CN102724879B - 杀真菌剂肟基-四唑衍生物 - Google Patents
杀真菌剂肟基-四唑衍生物 Download PDFInfo
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- CN102724879B CN102724879B CN201080060444.4A CN201080060444A CN102724879B CN 102724879 B CN102724879 B CN 102724879B CN 201080060444 A CN201080060444 A CN 201080060444A CN 102724879 B CN102724879 B CN 102724879B
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Abstract
Description
说明
本发明涉及肟基(hydroximoyl)-四唑衍生物,它们的制备方法,它们作为杀真菌活性剂的用途,特别是以杀真菌组合物的形式,以及用这些化合物或组合物来控制植物病原真菌(特别是植物中的植物病原真菌)的方法。
在欧洲专利申请第1426371号中,揭示了具有以下化学结构的一些四唑肟衍生物:
式中A表示四唑基,Het表示特定的吡啶基或特定的噻唑基。
在日本专利申请第2004-131392号中,揭示了具有以下化学结构的一些四唑肟衍生物:
式中Q可以选自15种不同的杂环基。
在国际专利申请第2009-130900号中,揭示了具有以下化学结构的一些四唑肟衍生物:
式中Q可以选自吡啶基或噻唑基。
这三篇文献中揭示的化合物未证实能够提供与本发明的化合物相当的实用性。
在农业领域中,为了避免或控制对活性成分有耐药性的菌株的产生,人们对于使用新型农药化合物一直很感兴趣。而且,为了减少活性化合物的用量,同时保持与已知化合物至少等同的效力,人们对于使用比那些已知的农药活性更高的新颖化合物也很感兴趣。本发明人现已发现一类具有上述效果或益处的新化合物。
因此,本发明提供通式(I)的四唑肟衍生物及其盐、N-氧化物、金属络合物和准金属络合物(metalloidic complex)或它们的(E)和(Z)异构体和它们的混合物
式中,
●X表示氢原子、卤原子、取代或未取代的C1-C8-烷基、取代或未取代的C1-C8-烷氧基、氰基、甲磺酰基(methanesulfonyl)、硝基、三氟甲基或芳基;
●A表示通式(A1)或(A2)的四唑基:
式中Y表示取代或未取代的C1-C8-烷基;
●Het表示通式(Het1)的吡啶基或通式(Het2)的噻唑基:
式中
○R表示氢原子或卤原子
○Q表示通式Z的基团;
式中,
○Ra表示氢原子、卤原子或取代或未取代的C1-C8-烷基,
○L1表示通式-(CR1R2)n-的二价基团,
其中
○n表示1或2;
○R1和R2独立的表示氢原子、卤原子、氰基、取代或未取代的C1-C8-烷基、取代或未取代的C3-C8-环烷基、取代或未取代的具有1-5个卤原子的C1-C8-卤代烷基、取代或未取代的具有1-5个卤原子的C1-C8-卤代环烷基、取代或未取代的C2-C8-烯基、取代或未取代的C2-C8-炔基、取代或未取代的C1-C8-烷氧基、取代或未取代的具有1-5个卤原子的C1-C8-卤代烷氧基、取代或未取代的C2-C8-烯氧基、取代或未取代的具有1-5个卤原子的C2-C8-卤代烯氧基、取代或未取代的C3-C8-炔氧基、取代或未取代的具有1-5个卤原子的C3-C8-卤代炔氧基;
○L2表示氧原子、硫原子、式-CH2-的二价基团或羰基;
○L3表示氧原子或硫原子;
○K1、K2、K3和K4独立的表示氢原子、卤原子、硝基、羟基、氰基、异腈基、氨基、硫烷基(sulphanyl)、甲酰基、取代或未取代的甲醛O-(C1-C8-烷基)肟、甲酰氧基、甲酰基氨基、氨基甲酰基、N-羟基氨基甲酰基、五氟-λ6-硫烷基、甲酰基氨基、取代或未取代的C1-C8-烷基、取代或未取代的C3-C8-环烷基、取代或未取代的具有1-5个卤原子的C1-C8-卤代烷基、取代或未取代的具有1-5个卤原子的C3-C8-卤代环烷基、取代或未取代的C2-C8-烯基、取代或未取代的C2-C8-炔基、取代或未取代的C1-C8-烷基氨基、取代或未取代的二-C1-C8-烷基氨基、取代或未取代的C1-C8-烷氧基、取代或未取代的具有1-5个卤原子的C1-C8-卤代烷氧基、取代或未取代的C1-C8-烷基硫烷基、取代或未取代的具有1-5个卤原子的C1-C8-卤代烷基硫烷基、取代或未取代的C2-C8-烯氧基、取代或未取代的具有1-5个卤原子的C2-C8-卤代烯氧基、取代或未取代的C3-C8-炔氧基、取代或未取代的具有1-5个卤原子的C3-C8-卤代炔氧基、取代或未取代的C1-C8-烷基羰基、取代或未取代的C1-C8-烷基氨基甲酰基、取代或未取代的二-C1-C8-烷基氨基甲酰基、取代或未取代的C1-C8-烷氧基羰基、取代或未取代的(C1-C6-烷氧基亚氨基)-C1-C6-烷基、取代或未取代的(C1-C6-烯氧基亚氨基)-C1-C6-烷基、取代或未取代的(C1-C6-炔氧基亚氨基)-C1-C6-烷基、取代或未取代的(苄氧基亚氨基)-C1-C6-烷基、取代或未取代的苄氧基、取代或未取代的苄基硫烷基、取代或未取代的苄基氨基、取代或未取代的苯氧基、取代或未取代的苯基硫烷基、取代或未取代的苯基氨基、取代或未取代的芳基、取代或未取代的杂环基、取代或未取代的三(C1-C8-烷基)-甲硅烷基氧基、取代或未取代的三(C1-C8-烷基)-甲硅烷基、取代或未取代的C5-C12-稠合双环烷基或者取代或未取代的C5-C12-稠合双环烯基;
或者
○Q表示通式Z1的基团;
式中,
○L1表示通式=(CR1)-的二价基团,
并且,R1、K1、K2、K3、K4、L2和L3如(Z)中所定义,
或者
○Q表示通式Z2的基团;
式中K1、K2、K3、K4、Ra、L1和L3如(Z)中所定义;
或者
○Q表示通式Z3的基团;
式中K1、K2、K3、K4、Ra、L1和L2如(Z)中所定义。
本发明的任何化合物可根据化合物中合成手性单元(stereogenic units)(根据IUPAC规则定义)的数目以一种或多种立体异构体的形式存在。因此,本发明同样涉及所有立体异构体以及所有可能的立体异构体以任何比例混合的混合物。可根据本领域普通技术人员已知的方法分离立体异构体。
值得注意的是,通式(I)的杂环基肟衍生物中存在的肟部分的立体结构包括(E)或(Z)异构体,这些立体异构体构成本发明的一部分。
依据本发明,以下专业术语通常为以下含义:
●卤素表示氟、氯、溴或碘;
●杂原子可以是氮、氧或硫;
●除非另有指示,否则,依据本发明的被取代的基团或取代基可以被以下基团或原子中的一个或多个取代:卤原子、硝基、羟基、氰基、异氰基、氨基、次磺酰基(sulphenyl)、五氟-λ6-次磺酰基、甲酰基、取代或未取代的甲醛O-(C1-C8-烷基)肟、甲酰氧基、甲酰基氨基、氨基甲酰基、N-羟基氨基甲酰基、甲酰基氨基、(羟基亚氨基)-C1-C6-烷基、C1-C8-烷基、三(C1-C8-烷基)甲硅烷基-C1-C8-烷基、C1-C8-环烷基、三(C1-C8-烷基)甲硅烷基-C1-C8-环烷基、具有1-5个卤原子的C1-C8-卤代烷基、具有1-5个卤原子的C1-C8-卤代环烷基、C2-C8-烯基、C2-C8-炔基、C2-C8-烯氧基、C2-C8-炔氧基、C1-C8-烷基氨基、二-C1-C8-烷基氨基、C1-C8-烷氧基、具有1-5个卤原子的C1-C8-卤代烷氧基、C1-C8-烷基次磺酰基、具有1-5个卤原子的C1-C8-卤代烷基次磺酰基、C2-C8-烯氧基、具有1-5个卤原子的C2-C8-卤代烯氧基、C3-C8-炔氧基、具有1-5个卤原子的C3-C8-卤代炔氧基、C1-C8-烷基羰基、具有1-5个卤原子的C1-C8-卤代烷基羰基、C1-C8-烷基氨基甲酰基、二-C1-C8-烷基氨基甲酰基、N-C1-C8-烷氧基氨基甲酰基、C1-C8-烷氧基氨基甲酰基、N-C1-C8-烷基-C1-C8-烷氧基氨基甲酰基、C1-C8-烷氧基羰基、具有1-5个卤原子的C1-C8-卤代烷氧基羰基、C1-C8-烷基羰氧基、具有1-5个卤原子的C1-C8-卤代烷基羰氧基、C1-C8-烷基羰基氨基、具有1-5个卤原子的C1-C8-卤代烷基羰基氨基、取代或未取代的C1-C8-烷氧基羰基氨基、取代或未取代的具有1-5个卤原子的C1-C8-卤代烷氧基羰基氨基、C1-C8-烷基氨基羰氧基、二-C1-C8-烷基氨基羰氧基、C1-C8-烷氧基羰氧基、C1-C8-烷基次磺酰基、具有1-5个卤原子的C1-C8-卤代烷基次磺酰基、C1-C8-烷基亚磺酰基(sulphinyl)、具有1-5个卤原子的C1-C8-卤代烷基亚磺酰基、C1-C8-烷基磺酰基(sulphonyl)、具有1-5个卤原子的C1-C8-卤代烷基磺酰基、C1-C8-烷基氨基氨磺酰基、二-C1-C8-烷基氨基氨磺酰基、(C1-C6-烷氧基亚氨基)-C1-C6-烷基、(C1-C6-烯氧基亚氨基)-C1-C6-烷基、(C1-C6-炔氧基亚氨基)-C1-C6-烷基、(苄氧基亚氨基)-C1-C6-烷基、C1-C8-烷氧基烷基、具有1-5个卤原子的C1-C8-卤代烷氧基烷基、苄氧基、苄基次磺酰基、苄基氨基、苯氧基、苯基次磺酰基、或苯基氨基;
●术语“芳基”表示苯基或萘基;
●术语“杂环基”表示最多包含4个选自N、O或S的杂原子的饱和或不饱和的4-、5-、6-、7-、8-、9-或10-元环。
优选的依据本发明的通式(I)的化合物是其中X的取代位置不特别限制的化合物。
其它优选的依据本发明的通式(I)的化合物是其中X表示以下原子或基团的化合物:氢原子、卤原子、取代或未取代的C1-C8-烷基、取代或未取代的C1-C8-烷氧基、氰基、甲磺酰基、硝基、三氟甲基或芳基。
X的卤原子的例子包括氯原子、溴原子、碘原子和氟原子。在这些卤原子中,特别优选的是氯原子或氟原子。
X表示的取代或未取代的C1-C8-烷基优选是具有1-4个碳原子的烷基,具体例子包括甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基和叔丁基。在这些烷基中,特别优选的是甲基或叔丁基。
X表示的烷氧基优选是取代或未取代的具有1-3个碳原子的C1-C8-烷氧基,具体例子包括甲氧基、乙氧基、丙氧基和异丙氧基。在这些烷氧基中,特别优选的是甲氧基或乙氧基。
更优选的依据本发明的通式(I)的化合物是其中X表示氢原子的化合物。
其它优选的依据本发明的通式(I)的化合物是其中Y表示取代或未取代的C1-C8-烷基的化合物。在这些烷基中,优选的是具有1-3个碳原子的烷基,例如甲基、乙基、正丙基或异丙基。在这些烷基中,特别优选的是甲基或乙基。
其它优选的依据本发明的通式(I)的化合物是具有以下特征的化合物:其中通式(Het1)的吡啶基上的R表示氢原子或卤原子,例如氯原子、溴原子、碘原子或氟原子。其中,特别优选的是氢原子或氯原子。
其它优选的依据本发明的通式(I)的化合物是具有以下特征的化合物:其中通式Q的基团中的Ra表示氢原子、氟原子或甲基。
