Synthesisandfungicidalactivityevaluationof2-thiazolylamidecyclohexane-sulfonamide
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摘要: 为进一步研究环烷基磺酰胺类化合物的杀菌活性与构效关系，在前期工作基础上，合成了11个未见文献报道的2-噻唑酰氨基环己烷基磺酰胺类化合物 ( 7a ~ 7k )，其结构均经1H NMR、13C NMR、质谱和元素分析确证。分别采用菌丝生长速率法、黄瓜活体叶片法、孢子萌发法和番茄活体盆栽法对目标化合物进行了生物活性测定。结果表明：目标化合物对番茄灰霉病菌Botrytis cinerea表现出较好的抑制活性，其中化合物 7a 和 7c 在10 mg/L下对番茄灰霉病菌孢子萌发的抑制率分别为90%和67%；在200 mg/L 施药剂量下，对活体黄瓜叶片、番茄叶片和番茄花上灰霉病的防治效果，化合物 7a 分别为75%、78%和30%，化合物 7c 分别为78%、62%和44%，均优于对照药剂腐霉利，有进一步研究的价值。
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关键词:
- 2-氨基环己烷基磺酰胺 /
- 噻唑酰胺 /
- 灰霉病菌 /
- 杀菌活性 /
- 构效关系
Abstract: In order to further explore the fungicidal activities and structure-activity relationship of cycloalkylsulfonamides, based on previous work, 11 novel 2-thiazolylamino cyclohexanesulfonamides were synthesized. Their structures were characterized by 1H NMR, 13C NMR, MS and elemental analysis. The bioactivities of the target compounds was determined by adopting mycelium growth rate method, in vivo cucumber leaves method, spore germination method and in vivo tomato potted method. The bioassay exhibited that the target compounds showed good inhibitory activities against Botrytis cinerea. Among them, the inhibitory rates of compounds 7a and 7c against spore germination of B. cinerea at 10 mg/L were respectively 90% and 67% . With the application dose of 200 mg/L, the control efficacy of compound 7a against gray mold on live cucumber leaves, tomato leaves and tomato flowers were respectively 75%, 78% and 30% and the corresponding control effects of compound 7c were respectively 78%, 62%, and 44%, which were better than procymidone and worth further research. -
1 一些商品化品种和活性化合物的结构式
1. Structural formula of some commercial products and active compounds
表 1 化合物7a~7k的理化数据、质谱及元素分析数据
Table 1. Physico-chemical data, mass spectrometry and elemental analysis data of compounds 7a-7k
化合物
Compd.物态 (室温)
State (r. t.)熔点
m.p./℃缩合收率
Condensation yield/%质谱
MS， m/z元素分析 (计算值，%) Elemental analysis(Calcd., %) C H N 7a 白色固体 White solid 175.0~176.0 82 558.03 (M) 51.54 (51.66) 3.98 (4.15) 7.65 (7.53) 7b 白色固体 White solid 173.0~174.5 84 627.35 (M+H+) 46.12 (45.98) 3.55 (3.38) 6.52 (6.70) 7c 白色固体 White solid 113.5~114.0 85 592.98 (M–H+) 48.66 (48.53) 3.40 (3.56) 6.98 (7.07) 7d 白色固体 White solid 168.0~170.0 86 588.06 (M) 49.89 (50.06) 7.05 (7.29) 7.27 (7.15) 7e 白色固体 White solid 167.0~168.0 83 576.02 (M) 50.17 (50.04) 3.99 (3.85) 7.12 (7.30) 7f 黄色固体 Yellow