenylbenzo[b]furan derivatives and screening the leading compounds with anti-tumor activity to lay the foundation of the development of new anti-tumor drugs.The results show that five new compounds(derivatives Ⅰ、Ⅴ~Ⅷ)have a dose-dependence on the inhibiting rate of lung cancer cell A 549 and have a certain antitumor activity.