CN106818771B - 吩嗪‑1‑甲酰胺改造化合物15‑1在抑制草莓灰霉病菌中的应用 - Google Patents
吩嗪‑1‑甲酰胺改造化合物15‑1在抑制草莓灰霉病菌中的应用 Download PDFInfo
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- CN106818771B CN106818771B CN201710169271.3A CN201710169271A CN106818771B CN 106818771 B CN106818771 B CN 106818771B CN 201710169271 A CN201710169271 A CN 201710169271A CN 106818771 B CN106818771 B CN 106818771B
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Classifications
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- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/60—1,4-Diazines; Hydrogenated 1,4-diazines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
- C07D241/46—Phenazines
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Pest Control & Pesticides (AREA)
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- Engineering & Computer Science (AREA)
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- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
本发明属于农药创制领域，特别涉及吩嗪‑1‑甲酰胺改造化合物15‑1在抑制草莓灰霉病菌中的应用，该吩嗪‑1‑甲酰胺改造化合物15‑1是以吩嗪‑1‑甲酰胺为母体，经结构改造获得。本发明采用生长速率法测定了该改造化合物15‑1对改草莓灰霉病菌的抑制作用，结果显示：改造化合物15‑1与其母体皆能对草莓灰霉病菌产生抑制作用，且抑制效果强于其母体吩嗪‑1‑甲酰胺，表明改造物15‑1可作为防控草莓灰霉病新农药的先导化合物。
Description
技术领域
本发明属于农药创制领域，特别涉及吩嗪-1-甲酰胺改造化合物15-1在抑制草莓灰霉病菌(Botrytis cinerea)中的应用。
背景技术
草莓是蔷薇科草莓属植物，具有多年生长的习性。原产南美，中国各地及欧洲等地广为栽培。草莓营养价值丰富，被誉为是“水果皇后”，含有丰富的维生素C、维生素A、维生素E、维生素PP、维生素B1、维生素B2、胡萝卜素、鞣酸、天冬氨酸、铜、草莓胺、果胶、纤维素、叶酸、铁、钙、鞣花酸与花青素等营养物质，深受消费者喜爱。草莓在生长的过程中常受外界环境条件的影响，例如：温度、湿度、光照、地势、病害等，其中草莓灰霉病是草莓生育期间的重要病害，每年由该病害造成的经济损失可达30-60％，甚至绝产。
目前，生产上防治草莓灰霉病的方法主要依靠化学农药，例如：腐霉利、多菌灵、乙霉威、异菌脲等。但长期大量使用化学农药不仅污染环境、破坏生态平衡，而且容易使病菌产生抗药性。前人的研究结果表明：草莓灰霉病菌已对多种化学农药产生了抗药性。因此，探寻防治草莓灰霉病的新农药刻不容缓。
现有开发新农药的途径主要有化学合成、已有化合物的结构改造、从植物或微生物体内筛选结构新颖的化合物等，其中已有化合物的结构改造是开发新农药的方法，不仅可以节约研发成本，而且短期效益显著。本课题组曾研究具有抑菌作用的吩嗪-1-甲酰胺，但其抑菌效果相对弱，因此，本课题组以吩嗪-1-甲酰胺为母体，通过结构改造并获得了吩嗪-1-甲酰胺改造化合物15-1。为明确该改造化合物的开发潜力，本发明评价了其对草莓灰霉病菌的抑制效果及增效作用，旨在为丰富防治草莓灰霉病的新农药提供理论依据和实践基础。
发明内容
