Studies On The Synthesis Of Benzofuran Neolignans Mannich Base And Ferulic Acid Amide Derivatives

Benzofuran neolignans are widespread in nature, exhibiting a broad range ofbiological activities and are potent ingredients of many medicine plants. They have abroad spectrum of biological activities including antitumo, antioxidation, antifangal,anti-imflammatory, analgesic. And many people pay attention to it. The amideof ferulic caid also has outstanding biological activities, such as anticanc-er, antioxidation, immunoregulation, neuroproctive and antiplatelets aggre-gation activity. They have a broad range of use in medicine, pesticides,cosmetics, food additives and other respects. In order to meet the needs forselecting the substances with biological activities and developing new drugs, the thesisattempted to facile synthesized an array of mannich base and a class of amide fromisoeugenol or vanillin.1、The natural dihydrobenzofuran neolignans(licarin A)1was synthesized fromisoeugenol through biomimetic oxidative coupling. Compound2(2-(3-methoxy-4-hydroxyphenyl)-3-methoxy carbonyl-5-methoxy carbonyl vinyl-7-mehoxy-2,3-dihydr-obenzofuran) was synthesized from licarin A through DDQ dehydrogenate reaction.Compound3(2-(3,4-dimethoxy-phenyl)-3-methoxy carbonyl-5-methoxy carbonylvinyl-7-methoxy-2,3-dihydrobenzofuran) was synthesized from licarin A throughO-methylation tow steps. Based on Mannich reaction with microwave heatingtechnology, seven benzofuran neolignans mannich base4~10were achieved, especiallythe compounds6,8,9and10were new compounds. This aminomethylation occurredpreferentially at5-C position of benzofuran neolignans.2、 Compound11(ferulic caid) was synthesized from vanillin throughKnoevenagel reaction. A series of amide derivertives were synthesized from feruliccaid and amine with anhydrous THF as solvent and DCC/DMAP as the phase transfercatalyst. The reaction under protecting with N2, stirrillg conditions and Compounds12~19were obtained, especially the compounds17,18were new compounds. Inaddition, we aslo study the preparation of compound20from vanillin and nitrometh-ane.3、The inhibitory effect on cervical cancer cell line of the synthesized compound6,8,9and10was evaluated by using the method of MTT. According to the bioactiveresearch, the compound6,8and10have an inhibitory effect on the cervical cancer cell(HeLa), especially the bioactivity of compound8was better(IC50is8.385μmol L-1, Positive control cisplatin and paclitaxel IC50were58.724μmol L-1,0.040μmol L-1).Compound9has no inhibitory effect on the cervical cancer cell.4、All of the synthesized compounds1~20have been confirmed by1H NMR,13CNMR, MS and IR.