天然产物Podophyllotoxin和Helioxanthin的全合成研究

发布时间：2018-03-24 08:47

本文选题：Podophyllotoxin　切入点：Helioxanthin　出处：《兰州理工大学》2016年硕士论文

【摘要】：本论文基于合成Podophllytoxin和Helioxanthin,且通过分子间Pd-catalyzed DominoHeck反应的成功,从而确定Domino反应的步骤。第一章:近期有关Podophyllotoxin生物活性的研究进展。由于这一系列化合物具有显著的细胞毒性,药剂师们的关注点在于一般的木酚素尤其是Podophyllotoxin,它是由几种植物物种堆积在2,7'-环木脂素Podophyllotoxin上,一般被用作生产三个半合成抗癌药物的起始化合物。从而促使大量的科学家寻找替代Podophllytoxin的来源。Podophllytoxin的化学合成是可能的,但该化合物复杂的立体化学闭环成为其合成较大阻碍。合成法生产,产率决定着成本。最为理想的是获得一个对环境适应性强,成熟期短,容易培养,木酚素含量高的植物。生物技术方法,则是在宿主细胞上合成Lignin,从而解决宿主细胞的致病性。第二章:通过Pd-catalyzed Domino-Heck反应合成Podophyllotoxin近年来,Podophyllotoxin的合成采用了不同的方法,我们采用Pd基催化剂催化Domino-Heck反应。一锅多步流程在此领域得到越来越多的关注和快速增长。Pd催化Domino-Heck反应最好的方法尚未提出。根据由Tietze提出的已被广泛认可的真理(Domino反应是将多个反应条件相似的反应结合起来一次性完成,将上一个反应得到的新官能团用于下一个反应,或是将上一个反应生成的活性中间体在合适的条件下,直接进行下一步反应而跨越了取出中间产物这一环节。在一次反应中形成多个化学键,从而将简单的原料经过很短的步骤转化成为复杂的分子)。我们看到在过去几年里,Pd-catalyzed Domino-Heck反应已经有了惊人的发展,因为钯具有可与许多官能团兼容的优势;它构成了Domino反应的理想催化剂。Domino反应已经被证明是非常有用的。Domino-Heck反应一直是学术和工业界关注的焦点。第三章:由金属钯催化的Heck反应合成Helioxanthin在先前的研究中,我们已经发现了几个抗病毒活性可与母体化合物相媲美的的物质。我们的研究还集中在通过使用高活性催化剂来减少这些反应的成本,以及通过开发基于芳香族酸酐作为芳基化因子的无卤化物Heck反应来减少浪费。我们使用有机汞试剂作为烷基转移或芳基转移的出处从而使Pd催化不饱和分子的芳基化和烷基化。我们努力探索各种抗HBV药物,不断地探究Helioxanthin类物质相关资料。我们的策略是确定Helioxanthin类物质抗乙肝病毒的结构。此关键结构将与芳萘骨架结合以产生更有效的抗乙肝病毒的Helioxanthin衍生物.第四章:Podophyllotoxin和Helioxanthin合成的实验结果。论文实验部分我们在综合文献的基础上,经过实验摸索,以Podophyllotoxin和Helioxanthin的结构特点为依据,用一个简单的胡椒醛作为起始原料,对α,β不饱和羰基化合物具有选择性还原的锂铝氢还原反应为关键步骤,先后经过knocvenagel缩合,间氯过氧苯甲酸环氧化,碱性过氧化氢环氧化,DCC缩合酯化反应合成了Podophyllotoxin和Helioxanthin中间体。
[Abstract]:This paper based on the synthesis of Podophllytoxin and Helioxanthin, and Pd-catalyzed through intermolecular DominoHeck reaction successfully, so as to determine the Domino reaction steps. The first chapter: the recent research progress on the biological activity of Podophyllotoxin. Because of this series of compounds have significant cytotoxicity, the focus is on general lignans, especially Podophyllotoxin, it it is composed of several plant species 2,7'- Podophyllotoxin accumulation in the open-loop lignan, is generally used as starting compounds in the production of 3.5 synthetic anticancer drugs. Chemical synthesis which prompted a large number of scientists to find the source of.Podophllytoxin instead of Podophllytoxin is possible, but the stereochemistry of the compound complex loop become the synthesis of larger obstacles. Synthesis production, yield determine the cost. The most ideal is to have a strong adaptability to environment, mature In short period, easy to culture, plant lignan content high. Biotechnology method is the synthesis of Lignin in host cells, so as to solve the pathogenicity of the host cell. The second chapter: the synthesis of Podophyllotoxin Pd-catalyzed Domino-Heck in recent years, the synthesis of Podophyllotoxin by different methods, we use Domino-Heck Pd based catalyst catalytic reaction a multi-step process in this field. The best way to get the attention and the rapid growth of.Pd Domino-Heck reaction catalyzed by more and more has not yet been put forward. According to the proposed by Tietze has been widely recognized the truth (Domino reaction is the reaction of multiple reaction conditions similar to the combined time of completion, will get a new functional response for the reaction next, or will generate a reaction of reactive intermediates under suitable conditions. For the next reaction across the An intermediate product in this part. The formation of multiple chemical bonds in one reaction, thus the simple raw material after very short steps into the complex molecules). We see that in the past few years, Pd-catalyzed Domino-Heck has reaction with a surprising development because the palladium have compatible with many functional advantages; it constitutes an ideal catalyst for.Domino reaction Domino reaction.Domino-Heck reaction has been proved to be very useful has been the focus of attention in the academic and industrial circles. The third chapter: the metal palladium catalyzed Heck reaction for the synthesis of Helioxanthin in prior studies, we have found several antiviral activity comparable to that of the parent compound material. Our research also focused on these reactions to reduce costs through the use of highly active catalyst, and through the development of aromatic acid anhydride based as arylation factor Halogen free Heck reaction to reduce waste. Arylation and alkylation we use organic mercury reagent as transfer of alkyl or aryl transfer source so that the Pd catalytic unsaturated molecules. We strive to explore a variety of anti HBV drugs, constantly explore Helioxanthin substances related information. Our strategy is to determine the structure of anti Helioxanthin compounds the hepatitis B virus. This key structure will be combined with the aromatic naphthalene skeleton to produce anti HBV Helioxanthin derivatives more effectively. The fourth chapter: the experimental results of Podophyllotoxin and Helioxanthin synthesis. In the experiments, we are integrated on the basis of the literature, through experiments, the structural features of Podophyllotoxin and Helioxanthin as the basis, with a simple piperonal as the starting materials of alpha, beta unsaturated carbonyl reduction reaction is the key step of selective reduction of lithium aluminum hydride The intermediates of Podophyllotoxin and Helioxanthin were synthesized through knocvenagel condensation, epoxidation of chlorooxy benzoic acid, alkaline hydrogen peroxide epoxidation and DCC condensation esterification.

【学位授予单位】：兰州理工大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：O629

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