Synthesis and biological activity of N-((5-alkylthio-1,3,4-oxadiazole)-2-ylmethyl) tralopyril
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摘要: 为了发现农药活性的新化合物，以溴代吡咯腈为原料，通过亲核取代、肼解和成环等反应，设计合成了一系列N-((5-烷硫基-1,3,4-噁二唑)-2-基)甲基溴代吡咯腈目标化合物( 5a ~ 5t )，所有化合物的结构均得到核磁共振氢谱和高分辨质谱确证。杀菌活性测定结果显示：在浓度为0.20 mmol/L时，大部分目标化合物具有一定的抑菌活性，其中化合物 5h 对水稻稻瘟病菌Magnaporthe oryzae的抑制率为60.07%，优于对照药剂咯菌腈(58.21%)。杀虫与杀螨活性测定结果显示：在浓度为0.20 mmol/L时，大部分目标化合物对斜纹夜蛾Spodoptera litura和朱砂叶螨Tetranychus cinnabarinus雌成螨具有一定的杀虫和杀螨活性，但均低于对照药剂虫螨腈(100%)。杀线虫生物测定结果显示：在浓度为0.20 mmol/L时，大部分目标化合物表现出优异的杀线虫活性，其中化合物 5k 、 5r 和 5s 对秀丽隐杆线虫Caenorhabditis elegans的LC50值分别为0.0918、0.0733和0.0810 mmol/L，优于对照药剂噻唑膦(0.2798 mmol/L)。本研究所合成的目标化合物具有一定的杀菌、杀虫、杀螨和杀线虫活性，可为溴代吡咯腈衍生物的设计和合成提供参考。Abstract: In order to find new compounds with pesticide activity, a series of N-((5-alkylthio-1,3,4-oxadiazole)-2-methyl) tralopyril were designed and synthesized from tralopyril by nucleophilic substitution, hydrazinolysis and cyclization. The structures of these derivatives were confirmed by 1H NMR and HRMS. The test against 5 pathogenic fungi showed that most of the target compounds had certain fungicidal activity at the concentration of 0.20 mmol/L, and the inhibitory rate of compound 5h against Magnaporthe oryzae was 60.07%, which was better than that of the control agent fludioxonil (58.21%). The results of insecticidal and acaricidal activities showed that at the concentration of 0.20 mmol/L, some of the target compounds had certain insecticidal and acaricidal activities against Spodoptera litura and adult mite of Tetranychus cinnabarinus,
while all were lower than the control agent chlorfenapyr (100%). The results of nematicidal activity showed that most of the compounds exhibited excellent nematicidal activity at the concentration of 0.20 mmol/L. The LC50 values of compounds 5k, 5r and 5s against Caenorhabditis elegans were 0.0918, 0.0733, 0.0810 mmol/L respectively, which were better than the control agent fosthiazate (0.2798 mmol/L). The target compounds synthesized in this study have certain fungicidal, insecticidal, acaricidal and nematicidal activities, which can provide a reference for the design and synthesis of tralopyril derivatives. -
Key words:
- tralopyril /
- 1,3,44-oxadiazole /
- sulfide /
- synthesis /
- biological activity
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表 1 目标化合物对5种植物病原菌菌丝生长的抑制作用
Table 1. Inhibition of target compounds against five pathogenic fungi in vitro
化合物
Compound抑制率 Inhibition rate/% 水稻纹枯病菌
Rhizoctonia solani油菜菌核病菌
Sclerotinia sclerotiorum玉米小斑病菌
Bipolaris maydis香樟炭疽病菌
Colletotrichum gloeosporioides水稻稻瘟病菌