solid 166.0~167.3 93 603.03 (M) 48.01 (47.80) 3.58 (3.68) 9.01 (9.29) 7g 白色固体 White solid 146.5~148.0 88 592.9 (M+H+) 48.88 (48.65) 3.91 (3.74) 6.92 (7.09) 7h 白色固体 White solid 137.0~138.0 86 626.03 (M) 48.11 (47.96) 3.68 (3.54) 6.51 (6.71) 7i 白色固体 White solid 198.0~199.5 87 626.03 (M) 47.73 (47.96) 3.41 (3.54) 6.90(6.71) 7j 白色固体 White solid 79.0~80.0 88 612.1 (M) 46.98 (47.10) 3.54 (3.29) 6.62 (6.87) 7k 白色固体 White solid 179.0~180.0 81 576.02 (M) 49.89 (50.04) 3.67 (3.85) 7.43 (7.3) 
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表 2 化合物 7a~7k 的 1H NMR 及 13C NMR 数据
Table 2. The 1H NMR and 13C NMR data of compounds 7a-7k
化合物Compd. 1H NMR ( DMSO-d6, 600MHz, TMS), δ 13C NMR (151 MHz, DMSO), δ 7a 9.42 (s, 1H), 8.12~7.52 (m, 9H), 4.72~4.70 (m, 1H), 3.53~3.56 (m, 1H), 2.59 (s, 3H), 2.06~1.39 (m, 8H). 166.4, 161.8, 154.4, 133.7, 132.9, 131.2, 130.8, 129.7, 127.2, 127.1, 127.0, 126.6, 123.9, 122.1, 63.0, 45.7, 30.5, 24.1, 21.8, 19.7, 17.3. 7b 9.41 (s, 1H), 8.27~7.60 (m, 7H), 4.77~4.66 (m, 1H), 3.59~3.48 (m, 1H), 2.62 (s, 3H), 2.05~1.37 (m, 8H). 170.7, 159.9, 152.1, 135.5, 135.1, 132.8, 131.7, 131.7, 130.5, 130.4, 130.0, 129.6, 128.4, 126.7, 126.3, 126.3, 60.1, 41.8, 26.9, 22.2, 21.1, 15.2, 14.5. 7c 9.42 (s, 1H), 8.29~7.28 (m, 7H), 4.73~4.71 (m, 1H), 3.56~3.53 (m, 1H), 2.62 (s, 3H), 2.05~1.38 (m, 8H). 161.7, 157.8, 153.8, 133.7, 131.3, 130.9, 130.5, 130.0, 128.0, 127.9, 127.0, 123.9, 122.1, 113.4, 113.3, 105.5, 62.9, 45.7, 30.4, 24.1, 21.8, 19.7, 17.1. 7d 9.45 (s, 1H), 8.30~7.09 (m, 8H), 4.72~4.71 (m, 1H), 4.03 (s, 3H),
3.56~3.53 (m, 1H), 2.61 (s, 3H), 2.06~1.35 (m, 8H).162.5, 160.4, 156.7, 152.7, 133.7, 132.0, 131.2, 130.8, 127.9, 127.7, 127.0, 123.9, 122.1, 121.3, 121.2, 112.7, 63.0, 56.4, 45.7, 30.5, 24.1, 21.8, 19.7, 17.3. 7e 9.42 (s, 1H), 8.18~7.36 (m, 8H), 4.73~4.71 (m, 1H), 3.57~3.53 (m, 1H), 2.61 (s, 3H), 2.06~1.36 (m, 8H). 164.8, 163.7, 162.0, 161.7, 154.7, 135.0, 133.7, 132.0, 131.9, 131.3, 130.9, 128.1, 127.0, 122.9, 118.0, 113.1, 62.9, 45.7, 30.5, 24.1, 21.8, 19.7, 14.5. 7f 9.41 (s, 1H), 8.36~8.22 (m, 8H), 4.74~4.72 (m, 1H), 3.57~3.54 (m, 1H), 2.63 (s, 3H), 2.06~1.37 (m, 8H). 163.6, 161.4, 155.3, 148.7, 138.3, 133.7, 131.3, 130.9, 129.4, 127.7, 127.1, 125.0, 123.9, 122.1, 62.9, 45.7, 30.5, 24.1, 21.7, 19.6, 17.2. 7g 9.41 (s, 1H), 8.18~7.54 (m, 8H), 4.72~4.71 (m, 1H), 3.56~3.53 (m, 1H), 2.61 (s, 3H), 2.06~1.35 (m, 8H). 164.6, 161.6, 154.7, 134.7, 134.5, 133.7, 131.7, 130.9, 128.1, 127.1, 127.0, 125.9, 125.4, 123.9, 122.1, 62.9, 45.7, 30.5, 24.1, 21.8, 19.7, 17.2. 