CN118754840A - 一类含羰基结构的α,β-不饱和酰胺或酰肼类化合物及其制备方法和应用 - Google Patents
一类含羰基结构的α,β-不饱和酰胺或酰肼类化合物及其制备方法和应用 Download PDFInfo
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- CN118754840A CN118754840A CN202410982648.7A CN202410982648A CN118754840A CN 118754840 A CN118754840 A CN 118754840A CN 202410982648 A CN202410982648 A CN 202410982648A CN 118754840 A CN118754840 A CN 118754840A
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Abstract
本发明涉及药物化学技术领域，具体涉及一种含羰基结构的α,β‑不饱和酰胺或酰肼类化合物及制备方法和应用。本发明主要制备了含羰基结构的α,β‑不饱和酰胺或酰肼类化合物，该类化合物结构新颖，且对植物病原真菌具有良好的抑制作用，尤其对植物病原真菌如葡萄座腔菌、水稻纹枯病菌、油菜菌核病菌、小麦赤霉病菌、番茄早疫病菌、烟草赤星病菌和茄子黄萎病菌等具有良好的抑制效果。该类化合物在植物真菌性病害的防治方面具有突出优势。
Description
技术领域
本发明涉及药物化学技术领域，具体涉及一种含羰基结构的α,β-不饱和酰胺或酰肼结构的化合物及制备方法与应用。
背景技术
植物真菌性病害可引起农作物减产以及品质降低，造成了严重的经济损失，同时，某些真菌会分泌毒力因子等对人和动物有害。常见的植物真菌性病害如油菜菌核病、小麦赤霉病、番茄早疫病、蓝莓根腐病、葡萄溃疡病、水稻纹枯病、烟草赤星病和茄子黄萎病等，能引起农作物枯萎、腐烂和坏死等症状，从而严重影响了农作物和经济作物的产量和质量。然而，由于长时间使用或滥用传统杀菌剂，从而导致耐药性和环境污染等问题。因此，迫切需要开发具有高活性、高选择性、作用机制新颖和对环境友好的新型杀菌剂。
目前，通过对天然产物进行结构修饰是发现新型绿色杀菌剂重要策略之一。色胺，是一种含有吲哚环结构的天然产物，存在于哺乳动物大脑和部分植物中，起到神经调节的作用，色胺及其衍生物具有多种生物学活性，包括抗菌、抗偏头痛、抗乙酰胆碱酯酶、舒张血管、抗心律失常等，例如：2021年Sheng等设计合成系列色胺衍生物，并测定其抗真菌活性，发现大部分化合物表现出较好的抗菌活性，[J].European Journal of MedicinalChemistry,2021,222:113563；2023年，Sheng等又制备了新的系列色胺衍生物，并评价了其抗真菌活性，大多化合物具有显著的抗菌活性，[J].Journalof Medicinal Chemistry,2023,66:9040-9056。此外，α,β-不饱和酰胺或酰肼结构由于其含有α,β-不饱和羰基片段可以通过Micheal加成反应与存在于DNA、RNA或某些重要酶中的活性亲电子基团发生反应，形成迈克尔加合物，使DNA分子断裂或失活。另一方面，许多天然产物和高活性化合物正是因为含有这种特殊的结构，才具有良好的生物学活性和临床应用潜力。因此，为寻找具有高效抗菌活性的天然先导化合物，本发明主要以色胺、3-(氨甲基)吲哚、苯胺和苯乙胺为基础，合成了一系列含羰基结构的α,β-不饱和酰胺或酰肼类化合物，并具有良好的抗植物病原微生物的生物活性。
发明内容
本发明的目的之一提供了一类含羰基结构的α,β-不饱和酰胺或酰肼类化合物或其立体异构体、或其盐或其溶剂化物。
