Fungicidal mixtures comprising streptamine and malinomycin

Abstract

Disclosed are a composition comprising a streptamine and a malinomycin, an agrochemical composition comprising the mixture, and methods and uses of these compositions in the control or prevention of plants or other substrates infected with fungi.

Description

[0001] The present invention relates to a mixture comprising two known compounds, streptimidone and malonomicin, and its use for controlling fungi, especially in agriculture or horticulture. The present invention also relates to fungicidal compositions, especially agrochemical fungicidal compositions comprising such a mixture, and processes for preparing these compositions.

[0002] Streptimidone is a compound having the formula (I)

[0003]

[0004] Streptimidone is described in Kondo, H., Oritani, T., and Kiyota, H. Synthesis and antifungal activity of the four stereoisomers of streptimidone, a glutarimide antibiotic from Streptomyces rimosus forma paromomycinus. Eur. J. Org. Chem. (20), 3459 - 3462 (2000). Streptimidone is expressed by many Streptomyces strains. Streptimidone is also commercially available.

[0005] Malonomicin (sometimes spelled "malonomycin") is {[(2S)-2-amino-3-hydroxypropanoyl]amino}{2-[(5S)-5-(aminomethyl)-4-hydroxy-2-oxo-2,5-dihydro-1H-pyrrol-3-yl]-2-oxoethyl}malonic acid having the formula (II).

[0006]

[0007] Malonomicin is a natural compound prepared by a fermentation process. US 3,536,811 discloses malonomicin as an antibiotic and protozoan growth inhibitor. EP 1,860,939 describes malonomicin as an agricultural fungicide.

[0008] It has now surprisingly been found that a mixture comprising streptimidone and malonomicin can exhibit an unexpected synergistic fungicidal effect.

[0009] According to a first aspect of the present invention, there is provided a mixture comprising streptimidone and malonomicin.

[0010] According to a second aspect of the present invention, there is provided an agrochemical composition comprising a fungicidally effective amount of a mixture comprising streptimidone and maridomycin. Such an agrochemical composition may further comprise an agrochemically acceptable diluent or carrier.

[0011] The term agrochemical composition herein includes chemical compositions and biological compositions, preferably non-natural biological compositions, such as biologically produced compositions, such as compositions produced by microorganisms or non-natural compositions.

[0012] The composition according to the present invention is an isolated composition. An isolated composition means a non-natural composition.

[0013] According to a third aspect of the present invention, there is provided a method for controlling or preventing fungal infestation of plants, wherein an agrochemical composition comprising a fungicidally effective amount of a mixture comprising streptimidone and maridomycin is applied to these plants, parts thereof or their sites.

[0014] According to a fourth aspect of the present invention, there is provided the use of a mixture comprising streptimidone and maridomycin as a fungicide. According to this particular aspect of the present invention, the use may not include methods for treating the human or animal body by surgery or therapy.

[0015] Many Streptomyces strains express streptimidone. Streptimidone is also commercially available.

[0016] Maridomycin can be prepared according to the methods disclosed in Examples I A and B of EP 1860939 or according to Law et al., 2018 (Nature Catalysis | Volume 1 | December 2018 | 977 - 984).

[0017] The mixture comprising streptimidone and maridomycin can be used in the agricultural sector and related fields of use as, for example, an active ingredient for controlling fungal plant pests, or on inanimate materials to control spoilage fungi or fungi potentially harmful to humans. The mixture comprising streptimidone and maridomycin has surprisingly high activity at low application rates and is well tolerated by plants. It has very useful therapeutic and prophylactic properties and can be used to protect a wide range of cultivated plants. The mixture comprising streptimidone and maridomycin additionally has a surprising synergistic effect. And the mixture can be used to inhibit or destroy fungi occurring on plants or plant parts (fruits, flowers, leaves, stems, tubers, roots) of different useful plant crops, while also protecting those plant parts that grow later.

