含噻嗪结构的新型HPPD抑制类除草剂的设计、合成及构效关系研究

One of the research focuses in the field of pesticide chemistry is to develop novel and practical HPPD inhibiting-based herbicides. In previous work, we were committed to develop novel HPPD inhibiting-based herbicides through modifying the cyclohexanedione part in triketone HPPD inhibitors. The preliminary study found that some of 3-benzoyl-4-hydroxylbenzothiazine derivatives displayed good herbicidal activity and strong HPPD inhibitory activity. Especially, compound NK-8 displayed good herbicidal activity against Brassica campestris, Amaranthus retroflexus and Echinochloa crusgalli at a dosage of 100 g/hm2. More importantly, compound NK-8 displayed significant inhibitory activity against HPPD and was identified as the most potent candidate with IC50 value of 0.48 μM, which comparable with the commercial herbicide mesotrione. These results indicated that NK-8 could be a potential lead structure for further development of novel and practical HPPD inhibiting-based herbicides. Thus, in our continuing study, new target compounds would be designed and synthesized, and their herbicidal activities would be evaluated. Then the qualitative and quantitative structure-activity relationships would be studied and used to guide the design of other target compounds. The research results is expected to produce 1-2 HPPD inhibiting-based herbicide lead compounds with higher biological activities, and provide a theoretical basis for developing novel and practical HPPD inhibiting-based herbicides. Therefore, this study is of great theoretical and practical significance.

开发高效、低毒、生态安全的新型HPPD抑制类除草剂是农药化学领域的研究热点之一。在前期工作中，申请人致力于改造三酮类HPPD抑制剂的环己二酮部分来寻找新型HPPD抑制类除草剂。经初步研究发现，苯并噻嗪类化合物NK-8在苗前100 克/亩的剂量下，对多种杂草的防治效果与商品化的除草剂－硝磺草酮相当，并且对拟南芥HPPD表现出了较强的抑制作用（IC50=0.48 μM），可以作为HPPD抑制类除草剂的先导化合物。因此，在继续的研究中，本项目将对先导化合物NK-8进行结构改造，设计合成新的目标化合物，建立相应的化合物库，测试其生物活性，并在此基础上开展构效关系研究。期望通过系统的结构修饰及构效关系研究，最终找到1-2个具有更高生物活性的新型HPPD抑制类除草剂先导化合物。本项目的研究结果将为我国创制具有自主知识产权的新型HPPD抑制类除草剂提供借鉴和思路，具有重要的学术价值和实际应用价值。

开发高效、低毒、生态安全的绿色除草功能分子是农药化学领域的研究热点之一。本项目在前期工作的基础上，对含苯并噻嗪结构的HPPD抑制剂进行结构改造，设计、合成了3-酰基-4-羟基-2,1-苯并噻嗪、3-苯氧乙酰基-4-羟基吡喃酮、3-苯氧乙酰基-4-羟基香豆素和3-苯氧乙酰基巴比妥酸等4个系列，共185个结构新颖的衍生物。随后，通过小杯平皿及温室盆栽法对化合物的除草活性进行测试，并系统的进行了构效关系研究。研究结果表明，部分化合物在187.5 g ha-1 的剂量下，对多种农田杂草展示出很好的防除效果，其表现出具有与商品化除草剂2,4-D相当的除草活性及更宽的除草谱，并且对玉米和小麦等作物安全，具有成为除草剂候选化合物的潜力。更重要的是，在除草机制研究过程中我们发现，将苯氧乙酰基引入至4-羟基吡喃酮衍生物及巴比妥酸的3-位置上，所构建的化合物具有缓释激素类除草剂的作用。在国家倡导生态文明建设及实施“药肥双减”政策的背景下，本项目的研究结果为我国创制具有自主知识产权的绿色除草剂提供了新的先导结构，具有十分重要的学术价值和实际应用价值。