论文总字数：20611字

摘 要

本文是对苯并吡喃衍生物的性质、用途、以及传统的化学催化合成法进行了系统的介绍与论述。说明了这些方法的优点与不足,如催化效率高但溶剂有毒或易挥发、催化剂制备困难且难以重复使用、产率低等，而且对环境有害,难以达到工业化规模。在此基础上探索出了一条由脂肪酶催化的环境友好的新型绿色合成方案, 相对于前述传统方法有一些显著优势。以4-羟基香豆素、芳香醛和丙二腈为原料,脂肪酶催化Knoevenagel缩合-Michael加成串联反应合成苯并吡喃衍生物。对酶源、最佳反应体系、反应温度、酶量、反应时间等工艺条件进行优化,最终发现了在有机相中、无水条件下、TLIM脂肪酶催化为最适反应方案。该方法具有反应条件温和、操作流程简单、催化剂便宜易得、收率高等优点。

关键词;苯并吡喃衍生物 脂肪酶 一锅法 串联反应

Synthesis of benzopyran derivatives by one - pot reaction catalyzed by organic phase medium and lipase TLIM

Abstract

In this paper, the properties and applications of benzopyran derivatives, as well as the traditional chemical catalytic synthesis methods were systematically introduced and discussed.The advantages and disadvantages of these methods are explained, such as high catalytic efficiency but toxic or volatile solvent, difficult preparation of catalysts and difficult reuse, low yield, etc.And it is harmful to the environment and difficult to reach the scale of industrialization.On this basis, a new environmentally friendly and green synthesis method catalyzed by lipase was explored.There are some significant advantages over the traditional methods described above.Benzopyranes derivatives were synthesized from 4-hydroxy coumarin, aromatic aldehyde and malononitrile via a series reaction catalyzed by lipase  knoevenagel-michael addition.The process conditions of enzyme source, optimal reaction system, reaction temperature, enzyme amount and reaction time were optimized.Finally, it was found that TLIM was the optimal reaction scheme with DMSO as the organic solvent and without water.The method has the advantages of mild reaction conditions, simple operation process, cheap and easy catalyst and high yield.

Key words:benzopyran derivatives;lipase;one-pot reaction ;cascade reaction

目 录

摘要…………………………………………………………………………….........I

ABSTRACT……………………………………………………………………….Ⅱ

第一章 引言…………………………………………………………………........1

1.1 苯并吡喃衍生物的性质及其生理用途………………………………....2

1.2 苯并吡喃衍生物合成方法的研究现状………………………………....3

第二章 实验部分……………………………………………………………......7

2.1 实验试剂与仪器………………………………………………………....7

2.2 四氢苯并吡喃衍生物合成的通用步骤……………………....................8

2.3 苯并吡喃衍生物的合成收集与液相色谱分析法的建立………………9

2.3.1 目标产物的合成…………………………………………...............8

2.3.2 目标产物液相色谱分析法的建立……………………………...…8

第三章 结果与讨论…………………………………………………………....10

3.1对酶源的筛选以及工艺条件优化……………………………………....10

3.1.1 脂肪酶的筛选……………………………………………………..10

3.1.2 溶剂的筛选……………………………………………………......11

3.1.3 对反应体系含水量的优化……………………………………......12

3.1.4 温度的筛选…………………………………………......................12

3.1.5 酶浓度和反应所需最适时间的筛选…………………………......13

3.2对芳香醛进行结构拓展考察底物的适用性……………………............14

3.3脂肪酶TLIM催化Knoevenagel -Michael串联反应可能的机理….....16

第四章 结论与展望…………………………………………………………....17

参考文献……………………………………………………………………….....18

致谢……………………………………………………………………………......22

第一章 引言

1.1 苯并吡喃衍生物的性质及其生理用途

四氢苯并吡喃及其衍生物是一类非常有药理生理价值的杂环化合物，不管是在动物体中存在，在植物体中也广泛存在^[1]。研究发现,苯并吡喃衍生物具有独特的结构模体,表现出广泛的生理活性^[2]和药学活性^[3]。如作为平滑肌解痉药^[4]、利尿药^[5]、抗肿瘤^[6]、细胞毒性^[7]、抗炎症^[8]、抗疟疾^[9]、抗高血糖、抗高血脂^[10]。并且也可以作为认知性增强剂治疗中枢神经退行性疾病，如阿尔兹海默症^[11]、帕金森综合征、亨廷顿病^[12]等。如图1-1-1展示了一些天然产生的具有生物活性的苯并吡喃衍生物,它们具有潜在的药理学价值。

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