其它优选的依据本发明的通式(I)的化合物是其中通式Q的基团中的n表示1的化合物。
其它优选的依据本发明的通式(I)的化合物是具有以下特征的化合物:通式Q的基团中的R1和R2独立的表示氢原子、卤原子、取代或未取代的C1-C8-烷基。
其它更优选的依据本发明的通式(I)的化合物是具有以下特征的化合物:通式Q的基团中的R1和R2独立的表示氢原子、氟原子或甲基。
其它优选的依据本发明的通式(I)的化合物是具有以下特征的化合物:通式Q的基团中的L2表示氧原子或式-CH2的二价基团。
其它优选的依据本发明的通式(I)的化合物是具有以下特征的化合物:通式Q的基团中的L3表示氧原子。
其它优选的依据本发明的通式(I)的化合物是具有以下特征的化合物:其中通式Q的基团中的K1、K2、K3和K4独立的表示氢原子、卤原子、氰基、取代或未取代的C1-C8-烷基、取代或未取代的C3-C8-环烷基、取代或未取代的具有1-5个卤原子的C1-C8-卤代烷基、取代或未取代的C1-C8-烷氧基、取代或未取代的具有1-5个卤原子的C1-C8-卤代烷氧基、取代或未取代的C2-C8-烯氧基、取代或未取代的C3-C8-炔氧基、取代或未取代的(C1-C6-烷氧基亚氨基)-C1-C6-烷基、取代或未取代的苯氧基、取代或未取代的芳基、取代或未取代的杂环基。
其它更优选的依据本发明的通式(I)的化合物是具有以下特征的化合物:其中通式Q 的基团中的K1、K2、K3和K4独立的表示氢原子、卤原子、氰基、取代或未取代的C1-C8-烷基、取代或未取代的具有1-5个卤原子的C1-C8-卤代烷基,取代或未取代的C1-C8-烷氧基。
其它更优选的依据本发明的通式(I)的化合物是具有以下特征的化合物:其中通式Q的基团中的K1、K2、K3和K4独立的表示氢原子、卤原子、氰基、C1-C2-烷基、具有1-5个卤原子的C1-C2-卤代烷基、C1-C2-烷氧基。
上述关于本发明通式(I)的化合物的取代基的优选方案可以任何方式进行组合。因此这些优选特征的组合提供了依据本发明的化合物的亚类(sub-class)。本发明优选化合物的这些亚类的例子可具有以下组合特征:
-X的优选特征与A1、A2、Y、Het1、Het2、R和Q中的一种或多种的优选特征;
-A1的优选特征与X、A2、Y、Het1、Het2、R和Q中的一种或多种的优选特征;
-A2的优选特征与X、A1、Y、Het1、Het2、R和Q中的一种或多种的优选特征;
-Y的优选特征与X、A2、A1、Het1、Het2、R和Q中的一种或多种的优选特征;
-Het1的优选特征与X、A1、A2、Y、Het2、R和Q中的一种或多种的优选特征;
-Het2的优选特征与X、A1、A2、Y、Het1、R和Q中的一种或多种的优选特征;
-R的优选特征与X、A1、A2、Y、Het1、Het2和Q中的一种或多种的优选特征;
-Q的优选特征与X、A1、A2、Y、Het1、Het2和R中的一种或多种的优选特征。
在这些依据本发明的化合物的取代基的优选特征的组合中,所述优选特征还可选自各X、A1、A2、Y、Het1、Het2、R和Q的更优选特征,以形成最优选的依据本发明的化合物的亚类。
本发明还涉及通式(I)的化合物的制备方法。因此,依据本发明的另一方面,提供一种制备文中定义的通式(I)的化合物的方法P1,如以下反应方案所示:
方法P1
其中A、X、Z、Q和Het如文中所定义,LG表示离去基团。合适的离去基团可选自卤原子或其它常规的离核基团(nucleofugal groups),例如三氟甲磺酸酯基(triflate)、甲磺酸酯基(mesylate)或甲苯磺酸酯基(tosylate)。
对于本发明的通式(Ia)的化合物,本发明的方法P1可通过另一步骤来完成,包括依据已知的方法对该基团进行额外的改性,特别是利用酰化或烷氧基羰基化反应,得到通式(Ib)的化合物。在该情况中,提供依据本发明的方法P2,该方法P2如以下反应方案所示:
方法P2
●其中A、X、Q和Het如文中所定义,LG’表示离去基团。Het’表示通式(Het’1)的吡啶基或通式(Het’2)的噻唑基:
其中R如文中所定义。
合适的离去基团可选自卤原子或其它常规的离核基团,例如醇盐、氢氧化物或氰化物.
对于通式(Ia)的化合物,方法P2的进行需先进行脱保护步骤,以产生氨基。氨基保护基团及其相关断裂方法是本领域普通技术人员已知的。
依据本发明,如果合适,方法P1和P2可以在溶剂存在下进行,如果合适,还可以在碱存在下进行。
依据本发明,如果合适,方法P1和P2可以在催化剂存在下进行。合适的催化剂可选自4-二甲基-氨基吡啶、1-羟基-苯并三唑或二甲基甲酰胺。
在LG’表示羟基的情况中,依据本发明的方法P2可以在缩合剂存在下进行。合适的缩合剂可选自酰卤形成剂,如光气、三溴化磷、三氯化磷、五氯化磷、三氯氧化磷或亚硫酰氯;酸酐形成剂,如氯甲酸乙酯、氯甲酸甲酯、氯甲酸异丙酯、氯甲酸异丁酯或甲磺酰氯;碳二亚胺,如N,N′-二环己基碳二亚胺(DCC)或其它常规缩合剂,如五氧化二磷、聚磷酸、N,N′-羰基二咪唑、2-乙氧基-N-乙氧基羰基-1,2-二氢喹啉(EEDQ)、三苯基膦/四氯甲烷、氯化4-(4,6-二甲氧基[1.3.5]三嗪-2-基)-4-甲基吗啉鎓水合物或溴代-三吡咯烷并(tripyrrolidino)--六氟磷酸盐。
适用于进行本发明的方法P1和P2的溶剂是普通惰性有机溶剂。优选使用任选卤代的脂族、脂环族或芳族烃,例如石油醚、己烷、庚烷、环己烷、甲基环己烷、苯、甲苯、二甲苯或萘烷;氯苯、二氯苯、二氯甲烷、氯仿、四氯化碳、二氯乙烷或三氯乙烷;醚,例如乙醚、二异丙基醚、甲基叔丁基醚、甲基叔戊基醚、二噁烷、四氢呋喃、1,2-二甲氧基乙烷、1,2-二乙氧基乙烷或茴香醚;腈,例如乙腈、丙腈、正丁腈、异丁腈或苯甲腈;酰胺,例如N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、N-甲基甲酰苯胺、N-甲基吡咯烷酮或六甲基磷酸三酰胺;酯,例如乙酸甲酯或乙酸乙酯;亚砜,例如二甲亚砜;或砜,例如环丁砜。
适用于进行依据本发明的方法P1和P2的碱是常用于这类反应的无机碱和有机碱。优选使用碱土金属、碱金属氢化物、碱金属氢氧化物或碱金属醇盐,例如氢氧化钠、氢化钠、氢氧化钙、氢氧化钾、叔丁醇钾或其它氢氧化铵;碱金属碳酸盐,例如碳酸钠、碳酸钾、碳酸氢钾、碳酸氢钠、碳酸铯;碱金属或碱土金属乙酸盐,例如乙酸钠、乙酸钾、乙酸钙;以及叔胺,例如三甲胺、三乙胺、二异丙基乙胺、三丁胺、N,N-二甲基苯胺、吡啶、N-甲基哌啶、N,N-二甲基氨基吡啶、1,4-二氮杂二环[2.2.2]辛烷(DABCO)、1,5-二氮杂二环[4.3.0]壬-5-烯(DBN)或1,8-二氮杂二环[5.4.0]十一碳-7-烯(DBU)。
当进行依据本发明的方法P1和P2,反应温度可以独立地在较宽的范围内变化。通常,依据本发明的方法P1在-20℃到160℃之间的温度下进行。
依据本发明的方法P1和P2一般独立地在大气压下进行。但是,也可以在升高或降低的压力下进行。
当进行依据本发明的方法P1时,每摩尔通式(II)的肟基四唑通常可使用1摩尔或更多的通式Het-CH2-LG的衍生物和1-3摩尔的碱。还可以使用其它比例的反应组分。
按照常规的方法进行后处理(work-up)。通常,用水处理反应混合物,分离出有机相,干燥后,在减压下浓缩。如果合适,通过常规的方法除去剩余的残余物中任何可能仍然存在的杂质,这些方法例如色谱法或重结晶。
本发明的化合物可依据上述方法制备。然而要理解,本领域技术人员基于其所掌握的常识和可获得的出版物,可以根据所需合成的各种具体的本发明化合物对本发明方法进行相应调整。
当A表示文中所述的通式A1的取代基时,可用作原料的通式(II)的化合物可通过例如羟胺与相应的酮反应制得,所述酮可例如依据R.Raap(Can.J.Chem.1971,49,2139)所述的方法,通过将四唑基锂物质加成到通式
的酯或者它们任何合适的合成等同物如
上制得。
当A表示文中所述的通式A2的取代基时,用作原料的通式(II)的化合物可依据J.Plenkiewicz等(Bull.Soc.Chim.Belg.1987,96,675)所述的方法,由通式如下的肟与5-取代四唑制得:
另一方面,本发明还涉及含有有效且非植物毒性量的通式(I)的活性化合物的杀真菌组合物。
“有效且非植物毒性量”的表达方式指本发明组合物的量足以控制或破坏存在于或易于出现在作物上的真菌,而该剂量并不会使所述作物产生任何可以观察到的植物毒性症状。该量根据以下因素可在很宽的范围内变化:要控制的真菌、作物的类型、气候条件和包含在本发明的杀真菌组合物中的化合物。该量可通过系统性田间试验来确定,这在本领域技术人员的能力范围内。
因此,依据本发明,提供一种杀真菌组合物,该组合物包含有效量的上述通式(I)的化合物作为活性组分以及农业上可接受的担体(support)、载体或填料(filler)。
依据本发明,术语“担体”表示天然或合成的有机或无机化合物,它与通式(I)的活性化合物组合或联合使用,使活性化合物更容易施用,特别是施用到植物各部分上。因此,此担体通常是惰性的,并且应该是农业上可接受的。担体可为固体或液体。合适的担体的例子包括粘土(clcans)、天然或合成的硅酸盐、氧化硅、树脂、蜡、固体肥料、水、醇(特别是丁醇)、有机溶剂、矿物油和植物油以及它们的衍生物。也可以使用这些担体的混合物。
依据本发明的组合物也可以包含其它的组分。具体地,所述组合物还可包含表面活性剂。表面活性剂可为离子或非离子型乳化剂、分散剂或润湿剂或这些表面活性剂的混合物。例如,聚丙烯酸盐、木质素磺酸盐、苯酚磺酸盐或萘磺酸盐、环氧乙烷与脂肪醇或脂肪酸或脂肪胺的缩聚物、取代的苯酚(特别是烷基苯酚或芳基苯酚)、磺基琥珀酸酯的盐、牛磺酸衍生物(特别是牛磺酸烷基酯(alkyl taurate))、聚氧乙基化醇或苯酚的磷酸酯、多元醇的脂肪酸酯,以及含有硫酸、磺酸和磷酸官能团的上述化合物的衍生物。当活性化合物和/或惰性担体不溶于水并且当施用的媒介试剂是水时,至少一种表面活性剂的存在通常是至关重要的。较佳地,以组合物的重量计,表面活性剂的含量为5重量%至40重量%。
任选地,还可包括附加的组分,例如,保护性胶体、胶粘剂、增稠剂、触变剂、渗透剂、稳定剂(stabilisers)、掩蔽剂(sequestering agent)。一般来说,活性化合物可根据常用的配方技术与任何固体或液体添加剂相混合。
本发明的组合物一般可含有0.05重量%至99重量%的活性化合物,较佳为10重量%至70重量%。
本发明的组合物可以各种形式使用,诸如气溶胶分散剂、胶囊悬浮剂(capsule suspension)、冷雾浓缩剂、可撒粉剂、可乳化的浓缩剂、水包油乳剂、油包水乳剂、微囊粒剂、细粒剂、种子处理用可流动的浓缩剂、气体制剂(在压力下)、气体发生剂、颗粒剂、热雾浓缩剂、大粒剂、微粒剂、油可分散性粉剂、油可混溶性可流动的浓缩剂、油可混溶液体、糊剂、植物棒剂、干种子处理用粉剂、农药包衣的种子、可溶性浓缩剂、可溶性粉剂、种子处理用溶液、悬浮浓缩剂(可流动的浓缩剂)、超低量(ULV)液体、超低量(ULV)悬浮剂、水可分散粒剂或片剂、浆液处理用水可分散性粉剂、水溶性粒剂或片剂、种子处理用水溶性粉剂和可润湿性粉剂。这些组合物不仅包括通过合适的设备如喷雾或撒粉设备施用到待处理的植物或种子上的现成组合物,还包括在施用到作物之前必须稀释的浓缩商品组合物。
