Pyripyropene derivative as well as composition and application thereof

Abstract

The invention belongs to the technical field of pesticides, and particularly relates to a pyripyropene derivative as well as a composition and application thereof. The compound is shown as a general formula I: # imgabs0 #, X1 represents hydrogen or fluorine, X2 represents hydrogen or fluorine, X3 represents hydrogen or fluorine, X4 represents hydrogen or fluorine, and X1, X2, X3 and X4 are not hydrogen at the same time; r1 and R2 respectively and independently represent hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkyl alkyl or-(CO) R3; y1 represents a hydroxyl group, an alkoxyalkyloxy group, a trialkylsilyloxy group or-O (CO) R3; y2 represents hydrogen or alkyl; or Y1, Y2 together form = O. The compound has excellent prevention and treatment effects on green peach aphids, green plant bugs, rhopalosiphum padi, bemisia tabaci and other pests.

Description

Technical Field

[0001] The invention belongs to the technical field of pesticides, and specifically relates to a pyripyropene derivative and a composition and use thereof. Background Art

[0002] So far, many pest control agents with insecticidal activity have been reported. However, insect species that are resistant to these pest control agents or difficult to control by these pest control agents have been found and further there are problems with safety for humans and animals. Thus, it is still desirable to develop new pest control agents with powerful insecticidal activity. Summary of the invention

[0003] In order to solve the above problems existing in the prior art, the present invention provides a pyripyropeptide derivative and its composition and use. The compound has excellent control effects on pests such as green myzus, green stink bug, cereal aphid, and whitefly.

[0004] The technical solution adopted by the present invention is as follows:

[0005] A pyripyropene derivative as shown in formula I,

[0006]

[0007] wherein X1 represents hydrogen or fluorine, X2 represents hydrogen or fluorine, X3 represents hydrogen or fluorine, X4 represents hydrogen or fluorine, and X1, X2, X3 and X4 are not hydrogen at the same time;

[0008] R1 and R2 independently represent hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl or -(CO)R3;

[0009] Y1 represents hydroxy, alkoxyalkyloxy, trialkylsilyloxy or -O(CO)R3; Y2 represents hydrogen or alkyl; or Y1 and Y2 together form =O;

[0010] R3 each independently represents hydrogen, an alkyl, alkenyl or alkynyl group which is unsubstituted or substituted by at least one of halogen, alkoxy, alkoxycarbonyl or alkylthio, a cycloalkyl group, a cycloalkenyl group, an aryl group or a heterocyclic group;

[0011] The aforementioned "cycloalkyl", "cycloalkenyl", "heterocyclyl" or "aryl" is optionally selected from oxo, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, cycloalkyl substituted by alkyl, -OR 10 、-SR 10 、-(CO)OR 10 、-(SO2)R 10 、-N(R 10 )2 or -O-alkylene-(CO)OR10 or two adjacent carbon atoms on the ring form a condensed ring with unsubstituted or halogen-substituted -OCH2CH2- or -OCH2O-;

[0012] R 10 Each is independently hydrogen, alkyl, haloalkyl, phenyl, or phenyl substituted by at least one group selected from halogen, cyano, nitro, alkyl, haloalkyl, alkoxycarbonyl, alkylthio, alkylsulfonyl, alkoxy or haloalkoxy.

[0013] In a specific embodiment,

[0014] R1 and R2 independently represent hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkylC1-C8 alkyl or -(CO)R3;

[0015] Y1 represents hydroxyl, C1-C8 alkoxy, C1-C8 alkyloxy, tri-C1-C8 alkylsilyloxy or -O(CO)R3;

[0016] Y2 represents hydrogen or C1-C8 alkyl; or Y1 and Y2 together form =O;

[0017] R3 each independently represents hydrogen, C1-C8 alkyl, C2-C8 alkenyl or C2-C8 alkynyl which is unsubstituted or substituted by at least one of halogen, C1-C8 alkoxy, C1-C8 alkoxycarbonyl or C1-C8 alkylthio, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclic group;

[0018] The aforementioned “C3-C8 cycloalkyl”, “C3-C8 cycloalkenyl”, “heterocyclyl” or “aryl” is optionally selected from oxo, halogen, cyano, nitro, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, halogenated C1-C8 alkyl, halogenated C2-C8 alkenyl, halogenated C2-C8 alkynyl, halogenated C3-C8 cycloalkyl, C3-C8 cycloalkyl substituted by C1-C8 alkyl, -OR 10 、-SR 10 、-(CO)OR 10 、-(SO2)R 10 、-N(R 10 )2 or -O-(C1-C8 alkylene)-(CO)OR 10 or two adjacent carbon atoms on the ring form a condensed ring with unsubstituted or halogen-substituted -OCH2CH2- or -OCH2O-;

[0019] R 10They are independently hydrogen, C1-C8 alkyl, halogenated C1-C8 alkyl, phenyl, or phenyl substituted by at least one group selected from halogen, cyano, nitro, C1-C8 alkyl, halogenated C1-C8 alkyl, C1-C8 alkoxycarbonyl, C1-C8 alkylthio, C1-C8 alkylsulfonyl, C1-C8 alkoxy or halogenated C1-C8 alkoxy.

[0020] In a specific embodiment,

[0021] R1 and R2 independently represent hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 cycloalkylC1-C6 alkyl or -(CO)R3;

[0022] Y1 represents hydroxyl, C1-C6 alkoxy, C1-C6 alkyloxy, tri-C1-C6 alkylsilyloxy or -O(CO)R3;

[0023] Y2 represents hydrogen or C1-C6 alkyl; or Y1 and Y2 together form =O;

[0024] R3 each independently represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 cycloalkenyl, aryl or heterocyclic group which is unsubstituted or substituted by at least one of halogen, C1-C6 alkoxy, C1-C6 alkoxycarbonyl or C1-C6 alkylthio;

[0025] The aforementioned “C3-C6 cycloalkyl”, “C3-C6 cycloalkenyl”, “heterocyclyl” or “aryl” is optionally selected from oxo, halogen, cyano, nitro, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, halogenated C1-C6 alkyl, halogenated C2-C6 alkenyl, halogenated C2-C6 alkynyl, halogenated C3-C6 cycloalkyl, C3-C6 cycloalkyl substituted by C1-C6 alkyl, -OR 10 、-SR 10 、-(CO)OR 10 、-(SO2)R 10 、-N(R 10 )2 or -O-(C1-C6 alkylene)-(CO)OR 10 or two adjacent carbon atoms on the ring form a condensed ring with unsubstituted or halogen-substituted -OCH2CH2- or -OCH2O-;

[0026] R 10Each of them is independently hydrogen, C1-C6 alkyl, halogenated C1-C6 alkyl, phenyl, or phenyl substituted by 1 to 3 groups selected from halogen, cyano, nitro, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxycarbonyl, C1-C6 alkylthio, C1-C6 alkylsulfonyl, C1-C6 alkoxy or halogenated C1-C6 alkoxy.

[0027] In a specific embodiment,

[0028] X1 represents hydrogen, X2 represents fluorine, X3 represents hydrogen, and X4 represents hydrogen; or X1 represents hydrogen, X2 represents hydrogen, X3 represents fluorine, and X4 represents hydrogen.

[0029] In a specific embodiment,

[0030] Y1 represents a hydroxyl group or -O(CO)R3; Y2 represents hydrogen; or Y1 and Y2 together form =O.

[0031] In the definition of the compounds represented by the above general formula and in all the following structural formulae, the technical terms used, whether used alone or in compound words, represent the following substituents: Alkyl groups with more than two carbon atoms can be straight-chain or branched. For example, the compound word "-O-alkylene-(CO)OR 10 " " in which the alkylene group can be -CH2-, -CH2CH2-, -CH(CH3)-, -C(CH3)2-, etc. The alkyl group is, for example, C1 alkyl-methyl; C2 alkyl-ethyl; C3 alkyl-propyl such as n-propyl or isopropyl; C4 alkyl-butyl such as n-butyl, isobutyl, tert-butyl or 2-butyl; C5 alkyl-pentyl such as n-pentyl; C6 alkyl-hexyl such as n-hexyl, isohexyl and 1,3-dimethylbutyl. Similarly, alkenyl is, for example, vinyl, allyl, 1-methylprop-2-en-1-yl, 2-methylprop-2-en-1-yl, but-2-en-1-yl, but-3-en-1 The term "cycloalkyl" refers to a cycloalkyl radical, ...

[0032] Unless otherwise specified, the "aryl" mentioned in the present invention includes but is not limited to phenyl, naphthyl, The "heterocyclic group" includes but is not limited to saturated or unsaturated non-aromatic cyclic groups

[0033] etc., also including but not limited to heteroaryl, i.e. aromatic cyclic groups containing, for example, 3 to 6 ring atoms and optionally fused to a benzo ring, wherein 1 to 4 (e.g. 1, 2, 3 or 4) heteroatoms among the ring atoms are selected from oxygen, nitrogen and sulfur, for example

[0034]

[0035] If a group is substituted by a group, this is understood to mean that the group is substituted by one or more identical or different groups selected from those mentioned. In addition, identical or different substitution characters contained in identical or different substituents are independently selected and may be identical or different. The same applies to ring systems formed by different atoms and units. At the same time, the scope of the claims will exclude compounds that are known to the person skilled in the art to be chemically unstable under standard conditions.

[0036] In addition, unless otherwise specified, the term "substituted by at least one group" in the present invention means substituted by 1, 2, 3, 4 or 5 groups; groups (including heterocyclic groups, aryl groups, etc.) without specific connection positions can be connected at any position, including the position connected to C or N; if it is substituted, the substituent can also be substituted at any position as long as it complies with the chemical bond connection rules. For example, a heteroaryl group substituted by 1 methyl group Can represent wait.