本发明的另一目的在提供了制备上述化合物或其立体异构体、或其盐或其溶剂化物的中间体化合物及其制备方法。
本发明还有一目的是提供了一种含有上述化合物或其立体异构体、或其盐或其溶剂化物的组合物。
本发明还有一目的是提供了上述化合物或其立体异构体、或其盐或其溶剂化物，或所述组合物的用途。
本发明另一目的是提供了利用上述化合物或其立体异构体、或其盐或其溶剂化物，或所述组合物防治农业病害的方法。
为实现上述目的，本发明采用了下述技术方案：
一种含羰基结构的α,β-不饱和酰胺或酰肼结构的化合物或其立体异构体、或其盐或其溶剂化物，该化合物具有如通式(Ⅰ)所示的结构：
其中，
R1选自色胺、3-(氨甲基)吲哚、苯胺和苯乙胺。
R2选自选自氢、氘、任意取代或未取代的烷基、任意取代或未取代的烯基、任意取代或未取代的炔基、任意取代或未取代的芳基、任意取代的苄基、任意取代或未取代的苯胺基、任意取代或未取代的杂芳基中的一个或多个；
优选地，R2选自氢、氘、任意取代或未取代的烷基、任意取代或未取代的烯基、任意取代或未取代的炔基、任意取代或未取代的芳基、任意取代的苄基、任意取代或未取代的苯胺基、任意取代或未取代的杂芳基中的一个或多个；优选地，R选自氢、氘、C1-C6烷基、C2-C6烯基、C2-C6炔基、C1-C6烷氧基、取代或未取代的C6-C15芳基、取代的C6-C15苄基、取代的C6-C15苯胺基、取代或未取代的C6-C10杂芳基中的一个或多个，其中，所述取代的指的是被C1-C6烷基、C1-C6烷氧基、氨基、羟基、卤素、硝基、三氟甲基中的一个或多个取代；更优选地，R选自氢、氘、甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、异戊基、新戊基、1,1-二甲基、1,5-二甲基己基、1,1-二乙醇基、丙烯基、烯丙基、甲氧基、乙氧基、丙氧基、丁氧基、取代或未取代的苯基、取代或未取代的苯胺基、取代的苄基，其中，所述取代的指的是被C1-C6烷基、C1-C6烷氧基、氨基、羟基、卤素、硝基、三氟甲基中的一个或多个取代；最优选地，R2选自：
最优选地，所述化合物或其立体异构体、或其盐或其溶剂化物等选自下述具体化合物：
本发明还提供了一种制备所述的各类含羰基结构的α,β-不饱和酰胺或酰肼结构的化合物或其立体异构体、或其盐或其溶剂化物制备方法，其特征在于包括下述步骤：
其中R1和R2如上所述。
本发明还提供了一种组合物，其含有所述的化合物或其立体异构体、或其盐或其溶剂化物，以及农业上可用的助剂或杀菌剂、杀虫剂或除草剂；优选地，所述组合物的剂型选自乳油(EC)、粉剂(DP)、可湿性粉剂(WP)、颗粒剂(GR)、水剂(AS)、悬浮剂(SC)、超低容量喷雾剂(ULV)、可溶性粉剂(SP)、微胶囊剂(MC)、烟剂(FU)、水乳剂(EW)、水分散性粒剂(WG)。
所述的化合物或其立体异构体、或其盐或其溶剂化物，或所述的组合物可用于防治农业病害，优选地，所述农业病害为植物真菌性病害；更优选地，所述农业病害为油菜菌核病、小麦赤霉病、番茄早疫病、葡萄溃疡病、水稻纹枯病、烟草赤星病、茄子黄萎病。
本发明还提供了一种防治农业病害的方法，使所述的化合物或其立体异构体、或其盐或其溶剂化物，或所述的组合物作用于有害物或其生活环境；优选地，所述农业病害为植物真菌性病害；更优选地，所述农业病害为油菜菌核病、小麦赤霉病、番茄早疫病、葡萄溃疡病、水稻纹枯病、烟草赤星病、茄子黄萎病、果生刺盘孢菌、胶孢炭疽菌、高粱刺盘孢菌、辣椒炭疽病菌、油菜菌核病菌、葡萄座腔菌、黄瓜灰霉病菌、辣椒枯萎病菌、马铃薯晚疫病菌、火龙果炭疽病菌、番茄早疫病菌、蓝莓根腐病菌、大豆茎溃疡菌、水稻穗腐病、花生网斑病菌、灰霉病菌引起的病害。
本发明还提供了一种用于保护植物免受农业病害侵害的方法，其包括其中使植物与所述的化合物或其立体异构体、或其盐或其溶剂化物，或所述的组合物接触的方法步骤。
