3-甲氧基黄酮的新合成研究

【作者】 姚国新；

【导师】 朱锦桃；

【作者基本信息】 浙江理工大学 ， 有机化学， 2011， 硕士

【摘要】 黄酮类化合物是自然界中分布最广的一类多酚类物质,其有着广泛且重要的生理药理活性,如抗氧化、抗癌、抗过敏、抗菌、抗炎活性以及抗心血管疾病和镇痛作用。3-甲氧基黄酮由于其特定的抗病毒活性和抗肿瘤活性,使得其合成研究备受人们的青睐。本论文研究了3-甲氧基黄酮的制备。首先通过邻羟基苯乙酮衍生物与苯甲醛衍生物发生Claisen-Schmidt缩合反应,得到查尔酮化合物,用SeO2氧化环合查尔酮得到系列黄酮化合物,接着在过溴化吡啶鎓盐的作用下,选择性溴化得到3-溴黄酮化合物,最后与甲醇钠反应,得到系列3-甲氧基黄酮化合物。首先邻羟基苯乙酮衍生物与苯甲醛衍生物在20%KOH溶液中,以TBAB为催化剂发生羟醛缩合反应,得到查尔酮化合物,其收率为60%~80%左右;同时采用固相研磨方法来合成2-硝基查尔酮。以2 equivalen SeO2作为氧化剂,正辛醇为溶剂,将查尔酮氧化环合得到黄酮化合物,收率为40%~60%左右。以过溴化吡啶鎓盐作为溴化剂,与黄酮化合物发生溴化反应,得到系列3-溴黄酮化合物,收率为70%~90%左右。甲氧基化反应是整条路线的关键步骤。以甲醇钠作为甲氧基化试剂,在TBAB催化下,与3-溴黄酮反应得到系列3-甲氧基黄酮化合物,收率为40%~60%左右。在本论文的主要目标(黄酮化合物转变成3-甲氧基黄酮化合物)实现的过程中,涉及到一系列的查尔酮、黄酮、3-溴黄酮以及3-甲氧基黄酮的合成,这为后来的生物活性检测或构效关系研究打下坚实的物质基础。上述所有目标产物及关键中间体的谱图数据,如:红外光谱、核磁共振氢谱、碳谱等,均符合各化合物的结构特征。更多还原

【Abstract】 Flavonoids from a class of polyphenos which are ubiquitous in nature, possess wide spectrum and importance of biological and pharmacological activities, such as antioxidant, anticarcinogenic, antiallergic, antimicrobial, antiinflammatory activity as well as anticardiovascular and analgesic properties. Due to specific antiviral activity and antitumor activity of 3-methoxyflavones, tremendous attentions are given to the synthesis of 3-methoxyflavones.In this paper, the process of preapring the 3-methoxyflavones was described concisely as follows. Firstly, chalcones were prepared from o-hydroxyacetophenone derivations and benzaldehyde derivations by Claisen-Schmidt reaction, which were oxidative cyclized under the effect of SeO2 to give flavones. Then, flavones were converted to 3-bromo?avones by selective bromination with Pyridinium bromide perbromide. At last, 3-methoxyflavones were obtained from 3-bromo?avones via methoxylation with sodium methoxide.Chalcones were prepared from o-hydroxyacetophenone derivations and benzal -dehyde derivations by Claisen-Schmidt reaction in 20% KOH solution and taking TBAB as catalyst, the yields were about 60%⁸0%; Meanwhile, 2-nitrochalcone was obtained by gringing method.The synthetic route for flavones were proposed. Under the condition of 2 equivalen SeO2 and octanol as solvent, a series of flavones were obtained, the yields were about 40%⁶0%.The transformation of flavones into the corresponding 3-bromo derivatives proceeded smoothly using the pyridinium bromide perbromide, the yields were about 70%⁹0%.The methoxylation is the key step of the whole reaction route. Under the effect of sodium methylate and TBAB as catalyst, 3-bromoflavones were converted to 3-methoxyflavones, the yields were about 40%⁶0%.In the process of achieving the main objective（flavones were convert to 3-methoxyflavones） of the thesis, some of flavonoids, such as chalcones、flavones、3-bromoflavones、3-methoxyflavones were synthesised, which were laid substantial material foundation for further study of the biological activity or structure-activity relationship.The structures of the target compounds and key intermediates were confirmed by IR, ¹H NMR and ¹³C NMR.更多还原