[0037] The types of pests against which the compound represented by Formula I or a salt thereof as an active ingredient has an insecticidal effect include, for example, lepidopteran pests, such as Spodoptera litura, Mamestrabrassicae, Pseudaletia separata, green caterpillar, Plutellaxylostella, Spodoptera exigua, Chilo suppressalis, Cnaphalocrocis medinalis, Tortricidae, Carposinidae, Lyonetiidae, Lymantriidae, Agrotis spp., Helicoverpa spp., or Heliothis spp. spp.); hemipteran pests, such as Aphididae, Adelgidae or Phylloxera

[0038] (Phylloxeridae), such as Myzus percicae, Aphis gossypii Glover,

[0039] Aphis fabae, Aphis maidis, Acyrthosiphon pisum, Aulacorthum solani, Aphis craccivora, Macrosiphum euphorbiae, Macrosiphum avenae, Metopolophium dirhodum, Rhopalosiphum padi, Schizaphis graminum, Brevicoryne brassicae, Lipaphis erysimi, Aphis citricola, Rosy apple aphid, Eriosoma lanigerum, Toxoptera aurantii, or Toxoptera serrata. citricidus, Deltocephalae, for example Nephotettix cincticeps, leafhoppers, for example Tea greenleafhopper, Delphacidae, for example Laodelphax striatellus, Nilaparvata lugens or Sogatella furcifera, Pentatomidae, for example Eysarcoris ventralis, Nezaviridula or Trigonotyluscaelestialium, Aleyrodidae, for example Bemisia tabaci or Trialeurodes vaporariorum, Coccoidea, for example Pseudococcus comstocki,Planococcus citri Risso or Aonidiella aurantii (e.g. Diaspididae, Margarodidae, Ortheziidae, Aclerdiae, Dactylopiidae, Kerridae, Pseudococcidae, Coccidae, Eriococcidae, Asterolecaniidae, Beesonidae, Lecanodiaspididae or Cerococcidae), and Psyllidae, for example Diaphorina citri; Coleoptera pests, for example, Lissorhoptrus oryzophilus, Callosobruchus chinensis, Tenebrio molitor, Diabrotica virgifera virgifera, Diabrotica undecimpunctatahowardi, Anomala cuprea, Anomala rufocuprea, Phyllotreta striolata, Aulacophora femoralis, Leptinotarsa ​​decemlineata, Oulema oryzae, Grapholita molesta or Cerambycidae; Acari, for example, Tetranychus urticae urticae), Tetranychus kanzawai or Panonychus citri; hymenopteran pests, such as Tenthredinoidea; Orthopteran pests, such as Acrididae; Dipteran pests, such as Musca domestica Linnaeus or Agromyzidae; Thysanopteran pests,For example, Thrips palmi KARNY or Frankliniella occidentalis; and plant parasitic nematodes, such as Meloidogynehapla, Pratylenchus, Aphelenchoides besseyi or Bursaphelenchus xylophilus. Examples of animal parasites include Siphonaptera, such as Ctenocephalides felis or Pulex irritans, Anoplura, such as Pediculus spp. or Phtirus spp.; Acari, such as Boophilus spp., Haemaphysalis longicornis,

[0040] (Haemaphysalis longicornis), Rhipicephalus sanguineus, Haemaphysalis longicornis

[0041] (Haemaphysalis flava), Sarcoptes spp., Dermanyssus spp., Ornithonyssus sylviarum, Ornithonyssus bacoti, and Leptotrombidium; Tabanidae; Diptera, for example, Lucilia spp.; Mosquitoes, for example, Stegomyia albopicta and Culex pipiens pallens; Simuliidae; Ceratidae

[0042] Ceratopogonidae; Nematoda, for example Strongyloides, for example Strongyloides papillosus or Strongyloides stercoralis, hookworms, for example A. caninum, Ancylostoma tubaeforme or Ancylostoma duodenale; Haemonchus spp.; Strongylida, for example Strongyloides mouse; hairworms; Metastrongyloidea, for example Metastrongylus spp., Angiostrongylus cantonensis or Strongyloides felis

[0043] Aelurostrongylus; Oxyurida; Heterakidae, e.g. Heterakidae

[0044] Heterakis gallinarum; Anisakis simplex; Ascaroidea, for example Ascaris suum, Parascaris equorum, Toxicara canis or Toxocara cati

[0045] (Toxocara cati); Subuluridae; Spiruroidea, for example Gnathostoma spinigerum, Phys aloptera, Ascarops strongylina, Draschia megastoma, Acuaria or Ostertagia ostertagi; Filariida, for example Dirofilaria or Onchocerca cervicalis; Order Dioctophymatida; Wipeworms and Trichinosis, for example Trichuris vulpis or Trichinella spiralis; Trematoda, for example, Schistosoma japonicum or Fasciola hepatica; Echinocephala

[0046] (Acanthocephala), such as Macracanthorhynchus hirudinaceus or Moniliformis moniliformis; Cestoda, such as Bothriocephaloidea, such as Diphyllobothrium mansoni; Cyclophyllidea, such as Dipylidium caninum, Hymenolepis diminuta, Echinococcus multilocularis or Echinococcus granulosus; and protozoa. Preferred pest species include Hemiptera, Diptera and Thysanoptera pests. Particularly preferred are Hemiptera pests.

[0047] Preferred Hemiptera pests include Aphididae, Aphididae or Phylloxera (preferably Aphididae); Leafhoppers, Whitefly, Pentatomidae or Coccoidea (Shield Scale, Arachnidae, Ichthyophthirius, Bessicidae, Coccoidea, Glechococcidae, Mealycocodidae, Lecanococcidae, Meatcocodidae, Chain Scale, Beesonidae, Chain Scale or Cypericocodidae); and Psyllidae, more preferably Myzus persicae, Aphid cotton, Tea green leafhopper, Bemisia tabaci, Whitefly greenhouse, Trigonotylus caelestialium or Consoni mealybug, Red round scale and Citrus psyllid.

[0048] When the compound represented by formula I is used as a harmful organism control agent, the compound represented by formula I can be used directly. Alternatively, the compound represented by formula I can be mixed with suitable agricultural or animal husbandry acceptable carriers such as solid carriers, liquid carriers and gaseous carriers, surfactants, dispersants or other adjuvants for formulation to prepare any suitable formulation, such as emulsifiable concentrates, EW (oil-in-water emulsions), liquid formulations, suspensions, wettable powders, water-dispersible granules, dusts, DL powders, granules, granules, tablets, oils, aerosols, sols (floable), xerosols or microcapsules.

[0049] Solid carriers include, for example, talc, bentonite, clay, kaolin, diatomaceous earth, vermiculite, white carbon or calcium carbonate.

[0050] Liquid carriers include, for example, alcohols such as methanol, n-hexanol or ethylene glycol; ketones such as acetone, methyl ethyl ketone or cyclohexanone; aliphatic hydrocarbons such as n-hexane, kerosine or kerosene; aromatic hydrocarbons such as toluene, xylene or methylnaphthalene; ethers such as diethyl ether, dioxane or tetrahydrofuran; esters such as ethyl acetate; nitriles such as acetonitrile or isobutyronitrile; amides such as dimethylformamide or dimethylacetamide; vegetable oils such as soybean oil or cottonseed oil; dimethyl sulfoxide; or water.

[0051] Gaseous carriers include, for example, LPG, air, nitrogen, carbon dioxide and dimethyl ether.

[0052] Surfactants or dispersants that can be used, for example, for emulsification, dispersion or spreading include, for example, alkyl sulfates, alkyl (aryl) sulfonates, polyoxyalkylene alkyl (aryl) ethers, polyol esters and lignin sulfonates. Auxiliary agents that can be used to improve the performance of formulations include, for example, carboxymethyl cellulose, gum arabic, polyethylene glycol and calcium stearate.

[0053] The above-mentioned carriers, surfactants, dispersants and adjuvants may be used alone or in combination as required.

[0054] The content of the active ingredient in these formulations is not particularly limited but is preferably 1-75% by weight for emulsifiable concentrates, 0.3-25% by weight for dusts, 1-90% by weight for wettable powders and 0.5-10% by weight for granules.

[0055] According to another aspect of the present invention, a method for controlling pests is provided, the method comprising applying an effective amount of a compound represented by formula I or a salt thereof to a surface selected from the group consisting of water, soil, nutrient solution in nutrient solution culture, solid medium in nutrient solution culture, and seeds, roots, tubers, bulbs and rhizomes of plants.

[0056] According to one embodiment of the present invention, there is provided a method for controlling harmful organisms, the method comprising applying an effective amount of a compound represented by Formula I or a salt thereof to harmful organisms or their habitats. According to a preferred embodiment of the present invention, there is provided a method for controlling harmful organisms, the method comprising applying an effective amount of a compound represented by Formula I or a salt thereof to plants or soil.

[0057] The compound represented by formula I or its salt directly plays a strong control effect on harmful organisms. In addition, it can be expected that the control effect played by the compound as a mixture with other harmful organism control agents is higher than the control effect reached when only using the compound or other harmful organism control agents. Therefore, according to the present invention, a kind of harmful organism control composition comprising at least one compound represented by formula I or its salt and at least one other harmful organism control agent is provided. In addition, according to another embodiment of the present invention, the harmful organism control composition is provided for protecting useful plants (cultivated plants) from harmful organisms. In addition, according to another embodiment, the harmful organism control composition is provided for preparing a reagent for protecting useful plants (cultivated plants) from harmful organisms.

[0058] The compositions or compounds useful as pest control agents of the present invention or their blends with other pest control agents are used to control a wide variety of pests on various plants. Target plants include wheat and barley, coarse grains such as corn, millet, millet, barnyard grass and edible sorghum, fruit trees such as orange, apple and grape, vegetables such as cucumber, pumpkin, melon, cabbage, eggplant, tomato and strawberry, tubers such as potato, sweet potato and taro, legumes such as red bean, kidney bean and soybean, oil crops such as rapeseed, fodder crops such as animal feed grass, sorghum and corn, ornamental plants, foliage plants, timber, tea, sugar beet, sugar cane, sunflower, hops, cotton, tobacco, Arabic coffee, turf grass and edible mushrooms.

[0059] The composition or compound useful as the pest control agent of the present invention or its blend with other pest control agents can be applied to pests, plants and plant propagation materials, specifically, for example, seeds, plant leaves, roots, soil, water surface, cultivation materials and spaces where pests should be prevented from entering. Treatment with the compounds, blends and compositions of the present invention can be carried out before and after pests enter.

[0060] The present invention includes killing animal parasitic harmful organisms. Killing of harmful organisms can be carried out by applying to habitats, livestock farms, feed, plants, seeds, soils, materials and growth environments where animal parasitic harmful organisms grow or will grow, or materials, plants, seeds, soils and water surfaces where animal parasitic harmful organisms should be prevented from entering.

[0061] The plant propagation material to which the present invention is applied refers to a plant having the ability to reproduce in plant growth, including but not limited to seeds, branches or lops, and the pullout part of a tuber, specifically seeds, roots, fruits, tubers, bulbs, underground stems, roots, branches and buds. It also includes rice seedlings or seedlings transplanted after germination or rooting. For prevention, plant protection agents are applied to these plant propagation materials during settled plating or transplanting.

[0062] The term "cultivated plants" is to be understood as including plants that have been modified by breeding, mutagenesis and / or genetic engineering. Genetically modified plants (GMOs) are plants whose genetic material has been modified by the use of recombinant DNA techniques that are not readily obtained under natural conditions by hybridization, mutation or natural recombination. One or more genes are usually integrated into the genetic material of a genetically modified plant in order to improve certain properties of the plant. Such genetic modifications also include, but are not limited to, targeted post-translational modifications of proteins (oligo- or polypeptides), for example by glycosylation or polymer addition such as prenylated, acetylated or farnesylated moieties or PEG moieties (e.g. as disclosed in Biotechnol Prog. 2001 Jul-Aug; 17(4):720-8., Protein Eng Des Sel. 2004 Jan; 17(1):57-66, Nat Protoc. 2007; 2(5):1225-35., Curr Opin Chem Biol. 2006 Oct; 10(5):487-91. Epub 2006 Aug 28, Biomaterials. 2001 Mar; 22(5):405-17, Bioconjug Chem. 2005 Jan-Feb; 16(1):113-21).