此处用到的术语“烷基”是包括具有特定数目碳原子的支链和直链饱和烃基。例如“C1-10烷基”(或亚烷基)目的是C1、C2、C3、C4、C5、C6、C7、C8、C9和C10烷基。另外，例如“C1-6烷基”表示具有1到6个碳原子的烷基。烷基可为非取代或取代的，以使一个或多个其氢原子被其它化学基团取代。烷基的实施例包括但不限于甲基(Me)、乙基(Et)、丙基(如正丙基和异丙基)、丁基(如正丁基、异丁基、叔丁基)、戊基(如正戊基、异戊基、新戊基)及其类似物。
“烯基”是既包括直链或支链结构的烃，且具有一个或多个出现在链中任何稳定点的碳-碳双键。例如“C2-6烯基”(或亚烯基)目的是包括C2、C3、C4、C5和C6烯基。烯基的实例包括但不限于乙烯基、1-丙烯基,2-丙烯基、2-丁烯基、3-丁烯基、2-戊烯基、3-戊烯基、4-戊烯基、2-己烯基、3己烯基、4-己烯基、5-己烯基、2-甲基-2-丙烯基、4-甲基-3-戊烯基及其类似物。
“炔基”是既包括直链或支链结构的烃，且具有一个或多个出现在链中任何稳定点的碳-碳叁键。例如“C2-6炔基”(或亚炔基)目的是包括C2、C3、C4、C5和C6炔基；如乙炔基、丙炔基、丁炔基、戊炔基、己炔基及其类似物。
此处用到的术语“取代的”指的是在指定原子或基团上的任意一个或多个氢原子以选择的指定基团取代，前提是不超过指定原子的一般化合价。如果没有其它说明，取代基命名至中心结构。例如，可以理解的是当(环烷基)烷基是可能的取代基，该取代基至中心结构的连接点是在烷基部分中。此处使用的环双键是形成于两个临近环原子之间的双键(如C＝C、C＝N或N＝N)。当提到取代时，特别是多取代时，指的是多个取代基在指定基团上的各个位置上取代，如二氯苯基指的是1,2-二氯苯基、1,3-二氯苯基、1,4-二氯苯基和2,4-二氯苯基。
取代基或变量的组合是允许的，仅当这些组合产生稳定的化合物或有用的合成中间体。稳定的化合物或稳定结构暗示所述化合物以有用的纯度从反应混合物分离出来时是足够稳定的，随之配制形成有效的治疗试剂。优选地，目前所述化合物不包含N-卤素、S(O)2H或S(O)H基。
术语“芳基”指的是在环部分具有6到12个碳原子的单环或双环芳香烃基，如苯基和萘基，每个可被取代的。
术语“卤素”或“卤素原子”指的是氯、溴、氟和碘。
术语“卤代烷基”指的是具有一个或多个卤素取代基的取代烷基。例如“卤代烷基”包括单、双和三氟甲基；即便卤代烷基中的卤代被明确为氟、氯、溴、碘，同样指的是具有一个或多个氟、氯、溴、碘取代基的取代烷基。
术语“杂芳基”指的是取代和非取代芳香5或6元单环基团，9-或10-元双环基团，和11到14元三环基团，在至少一个环中具有至少一个杂原子(O,S或N)，所述含杂原子的环优选具有1、2或3个选自O、S和N中的杂原子。含杂原子的杂芳基的每个环可含一个或两个氧或硫原子和/或由1到4个氮原子，前提是每个环中杂原子的总数是4或更少，且每个环具有至少一个碳原子。完成双环和三环基团的稠合环可仅含有碳原子，并可以是饱和、部分饱和或不饱和。氮和硫原子可任选被氧化且氮原子可任选被季铵化。双环或三环的杂芳基必须包括至少一个全芳香环，氮其它稠合环可为芳香性或非芳香性的。杂芳基可在任何环的任何可利用氮或碳原子上连接。当化合价允许，如果所述其它环是环烷基或杂环，其另外任选以＝O(氧)取代。
示例性单环杂芳基包括吡咯基、吡唑基、吡唑啉基、咪唑基、噁唑基、异噁唑基、噻唑基、噻二唑基、呋喃基、噻吩基、噁二唑基、吡啶基、吡嗪基、嘧啶基、哒嗪基、三嗪基及其类似物。
示例性双环杂芳基包括吲哚基、螺色酮基、苯并二氧杂环戊烯基、苯并噁唑基、苯并噻吩基、喹啉基、四氢异喹啉基、异喹啉基、苯并咪唑基、苯并呋喃基、吲哚嗪基、苯并呋喃基、色酮基、香豆素基、苯并呋喃基、噌啉基、喹喔啉基、吲唑基、吡咯并吡啶基、氟代吡啶基、二氢异吲哚基、四氢喹啉基及其类似物。
