CN107721945B - 手性补身烷并噁嗪酮类化合物及其作为杀菌剂的用途 - Google Patents
手性补身烷并噁嗪酮类化合物及其作为杀菌剂的用途 Download PDFInfo
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- CN107721945B CN107721945B CN201710820167.6A CN201710820167A CN107721945B CN 107721945 B CN107721945 B CN 107721945B CN 201710820167 A CN201710820167 A CN 201710820167A CN 107721945 B CN107721945 B CN 107721945B
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- oryzae
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- rhizoctonia
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- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/86—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms six-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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Abstract
本发明涉及手性补身烷并噁嗪酮类化合物及其作为杀菌剂的用途,该类化合物的化学结构式如下式(I)所示:
Description
技术领域
本发明涉及一类新的手性补身烷并噁嗪酮类化合物及其作为杀菌剂的用途;特别是指该类化合物在农业真菌病害和细菌病害防治中的应用,属于农药技术领域。
背景技术
农药作为农业生产不可缺少的重要物资,对控制病虫草害、调节植物生长以及农作物稳产、丰产起着十分重要的作用。据联合国粮农组织统计,全球每年因病害造成的损失在11%以上,如马铃薯晚疫病每年在全球造成的损失约67亿美元,稻瘟病每年在全球造成的损失可养活6千万人,小麦赤霉病在美国的年损失高达30亿美元。另一方面农药残留残毒、对环境的负面影响及有害生物的抗药性等问题日趋严重(Thornton,J.PureAppl.Chem.2001,73,1231~1236.)。2016年中央一号文件强调加强农业供给侧改革、提高粮食等农产品的有效供给;目前农药化肥减施增效的要求为绿色植保指出新方向,为新农药创制提出新要求;从分子水平角度讲,农药分子在生物体内发挥药效是一个手性识别过程,配体和受体的匹配性将关系到活性大小和安全性,手性的重要性在现代农药开发中也越来越得到凸显,目前商品化手性农药在农药市场中已超过三分之一(Lamberth,C.,etal.,Science,2013,341,742-746.)。手性农药创制使化学品的精准高效使用成为可能,符合绿色新农药创制的要求。由于天然产物具有化学结构新颖,作用方式多样,环境相容性好等诸多优点,不仅在医药开发中占有重要地位,也是新农药创制的重要途径之一。(吴文君.从天然产物到新农药创制-原理.方法.,2006,北京:化学工业出版社。Newman,D.J.etal.J.Med.Chem.2008,51,2589-2599.ACS Symposium Series 2015,1204,55-62.Pestmanagement science 2017,73,700-715.)。
Drimane类倍半萜是一类重要的天然产物,在自然界中广泛分布,具有广泛的生物活性,如抗肿瘤、拒食活性、植物生长调节性、神经毒性、抗疟活性、强心活性、抗菌活性、抗过敏、抗炎和镇痛、细胞毒性、植物毒性、杀鱼和灭螺活性等(B.J.M.Jansen and Ae.deGroot,Nat.Prod.Rep.,2004,21,449-477)。近年来,关于Drimane类倍半萜及其类似物的构效关系成为医药研究的热点之一,如MacKenzie等人对此类化合物及其类似物的SHIP1调节活性进行了广泛的专利保护(MacKenzie,L.F.,WO 2014110036A1,2014)。Hayakawa最近进行Drimane生物碱的合成并发现其有较好的细胞毒活性。天然产物drimenal对番茄灰霉病菌和马铃薯晚疫病菌都表现出很好的抑制作用(Jochen M.Scher etal..Phytochemistry,2004,65,2583-2588),但文献调研发现此类化合物在农药领域的研究较少,我们发现了手性8-羟基升补身烷倍半萜酰胺类化合物具有较好的抑菌活性(中国发明专利,申请号201610762193.3;申请公布号CN106397254A;Eur.J.Med.Chem.2017,136,114-121.)
