论文总字数：13794字

摘 要

穿心莲发现于印度种植于中国东部、中南和西南地区。穿心莲内酯是我国传统中草药穿心莲的主要有效成分之一。穿心莲具有清热解毒，凉血消肿之功效^[1]。Nanduri报道了一系列穿心莲内酯类似物的合成及抗癌活性^[2]。近年来的研究表明以穿心莲内酯为代表的二萜内酯类成分具有广谱的抗肿瘤活性。穿心莲内酯，具有毒性小, 价格低的特点^[3]，很多年来被用作治疗许多疾病，包括细菌和滤过性病毒引起的感染。穿心莲类酯作为抗肿瘤、抗病毒药物开发的先导化合物已成为基于穿心莲类酯新药开发的热点之一^[4]。本课题结合计算机辅助药物设计，发现穿心莲内酯对一类核受体具有良好的拮抗作用，可达到抗肿瘤的功效。所以本课题拟通过对穿心莲内酯进行结构改造，以增强对该核受体的拮抗作用，从而增强对恶性肿瘤治疗的功效。

关键词： 穿心莲内酯 抗肿瘤 结构改造

Abstract

Andrographis paniculata(Burm.f.)Nees was found in India and planted in east, middlesouth and southwest China. Andrographolide(AD) is one of the major active constituents form Andrographis, a traditional Chinese herbal medicine. Andrographis is used extensively as antipyretic,anti-infammtory and antivirus medicine for a long time^[1]. Nanduri et al. reported the synthesis and anticancer activity of a series of Andro analogues^[2].Recently, it’s newly pharmacological activities were found, AD has strongly anti-tumour effect. Andrographolide (Andro), It is characterized by low toxicity, low price^[3]. It has been used for many years to treat a variety of diseases including bacterial and viral infections.It as a lead compound for the synthesis of anti-tumor and anti-viral drugs, has become one of the hot spots in the new drug development area^[4]. This topic combined with computer aided drug design, the combination of AD and a kind of nuclear receptor pruduce antagonism action, can achieve antitumor efficacy. So this topic proposed to modify the AD structure, to strengthen the antagonism between the nuclear receptor, thereby enhancing the malignant tumor therapy.

Key Words: Andrographolide; antineoplastic; structure modification

目录

摘要…………………………………………………………………………………Ⅰ

ABSTRACT………………………………………………………………………Ⅱ

第一章 绪论………………………………………………………………………1

1.1炎症与肿瘤的关系…………………………………………………………1

1.1.1炎症相关性肿瘤……………………………………………………1

1.1.2炎症与肿瘤的发生…………………………………………………1

1.2肿瘤治疗方法………………………………………………………………1

1.2.1化学治疗……………………………………………………………1

1.2.2手术治疗……………………………………………………………2

1.2.3自然治疗……………………………………………………………2

1.2.4放射治疗……………………………………………………………3

1.2.5中医治疗……………………………………………………………3

1.3 穿心莲内酯及其衍生物直接的抗肿瘤作用………………………………3

1.3.1穿心莲内酯的理化性质……………………………………………3

1.3.2穿心莲的抗肿瘤作用………………………………………………4

1.4穿心莲内酯衍生物抗肿瘤构效关系………………………………………4

1.5选题目的及意义……………………………………………………………5

第二章 实验部分………………………………………………………………6

2.1 穿心莲内酯结构改造的合成路线设计……………………………………6

2.2 实验试剂及仪器……………………………………………………………6

2.2.1实验试剂……………………………………………………………6

2.2.2主要仪器设备………………………………………………………7

2.3 实验操作步骤………………………………………………………………7

2.3.1 14-(R)-苯氧基-3,19-异亚丙基穿心莲内酯的还原……………7

2.3.2 14-(R)-苯氧基-15-羟基-16-醛基穿心莲内酯的合成…………8

2.4 三废处理……………………………………………………………………9

第三章 结果与讨论……………………………………………………………10

3.1 14-(R)-苯氧基-3,19-异亚丙基穿心莲内酯的还原合成方法研究……10

3.1.1反应溶剂对产物收率的影响………………………………………10

3.1.2投料比对产物收率的影响…………………………………………10

3.1.3反应时间对产物收率的影响………………………………………11

3.1.4反应温度对产物收率的影响………………………………………11

3.2 14-(R)-苯氧基-15-羟基-16-醛基穿心莲内酯的合成方法研究………11

3.2.1 3,19-异亚丙基脱除剂的选择对反应产物的影响…………………11

3.2.2乙酸和水体积比对产物收率的影响………………………………12

3.2.3投料比对产物收率的影响…………………………………………12

3.2.4反应温度对产物收率的影响………………………………………13

第四章 总结与展望……………………………………………………………14

参考文献…………………………………………………………………………15

致谢…………………………………………………………………………………17

第一章 绪论

请支付后下载全文，论文总字数：13794字