[0018] The present invention further relates to a method for controlling or preventing infestation of plants or plant propagation materials and / or harvested food crops susceptible to fungal attack by treating the plants or plant propagation materials and / or harvested food crops, wherein a fungicidally effective amount of a mixture comprising streptimidone and malonomycin is applied to the plants, parts thereof or the sites thereof.

[0019] The mixture comprising streptimidone and malonomycin can also be used more widely as a fungicide. As used herein, the term "fungicide" means a compound that controls, modifies, or prevents fungal growth. The term "fungicidally effective amount" when used means the amount of such a compound or combination of such compounds that is capable of having an effect on fungal growth. The effects of control or modification include all deviations from natural development, such as killing, retardation, etc., and prevention includes forming a barrier or other defense within or on the plant to prevent fungal infestation.

[0020] It may also be possible to use the mixture comprising streptimidone and malonomycin as a seed dressing agent for treating plant propagation materials (e.g., seeds, fruits, tubers or grains, or plant cuttings) for protection against fungal infections as well as against phytopathogenic fungi present in the soil. The propagation materials can be treated with the composition comprising streptimidone and malonomycin before planting: for example, seeds can be dressed before sowing. Streptimidone and malonomycin can also be applied to grains (coating) by impregnating the seeds in a liquid formulation or by coating them with a solid formulation. The composition can also be applied to the planting site when planting the propagation materials, for example, applied to the furrow of the seeds during sowing. The present invention also relates to such a method for treating plant propagation materials and to plant propagation materials so treated.

[0021] In addition, the mixture comprising streptimidone and malonomycin can be used in relevant fields for controlling fungi, for example, for the protection of industrial materials (including wood and wood-related industrial products), food storage, pharmaceutical applications, veterinary applications and hygiene management.

[0022] In addition, the present invention can be used to protect inanimate materials (such as wood, wall panels, wallpaper and paints) from fungal attack.

[0023] Examples of important fungi that need to be controlled in agriculture and other fields are:

[0024] Botrytis cinerea, Cercospora kikuchii, Cercospora sojina, Cochliobolus sativus, Colletotrichum lindemuthianum, Colletotrichum orbiculare, Corynespora cassiicola, Fusarium avenaceum, Fusarium culmorum, Fusarium langsethiae, Fusarium poae, Fusarium sporotrichioides, Fusarium tricinctum, Fusarium virguliforme, Gibberella avenacea, Gibberella fujikuroi, Gibberella zeae, Microdochium majus, Monographella nivalis, Mycosphaerella arachidis, Phakopsora pachyrhizi, Puccinia triticina (= Puccinia recondita), Pyrenophora tritici-repentis, Ramularia collo-cygni, Rhynchosporium secalis, Septoria glycines, Tilletia tritici, Ustilago segetum var. Tritici, Venturia inaequalis, and Zymoseptoria tritici.

[0025] Examples of preferred fungi are Gibberella species including Gibberella zeae (also known as Fusarium graminearum), Fusarium species including Fusarium solani (also known as Fusarium solani f.sp. glycines or sudden death syndrome pathogen of soybean), Microdochium species such as Microdochium nivale (also known as Microdichium nivale or Cereal Head Blight), and Zymoseptoria or Mycosphaerella species such as Septoria tritici (also known as Septoria tritici), Mycosphaerella graminicola or Septoria Leaf Blotch, especially Septoria tritici, Microdochium nivale (= Microdochium nivale) and Gibberella zeae (= Fusarium graminearum).

[0026] Particularly preferred are Fusarium avenaceum, Fusarium culmorum, Fusarium langsethiae, Fusarium poae, Fusarium sporotrichioides, Fusarium tricinctum, Fusarium solani, Fusarium verticillioides, Fusarium subglutinans, Septoria tritici, Puccinia recondita (= Puccinia recondita), Mycosphaerella fijiensis, Puccinia striiformis, Magnaporthe grisea and Rhizoctonia solani.