依据本发明的化合物还可与一种或多种以下物质混合:杀虫剂、杀真菌剂、杀细菌剂、引诱剂、杀螨剂或信息素活性物质或其它有生物活性的化合物。这样得到的混合物具广谱的活性。与其它杀真菌化合物的混合物尤其有利。依据本发明的包含通式(I)的化合物与杀细菌化合物的混合物的组合物特别有利。
合适的可进行混合的杀真菌剂的例子选自以下:
(1)核酸合成抑制剂,例如苯霜灵、苯霜灵-M(benalaxyl-M)、乙嘧酚磺酸酯、柯罗泽尔昆(clozylacon)、甲菌定、乙嘧酚、呋霜灵、恶霉灵、甲霜灵、高效甲霜灵、呋酰胺、恶霜灵和恶喹酸。
(2)有丝分裂和细胞分裂抑制剂,例如苯菌灵、多菌灵、氯芬唑(chlorfenazole)、乙霉威、噻唑菌胺、麦穗宁、戊菌隆、噻菌灵、硫菌灵、甲基硫菌灵和苯酰菌胺。
(3)呼吸抑制剂,例如作为CI-呼吸抑制剂的氟嘧菌胺(diflumetorim);作为CII-呼吸抑制剂的百克芬(bixafen)、啶酰菌胺(boscalid)、萎锈灵、甲呋酰胺、氟酰胺、氟吡菌酰胺(fluopyram)、呋吡菌胺(furametpyr)、弗灭克(furmecyclox)、异皮姆(isopyrazam)(顺差向异构(syn-epimeric)外消旋1RS,4SR,9RS和反差向异构(anti-epimeric)外消旋体1RS,4SR,9SR的混合物)、异皮姆(顺差向异构外消旋体1RS,4SR,9RS)、异皮姆(顺差向异构对映异构体1R,4S,9R)、异皮姆(顺差向异构对映异构体1S,4R,9S)、异皮姆(反差向异构外消旋体1RS,4SR,9SR)、异皮姆(反差向异构对映异构体1R,4S,9S)、异皮姆(反差向异构对映异构体1S,4R,9R)、灭锈胺、氧化萎锈灵(oxycarboxine)、皮弗芬(penflufen)、吡噻菌胺(penthiopyrad)、斯德恩(sedaxane)、噻氟菌胺;作为CIII-呼吸抑制剂的吲唑磺菌胺(amisulbrom)、嘧菌酯、氰霜唑、醚菌胺(dimoxystrobin)、厄内斯卓宾(enestrobin)、恶唑菌酮、咪唑菌酮、氟嘧菌酯(fluoxastrobin)、醚菌酯、苯氧菌胺、肟醚菌胺(orysastrobin)、啶氧菌酯(picoxystrobin)、唑菌胺酯(pyraclostrobin)、唑菌酯(pyraoxystrobin)、唑胺菌酯(pyrametostrobin)、派本卡必(pyribencarb)、肟菌酯。
(4)能起解偶联剂作用的化合物,例如乐杀螨、消螨普、氟啶胺和密特克(meptyldinocap)。
(5)ATP产生抑制剂,例如三苯基乙酸锡、三苯基氯化锡、三苯基氢氧化锡和硅噻菌胺。
(6)氨基酸和/或蛋白质生物合成抑制剂,例如胺扑灭(andoprim)、杀稻瘟菌素-S、嘧菌环胺、春雷霉素、水合盐酸春雷霉素(kasugamycin hydrochloridehydrate)、嘧菌胺和嘧霉胺。
(7)信号转导抑制剂,例如拌种咯、咯菌腈和苯氧喹啉。
(8)脂质和膜合成抑制剂,例如联苯、乙菌利、敌瘟磷、土菌灵、依杜卡(iodocarb)、异稻瘟净、异菌脲、稻瘟灵、腐霉利、霜霉威、霜霉威盐酸盐、吡菌磷、甲基立枯磷和乙烯菌核利。
(9)麦角固醇生物合成抑制剂,例如阿尔迪莫(aldimorph)、氧环唑、联苯三唑醇、糠菌唑、环丙唑醇、苄氯三唑醇(diclobutrazole)、苯醚甲环唑、烯唑醇、烯唑醇-M(diniconazole-M)、十二环吗啉、十二环吗啉乙酸酯(dodemorph acetate)、氟环唑、乙环唑、氟苯嘧啶醇、腈苯唑、环酰菌胺、苯锈啶、丁苯吗啉(fenpropimorph)、氟喹唑、呋嘧醇(flurprimidol)、氟硅唑、粉唑醇、呋菌唑、呋醚唑、己唑醇、抑霉唑、抑霉唑硫酸盐(imazalil sulfate)、亚胺唑、种菌唑、叶菌唑、腈菌唑、萘替芬(naftifine)、氯苯嘧啶醇、恶咪唑、多效唑、稻瘟酯、戊菌唑、病花灵、咪鲜胺、丙环唑、丙硫菌唑(prothioconazole)、稗草丹、啶斑肟、喹唑(quinconazole)、硅氟唑、螺环菌胺、戊唑醇、特比萘芬(terbinafine)、四氟醚唑、三唑酮、三唑醇、十三吗啉、氟菌唑、嗪胺灵、灭菌唑、烯效唑、烯霜苄(viniconazole)和伏立康唑(voriconazole)。
(10)细胞壁合成抑制剂,例如苯噻菌胺(benthiavalicarb)、烯酰吗啉、氟吗啉、异丙菌胺、双炔酰菌胺(mandipropamid)、多抗霉素(polyoxins)、多氧霉素(polyoxorim)、硫菌威、有效霉素A和维芬乐特(valifenalate)。
(11)黑素生物合成抑制剂,例如环丙酰菌胺、双氯氰菌胺、氰菌胺、四氯苯酞(phthalide)、咯喹酮和三环唑。
(12)能诱导宿主防御的化合物,例如活化酯-S-甲基(acibenzolar-S-methyl)、噻菌灵和噻酰菌胺(tiadinil)。
(13)具有多位点(multisite)作用的化合物,例如波尔多液、敌菌丹、克菌丹、百菌清、环烷酸铜、氧化铜、氧氯化铜、铜制剂如氢氧化铜、硫酸铜、抑菌灵、二噻农、多果定、多果定游离碱、福美铁、氟佛匹特(fluorofolpet)、灭菌丹、双胍辛(guazatine)、双胍辛乙酸盐、双胍辛胺、双胍三辛烷基苯磺酸盐(iminoctadine albesilate)、双胍辛胺三乙酸盐、代森锰铜、代森锰锌、代森锰、代森联(metiram)、代森联锌(metiram zinc)、喹啉铜、普罗帕脒(propamidine)、丙森锌、硫和硫制剂,包括多硫化钙、福美双、甲苯氟磺胺、代森锌和福美锌。
(14)其它化合物例如2,3-二丁基-6-氯噻吩并[2,3-d]嘧啶-4(3H)-酮、(2Z)-3-氨基-2-氰基-3-苯基丙-2-烯酸乙酯、N-[2-(1,3-二甲基丁基)苯基]-5-氟-1,3-二甲基-1H-吡唑-4-羧酰胺、3-(二氟甲基)-1-甲基-N-(3′,4′,5′-三氟联苯-2-基)-1H-吡唑-4-羧酰胺、3-(二氟甲基)-N-[4-氟-2-(1,1,2,3,3,3-六氟丙氧基)苯基]-1-甲基-1H-吡唑-4-羧酰胺、(2E)-2-(2-{[6-(3-氯-2-甲基苯氧基)-5-氟嘧啶-4-基]氧基}苯基)-2-(甲氧基亚氨基)-N-甲基乙酰胺、(2E)-2-{2-[({[(2E,3E)-4-(2,6-二氯苯基)丁-3-烯-2-亚基(ylidene)]氨基}氧基)甲基]苯基}-2-(甲氧基亚氨基)-N-甲基乙酰胺、2-氯-N-(1,1,3-三甲基-2,3-二氢-1H-茚-4-基)吡啶-3-羧酰胺、N-(3-乙基-3,5,5-三甲基环己基)-3-(甲酰基氨基)-2-羟基苯甲酰胺、5-甲氧基-2-甲基-4-(2-{[({(1E)-1-[3-(三氟甲基)苯基]亚乙基(ethylidene)}氨基)氧基]甲基}苯基)-2,4-二氢-3H-1,2,4-三唑-3-酮、(2E)-2-(甲氧基亚氨基)-N-甲基-2-(2-{[({(1E)-1-[3-(三氟甲基)苯基]亚乙基}氨基)氧基]甲基}苯基)乙酰胺、(2E)-2-(甲氧基亚氨基)-N-甲基-2-{2-[(E)-({1-[3-(三氟甲基)苯基]乙氧基}亚氨基)甲基]苯基}乙酰胺、(2E)-2-{2-[({[(1E)-1-(3-{[(E)-1-氟-2-苯基乙烯基]氧基}苯基)亚乙基]氨基}氧基)甲基]苯基}-2-(甲氧基亚氨基)-N-甲基乙酰胺、1-(4-氯苯基)-2-(1H-1,2,4-三唑-1-基)环庚醇、1-(2,2-二甲基-2,3-二氢-1H-茚-1-基)-1H-咪唑-5-羧酸甲酯、N-乙基-N-甲基-N′-{2-甲基-5-(三氟甲基)-4-[3-(三甲基甲硅烷基)丙氧基]苯基}亚氨基(imido)甲酰胺、N′-{5-(二氟甲基)-2-甲基-4-[3-(三甲基甲硅烷基)丙氧基]苯基}-N-乙基-N-甲基亚氨基甲酰胺、O-{1-[(4-甲氧基苯氧基)甲基]-2,2-二甲基丙基}1H-咪唑-1-硫代羟酸酯(carbothioate)、N-[2-(4-{[3-(4-氯苯基)丙-2-炔-1-基]氧基}-3-甲氧基苯基)乙基]-N2-(甲基磺酰基)缬氨酰胺、5-氯-7-(4-甲基哌啶-1-基)-6-(2,4,6-三氟苯基)[1,2,4]三唑并[1,5-a]嘧啶、5-氨基-1,3,4-噻二唑-2-硫醇、霜霉威乙膦酸盐(propamocarb-fosetyl)、1H-咪唑-1-羧酸1-[(4-甲氧基苯氧基)甲基]-2,2-二甲基丙基酯、1-甲基-N-[2-(1,1,2,2-四氟乙氧基)苯基]-3-(三氟甲基)-1H-吡唑-4-羧酰胺、2,3,5,6-四氯-4-(甲基磺酰基)吡啶、2-丁氧基-6-碘-3-丙基-4H-色烯-4-酮、2-苯基苯酚及盐、3-(二氟甲基)-1-甲基-N-[2-(1,1,2,2-四氟乙氧基)苯基]-1H-吡唑-4-羧酰胺、3,4,5-三氯吡啶-2,6-二腈、3-[5-(4-氯苯基)-2,3-二甲基异噁唑烷-3-基]吡啶、3-氯-5-(4-氯苯基)-4-(2,6-二氟苯基)-6-甲基哒嗪、4-(4-氯苯基)-5-(2,6-二氟苯基)-3,6-二甲基哒嗪、喹啉-8-醇,喹啉-8-醇硫酸盐(2∶1)(盐)、特弗喹啉(tebufloquin)、5-甲基-6-辛基-3,7-二氢[1,2,4]三唑并[1,5-a]嘧啶-7-胺、5-乙基-6-辛基-3,7-二氢[1,2,4]三唑并[1,5-a]嘧啶-7-胺、辛唑嘧菌胺(ametoctradin)、苯并噻唑、贝斯氧杂嗪(bethoxazin)、卡巴西霉素(capsimycin)、香芹酮(carvone)、灭螨猛、氯苯甲醚、硫杂灵(cufraneb)、环氟菌胺(cyfiufenamid)、霜脲氰、赛皮磺酰胺(cyprosulfamide)、棉隆、咪菌威、双氯酚、哒菌酮、氯硝胺、野燕枯、野燕枯甲基硫酸盐(difenzoquat methylsulphate)、二苯胺、埃克玛(ecomate)、嘧菌腙、氟酰菌胺、氟吡菌胺(fluopicolide)、氟氯菌核利(fluoroimide)、磺菌胺、福多宁(flutianil)、三乙膦酸铝(fosetyl-aluminium)、乙膦酸钙(fosetyl-calcium)、乙膦酸钠(fosetyl-sodium)、六氯苯、人间霉素(irumamycin)、异太乐(isotianil)、磺菌威(methasulfocarb)、(2E)-2-{2-[({环丙基[(4-甲氧基苯基)亚氨基]甲基}硫代(thio))甲基]苯基}-3-甲氧基丙烯酸甲酯、异硫氰酸甲酯、苯菌酮(metrafenone)、(5-氯-2-甲氧基-4-甲基吡啶-3-基)(2,3,4-三甲氧基-6-甲基苯基)甲酮、米多霉素(mildiomycin)、特尼芬德(tolnifanide)、N-(4-氯苄基)-3-[3-甲氧基-4-(丙-2-炔-1-基氧基)苯基]丙酰胺、N-[(4-氯苯基)(氰基)甲基]-3-[3-甲氧基-4-(丙-2-炔-1-基氧基)苯基]丙酰胺、N-[(5-溴-3-氯吡啶-2-基)甲基]-2,4-二氯吡啶-3-羧酰胺、N-[1-(5-溴-3-氯吡啶-2-基)乙基]-2,4-二氯吡啶-3-羧酰胺、N-[1-(5-溴-3-氯吡啶-2-基)乙基]-2-氟-4-碘吡啶-3-羧酰胺、N-{(Z)-[(环丙基甲氧基)亚氨基][6-(二氟甲氧基)-2,3-二氟苯基]甲基}-2-苯基乙酰胺、N-{(E)-[(环丙基甲氧基)亚氨基][6-(二氟甲氧基)-2,3-二氟苯基]甲基}-2-苯基乙酰胺、纳他霉素(natamycin)、二甲基二硫代氨基甲酸镍、酞菌酯、辛噻酮、奥克斯莫卡宾(oxamocarb)、氧代奋欣(oxyfenthiin)、五氯苯酚和盐、吩嗪-1-羧酸、苯醚菊酯、亚磷酸及其盐、霜霉威乙膦酸盐(propamocarb