摘要:流感通常由流感病毒引起，是一种经常遇到的呼吸系统疾病，对人们的身体健康有重大影响。 当前，防治流感的主要措施是接种疫苗和药物。神经氨酸酶抑制剂是当前治疗效果最好的抗流感病毒药物，通过选择性地控制流感病毒表面的神经氨酸酶，使得流感病毒在寄主细胞内不能进行复制和传播，从而有效治疗流感。板蓝根生药和现有制剂具有良好的抗病毒作用，研究表明表告依春是板蓝根抗流感病毒的主要活性成分之一。

本论文研究以板蓝根中的主要活性成分表告依春为前提，对其结构进行修饰与优化，得到一系列具有较好活性的神经氨酸酶抑制剂。主要研究工作为以商品化的芳香醛为起始原料，通过醛基加成，氰基还原等化学反应得到目标化合物，所制备的目标化合物进行结构表征是利用氢谱，碳谱，红外等方法；所得化合物利用荧光底物检测原理测定其NA抑制活性，并计算出目标化合物的半数抑制浓度IC50值。

关键字：流感病毒；神经氨酸酶抑制剂；板蓝根；活性测试

Chemical synthesis and neuraminidase inhibitory activity assay for tables and reports of ephryn derivatives

Abstract:Influenza is usually caused by influenza virus and is a common respiratory disease that has a major impact on human health. At present, the main measures to prevent influenza are vaccination and drugs. Neuraminidase inhibitors are the best anti-influenza virus drugs currently used for the treatment of flu by selectively inhibiting the neuraminidase on the surface of the influenza virus and preventing the virus particles from replicating and releasing in the host cells. Radix Isatidis crude drugs and existing preparations have good antiviral effects, and studies have shown that Epimedium is one of the main active ingredients of Isatis Indica against influenza virus.

In this dissertation, the main active compounds in Isatis indigotica were reported as the lead compounds, and their structures were modified and optimized to obtain a series of neuraminidase inhibitors with good activity. The main research work is to use commercially available aromatic aldehydes as starting materials to obtain target compounds through chemical reactions such as aldehyde group addition and cyano reduction. The prepared target compounds are analyzed by hydrogen spectrum, carbon spectrum, infrared spectrum and high resolution mass spectrometry. Methods Structural characterization was performed. The compounds were measured for their NA inhibitory activity using the fluorescent substrate detection principle, and the IC50 value of the target compounds was calculated.

Keywords: Influenza virus; Neuraminidase inhibitors; Isatis root; Activity test

目录

摘要 I

Abstract II

第一章  文献综述 1

1.1  流感和流感病毒 1

1.1.1  流感病毒的分子结构与分类 1

1.1.2  流感病毒的复制与感染机制 2

1.2  神经氨酸酶 2

1.2.1  神经氨酸酶（NA）的结构和作用方式 2

1.2.2  神经氨酸酶抑制剂 3

1.2.3  NA与配体的作用机制 4

1.3  神经氨酸酶抑制剂的分类 5

1.3.1  唾液酸类神经氨酸酶抑制剂 5

1.3.2  苯甲酸类神经氨酸酶抑制剂 5

1.3.3  吡咯烷类神经氨酸酶抑制剂 6

1.3.4  环戊烷类神经氨酸酶抑制剂 6

1.3.5  环己烯类神经氨酸酶抑制剂 6

1.3.6  天然产物类神经氨酸酶抑制剂 6

第二章  目标化合物的合成 7

2.1  前言 7

2.2  试剂与仪器 8

2.3  目标化合物合成路线设计 8

2.4  结果与讨论 8

2.4.1  芳香醛的硅氰化反应 8

2.4.2  氰基还原反应 9

第三章  活性测试实验 9

3.1  目标化合物的活性测试 10

3.1.1  背景资料 10