[0063] The term "cultivated plants" is to be understood as also including plants that have been made tolerant to the application of special classes of herbicides, such as hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors; acetolactate synthase (ALS) inhibitors, for example sulfonylureas (see, for example, US 6,222,100, WO 01 / 82685, WO 00 / 26390, WO 97 / 41218, WO 98 / 02526, WO 98 / 02527, WO 04 / 106529, WO 05 / 20673, WO 03 / 14357, WO 03 / 13225, WO 03 / 14356, WO 04 / 16073) or imidazolinones (see, for example, US 6,222,100, WO 01 / 82685, WO 00 / 26390, WO97 / 41218, WO98 / 02526, WO 98 / 02527, WO 04 / 106529, WO 05 / 20673, WO 03 / 14357, WO 03 / 13225, WO 03 / 14356, WO 04 / 16073); Enolpyruvylshikimate 3-phosphate synthase (EPSPS) inhibitors, such as glyphosate (glyphosate) (see, for example, WO 92 / 00377); Glutamine synthetase (GS) inhibitors, such as glufosinate (glufosinate) (see, for example, EP-A-0242236, EP-A-242246) or oxynil herbicides (see, for example, US5,559,024). Plants tolerant to these herbicides can be obtained by conventional breeding or genetic engineering methods.

[0064] Several cultivated plants have been made tolerant to herbicides by conventional breeding (mutagenesis) methods, for example Clearfield (registered trademark) summer rapeseed (Canola), which tolerates imidazolinones such as imazamox. Genetic engineering methods have been used to make cultivated plants such as soybean, cotton, corn, sugar beet and rape tolerant to herbicides such as glyphosate and glufosinate, some of which are available under the trade names RoundupReady (registered trademark) (tolerant to glyphosate) and LibertyLink (registered trademark) (tolerant to glufosinate).

[0065] The term "cultivated plants" is to be understood as also including plants that are capable of synthesizing one or more insecticidal proteins by the use of recombinant DNA techniques, such as delta-endotoxins, for example CryIA(b), CryIA(c), CryIF, CryIF(a2), CryIIA(b), CryIIIA, CryIIIB(b1) or Cry9c; asexual insecticidal proteins (VIP), for example VIP1, VIP2, VIP3 or VIP3A; insecticidal proteins of nematode-colonizing bacteria, for example Photorhabdus spp. or Xenorhabdus spp. spp.); toxins produced by animals such as scorpion toxins, spider toxins, wasp toxins or other insect-specific neurotoxins; toxins produced by fungi, such as Streptomycetes toxins; plant lectins, such as pea or barley lectins; lectins, protease inhibitors, such as trypsin inhibitors, serine protease inhibitors, patatin, cysteine ​​protease inhibitors or papain inhibitors, ribosome inactivating proteins (RIPs), such as ricin, maize-RIP, abrin, luffa seed protein, saporin or bryodin; steroid metabolizing enzymes, such as 3-hydroxysteroid oxidase, ecdysteroid-IDP glycosyltransferase, cholesterol oxidase, ecdysone inhibitor or HMG-CoA reductase; ion channel blockers, such as sodium channel or calcium channel blockers; juvenile hormone esterase; diuretic hormone receptor (helicokinin receptor); synthase, bibenzyl synthase, chitinase or glucanase.

[0066] In the context of the present invention, these insecticidal proteins or toxins are also to be understood in particular as pretoxins, hybrid proteins, truncated or otherwise modified proteins.

[0067] Hybrid toxins are produced by recombinant technology using novel combinations of protein domains (see, for example, WO 02 / 015701). Other examples of such toxins or genetically modified plants capable of synthesizing such toxins are disclosed, for example, in EP-A 374753, WO 93 / 007278, WO 95 / 34656, EP-A 427529, EP-A 451878, WO 03 / 018810 and WO 03 / 052073. The methods for producing these genetically modified plants are generally known to those skilled in the art and are described, for example, in the above-mentioned publications.

[0068] These insecticidal proteins contained in genetically modified plants confer resistance to certain taxonomic arthropod pests, especially beetles (Coleoptera), dipteran pests (Diptera), butterflies and moths (Lepidoptera) and plant-parasitic nematodes (Nematoda) on the plants producing these proteins.

[0069] The term "cultivated plants" is to be understood as also including plants which are able to synthesize one or more proteins which increase tolerance to bacterial, viral or fungal pathogens by using recombinant DNA technology. Examples of such proteins are so-called "pathogenesis-related proteins" (PR proteins, see, for example, EP-A 0 392 22), plant disease resistance genes (e.g. potato cultivars expressing resistance genes acting against Phytophthora infestans from the wild Mexican potato Solanum bulbocastanum) or T4 lysozyme (e.g. potato cultivars which are able to synthesize these proteins and have increased tolerance to bacteria such as Erwinia amylvora). Methods for producing such genetically modified plants are generally known to those skilled in the art and are described, for example, in the above-mentioned publications.

[0070] The term "cultivated plants" is to be understood as also including plants which are capable, by the use of recombinant DNA techniques, of synthesizing one or more proteins to increase yield (e.g. biomass yield, grain yield, sugar content, oil content or protein content), tolerance to drought, salt or other growth-limiting environmental factors, or tolerance to pests and fungal, bacterial or viral pathogens thereof.

[0071] The term "cultivated plants" is to be understood as also including plants which have altered or novel content of substances, in particular for improved human or animal nutrition, by the use of recombinant DNA technology, for example oil crops which produce health-promoting long-chain ω-3 fatty acids or unsaturated ω-9 fatty acids (e.g. Nexera (registered trademark) rapeseed).

[0072] The term "cultivated plants" is to be understood as also including plants which have altered or novel substance contents, in particular by the use of recombinant DNA techniques, in particular for improved raw material production, for example potatoes with an increased amylopectin content (eg Amflora (registered trademark) potatoes).

[0073] The preferred method of applying the compound represented by Formula I or the composition comprising the compound as a pest control agent to plants or soil includes spreading treatment, soil treatment, surface treatment or fumigation treatment. The example of spreading treatment includes spreading, spraying (spraying), spraying (misting), atomization (atomizing), granule application or water surface application. The example of soil treatment includes soil perfusion or soil mixing. The example of surface treatment includes coating, dust coating (dust coating) or covering. In addition, the example of fumigation treatment includes covering the soil with a polyethylene film after injecting the soil. Therefore, the control method of the present invention also includes a method in which the compound represented by Formula I or the preparation comprising the compound is applied by fumigation treatment in a confined space.

[0074] Other harmful biological control agents that can be incorporated into the compound represented by Formula I or its salt include insecticides, fungicides, miticides or tickicides, herbicides and plant growth regulators. Specific agents include, for example, those described in

[0075] The Pesticide Manual, 13th edition, published by The British Crop Protection Council; and those in SHIBUYA INDEX, 14th edition, 2009, published by SHIBUYA INDEX RESEARCH GROUP. More specific examples thereof are M.1.-M.27. described below:

[0076] M.1. Organophosphate insecticides: acephate, azamethiphos, azinphos-ethyl, azinphos-methyl, chlorethoxyfos, chlorfenapyr

[0077] (chlorfenvinphos), chlormephos, chlorpyrifos, chlorpyrifos-methyl, coumaphos, cyanophos, demeton-S-methyl, diazinon, dichlorvos / DDVP, dicrotophos, dimethoate, dimethylvinphos, disulfoton, EPN, ethion, ethoprophos, famphur, fenamiphos, fenitrothion, fenthion, flupyrazophos, fosthiazate, heptenophos, isoxathion, malathion, mecarbam, methamidophos, methidathion, mefenphos mevinphos, monocrotophos, naled, omethoate, oxydemeton-methyl, parathion, parathion-methyl, phenthoate, phorate, phosalone, phosmet, phosphamidon, phoxim, pirimiphos-methyl, profenofos nofos), propetamphos, prothiofos, pyraclofos, pyridaphenthion, quinalphos, sulfotep, tebupirimfos, temephos, terbufos, tetrachlorvinphos, thiometon, triazophos, trichlorfon, and vamidothion;

[0078] M.2. Carbamate insecticides: aldicarb, alanycarb, bendiocarb, benfuracarb, butocarboxim, butoxycarboxim, carbaryl, carbofuran, carbosulfan, ethiofencarb, fenobucarb, formetanat e), furathiocarb, isoprocarb, methiocarb, methomyl, metolcarb, oxamyl, pirimicarb, propoxur, thiodicarb, thiofanox, trimethacarb, XMC, xylylcarb and triazamate;

[0079] M.3. Synthetic pyrethroid insecticides: acrinathrin, allethrin, d-cis-trans allethrin, d-trans allethrin, bifenthrin, bioallethrin, bioallethrin S-cylclopentenyl, bioresmethrin, cycloprothrin, cyfluthrin, β-cyfluthrin, (RS) cyhalothrin, λ-(RS) cyhalothrin, γ-(RS) cyhalothrin, cypermethrin, alpha-cypermethrin

[0080] alpha-cypermethrin, beta-cypermethrin, theta-cypermethrin, zeta-cypermethrin, cyphenothrin, deltamethrin, empenthrin, esfenvalerate, etofenprox, fenpropathrin, fenvalerate, flucythrinate, flumethrin, fluvalinate u-fluvalinate), halfenprox, imiprothrin, metofluthrin, permethrin, phenothrin, prallethrin, profluthrin, pyrethrin (pyrethrum), resmethrin, silafluofen, tefluthrin, tetramethrin, tralomethrin and transfluthrin;

[0081] M.4. Juvenile hormone mimics: hydroprene, kinoprene, methoprene, fenoxycarb and pyriproxyfen;

[0082] M.5. Nicotinic receptor agonist / antagonist compounds: acetamiprid, bensultap, cartap hydrochloride, clothianidin, dinotefuran, imidacloprid, thiamethoxam, nitenpyram, nicotine, spinosad (allosteric agonist), spinetoram (allosteric agonist), thiacloprid, thiocyclam, thiosultap-sodium and AKD1022;

[0083] M.6. GABA-gated chloride channel antagonist compounds: chlordane, endosulfan, gamma-HCH, ethiprole, fipronil, pyraflprole and pyriprole;

[0084] M.7. Chloride channel activators: abamectin, emamectinbenzoate, milbemectin, lepimectin;

[0085] M.8.METI I compounds: fenazaquin, fenpyroximate, pyrimidifen, pyridaben, tebufenpyrad, tolfenpyrad, flufenerim and rotenone;