本发明发现手性补身烷并噁嗪酮类化合物具有较好的抗真菌和抗细菌活性,这对开发绿色、环境友好的新型杀菌剂具有重要意义。
发明内容
本发明要解决的技术问题是提供手性补身烷并噁嗪酮类化合物的制备方法及其在防治植物真菌病害和细菌病害中的应用。本发明的手性补身烷并噁嗪酮类化合物表现出很好的抑制真菌病害和细菌病害的作用,并且8-号位的手性(立体构型)对抑菌活性有显著的影响。
本发明提供的手性补身烷并噁嗪酮类化合物具有如下通式(I)所示的结构,
通式(I)中8位的立体构型为R或者S,
通式(I)中R代表:
(1)简单脂肪取代基:含有C1~C18的骨架的脂肪烃基取代基,具体包括如下所示的取代基:
(2)卤素原子取代基:主要是指NH中氢被氟,氯,溴和碘取代对应的手性补身烷并噁嗪酮:
(3)苯基,苄基和取代苯乙基类取代基:主要是指卤代苯,卤化苄和2-卤代乙基苯类化合物对应的手性补身烷并噁嗪酮,具体包括如下所示的取代基(n=0,1,2):
(4)吡啶亚甲基类取代基:主要是指N-吡啶亚甲基取代的手性补身烷并噁嗪酮类化合物,具体包括如下所示的取代基:
(5)杂环取代基:主要是指N-杂环取代的手性补身烷并噁嗪酮类化合物,具体包括如下所示的取代基:
本发明还包括如通式(I)所示的手性8-羟基升补身烷倍半萜酰胺类化合物在农药化学上可以接受的盐。
本发明涉及的化合物可以根据如下合成路线来进行化学完成。
合成方法一:
当手性补身烷并噁嗪酮类化合物8位的立体构型为R构型时,通过中间体酰肼的Curtis重排,快速合成手性补身烷并噁嗪酮的母体骨架,当对应的取代试剂为廉价易得的卤代烃时,可按照如下的合成路线来进行N-取代-8-R-补身烷并噁嗪酮类化合物的制备。
该合成路线以廉价易得的天然产物香紫苏醇为起始原料,首先在高锰酸钾氧化条件下对其进行氧化降解获得升补身烷羧酸盐,然后酸性条件下处理环化,制备香紫苏内酯。香紫苏内酯在过量的水合肼乙醇溶液进行肼解,获得酰肼化合物,酰肼化合物再进行Curtius重排反应生成内氨基甲酸酯中间体,通过卤代烃取代反应或者ullmann反应得到N-取代的手性补身烷并噁嗪酮类化合物。
合成方法二:
该合成路线以合成方法一中获得的分子内氨基甲酸酯中间体为起始原料,通过卤代烃取代反应得到N-取代的手性补身烷并噁嗪酮类化合物。
合成方法三:
当手性补身烷并噁嗪酮倍半萜生物碱类化合物8位的立体构型为R构型时,对应的取代基为氯原子时,可按照如下的合成路线来进行N-Cl-8-R-补身烷并噁嗪酮倍半萜生物碱的制备:
该合成路线以合成方法一获得的分子内氨基甲酸酯中间体为起始原料,利用三聚氯氰完成内氨基甲酸酯化合物的N氯代反应,获得目标化合物。
合成方法四:
当手性补身烷并噁嗪酮倍半萜生物碱类化合物8位的立体构型为S构型时,对应的取代试剂为脂肪卤代烃,卤化苄及杂环卤化苄类化合物时,可按照如下的合成路线来进行8-S-补身烷并噁嗪酮倍半萜生物碱的制备。
该合成路线以合成方法一中获得的香紫苏内酯为起始原料,在甲酸/硫酸的混酸体系中完成异构化反应,制备香紫苏内酯的非对映异构体8-epi-香紫苏内酯,然后按照上述方法一获得的分子内氨基甲酸酯,通过方法一或二进行取代反应得到8-S-补身烷并噁嗪酮倍半萜生物碱类化合物。
本发明所提供的手性补身烷并噁嗪酮类化合物具有原料廉价易得和合成步骤少的特点。
本发明所涉及的化合物还包括由通式(I)所示的手性补身烷并噁嗪酮类化合物在药物化学上可以接收的盐。
本发明所提供的手性补身烷并噁嗪酮类化合物的抑菌活性包括抑制真菌活性和抑制细菌活性。选用的真菌包括水稻纹枯病菌(Rhizoctonia solani),小麦纹枯病菌(Rhizoctonia cerealis),油菜菌核病菌(Sclerotinia scleotiorum),小麦赤霉病菌(Fusarium graminearum),小麦全蚀病菌(Gaeumanomyce graminis),番茄灰霉病菌(Botrytis cinerea),马铃薯晚疫病菌(Phytophthora infestans),辣椒疫霉病菌(Phytophthora capsici),番茄早疫病菌(Alternaria solani),水稻恶苗病菌(Fusariumfujikuroi),马铃薯干腐病菌(Fusarium sulphureum),黄瓜炭疽病菌(Colletotrichumlagenarium),水稻稻瘟病菌(Phyricularia cerealis)。