Magnaporthe oryzae2 43.08 ± 2.05 67.62 ± 1.88 35.11 ± 1.75 39.85 ± 0.65 81.72 ± 0.65 4 57.71 ± 0.68 77.05 ± 0.71 37.79 ± 2.38 71.05 ± 1.72 20.52 ± 1.94 5a 3.95 ± 0.00 16.39 ± 3.25 13.74 ± 0.66 14.66 ± 0.65 23.13 ± 0.65 5b 21.34 ± 1.37 7.79 ± 2.13 19.08 ± 0.66 12.03 ± 1.13 13.43 ± 1.71 5c 0.40 ± 1.19 8.20 ± 3.09 18.70 ± 3.44 5.64 ± 2.35 16.42 ± 2.82 5d 1.58 ± 2.05 13.52 ± 2.56 20.99 ± 1.98 13.53 ± 0.65 23.13 ± 1.71 5e 1.19 ± 2.47 15.98 ± 3.55 16.03 ± 2.38 9.40 ± 0.65 17.16 ± 2.24 5f 12.65 ± 1.37 25.82 ± 1.42 10.31 ± 2.64 11.28 ± 0.65 17.16 ± 1.12 5g 9.09 ± 0.68 12.70 ± 1.23 10.69 ± 1.15 7.52 ± 1.13 18.66 ± 2.33 5h 11.86 ± 1.81 29.51 ± 2.84 31.68 ± 0.66 16.54 ± 1.13 60.07 ± 0.65 5i 9.88 ± 1.19 13.11 ± 2.84 19.85 ± 1.98 10.53 ± 2.35 24.63 ± 1.71 5j 3.56 ± 0.68 9.84 ± 1.88 4.58 ± 1.75 2.26 ± 0.65 6.34 ± 0.65 5k 0.40 ± 3.14 6.15 ± 1.42 3.82 ± 1.15 6.02 ± 0.65 11.57 ± 2.24 5l 1.58 ± 1.19 3.69 ± 1.42 8.02 ± 2.38 9.40 ± 1.30 8.58 ± 0.65 5m 4.35 ± 0.68 26.23 ± 3.25 8.78 ± 3.31 14.66 ± 0.65 23.13 ± 1.29 5n 9.49 ± 1.37 16.80 ± 1.88 14.89 ± 0.66 6.77 ± 0.65 10.82 ± 0.65 5o 24.90 ± 3.42 23.77 ± 3.69 12.74 ± 0.66 12.78 ± 1.72 17.54 ± 2.82 5p 16.09 ± 2.67 17.21 ± 3.76 3.82 ± 1.15 9.77 ± 1.13 17.91 ± 2.33 5q 9.09 ± 0.68 12.70 ± 2.13 1.53 ± 1.15 9.02 ± 1.72 19.79 ± 0.65 5r 15.42 ± 0.68 9.43 ± 1.88 12.21 ± 1.32 13.53 ± 0.65 22.39 ± 2.33 5s 11.86 ± 1.37 10.25 ± 0.00 1.53 ± 1.15 4.89 ± 1.30 15.3 ± 0.65 5t 4.74 ± 1.37 13.11 ± 0.71 4.58 ± 2.88 9.02 ± 0.65 5.60 ± 1.71 溴代吡咯腈
tralopyril61.66 ± 2.74 88.11 ± 0.71 85.88 ± 1.32 66.54 ± 0.65 100.00 ± 0.00 咯菌腈
fludioxonil100.00 ± 0.00 100.00 ± 0.00 100.00 ± 0.00 76.69 ± 0.65 58.21 ± 0.65 注：每个处理重复 3 次 (平均值 ± 标准差)。化合物浓度为 0.20 mmol/L。Note: Each treatment had three replicates (mean ± SD). Inhibition rate was measured at a concentration of 0.20 mmol/L. 
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表 2 目标化合物对斜纹夜蛾杀虫活性
Table 2. Insecticidal activity of target compounds against Spodoptera litura
化合物
Compound校正死亡率
Corrected mortality/%化合物
Compound校正死亡率
Corrected mortality/%2 15.56 ± 5.09 5j 23.33 ± 2.89 4 100.00 ± 0.00 5k 0.00 ± 0.00 5a 0.00 ± 0.00 5l 18.65 ± 5.63 5b 0.00 ± 0.00 5m 23.48 ± 4.73 5c 36.67 ± 5.77 5n 26.67 ± 2.89 5d 13.43 ± 2.89 5o 12.63 ± 1.59 5e 29.52 ± 0.82 5p 19.63 ± 2.80 5f 12.04 ± 0.80 5q 13.33 ± 5.77 5g 0.00 ± 0.00 5r 10.83 ± 1.44 5h 36.94 ± 3.37 5s 13.10 ± 1.03 5i 0.00 ± 0.00 5t 14.48 ± 2.09 溴代吡咯腈 tralopyril 100.00 ± 0.00 虫螨腈 chlorfenapyr 100.00 ± 0.00 注：每个处理重复3次 (平均值 ± 标准差)。化合物浓度为0.20 mmol/L。Note: Each treatment had three replicates (mean ± SD). Corrected mortality was measured at a concentration of 0.20 mmol/L.