fosetylate)、普罗帕诺欣钠(propanosine-sodium)、丙氧喹啉(proquinazid)、吡咯叠氮(pyrrolnitrine)、五氯硝基苯、S-丙-2-烯-1-基5-氨基-2-(1-甲基乙基)-4-(2-甲基苯基)-3-氧代-2,3-二氢-1H-吡唑-1-硫代羟酸酯、叶枯酞、四氯硝基苯、咪唑嗪、水杨菌胺、5-氯-N′-苯基-N′-丙-2-炔-1-基噻吩-2-磺酰肼(sulfonohydrazide)、氰菌胺、N-甲基-2-(1-{[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙酰基}哌啶-4-基)-N-[(1R)-1,2,3,4-四氢萘-1-基]-1,3-噻唑-4-羧酰胺、N-甲基-2-(1-{[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙酰基}哌啶-4-基-N-(1,2,3,4-四氢萘-1-基)-1,3-噻唑-4-羧酰胺、3-(二氟甲基)-N-[4-氟-2-(1,1,2,3,3,3-六氟丙氧基)苯基]-1-甲基-1H-吡唑-4-羧酰胺和{6-[({[(1-甲基-1H-四唑-5-基)(苯基)亚甲基]氨基}氧基)甲基]吡啶-2-基}氨基甲酸戊酯。
依据本发明的另一个目的,提供一种控制植物、作物或种子的植物病原真菌的方法,该方法的特征是将依据本发明的农学有效且基本无植物毒性量的农药组合物以种子处理、叶施用、茎施用、浸透或滴注施用(灌溉施肥(chemigation))的方式施用到种子、植物、植物果实或植物正在其中生长或需要在其中生长的土壤或惰性基质(例如,无机基质,诸如沙子、岩棉、玻璃棉;膨胀型矿物,诸如珍珠岩、蛭石、沸石或膨胀粘土),浮石,火山碎屑物或材料,合成有机基质(例如,聚氨酯)、有机基质(例如泥炭、堆肥、树木废产品,诸如椰子壳的纤维、木纤维或木屑、树皮)或液体基质(例如浮板式水耕系统,营养液膜技术,气栽法(Aeroponics))上。
在本发明中,“施用到待处理的植物上”的表述应理解为是指本发明的主题农药组合物可以通过不同的处理方法施用,这些方法例如:
-将包含所述组合物之一的液体喷洒到所述植物的地上部分,
-撒粉,在土壤中掺入颗粒或粉末,在所述植物周围喷洒,并且在树木的情况下为注射或涂抹,
-借助于包含所述组合物之一的保护植物的混合物,对所述植物的种子进行包覆或薄膜涂布。
依据本发明的方法可以是治疗、预防或根除方法。
在该方法中,使用的组合物可以预先通过将两种或更多种本发明的活性化合物混合在一起而制得。
依据这种方法的另一可选方案,还可以同时、连续或单独施用化合物(A)和(B),使得各含有两种或三种活性组分中的一种(A)或(B)的组合物具有结合的(A)/(B)效应。
依据本发明的处理方法中施用的活性化合物的剂量通常且适宜为:
-对于叶处理:0.1-10,000克/公顷,优选10-1,000克/公顷,更优选50-300克/公顷;在浸透或滴注施用的情况中,剂量甚至可以减少,尤其是在使用岩棉或珍珠岩之类的惰性基质时;
-对于种子处理:2-200克/100千克种子,优选3-150克/100千克种子;
-对于土壤处理:0.1-10,000克/公顷,优选1-5,000克/公顷。
在此所述的剂量是作为本发明方法的示例性例子给出。本领域技术人员了解如何调整施用剂量,特别是依据待处理的植物或作物的天性进行调节。
在特定情况下,例如,依据待处理或控制的植物病原真菌的特性,较低的剂量就可以提供足够的保护。某些气候条件、耐受性或其它因素如植物病原真菌的特性或(例如)植物受这些真菌侵染的程度,可能需要较高剂量的组合活性成分。最佳的剂量通常取决于若干因素,例如,待处理的植物病原真菌的类型、受侵染植物的类型或发育的水平、植被的密度或施用的方法。
用依据本发明的农药组合物或组合处理的作物是例如但不限于葡萄树,可以是谷类、蔬菜、苜蓿、大豆、市场菜园作物、草皮、木材、树木或园艺植物。
本发明的处理方法还可用于处理繁殖材料如块茎或根茎,并且可用于处理种子、幼苗或移植(pricking out)苗以及植物或移植植物。该处理方法也可用于处理根。本发明的处理方法也可用于处理植物的地上部分如有关植物的干、茎或梗、叶子、花和果实。
在可用本发明的方法保护的植物中,包括棉花;亚麻;葡萄藤;水果或蔬菜作物,如蔷薇科(Rosaceae sp.)(例如,仁果类水果,如苹果和梨,还有核果,诸如杏、杏仁和桃子)、茶蔗子科(Ribesioidae sp.)、胡桃科(Juglandaceae sp.)、桦木科(Betulaceae sp.)、漆树科(Anacardiaceae sp.)、山毛榉科(Fagaceae sp.)、桑科(Moraceae sp.)、木犀科(Oleaceae sp.)、猕猴桃科(Actinidaceae sp.)、樟科(Lauraceae sp.)、芭蕉科(Musaceae sp.)(例如香蕉树和粉芭蕉(plantins))、茜草科(Rubiaceae sp.)、山茶科(Theaceae sp.)、梧桐科(Sterculiceae sp.)、芸香科(Rutaceae sp.)(例如柠檬、橙子和葡萄柚);茄科(Solanaceae sp.)(例如,西红柿)、百合科(Liliaceae sp.)、紫菀科(Asteraceae sp.)(例如莴苣)、伞形科(Umbelliferaesp.)、十字花科(Cruciferae sp.)、藜科(Chenopodiaceae sp.)、葫芦科(Cucurbitaceaesp.)、蝶形花科(Papilionaceae sp.)(例如豌豆)、蔷薇科(Rosaceae sp.)(例如草莓);大作物,诸如禾本科(Graminae sp.)(例如玉米、菌苔或谷物如小麦、稻、大麦和黑小麦)、紫菀科(Asteraceae sp.)(例如向日葵)、十字花科(Cruciferae sp.)(例如油菜)、豆科(Fabacae sp.)(例如花生)、蝶形花科(Papilionaceae sp.)(例如大豆)、茄科(Solanaceae sp.)(例如马铃薯)、藜科(Chenopodiaceae sp.)(例如甜菜根);园艺作物和森林作物;以及这些作物的遗传修饰的同系物。
本发明的组合物也可以用于处理用本发明的化合物或本发明的农用化学组合物遗传修饰的生物体。遗传修饰的植物是其基因组被稳定地整合入编码感兴趣蛋白的异源基因的植物。“编码感兴趣蛋白的异源基因”主要是指给予转化植物新的农学性质的基因,或指改善改良植物的农学性质的基因。
本发明的组合物还可以用来抵抗易于生长在木材上或木材内部的真菌疾病。术语“木材”指所有种类的木材,和所有用于建筑的此类木材的加工材料,例如实木、高密度木材、层压木材和胶合板。本发明的处理木材的方法主要包括:使木材与本发明的一种或多种化合物或本发明的组合物接触;这包括例如直接施涂、喷涂、浸涂、注入或任何其它合适的方式。
在可通过本发明方法控制的植物或作物疾病中,可提及的有:
白粉病(powdery mildew),例如:
小麦白粉病(Blumeria diseases),例如由小麦白粉菌(Blumeria graminis)引起;
叉丝单囊壳属病(Podosphaera diseases),例如由白叉丝单囊壳(Podosphaera leucotricha)引起;
单丝壳属病(Sphaerotheca diseases),例如由苍耳单丝壳(Sphaerothecafuliginea)引起;
钩丝壳属病(Uncinula diseases),例如由葡萄钓丝壳(Uncinula necator)引起;
锈病,例如:
胶锈属病(Gymnosporangium diseases),例如由赛宾锈菌(Gymnosporangium sabinae)引起;
驼孢锈病(Hemileia diseases),例如由咖啡驼孢锈菌(Hemileia vastatrix)引起;
层锈菌属病(Phakopsora diseases),例如由豆薯层锈菌(Phakopsorapachyrhizi)或山马蝗层锈菌(Phakopsora meibomiae)引起;
柄锈菌属病(Puccinia diseases),例如由隐匿柄锈菌(Puccinia recondita)引起;
单孢锈菌属病(Uromyces diseases),例如由疣顶单胞锈菌(Uromycesappendiculatus)引起;
卵菌病(Oomycete diseases),例如:
盘梗霉属病(Bremia diseases),例如由莴苣盘梗霉(Bremia lactucae)引起;
霜霉属病(Peronospora diseases),例如由豌豆霜霉(Peronospora pisi)或芸苔霜霉(P.brassicae)引起;
疫霉属病(Phytophthora diseases),例如由致病疫霉(Phytophthora infestans)引起;
单轴霉属病(Plasmopara diseases),例如由葡萄生单轴霉(Plasmoparaviticola)引起;
假霜霉属(Pseudoperonospora diseases),例如由葎草假霜霉(Pseudoperonospora humuli)或古巴假霜霉(Pseudoperonospora cubensis)引起;
腐霉属病(Pythium diseases),例如由终极腐霉(Pythium ultimum)引起;
叶斑病(Leafspot disease)、污叶病(leaf blotch disease)和叶枯病(leaf blightdisease),例如:
支链孢属病(Alternaria diseases),例如由茄链格孢(Alternaria solani)引起;
尾孢霉属病(Cercospora diseases),例如由甜菜生尾孢(Cercospora beticola)引起;
金孢子菌属病(Cladiosporum diseases),例如由瓜枝孢(Cladiosporiumcucumerinum)引起;
旋孢腔菌病(Cochliobolus diseases),例如由禾旋孢腔菌(Cochliobolussativus)引起;
刺盘孢属病(Colletotrichum diseases),例如由豆刺盘孢(Colletotrichumlindemuthanium)引起;