病原细菌包括水稻黄单胞杆菌(Xanthomonas oryzae pv.oryzae),枯草芽孢杆菌(Bacillus subtilis),白菜软腐病菌(Erwinia carotovora),水稻细菌性条斑病菌(Xanthomonas oryzae pv.oryzicola),番茄青枯病菌(Ralstonia solanacearum),黄瓜细菌性角斑病菌(Pseudomonas syringaepv.lachrymans),马铃薯环腐病菌(Clavibacter michiganensis subsp.sepedonicus)。
具体实施方式
通过下述实施例和生物活性测定实验结果,可进一步说明和理解本发明,但并不意味着限制本发明。
实施例一:(4aR,6aS,10aS,10bS)-4a,7,7,10a-四甲基十氢化萘-3H-萘并[1,2-e][1,3]噁嗪-3-酮的合成
第一步:香紫苏内酯的((+)-sclareolide)的合成;
将天然产物香紫苏醇(-)-sclareol(10.0g,32.4mmol,1.0equiv)溶于200mL无水丙酮中,将体系置于冰浴中,向其中加入乙酸酐60mL;随后分批加入高锰酸钾粉末(30.7g,194.5mol,6equiv)。体系逐渐回复至室温,磁力搅拌,薄层层析(TLC)跟踪检测反应进程。原料消耗完毕后,向其中缓慢加入碳酸钠水溶液(20.0g/150mL)淬灭反应,继续搅拌0.5小时,过滤,减压下蒸除丙酮,获得香紫苏内酯和升补身烷羧酸的混合物。
向此混合物中加入2N氢氧化钠水溶液(50mL),回流反应2小时,恢复至室温,用2N盐酸酸化反应体系至pH=3。有沉淀析出,用冷水洗滤饼,将滤饼在真空下干燥获得浅黄色固体,硅胶柱层析(200-300m,PE/EtOAc=8∶1)分离后获得白色固体香紫苏内酯4.95g,产率61%。
第二步:升补身烷酰肼中间体的合成;
称取香紫苏内酯(+)-sclareolide(10.0g,39.9mmol,1.0equiv)于500mL茄型瓶中,用乙醇溶解(100mL),加入水合肼(20mL),在室温下搅拌反应约1小时(TLC监测反应完全),减压蒸除溶剂及过量的水合肼并且常温干燥后直获得酰肼化合物中间体,白色固体,产率93%,熔点150.5-153.5(℃)。
第三步:(4aR,6aS,10aS,10bS)-4a,7,7,10a-四甲基十氢化萘-3H-萘并[1,2-e][1,3]噁嗪-3-酮(D)的合成;
称取亚硝酸钠(51mg,0.74mmol,1.37equiv)和酰肼化合物(4)(143mg,0.54mmol,1.0equiv)于50mL茄型瓶中,加入THF/H2O的混合溶液(10mL/10mL),冷却至-10℃,加入1.44mL 0.5M盐酸溶液,在此温度下继续搅拌反应20分钟(TLC监测反应完全),用二氯甲烷萃取反应,5%碳酸氢钠洗涤,水洗,无水硫酸钠干燥,然后减压蒸除溶剂后快速硅胶柱层析获得(4aR,6aS,10aS,10bS)-4a,7,7,10a-四甲基十氢化萘-3H-萘并[1,2-e][1,3]噁嗪-3-酮,白色固体,回收产率35.5%,熔点188.2-189.3(℃)。1H NMR(400MHz,CDCl3)δ0.82(s,3H,CH3),0.87(s,3H,CH3),0.90(s,3H,CH3),1.01~1.07(m,2H,H in naphthane ring),1.18(td,J1=14.80Hz,J2=3.84Hz,1H,H in naphthane ring),1.31(m,1H,H in naphthanering),1.39(s,3H,CH3),1.42~1.55(m,3H,H in naphthane ring),1.60(m,1H,H innaphthane ring),1.64~1.71(m,2H,H in naphthane ring),1.76(m,1H),2.02(dt,J1=12.64Hz,J2=3.16Hz,1H),3.19(m,1H),3.27(m,1H),6.28(br,s,1H,NH).LC-MS(ESI+)m/z:Calcd.for C16H27NO2Na[M+Na]+288.19,Found:288.35.
