论文总字数：17825字
摘 要
本文以抗肿瘤铂药为基础，合成了一种新型偶联生物素的铂配合物。
自从顺铂抑制大肠杆菌的活性被偶然发现后，研究人员不断的对铂类配合物进行研究和开发，旨在攻克癌症治疗的世界性难题。1978年，顺铂作为第一代抗肿瘤药物批准上市，用于治疗睾丸癌和卵巢癌。之后，卡铂作为第二代抗肿瘤铂药获得批准上市，其化学性质稳定，溶解度高，毒副作用低于顺铂，作用效果与顺铂相似，在某些癌症治疗中可代替顺铂。尽管顺铂和卡铂有很好的治疗效果，应用广泛，但也有其缺点，其毒副作用，以及顺铂产生耐药性的病人再用卡铂时效果会更差，主要原因是两者有相同的载体基团，产生了交叉耐药性，这也就成了第三代铂抗癌药物研发的焦点和急需解决的问题之一。能克服与顺铂产生交叉耐药性的铂类配合物—奥沙利铂应运而生。
在本研究中，我们用环己二胺为载体，乙二酸做为离去基团，合成了四价铂配合物，并将铂配合物与生物素偶联，合成了一种新型的抗肿瘤化合物,旨在同时发挥生物素分子的靶向受体作用和铂药的细胞毒作用。
关键词：抗肿瘤，铂（IV）配合物，生物素
THE SYNTHESIS OF CONJUGATION OF BIOTIN TO Pt(IV) COMPLEXES
FENG Min-chang
Supervised by Professor Gou Shao-hua
(School of Chemistry and Chemical Engineering. Southeast University. Nanjing 211189)
Abstract
In this paper, we synthesized a new biotin-conjugated platinum complexes based on the anti-tumor platinum drugs.
Since cisplatin inhibit the activity of E.coli were discovered by accident, the researchers continued to research and develop the Pt compounds, it aims to overcome the cancer treatment worldwide problem. In 1978, cisplatin as a first-generation anticancer drugs was approved for the treatment of testicular and ovarian cancer. Researchers have synthesized thousands of platinum complexes, the second generation anti-tumor platinum drugs—carboplatin approved. Carboplatin was stable chemical properties, high solubility, lower toxic side effects than cisplatin and a similar effect with cisplatin. So carboplatin can replace cisplatin in the treatment of some cancers. Although cisplatin and carboplatin have a good therapeutic effect, is widely used, but it also has its drawbacks. Resulting in a cross-resistance, which will become the focus of the third generation platinum anti-cancer drug development and one of the urgent need to solve the problems. Overcome with cisplatin cross-resistance of platinum complexes - oxaliplatin emerged.
In this paper, ethane diacid is used as the leaving group, we synthesize a Pt（IV） compound which then was connected with biotin. So the biotin can target the cancer cells.
Key words: anti-cancer, Pt（IV） compounds, biotin
目 录
摘要···························································· | I |
Abstract························································· | II |
第一章 绪论····················································· | 1 |
1.1 引言···················································· | 1 |
1.2 具有经典构效关系的铂类抗肿瘤药物的发展历程及临床评价···· | 2 |
1.2.1 第一代铂类抗肿瘤药物—顺铂························· | 2 |
1.2.2 第二代铂类抗肿瘤药物—卡铂及其类似物··············· | 3 |
1.2.3 含手性配体的铂配合物—1,2-环己二胺类铂配合物······· | 3 |
1.3 非经典铂类抗肿瘤药物···································· | 5 |
1.3.1 铂（IV）配合物······································ | 5 |
1.3.2 多核铂配合物······································· | 5 |
1.3.3 具有空间位阻的铂（II）配合物························· | 6 |
1.4 铂类配合物的作用机理···································· | 7 |
1.5 生物素·················································· | 7 |
1.6 选题依据及意义·········································· | 7 |
1.7 结语···················································· | 8 |
第二章 实验部分················································· | 10 |
2.1 试剂与仪器·············································· | 10 |
2.2 铂（II）配合物············································· | 10 |
2.2.1 铂（II）配合物的制备································· | 10 |
2.2.2 铂（II）配合物的表征································· | 11 |
2.3 铂（IV）配合物············································ | 12 |
2.3.1 铂（IV）配合物的制备································ | 12 |
2.3.2 铂（IV）配合物的表征································ | 13 |
2.4 铂（IV）配合物与生物素偶联································ | 15 |
2.4.1 偶联生物素的铂（IV）配合物的制备···················· | 15 |
2.4.2 偶联生物素的铂（IV）配合物的表征···················· | 16 |
2.5 实验结果与讨论·········································· | 17 |
致谢···························································· | 18 |
参考文献(References) ············································ | 19 |
第一章 绪 论
1.1 引言
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