[0027] Target crops and / or useful plants to be protected typically include perennial and annual crops, such as berry plants, e.g., blackberry, blueberry, cranberry, raspberry, and strawberry; cereals, e.g., barley, maize (corn), millet, oats, rice, rye, sorghum, triticale, and wheat; fiber plants, e.g., cotton, flax, hemp, jute, and sisal; field crops, e.g., sugar beet and fodder beet, coffee bean, hops, mustard, rapeseed (canola), poppy, sugar cane, sunflower, tea, and tobacco; fruit trees, e.g., apple, apricot, avocado, banana, cherry, citrus, nectarine, peach, pear, and plum; grasses, e.g., Bermuda grass, bluegrass, bent grass, centipede grass, foxtail, ryegrass, St. Augustine grass, and zoysia grass; herbs, such as basil, borage, chives, coriander, lavender, lovage, mint, oregano, parsley, rosemary, sage, and thyme; legumes, e.g., kidney bean, lentil, pea, and soybean; nuts, e.g., almond, cashew, groundnut, hazelnut, peanut, pecan, pistachio, and walnut; palm plants, e.g., oil palm; ornamental plants, e.g., flowers, shrubs, and trees; other trees, e.g., cacao tree, coconut tree, olive tree, and rubber tree; vegetables, e.g., asparagus, eggplant, broccoli, cabbage, carrot, cucumber, garlic, lettuce, zucchini, melon, okra, onion, pepper, potato, pumpkin, rhubarb, spinach, and tomato; and vines, e.g., grapevine.

[0028] The term "crop" or "useful plant" should be understood to also include useful plants that have been made tolerant to herbicides (such as bromoxynil) or herbicide classes (e.g., such as HPPD inhibitors, ALS inhibitors, e.g., flupyrsulfuron, prosulfuron, and trifloxysulfuron, EPSPS (5-enolpyruvyl-shikimate-3-phosphate synthase) inhibitors, GS (glutamine synthetase) inhibitors, or PPO (protoporphyrinogen oxidase) inhibitors) by conventional breeding methods or genetic engineering. Examples of crops that have been made tolerant to imidazolinones (e.g., imazamox) by conventional breeding methods (mutation) are summer rape (canola). Examples of crops that have been made tolerant to herbicides or herbicide classes by genetic engineering methods include glyphosate-resistant and glufosinate-resistant maize varieties, which are commercially available under the trade names and commercially available.

[0029] The term "crop" or "useful plant" should be understood to also include useful plants that have been so transformed by the use of recombinant DNA technology that they are capable of synthesizing one or more selectively acting toxins, such as those known, for example, from toxin-producing bacteria, in particular bacteria of the genus Bacillus.

[0030] Mixtures comprising streptolydigin and malinomycin can also be used, for example, for lawns, ornamental plants such as flowers, shrubs, broad-leaved trees or evergreens, such as conifers, and tree injections, pest management, etc.

[0031] Preferred crops on which mixtures comprising streptolydigin and malinomycin can be used include bananas, cereals and legumes (such as peanuts or soybeans), and grains (such as wheat, barley, rice or maize).

[0032] As used herein, the term "site" means the place where a plant grows in or on, or the place where seeds of a cultivated plant are sown, or the place where seeds are to be placed in the soil. It includes soil, seeds, and seedlings, together with established vegetation.

[0033] The term "plant" refers to all the tangible parts of a plant, including seeds, seedlings, young trees, roots, tubers, stems, stalks, leaves, and fruits.

[0034] The term "plant propagation material" shall be understood to mean the reproductive parts of a plant, such as seeds, which can be used for the propagation of the plant, and vegetative material, such as cuttings or tubers (such as potatoes). Seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes, and parts of plants can be mentioned, for example. Germinated plants and young plants that are to be transplanted after germination or after emergence can also be mentioned. These young plants can be protected by complete or partial treatment by dipping before transplantation. Preferably, "plant propagation material" shall be understood to mean seeds.