将(4aR,6aS,10aS,10bS)-4a,7,7,10a-四甲基十氢化萘-3H-萘并[1,2-e][1,3]噁嗪-3-酮溶于二氯甲烷中,缓慢挥发掉溶剂,获得化合物的单晶,结构经X-单晶衍射证实(CCDC:1569963)。
实施例二:(4aR,6aS,10aS,10bS)-2-苄基-4a,7,7,10a-四甲基十氢化萘-3H-萘基[1,2-e][1,3]噁嗪-3-酮的合成
称取手性补身烷并噁嗪酮化合物D(265mg,1.0mmol,1.0equiv)溶于N,N-二甲基甲酰胺溶液中(2mL),在室温下加入NaH(60%dispersion in mineral oil,0.080g,2.0mmol,2.0equiv)并在该温度下搅拌反应30分钟,然后加入氯化苄(0.145mL,1.2mmol,1.2equiv),室温条件下反应,薄层层析(TLC)跟踪检测反应进程。反应完毕后,温度降至室温,然后逐滴加入水进行淬灭反应。加入饱和氯化铵溶液中和至pH约为7,然后用乙酸乙酯萃取3次(3x20mL),有机相依次用水洗,饱和氯化钠洗,无水硫酸钠干燥后,在减压下蒸除溶剂,硅胶柱层析分离(200-300m,PE/EtOAc=2∶1),获得(4aR,6aS,10aS,10bS)-2-苄基-4a,7,7,10a-四甲基十氢化萘-3H-萘基[1,2-e][1,3]噁嗪-3-酮,白色固体,产率84%,熔点:138.6-139.4(℃).1H NMR(400MHz,CDCl3)δ0.79(s,3H,CH3),0.80(s,3H,CH3),0.93~1.02(m,2H,Hin naphthane ring),1.14(td,J1=14.16Hz,J2=4.56Hz,1H,H in naphthane ring),1.28(m,1H,H in naphthane ring),1.33(s,3H,CH3),1.35~1.44(m,3H,H in naphthanering),1.53(m,1H,H in naphthane ring),1.65(td,J1=13.68Hz,J2=4.44Hz,1H,H innaphthane ring),1.71~1.78(m,2H,H in naphthane ring),2.02(dt,J1=12.72Hz,J2=3.20Hz,1H,H in naphthane ring),2.97~3.09(m,2H,NCH2CH),4.48(dd,J=14.88Hz,1H,CH2Ph),4.66(dd,J=14.88Hz,1H,CH2Ph),7.22~7.36(m,5H,Aromatic H).13C NMR(100MHz,CDCl3)δ15.20(CH3),18.22(CH2),19.45(CH2),21.41(CH3)21.45(CH3),33.06(C),33.33(CH3),36.27(C),39.06(CH2),40.08(CH2),41.59(CH2),42.45(CH2),51.73(CH),52.73(CH2),55.74(CH),80.02(C),127.56(CH),127.87(2×CH),128.69(2×CH),136.89(C),153.82(C).LC-MS(ESI+)m/z:Calcd.for C23H34NO2[M+H]+ 356.26,Found 356.33;C23H33NO2Na[M+Na]+378.24,Found:378.31.