本发明所要解决的技术问题是，针对上述现有技术的不足，提供一种改造化合物15-1在抑制草莓灰霉病菌中的应用，该改造化合物15-1是以吩嗪-1-甲酰胺为母体经结构改造得到。本发明采用菌丝生长速率法测定了该改造化合物15-1对草莓灰霉病菌的抑制作用，结果表明改造化合物15-1对草莓灰霉病菌有抑制效果，而且该抑菌效果要强于其母体吩嗪-1-甲酰胺。
为解决上述技术问题，本发明所采用的技术方案是：一种吩嗪-1-甲酰胺改造化合物15-1在抑制草莓灰霉病菌中的应用。
本发明同时提供一种吩嗪-1-甲酰胺改造化合物15-1在制备防控草莓灰霉病农药中的应用。
上述吩嗪-1-甲酰胺改造化合物15-1的结构式如下：
上述吩嗪-1-甲酰胺改造化合物15-1是以吩嗪-1-甲酰胺为母体，将其在酸性条件下水解生成吩嗪-1-羧酸；再以吩嗪-1-羧酸和亚硫酰氯进行回流反应获得中间产物吩嗪-1-甲酰氯；最后将吩嗪-1-甲酰氯溶于干燥二氯甲烷，置于冰水浴中冷却，0℃条件下先后加入三乙胺和3-甲氧基-1-丙胺，于室温下反应制得。
与现有技术相比，本发明具有的优点为：本发明的改造化合物15-1对草莓灰霉病菌具有较强的毒力，其EC50为4.25μg/mL，比对照药剂(其母体吩嗪-1-甲酰胺)的EC50低；本改造化合物15-1不易使病菌产生抗药性，其对草莓灰霉病菌的抑制作用强于其母体吩嗪-1-甲酰胺，丰富了防治草莓灰霉病菌的新农药。
附图说明
图1是本发明吩嗪-1-甲酰胺改造化合物15-1的质谱图。
具体实施方式
下面结合具体试验和实施例对本发明的技术方案作进一步说明，本发明试验和实施例中涉及的百分比均为质量百分比。
本发明所用的改造化合物的原材料为市售。
实施例1改造化合物15-1的制备
合成方法具体为：将吩嗪-1-甲酰胺在酸性条件(如硫酸)下水解生成吩嗪-1-羧酸。取20mmol吩嗪-1-羧酸(0.4577g)和200ml亚硫酰氯加入到500ml圆底烧瓶中，安装回流反应装置(使用无水氯化钙干燥管)，磁力搅拌，回流反应6h。反应液冷却后，旋蒸移除亚硫酰氯，获得中间产物吩嗪-1-甲酰氯，不需纯化直接用于下一步反应。将获得的吩嗪-1-甲酰氯溶于200ml干燥二氯甲烷(DCM)，加入到500ml干燥圆底烧瓶中，氮气保护，磁力搅拌，置于冰水浴中冷却，0℃条件下先后加入11.15ml三乙胺(80mmol，4equiv.)和2.367g 3-甲氧基-1-丙胺(20mmol，1equiv.)，加料完毕后撤除冰水浴，室温条件下反应14h，间歇取样，TLC监测反应。反应完毕后将反应物旋蒸移除DCM，然后萃取三次，每次使用450ml液体(乙酸乙酯与H2O按2:1的体积比混合)萃取。合并有机相，使用无水硫酸钠干燥12h。过滤，使用EA洗涤固体硫酸钠。旋蒸，得改造化合物产品15-1，1.4833g，产率22.93％。
实施例2改造化合物15-1的结构鉴定
采用核磁共振氢谱(1H NMR)，核磁共振碳谱(13C NMR)技术对获得的改造化合物15-1进行测定。经氢谱(1H NMR(500MHz,CDCl3)δ11.03(s,12H),9.25–8.90(m,59H),8.90–7.86(m,427H),8.11–7.73(m,224H),8.11–7.73(m,223H),7.82(dd,J＝16.5,10.4Hz,19H),7.29(s,16H),7.10–6.85(m,6H),5.86–5.75(m,8H),5.33–5.23(m,9H),4.82(t,J＝9.7Hz,9H),4.89–4.39(m,14H),4.89–4.24(m,19H),4.89–4.18(m,23H),4.89–4.07(m,29H),4.89–4.02(m,32H),4.89–3.71(m,81H),3.68(d,J＝20.8Hz,17H),3.71–3.51(m,22H),3.71–3.30(m,38H),3.71–3.26(m,43H),3.71–3.20(m,53H),3.71–3.03(m,80H),3.71–3.05(m,80H),3.71–2.93(m,83H),3.71–2.88(m,84H),3.71–2.81(m,85H),3.71–2.45(m,128H),3.71–2.41(m,133H),3.71–2.27(m,150H),3.71–2.17(m,155H),3.71–2.12(m,159H),3.71–2.07(m,169H),3.71–2.01(m,175H),3.71–1.70(m,258H),3.71–1.62(m,273H),3.71–1.54(m,292H),3.71–1.40(m,351H),1.24(dd,J＝37.1,31.7Hz,182H),1.04(t,J＝6.9Hz,19H),0.92(dd,J＝41.2,7.3Hz,48H),0.18–-0.07(m,161H).)