[0035] Mixtures comprising streptolydigin and malinomycin can be used in an unmodified form, or preferably, together with adjuvants conventionally used in the formulation art. For this purpose, it can be conveniently formulated in a known manner as an emulsifiable concentrate, a coatable paste, a directly sprayable or dilutable solution or suspension, a dilute emulsion, a wettable powder, a soluble powder, a dust powder, a granule, and also capsules (such as in polymeric substances). For the type of composition, the application method is selected according to the intended purpose and the circumstances at the time, such as spraying, atomizing, dusting, sowing, coating, or watering. The composition can also contain additional adjuvants, such as stabilizers, defoamers, viscosity regulators, binders or tackifiers, and fertilizers, micronutrient donors, or other formulations for obtaining special effects.

[0036] When streptoviridene is produced by a microorganism, it can be isolated from the microorganism. Alternatively, a significant amount of streptoviridene may be present in the culture medium in which the microorganism grows, in which case the culture medium or broth together with malonomycin can be used to formulate a fungicidal composition. As a further alternative, the microorganism can produce both streptoviridene and malonomycin, in which case the microorganism itself can be used to formulate the composition. Accordingly, a process for producing streptoviridene and malonomycin is disclosed, which process comprises fermenting a microorganism in a suitable fermentation medium under conditions permitting the production of streptoviridene and malonomycin. In such a case, the microorganism can be formulated as live cells actively producing streptoviridene and malonomycin, or it can be inactivated, for example by heat treatment. If desired, the microorganism can be concentrated by a centrifuge or other conventional techniques.

[0037] Suitable carriers and adjuvants, for example for agricultural use, can be solid or liquid and are substances useful in formulation technology, such as natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers. Such carriers are described, for example, in WO 97 / 33890.

[0038] Suspension concentrates are formulations in which finely divided solid particles of the active compound are suspended in a liquid. Such formulations contain anti-settling agents and dispersants and may further contain wetting agents to enhance activity, as well as anti-foaming agents and crystal growth inhibitors. In use, these concentrates are diluted in water and are usually applied as sprays to the area to be treated. The amount of the active ingredient can range from 0.5% to 95% of the concentrate.

[0039] Wettable powders are in the form of finely divided particles that are readily dispersible in water or other liquid carriers. These particles contain the active ingredient retained in a solid matrix. Typical solid matrices include fuller's earth, kaolin, silica and other readily wettable organic or inorganic solids. Wettable powders usually contain from 5% to 95% of the active ingredient plus small amounts of wetting agents, dispersants or emulsifiers.

[0040] Emulsifiable concentrates are homogeneous liquid compositions that are dispersible in water or other liquids and can consist entirely of the active compound with liquid or solid emulsifiers, or can also contain liquid carriers such as xylene, heavy aromatic naphtha, isophorone and other non-volatile organic solvents. In use, these concentrates are dispersed in water or other liquids and are usually applied as sprays to the area to be treated. The amount of the active ingredient can range from 0.5% to 95% of the concentrate.

[0041] The particulate formulation includes both extrudates and coarser particles and is typically applied undiluted to the area to be treated. Typical carriers for particulate formulations include sand, fuller's earth, attapulgite clay, bentonite, montmorillonite, vermiculite, perlite, calcium carbonate, brick, pumice, pyrophyllite, kaolin, dolomite, plaster, wood flour, ground corn cobs, ground peanut hulls, sugar, sodium chloride, sodium sulfate, sodium silicate, sodium borate, magnesium oxide, mica, iron oxide, zinc oxide, titanium oxide, antimony oxide, cryolite, gypsum, diatomaceous earth, calcium sulfate, and other organic or inorganic absorbent and active compounds or materials that can be coated with active compounds. Particulate formulations typically contain 5% to 25% active ingredient, which can include surfactants such as heavy aromatic naphtha, kerosene, and other petroleum fractions, or vegetable oils; and / or adhesives such as dextrin, gum, or synthetic resins.

