脱氢枞胺基含氮杂环化合物的合成及与DNA的作用 (1)-毕业(学术)论文设计.docVIP

l 南京林业大学 本科毕业设计（论文） 题 目：脱氢枞胺基含氮杂环化合物的合成及与DNA的作用 学 院： 南方学院 _ 专 业： 精细化工 _ 学 号： n080203101 _ 学生姓名： _ 指导教师： __ _ 职 称： 教授 _ 二O一二年五月十八日 摘 要 脱氢枞胺是一种重要的松香改性产品，其特有的三环二萜结构赋予其抗菌、抗病毒、抗癌等生物活性。本文的研究目的是对脱氢枞胺的B环进行改性，合成新的脱氢枞胺衍生物，并测试其与DNA的相互作用，希望能将脱氢枞胺衍生物的应用领域拓展到生物制药领域，促进松香产品深加工的发展。 本文以脱氢枞胺为原料，经过乙酰化、铬酸氧化在B环引入羰基，得到氧化乙酰脱氢枞胺，再通过Beckmann重排在B环引入氮原子扩环得到新化合物N-(3-异丙基-8,11a-二甲基-6-氧代-6,7,7a,8,9,10,11,11a-八氢-5H-二苯并[b,d]氮杂卓-8-基甲基)-乙酰胺，氢化铝锂还原得到新化合物乙基-(3-异丙基l-8,11a-二甲基-6,7,7a,8,9, 10,11,11a-八氢-5H-二苯并[b,d氮杂卓-8-基甲基)-胺。将7-氧代乙酰脱氢枞胺溴化，得到新化合物6-溴-7-氧代乙酰脱氢枞胺。作者还尝试用6-溴-7-氧代乙酰脱氢枞胺构造呋喃、吡咯杂环，却意外地得到了原来的7-氧代乙酰脱氢枞胺和消除产物5,6-烯-7-氧代乙酰脱氢枞胺。 将合成的4种化合物与E. coli质粒DNA作用，经琼脂糖凝胶电泳分析，发现它们都能切割E. coli质粒DNA，形成新的条带。 关键词：脱氢枞胺；Beckmann重排；DNA切割 Abstract Dehydroabietic amine is one of the rosin derivatives. Its characteristic tricyclic diterpene structure feature the molecule with antibacterial, antivirus and anticancer activities. The purpose of this paper is to modify the B ring of dehydroabietic amine, synthesize new derivatives of dehydroabietic amine and investigate its interaction with DNA. It is hoped that the further processing industry of rosin can be promoted, while these rosin derived compounds applied to bio pharmaceutical fields. Starting from dehydroabietic amine, a carbonyl group is introduced to B ring by chromic acid oxidation, a ketone is obtained. A nitrogen atom is inserted to B ring via Beckmann rearrangement with ring extension, then reduce it to Ethyl- (3-isopropyl- 8,11a-dimethyl-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[b,d]azepin-8-ylmethyl)-amine by lithium aluminum hydride. The author also attempt to construct furan and pyrrole heterocycles fused with B ring, but the original ketone and an elimination product is obtained. The interation of those 4 compounds with DNA is analysed by gel electrophoresis. They are all able to cleavage plasmid DNA of E. coli. Keywords: dehydroabietic amine, Beckmann rearr