如果没有其它说明，本发明的化合物理解为包括游离态和其盐。术语“盐”表示以无机和/或有机酸和碱形成酸式和/或碱式盐。
优选地，C1-C10烷基指的是甲基、乙基、丙基、丁基、戊基、己基、庚基、辛基、壬基、癸基及其同分异构体；C1-C10烷氧基指的是甲氧基、乙氧基、丙氧基、丁氧基、戊氧基、己氧基、庚氧基、辛氧基、壬氧基、癸氧基及其同分异构体；C2-C5烯基指的是乙烯基、丙烯基、烯丙基、丁烯基、戊烯基及其同分异构体。
当提到取代基为烯基、炔基、烷基、卤素、芳基、杂芳基、烷氧基、环烷基、羟基、氨基、巯基、膦基时，或这些取代基具体的为某个具体的烯基、炔基、烷基、卤素、芳基、杂芳基、烷氧基、环烷基、羟基、氨基、巯基、膦基时，指的是一个到三个上述取代基。如甲基苯基指的是一个到三个甲基取代的苯基。
通过采用上述技术方案，本发明以色胺、3-(氨甲基)吲哚、苯胺和苯乙胺类化合物为基础，合成一系列含羰基结构的α,β-不饱和酰胺或酰肼类衍生物，且发现该系列化合物对植物病原真菌具有良好的抑制作用，针对病原真菌[如葡萄座腔菌(Botryosphaeriadothidea,B.d)、水稻纹枯病菌(Rhizoctonia solani,R.s)、油菜菌核病菌(Sclerotiniasclerotiorum,S.s)、小麦赤霉病菌(Gibberella zeae,G.z)、番茄早疫病菌(Alternariasolani,A.s)、烟草赤星病菌(Alternaria alternata,A.a)和茄子黄萎病菌(Verticilliumdahliae,V.d)]均具有良好的抑制效果，为新农药的研发和创制提供重要的科学基础。
具体实施方式
下面将结合本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
若未特别指明，实施举例中所用的技术手段为本领域技术人员所熟知的常规手段。实施例中用到的所有原料和溶剂均为市售产品。
实施例1：中间体1的制备
将马来酸酐(1g,10.2mmoL)加入到15mL二氯甲烷中，室温搅拌10min，然后缓慢加入色胺(1.63g,10.2mmoL)，搅拌过夜。抽滤，得淡黄固体，收率90％。
其他中间体，参考实施例1的步骤分别以3-(氨甲基)吲哚、苯胺和苯乙胺为原料与马来酸酐合成相应的中间体。
实施例2：目标化合物N1-(2-(1H-indol-3-yl)ethyl)-N4-(4-methoxyphenyl)maleamide将中间体1(0.5g,1.94mmol)、1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(0.44534g,2.32mmol)和1-羟基苯并三唑(0.15695g，1.16mmol)加入到50mL圆底烧瓶中，加入10mL二氯甲烷作溶剂，三乙胺(0.23508g,2.32mmol)加入其中，常温搅拌30min，加入4-甲氧基苯胺(0.47683g,3.87mmol)，直到中间体1完全反应。反应混合物用水(20mL)萃取分液，二氯甲烷提取(30mL×2)，有机层用无水Na2SO4干燥，真空蒸发。目标化合物使用CH2Cl2和CH3OH(200:1；V/V)作为洗脱剂进行柱层析分离和提纯。最终得到黄色液体目标化合物1，产率70.1％。
其他目标化合物，采用相应的原料或取代基，参照实施例2步骤合成。
合成的含羰基结构的α,β-不饱和酰胺或酰肼类化合物的结构及核磁共振氢谱和碳谱数据如表1所示，物化性质如表2所示。
表1部分化合物的核磁共振氢谱和碳谱数据
表2目标化合物的理化性质
药理实施例1：