油橄榄孔雀斑病(Cycloconium diseases),例如由油橄榄孔雀斑菌(Cycloconium oleaginum)引起;
腐皮壳菌层病(Diaporthe diseases),例如由桔柑间座壳(Diaporthe citri)引起;
痂囊腔菌属病(Elsinoe diseases),例如由桔柑痂囊腔菌(Elsinoe fawcettii)引起;
长孢属病(Gloeosporium diseases),例如由悦色盘长孢(Gloeosporiumlaeticolor)引起;
小丛壳属病(Glomerella diseases),例如由围小丛壳(Glomerella cingulata)引起;
球座菌属病(Guignardia diseases),例如由葡萄球座菌(Guignardia bidwelli)引起;
小球腔菌属病(Leptosphaeria diseases),例如由十字花科小球腔菌(Leptosphaeria maculans);颖枯小球腔菌(Leptosphaeria nodorum)引起;
稻瘟病(Magnaporthe diseases),例如由稻瘟菌(Magnaporthe grisea)引起;
球腔菌属病(Mycosphaerella diseases),例如由禾生球腔菌(Mycosphaerellagraminicola);落花生球腔菌(Mycosphaerella arachidicola);香蕉黑条叶斑病菌(Mycosphaerella fijiensisi)引起;
壳针孢属病(Phaeosphaeria diseases),例如由颖枯壳针孢(Phaeosphaerianodorum)引起;
核腔菌属病(Pyrenophora diseases),例如由圆核腔菌(Pyrenophora teres)引起;
柱隔孢属病(Ramularia diseases),例如由辛加柱隔孢(Ramularia collo-cygni)引起;
喙孢属病(Rhynchosporium diseases),例如由黑麦喙孢(Rhynchosporiumsecalis)引起;
壳针孢属病(Septoria diseases),例如由芹菜小壳针孢(Septoria apii)或番茄壳针孢(Septoria lycopercisi)引起;
核瑚菌属病(Typhula diseases),例如由肉孢核瑚菌(Typhula incarnata)引起;
黑星菌属病(Venturia diseases),例如由苹果黑星菌(Venturia inaequalis)引起;
根和茎疾病,例如:
伏革菌病(Corticium diseases),例如由禾伏革菌(Corticium graminearum)引起;
镰孢菌(霉)属病(Fusarium diseases),例如由尖镰孢(Fusarium oxysporum)引起;
鲟形属病(Gaeumannomyces diseases),例如由禾顶囊壳(Gaeumannomycesgraminis)引起;
丝核菌属病(Rhizoctonia diseases),例如由立枯丝核菌(Rhizoctonia solani)引起;
塔普斯(Tapesia)病,例如由塔普斯梭状芽胞杆菌(Tapesia acuformis)引起;
根串珠霉属病(Thielaviopsis diseases),例如由根串珠霉(Thielaviopsisbasicola)引起;
耳穗和圆锥花序疾病,例如:
链格孢属病(Alternaria diseases),例如由链格孢(Alternaria spp.)引起;
曲霉病(Aspergillus diseases),例如由黄曲霉(Aspergillus flavus)引起;
枝孢属病(Cladosporium diseases),例如由枝孢(Cladosporium spp.)引起;
麦角菌属病(Claviceps diseases),例如由麦角菌(Claviceps purpurea)引起;
镰孢菌(霉)属病(Fusarium diseases),例如由大刀镰孢菌(Fusariumculmorum)引起;
赤霉属病(Gibberella diseases),例如由玉米赤霉(Gibberella zeae)引起;
水稻云形病(Monographella diseases),例如由水稻云形菌(Monographellanivalis)引起;
黑穗病和腥黑穗病,例如:
轴黑粉菌属病(Sphacelotheca diseases),例如由丝轴黑粉菌(Sphacelothecareiliana)引起;
腥黑粉菌属病(Tilletia diseases),例如由小麦网腥黑粉菌(Tilletia caries)引起;
条黑粉菌属病(Urocystis diseases),例如由隐条黑粉菌(Urocystis occulta)引起;
黑粉菌属病(Ustilago diseases),例如由裸黑粉菌(Ustilago nuda)引起;
果实腐烂和霉菌病,例如:
曲霉病(Aspergillus diseases),例如由黄曲霉(Aspergillusflavus)引起;
葡萄孢属病(Botrytis diseases),例如由灰葡萄孢(Botrytis cinerea)引起;
青霉菌病(Penicillium diseases),例如由扩展青霉(Penicillium expansum)引起;
核盘菌属病(Sclerotinia diseases),例如由核盘菌(Sclerotinia sclerotiorum)引起;
轮枝孢属病(Verticillium diseases),例如由黑白轮枝孢(Verticilliumalboatrum)引起;
种子和土壤传播的腐烂,霉菌,枯萎,腐烂和猝倒病:
链格孢属病(Alternaria diseases),例如由芥生链格孢(Alternariabrassicicola)引起;
丝囊霉病(Aphanomyces diseases),例如由豌豆丝囊霉(Aphanomyceseuteiches)引起;
壳二孢病(Ascochyta diseases),例如由壳二孢(Ascochyta lentis)引起;
曲霉病(Aspergillus diseases),例如由黄曲霉(Aspergillus flavus)引起;
枝孢病(Cladosporium diseases),例如由多主枝孢(Cladosporium herbarum)引起;
旋孢腔菌病(Cochliobolus diseases),例如由禾旋孢腔菌(Cochliobolussativus)(Conidiaform:Drechslera,Bipolaris Syn:Helminthosporium)引起;
刺盘孢属病(Colletotrichum diseases),例如由番茄刺盘孢(Colletotrichumcoccodes)引起;
镰孢菌(霉)属病(Fusarium diseases),例如由大刀镰孢菌(Fusariumculmorum)引起;
赤霉属病(Gibberella diseases),例如由玉蜀黍赤霉(Gibberella zeae)引起;
球孢菌病(Macrophomina diseases),例如由豆类球孢菌(Macrophominaphaseolina)引起;
雪霉病(Monographella diseases),例如由小麦雪霉(Monographella nivalis)引起;
青霉菌病(Penicillium diseases),例如由扩展青霉(Penicillium expansum)引起;
茎点霉属病(Phoma diseases),例如由黑胫茎点霉(Phoma lingam)引起;
拟茎点霉属病(Phomopsis diseases),例如由大豆拟茎点霉(Phomopsissojae)引起;
疫霉属病(Phytophthora diseases),例如由恶疫霉(Phytophthora cactorum)引起;
核腔菌病(Pyrenophora diseases),例如由麦类核腔菌(Pyrenophoragraminea)引起;
梨孢属病(Pyricularia diseases),例如由稻梨孢菌(Pyricularia oryzae)引起;
腐霉属病(Pythium diseases),例如由终极腐霉(Pythium ultimum)引起;
丝核菌属病(Rhizoctonia diseases),例如由立枯丝核菌(Rhizoctonia solani)引起;
根霉病(Rhizopus diseases),例如由米根霉(Rhizopus oryzae)引起;
小核菌病(Sclerotium diseases),例如由齐整小核菌(Sclerotium rolfsii)引起;
壳针孢属病(Septoria diseases),例如由颖枯壳针孢(Septoria nodorum)引起;
核瑚菌病(Typhula diseases),例如由肉孢核瑚菌(Typhula incarnata)引起;
轮枝孢属病(Verticillium diseases),例如由大丽花轮枝孢(Verticilliumaahliae)引起;
溃疡病(Canker)、松碎(broom)和梢枯病,例如:
丛赤壳属病(Nectria diseases),例如由干癌丛赤壳菌(Nectria galligena)引起;
枯萎病,例如:
链核盘菌属病(Monilinia diseases),例如由核果链核盘菌(Monilinia laxa)引起;
叶疱病或缩叶病,例如:
外囊菌属病(Taphrina diseases),例如由畸形外囊菌(Taphrina deformans)引起;
木质植物的衰退病,例如:
依科病(Esca diseases),例如由根霉格孢菌(Phaemoniella clamydospora)、引起;
葡萄顶枯病(Eutypa dyeback),例如由葡萄弯孢壳(Eutypa lata)引起;
荷兰榆树病(Dutch elm disease),例如由榆枯萎病菌(Ceratocystsc ulmi)引起;
花和种子的疾病,例如:
葡萄孢属病(Botrytis diseases),例如由灰葡萄孢(Botrytis cinerea)引起;
根茎类疾病,例如:
丝核菌属病(Rhizoctonia diseases),例如由立枯丝核菌(Rhizoctonia solani)引起;
长蠕孢属病(Helminthosporium diseases),例如由茄病长蠕孢(Helminthosporium solani)引起。
依据本发明的处理方法可用于处理遗传修饰生物体(GMOs),例如植物或种子。遗传修饰植物(或转基因植物)是异源基因已经稳定整合到基因组中的植物。术语“异源基因”本质上是这样一种基因,该基因在植物外部提供或组装,当该基因被引入核基因组、叶绿体基因组或线粒体基因组时,通过表达感兴趣的蛋白质或多肽或者通过下调植物中存在的其它基因或使这些基因沉默来得到具有新的或改进的农学性质或其它性质的转化植物(使用例如反义技术、共抑制技术或RNA干扰-RNAi技术)。位于基因组中的异源基因也称为转基因。通过其在植物基因组中的特定位置定义的转基因称为转化或转基因事件。
