大位阻非膦配体钯配合物催化合成含芳香偶联结构的中药活性物质的研究

发布时间：2018-03-28 13:53

  本文选题：天然产物　切入点：结构修饰　出处：《广东药科大学》2016年硕士论文

【摘要】：中药材的使用在我国的临床用药中占有很大的比重,而且几千年以来一直是我们治疗和预防疾病的主要手段。而随着科学水平的提高,研究人员发现中药能实现治疗和预防疾病的效果主要是在于中药材中含有对疾病有预防或治疗作用的活性成分。正是因为这些活性成分的影响,从而达到了对疾病的治疗。然而,这些活性成分通常在中药材中的含量很低,不容易对其进行提取和分离,从而限制了它的发展和应用。随着社会的进步,科研人员发现了能以化学合成方法对中药活性成分进行合成或修饰,从而合成治疗效果更好的药物成分。联芳类化合物广泛存在于天然产物中,对其的合成及修饰手法很多,其中通过C-C偶联反应直接引入芳香环类化合物或芳香杂环类化合物是中药材中化学活性成分修饰中的一种重要的方法。在C-C偶联反应中,过渡金属作为催化剂是反应中的重要部分。然而,大部分的催化体系都存在一定的缺陷,如:选用有毒的有机膦化合物作为配体、催化剂用量大、需要无水无氧条件等。针对这些弊端,本文主要从经济、催化剂稳定、反应活性高、底物适用范围广等方面设计合成2个体系10个不同结构的大位阻非膦配体钯配合物C1-C5和K1-K5,并对其催化C-C偶联反应进行了探究,为中药材中化学活性成分修饰与设计提供一种重要的方法。1、氮杂环卡宾钯配合物催化Suzuki偶联反应的研究合成并表征了5个N-杂环卡宾钯配合物。结果表明:K1-K5都能有效催化芳香卤代物与芳香苯硼酸类化合物的Suzuki偶联反应,其中催化剂K5的活性最高,最佳反应条件为:K5(0.5 mol%)、KOH(2.0 eq)、异丙醇作为为溶剂,在60℃反应4 h,即可达到很好的催化产率。2、胺基钯配合物催化的C-H活化偶联反应的研究合成并表征了5个催化剂,结果表明:C1-C5都能有效催化芳香溴代物与噻唑类化合物的C-H直接芳基化反应,催化剂量可低至0.05 mol%,其中催化剂C2的活性最高,最佳反应条件为:C2(0.5 mol%)、Piv OH(30 mol%)、K2CO3(1.5 eq)、DMAc为溶剂,反应24 h,催化产率最高可达98%。
[Abstract]:The use of Chinese medicinal materials occupies a large proportion in clinical use in China, and for thousands of years has been our main means of treatment and prevention of diseases. But with the improvement of the scientific level, The researchers found that the effect of traditional Chinese medicine on the treatment and prevention of diseases is mainly due to the fact that Chinese herbal medicines contain active ingredients that have preventive or therapeutic effects on diseases. It is precisely because of the effects of these active ingredients. Thus, the treatment of diseases is achieved. However, these active ingredients are usually very low in Chinese medicinal materials, and it is not easy to extract and separate them, thus limiting its development and application. The researchers have found that the active components of traditional Chinese medicine can be synthesized or modified by chemical synthesis method, so as to synthesize and treat the better drug components. Biarboxylic compounds are widely found in natural products, and there are many ways to synthesize and modify them. Among them, the direct introduction of aromatic ring compounds or aromatic heterocyclic compounds through C-C coupling reaction is an important method in the modification of chemical active components in Chinese medicinal materials. Transition metal is an important part of the reaction. However, most of the catalyst systems have some defects, such as the selection of toxic organic phosphine compounds as ligands, the amount of catalyst is large, It needs anhydrous and anaerobic conditions. In view of these disadvantages, this paper mainly focuses on economy, stability of catalyst, high activity of reaction, and so on. C1-C5 and K1-K5 ligands with 10 different structures were designed and synthesized from two systems in a wide range of substrates, and their catalytic activity for C-C coupling reaction was investigated. This paper provides an important method for the modification and design of chemical active components in Chinese medicinal materials. 1. Five N-heterocyclic carbene palladium complexes were synthesized and characterized by Suzuki coupling reaction catalyzed by carbene palladium complexes. The results show that: K1-K5 can be used as catalyst. The Suzuki coupling reaction of aromatic halides with aromatic phenylborates was effectively catalyzed. The activity of catalyst K5 was the highest, and the optimum reaction conditions were as follows: K5, 0.5 mol / mol, and Koh, 2.0 eqn, isopropanol as solvent, At 60 鈩，

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