长链烃基水杨酸、酰胺的合成及灭螺活性研究

发布时间：2018-03-23 05:12

本文选题：长链烃基水杨酸　切入点：灭螺活性　出处：《复旦大学》2014年硕士论文　论文类型：学位论文

【摘要】：由日本血吸虫导致的人畜共患血吸虫病是我国一种常见的慢性消耗性疾病。钉螺(Oncomelania hupensis)是血吸虫病传播途径的主要中间宿主,其地理分布与日本血吸虫病一致,因此消灭钉螺是防治血吸虫病的重要措施之一。氯硝柳胺是wHO唯一推荐商业应用的杀螺剂,但带来的对水生生物的毒性及对环境的影响是其主要问题。近年来对新型灭螺剂的研究更多的集中在来自植物的环境友好具有灭螺活性的成分及其合成的衍生物上。银杏酸是银杏叶及外种皮的主要成分,具有较强的杀灭钉螺活性,且具有开发成高效、低毒、价廉的新型灭螺药物的潜力。在本课题组前期研究的基础上,本实验从4-及5-甲基水杨酸出发,共合成了18个碳链长度为7-13的长链烃基水杨酸类衍生物,包括Z式、E式以及饱和侧链。同时在这基础上,以长链烷基水杨酸为原料合成了14个长链烷基水杨酰胺类化合物。并分别根据波谱数据确定了这些化合物的结构。对合成的长链烃基水杨酸和长链烷基水杨酰胺进行了灭螺活性的研究发现,长链烃基水杨酸的碳链长度对活性的影响要比取代位置更大,其灭螺活性随着链长的增长而增强,且以碳链长度为13个碳原子的活性为最好,长链中双键为反式的化合物的活性与对应的饱和长链化合物活性相当,且都比顺式强；长链烷基水杨酰胺灭螺活性比对应的长链烷基水杨酸好,同样也以碳链长度为13的酰胺类化合物活性为最好。急性鱼毒性实验结果显示长链烷基水杨酸化合物对鱼的毒性浓度远高于对钉螺的杀伤浓度,与氯硝柳胺相比,毒性更低,说明了这类化合物在实际应用中要比氯硝柳胺安全。
[Abstract]:Zoonotic schistosomiasis caused by Schistosoma japonicum is a common chronic and expendable disease in China. Oncomelania hupensis is the main intermediate host of schistosomiasis transmission and its geographical distribution is consistent with that of schistosomiasis japonicum. Therefore, the elimination of snail is one of the important measures to control schistosomiasis. Niclosamide is the only snail killer recommended for commercial use by wHO. However, the toxicity to aquatic organisms and the impact on the environment are the main problems. In recent years, the research on new snail repellents has focused more on the environmentally friendly components with snail killing activity from plants and their synthetic derivatives. Ginkgolic acid is the main component of ginkgo biloba leaves and exocarps. It has the potential to develop new snail killing drugs with high efficiency, low toxicity and low price. Based on the previous research of our group, the experiment starts from 4- and 5-methylsalicylic acid. A total of 18 long-chain alkyl salicylic acid derivatives with a length of 7-13 carbon chains were synthesized, including Z type E and saturated side chains. Fourteen long chain alkyl salicylic amides were synthesized from long chain alkyl salicylic acid. The structures of these compounds were determined based on the spectral data. The synthesis of long chain alkyl salicylic acid and long chain alkyl salicylidene amide were studied. The activity of snail killing was studied. The carbon chain length of long chain alkyl salicylic acid has more influence on the activity than the substitution position. The snail killing activity increases with the increase of chain length, and the carbon chain length of 13 carbon atoms is the best. The activity of the double bond trans compounds in the long chain is equal to that of the corresponding saturated long chain compounds, and the activity of the long chain alkyl salicylic amide is better than that of the corresponding long chain alkyl salicylic acid, and the activity of the long chain alkyl salicyamide is better than the corresponding long chain alkyl salicylic acid. The results of acute fish toxicity test showed that the toxicity concentration of long chain alkyl salicylic acid compounds to fish was much higher than the killing concentration of Oncomelania hupensis, and the toxicity was lower than that of niclosamide. It shows that this kind of compound is safer than niclosamide in practical application.
【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914;R96

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