根据植物物种或植物品种以及它们的场所和生长环境(土壤、气候、生长期、饮食),依据本发明的处理也可能产生超加(“协同”)效应。因此,例如,减少可依据本发明使用的活性化合物和组合物的施用率和/或拓宽其活性范围和/或增加其活性,有可能获得以下效果:更好的植物生长,对高温或低温的耐受性增加,对干旱或水或土壤盐含量的耐受性增加,开花性能提高,更容易收获,加快的成熟,更高的收获率,更大的果实,更高的植物高度,叶子的颜色更绿,开花更早,收获的产品的品质或营养价值更高,果实中糖浓度更高,收获的产品的储存稳定性和/或加工性更佳,这些益处超过了实际预估的效应。
在某些施用率下,依据本发明的活性化合物组合还可能在植物中产生加强效应。因此,它们也适用于动员植物的防御系统来抵抗不利的植物病原真菌和/或微生物和/或病毒的进攻。如果合适,这种作用可能是依据本发明的组合例如在抵抗真菌方面活性增强的原因之一。在本申请上下文中,植物加强(抗性诱导)物质应理解为是指能以某种方式刺激植物的防御系统从而在随后被不利的植物病原真菌和/或微生物和/或病毒接种时经过处理的植物对这些不利的植物病原真菌和/或微生物和/或病毒表现出明显的抵抗性的物质或物质的组合。在此情况中,不利的植物病原真菌和/或微生物和/或病毒应理解为是指植物病原真菌、细菌和病毒。因此,依据本发明的物质可用于保护植物,使其在经过处理后的一段时间内能抵抗上述病原体的攻击。保护起作用的时间通常为在用活性化合物处理植物后1-10天,优选1-7天。
适宜依据本发明处理的植物和栽培植物包括所有具有遗传物质的植物,这些遗传物质赋予这些植物特别有利且有用的性质(无论是通过培育和/或生物技术手段获得的)。
也适宜依据本发明处理的植物和栽培植物能抵抗一种或多种生物胁迫,即所述植物对动物和微生物害虫表现出更佳的防御性,例如抵抗线虫、昆虫、螨、植物病原真菌、细菌、病毒和/或类病毒。
也可以依据本发明处理的植物和栽培植物是对一种或多种非生物胁迫具有抵抗性的植物。非生物胁迫情况可包括例如干旱、冷温暴露、热暴露、渗透性应激、水灾、增加的土壤盐渍度、增加的矿物暴露、臭氧暴露、高光暴露、氮营养成分的有限利用率、磷营养成分的有限利用率、蔽阴。
也可以依据本发明处理的植物和栽培植物是具有增强的产率特征的植物。所述植物的产率提高的原因可能是例如改进的植物生理学、生长和发育,例如水利用效率、水保持效率、改进的氮利用、增强的碳同化作用、改进的光合作用、提高的发芽效率和加快的成熟。产率还可能受到植物结构(plant architecture)改进(在胁迫和非胁迫条件下)的影响,包括但不限于早期开花,对杂交种子生产的开花控制,幼苗活力、植物尺寸、节间数目和距离、根生长、种子尺寸、果实尺寸、豆荚尺寸、豆荚或穗数目、每豆荚或穗的种子数目、种子质量、加强的种子填充、减小的种子散布、减小的豆荚开裂和抗倒伏性。其它产率特征包括种子组成,例如碳水化合物含量、蛋白质含量、油含量和组成、营养价值、抗营养化合物的减少、改进的加工性和更佳的储存稳定性。
可依据本发明处理的植物是已经表现出杂种或杂交活力特征并由此产生更佳的产率、活力、健康状况和对生物和非生物胁迫的耐受性的杂交植物。这类植物通常通过将一个近亲交配的雄性不育的亲代系(母本)与另一个近亲交配的雄性能育的亲代系(父本)杂交而制得。杂种种子通常从雄性不育植物采集,出售给种植者。雄性不育植物有时(例如,在玉米中)可以通过去雄来生产,即机械除去雄性生殖器官(或雄花),但是更通常的是,雄性不育是植物基因组中遗传定子的结果。在那种情况中,特别是在种子是要从杂交植物中采集的所需产品时,通常可用于确保杂交植物的雄性能育性得到完全恢复。这可以通过确保父本具有合适的育性恢复基因来实现,该育性恢复基因能恢复含有造成雄性不育的遗传定子的杂交植物的雄性能育性。造成雄性不育的遗传定子位于细胞质中。例如,描述了芸苔属的细胞质雄性不育(CMS)的例子(WO 1992/005251、WO1995/009910、WO 1998/27806、WO 2005/002324、WO 2006/021972和US6,229,072)。但是,造成雄性不育的遗传定子也可位于核基因组中。雄性不育植物也可通过植物生物技术方法得到,例如遗传工程。获得雄性不育植物的特别有用的手段参见例如WO 89/10396,其中,核糖核酸酶如芽孢杆菌RNA酶选择性地表达在雄蕊的毯毡层细胞中。然后,可通过在毯毡层细胞中表达核糖核酸酶抑制剂如芽孢杆菌RNA酶抑制剂来恢复能育性(例如WO 1991/002069)。
可依据本发明处理的植物或栽培植物(通过植物生物技术方法如遗传工程获得)是耐受除草剂的植物,即能耐受一种或多种给定的除草剂的植物。这种植物可通过遗传转化或通过选择含赋予这种除草剂耐受性的突变的植物来获得。
例如,耐除草剂的植物是耐草甘膦的植物,即对除草剂草甘膦或其盐具有耐受性的植物。可通过不同的手段使植物对草甘膦具有耐受性。例如,耐草甘膦的植物可通过用编码5-烯醇丙酮莽草酸-3-磷酸合酶(5-enolpyruvylshikimate-3-phosphate synthase,EPSPS)的基因转化植物而获得。这类EPSPS基因的例子是细菌鼠伤寒杆菌(Salmonella typhimurium)的AroA基因(突变体CT7)(Comai等,Science(1983),221,370-371),细菌农杆菌属(Agrobacterium sp.)的CP4基因(Barry等,Curr.Topics Plant Physiol.(1992),7,139-145),编码矮牵牛EPSPS(Petunia EPSPS)的基因(Shah等,Science(1986),233,478-481),番茄EPSPS(Tomato EPSPS)(Gasser等,J.Biol.Chem.(1988),263,4280-4289),或牛筋草EPSPS(Eleusine EPSPS)(WO 2001/66704)。这类基因还可以是突变的EPSPS,如EP-A 0837944、WO 2000/066746、WO 2000/066747或WO2002/026995中所述的。耐草甘膦的植物还可以通过表达编码草甘膦氧化还原酶的基因来得到,例如如US 5,776,760和US 5,463,175号中所描述的。耐草甘膦的植物还可以通过表达编码草甘膦乙酰转移酶的基因来得到,例如如WO 2002/036782、WO2003/092360、WO 2005/012515和WO 2007/024782中所描述的。耐草甘膦的植物还可以通过选择含上述基因的自然发生突变体的植物来得到,例如如WO2001/024615或WO 2003/013226中所描述的。
其它耐受除草剂的植物例如是能耐受抑制谷氨酰胺合酶的除草剂(例如双丙氨磷、草胺膦(phosphinothricin)或草铵膦(glufosinate))的植物。这类植物可通过表达解毒除草剂的酶或对抑制作用具有耐受性的突变谷氨酰胺合酶而得到。一种有效的解毒酶是编码草胺膦乙酰转移酶的酶(例如来自链霉菌属的BAR或PAT蛋白)。例如,在US 5,561,236、US 5,648,477、US 5,646,024、US5,273,894、US 5,637,489、US 5,276,268、US 5,739,082、US 5,908,810和US7,112,665中描述了表达外源草胺膦乙酰转移酶的植物。
其它能耐受除草剂的植物还有能耐受抑制羟苯丙酮酸二加氧酶(HPPD)的除草剂的植物。羟苯丙酮酸二加氧酶是催化对羟苯丙酮酸(HPP)转化为高龙胆酸盐的反应的酶。对HPPD抑制剂具有耐受性的植物可用编码天然产生的耐HPPD酶的基因或编码突变HPPD酶的基因进行转化,如WO 1996/038567、WO1999/024585和WO 1999/024586中所描述的。对HPPD抑制剂的耐受性还可以通过用编码某些能形成高龙胆酸盐的酶的基因来转化植物而获得,虽然天然HPPD酶受到HPPD抑制剂的抑制。WO 1999/034008和WO 2002/36787中描述了这些植物和基因。植物对HPPD抑制剂的耐受性还可以通过用编码预苯酸脱氢酶的基因以及编码HPPD耐受酶的基因来转化植物而得到提高,如WO2004/024928中所描述的。
其它耐除草剂的植物是对乙酸乳酸合酶(ALS)抑制剂具有耐受性的植物。已知的ALS抑制剂包括例如磺酰脲、咪唑啉酮、三唑并嘧啶、吡啶氧基(硫代)苯甲酸盐/酯、和/或磺酰基氨基羰基三唑啉酮除草剂。已经知道,ALS酶(也称为乙酰羟酸合酶,AHAS)中的不同突变体能提供对不同除草剂和除草剂组的耐受性,例如如Tranel和Wright(Weed Science(2002)50:700-712)以及US5,605,011、US 5,378,824、US 5,141,870和US 5,013,659中所述的。在US5,605,011、US 5,013,659、US 5,141,870、US 5,767,361、US 5,731,180、US5,304,732、US 4,761,373、US 5,331,107、US 5,928,937和US 5,378,824以及国际公开WO 1996/033270中描述了磺酰脲耐受植物和咪唑啉酮耐受植物的生产。例如,在WO 2004/040012、WO 2004/106529、WO 2005/020673、WO2005/093093、WO 2006/007373、WO 2006/015376、WO 2006/024351和WO 2006/060634中还描述了其它咪唑啉酮耐受植物。例如,在WO 2007/024782中还描述了其它耐受磺酰脲和咪唑啉酮的植物。
其它耐受咪唑啉酮和/或磺酰脲的植物可通过在除草剂或诱变育种存在下进行诱变、细胞培养选择来获得,如US 5,084,082所述的用于大豆的,WO1997/41218所述的用于大米的,US 5,773,702和WO 1999/057965所述的用于甜菜的,US 5,198,599所述的用于莴苣的,或WO 2001/065922所述用于向日葵的。
也可以依据本发明处理的植物或栽培植物(通过植物生物技术方法如遗传工程得到)是抗虫的转基因植物,即能抵抗某些靶虫攻击的植物。这类植物可通过遗传转化或通过选择含有赋予这种抗虫性的突变的植物来获得。
文中使用的“抗虫转基因植物”包括含有至少一个包含编码序列的转基因的任何植物,所述编码序列编码:
1)来自苏云金芽孢杆菌(Bacillus thuringiensis)的杀虫晶体蛋白或其杀虫部分,例如Crickmore等(,微生物学和分子生物学综述(Microbiology and MolecularBiology Reviews)(1998),62,807-813)列出的杀虫晶体蛋白,Crickmore等(2005)对苏云金芽孢杆菌毒素命名进行了更新,见http://www.lifesci.sussex.ac.uk/Home/Neil_Crickmore/Bt/),或其杀虫部分,例如Cry蛋白类的蛋白Cry1Ab、Cry1Ac、Cry1F、Cry2Ab、Cry3Aa或Cry3Bb或其杀虫部分;或