将(4aR,6aS,10aS,10bS)-2-苄基-4a,7,7,10a-四甲基十氢化萘-3H-萘基[1,2-e][1,3]噁嗪-3-酮溶于二氯甲烷中,缓慢挥发掉溶剂,获得化合物的单晶,结构经X-单晶衍射证实(CCDC:1569965).。
实施例三:
称取手性补身烷并噁嗪酮化合物D(432mg,1.6mmol,1.0equiv)于50mL茄型瓶中,加入二氯甲烷溶液(4mL),依次加入甲醇加入(250μL),三氯异氰尿酸(370mg,1.6mmol,1.0equiv),室温下搅拌反应4小时(TLC监测反应完全),然后减压蒸除溶剂后快速硅胶柱层析获得化合物(4aR,6aS,10aS,10bS)-2-氯-4a,7,7,10a-四甲基十氢化萘-3H-萘基[1,2-e][1,3]噁嗪-3-酮,白色固体,产率96.4%,熔点140.3-140.7(℃)。1H NMR(400MHz,CDCl3):δ3.71-3.63(m,1H,CH2N),3.60(dd,J=10.5,6.1Hz,1H,CH2N),2.03(dt,J=12.9,3.2Hz,1H,CH-9),1.97(dd,J=12.3,6.1Hz,1H),1.77(d,J=14.2Hz,1H),1.63(ddd,J=25.6,13.1,7.5Hz,3H),1.48(dd,J=16.6,6.1Hz,3H),1.43(s,3H,CH3),1.36-1.24(m,2H),1.19(td,J=13.4,3.7Hz,1H),1.09(dd,J=12.3,3.5Hz,1H),1.01(dd,J=12.4,1.9Hz,1H),0.91(s,3H,CH3),0.90(s,3H,CH3),0.82(s,3H,CH3).13C NMR(100MHz,CDCl3):δ151.64,82.20,55.53,53.52,53.07,41.47,39.72,39.04,36.93,33.30,33.07,21.42,21.33,19.38,18.18,15.22.LC-MS(ESI+)m/z:Calcd.for C16H27ClNO2,[M+H]+:300.17,Found:300.17,C16H26ClNO2Na,[M+Na]+:322.15,Found:322.16,C38H52Cl2N2O4Na,[2M+Na]+:621.32,Found:621.31.
