Zhang Shuyun, Liu Hang, Yang Na, Xiong Lixia, Wang Baolei
State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin, China.
Pest Manag Sci. 2022 May;78(5):2086-2095. doi: 10.1002/ps.6834. Epub 2022 Mar 1.
The design and discovery of novel pesticidal agents according to bioactive natural products is an important aspect of agrochemical innovation. New xanthine derivatives derived from natural xanthine or methylxanthines are rich resources that possess great potential to afford new active pesticidal molecules. Herein novel xanthine derivatives were designed through a strategy of combining the methylxanthine caffeine skeleton with the acrylamide or acrylate motif of cinnamic acid derivatives.
A series of novel (E)-3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)acrylic acid derivatives, caffeine-(E)-acrylamides and caffeine-(E)-acrylates, were synthesized and confirmed via melting points, H NMR, C NMR and high-resolution mass spectrometry. A single crystal of compound I12 was obtained to illustrate the trans-configuration of the vinyl double bond. Preliminary insecticidal evaluations showed that some of the compounds had favorable insecticidal potentials against Mythimna separata Walker at 200 mg L . Some of the compounds exhibited excellent insecticidal activity against Plutella xylostella L. at low test concentrations, e.g. I18 and I24 with LC values of 0.0435 and 0.0133 mg L , respectively, were found to be more potent than the insecticide control triflumuron. The structure-activity relationship (SAR) analysis is also given in detail.
Compounds I12, I18, I24 and I26 generated from the integration of natural methylxanthine (caffeine) and acrylate moieties could be novel insecticidal leading compounds for further structural optimization. The SAR analysis may bring a new inspiration to the extensive and deep investigations on new xanthine derivatives in the agrochemical area.
依据生物活性天然产物设计与发现新型农药是农用化学品创新的一个重要方面。源自天然黄嘌呤或甲基黄嘌呤的新型黄嘌呤衍生物是丰富的资源，具有提供新型活性农药分子的巨大潜力。在此，通过将甲基黄嘌呤咖啡因骨架与肉桂酸衍生物的丙烯酰胺或丙烯酸酯基序相结合的策略设计了新型黄嘌呤衍生物。
合成了一系列新型（E）-3-（1,3,7-三甲基-2,6-二氧代-2,3,6,7-四氢-1H-嘌呤-8-基）丙烯酸衍生物、咖啡因-（E）-丙烯酰胺和咖啡因-（E）-丙烯酸酯，并通过熔点、1H NMR、13C NMR和高分辨率质谱进行了确证。获得了化合物I12的单晶以说明乙烯基双键的反式构型。初步杀虫活性评价表明，部分化合物在200 mg L-1时对粘虫具有良好的杀虫潜力。部分化合物在低测试浓度下对小菜蛾表现出优异的杀虫活性，例如I18和I24的LC50值分别为0.0435和0.0133 mg L-1，发现它们比杀虫剂对照氟虫脲更有效。还详细给出了构效关系（SAR）分析。
由天然甲基黄嘌呤（咖啡因）和丙烯酸酯部分整合生成的化合物I12、I18、I24和I26可能是用于进一步结构优化的新型杀虫先导化合物。SAR分析可能为农用化学品领域对新型黄嘌呤衍生物进行广泛而深入的研究带来新的启发。