EC50(median effective concentration)是评价植物病原菌对化合物敏感性的重要指标，同时也是对目标化合物作用机制研究时，化合物浓度设置的重要参数。在浓度梯度实验中，采用二倍稀释法设定合适的5个浓度，最后将药剂对植物病原菌的抑制率、药剂浓度换算成对数值，通过SPSS软件回归分析得到毒力曲线，计算出EC50。
抗病原真菌的离体测试采用菌丝体生长速率抑制法测试所合成目标化合物对葡萄座腔菌(Botryosphaeria dothidea,B.d)、水稻纹枯病菌(Rhizoctonia solani,R.s)、油菜菌核病菌(Sclerotinia sclerotiorum,S.s)、小麦赤霉病菌(Gibberella zeae,G.z)、番茄早疫病菌(Alternaria solani,A.s)、烟草赤星病菌(Alternaria alternata,A.a)和茄子黄萎病菌(Verticillium dahliae,V.d)等植物病原真菌在PDA培养基的抗菌活性。用万分之一天平称量待测目标化合物，加入所称取待测目标化合物质量的20倍体积的DMSO溶解后，待完全溶解后母液浓度为50μg/mL，再所测相应浓度下取相应体积母液于2mL离心管中，再加入DMSO配平至终体积为1mL，在无菌操作台中转移至15mL灭菌的离心管中，加入9mL吐温水(Tween-20)，充分震荡混匀后倒入培养基中，混匀后平均分装至9个培养皿中冷却备用；在无菌操作台内，以灭菌的打孔器(5mm)将生长正常的菌落制成菌饼(菌饼直径5mm)，用接菌环将菌饼倒扣于培养基中央，于28℃条件下培养3-7天，待对照组菌落生长至直径的5.0-7.0cm时用直尺按十字交叉法测量2次，以平均值计算菌落直径大小。初步筛选试验浓度我们选择为50μg/mL，所测目标化合物在此浓度下对相应的病菌抑制率大于80％时再对其进行EC50测试，根据下列公式求出菌丝生长抑制率。将嘧菌酯、烯酰吗啉、腈菌唑作为对照药剂一起进行测试。计算公式如下：
抑制率(％)＝(C1-C2)/(C1-0.5)×100公式中：
C1为对照菌落直径即DMSO处理的菌落直径(即CK)；
C2为处理菌落直径即加药处理的菌落直径；
0.5为母菌菌饼的直径。
PDA培养基的配方：马铃薯,琼脂粉,葡萄糖,硫酸镁,磷酸二氢钾，维生素B1，自然PH，灭菌(120℃,30min)。1000mL马铃薯煮汁：将马铃薯去皮洗净切丝后称200g于1L二次水中煮至土豆丝可用手指轻轻捻碎，纱布过滤；称取20g琼脂粉于烧杯中，加入少量冷水划散后将其倒入沸腾的马铃薯溶液中，煮至琼脂粉融化，期间需不断快速搅拌，称取20g葡萄糖，硫酸镁1.5g，磷酸二氢钾3.0g、维生素B1 10mg，加至滤液中，搅拌溶解，补加二次水至1L，自然PH，趁热量取90mL分装至200mL的锥形瓶中，用半透滤膜密封于120℃高压灭菌锅中灭菌30min备用。
本发明实施例辅以说明本发明的技术方案，但实施例的内容并不局限于此，目标化合物实验结果如表3和表4所示。
表3所有目标化合物对7种植物病原真菌的抑制活性(50μg/mL)
从表3中可以看出，在离体试验中，大部分化合物对所测试的7种植物病原真菌均具有良好的抗菌活性，其中，化合物28对水稻纹枯病菌具有显著的抗菌活性，在50μg/mL下抑制率为100％，显著优于商品药嘧菌酯(81.8％)、烯酰吗啉(54.2％)、腈菌唑(70.6％)；化合物29和35对上述7种真菌均表现出优异的抗菌活性。为进一步探究高活性化合物的抗菌活性，对表3中抑制率大于和等于80％的目标化合物进行其EC50值的测定，结果如表4中所示。
表4本发明高活性化合物对七种植物病原真菌的EC50
