Study On The Total Synthesis Of Imidazolyl Isoflavone Derivatives

Ten kinds of imidazolyl isoflavone derivatives were designed and synthesized in this thesis based on references, which have thirty-seven compounds containing the middle compounds in all and a large number of which are oxygen heterocycle compounds. The twenty-two of these compounds are never reported so far by way of searching CA. All of these compounds were synthesized via five steps. The middle compounds andgoal products were confirmed by IR, 1H NMR, 13C NMR, elemental analysis and so on. We summarized optimal conditions on constructing C-O and C-N bond of complicated molecular structure. The reaction time has been shortened greatly in the reaction process by virtue of microwave-mediated synthesis. And then we gave pilot study on the antioxidative ability of ten target compounds, 4'-hydroxy-2-methy1-7-(3-(1-imidazolyl)propoxy)-isoflavone of which possesses strong radical scavenging effect. The results of experiment on radical scavenging effect indicate that the ability of scavenging radical relates not only to the numbers of hydroxyl but also to the length of allyl which join with 7-hydroxy. This is important progress on the knowledge of the ability of scavenging radical of isoflavones and its derivatives. The other actives of ten target products will be further studied in future. This thesis is constituted by four parts:In the first part a summarization is given on the main total synthetic methods of isoflavones, for example, deoxybenzoin method which generally involves two steps wherein a phenol is reacted in the presence of a Lewis acid with phenylacetic acid to generate an intermediate deoxybenzoin which is then cyclized with a one carbon electrophile. At present, this method is applied extensively because of facile materials and mild reaction condition. We also briefly introduce microwave-mediated synthesis, oxidation rearrangement and Pd-catalyzed cross-coupling methods. Furthermore, we give a summary on the pharmacological effects of isoflavones such as estrogenic, anticancer, antifungal and antimicrobial.In the second part, 7-acetoxy-2-methyl isoflavone derivatives were synthesized by reacting five deoxybenzoins produced by using microwave-mediated synthesis with acetic anhydride, respectively. And then 7-hydroxy-2-methyl isoflavones were gained by hydrolyzing 7-acetoxy-2-methyl isoflavone derivatives in the acid condition. The reaction time was changed from 10 h reported to 2 min. Deoxybenzoins, 7-hydroxy-2- methyl isoflavones and 7-acetoxy-4'-chloro-2-methyl isoflavone were confirmed by IR, 1H NMR, of which 7-acetoxy-4'-chloro-2-rnethyl isoflavone and 4'-chloro-7-hydroxy- 2-methyl isoflavone are rarely reported so far.4'-chloro-2-methyl-7-(2-bromoethoxy) isoflavone, 2, 4'-dimethyl-7-(2-bromo- propoxy)isoflavone, 2-methyl-7-(2-bromoethoxy) isoflavone, 4'-methoxy-2-methyl-7- (2-bromoethoxy) isoflavone and 4'-hydroxy-2-methyl-7-(2-bromoethoxy) isoflavone were gained by reacting 7-hydroxy-2-methyl is0flavone derivatives with 1, 2-d.ibromo- ethane. Their structures were characterized by IR, 1H NMR, of which 4-chloro- 2-methyl-7-(2-bromoethoxy) isoflavone, 2, 4'-dimethyl-7-(2-bromo-ethoxy)isoflavone and 2-methyl-7-(2-bromoethoxy) isoflavone are rarely reported so far.4'-chloro-2-methyl-7-(3-bromopropoxy)isoflavone, 2, 4'-dimethyl-7-(3-bromo- propoxy) isoflavone, 2-methyl-7-(3-bromopropoxy) isoflavone, 4'-methoxy-2-methyl-7- (3-bromopropoxy) isoflavone and 4'-hydroxy-2-methyl-7-(3-bromopropoxy) isoflavone were gained by reacting 7-hydroxy-2-methyl isoflavone derivatives with 1, 3-dibromo- propane, respectively. All of the structures were characterized by IR, 1H NMR, all of which are rarely reported so far.In the third part the title compounds were synthesized in high yield by refluxing bromoethoxy or bromopropoxy isoflavones with imidazole and potassium carbonate in acetone solution, respectively. The title compounds that never reported contain 4'-chloro-7-(2-(1H-imidazol- l-yl)ethoxy)-2-methyl isoflavone, 2, 4'-dimethyl-7-(2-1H- imidazo1-1-y1)ethoxy) isoflavone, 7-(2-(1H-imidazo1-1-y1)ethoxy)-2-methyl isoflavone, 7-(2-(1H-imidazol-1-yl)ethoxy)-4'-methoxy-2-methyl isoflavone, 7-(2-(1H-imidazo1-1- y1)ethoxy)-4'-hydroxy-2-methyl isoflavone, 7-(3-(1H-imidazo1-1-y1)propoxy)-4'-chloro- 2-methyl isoflavone, 2, 4'-dimethyl-7-(3-(1H-imidazo1-1-y1)prop-oxy) isoflavone, 7-(3-(1H-imidazo1-1-y1)propoxy)-2-methyl isoflavone, 2-methyl-7-(3-(1H-imidazol- 1-y1)propoxy) isoflavone, 4'-hydroxy-2-methyl-7-(3-(1H-imidazol-1-yl)propoxy) isoflavone. The structures of the target compouds were confirmed by IR, 1H NMR, 13C NMR and element analysis.In the last part, we give a pilot evaluation on antioxidative activity of the tiele compounds we have gained using phenanthroline-iron (â…¡) method. The results indicated that 4'-hydroxy-2-methyl-7-(3-(1H-imidazol-1-yl)propoxy) isoflavone possesses strong radical scavenging effect. But the others were not found obvious inhibition on hydroxyl free radical.