2)来自苏云金芽孢杆菌的晶体蛋白或其部分,该晶体蛋白或其部分在来自苏云金芽孢杆菌的第二其它晶体蛋白或其部分存在下具有杀虫性,例如由Cry34和Cry35晶体蛋白构成的二元毒素(Moellenbeck等,Nat.Biotechnol.(2001),19:668-72;Schnepf等,Applied Environm.Microbiol.(2006),71,1765-1774);或
3)杂化杀虫蛋白,其包含不同的来自苏云金芽孢杆菌的杀虫晶体蛋白的部分,例如1)中所述蛋白的杂化或2)中所述蛋白的杂化,例如通过玉米事件MON89034生产的Cry1A.105蛋白(WO 2007/027777);或
4)上述1)-3)中任何一种蛋白,其中一些(特别是1-10)氨基酸已经被另一种氨基酸替换,以得到对靶虫物种更高的杀虫活性,以及/或者扩大受影响的靶虫物种的范围,以及/或者由于在克隆或转化过程中在编码DNA中引入变化,例如玉米事件MON863或MON88017中的Cry3Bb1蛋白或玉米事件MIR604中的Cry3A蛋白;或
5)来自苏云金芽孢杆菌或蜡样芽孢杆菌(Bacillus cereus)的杀虫分泌性蛋白,或其杀虫部分,例如http://www.lifesci.sussex.ac.uk/home/Neil_Crickmore/Bt/vip.html中所列的营养期杀虫蛋白(VIP),例如来自VIP3Aa蛋白类的蛋白;或
6)来自苏云金芽孢杆菌或蜡样芽孢杆菌的分泌性蛋白,该蛋白在来自苏云金芽孢杆菌或蜡样芽孢杆菌的第二分泌性蛋白存在下具有杀虫性,例如由VIP1A和VIP2A蛋白构成的二元毒素(WO 1994/21795);或
7)杂化杀虫蛋白,其包含不同的来自苏云金芽孢杆菌或蜡样芽孢杆菌的分泌性蛋白的部分,例如1)中所述蛋白的杂化或2)中所述蛋白的杂化;或
8)上述1)-3)中任何一种蛋白,其中一些(特别是1-10)氨基酸已经被另一种氨基酸替换,以得到对靶虫物种更高的杀虫活性,以及/或者扩大受影响的靶虫物种的范围,以及/或者由于在克隆或转化过程中在编码DNA中引入变化(同时仍然编码杀虫蛋白),例如棉花事件COT102中的VIP3Aa蛋白。
当然,文中所用的抗虫转基因植物还包括包含编码上述1-8类中任何一种蛋白质的基因的组合的任何植物。在一个实施方式中,抗虫植物含有不止一个编码上述1-8类中任何一种蛋白质的转基因,以扩大在使用指向不同靶虫物种的不同蛋白质时受影响的靶虫物种的范围,或者通过使用对相同靶虫物种具有杀虫性但具有不同作用模式的不同蛋白质来延迟对植物的抗虫性发展,例如结合到昆虫不同受体结合位点。
也可依据本发明处理的植物或栽培植物(通过植物生物技术方法如遗传工程得到)对非生物胁迫具有耐受性。这类植物可通过遗传转化或通过选择含有能赋予这种抗胁迫性的突变的植物来获得。特别有用的抗胁迫植物包括:
a.含有能减少植物细胞或植物中聚(ADP-核糖)聚合酶(PARP)基因表达和/或活性的转基因的植物,如WO 2000/004173、WO2006/045633或PCT/EP07/004142中所述的。
b.含有能减少植物或植物细胞中PARG编码基因表达和/或活性的抗胁迫增强转基因的植物,如WO 2004/090140中所述的。
c.含有一种抗胁迫增强转基因的植物,该转基因编码烟酰胺腺嘌呤二核苷酸补救合成路径的植物功能酶,该酶包括烟酰胺酶,烟酰酸磷酸核糖基转移酶,烟酸单核苷酸磷酸腺苷转移酶、烟酰胺腺嘌呤二核苷合成酶或烟酰胺磷酸核糖基转移酶,如WO2006/032469或WO2006/133827或PCT/EP07/002433。
也可依据本发明处理的植物或栽培植物(通过植物生物技术方法如遗传工程制得)表现出收获产品数量、品质和/或储存稳定性的改变,以及/或者收获产品特定成分的性质改变,例如:
1)合成变性淀粉的转基因植物,该变性淀粉与野生型植物细胞或植物中的合成淀粉相比,其物理化学性质,尤其是直链淀粉含量或直链淀粉/支链淀粉比值、支化度、平均链长、侧链分布、粘度行为、凝胶强度、淀粉粒度和/或淀粉颗粒形态改变,因而更适宜用于一些特殊应用。所述合成变性淀粉的转基因植物例如在以下文献中进行了揭示:EP 0571427、WO 1995/004826、EP0719338、WO 1996/15248、WO 1996/19581、WO 1996/27674、WO1997/11188、WO 1997/26362、WO 1997/32985、WO 1997/42328、WO1997/44472、WO 1997/45545、WO 1998/27212、WO 1998/40503、WO99/58688、WO 1999/58690、WO 1999/58654、WO 2000/008184、WO2000/008185、WO 2000/008175、WO 2000/28052、WO 2000/77229、WO2001/12782、WO 2001/12826、WO 2002/101059、WO 2003/071860、WO2004/056999、WO 2005/030942、WO 2005/030941、WO 2005/095632、WO2005/095617、WO 2005/095619、WO 2005/095618、WO 2005/123927、WO2006/018319、WO 2006/103107、WO 2006/108702、WO 2007/009823、WO2000/22140、WO 2006/063862、WO 2006/072603、WO 2002/034923、EP06090134.5、EP 06090228.5、EP 06090227.7、EP 07090007.1、EP 07090009.7、WO 2001/14569、WO 2002/79410、WO 2003/33540、WO 2004/078983、WO2001/19975、WO 1995/26407、WO 1996/34968、WO 1998/20145、WO1999/12950、WO 1999/66050、WO 1999/53072、US 6,734,341、WO2000/11192、WO 1998/22604、WO 1998/32326、WO 2001/98509、WO2001/98509、WO 2005/002359、US 5,824,790、US 6,013,861、WO1994/004693、WO 1994/009144、WO 1994/11520、WO 1995/35026、WO1997/20936;
2)合成非淀粉碳水化合物聚合物的转基因植物,或与未经过遗传修饰的野生型植物相比具有改变的性质的合成非淀粉碳水化合物聚合物的转基因植物。例子是:产生聚果糖,特别是菊糖和果聚糖类型的植物,如EP 0663956、WO1996/001904、WO 1996/021023、WO 1998/039460和WO 1999/024593所述的;产生α-1,4-葡聚糖的植物,如WO 1995/031553、US 2002/031826、US6,284,479、US 5,712,107、WO 1997/047806、WO 1997/047807、WO1997/047808和WO 2000/014249所述的;产生α-1,6支化的α-1,4-葡聚糖的植物,如WO 2000/73422所述的;产生阿塔娜(alternan)的植物,如WO2000/047727、EP 06077301.7、US 5,908,975和EP 0728213中所述的;
3)产生透明质烷(hyaluronan)的转基因植物,例如,如WO 2006/032538、WO 2007/039314、WO 2007/039315、WO 2007/039316、JP 2006/304779和WO2005/012529中所述的。
也可依据本发明处理的植物或栽培植物(可通过植物生物技术方法如遗传工程获得)是具有改变的纤维性质的植物,如棉花植物。这类植物可通过遗传转化或通过选择含有赋予这种改变的纤维性质的突变的植物来获得,这类植物包括:
a)含有改变形式的纤维素合酶基因的植物,例如棉花植物,如WO1998/000549中所述的;
b)含有改变形式的rsw2或rsw3同源核酸的植物,例如棉花植物,如WO2004/053219中所述的;
c)具有增强的蔗糖磷酸合酶表达的植物,例如棉花植物,如WO2001/017333中所述的;
d)具有增强的蔗糖合酶表达的植物,例如棉花植物,如WO 02/45485中所述的;
e)植物,例如棉花植物,其中在纤维状细胞基础上的胞间连丝的定时改变,例如通过下调纤维选择性β-1,3-葡聚糖酶来实现,如WO 2005/017157中所述的;
f)具有纤维的植物,例如棉花植物,所述纤维具有改变的反应活性,例如通过包括nodC的N-乙酰基葡糖胺转移酶基因和几丁质合成酶基因的表达来实现,如WO 2006/136351中所述的。
也可以依据本发明处理的植物或栽培植物(可通过植物生物技术方法如遗传工程获得)是具有改变的油曲线(oil profile)性质的植物,例如油籽油菜(oilseedrape)或相关的芸苔属植物。这类植物可通过遗传转化或通过选择含有赋予这种改变的油性质的突变的植物来获得,这类植物包括:
a)产生具有高油酸含量的油的植物,例如油籽油菜植物,如US5,969,169、US 5,840,946、US 6,323,392或US 6,063,947中所述的;
b)产生具有低亚麻酸含量的油的植物,例如油籽油菜植物,如US6,270,828、US 6,169,190或US 5,965,755中所述的;
c)产生具有低含量饱和脂肪酸的油的植物,例如油籽油菜植物,例如,如US 5,434,283中所述的。
可依据本发明处理的特别有用的转基因植物是包含一种或多种编码一种或多种毒素的基因的植物,例如以以下商品名出售的植物:YIELD GARD3(例如玉米、棉花、大豆),KnockOut3(例如玉米),BiteGard3(例如玉米),Bt-Xtra3(例如玉米),StarLink3(例如玉米),Bollgard3(棉花),Nucotn3(棉花),Nucotn33B(棉花),NatureGard3(例如玉米),Protecta3和NewLeaf3(马铃薯)。可提及的能耐受除草剂的植物的例子是以以下商品名出售的玉米品种、棉花品种和大豆品种:Roundup Ready3(耐受草甘膦,例如玉米、棉花、大豆),Liberty Link3(耐受膦基霉素(phosphinotricin),例如含油种子),IMI3(耐受咪唑啉酮)和STS3(耐受磺酰基脲,例如玉米)。可提及的耐受除草剂的植物(以常规方式培养耐受除草剂的植物)包括以名称Clearfield3(例如玉米)出售的品种。
可依据本发明处理的特别有用的转基因植物是含转化事件或转化事件组合的植物,它们例如在各个国家或地方性管理机构的数据库中列出(参见,例如http://gmoinfo.jrc.it/gmp_browse.aspx和http://www.agbios.com/dbase.php)。
本发明的化合物也可以用于制备对于治疗性或预防性治疗人或动物真菌疾病有用的组合物,这些疾病例如霉菌病(mycose)、皮肤病、藓菌病和念珠菌病或由曲霉属(Aspergillus spp.)如烟曲霉(Aspergillus fumigatus)引起的疾病。
