本文選題：天然產(chǎn)物　切入點(diǎn)：結(jié)構(gòu)修飾　出處：《廣東藥科大學(xué)》2016年碩士論文

【摘要】：中藥材的使用在我國的臨床用藥中占有很大的比重,而且?guī)浊暌詠硪恢笔俏覀冎委熀皖A(yù)防疾病的主要手段。而隨著科學(xué)水平的提高,研究人員發(fā)現(xiàn)中藥能實(shí)現(xiàn)治療和預(yù)防疾病的效果主要是在于中藥材中含有對(duì)疾病有預(yù)防或治療作用的活性成分。正是因?yàn)檫@些活性成分的影響,從而達(dá)到了對(duì)疾病的治療。然而,這些活性成分通常在中藥材中的含量很低,不容易對(duì)其進(jìn)行提取和分離,從而限制了它的發(fā)展和應(yīng)用。隨著社會(huì)的進(jìn)步,科研人員發(fā)現(xiàn)了能以化學(xué)合成方法對(duì)中藥活性成分進(jìn)行合成或修飾,從而合成治療效果更好的藥物成分。聯(lián)芳類化合物廣泛存在于天然產(chǎn)物中,對(duì)其的合成及修飾手法很多,其中通過C-C偶聯(lián)反應(yīng)直接引入芳香環(huán)類化合物或芳香雜環(huán)類化合物是中藥材中化學(xué)活性成分修飾中的一種重要的方法。在C-C偶聯(lián)反應(yīng)中,過渡金屬作為催化劑是反應(yīng)中的重要部分。然而,大部分的催化體系都存在一定的缺陷,如:選用有毒的有機(jī)膦化合物作為配體、催化劑用量大、需要無水無氧條件等。針對(duì)這些弊端,本文主要從經(jīng)濟(jì)、催化劑穩(wěn)定、反應(yīng)活性高、底物適用范圍廣等方面設(shè)計(jì)合成2個(gè)體系10個(gè)不同結(jié)構(gòu)的大位阻非膦配體鈀配合物C1-C5和K1-K5,并對(duì)其催化C-C偶聯(lián)反應(yīng)進(jìn)行了探究,為中藥材中化學(xué)活性成分修飾與設(shè)計(jì)提供一種重要的方法。1、氮雜環(huán)卡賓鈀配合物催化Suzuki偶聯(lián)反應(yīng)的研究合成并表征了5個(gè)N-雜環(huán)卡賓鈀配合物。結(jié)果表明:K1-K5都能有效催化芳香鹵代物與芳香苯硼酸類化合物的Suzuki偶聯(lián)反應(yīng),其中催化劑K5的活性最高,最佳反應(yīng)條件為:K5(0.5 mol%)、KOH(2.0 eq)、異丙醇作為為溶劑,在60℃反應(yīng)4 h,即可達(dá)到很好的催化產(chǎn)率。2、胺基鈀配合物催化的C-H活化偶聯(lián)反應(yīng)的研究合成并表征了5個(gè)催化劑,結(jié)果表明:C1-C5都能有效催化芳香溴代物與噻唑類化合物的C-H直接芳基化反應(yīng),催化劑量可低至0.05 mol%,其中催化劑C2的活性最高,最佳反應(yīng)條件為:C2(0.5 mol%)、Piv OH(30 mol%)、K2CO3(1.5 eq)、DMAc為溶劑,反應(yīng)24 h,催化產(chǎn)率最高可達(dá)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，

本文編號(hào)：1676601