论文总字数：25800字

摘 要

穿心莲，俗称“苦涩之王”，是一种属于爵床科的药用草本植物。穿心莲内酯又名雄茸内酯、穿心莲乙素，是从沙地松的地上部分中分离出来的，在穿心莲中含量仅有2%左右，属二萜内酯类天然产物，最主要的用处是作为合成类似物的原料，其衍生物具有抗炎、抗菌、抗病毒（抗HIV活性）、抗高血压、抗血栓形成、抗肿瘤、免疫调节、保肝利胆等药理作用，而且毒性小、价格低廉，特别是针对上呼吸道感染疗效显著，被誉为天然抗生素药物，在中国、泰国、印度和其他东南亚国家已经被广泛用于治疗病毒感染和传染性疾病。

目前，针对穿心莲内酯的改造及修饰的方法很多，但这些方法都有着共同的特点，那就是——均保留α，β-不饱和-γ-丁内酯，或者用其他药效基团替换该官能团的方法。常见的改造对象有C-3,14,19位羟基和Δ^12（13）、Δ^8（17）的烯基，前者目的主要是增加水溶性，后者目的是增加药理活性，通过对其相关结构的改造和修饰，能显著增强其多个方面的活性。

本文以穿心莲内酯（AG）为原料，设计并逐步合成穿心莲内酯衍生物：可分别选择丙酮和2，2-二甲氧基丙烷与AG反应，得到环醚的结构的A-1， 该产物C-14位羟基β-消除后能得到A-2，可通过引入易离去的对甲基苯磺酸在碱性条件下消除，又可用酸酐进行脱水获得，再将产物A-2选择性氧化Δ^(12,13)烯基得到Z-2，这产物又可以用两种方式反应得到，其一是用催化量的OoO₄和定量的NaIO₄作氧化剂氧化获得，其二是用KMnO₄氧化获得。合成的衍生物在分离提纯后，均可通过核磁共振氢谱证实其结构。

关键词：穿心莲内酯； 抗病毒；衍生物；天然抗生素

Synthesis of Andrographolide Derivatives

Abstract

Andrographis paniculata, commonly known as the "king of bitterness", is a medicinal herb belonging to the family Cymbidium. Andrographolide, also known as andrographolide and andrographolide, is isolated from the aerial part of sand pine and contains only about 2% of andrographolide. It is a natural product of diterpene lactones and the most important use It is a raw material for synthetic analogues, and its derivatives have anti-inflammatory,antibacterial, antiviral (anti-HIV activity),anti-hypertensive,anti-thrombotic, anti-tumor, immunomodulatory, hepatoprotective and choleretic effects. It is small and inexpensive, especially for upper respiratory tract infections. It is known as a natural antibiotic medicine and has been widely used to treat viral infections and infectious diseases in China, Thailand, India, and other Southeast Asian countries.

At present, there are many methods for the modification and modification of andrographolide, but these methods all have the common characteristics, that is, they all retain α, β-unsaturated-γ-butyrolactone, or replace them with other pharmacophore The functional group method. Commonly modified objects are C-3, 14, 19 hydroxyl group and Δ^{12 (13)}, Δ^{8 (17)} alkenyl group, the former purpose is mainly to increase water solubility, the latter purpose is to increase pharmacological activity, through its related structure Transformation and modification can significantly enhance the activity of many aspects.

In this paper, andrographolide (AG) is used as raw material to gradually synthesize andrographolide derivatives: acetone and 2,2-dimethoxypropane can be selected to react with AG to obtain A-1 with cyclic ether structure. The product C A-2 can be obtained after the -14-hydroxy β-elimination, which can be eliminated by introducing easy-to-lease p-toluenesulfonic acid under alkaline conditions, and can be obtained by dehydration with acid anhydride, and then selectively oxidize the product A-2 The Δ ¹²⁽¹³⁾ alkenyl group obtains Z-1. This product can be obtained by two ways of reaction. One is obtained by oxidation with a catalytic amount of OoO₄ and a quantitative amount of NaIO₄ as an oxidant, and the other is obtained by oxidation with KMnO₄. After separation and purification of the synthesized derivatives, the structure can be confirmed by nuclear magnetic resonance hydrogen spectroscopy.

Keywords: andrographolide; antiviral; derivatives; natural antibiotics

目录

摘要 I

Abstract II

目录 I

第一章 文献综述 1

1.1 抗病毒作用 2

1.2抗菌消炎作用 4

1.3抗高血压抗血栓作用 5

1.4保肝利胆作用 6

1.5抗肿瘤作用 8

1.6本文研究目的及意义 9

第二章 材料与方法 11

2.1 穿心莲内酯衍生物合成路线的设计 11

2.2主要实验试剂 11

2.3主要实验仪器 12

2.4衍生物A-1的合成 13

2.5衍生物A-2的合成 14

2.6衍生物Z-1的合成 15

2.7废弃物的处理 15

第三章 结果与讨论 16

3.1衍生物A-1最优合成路线的研究 16

3.1.1合成方法对A-1产率的影响 16

3.1.2投料比对A-1产率的影响 16

3.1.3温度对A-1产率的影响 17

3.1.4反应时间对A-1产率的影响 18

3.1.5酸洗剂对A-1产率的影响 18

3.2衍生物A-2最优合成路线的研究 19

3.2.1合成方法对A-2产率的影响 19

3.2.2投料比对A-2产率的影响 20

3.2.3温度对A-2产率的影响 20

3.2.4反应时间对A-2产率的影响 21

3.2.5酸洗剂对A-2产率的影响 22

3.3衍生物Z-1最优合成路线的研究 22

3.3.1合成方法对Z-1产率的影响 22

3.3.2投料比对Z-1产率的影响 23

3.3.3温度对Z-1产率的影响 24

3.3.4反应时间对Z-1产率的影响 24

3.3.5酸洗剂对Z-1产率的影响 25

第四章 总结和展望 26

参考文献 27

致谢 31

第一章 文献综述

请支付后下载全文，论文总字数：25800字