[0086] M.9.METI II compounds: acequinocyl, fluacyprim and hydramethylnon;

[0087] M.10. Uncoupler for oxidative phosphorylation: chlorfenapyr, dinitrocresol (DNOC);

[0088] M.11. Other oxidative phosphorylation inhibitors: azocyclotin, cyhexatin, diafenthiuron, fenbutatin oxide, propargite and tetradifon;

[0089] M.12. Moulting disruptors: cryomazine, chromafenozide, halofenozide, methoxyfenozide and tebufenozide;

[0090] M.13. Synergists: piperonyl butoxide, tribufos;

[0091] M.14. Sodium channel blocker compounds: indoxacarb and metaflumizone;

[0092] M.15. Fumigants: methyl bromide, chloropicrin, sulfuryl fluoride

[0093] M.16. Selective feeding blockers: crylotie, pymetrozine and flonicamid;

[0094] M.17. Mite growth inhibitors: clofentezine, hexythiazox and etoxazole;

[0095] M.18. Chitin synthesis inhibitors: buprofezin, bistrifluron, chlorfluazuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, teflubenzuron and triflumuron;

[0096] M.19. Lipid biosynthesis inhibitors: spirodiclofen, spiromesifen and spirotetramat;

[0097] M.20. Octapamine agonists: amitraz;

[0098] M.21. ryanodine receptor modulators: flubendiamide and phtalamid compounds (R)-, (S)-3-chloro-N1-{2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl}-N2-(1-methyl-2-methylsulfonylethyl)phthalamide (M21.1);

[0099] M.22. Isoxazoline compounds: 4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-N-pyridin-2-ylmethyl-benzamide (M22.1), 4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-N-(2,2,2-trifluoroethyl)-benzamide (M22.2), 4 -[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-N-[(2,2,2-trifluoroethylcarbamoyl)-methyl]-benzamide (M22.3), 4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-naphthalene-1-carboxylic acid [(2,2,2-trifluoroethylcarbamoyl)-methyl]-amide (M22.4), .4), 4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-N-[(methoxyimino)methyl]-2-methylbenzamide (M22.5), 4-[5-(3-chloro-5-trifluoromethyl-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-N-[(2,2,2-trifluoroethylcarbamoyl)-methyl]-benzamide (M22 .6), 4-[5-(3-chloro-5-trifluoromethyl-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-naphthalene-1-carboxylic acid [(2,2,2-trifluoroethylcarbamoyl)-methyl]-amide (M22.7) and 5-[5-(3,5-dichloro-4-fluorophenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-[1,2,4]triazol-1-yl-benzonitrile (M22.8);

[0100] M.23. Anthranilamide compounds: chloranthraniliprole, cyantraniliprole; 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carboxylic acid [4-cyano-2-(1-cyclopropyl-ethylcarbamoyl)-6-methylphenyl]-amide (M23.1), 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carboxylic acid [2-chloro-4-cyano-6-(1-cyclopropyl-ethylcarbamoyl)-phenyl]-amide (M23.2), 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carboxylic acid [2-chloro-4-cyano-6-(1-cyclopropyl-ethylcarbamoyl)-phenyl]-amide (M23.3), 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carboxylic acid [2-chloro-4-cyano-6-(1-cyclopropyl-ethylcarbamoyl)-phenyl]-amide (M23.4), 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carboxylic acid [2-chloro-4-cyano-6-(1-cyclopropyl-ethylcarbamoyl)-phenyl]-amide (M23.5), 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carboxylic acid [2-chloro-4-cyano-6-(1-cyclopropyl-ethylcarbamoyl)-phenyl]-amide (M23.6), 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carboxylic acid [2-chloro-4-cyano-6-(1-cyclo -2H-pyrazole-3-carboxylic acid [2-bromo-4-cyano-6-(1-cyclopropyl-ethylcarbamoyl)-phenyl]-amide (M23.3), 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carboxylic acid [2-bromo-4-chloro-6-(1-cyclopropyl-ethylcarbamoyl)-phenyl]-amide (M23.4), 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carboxylic acid [2,4-dichloro-6-(1-cyclopropyl-ethylcarbamoyl)-phenyl]-amide (M23.5), 5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carboxylic acid [4-chloro-2-(1-cyclopropyl-ethylcarbamoyl)-phenyl]-amide 1-[(2-{[5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl]-amino}-5-chloro-3-methylbenzoyl)-N'-methylhydrazinecarboxylic acid methyl ester (M23.7), N'-(2-{[5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl]-amino}-5-chloro-3-methylbenzoyl)-N'-methylhydrazinecarboxylic acid methyl ester (M23.8), N'-(2-{[5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl]-amino}-5-chloro-3-methylbenzoyl)-N,N'-dimethyl Methyl hydrazinecarboxylate (M23.9), methyl N'-(3,5-dibromo-2-{[5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl]-amino}-benzoyl)-hydrazinecarboxylate (M23.10), methyl N'-(3,5-dibromo-2-{[5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl]-amino}-benzoyl)-N'-methylhydrazinecarboxylate (M23.11) and methyl N'-(3,5-dibromo-2-{[5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl]-amino}-benzoyl)-N,N'-dimethylhydrazinecarboxylate (M23.12);

[0101] M.24. Malononitrile compounds: 2-(2,2,3,3,4,4,5,5-octafluoropentyl)-2-(3,3,3-trifluoropropyl)-malononitrile (CF2H-CF2-CF2-CF2-CH2-C(CN)2-CH2-CH2-CF3) (M24.1) and 2-(2,2,3,3,4,4,5,5-octafluoropentyl)-2-(3,3,4,4,4-pentafluorobutyl)-malononitrile (CF2H-CF2-CF2-CF2-CH2-C(CN)2-CH2-CH2-CF2-CF3) (M24.2);

[0102] M.25. Microbial disruptors: Bacillus thuringiensis subsp. Israelensi, Bacillus sphaericus, Bacillus thuringiensis subsp. Aizawai, Bacillus thuringiensis subsp. Kurstaki, Bacillus thuringiensis subsp. Tenebrionis;

[0103] M.26. Aminofuranone compounds: 4-{[(6-bromopyridin-3-yl)methyl](2-fluoroethyl)amino}furan-2(5H)-one (M26.1), 4-{[(6-fluoropyridin-3-yl)methyl](2,2-difluoroethyl)amino}furan-2(5H)-one (M26.2), 4-{[(2-chloro1,3-thiazol-5-yl)methyl](2-fluoroethyl)amino}furan-2(5H)-one (M26.3), 4-{[(6-chloropyridin-3-yl)methyl](2-fluoroethyl)amino}furan-2(5H)-one (M26.4), 4-{[(6-chloropyridin-3-yl)methyl](2,2-difluoroethyl)amino}furan-2(5 H)-one (M26.5), 4-{[(6-chloro-5-fluoropyridin-3-yl)methyl](methyl)amino}furan-2(5H)-one (M26.6), 4-{[(5,6-dichloropyridin-3-yl)methyl](2-fluoroethyl)amino}furan-2(5H)-one (M26.7), 4-{[(6-chloro-5-fluoropyridin-3-yl)methyl](cyclopropyl)amino}furan-2(5H)-one (M26.8), 4-{[(6-chloropyridin-3-yl)methyl](cyclopropyl)amino}furan-2(5H)-one (M26.9) and 4-{[(6-chloropyridin-3-yl)methyl](methyl)amino}furan-2(5H)-one (M26.10);

[0104] M.27. Other insecticides: aluminum phosphide, amidoflumet, benclothiaz, benzoximate, bifenazate, borax, bromopropylate, cyanide, cyenopyrafen, cyflumetofen, chinomethionate, dicofol, fluoroacetate, phosphine, pyridalyl, pyrifluquinazon, sulfur, organic sulfur compounds, tartaremetic, sulfoxaflor, N-R'-2,2-dihalo-1-R"cyclopropanecarboxamide-2-(2,6-dichloro-α,α,α-trifluorotolyl)hydrazone or N-R'-2,2-bis(R"')propionamide-2-(2,6-dichloro-α,α,α -trifluoro-p-tolyl)-hydrazone, wherein R' is methyl, ethyl or a halogen selected from chlorine or bromine, R" is a hydrogen atom or a methyl group and R"' is methyl or ethyl, 4-but-2-ynyloxy-6-(3,5-dimethyl-piperidin-1-yl)-2-fluoropyrimidine (M27.1), cyclopropaneacetic acid, 1,1'-[(3S,4R,4aR,6S,6aS,12R,12aS,12bS)-4-[[(2-cyclopropylacetyl)oxy]methyl]-1,3,4, 4a,5,6,6a,12,12a,12b-decahydro-12-hydroxy-4,6a,12b-trimethyl-11-oxo-9-(3-pyridyl)-2H,11H-naphtho[2,1-b]pyrano[3,4-e]pyran-3,6-diyl]ester (M27.2) and 8-(2-cyclopropylmethoxy-4-trifluoromethylphenoxy)-3-(6-trifluoromethylpyridazin-3-yl)-3-azabicyclo[3.2.1]octane (M27.3).

[0105] Paraoxon and its preparation are described in Farm Chemicals Handbook, Vol. 88, Meister Publishing Company, 2001. Flupyrazofos is described in

[0106] Pesticide Science 54, 1988, pp. 237-243 and US 4822779. AKD 1022 and its preparation are described in US 6300348. Anthranilic acid amides M23.1-M23.6 are described in WO 2008 / 72743 and WO 200872783, those M23.7-M23.12 are described in WO 2007 / 043677. Phthalic acid amide M 21.1 is known from WO 2007 / 101540. Alkyne ether compound M27.1 is described, for example, in JP 2006131529. Organosulfur compounds are described in WO 2007060839. Isoxazolines M 22.1 to M 22.8 are described, for example, in WO 2005 / 085216, WO 2007 / 079162, WO 2007 / 026965, WO 2009 / 126668 and WO 2009 / 051956. Aminofuranones M 26.1 to M 26.10 are described, for example, in WO 2007 / 115644. Pyripyropene derivatives M 27.2 are described in WO 2008 / 66153 and WO 2008 / 108491. Pyridazine compounds M 27.3 are described in JP 2008 / 115155. Malononitrile compounds such as those (M24.1) and (M24.2) have been described in WO 02 / 089579, WO 02 / 090320, WO 02 / 090321, WO 04 / 006677, WO 05 / 068423, WO 05 / 068432 and WO 05 / 063694.

