苯并吡喃衍生物合成新方法研究及体外抗肿瘤活性的初步筛选-中药学专业论文.docx

成都中医药大学硕士学位论文 万方数据 苯并吡喃衍生物合成新方法研究及体外抗 肿瘤活性的初步筛选 摘 要 苯并吡喃及其衍生物是一类非常重要的含氧杂环化合物，这些结构广泛存在 于许多具有生理活性和药理活性的天然产物及其合成类似物中，由于该类化合物 具有抗肿瘤、抗菌、抗病毒、抗高血压、抗抑郁、抗氧化等广泛而显著的生物活 性，具有潜在的药物开发前景，引起了有机化学家和药物化学家的关注。因此， 研究含有苯并吡喃环的合成与反应具有十分重要的意义。本论文主要分为三部分 来具体进行阐述。 第一部分，目标化合物合成方法的研究。以不同取代的水杨醛与吲哚酮、吡 唑啉酮、硝基甲烷、N,N-2-甲基-巴比妥酸、茚满二酮等在哌啶的催化下发生 Knoevenagel 缩合反应，得到不同的 Knoevenagel 加合物（4a-q），再与丙二腈在 四氢呋喃（THF）作溶剂、碳酸钾做催化剂下，于 60℃反应生成 17 种苯并吡喃 衍生物（6a-6q）。所有的化合物都通过了质谱、氢谱以及碳谱鉴定，收率在 70%-98%之间。 第二部分，体外抗肿瘤活性的初步筛选。采用 MTT 法研究目标化合物对 A549、U87、MCF-7 三种肿瘤细胞抑制作用。初步试验结果表明，抑制效果不 理想，有待进一步深入研究。 第三部分，在查阅相关文献的基础上，对苯并吡喃及其衍生物的性质、应用 以及合成方法进行了简单综述。 关键词：苯并吡喃 Knoevenagel 反应 抗肿瘤 合成 MTT I  Study on the synthesis of chromene derivatives and their preliminary antitumor evaluation Abstract Chromene and its derivatives are a very important class of important oxygen-containing heterocyclic compounds. These structures are widely present in nature products and their derivatives which posses significant biological activities, such as antitumor, antibacterial, antiviral, antihypertensive, antidepressant, antioxidat- -ive and so on. The chromenes were paid more and more attention because of their broad drug development prospects. Therefore, it is a significant work to the research on synthesis reaction of the containing chromene ring heterocyclic compounds. This dissertation is mainly composed of three parts. In the first part, the study of synthesis target compounds. The compounds 4a-q have been achieved via Knoevenagel condensation with different salicylaldehyde and oxindole, pyrazolone, nitromethane, N,N-2-methyl-barbituric acid and indanedione, using piperidine as catalyst. Then ， the mixture reacted with malononitrile in tetrahydrofuran (THF) as solvent and potassium carbonate as catalyst at 60℃, which generated 17 kinds of benzopyrapon derivatives (6a-6q). All the compounds were characterized by MS, 1HNMR, 13CNMR and the yields were obtained between 70%-98%. In the second part, Preliminary screening of antitumor activity was stu