[0042] Dusts are free-flowing mixtures of active ingredients with finely divided solids such as talc, clay, flour, and other organic and inorganic solids that act as dispersants and carriers.

[0043] Microcapsules are typically microdroplets or particles of active ingredient encapsulated within an inert porous shell that permits the encapsulated material to escape into the environment at a controlled rate. The diameter of the encapsulated microdroplets is typically 1 to 50 microns. The encapsulated liquid typically comprises 50% to 95% of the weight of the capsule and may contain solvents in addition to the active compound. The encapsulated particles are generally porous particles in which a porous membrane seals the particle orifice, retaining the active species in liquid form within the particle pores. The diameter of the particles typically ranges from 1 mm to 1 cm and preferably 1 to 2 mm. The particles are formed by extrusion, aggregation, or spheronization, or are naturally occurring. Examples of such materials are vermiculite, sintered clay, kaolin, attapulgite clay, sawdust, and carbon grains. The shell or membrane materials include natural and synthetic rubbers, fibrous materials, styrene-butadiene copolymers, polyacrylonitrile, polyacrylates, polyesters, polyamides, polyureas, polyurethanes, and starch xanthate.

[0044] Other useful formulations for agrochemical applications include simple solutions of the active ingredient in solvents such as water, acetone, alkylated naphthalenes, xylene, and other organic solvents in which the active ingredient is completely soluble at the desired concentration. Pressurized sprays can also be used, in which the active ingredient is dispersed in finely divided form due to the evaporation of a low-boiling dispersant solvent carrier.

[0045] Suitable agricultural adjuvants and carriers useful for formulating the compositions of the present invention in the above formulation types are well known to those skilled in the art.

[0046] Liquid carriers that can be used include, for example, water, vegetable oils, toluene, xylene, naphtha, crop oil, acetone, methyl ethyl ketone, cyclohexanone, acetic anhydride, acetonitrile, acetophenone, amyl acetate, 2-butanone, chlorobenzene, cyclohexane, cyclohexanol, alkyl acetate, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diglycol rosin acid ester, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, dipropylene glycol (diproxitol), alkyl pyrrolidone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1,1,1-trichloroethane, 2-heptanone, α-pinene, d-limonene, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, γ-butyrolactone, glycerol, glycerol diacetate, glycerol monoacetate, glycerol triacetate, hexadecane, hexanediol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, cumene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxypropanol, methyl isopentanone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, dichloromethane, m-xylene, n-hexane, n-octylamine, stearic acid, octylamine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol (PEG400), propionic acid, propylene glycol, propylene glycol monomethyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylene sulfonic acid, paraffin wax, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, methanol, ethanol, isopropyl alcohol, and higher molecular weight alcohols (such as pentanol, tetrahydrofurfuryl alcohol, hexanol, octanol, etc.), ethylene glycol, propylene glycol, glycerol, and N-methyl-2-pyrrolidone. Water is usually the preferred carrier for diluting the concentrate.

[0047] Suitable solid carriers include, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, chalk, diatomaceous earth, lime, calcium carbonate, bentonite, fuller's earth, cottonseed hulls, wheat flour, soybean flour, pumice, wood flour, walnut shell powder, and lignin.

[0048] A wide range of surfactants can advantageously be employed in the liquid and solid compositions, especially those designed to be diluted with a carrier prior to application. These agents typically comprise from 0.01% to 15% by weight of the formulation when in use. They can be anionic, cationic, nonionic or polymeric in nature and can be used as emulsifiers, wetting agents, suspending agents or for other purposes. Typical surfactants include Tween 20, alkyl sulfates such as diethanolammonium lauryl sulfate; alkyl aryl sulfonates such as calcium dodecylbenzenesulfonate; alkylphenol-alkylene oxide adducts such as nonylphenol-C18 ethoxylate; alcohol-alkylene oxide adducts such as tridecanol-C16 ethoxylate; soaps such as sodium stearate; alkylnaphthalenesulfonates such as sodium dibutylnaphthalenesulfonate; salts of dialkyl esters of sulfosuccinic acid such as sodium di(2-ethylhexyl) sulfosuccinate; sorbitan esters such as sorbitan oleate; quaternary amines such as lauryl trimethylammonium chloride; polyethylene glycol esters of fatty acids such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono- and dialkyl phosphates.

