兰州大学机构库 >化学化工学院
(-)-Isatisine A 的仿生合成研究
其他题名The Biomimetic Synthesis of (-)-Isatisine A
伍伟
导师谢志翔
学位类别博士
2013-05-31
关键词生物碱 抗HIV 仿生合成 二苯乙二酮重排 (-)-Isatisine A
中文摘要菘蓝是著名的传统中药,它的根和叶分别称为板蓝根和大青叶;板蓝根,性寒,味苦,具有清热解毒、凉血利咽之功效,临床上广泛用于抗病毒、抗菌、抗肿瘤、增强机体免疫力等。大青叶主要用于热毒发斑、丹毒、咽喉肿痛、口舌生疮、疮痈肿毒等症。本论文以中国科学院昆明植物研究所的陈纪军研究员从大青叶中分离得到的具有潜在抗HIV活性的(-)-Isatisine A为目标分子,进行合成研究,分为两章; 第一章对 (-)-Isatisine A 的合成进行了综述:(-)-Isatisine A是一个结构新颖的生物碱,其含有两个吲哚环、一个多取代的四氢呋喃环和内酰胺部分,是一个具有六环和五手性中心的复杂天然产物,而且具有潜在的抗HIV活性,因此它受到合成化学家的极大关注。从2007年发表以来到2012年底共有包括我们研究小组在内的五个研究组对(-)-Isatisine A的全合成进行了报道,本章对其他四个研究组的(-)-Isatisine A 合成路线及特点进行了综述。 第二章 天然产物(-)-Isatisine A的仿生合成研究:本章介绍我们课题组对 (-)-Isatisine A的仿生合成研究,在广泛的文献调研基础上提出(-)-Isatisine A的生源合成途径,认为其生源合成前体化合物是靛甙(Indican),经重排、氧化及酸催化等反应得到关键中间体,此中间体经二苯乙二酮重排类型的反应得到目标分子(-)-Isatisine A。据此我们设计二苯乙二酮类重排反应为模型反应,对该目标分子进行模型反应研究,在此基础上设计了以仿生的二苯乙二酮重排和吲哚对亚胺的加成为关键反应的合成路线,由于此路线的关键中间体未能氧化得到,且合成路线过长而设计新的合成路线。新的合成路线采用汇聚式的合成策略,以酮糖衍生物对亚胺的加成和二苯乙二酮重排为关键反应,来合成(-)-Isatisine A,由于酮糖衍生物对亚胺加成时发生了E1cb反应致使新产生的连氧手性中心构型稳定但与天然产物 (-)-Isatisine A 不一致,导致首先完成Isatisine A异构体合成;后经尝试转换保护基消除不利影响,成功地仿生合成了具有潜在抗HIV活性的天然产物 (-)-Isatisine A。 从已知的葡萄糖衍生物出发,经8步反应以8.6%的总收率仿生合成了具有潜在抗HIV活性的天然产物 (-)-Isatisine A,由于采用了二苯乙二酮重排为关键反应,此合成路线简洁高效,这也是二苯乙二酮重排运用于天然产物全合成中为数不多的例子之一。
英文摘要Woad is one famous traditional Chinese herbal medicine, of which the roots and leaves are respectively called “Ban-Lan-Gen” and “Da-Qing-Ye” in traditional chinese medicine. The Ban-Lan-Gen that is cold in nature and Da-Qing-Ye in taste can clear away heat and toxic materials inside the body, remove heat from the blood and relieve sore throat, so it is widespread used clinically for anti-virus, anti-bacteria, anti-tumor and enhancement of immunity. Folium is mainly suitable for the treatment of syndrome of toxic heat , hot spots injured by heat toxicity, erysipela , sore throat, mouth sores, carbuncles and pyogenic infections. The targeted molecule we have researched and synthesized is (-)-Isatisine A, which has potential anti-HIV-1 activity and was isolated from the leaves of Isatis indigotica Fort with by Chen Jijun researcher in Kunming Institute of Botany of Chinese Academy of Sciences. Our work is presented in the following two chapters. The first chapter is dedicated to review documents related to the synthesis of the (-)-Isatisine A. (-)-Isatisine A is a novel alkaloid which possesses a fused pentacyclic framework containing a densely substituted furan subunit, one aza-quaternary carbon center, and one oxo-quaternary carbon center with potential anti-HIV-1 activity. Thus it has drawn a great amount of attention from the synthetic community and the total synthesis routes of five research groups including ours have been reported from 2007 to 2012. The routes and features of other four groups are generalized in the first chapter. Chapter two is used to introduce our research work of the biomimetic synthesis of the natural product (-)-Isatisine A. On the base of extensive literature research,we proposed the biomimetic synthetic approach that from biomimetic Precursor Indican the key mediate compound can be obtained through rearrangement, oxidation and acid catalysis, which would then be converted to the targeted molecule by actions like the type of the benzilic ester rearrangement. We used the benzilic ester rearrangement as a model reaction to explore the synthesis of the targeted molecule. Based on our results we designed the synthetic route with biomimetic benzilic ester rearrangement and the addition of the indole to the imine as key reactions. Unfortunely the critical intermediate could not be obtained by oxidation and the route is too long, leading to the redesign of our route. Then a convergent synthetic strategy with the addition of the ...
全文链接查看原文
授予单位兰州大学
授予地点兰州
语种中文
文献类型学位论文
条目标识符http://ir.lzu.edu.cn/handle/262010/238706
Collection化学化工学院
Recommended Citation:
GB/T 7714
伍伟. (-)-Isatisine A 的仿生合成研究[D]. 兰州. 兰州大学,2013.
Files in This Item:
There are no files associated with this item.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Altmetrics Score
谷歌学术
谷歌学术Similar articles in Google Scholar
[伍伟]'s Articles
百度学术
百度学术Similar articles in Google Scholar
[伍伟]'s Articles
必应学术
必应学术Similar articles in Google Scholar
[伍伟]'s Articles
Related Copyright Policies
Null
???item.sidebar.baidu.bookmark-share???
???jsp.display-item.all??? (0)
[???jsp.display-item.idea???]
???jsp.display-item.comment-text2???
Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.