实施例四:手性补身烷并噁嗪酮倍半萜生物碱类化合物的抑菌活性测定
采用平板抑制菌丝生长速率法进行离体抑菌活性评价,选取测试菌株于PDA平板进行活化,包括水稻纹枯病菌(Rhizoctonia solani),油菜菌核病菌(Sclerotiniascleotiorum),小麦赤霉病菌(Fusarium graminearum),小麦全蚀病菌(Gaeumanomycegraminis),番茄灰霉病菌(Botrytis cinerea),马铃薯晚疫病菌(Phytophthorainfestans),辣椒疫霉病菌(Phytophthora capsici),番茄早疫病菌(Alternariasolani),水稻恶苗病菌(Fusarium fujikuroi),马铃薯干腐病菌(Fusarium sulphureum),黄瓜炭疽病菌(Colletotrichum lagenarium),水稻稻瘟病菌(Phyricularia cerealis)。将化合物配置成系列梯度浓度的PDA含药平板,将测试菌株制成5mm直径菌饼置于含药培养皿中央,25℃恒温培养至空白对照皿的测试菌株长至接近培养皿边缘时,用十字交叉法测量各含药平板的菌落直径,计算化合物对菌丝生长的抑制率,对病害的抑制率按照如下公式计算:
使用统计软件SPSS20.0计算抑制率为50%时化合物的浓度,即EC50值。重复3次取平均值。以多菌灵(carbendazim)为阳性对照,各化合物对植物病原真菌的EC50值(μg/mL)。
表1手性补身烷并噁嗪酮类化合物8-位的立体构型对抑菌活性的影响(100μg/mL,%)
表2手性补身烷并噁嗪酮倍类化合物的抑菌活性(EC50值,单位:μg/mL)
实施例五:采用滤纸片扩散法,选取了水稻黄单胞杆菌(Xanthomonas oryzaepv.oryzae),枯草芽孢杆菌(Bacillus subtilis),白菜软腐病菌(Erwinia carotovora),水稻细菌性条斑病菌(Xanthomonas oryzae pv.oryzicola),番茄青枯病菌(Ralstoniasolanacearum),黄瓜细菌性角斑病菌(Pseudomonas syringae pv.lachrymans),马铃薯环腐病菌(Clavibacter michiganensis subsp.sepedonicus)7种重要的植物病原细菌作为供试菌种进行细菌活性初筛测定。采用滤纸片扩散法进行初筛测定化合物对这7种病原细菌的抑制活性。化合物溶解在二甲基亚砜溶液中配成1.0×104μg·mL-1待用,我们将直径为5mm的滤纸片放置在提前倒好的含108CFU·mL-1供试细菌的LB琼脂平板上,每皿两个滤纸片,然后移取浓度为1.0×104μg·mL-1的母液2μL到每一个滤纸片上,待溶剂挥干后放置于28℃培养箱中培养,16h后测量抑菌圈直径,重复3次求平均值。
采用琼脂稀释法测定MIC值。化合物在初筛浓度下有相应的抑菌圈出现时,再采用琼脂稀释法将母液稀释为100、50、25、12.5、6.25、3.125μg·mL-1或128、64、32、16、8、4、2μg·mL-1不同浓度梯度进一步测试化合物的最低抑制浓度(MIC),每个实验重复3次,以硫酸链霉素(抑制革兰氏阴性菌)和氨苄青霉素(抑制革兰氏阳性菌)为阳性对照。
表3 N-取代的Drimane并噁嗪酮类化合物对3种病原细菌活性(MIC值,单位:μg/mL)
结合表1数据,从中可以看出,手性补身烷并噁嗪酮8位的手性对活性有显著的影响,8位的立体构型由R构型变为S构型后,对所测试的11种病原真菌抑制活性有明显的降低。
从表1和表2中可以看出,手性补身烷并噁嗪酮类化合物(8位为R构型)对植物病害有较好的抑制作用。正丁基取代的补身烷并噁嗪酮类化合物对所测定的6种病原真菌均表现出了强烈的抑制作用,抑制中浓度分别为11.40mg/L,7.70mg/L,11.91mg/L,1.18mg/L,11.91mg/L和24.58mg/L;其对番茄灰霉病菌和番茄早疫病菌的活性明显高于阳性对照多菌灵。