[0107] In one embodiment, the insecticidal composition comprises a biologically effective amount of at least one of the pyripyropene derivatives (component A), and at least one other active ingredient (component B) selected from the following compounds:

[0108] (1) Acetylcholinesterase (AChE) inhibitors: chlorpyrifos (CAS No.: 2921-88-2), acephate (CAS No.: 30560-19-1);

[0109] (2) GABA-gated chloride channel antagonist: fipronil (CAS No. 120068-37-3);

[0110] (3) Sodium channel regulators: highly effective cyhalothrin (CAS No.: 91465-08-6), bifenthrin (CAS No.: 82657-04-3), deltamethrin (CAS No.: 52918-63-5), highly effective cypermethrin (CAS No.: 1224510-29-5), cis-cypermethrin (CAS No.: 67375-30-8);

[0111] (4) Competitive modulators of nicotinic acetylcholine receptor (nAChR): imidacloprid (CAS No.: 138261-41-3), thiamethoxam (CAS No.: 153719-23-4), acetamiprid (CAS No.: 135410-20-7), furodifloxacin (CAS No.: 165252-70-0), clothianidin (CAS No.: 210880-92-5), sulfoxaflor (CAS No.: 946578-00-3), flupyralidone (CAS No.: 951659-40-8), thiamethoxam (CAS No.: 111988-49-9), trifluanid (CAS No.: 1263133-33-0), and pyrimidine (CAS No.: 948994-16-9);

[0112] (5) Allosteric modulators of glutamate-gated chloride channels (GluCl): avermectin (CAS No. 71751-41-2), avermectin benzoate (CAS No. 155569-91-8);

[0113] (6) Bionic juvenile hormone: pyriproxyfen (CAS No.: 95737-68-1);

[0114] (7) Nicotinic acetylcholine receptor (nAChR) channel blocker: cartap (CAS No.: 15263-53-3);

[0115] (8) Chitin biosynthesis inhibitors (type 1): buprofezin (CAS No.: 69327-76-0), spiromesifen (CAS No.: 283594-90-1);

[0116] (9) Acetyl CoA carboxylase inhibitors: spirotetramat (CAS No.: 203313-25-1), methoxyfenapyr (CAS No.: 1229023-00-0);

[0117] (10) Nicotinic acid receptor modulator: cyantraniliprole (CAS No.: 736994-63-1);

[0118] (11) String modulators - unknown target sites: flonicamid (CAS No.: 158062-67-0), anthracene (CAS No.: 1403615-77-9);

[0119] (12) GABA-gated chloride channel allosteric modulators: bromofenac (CAS No. 1207727-04-5), flufenac (CAS No. 928783-29-3), isoxathiapiprole (CAS No. 2061933-85-3), and compound W (CAS No. 2892524-05-7);

[0120] (13) Nicotinic acetylcholine receptor (nAChR) allosteric modulator: spinosad (CAS No.: 168316-95-8);

[0121] (14) Others: Metarhizium anisopliae.

[0122] In another specific embodiment, the weight ratio of the active ingredients A and B in the insecticidal composition is 1:150-150:1, 1:100-100:1, 1:80-80:1, 1:60-60:1, 1:40-40:1, 1:20-20:1, 1:10-10:1, 1:8-8:1, 1:5-5:1 or 1:3-1:1.

[0123] The term "biologically effective amount" refers to an amount of a biologically active compound (e.g., a compound of Formula I) sufficient to produce the desired biological effect when applied to (i.e., contacted with) the pest to be controlled or its environment, or the plant, the seed from which the plant grows, or the locus of the plant (e.g., the growth medium), thereby protecting the plant from damage by the pest or achieving other desired effects (e.g., increasing plant vigor). The compounds of the present invention can also be applied preventively to locations where pests or parasites are expected to appear.

[0124] The present invention also provides a method for preparing the pyripyropene derivative, which comprises the following steps: Made for the intermediate system.

[0125] In a specific embodiment, the method comprises at least one of the following steps (the specific steps are selected according to the structure of the target product):

[0126]

[0127] Wherein, the definitions of X1, X2, X3, X4 and R3 are as described above.

[0128] Wherein, the reactions in step 1 and step 3 are both carried out in the presence of a solvent and a base; the reactions in step 2, step 5 and step 9 are carried out in the presence of a solvent, preferably, a condensing agent is added during the reactions in step 2, step 5 and step 9, with or without the addition of a base; the reaction in step 4 is carried out in the presence of an oxidant and a solvent; the reaction in step 6 is carried out in the presence of an acidic catalyst and a solvent; the reaction in step 7 is carried out in the presence of an organic base and a solvent; the reaction in step 8 is carried out in the presence of an acid (such as acetic acid) and a solvent; the reaction in step 10 is carried out in the presence of pyridine hydrofluoride and a solvent.

[0129] In another specific embodiment, the solvent is selected from at least one of water, THF, pyridine, DMF, DMA, methanol, ethanol, acetonitrile, dichloroethane, DMSO, Dioxane, dichloromethane (DCM) or ethyl acetate.

[0130] In another specific embodiment, the base is selected from at least one of an inorganic base (such as K2CO3, Na2CO3, Cs2CO3, NaHCO3, KHCO3, KF, CsF, KI, NaI, K3PO4, K2HPO4, NaOH, KOH, NaH, KH, etc.) or an organic base (such as DBU, DMAP, imidazole, pyrazole, triethylamine, DIEA, potassium trimethylsilanolate, AcOK, AcONa, MeONa, EtONa, t-BuONa, etc.).

[0131] In another specific embodiment, the condensing agent is selected from at least one of Py-BOP, Py-AOP, HOBT (1-hydroxybenzotriazole), EDCI (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride), DMAP (4-dimethylaminopyridine), DCC, HBTU or HATU.

[0132] In another specific embodiment, the oxidant is a Dess-Martin oxidant or a PCC oxidant.

[0133] In another specific embodiment, the acidic catalyst is pyridinium p-toluenesulfonate (PPTS) or p-toluenesulfonic acid.

[0134] In another specific embodiment, the compound II is prepared by fermenting Pseudomonas sartorii with pentafluoronicotinic acid as a substrate.

[0135] In addition, the compounds of the present invention can also be prepared by referring to the methods shown in WO2011093186, WO2010010955, WO2011148886, etc.

[0136] The present invention also provides an intermediate, as shown in Formula II.

[0137] The present invention also provides a method for preparing the pyripyropene derivative, comprising: It is prepared by reduction reaction, wherein X1, X2, X3, X4, Y1, Y2, R1 and R2 are as defined above.

[0138] In a specific embodiment, the reduction reaction is carried out in the presence of sodium borohydride and a solvent, and preferably, cerium trichloride can be added.

[0139] In another specific embodiment, the solvent is selected from at least one of THF, DMF, DMA, methanol, ethanol, acetonitrile, dichloroethane, DMSO, Dioxane, dichloromethane or ethyl acetate.

[0140] The present invention also provides an intermediate, as shown in formula III.

[0141] According to another aspect of the present invention, there is provided use of a compound represented by formula I or an agriculturally or zootechnically acceptable salt thereof as a pest control agent. DETAILED DESCRIPTION

[0142] The following examples are used to illustrate the present invention and should not be considered to limit the present invention in any way. The scope of the rights required to be protected by the present invention is described by the claims.

[0143] In view of the economic efficiency and diversity of the compounds, we preferably synthesized some compounds, and among the many synthesized compounds, some are selected and listed in the following Table 1. The specific compound structures and corresponding compound information are shown in Table 1. The compounds in Table 1 are only for better illustrating the present invention, but not for limiting the present invention. For those skilled in the art, this should not be understood as the scope of the above subject matter of the present invention is limited to the following compounds.

[0144] Table 1 Compound structures and 1 H NMR values

[0145]

[0146]

[0147]

[0148]

[0149]

[0150]

[0151]

[0152]

[0153]

[0154]

[0155]

[0156] Several methods for preparing the compounds of the present invention are described in detail in the following schemes and examples. The raw materials can be purchased from the market or can be prepared by methods known in the literature or as shown in the detailed description. It will be appreciated by those skilled in the art that other synthetic routes can also be used to synthesize the compounds of the present invention. Although the specific raw materials and conditions in the synthetic route have been described below, it can be easily replaced with other similar raw materials and conditions, and these modifications or variations of the preparation method of the present invention such as various isomers of the compound are included within the scope of the present invention. In addition, the preparation method described below can be further modified according to the disclosure of the present invention using conventional chemical methods well known to those skilled in the art. For example, appropriate groups are protected during the reaction, etc.

[0157] The method examples provided below are used to promote further understanding of the preparation method of the present invention. The specific substances, types and conditions used are determined to further illustrate the present invention and are not intended to limit its reasonable scope. The reagents used in the synthetic compounds shown in the following table can be purchased commercially or can be easily prepared by a person of ordinary skill in the art.

[0158] Examples of representative compounds are as follows. The synthesis methods of other compounds are similar and will not be described in detail here.

[0159] 1. Synthesis of compounds 5 and 38

[0160] (1) Fermentation production of compound 38

[0161] Pseudofibrilla neosartorii was used for fermentation with pentafluoronicotinic acid as substrate, and then the fermentation liquid was filtered to collect the bacteria, methanol was added for stirring, filtered, and the methanol extract of the bacteria was collected, and the oily concentrate was obtained by vacuum concentration. Compound 38 was obtained by normal phase silica gel column chromatography.

[0162] (2) Compound 38 (30 mg) was dissolved in methanol (2 ml), and 30% sodium methoxide solution (72 mg, 8 eq) was added, followed by stirring at room temperature overnight. The reaction was monitored by central control to ensure complete reaction of the raw material, and then an aqueous ammonium chloride solution (0.2 ml) was added to the system to quench the reaction. After the reaction solution was dried, the obtained solid was dissolved in ethyl acetate (4 ml), filtered, and the obtained solid after the filtrate was dried was washed with a small amount of water to remove the residual ammonium chloride. The obtained solid was dried to obtain compound 5-2 (23 mg, yield 97%).

[0163]

[0164] (3) 5-2 (23 mg) was dissolved in dichloromethane (5 ml), and 4-dimethylaminopyridine (35 mg, 6 eq), triethylamine (29 mg, 6 eq), cyclopropionic acid (58 mg, 14 eq) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (110 mg, 12 eq) were added to the system in sequence under stirring at room temperature. After reacting for 1 hour, the reaction was monitored to be complete. Water (2 ml) was added to the system, and the layers were separated. The dichloromethane phase was washed with 0.05 M hydrochloric acid, sodium bicarbonate and sodium chloride in sequence. The obtained organic phase was spin-dried and purified by normal phase silica gel column chromatography to obtain compound 5-3 (32 mg, yield 97%).

[0165]

[0166] (4) 5-3 (32 mg) was dissolved in methanol (5 ml), and a small amount of water and 1,8-diazabicyclo[5.4.0]undec-7-ene (8 mg, 1.1 eq) were added to the system in sequence. The reaction was stirred at room temperature for 2 h. The reaction of the raw materials was completed during central control monitoring. Compound 5 (13 mg, yield 45%) was purified by normal phase silica gel column chromatography.

