3-氨基喹啉衍生物的合成研究

发布时间：2019-03-15 07:41

【摘要】：氨基喹啉(Aminoquinoline, AQ)是喹啉的一类重要衍生物,相对比于其他的喹啉衍生物具有更高的药物活性,因而被广泛应用于药物的筛选和修饰。AQ和其衍生物目前不仅在抗生素药物、抗高血压和在抗疟疾中占有非常重要的位置,而且由于AQ对金属离子具有很好的配位性和非常高的选择性,使其在化学分析方面也得到了越来越多的关注和研究。同时,AQ作为DNA、RNA等一些生物大分子的嵌入体、荧光探针等,使它在分子生物学中也得到了广泛应用和研究。本文详细阐述了3-氨基喹啉衍生物的合成。在对过往文献大量查阅的基础上，笔者首先阐述了氨基喹啉及其衍生物的化学性质、合成方法及应用应用研究进展，并通过对文献报道方法的优化和改进成功地设计合成了8-硝基-3-AQ、7-硝基-3-AQ、6-硝基-3-AQ、5-硝基-3-AQ、8-甲氧基-3-AQ、7-甲氧基-3-AQ、6-甲氧基-3-AQ、5-甲氧基-3-AQ8-氯-3-AQ、7-氯-3-AQ、6-氯-3-AQ、5-氯-3-AQ12种3-AQ的衍生物作为研究新型药物中间体。本实验中3-AQ的合成尝试了3种不同的路线：Doebner-Miller环合；通过喹啉环的溴化然后以Buchwald Hartwig反应形成C-N键； Friedl nder环合。 Doebner-Miller环合，，通过芳香氨基化合物和乙氧甲叉关环，脱氢脱氯，水解，Curtius重排，原料易得每一步收率高，但是路线冗长，最后放弃该路线。第二条路线通过喹啉化合物溴化后和氨基化合物Buchwald Hartwig反应形成氨基喹啉化合物，收率好，路线简单，但是在含有给电子基团的喹啉环的溴化选择性不好。针对这一缺点我们设计第三条路线通过氨基苯甲醛类衍生物和硝基乙醛缩二甲醇通过Friedl nder环合得到3-硝基喹啉然后还原得到目标化合物，步骤简单收率好。
[Abstract]:Aminoquinoline (Aminoquinoline, AQ) is a kind of important derivatives of quinoline. Compared with other quinoline derivatives, AQ and its derivatives have been widely used in drug screening and modification. AQ and its derivatives are not only used in antibiotic drugs, but also have higher drug activity than other quinoline derivatives. Anti-hypertension and anti-malaria play a very important role in the field of anti-malaria, and because AQ has good ligand and high selectivity to metal ions, it has been paid more and more attention and research in the field of chemical analysis. At the same time, AQ has been widely used and studied in molecular biology because of its application as a chimeric and fluorescent probe of some biomolecules, such as DNA,RNA and so on. In this paper, the synthesis of 3-aminoquinoline derivatives is described in detail. On the basis of a large number of references in the past, the chemical properties, synthesis methods and application of aminoquinoline and its derivatives are reviewed in this paper. We have successfully designed and synthesized 8-nitro-3, 7-nitro-3, 6-nitro-3, 5-nitro-3, 8-methoxy-3-AQQ by optimizing and improving the methods reported in the literature. 7-methoxy-3, 6-methoxy-3, 5-methoxy-3, chloro-3, 7-chloro-3, 6-chloro-3, aquaporb, 6-methoxy-3, 5-methoxy-3, chloro-3, 5-methoxy-3. The derivatives of 5-chloro-3-AQ12 species 3-AQ were used as new drug intermediates. In this experiment, three different routes for the synthesis of 3-AQ were attempted: Doebner-Miller cyclization, bromination of quinoline ring and formation of C _ (N) N bond; Friedl nder cyclization by Buchwald / Hartwig reaction. Doebner-Miller cyclization, dehydrodechlorination, hydrolysis, Curtius rearrangement through aromatic amino compounds and ethoxymethyl-ethylidene ring closure, easy to obtain high yield of each step, but the route is lengthy, and finally abandoned the route. The second route reacts with amino compound Buchwald / Hartwig after bromination of quinoline compound to form amino quinoline compound. The yield is good and the route is simple, but the bromination selectivity of quinoline ring containing donor group is not good. To solve this problem, we design a third route to give 3-nitroquinoline through Friedl nder cyclization of aminobenzaldehyde derivatives and nitroacetaldehyde acetal dimethyl alcohol, and then reduce to the target compound. The yield of the first step is simple and the yield is good.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914.5

【共引文献】