结合表3数据,从中可以看出,8位的立体构型对细菌活性也有显著的影响,手性补身烷并噁嗪酮类母体化合物8位由原来的R构型变为S构型后,对所测的3种细菌的抑制活性(MIC值)都有显著的降低。R构型N-取代的补身烷并噁嗪酮类化合物的细菌活性与真菌活性存在明显的差异,正己烷取代的化合物对细菌抑制活性最好,对枯草芽孢杆菌、水稻细菌性条斑病和番茄青枯病菌的MIC值,分别低至8mg/L,12.5mg/L和8mg/L。
本发明所涉及的手性补身烷并噁嗪酮类化合物作为杀菌剂的用途已经通过具体的实例进行了描述,本领域技术人员可借鉴本发明内容,适当改变原料、工艺条件等环节来实现相应的其它目的,其相关改变都没有脱离本发明的内容,所有类似的替换和改动对于本领域技术人员来说是显而易见的,都被视为包括在本发明的范围之内。
Claims (7)
2.权利要求1所示的手性补身烷并噁嗪酮类化合物在防治农业植物病原真菌上的应用,所述农业植物病原真菌选自:水稻纹枯病菌(Rhizoctonia solani),小麦纹枯病菌(Rhizoctonia cerealis),油菜菌核病菌(Sclerotinia scleotiorum),小麦赤霉病菌(Fusarium graminearum),小麦全蚀病菌(Gaeumanomyce graminis),番茄灰霉病菌(Botrytis cinerea),马铃薯晚疫病菌(Phytophthora infestans),辣椒疫霉病菌(Phytophthora capsici),番茄早疫病菌(Alternaria solani),水稻恶苗病菌(Fusariumfujikuroi),马铃薯干腐病菌(Fusarium sulphureum),黄瓜炭疽病菌(Colletotrichumlagenarium),水稻稻瘟病菌(Phyricularia cerealis)。
3.权利要求1所示的手性补身烷并噁嗪酮类化合物在防治农业植物病原细菌上的应用,所述农业植物病原细菌选自:水稻黄单胞杆菌(Xanthomonas oryzae pv.oryzae),枯草芽孢杆菌(Bacillus subtilis),白菜软腐病菌(Erwinia carotovora),水稻细菌性条斑病菌(Xanthomonas oryzae pv.oryzicola),番茄青枯病菌(Ralstonia solanacearum),黄瓜细菌性角斑病菌(Pseudomonas syringae pv.lachrymans),马铃薯环腐病菌(Clavibactermichiganensis subsp.sepedonicus)。
4.如权利要求2所述的应用,其特征在于,所述的农业植物病原真菌为油菜菌核病菌(Sclerotinia scleotiorum),小麦赤霉病菌(Fusarium graminearum)和番茄灰霉病菌(Botrytis cinerea)。
5.如权利要求3所述的应用,其特征在于,所述的农业植物病原细菌为枯草芽孢杆菌(Bacillus subtilis),水稻细菌性条斑病菌(Xanthomonas oryzae pv.oryzicola)和番茄青枯病菌(Ralstonia solanacearum)。
6.根据权利要求2-5任一项所述的应用,所述化合物被加工成乳油、水乳剂、微乳剂、可湿性粉剂、水分散粒剂或悬浮剂。
7.权利要求1所述手性补身烷并噁嗪酮类化合物在防治植物病害中的应用,其特征在于它作为抑菌剂与商品化杀菌剂中的一种或多种组合在制备复配杀菌剂中的用途;商品化杀菌剂选自嘧菌酯、吡唑醚菌酯、嘧霉胺、氟唑菌酰胺、苯并烯氟菌唑、联苯吡菌胺、氟唑菌苯胺、氟吡菌胺、氟吡菌酰胺、异噻菌胺、氟嘧菌酯、肟醚菌胺、苯菌酮、氟噻唑吡乙酮、丙硫菌唑、肟菌酯、环菌唑、代森锰锌、氟环唑、戊唑醇、啶酰菌胺、甲霜灵、啶氧菌酯、苯醚甲环唑、丙环唑、百菌清、噻酰菌胺、甲噻诱胺、异噻菌胺、宁南霉素、烯丙异噻唑、氟吗啉、烯酰吗啉、氢氧化铜、硫酸铜、氧氯化铜、链霉素、春雷霉素、乙蒜素、二氯异氰尿酸、三氯异氰尿酸、氯溴异氰尿酸;所述植物病害为权利要求2中所述的农业植物病原真菌或权利要求3中所述的农业植物病原细菌。
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