7h 9.42 (s, 1H), 8.25~7.64 (m, 8H), 4.74~4.72 (m, 1H), 3.58~3.55 (m, 1H), 2.63 (s, 3H), 2.07~1.38 (m, 8H). 164.4, 161.6, 154.9, 133.7, 131.2, 130.7, 128.3, 127.5, 127.0, 125.1, 123.9, 123.3, 122.5, 122.1, 121.5, 120.2, 62.9, 45.7, 30.5, 24.1, 21.8, 19.7, 17.2. 7i 9.42 (s, 1H), 8.12~7.49 (m, 8H), 4.72~4.70 (m, 1H), 3.56~3.53 (m, 1H), 2.60 (s, 3H), 2.06~1.35 (m, 8H). 166.8, 163.1, 160.2, 155.0, 136.2, 133.7, 131.3, 131.0, 128.2, 127.6, 127.3, 126.7, 125.2, 124.6, 123.4, 109.9, 62.9, 45.7, 30.5, 26.7, 24.1, 21.7, 19.7. 7j 9.41 (s, 1H), 8.24~7.62 (m, 6H), 4.73~4.71 (m, 1H), 3.56~3.53 (m, 1H), 2.62 (s, 3H), 2.06~1.37 (m, 8H). 161.5, 156.6, 153.9, 133.9, 133.7, 131.3, 130.9, 128.7, 127.1, 123.9, 122.0, 117.8, 116.2, 116.1, 107.8, 62.9, 45.7, 30.4, 24.1, 21.79, 19.7, 17.1. 7k 9.42 (s, 1H), 8.26~7.38 (m, 8H), 4.73~4.72 (m, 1H), 3.56~3.53 (m, 1H), 2.63 (s, 3H), 2.06~1.37 (m, 8H). 161.8, 160.6, 159.0, 153.8, 133.7, 132.8, 130.8, 128.8, 128.8, 128.2, 127.1, 125.7, 123.9, 122.1, 120.4, 117.0, 62.9, 45.7, 30.5, 24.1, 21.8, 19.7, 17.1.
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表 3 目标化合物7a~7k对灰霉病菌菌丝生长的抑制作用及对黄瓜叶片灰霉病的防治效果
Table 3. Inhibitory effect of target compound 7a-7k on mycelium growth of B. cinerea and control effect on B. cinerea of cucumber leaves
化合物
Compd.菌丝生长速率法
Mycelium growth rate method黄瓜活体叶片法
In vivo cucumber leaves
method (200 mg/L)EC50(95%置信区间)
(95% Confidence interval)/(mg/L)防治效果
Control efficacy/%7a 23.5(9.70~57.01) 75 7b > 50 88 7c > 50 78 7d > 50 65 7e > 50 96 7f > 50 53 7g > 50 59 7h > 50 1 7i 10.6(2.71~41.6) 29 7j > 50 60 7k 15.7(9.58~25.7) 4 啶酰菌胺
boscalid1.32(0.68~2.55) 98 腐霉利
procymidone1.79(1.42~2.24) 70
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表 4 部分化合物对灰霉病菌孢子萌发的抑制作用及对番茄叶片灰霉病的防治效果
Table 4. Fungicidal activities of selected compounds determined by spore germination methods and in vivo tomato leaves method
化合物
Compd.孢子萌发法
Spore germination
methods (10 mg/L)番茄活体叶片法
In vivo tomato leaves
method (200 mg/L)抑制率
Inhibition rate/%防治效果
Control efficacy /%7a 90 78 7b 84 55 7c 67 62 7d 44 53 7e 60 30 啶酰菌胺
boscalid97 60 腐霉利
procymidone82 45
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表 5 化合物7a和7c在200 mg/L下对番茄花灰霉病的防治效果
Table 5. Fungicidal activities of compounds 7a and 7c against B. cinerea of in vivo tomato flower
化合物
Compd.防治效果
Control efficacy/%7a 30 7c 44 啶酰菌胺 boscalid 30 腐霉利 procymidone 29
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