含1,2,3-噻二唑环(E)-β-farnesene类似物的设计、合成及生物活性研究

Design, Synthesis and Biological Activity of (E)-β-Farnesene Analogues Containing 1,2,3-Thiadiazole

为了发现控制蚜虫的新型高活性化合物,以蚜虫报警信息素(E)-/β-farnsene(EBF)为先导化合物,用1,2,3-噻二唑环替代EBF结构中不稳定的共轭双键,设计、合成了15个EBF类似物,所有化合物结构均通过1H NMR、13C NMR、IR及HRMS确证.生物活性测试结果表明:化合物对桃蚜表现出较好的驱避活性,其中以N-((E)-3,7-二甲基-2,6-辛二烯-1-基)-N-(2-萘基)-4-甲基-1,2,3-噻二唑-5-甲酰胺(8d)、N-((E)-3,7-二甲基-2,6-辛二烯-1-基)-N-(4-甲基-吡啶-2-基)-4-甲基-1,2,3-噻二唑-5-甲酰胺(81)和N-((E)-3,7-二甲基-2,6-辛二烯-1-基)-N-(5-甲基-吡啶-2-基)-4-甲基-1,2,3-噻二唑-5-甲酰胺(8m)最为显著,驱避率分别为63.1%、61.3%和63.4%;化合物对桃蚜的毒杀活性均高于EBF,其中N-((E)-3,7-二甲基-2,6-辛二烯-1-基)-N-(4-氰基-苯基)-4-甲基-1,2,3-噻二唑-5-甲酰胺(8b)、N-((E)-3,7-二甲基-2,6-辛二烯-1-基)-N-(6-甲基-吡啶-2-基)-4-甲基-1,2,3-噻二唑-5-甲酰胺(8g)、N-((E)-3,7-二甲基-2,6-辛二烯-1-基)-N-(吡啶-2-基)-4-甲基-1,2,3-噻二唑-5-甲酰胺(8j)、N-((E)-3,7-二甲基-2,6-辛二烯-1-基)-N-(3-甲基-吡啶-2-基)-4-甲基-1,2,3-噻二唑-5-甲酰胺(8k)、81、8m和N-((E)-3,7-二甲基-2,6-辛二烯-1-基)-N-(5-甲基-1,3,4-噻二唑-2-基)-4-甲基-1,2,3-噻二唑-5-甲酰胺(8o)的杀蚜活性比较突出(LC50分别是10.2、9.0、25.1、31.7、8.4、12.8和9.6μg/mL),但活性略低于对照药剂吡蚜酮(LC50值7.1μg/mL).

In order to discover novel compounds with high-activity to control aphid,aphid alarm pheromone(E)-β-farnesene(EBF)was chosen as lead compound and 15 EBF analogues were designed and synthesized by replacing unstable conjugated double bond of EBF with 1,2,3-thiadiazole.Their structures were confirmed by 1 H NMR,13C NMR,IR and HRMS analysis.Repellent activity results indicated that analogues displayed better repellent activity against Myzus persicae(Sulzer).Among which compounds N-((E)-3,7-dimethyl-2,6-octadien-1-yl)-N-(2-naphthyl)-4-methyl-1,2,3-thiadiazole-5-carboxamide(8 d),N-((E)-3,7-dimethyl-2,6-octadien-1-yl)-N-(4-methy 1-pyridine-2-yl)-4-methyl-1,2,3-thiadiazole-5-carboxamide(81)and N-((E)-3,7-dimethyl-2,6-octadien-1-yl)-N-(5-methyl-pyridine-2-yl)-4-methy 1-1,2,3-thiadiazole-5-carboxamide(8 m)exhibited excellent repellent activity of 63.1%,61.3%and 63.4%respectively.The aphicidal bioassay results showed that most analogues exhibited considerable aphicidal activity against Myzus persicae.Especially,analogues N-((E)-3,7-dimethyl-2,6-octadienyl)-N-(4-CN-phenyl)-4-methyl-1,2,3-thiadiazole-5-carb oxamide(8 b),N-((E)-3,7-dimethyl-2,6-octadien-1-yl)-N-(6-methylpyridine-2-yl)-4-methyl-1,2,3-thiadiazole-5-carboxamide(8g),N-((E)-3,7-dimethyl-2,6-octadien-1-yl)-N-(2-pyridyl)-4-methyl-1,2,3-thiadiazole-5-carboxamide(8 j),N-((E)-3,7-dimethyl-2,6-octadien-1-yl)-N-(3-methyl-pyridine-2-yl)-4-methyl-1,2,3-thiadiazole-5-carboxamide(8 k),81,8 m and N-((E)-3,7-dimethyl-2,6-octadien-1-yl)-N-(5-methyl-1,3,4-thiadiazole-2-yl)-4-methyl-1,2,3-thiadiazole-5-carboxamide(8 o)exhibited high activity with LC50 values of 10.2,9.0,25.1,31.7,8.4,12.8 and 9.6μg/mL,respectively,which were higher than the lead compound(E)-β-farnesene,but lower than commercial insecticide pymetrozine with LC50 of 7.1μg/mL.