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表 3 化合物4对斜纹夜蛾的 LC50值
Table 3. The LC50 value of compound 4 against Spodoptera litura
化合物
Compound回归方程
Regression equation相关系数
Correlation coefficient, rLC50/(mmol/L) 95% 置信限
95% Confidence limit/(mmol/L)4 y = 9.4038 + 4.6278x 0.9775 0.1118 0.0990~0.1263 虫螨腈 chlorfenapyr y = 14.9148 + 4.4421x 0.9565 0.0059 0.0049~0.0070
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表 4 目标化合物对朱砂叶螨雌成螨杀螨活性
Table 4. Insecticidal activity of some target compounds against adult mite of Tetranychus cinnabarinus
化合物
Compound校正死亡率
Corrected mortality/%化合物
Compound校正死亡率
Corrected mortality/%2 31.47 ± 2.73 5j 15.37 ± 1.21 4 0.00 ± 0.00 5k 15.27 ± 1.71 5a 2.30 ± 1.99 5l 9.26 ± 0.67 5b 2.56 ± 2.27 5m 31.05 ± 2.39 5c 3.96 ± 1.53 5n 7.72 ± 2.00 5d 4.53 ± 1.67 5o 6.31 ± 2.37 5e 5.88 ± 2.03 5p 11.91 ± 3.01 5f 6.91 ± 3.33 5q 9.29 ± 1.89 5g 5.27 ± 2.00 5r 9.18 ± 2.78 5h 30.69 ± 1.61 5s 9.94 ± 3.60 5i 7.95 ± 3.92 5t 10.41 ± 0.99 溴代吡咯腈
tralopyril94.79 ± 1.96 虫螨腈
chlorfenapyr100.00 ± 0.00 注：每个处理重复3次 (平均值 ± 标准差)。化合物浓度为0.20 mmol/L。Note: Each treatment had three replicates (mean ± SD). Corrected mortality was measured at a concentration of 0.20 mmol/L.
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表 5 目标化合物对秀丽隐杆线虫杀线虫活性
Table 5. Nematicidal activity of target compunds against Caenorhabditis elegans
化合物
Compound校正死亡率
Corrected mortality/%化合物
Compound校正死亡率
Corrected mortality/%2 100.00 ± 0.00 5j 31.18 ± 3.39 4 25.19 ± 4.81 5k 85.14 ± 2.78 5a 77.16 ± 3.59 5l 79.54 ± 4.00 5b 73.50 ± 3.18 5m 29.54 ± 2.10 5c 63.24 ± 1.20 5n 41.22 ± 2.14 5d 30.74 ± 1.45 5o 49.00 ± 6.51 5e 25.65 ± 1.65 5p 50.66 ± 2.68 5f 51.34 ± 3.52 5q 74.36 ± 3.33 5g 48.96 ± 3.08 5r 90.47 ± 4.48 5h 73.25 ± 2.59 5s 87.99 ± 2.37 5i 30.96 ± 3.70 5t 49.26 ± 2.85 溴代吡咯腈
tralopyril100.00 ± 0.00 噻唑膦
fosthiazate43.89 ± 2.78 注：每个处理重复3次 (平均值 ± 标准差)；化合物浓度为0.20 mmol/L。Note: Each treatment had three replicates (mean ± SD). Corrected mortality was measured at a concentration of 0.20 mmol/L.
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表 6 部分目标化合物对秀丽隐杆线虫的 LC50值
Table 6. The LC50 value of some target compounds against Caenorhabditis elegans
化合物
Compound回归方程
Regression equation相关系数
Correlation cofficient, rLC50/
(mmol/L)95% 置信区间
95% Confidence limit/(mmol/L)2 y = 13.4860 + 4.5436x 0.9433 0.0136 0.0071~0.0260 5k y = 7.1526 + 2.0754x 0.9527 0.0918 0.0605~0.1392 5r y = 7.5282 + 2.2273x 0.9925 0.0733 0.0633~0.0848 5s y = 7.0517 + 1.8797x 0.9733 0.0810 0.0605~0.1084 噻唑膦 fosthiazate y = 6.5220 + 2.7518x 0.9935 0.2798 0.2426~0.3227 溴代吡咯腈 tralopyril y = 12.7985 + 2.2790x 0.9889 0.0004 0.0003~0.0005
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