[0167]

[0168] 2. Synthesis of Compound 9

[0169] (1) Under ice bath, TMEDA (0.1 eq) was added to a nitrogen-protected three-necked flask, LHMDS (5 eq) was added dropwise, and the mixture was kept warm for 10 minutes. A THF solution of compound 9-1 (1 g) was added, and the mixture was kept warm for half an hour and then heated to room temperature for 1 hour. Under ice bath, a THF solution of 9-2 (3 eq) was added to the system and kept warm for 1 hour. After the reaction, the reaction solution was poured into an aqueous ammonium chloride solution, extracted with ethyl acetate, and the organic phase was dried and concentrated, and purified by normal phase to obtain 430 mg of compound 9-3 with a yield of 34%.

[0170]

[0171] (2) Compound 9-3 (430 mg) was reacted in an oil bath at 150°C for 15 min under a negative pressure of 0 mmHg to obtain a crude compound 9-4, which was directly used in the next step.

[0172]

[0173] (3) The crude compound 9-4 was dissolved in 10 mL THF, and 10 mL 80% acetic acid solution was added and stirred at room temperature. After the reaction of the raw materials was completed, the reaction solution was poured into a saturated sodium bicarbonate solution under ice bath, extracted with ethyl acetate, and the organic phase was dried and concentrated to obtain 380 mg of the crude compound 9-5, with a crude yield of 99%.

[0174]

[0175] (4) The crude product of compound 9-5 (380 mg), DMAP (6 eq), EDCI (4 eq) and cyclopropanecarboxylic acid (5 eq) were added to 10 mL of DCM in sequence and reacted at room temperature. After the reaction was completed, water was added for extraction. The organic phase was washed once with dilute hydrochloric acid, once with a saturated sodium bicarbonate solution, and once with a sodium chloride solution. The mixture was dried and concentrated to obtain 460 mg of the crude product of compound 9-6, with a crude yield of 98%.

[0176]

[0177] (5) The crude product of compound 9-6 (460 mg) was dissolved in 10 mL THF, and 3 mL pyridine and 2 mL hydrogen fluoride pyridine solution were added under ice bath. After the reaction was completed, the reaction solution was poured into ice water for extraction. The organic phase was washed with saturated sodium bicarbonate solution, dried and concentrated to obtain 240 mg of crude product of compound 9-7. The crude product yield was 62%.

[0178]

[0179] (6) The crude product of compound 9-7 (240 mg) was dissolved in 10 mL of THF, and cerium chloride heptahydrate (1.2 eq) and sodium borohydride (2.4 eq) were added in sequence. The reaction was carried out at room temperature. After the reaction was completed, the reaction solution was filtered through diatomaceous earth, and the filtrate was mixed with silica gel and purified by normal phase to obtain 60 mg of compound 9 (light yellow solid, yield 25%).

[0180]

[0181] 3. Synthesis of compound 9

[0182] (1) Compound 9-6 (950.0 mg, 1.62 mmol) was dissolved in 5 ml of dichloromethane, and triethylamine (TEA, 1.32 g, 12.96 mmol), cyclopropanecarboxylic acid (696.6 mg, 8.10 mmol), 4-dimethylaminopyridine (DMAP, 395.3 mg, 3.24 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 1.55 g, 8.10 mmol) were added in sequence under an ice-water bath, and stirred at room temperature for 30 min. LCMS showed that the reaction was complete. Water and dichloromethane were added to the reaction solution to dilute it, and the organic phase was washed with saturated ammonium chloride solution and saturated brine in sequence, dried and concentrated to obtain compound 9-8 (600.0 mg, yield 51%, light yellow solid).

[0183]

[0184] (2) Compound 9-8 (300.0 mg, 0.41 mmol) was dissolved in a mixed solvent of pyridine / tetrahydrofuran (2 ml / 10 ml), pyridine hydrofluoride (5 ml) was added dropwise at 0°C, and the mixture was stirred at room temperature for 12 h. The reaction was completed by LCMS monitoring. The reaction solution was quenched with a saturated aqueous sodium bicarbonate solution, the aqueous phase was extracted with ethyl acetate, the organic phase was washed with saturated brine, dried and concentrated, and the residue was purified by column chromatography (EA / PE=30-60%) to obtain compound 9 (150.0 mg, 59.6 mmol, yield 60%, white solid).

[0185]

[0186] 4. Synthesis of Compound 43

[0187] Compound 9 (20 mg, 0.03 mmol) was dissolved in 1 ml of dichloromethane, and triethylamine (32 mg, 0.06 mmol), acetic anhydride (6.1 mg, 0.06 mmol) and 4-dimethylaminopyridine (2 mg, 0.03 mmol) were added, and the reaction was carried out at room temperature for 0.5 h. LCMS monitored the reaction to be complete. The reaction solution was quenched with sodium bicarbonate aqueous solution, extracted with ethyl acetate, and the organic phase was washed with saturated brine, dried and concentrated. The residue was purified by column chromatography (EA / PE=1 / 2) to obtain compound 43 (10 mg, yield 47%, light yellow solid).

[0188]

[0189] 5. Synthesis of Compound 61

[0190] Compound 5 (100 mg, 0.16 mmol) was dissolved in 1 ml of DMF, and triethylamine (32 mg, 0.32 mmol), 61-1 (67 mg, 0.32 mmol) and 4-dimethylaminopyridine (2 mg, 0.016 mmol) were added, and the mixture was reacted at room temperature for 0.5 h. The reaction was complete after LCMS monitoring. The reaction solution was quenched with aqueous sodium bicarbonate solution, extracted with ethyl acetate, and the organic phase was washed with saturated brine, dried and concentrated. The residue was purified by column chromatography (MeOH:DCM=1:15) to obtain compound 61 (10 mg, yield 9%, light yellow solid).

[0191]

[0192] 6. Synthesis of Compound 95

[0193] Compound 5 (0.50 g, 0.82 mmol) was added to a 100 ml three-necked flask, and 5 ml of dichloromethane was added to dissolve it. The reaction was placed in an ice-salt bath, and Dess-Martin periodinant (0.52 g, 1.22 mmol) was slowly added, and the temperature was controlled not to exceed 5°C, and then the reaction was placed at room temperature for 4 hours. After the reaction was completed by LCMS monitoring, a small amount of saturated sodium thiosulfate solution was added to quench the reaction, and the reaction was extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and concentrated. The residue was purified by column chromatography (PE:EA=1:1) to obtain compound 95 (0.11 g, yield 22%, yellow solid).

[0194]

[0195] 7. Synthesis of Compound 126

[0196] (1) Preparation of compound 126-1 Refer to compound 9-7. Dissolve compound 126-1 (300 mg, 0.48 mmol) in 2 ml of 1,2-dichloroethane, add bromomethyl methyl ether (306 mg, 2.46 mmol), TBAI (48 mg, 0.39 mmol) and DIEA (906 mg, 2.46 mmol) in sequence, and react at room temperature for 12 h. LCMS monitored the reaction to be complete. Dilute the reaction solution with water and dichloromethane, wash the organic phase with saturated brine, dry and concentrate, and purify the residue by column chromatography (EA:PE=1:5) to obtain compound 126-2 (150 mg, yield 47%, light yellow solid).

[0197]

[0198] (2) Compound 126-2 (150 mg, 0.23 mmol) was dissolved in 2 ml of anhydrous ethanol, and CeCl3·7H2O (85 mg, 0.23 mmol) and NaBH4 (16 mg, 0.46 mmol) were added in turn under an ice-water bath, and the mixture was reacted at room temperature for 30 min. LCMS monitored the reaction to be complete. The reaction solution was quenched with saturated aqueous NaHCO3 solution, extracted with ethyl acetate, and the organic phase was washed with water and saturated brine, dried and concentrated. The residue was purified by column chromatography (EA:PE=1:1) to obtain compound 126 (59 mg, yield 38%, light yellow solid).

[0199]

[0200] 8. Synthesis of Compound 128

[0201] (1) Compound 5-2 (25.0 g crude product) was dissolved in 200 mL DMF, 128-1 (64.3 mL, 526.3 mmol) and 4-methylbenzenesulfonic acid pyridine (6.6 g, 26.3 mmol) were added under ice-water bath, and stirred at room temperature for 30 min. LCMS monitored the reaction to be complete. Saturated sodium bicarbonate aqueous solution was added to the reaction solution for quenching, and dichloromethane was extracted. The organic phase was washed with water and saturated brine, dried and concentrated to obtain a crude product. The crude product was slurried with PE:EA=10:1, and the filter cake was collected and dried in vacuo to obtain a crude compound 128-2 (28.0 g, light yellow solid), which was directly used in the next step.

[0202]

[0203] (2) Compound 128-2 (28.0 g, crude product) was dissolved in 150 mL of DMF, and tert-butyldimethylsilyl chloride (TBSCl, 16.4 g, 108.8 mmol) and imidazole (7.4 g, 108.8 mmol) were added in turn under an ice-water bath, and stirred at room temperature for 12 h. LCMS monitored the reaction to be complete, and saturated aqueous ammonium chloride was added to the reaction solution for quenching, and dichloromethane was extracted. The organic phase was washed with water and saturated brine, dried and concentrated to obtain a crude product, which was slurried with petroleum ether, and the filter cake was collected and dried in vacuo to obtain a crude compound 128-3 (28 g, light yellow solid), which was directly used in the next step.

[0204]

[0205] (3) Compound 128-3 (28.0 g, crude product) was dissolved in 100 mL THF, 1500 mL 80% AcOH aqueous solution was added under ice-water bath, and stirred at room temperature for 24 h. LCMS monitored the reaction to be complete. The pH was adjusted to 7-8 with saturated sodium bicarbonate aqueous solution, the aqueous phase was extracted with ethyl acetate, the organic phase was washed with saturated brine, dried and concentrated, and the residue was purified by column chromatography (EA:PE=1:5-3:5) to give compound 128-4 (21.0 g, 35.6 mmol, light yellow solid).

[0206]

[0207] (4) Compound 128-4 (500 mg, 0.85 mmol) was dissolved in 2 ml of dichloromethane, 4-dimethylaminopyridine (104 mg, 0.85 mmol) and 128-5 (110 mg, 0.85 mmol) were added, and the mixture was reacted at room temperature for 10 h. The reaction was completed by LCMS monitoring. The reaction solution was quenched with aqueous sodium bicarbonate solution, extracted with dichloromethane, and the organic phase was washed with water and saturated brine, dried and concentrated. The residue was purified by column chromatography (THF:PE=1:4) to give compound 128-6 (500 mg, yield 91%, light yellow solid).

[0208]

[0209] (5) Compound 128-6 (500 mg, 0.77 mmol) was dissolved in 2 ml of dichloromethane, and triethylamine (623 mg, 6.16 mmol), cyclopropanecarboxylic acid (265 mg, 3.08 mmol), EDCI (590 mg, 3.08 mmol) and 4-dimethylaminopyridine (188 mg, 1.54 mmol) were added at room temperature and reacted for 2 h. LCMS monitored the reaction to be complete. The reaction solution was diluted with water and dichloromethane, the organic phase was washed with saturated ammonium chloride and saturated brine, dried and concentrated, and the residue was purified by column chromatography (THF:PE=1:1) to obtain compound 128-7 (450 mg, yield 82%, light yellow solid).

