吖啶类化合物及麦角醇重要中间体的合成

发布时间：2018-06-19 15:43

本文选题：吖啶化合物 + 氢转移　；参考：《哈尔滨工业大学》2017年硕士论文

【摘要】：吖啶类化合物是一类由蒽中间环系上的一个碳原子被氮原子取代而成的杂环化合物,具有非常独特的生物活性,广泛应用于医疗方面,具有抗肿瘤、抗菌、消炎、治疗艾滋病以及老年痴呆症等药效。本课题建立了一种以邻氨基二苯甲酮和环己酮为底物,通过钯催化氢转移法生成吖啶类化合物的合成方法学。麦角醇是从裂叶牵牛花中提取出来的一种麦角生物碱。常被用作治疗低血压、精神镇痛、子宫和肠道刺激药物。同时也是合成麦角生物碱类化合物的重要前躯体,因而具有重要的药物合成价值。本论文在查阅大量文献和一定化学知识积累的基础上,发展了一种麦角醇全合成的方法。本论文研究内容主要分为以下两个方面:1.吖啶类化合物的合成。本文提出了“两步法”利用廉价易得的原料邻氨基二苯甲酮和环己酮,通过Friedl?nder经典方法合成喹啉化合物,继而将喹啉化合物经过渡金属Pd脱氢氧化为吖啶化合物;提出“一锅法”合成吖啶类化合物方法,直接由原料邻氨基二苯甲酮和环己酮经过渡金属Pd一步反应得到吖啶类化合物;在已建立的“一锅法”合成吖啶类化合物方法优化条件的基础上,对不同取代基团的底物进行普适性研究;最后,在催化脱氢研究的基础上,我们另外发展了一种喹啉化合物在碱性条件下生成吖啶化合物的方法。2.天然产物麦角醇的全合成。以3,4桥环化合物乌勒酮衍生物为重要中间体经过氨基烷基化反应、氨基缩合反应、关环、扩环、还原反应。根据实验的合成路径,通过对实验路线的探索及修正,预期得到天然产物麦角醇。本课题设计了两条路线来合成麦角醇重要中间体乌勒酮衍生物。路线一利用含有吲哚母核的L-色氨酸为原料经过甲酯化和氨基保护反应,在过渡金属Pd的作用下,通过正丁基锂实现区域选择性关环,构建麦角醇C环。路线二利用L-丝氨酸为原料经过甲酯化,氨基保护反应,羟基保护反应生成中间体产物12继而与4-溴吲哚-2-酮进行3-位偶联反应,再经过还原,关环,脱保护反应预期得到乌勒酮衍生物,为天然产物麦角醇合成奠定了基础。
[Abstract]:Acridine compounds are a class of heterocyclic compounds which are replaced by nitrogen atoms by a carbon atom in the anthracene intermediate ring system. They have very unique biological activity and are widely used in medical treatment. They have anti-tumor, antibacterial and anti-inflammatory properties. Treatment of AIDS and Alzheimer's disease and other drug effects. In this paper, a palladium catalyzed hydrogen transfer method for the synthesis of acridine compounds using o-aminobenzophenone and cyclohexanone as substrates was established. Ergotanol is a kind of ergot alkaloid extracted from the fractionated petunia. It is often used in the treatment of hypotension, mental analgesia, uterine and intestinal irritants. It is also an important precursor for the synthesis of ergot alkaloids, so it has important drug synthesis value. In this paper, a method for the total synthesis of ergol was developed on the basis of consulting a lot of literatures and accumulating some chemical knowledge. The research content of this thesis is divided into two aspects as follows: 1. Synthesis of acridine compounds. In this paper, a "two-step method" was proposed to synthesize quinoline compounds by using cheap and easily available raw materials, o-aminobenzophenone and cyclohexanone, and then oxidize quinoline compounds to acridine compounds by dehydrogenation of quinoline compounds through PD. A one-pot method for the synthesis of acridine compounds was proposed. The acridine compounds were synthesized directly from o-aminobenzophenone and cyclohexanone through the one-step reaction of metal PD. Based on the optimized conditions of the established one-pot method for the synthesis of acridine compounds, the universality of substrates with different substituents was studied. Finally, on the basis of catalytic dehydrogenation, In addition, we have developed a method of producing acridine compounds from quinoline compounds under alkaline conditions. The total synthesis of ergot alcohol, a natural product. Wu Le ketone derivatives were used as important intermediates through amino-alkylation, amino condensation, ring closure, ring expansion and reduction reactions. According to the synthetic path of the experiment, the natural product ergol is expected to be obtained by exploring and modifying the experimental route. In this paper, two routes were designed to synthesize Wu Le ketone derivatives, an important intermediate of ergol. Route one: using L- tryptophan containing indole mother nucleus as raw material, through methyl ester reaction and amino protection reaction, under the action of transition metal PD, the region selective closure ring of ergol C ring was constructed by Ding Ji lithium. The second route uses L-serine as raw material through methyl ester reaction, amino protection reaction, hydroxyl protection reaction to form intermediate product 12 and then 3-position coupling reaction with 4-bromoindole -2-one, and then after reduction, closing the ring, The deprotection reaction anticipates the Wu Le ketone derivative, which lays the foundation for the natural product ergol synthesis.
【学位授予单位】：哈尔滨工业大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O621.3

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