[0049] Other adjuvants commonly used in agricultural compositions include crystallization inhibitors, viscosity modifiers, suspending agents, spray droplet modifiers, pigments, antioxidants, foaming agents, defoaming agents, light blockers, compatibility agents, defoamers, masking agents, neutralizing agents and buffers, corrosion inhibitors, dyes, flavorants, spreading agents, penetration aids, micronutrients, emollients, lubricants and sticking agents.

[0050] Furthermore, other agrochemical active ingredients or compositions can be combined with the compositions of the invention and used in the methods of the invention and applied simultaneously or sequentially with the compositions of the invention. When applied sequentially, the compositions of the invention can be applied to plants during a different growth period from other agrochemical active ingredients. When applied simultaneously, these additional active ingredients can be formulated together with the compositions of the invention or mixed, for example, in a spray tank. These additional agrochemical active ingredients can be fungicides, herbicides, insecticides, bactericides, acaricides, nematicides, growth stimulants and / or plant growth regulators.

[0051] The pesticidal agents mentioned herein by their common names are known, for example, from "The Pesticide Manual", 19th Edition, British Crop Protection Council 2021.

[0052] The mixtures according to the invention can be mixed with one or more insecticides known in the art.

[0053] The mixtures according to the invention can be mixed with one or more fungicides known in the art, including biocides.

[0054] Mixtures comprising streptimidone and malenomycin can be used in the form of agrochemical compositions and can be applied to crop areas or plants to be treated simultaneously or sequentially with further compounds. For example, these further compounds can be fertilizers or micronutrient donors or other preparations which influence plant growth. They can also be selective or non-selective herbicides, as well as insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or application-promoting adjuvants customarily used in the formulation art.

[0055] Mixtures comprising streptimidone and malenomycin can be used in the form of (fungicidal) compositions for controlling or protecting against phytopathogenic microorganisms, these compositions comprising streptimidone and malenomycin as active ingredients and at least one of the abovementioned adjuvants.

[0056] Accordingly, the invention provides a composition, preferably a fungicidal composition, which comprises streptimidone, malenomycin, an agriculturally acceptable carrier and optionally adjuvants. An agriculturally acceptable carrier is, for example, a carrier suitable for agricultural use. Agricultural carriers are well known in the art. Preferably, in addition to comprising streptimidone and malenomycin, the composition can comprise at least one or more pesticidal active compounds, for example further fungicidal active ingredients.

[0057] The compositions according to the invention can also comprise further solid or liquid auxiliaries, such as stabilizers, for example unepoxidized or epoxidized vegetable oils (such as epoxidized coconut oil, rapeseed oil or soybean oil), defoamers (such as silicone oils), preservatives, viscosity regulators, binders and / or tackifiers, fertilizers or other active ingredients for obtaining specific effects, such as bactericides, fungicides, nematicides, plant activators, molluscicides or herbicides.

[0058] The compositions according to the invention are prepared in a manner known per se, in the absence of auxiliaries, for example by grinding, screening and / or compressing the solid active ingredients; and in the presence of at least one auxiliary, for example by intimately mixing the active ingredients with one or more auxiliaries and / or grinding the active ingredients together with one or more auxiliaries. These methods for preparing the compositions and the use of the compounds (I) for preparing these compositions are also the subject of the invention.

[0059] Another aspect of the invention relates to the use of a composition comprising streptimidone and malonomycin, or a fungicidal or insecticidal mixture comprising streptimidone and malonomycin (mixed with other fungicides or insecticides as described above), for controlling or preventing infestation of plants (such as useful plants (e.g., crop plants)), their propagation material (e.g., seeds), harvested crops (e.g., harvested food crops), or inanimate materials by insects or phytopathogenic microorganisms (preferably fungal organisms).