[0210]

[0211] (6) Compound 128-7 (450 mg, 0.63 mmol) was dissolved in 1 ml of tetrahydrofuran, and pyridine (0.5 ml, 6.3 mmol) and hydrofluoric acid / pyridine (0.5 ml, 5.0 mmol) were added under an ice-water bath, and the reaction was carried out at room temperature for 12 h. LCMS monitored the reaction to be complete. The reaction solution was quenched with sodium bicarbonate aqueous solution, extracted with ethyl acetate, and the organic phase was washed with saturated brine, dried and concentrated. The residue was purified by column chromatography (MeOH:DCM=1:20) to obtain compound 128 (49 mg, yield 13%, light yellow solid).

[0212]

[0213] 9. Synthesis of Compound 5

[0214] (1) Compound 128-4 (21.0 g, 35.6 mmol) was dissolved in 150 mL DCM, triethylamine (TEA, 28.7 g, 284.8 mmol), cyclopropanecarboxylic acid (15.3 g, 178.0 mmol), 4-dimethylaminopyridine (DMAP, 8.7 g, 71.2 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 27.2 g, 142.4 mmol) were added in turn under ice-water bath, and stirred at room temperature for 12 h. LCMS showed that the reaction was complete. The reaction solution was diluted with water and dichloromethane, the organic phase was washed with saturated ammonium chloride solution and saturated brine, dried and concentrated, and the residue was purified by column chromatography (EA / PE=10-50%) to obtain compound 5-4 (17.5 g, 24.1 mmol, white solid).

[0215]

[0216] (2) Compound 5-4 (17.5 g, 24.1 mmol) was dissolved in a mixed solvent of pyridine / tetrahydrofuran (20 mL / 100 mL), pyridine hydrofluoride (30 mL) was added dropwise at 0°C, and the mixture was stirred at room temperature for 24 h. The reaction was completed by LCMS monitoring. The reaction solution was quenched with a saturated aqueous sodium bicarbonate solution, the aqueous phase was extracted with ethyl acetate, the organic phase was washed with water and saturated brine, dried and concentrated, and the residue was purified by column chromatography (EA / PE=30-60%) to obtain compound 5 (13.4 g, 21.9 mmol, white solid).

[0217]

[0218] 10. Synthesis of Compound 131

[0219] (1) Compound 9-7 (120.0 mg, 0.25 mmol) was dissolved in 2 ml of 1,2-dichloroethane, and bromomethyl methyl ether (31.0 mg, 0.25 mmol), TBAI (11.0 mg, 0.03 mmol) and DIEA (32.3 mg, 0.25 mmol) were added in sequence, and the mixture was reacted at room temperature for 3 h. The reaction was completed by LCMS monitoring. The reaction solution was diluted with water and dichloromethane, the organic phase was washed with saturated brine, dried and concentrated, and the residue was purified by column chromatography (EA / PE=1 / 5) to obtain compound 131-1 (30.0 mg, yield 47%, light yellow solid).

[0220]

[0221] (2) Compound 131-1 (30.0 mg, 0.05 mmol) was dissolved in 1 ml of tetrahydrofuran, and CeCl3·7H2O (18.6 mg, 0.05 mmol) and NaBH4 (3.8 mg, 0.10 mmol) were added in turn under an ice-water bath, and the mixture was reacted at room temperature for 30 min. LCMS monitored the reaction to be complete. The reaction solution was quenched with saturated aqueous NaHCO3 solution, extracted with ethyl acetate, and the organic phase was washed with water and saturated brine, dried and concentrated. The residue was purified by column chromatography (EA / PE=1 / 1) to obtain compound 131 (8.0 mg, yield 27%, light yellow solid).

[0222]

[0223] 11. Synthesis of Compound 133

[0224] (1) Compound 9-5 (350 mg, 0.60 mmol) was dissolved in 2 ml of dichloromethane, 4-dimethylaminopyridine (77.5 mg, 0.60 mmol) and propionic anhydride (72.8 mg, 0.60 mmol) were added, and the mixture was reacted at room temperature for 30 min. The reaction was completed by LCMS monitoring. The reaction solution was quenched with aqueous sodium bicarbonate solution, extracted with dichloromethane, and the organic phase was washed with saturated brine, dried and concentrated. The residue was purified by column chromatography (THF / PE=1 / 4) to obtain compound 133-1 (140 mg, yield 37%, light yellow solid).

[0225]

[0226] (2) Compound 133-1 (140 mg, 0.22 mmol) was dissolved in 2 ml of dichloromethane, and triethylamine (175 mg, 1.74 mmol), cyclopropanecarboxylic acid (73.5 mg, 0.87 mmol), EDCI (164.5 mg, 0.87 mmol) and 4-dimethylaminopyridine (52.5 mg, 0.43 mmol) were added at room temperature, and the mixture was reacted for 2 h at room temperature. The reaction was completed by LCMS monitoring. The reaction solution was diluted with water and dichloromethane, and the organic phase was washed with saturated ammonium chloride and saturated brine, dried and concentrated, and the residue was purified by column chromatography (THF / PE=1 / 3) to obtain compound 133-2 (80 mg, yield 52%, light yellow solid).

[0227]

[0228] (3) Compound 133-2 (80 mg, 0.63 mmol) was dissolved in 1 ml of tetrahydrofuran, and pyridine (0.5 ml, 6.3 mmol) and hydrofluoric acid / pyridine (0.5 ml, 5.0 mmol) were added under an ice-water bath, and the reaction was carried out at room temperature for 12 h. LCMS monitored the reaction to be complete. The reaction solution was quenched with sodium bicarbonate aqueous solution, extracted with ethyl acetate, and the organic phase was washed with saturated brine, dried and concentrated. The residue was purified by column chromatography (THF / PE=1 / 1) to obtain compound 133-3 (50 mg, yield 75%, light yellow solid).

[0229]

[0230] (4) Compound 133-3 (50 mg, 0.08 mmol) was dissolved in 1 ml of tetrahydrofuran, and CeCl3·7H2O (30 mg, 0.08 mmol) and NaBH4 (6.5 mg, 0.17 mmol) were added under ice-water bath, and the mixture was reacted at room temperature for 30 min. LCMS monitored the reaction to be complete. The reaction solution was quenched with aqueous sodium bicarbonate solution, extracted with ethyl acetate, and the organic phase was washed with saturated brine, dried and concentrated. The residue was purified by column chromatography (THF / PE=1 / 1) to give compound 133 (30 mg, yield 40%, light yellow solid).

[0231] DETAILED DESCRIPTION

[0233] Biological activity evaluation:

[0234] (1) Insecticidal activity test:

[0235] 1.1) Spray treatment test

[0236] After the original drug is dissolved in acetone, the solution is diluted to a gradient dose with distilled water. Select potted radish seedlings with insects that are consistent with the age of peach aphids and seedlings, use a handheld sprayer to spray, spray evenly on both sides, spray 8-10 times per pot of radish, use clean water as a control, repeat 3 times, and transfer to breeding conditions after application. Select 3-year-old green stink bug test insects with consistent physiological states raised indoors, put them in disposable transparent plastic cups, put 20 test insects in each cup, and put 4 fruit corn kernels, then use a spray tower to spray, cover the cup mouth with a cup after spraying, repeat 3 times, use clean water as a control, and transfer to breeding conditions after application. Select potted wheat seedlings with insects that are consistent with the age of cereal aphids and seedlings, use a handheld sprayer to spray, spray evenly on both sides, spray 8-10 times per pot of wheat, use clean water as a control, repeat 3 times, and transfer to breeding conditions after application. After n days, the results were investigated and the mortality of each treatment was counted to calculate the mortality rate: mortality rate (%) = (number of dead insects / number of test insects) * 100.

[0237] Table 2 Insecticidal test results

[0238]

[0239] Note: N means no data; Reference compound A:

[0240] 1.2) Top conduction capacity test

[0241] The radish seedlings with insects were planted in disposable transparent plastic cups, with 3 radish seedlings in each cup. The radish seedlings were drought-treated for 24 hours before the test. The prepared 20 mL of the solution was poured into the roots of the radish seedlings. Three replicates were set for each treatment, and a clear water control was set. Normal light and culture conditions were given. The results were investigated 6 days after the treatment. The deaths of each treatment were counted and the mortality rate was calculated. The representative test results are shown in Table 3.

[0242] Mortality rate = (number of dead insects / number of test insects) × 100%

[0243] Table 3 Test results of top conduction capacity

[0244]

[0245] Note: Control compound B: diprofenocarp.

[0246] (2) Composition insecticide activity determination test:

[0247] 2.1) Test conditions and operation steps

[0248] Test targets: Myzus persicae, Bemisia tabaci

[0249] Green peach aphid: After the original drug is dissolved in acetone, the solution is diluted with distilled water to a gradient dose. Select potted radish seedlings with the same age of peach aphids and seedlings, and use a handheld sprayer to spray evenly from the front and back. Spray each pot of radish 8-10 times, with clean water as the control, repeat 3 times, and transfer to the breeding conditions after application. Investigate the results after 6 days, and count the deaths of each treatment separately, and calculate the mortality rate: mortality rate (%) = (number of dead insects / number of test insects) * 100.

[0250] Bemisia tabaci: After the original drug is dissolved in acetone, dilute the solution with distilled water to a gradient dose. Use a one-liter plastic cup with a lid as a test vessel, cut off two true leaves of the Beibei pumpkin and insert them on a plastic sponge. Add an appropriate amount of water to the sponge to moisturize the pumpkin seedlings, and put the treated pumpkin seedlings into the plastic cup to make a test device. About 200 adult Bemisia tabaci are sucked and concentrated into the test device. Use a handheld electric sprayer to evenly spray the prepared solution from the hole cover above. Each treatment is repeated 3 times. After the application of the drug, place it in a treatment room with a temperature of 25°C and a humidity of 60%. Investigate the results after 3 days. Count the deaths of each treatment separately and calculate the mortality rate: mortality rate (%) = (number of dead insects / number of test insects) * 100.

[0251] 2.2) Qualitative evaluation of efficiency

[0252] Different ratios are set within the selected ratio range for toxicity determination, and the best ratio is selected based on the synergistic effect. When the synergistic effect is > 0, it indicates a synergistic effect; when the synergistic effect is close to 0, it indicates an additive effect; when the synergistic effect is < 0, it indicates an antagonistic effect.

[0253] Synergistic effect = actual mortality rate - theoretical mortality rate

[0254] Theoretical mortality rate = 1-(1-P1)(1-P2)

[0255] Where, P1, P2 are the mortality rates of each single dose in the mixture.