依据EEC Directive 79/831Annex V.A8,通过HPLC(高效液相色谱)在反相柱上使用以下方法测量logP值:
在pH 2.7,用0.1%的甲酸水溶液和乙腈(含0.1%甲酸)作为洗脱剂,以10%乙腈到95%乙腈的线性梯度进行LC-MS测量。
使用logP值已知的非支链烷-2-酮(包含3-16个碳原子)进行校准(logP值是通过采用两个相邻烷酮之间的线性内插法由保留时间确定的)。使用200纳米至400纳米的紫外光谱,在色谱信号最大值处确定λmax值。
在表1中,质谱中所观察到的M+H(或M-H)分别指正或负1a.m.u.(原子质量单位)的分子离子峰,M(ApcI+)指通过质谱中的正大气压化学电离发现的分子离子峰。
在表1的所有实施例中,测量M+1峰。
以下实施例以非限制性的方式说明了依据本发明的通式(I)的化合物的制备和药效。
制备实施例1:N-{4-[({[(1-甲基-1H-四唑-5-基)(苯基)亚甲基]氨基}氧基)甲基]-1,3-噻唑-2-基}色满(chromane)-2-羧酰胺(化合物10)
向搅拌着的4-[({[(1-甲基-1H-四唑-5-基)(苯基)亚甲基]氨基}氧基)甲基]-1,3-噻唑-2-胺(200毫克,0.63毫摩尔)的二甲基甲酰胺(1.5毫升)溶液中加入色满-2-羧酸(124毫克,0.70毫摩尔)和1H-苯并三唑-1-醇(94毫克,0.70毫摩尔)。将反应混合物在室温下倒在填充了负载N,N′-二环己基碳二亚胺(负载量:1.05毫摩尔/克)的1.44克二氧化硅的滤筒上。在室温下放置一夜后,用1毫升二甲基甲酰胺洗脱滤筒。然后,将滤液倒在填充了1.5克碱性氧化铝的滤筒上。在室温下反应2小时后,用10毫升乙酸乙酯洗涤滤筒两次。合并的滤液在真空下蒸发,得到黄色油。在硅胶上纯化,得到无色油状的N-{4-[({[(1-甲基-1H-四唑-5-基)(苯基)亚甲基]氨基}氧基)甲基]-1,3-噻唑-2-基}色满-2-羧酰胺[150毫克,产率44%;HPLC/MS:m/z=476(M+H);logP(HCOOH)=3.78]。
制备实施例2:N-{6-[({[(1-甲基-1H-四唑-5-基)(苯基)亚甲基]氨基}氧基)甲基]吡啶-2-基}-2,3-二氢-1-苯并呋喃-2-羧酰胺(化合物41)
在室温下,在氮气下向搅拌着的6-[({[(1-甲基-1H-四唑-5-基)(苯基)亚甲基]氨基}氧基)甲基]吡啶-2-胺(100毫克,0.32毫摩尔)的干二氯甲烷(4毫升)溶液加入吡啶(39微升,0.48毫摩尔),15分钟后,加入2,3-二氢-1-苯并呋喃-2-酰氯(88毫克,0.48毫摩尔)。将反应混合物在室温搅拌过夜,通过在填充了1.4克碱性氧化铝和1克二氧化硅的双层滤筒上过滤而猝灭。用10毫升二氯甲烷洗涤滤筒两次。合并的滤液在真空下蒸发,得到无色油。在硅胶上纯化,得到无色油状的N-{6-[({[(1-甲基-1H-四唑-5-基)(苯基)亚甲基]氨基}氧基)甲基]吡啶-2-基}-2,3-二氢-1-苯并呋喃-2-羧酰胺[150毫克,产率96%;HPLC/MS:m/z=456(M+H);logP(HCOOH)=3.67]。
实施例A
疫霉(Phytophthora)测试(番茄)/预防性的
溶剂:49重量份N,N-二甲基甲酰胺
乳化剂:1重量份烷基芳基聚乙二醇醚
为了生产活性化合物的合适制剂,将1重量份活性化合物与所述量的溶剂和乳化剂混合,用水稀释该浓缩物至所需浓度。
为了测试预防性活性,用活性化合物制剂以所述的施用率喷洒幼小植物。在该处理1天后,用致病疫霉(Phytophthora infestans)的孢子水悬浮液对植物进行接种。将所述植物在约22℃、相对大气湿度为100%的温育箱中保持1天。然后将所述植物放置在约20℃、相对大气湿度为96%的温育箱中。
在接种后7天,对测试结果进行评价。0%表示相当于未处理的对照样的药效,100%的药效表示无病症出现。
在该测试中,依据本发明的以下化合物在活性成分浓度为100ppm的情况下表现出等于或高于70%的药效。
实施例号[表1](药效%):
1(93%),2(95%),3(95%),4(95%),5(95%),6(93%),7(95%),8(95%),9(85%),10(100%),11(95%),12(95%),13(98%),14(90%),15(90%),16(93%),17(93%),18(95%),19(95%),20(93%),21(80%),22(80%),23(90%),24(93%),25(93%),26(95%),27(95%),28(98%),29(90%),30(95%),31(95%),32(95%),33(90%),34(95%),35(95%),36(95%),37(95%),38(95%),39(95%),40(98%),41(89%),42(89%),43(85%),44(95%),45(98%),46(75%),47(70%),48(80%),56(100%),57(88%),59(95%),60(95%),60(95%)。
实施例B
单轴霉属(Plasmopara)测试(葡萄藤)/预防性的
溶剂:24.5重量份丙酮
24.5重量份二甲基乙酰胺
乳化剂:1重量份烷基芳基聚乙二醇醚
为了生产活性化合物的合适制剂,将1重量份活性化合物与所述量的溶剂和乳化剂混合,用水稀释该浓缩物至所需浓度。
为了测试预防性活性,用活性化合物制剂以所述的施用率喷洒幼小植物。在喷洒的涂层干燥后,用葡萄生单轴霉(Plasmopara viticola)的孢子水悬浮液对植物进行接种,然后在约20℃、相对大气湿度为100%的温育箱中保持1天。然后将所述植物在约21℃、相对大气湿度为90%的温室中放置4天。然后,将植物在温育箱中被喷雾并放置1天。
在接种后6天,对测试结果进行评价。0%表示相当于未处理的对照样的药效,100%的药效表示无病症出现。
在该测试中,依据本发明的以下化合物在活性成分浓度为100ppm的情况下表现出等于或高于70%的药效。
实施例号[表1](药效%):
5(89%),7(75%),8(87%),9(97%),10(100%),11(98%),40(96%),41(97%),41(91%),42(100%),45(96%),56(85%),60(97%)。
实施例C
腐霉属(Pythium)测试(棉花)/种子处理
在温室条件下进行测试。
用溶解在N-甲基-2-吡咯烷酮中并用水稀释到所需剂量的活性化合物或化合物组合处理棉花种子,然后播种到含4cm的经过蒸煮的田土和砂子的1∶1混合物的6*6cm罐子中。
用终极腐霉(Pythium ultimum)的菌丝体片断温育珍珠岩(Perlite)。1毫升被感染的珍珠岩在经过处理的棉花种子之间分散。然后用轻度膨胀粘土聚集体覆盖种子。将罐子在温室中在20℃和80%相对湿度下温育7天。
通过对萌芽幼苗的计数进行评论。0%表示相当于对照样的药效,100%的药效表示所有幼苗都萌芽。
在该测试中,依据本发明的以下化合物在活性成分剂量为10g/dt种子的情况下表现出等于或高于70%的药效。
实施例号[表1](药效%):
10(86%),11(77%),41(92%)。
Claims (9)
1.一种通式(I)的化合物,
式中,
·X表示氢原子;
·A表示通式(A1)或(A2)的四唑基:
式中Y表示具有1-3个碳原子的烷基;
·Het表示通式(Het1)的吡啶基或通式(Het2)的噻唑基;
式中,
o R表示氢原子或卤原子,
o Q表示通式Z的基团;
式中,
o Ra表示氢原子,
o L1表示通式-(CR1R2)n-的二价基团,
其中
o n表示1或2;
o R1和R2独立的表示氢原子、未取代的C1-C8-烷基;
o L2表示氧原子、式-CH2-的二价基团或羰基;
o L3表示氧原子;
o K1表示氢原子;K2表示氢原子或卤原子,K3和K4独立的表示氢原子、卤原子、未取代的C1-C8-烷基、未取代的C1-C8-烷氧基;
或者
o Q表示通式Z1的基团;
式中
o L1表示通式=(CR1)-的二价基团,
R1、K1、K2、K3、K4、L2和L3如(Z)中所定义,
或者
o Q表示通式Z2的基团;
其中K1、K2、K3、K4、Ra、L1和L3如(Z)中所定义;
或者
o Q表示通式Z3的基团;
·其中K1、K2、K3、K4、Ra、L1和L2如(Z)中所定义,
以及所述化合物的盐、以及它们的混合物。
2.如权利要求1所述的化合物,其特征在于,通式(Het1)的吡啶基中的R表示氢原子或卤原子。
3.如权利要求1所述的化合物,其特征在于,通式(Het1)的吡啶基中的R表示氢原子或氯原子。
4.如权利要求1-3中任一项所述的化合物,其特征在于,n表示1。
5.如权利要求1-3中任一项所述的化合物,其特征在于,R1和R2独立的表示氢原子或甲基。
6.如权利要求1-3中任一项所述的化合物,其特征在于,L2表示氧原子或式-CH2的二价基团。
7.如权利要求1-3中任一项所述的化合物,其特征在于,K1表示氢原子、K2表示氢原子、卤原子,K3和K4独立的表示氢原子、卤原子、C1-C2-烷基、C1-C2-烷氧基。
8.一种杀真菌组合物,其包含有效量的作为活性成分的如权利要求1-7所述的通式(I)的化合物和农学上可接受的担体、载体或填料。
9.一种控制作物的植物病原真菌的方法,该方法的特征在于将农学有效且基本无植物毒性量的权利要求1-7所述的化合物或权利要求8所述的组合物施用到植物在其中生长或能够在其中生长的土壤中,或施用到植物的叶子和/或果实上,或施用到植物的种子上。
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Publication number | Publication date |
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EP2519103A1 (en) | 2012-11-07 |
US20130123305A1 (en) | 2013-05-16 |
BR112012012107B1 (pt) | 2019-08-20 |
TW201138624A (en) | 2011-11-16 |
WO2011080256A1 (en) | 2011-07-07 |
JP5782658B2 (ja) | 2015-09-24 |
CN102724879A (zh) | 2012-10-10 |
JP2013515702A (ja) | 2013-05-09 |
KR20120102133A (ko) | 2012-09-17 |
BR112012012107A2 (pt) | 2016-04-05 |
EP2519103B1 (en) | 2014-08-13 |
US8796463B2 (en) | 2014-08-05 |
MX2012007539A (es) | 2012-07-23 |
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