、碳谱(13C NMR(126MHz,CDCl3)δ165.89(s),143.98(s),143.26(s),142.68(s),139.95(s),139.75(s),137.35(s),135.44(s),135.02(s),133.48(s),133.17(s),131.73(d,J＝9.5Hz),131.12(s),130.58(s),130.32–129.88(m),129.80–129.54(m),129.45(s),128.99(s),127.89(s),124.85(s),77.26(s),77.00(s),76.75(s),46.33(s),39.50(s),39.14(s),33.58(s),28.91(s),22.52(s),14.00(s),0.96(s).)，结合质谱(分子量：323.20，图1)检测合成的化合物与预期目标吻合，其分子式为C18H17N3O3，结构式如下所示：
实施例3改造化合物15-1对草莓灰霉病菌的抑制作用
⑴仪器及相关材料
YJ-VS-2型超净工作台(无锡一净净化设备有限公司)，LDZX-30E灭菌锅(上海申安医疗器械厂)，MPJ-250型培养箱(上海森信实验仪器有限公司)，QHX-400B-III型光照培养箱(上海新苗医疗器械制造有限公司)，电炉(北京中兴伟业仪器有限公司)等以及量筒、玻璃棒、烧杯、三角瓶、直尺、铅笔、标签纸、封口膜、挑针、容量瓶、接种针、ph-101喷壶、打孔器、培养皿、菜刀、纱布。
⑵药剂
实施例1制备得到的92.26％吩嗪-1-甲酰胺改造物15-1原药(简称：改造物15-1)；琼脂、葡萄糖、丙酮和吐温80等药剂均从国药集团购买。
⑶菌株
试验用野生敏感型的草莓灰霉病菌(Botrytis cinerea)由湖南农业大学植物病理实验室分离、鉴定和保存。
⑷改造物15-1对草莓灰霉病菌的抑制作用
采用生长速率法测定改造物15-1对草莓灰霉病菌(Botrytis cinerea)的抑制作用。取适量丙酮将改造物15-1原药溶解，然后配制成质量浓度为1000μg/mL的母液，按药液与PDA培养基按1：9的体积比配制成最终含药量为2.5、5、10、20、40μg/mL的含药平板，以少量丙酮和清水的混合物作对照，用直径5mm的打孔器在预培养2d的草莓灰霉病菌菌落边缘打取，菌饼正面朝下接种到含药平板上，每处理重复3次，并以无药平板作对照，置于26-28℃培养箱中，待对照菌落直径长至整个培养的2/3时，采用十字交叉法测量各处理的菌落直径。
同时，采用同样的方法测试吩嗪-1-甲酰胺(最终含药量为0.625、1.25、2.5、5、10μg/mL)对草莓灰霉病的抑制作用。计算抑制率、EC50值、相关系数及回归方程。
⑸结果与分析
由表1可知，改造物15-1浓度越高，抑菌效果越好。当改造物15-1浓度为40μg/mL时，抑菌效果最好，其抑制率为92.49％；其次，改造物15-1浓度为20μg/mL时，抑菌效果次之；其他处理的抑制率低于80％。该药剂对草莓灰霉病菌具有较强毒力效果(EC50为4.71μg/mL，回归方程为Y＝1.6193X+3.9100，相关系数为0.9878)，其毒力强于对照药剂吩嗪-1-甲酰胺(EC50为21.62μg/mL，回归方程为Y＝1.0821x+3.5556，相关系数为0.9714)，抑制率明显高于对照药剂吩嗪-1-甲酰胺(见表2)，说明改造物15-1可作为防控草莓灰霉病新农药的先导化合物。
表1吩嗪-1-甲酰胺改造物15-1对草莓灰霉病菌的抑制作用
表2吩嗪-1-甲酰胺对草莓灰霉病菌的抑制作用
Claims (3)
1.一种吩嗪-1-甲酰胺改造化合物15-1在抑制草莓灰霉病菌中的应用，该吩嗪-1-甲酰胺改造化合物15-1的结构式如下：
2.一种吩嗪-1-甲酰胺改造化合物15-1在制备防控草莓灰霉病农药中的应用，该吩嗪-1-甲酰胺改造化合物15-1的结构式如下：
3.如权利要求1或2所述的应用，其特征在于，所述吩嗪-1-甲酰胺改造化合物15-1是以吩嗪-1-甲酰胺为母体，将其在酸性条件下水解生成吩嗪-1-羧酸；再以吩嗪-1-羧酸和亚硫酰氯进行回流反应获得中间产物吩嗪-1-甲酰氯；最后将吩嗪-1-甲酰氯溶于干燥二氯甲烷，置于冰水浴中冷却，0℃条件下先后加入三乙胺和3-甲氧基-1-丙胺，于室温下反应制得。
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