[0256] Table 4 Results of qualitative evaluation of the synergistic effect of the composition

[0257]

[0258]

[0259] At the same time, after many tests, it was found that the compounds and compositions of the present invention have good control effects on piercing-sucking mouthparts pests (such as aphids, whiteflies, stink bugs, psyllids, scale insects, mealybugs and leafhoppers, etc.), can reduce the occurrence of viral diseases and bacterial diseases transmitted by insect vectors, are suitable for economic crops, field crops and ornamental plants, etc., can be used for foliar treatment, seed treatment or soil treatment, and have little effect on beneficial arthropods such as natural enemy insects and pollinating insects, can effectively reduce the environmental burden of sustainable agricultural development, are suitable for pest resistance management and comprehensive control of harmful organisms, and have certain commercial value.

Claims

1. A pyripyropene derivative as shown in formula I, in, X1 represents hydrogen or fluorine, X2 represents hydrogen or fluorine, X3 represents hydrogen or fluorine, X4 represents hydrogen or fluorine, and X1, X2, X3 and X4 are not hydrogen at the same time; R1 and R2 independently represent hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl or -(CO)R3; Y1 represents hydroxy, alkoxyalkyloxy, trialkylsilyloxy or -O(CO)R3; Y2 represents hydrogen or alkyl; or Y1 and Y2 together form =O; R3 each independently represents hydrogen, an alkyl, alkenyl or alkynyl group which is unsubstituted or substituted by at least one of halogen, alkoxy, alkoxycarbonyl or alkylthio, a cycloalkyl group, a cycloalkenyl group, an aryl group or a heterocyclic group; The aforementioned "cycloalkyl", "cycloalkenyl", "heterocyclyl" or "aryl" is optionally selected from oxo, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, haloalkenyl, haloalkynyl, halocycloalkyl, cycloalkyl substituted by alkyl, -OR 10 、-SR 10 、-(CO)OR 10 、-(SO2)R 10 、-N(R 10 )2 or -O-alkylene-(CO)OR 10 or two adjacent carbon atoms on the ring form a condensed ring with unsubstituted or halogen-substituted -OCH2CH2- or -OCH2O-; R 10 Each is independently hydrogen, alkyl, haloalkyl, phenyl, or phenyl substituted by at least one group selected from halogen, cyano, nitro, alkyl, haloalkyl, alkoxycarbonyl, alkylthio, alkylsulfonyl, alkoxy or haloalkoxy.

2. The pyripyropene derivative according to claim 1, characterized in that R1 and R2 independently represent hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkylC1-C8 alkyl or -(CO)R3; Y1 represents hydroxyl, C1-C8 alkoxy, C1-C8 alkyloxy, tri-C1-C8 alkylsilyloxy or -O(CO)R3; Y2 represents hydrogen or C1-C8 alkyl; or Y1 and Y2 together form =O; R3 each independently represents hydrogen, C1-C8 alkyl, C2-C8 alkenyl or C2-C8 alkynyl which is unsubstituted or substituted by at least one of halogen, C1-C8 alkoxy, C1-C8 alkoxycarbonyl or C1-C8 alkylthio, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclic group; The aforementioned "C3-C8 cycloalkyl", "C3-C8 cycloalkenyl", "heterocyclyl" or "aryl" is optionally selected from oxo, halogen, cyano, nitro, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, halogenated C1-C8 alkyl, halogenated C2-C8 alkenyl, halogenated C2-C8 alkynyl, halogenated C3-C8 cycloalkyl, C3-C8 cycloalkyl substituted by C1-C8 alkyl, -OR 10 、-SR 10 、-(CO)OR 10 、-(SO2)R 10 、-N(R 10 )2 or -O-(C1-C8 alkylene)-(CO)OR 10 or two adjacent carbon atoms on the ring form a condensed ring with unsubstituted or halogen-substituted -OCH2CH2- or -OCH2O-; R 10 They are independently hydrogen, C1-C8 alkyl, halogenated C1-C8 alkyl, phenyl, or phenyl substituted by at least one group selected from halogen, cyano, nitro, C1-C8 alkyl, halogenated C1-C8 alkyl, C1-C8 alkoxycarbonyl, C1-C8 alkylthio, C1-C8 alkylsulfonyl, C1-C8 alkoxy or halogenated C1-C8 alkoxy.

3. The pyripyropene derivative according to claim 1 or 2, characterized in that: R1 and R2 independently represent hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 cycloalkylC1-C6 alkyl or -(CO)R3; Y1 represents hydroxyl, C1-C6 alkoxy, C1-C6 alkyloxy, tri-C1-C6 alkylsilyloxy or -O(CO)R3; Y2 represents hydrogen or C1-C6 alkyl; or Y1 and Y2 together form =O; R3 each independently represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 cycloalkenyl, aryl or heterocyclic group which is unsubstituted or substituted by at least one of halogen, C1-C6 alkoxy, C1-C6 alkoxycarbonyl or C1-C6 alkylthio; The aforementioned "C3-C6 cycloalkyl", "C3-C6 cycloalkenyl", "heterocyclyl" or "aryl" is optionally selected from oxo, halogen, cyano, nitro, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, halogenated C1-C6 alkyl, halogenated C2-C6 alkenyl, halogenated C2-C6 alkynyl, halogenated C3-C6 cycloalkyl, C3-C6 cycloalkyl substituted by C1-C6 alkyl, -OR 10 、-SR 10 、-(CO)OR 10 、-(SO2)R 10 、-N(R 10 )2 or -O-(C1-C6 alkylene)-(CO)OR 10 or two adjacent carbon atoms on the ring form a condensed ring with unsubstituted or halogen-substituted -OCH2CH2- or -OCH2O-; R 10 Each of them is independently hydrogen, C1-C6 alkyl, halogenated C1-C6 alkyl, phenyl, or phenyl substituted by 1 to 3 groups selected from halogen, cyano, nitro, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxycarbonyl, C1-C6 alkylthio, C1-C6 alkylsulfonyl, C1-C6 alkoxy or halogenated C1-C6 alkoxy.

4. The pyripyropene derivative according to any one of claims 1 to 3, characterized in that: X1 represents hydrogen, X2 represents fluorine, X3 represents hydrogen, and X4 represents hydrogen; or X1 represents hydrogen, X2 represents hydrogen, X3 represents fluorine, and X4 represents hydrogen; Preferably, the compound is selected from Table 1 of the specification.

5. A method for preparing a pyripyropene derivative according to any one of claims 1 to 4, characterized in that: Its obtained by an intermediate; or Prepared by reduction reaction; or Includes at least one of the following steps: Wherein, the definitions of X1, X2, X3, X4, and R3 are as described in any one of claims 1 to 4; Wherein, the reactions in step 1 and step 3 are both carried out in the presence of a solvent and a base; the reactions in step 2, step 5 and step 9 are carried out in the presence of a solvent, preferably, a condensing agent is added during the reactions in step 2, step 5 and step 9, with or without the addition of a base; the reaction in step 4 is carried out in the presence of an oxidant and a solvent; the reaction in step 6 is carried out in the presence of an acidic catalyst and a solvent; the reaction in step 7 is carried out in the presence of an organic base and a solvent; the reaction in step 8 is carried out in the presence of an acid (such as acetic acid) and a solvent; the reaction in step 10 is carried out in the presence of pyridine hydrofluoride and a solvent; More preferably, the solvent is selected from at least one of water, THF, pyridine, DMF, DMA, methanol, ethanol, acetonitrile, dichloroethane, DMSO, Dioxane, dichloromethane or ethyl acetate, the base is selected from at least one of an inorganic base or an organic base, the condensing agent is selected from at least one of Py-BOP, Py-AOP, HOBT, EDCI, DMAP, DCC, HBTU or HATU, the oxidant is a Dess-Martin oxidant or a PCC oxidant, or the acidic catalyst is pyridine p-toluenesulfonate (PPTS) or p-toluenesulfonic acid; Preferably, the reduction reaction is carried out in the presence of sodium borohydride and a solvent, more preferably, cerium trichloride may be added; or the solvent is selected from at least one of THF, DMF, DMA, methanol, ethanol, acetonitrile, dichloroethane, DMSO, Dioxane, dichloromethane or ethyl acetate.

6. The method according to claim 5, characterized in that The compound II is prepared by fermenting and culturing Pseudomonas saturnalis with pentafluoronicotinic acid as a substrate.

7. An insecticidal composition, characterized in that: Comprising a biologically effective amount of at least one of the pyripyropene derivatives according to any one of claims 1 to 4; preferably, further comprising a formulation adjuvant; more preferably, further comprising other active ingredients; further preferably, the other active ingredients are selected from at least one of the following compounds: (1) Acetylcholinesterase (AChE) inhibitors: chlorpyrifos, acephate; (2) GABA-gated chloride channel antagonist: fipronil; (3) Sodium channel regulators: highly effective chlorfenapyr, bifenthrin, deltamethrin, highly effective cypermethrin, cis-cypermethrin; (4) Competitive modulators of nicotinic acetylcholine receptors (nAChR): imidacloprid, thiamethoxam, acetamiprid, dinotefuran, clothianidin, sulfoxaflor, flupyralidone, thiamethoxam, trifluanid, and pyrimidine; (5) Allosteric modulators of glutamate-gated chloride channels (GluCl): avermectin, avermectin benzoate; (6) Bionic juvenile hormone: pyriproxyfen; (7) Nicotinic acetylcholine receptor (nAChR) channel blockers: cartap; (8) Chitin biosynthesis inhibitors (type 1): buprofezin, spiromesifen; (9) Acetyl CoA carboxylase inhibitors: spirotetramat, methoxyfentamethylenetetramine; (10) Nicotinic acid receptor modulators: cyantraniliprole; (11) String modulators - unknown target sites: flonicamid, anthracene; (12) GABA-gated chloride channel allosteric modulators: bromofenac, fluoxathiapiprolin, isoxathiapiprolin, and compound W (CAS No. 2892524-05-7); (13) Nicotinic acetylcholine receptor (nAChR) allosteric modulators: spinosad; (14) Others: Metarhizium anisopliae; More preferably, the weight ratio of the pyriproxypyrimidine derivative to other active ingredients in the insecticidal composition is 1:150-150:1, 1:100-100:1, 1:80-80:1, 1:60-60:1, 1:40-40:1, 1:20-20:1, 1:10-10:1, 1:8-8:1, 1:5-5:1 or 1:3-1:

1.

8. A method for controlling pests, characterized in that: The method comprises contacting the pest or its environment with a biologically effective amount of the pyripyropene derivative according to any one of claims 1 to 4 or the composition according to claim 7.

9. Use of the pyripyropene derivative according to any one of claims 1 to 4 or the composition according to claim 7 in controlling pests.

10. An intermediate as shown in formula II or III of claim 5.

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