基于天然产物细辛素的新型杀虫剂分子设计、合成及构效关系研究

With the rising of public awareness of the manifold dangers for the environment and human health posed by the wanton use of chemical pesticides, the discovery of new insecticidal compounds from natural products, or followed by using them as the lead-compounds for further structural modifications has recently been one of the important methods for research and development of new pesticides. Sarisan, a natural product with insecticidal activity will be used as the lead compound in this subject, and series of novel and various sarisan derivatives modified at the A ring, C-2, 3 position of B ring, and C-2', 3' of allyl group will be prepared by strategies of multi-component reactions and activity sub-structure combination; Besides, the sarisan derivatives with more promising insecticidal activity and synergetic effects will be screened out by investigating insecticidal activity and synergetic effects of all sarisan derivatives. Finally, quantitative structure-activity relationship will also be investigated by combining with insecticidal activity of sarisan derivatives, which aims to find out structural characteristics influenced the insecticidal activity of sarisan derivatives among the A ring, C-2, 3 position of B ring, and C-2', 3' of allyl group, and construct the ideal structure model of insecticide. This work will provide a sound theoretical basis for development of sarisan as new insecticidal agents.

随着人们对化学杀虫剂长期大量使用对环境以及人类健康所带来诸多威胁的日益认识，从天然产物中寻找杀虫性化合物或以其为先导进行结构优化已成为新型杀虫剂创制的重要途径之一。本项目拟选具杀虫活性的天然产物细辛素(sarisan)为先导化合物，采用多组分一锅煮和活性亚结构拼接策略对其A环、B环碳2、3位和烯丙基碳2'、3'位等活性位点进行结构修饰，多样性导向合成系列结构新颖、多样的细辛素类衍生物；通过对目标衍生物杀虫活性和增效作用的测定，筛选出具有杀虫活性和增效作用的高活性化合物；最后，结合目标衍生物的杀虫活性，进行定量构效关系的研究，从而探明细辛素A环、B环碳2、3位和烯丙基碳2'、3'位对杀虫活性的影响，明确其构效关系，构建出具杀虫活性的理想结构模型。为今后开发利用该类化合物作为新型杀虫剂提供重要的理论依据。

随着人们对化学杀虫剂长期大量使用对环境以及人类健康所带来诸多威胁的日益认识，从天然产物中寻找杀虫性化合物或以其为先导进行结构优化已成为新型杀虫剂创制的重要途径之一。细辛素具有多种生物活性，包括抗败血症、神经药理活性、抗微生物活性等，特别是其具有较好的杀虫和抑制真菌活性。然而由于细辛素结构简单，活性修饰位点较少，有关细辛素的类似物合成及结构修饰的研究报道相对较少。为此，本课题通过活性亚结构拼接策略，在细辛素C-3和3'位引入1,3,4-噁二唑环、吡唑环以及异噁唑啉环，制备了三系列含氮杂环细辛素类似物，并测定了目标化合物的相关生物活性。结果表明在细辛素的C-3位引入含芳杂环的1,3,4-噁二唑以及引入N-氟苯基吡唑环或多卤代苯基吡唑环时对杀虫活性有明显的提高作用。以上研究结果，将为我们今后以细辛素为先导，设计合成其类似物开发新型绿色农药在绿色高效农业领域奠定一定理论基础。