新型呋喃α-丁烯内酯类化合物的设计、合成及其生物活性研究
收稿日期: 2022-06-08
修回日期: 2022-08-01
网络出版日期: 2022-09-09
基金资助
国家自然科学基金(31972289)
Design, Synthesis and Bioactivity Study on Novel Furan α-Butenolactone Compounds
Received date: 2022-06-08
Revised date: 2022-08-01
Online published: 2022-09-09
Supported by
National Natural Science Foundation of China(31972289)
近年来, 新烟碱杀虫剂的广泛使用不但导致害虫对其抗性逐渐增强, 而且其对蜜蜂的毒性影响也越来越受到关注, 因此设计合成生态友好型的新烟碱杀虫剂替代品显得迫在眉睫. 实验室前期以低蜂毒杀虫剂氟吡呋喃酮的丁烯内酯为骨架, 基于骨架相似性搜索发现, 新型呋喃α-丁烯内酯骨架具有一定杀蚜活性. 基于烟碱乙酰胆碱受体蛋白特征融合经验方法, 设计并合成了一系列新型呋喃α-丁烯内酯类化合物. 在500 μg/mL浓度下对目标化合物进行大豆蚜和桃蚜的杀虫活性测试, 结果表明该系列化合物对大豆蚜和桃蚜均表现一定的致死活性, 其中(E)-3-((5-(3-氯苯基)呋喃- 2-基)亚甲基)-5-甲基呋喃-2(3H)-酮(7bh)和(E)-3-((5-乙基呋喃-2-基)亚甲基)-5-(对甲苯基)呋喃-2(3H)-酮(7ch)对大豆蚜和桃蚜的致死率均达到70%以上, 并且7bh对大豆蚜(LC50=70.83 μg/mL)和桃蚜(LC50=71.96 μg/mL)的杀虫活性与吡蚜酮在同一个数量级. 意外发现该类化合物在50 μg/mL浓度下对水稻纹枯病菌也表现出一定的离体抑菌活性. 分子对接研究推测可能是呋喃α-丁烯内酯类化合物保留了与氟吡呋喃酮部分类似的受体间作用力, 使其表现较好的杀蚜活性. 本研究发现的新型呋喃α-丁烯内酯类化合物将为开发高效低蜂毒的新型丁烯内酯类杀蚜剂候选物奠定基础.
李想 , 朱凯 , 韩清 , 路星星 , 李明君 , 凌云 , 段红霞 . 新型呋喃α-丁烯内酯类化合物的设计、合成及其生物活性研究[J]. 有机化学, 2023 , 43(1) : 202 -213 . DOI: 10.6023/cjoc202206010
In recent years, the widespread use of neonicotinoid insecticides caused the resistance of pests to gradually become stronger, especially more and more attention on the toxic effect on bees. Therefore, it is urgent to design and synthesize novel eco-friendly alternatives to neonicotinoid insecticides. In our previous study, a novel furan α-butenolactone skeleton was found to have aphicidal activity based on the structrue similariy searching strategy to the butenolide pharmacophore from the low-bee toxicity commercial insecticide flupyradifurone. In this work, a series of novel furan α-butenolactone compounds were designed and synthesized combined the characteristics of nicotinic acetylcholine receptor protein and empirical design method. The bioassay results at the concentration of 500 μg/mL showed that all target compounds exhibited some aphicidal activity against soybean aphid and peach aphid. Especially, (E)-3-((5-(3-chlorophenyl)furan-2-yl)methylene)-5-methylfuran-2(3H)- one (7bh) and (E)-3-((5-ethylfuran-2-yl)methylene)-5-(p-tolyl)furan-2(3H)-one (7ch) were found to be more than 70% with a mortality rate against not only soybean aphid but also peach aphid. Furthermore, the insecticidal activities of 7bh were the same order of magnitude with pymetrozine against soybean aphid (LC50=70.83 μg/mL) and green peach aphid (LC50=71.96 μg/mL). To our surprised, these target compounds also showed certain antifungal activity in vitro against Rhizoctonia solani at the concentration of 50 μg/mL. Molecular docking studies indicated that the furan α-butenolactone compounds displayed moderate aphicidal activity due to their similar interaction with flupyradifurone toward nicotinic acetylcholine receptor. The study on new furan α-butenolactone compounds will lay a foundation for the development of new aphicidal candidates with high efficiency and low bee-toxicity in the future.
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