从表4中可以看出，化合物35对上述7种真菌均表现出优异的抗菌活性，其对7种菌的EC50为0.34-7.38μg/mL，尤其对油菜菌核病菌(EC50＝0.34μg/mL)，表现出显著的抗菌活性，明显优于商品药腈菌唑(EC50＝16.6μg/mL)；化合物25、29、33和35对葡萄座腔菌均具有极为优异的活性，其EC50为1.89-3.15μg/mL，优于商品药嘧菌酯(EC50＝3.19μg/mL)和腈菌唑(EC50＝3.74μg/mL)；化合物29和35对烟草赤星病菌表现出显著的抗菌活性，其EC50分别为1.98和1.49μg/mL，明显优于商品药腈菌唑(EC50＝10.5μg/mL)。
由此，可知此类化合物极具研究前景，可用于制备抗植物致病病原真菌农药。
以上所述的实施例仅是对本发明的优选方式进行描述，并非对本发明的范围进行限定，在不脱离本发明设计精神的前提下，本领域普通技术人员对本发明的技术方案做出的各种变形和改进，均应落入本发明权利要求书确定的保护范围内。
Claims (10)
1.一种含羰基结构的α,β-不饱和酰胺或酰肼类化合物，其特征在于：该化合物具有如通式(Ⅰ)所示的结构：
其中，
R1选自色胺、3-(氨甲基)吲哚、苯胺和苯乙胺。R2选自选自氢、氘、任意取代或未取代的烷基、任意取代或未取代的烯基、任意取代或未取代的炔基、任意取代或未取代的芳基、任意取代的苄基、任意取代或未取代的苯胺基或任意取代或未取代的杂芳基。
2.根据权利要求1所述的一种含羰基结构的α,β-不饱和酰胺或酰肼类化合物，其特征在于：
R2选自氢、氘、C1-C6烷基、C2-C6烯基、C2-C6炔基、C1-C6烷氧基、取代或未取代的C6-C15芳基、取代的C6-C15苄基、取代的C6-C15的苯胺基、取代或未取代的C6-C10杂芳基，其中，所述取代的指的是被C1-C6烷基、C1-C6烷氧基、氨基、羟基、卤素、硝基、三氟甲基中的一个或多个取代。
3.根据权利要求2所述的一种含羰基结构的α,β-不饱和酰胺或酰肼类化合物，其特征在于：R2选自氢、氘、甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、异戊基、新戊基、1,1-二甲基、1,5-二甲基己基、1,1-二乙醇基、丙烯基、烯丙基、甲氧基、乙氧基、丙氧基、丁氧基、取代或未取代的苯基、取代的苄基、取代或未取代的苯胺基，其中，所述取代的指的是被C1-C6烷基、C1-C6烷氧基、氨基、羟基、卤素、硝基、三氟甲基。
4.根据权利要求3所述的一种含羰基结构的α,β-不饱和酰胺或酰肼类化合物，其特征在于：R2选自：
5.根据权利要求3所述的一种含羰基结构的α,β-不饱和酰胺或酰肼类化合物，其特征在于选自下述化合物：
6.权利要求1-5任一所述一种含羰基结构的α,β-不饱和酰胺或酰肼类化合物的制备方法，其特征在于包括下述步骤：
其中R1和R2如上所述。
7.一种组合物，其特征在于含有权利要求1-5任一所述的化合物或其立体异构体、或其盐或其溶剂化物，以及农业上可用的助剂或杀菌剂、杀虫剂或除草剂。
8.根据权利要求7所述的一种组合物，其特征在于：所述组合物的剂型选自乳油、粉剂、可湿性粉剂、颗粒剂、水剂、悬浮剂、超低容量喷雾剂、可溶性粉剂、微胶囊剂、烟剂、水乳剂、水分散性粒剂。
9.权利要求1-5任一所述的化合物或其立体异构体、或其盐或其溶剂化物，或权利要求7所述的组合物在防治农业病害方面的用途，其特征在于：所述农业病害为植物真菌性病害。
10.根据权利要求9所述的组合物在防治农业病害方面的用途，其特征在于：所述植物真菌性病害为油菜菌核病、小麦赤霉病、番茄早疫病、葡萄溃疡病、水稻纹枯病、烟草赤星病、茄子黄萎病、果生刺盘孢菌、胶孢炭疽菌、高粱刺盘孢菌、辣椒炭疽病菌、油菜菌核病菌、葡萄座腔菌、黄瓜灰霉病菌、辣椒枯萎病菌、马铃薯晚疫病菌、火龙果炭疽病菌、番茄早疫病菌、蓝莓根腐病菌、大豆茎溃疡菌、水稻穗腐病、花生网斑病菌、灰霉病菌引起的病害。
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