兼具杀虫与保幼激素活性的蒎烯基杀蚊幼剂的设计合成与构效关系研究

Mosquitoes can spread deadly diseases and seriously endanger human health. Using mosquito larvicide to kill mosquito larvae is a key measure for mosquito control. However, at present, the mosquito larvicide only has a single target and the mosquito larvae easily form resistance to it, resulting in a decrease in the control effect of mosquito larvae. Therefore, it is of great significance to develop a novel mosquito larvicide having a multi-target effect. We have found in previous studies that terpenes, the main component of turpentine, have potential insecticidal and juvenile hormone activity and are ideal raw materials for the development of multi-target mosquito larvicide. Based on our previous work, this project intends to design and synthesize a series of novel pinene-based acylurea derivatives, according to the terpenes' molecular framework characteristics and different active substructure splicing and modification principles. The insecticidal activity and juvenile hormone activity are tested. Through the structure-activity relationship analysis, the structure-activity relationships between the molecular structure of pinene-based acylurea derivatives and their insecticidal and juvenile hormone activity are revealed, and the structural construction law of the pinene-based acylurea derivatives possessed good insecticidal and juvenile hormone activity is mastered. Finally, novel mosquito larvicides that have both insecticidal and juvenile targets synergistically killing mosquito larvae are screened out. The execution of this project can provide new ideas for the development of new mosquito larvicide, and can give support to the innovative deep processing and high-value utilization of turpentine oil.

蚊虫会传播致命疾病，严重危害人类生命健康。采用杀蚊幼剂杀灭蚊虫幼虫（孑孓）是蚊虫防治的关键措施。但目前杀蚊幼剂作用靶标单一，孑孓易对其形成抗药性，从而导致孑孓的防治效果下降，因此开发具有多靶标作用的新型杀蚊幼剂具有重要意义。申请者在前期研究中发现，松节油主成分蒎烯兼具潜在的杀虫和保幼激素活性，是开发具有多靶标作用杀蚊幼剂的理想原料。本项目拟在前期基础上，以蒎烯为原料，基于蒎烯的分子骨架特性以及不同活性亚结构的拼接和修饰原理，设计并合成系列新型蒎烯基酰基脲衍生物；测试衍生物对孑孓的杀虫活性和保幼激素活性，并通过构效关系分析，揭示蒎烯基酰基脲衍生物分子结构与杀虫和保幼激素活性之间的构效关系，掌握兼具良好杀虫和保幼激素活性的衍生物的结构构建规律，最终筛选获得兼具杀虫和保幼两种靶标作用协同杀虫的新型杀蚊幼剂。项目的开展可为新型杀蚊幼剂的开发提供新思路，并为松节油的创新深加工及高值化利用提供助力。

松节油、山苍子精油、樟树精油等天然植物精油体现出丰富的生物活性，在植物源农药领域具有广阔的应用前景。本研究以上述精油的主成分萜类化合物α-蒎烯、柠檬醛和樟脑为原料，开展了萜类衍生物的合成、生物活性（杀孑孓活性、保幼激素活性、抗菌活性等）和构效关系研究。制备获得了蒎烯衍生物、柠檬醛衍生物、樟脑衍生物等共计146个萜类衍生物。筛选获得了9个对白纹伊蚊孑孓具有良好杀虫活性的衍生物，筛选获得了众多具有良好抗菌活性的萜类衍生物。基本掌握了蒎烯基酰基脲衍生物分子结构与其杀孑孓活性和保幼激素活性之间的初步构效关系，掌握了蒎烯基酰胺衍生物、柠檬醛衍生物、樟脑衍生物分子结构与其抗植物病原真菌活性之间的定量构效关系。项目的开展可为新型杀蚊幼剂和新型杀菌剂的开发提供理论依据，并为松节油、山苍子精油和樟树精油的创新深加工及高值化利用新思路。