[0060] A further aspect of the invention relates to a method for controlling or preventing infestation of plants (such as useful plants (e.g., crop plants)), their propagation material (e.g., seeds), harvested crops (e.g., harvested food crops), or inanimate materials by insects or phytopathogenic or spoilage microorganisms or organisms potentially harmful to humans (especially fungal organisms), which method comprises applying a mixture comprising streptimidone and malonomycin as an active ingredient to these plants, parts of these plants or their sites, their propagation material, or any part of these inanimate materials.

[0061] Controlling or preventing means reducing infestation by phytopathogenic or spoilage microorganisms or organisms potentially harmful to humans (especially fungal organisms) to a demonstrably improved level.

[0062] A preferred method for controlling or preventing infestation of crop plants by phytopathogenic microorganisms (especially fungal organisms) or insects is foliar application, which comprises applying a compound of formula (I) and a compound of formula (II), or an agrochemical composition comprising at least one of said compounds. The frequency and rate of application will depend on the risk of infestation by the respective pathogen. However, the compositions of the invention can also penetrate plants via the soil through the roots by wetting the site of the plants with a liquid formulation or by applying the compound in solid form, for example in the form of granules, to the soil (soil application). In rice crops, such granules can be applied to flooded paddy fields. The mixtures of the invention can also be applied to seeds (coating) by impregnating the seeds or tubers with a liquid formulation of the fungicide or by coating them with a solid formulation.

[0063] Formulations (such as compositions comprising the mixtures of the invention and, if desired, solid or liquid auxiliaries or monomers for encapsulating the mixtures of the invention) can be prepared in a known manner, typically by intimately mixing and / or grinding the compounds with extenders (such as solvents, solid carriers and optionally surface-active compounds (surfactants)).

[0064] The weight / mole ratio of streptimidone to maridomycin is preferably from 10:1 to 1:500, more preferably from 1:1 to 1:300, and most preferably from 1:10 to 1:100.

[0065] The preferred application rate is generally from 0.1 g to 6 kg of active ingredient (a.i.; combined weight of streptimidone and maridomycin) / hectare (ha), preferably from 0.1 g to 1 kg a.i. / ha, and most preferably from 10 g to 800 g a.i. / ha.

[0066] When the combination of the present invention is used for treating seeds, a rate of 0.001 to 100 g of active ingredient / kg of seeds, preferably 0.01 to 10 g / kg of seeds, is generally sufficient.

[0067] Suitably, a composition comprising streptimidone and maridomycin according to the present invention is applied prophylactically (i.e., before the development of the disease) or therapeutically (i.e., after the development of the disease).

[0068] Certain mixtures of streptimidone and maridomycin may exhibit a synergistic effect. A synergistic effect exists as long as the action of the combination of active ingredients is greater than the sum of the actions of the individual components. For a given combination of active ingredients, the expected action E follows the so-called COLBY formula and can be calculated as follows (COLBY, S.R. “Calculating synergistic and antagonistic responses of herbicide combination”. Weeds, Vol. 15, pp. 20 - 22; 1967):

[0069] ppm = milligrams of active ingredient (= a.i.) per liter of spray mixture

[0070] X = % action of active ingredient A), using p ppm of active ingredient

[0071] Y = % action of active ingredient B), using q ppm of active ingredient.

[0072] According to COLBY, the expected (additive) action of active ingredient A) + B), using p + q ppm of active ingredient, is

[0073]

[0074] If the actually observed effect (O) is greater than the expected effect (E), then the effect of the combination is super-additive, i.e., there is a synergistic effect. Mathematically, the synergistic effect corresponds to the positive value of the difference (O - E). In the case of a purely complementary addition of active substances (expected activity), the difference (O - E) is zero. A negative value of the difference (O - E) signals a loss of activity compared to the expected activity.

[0075] However, in addition to the actual synergistic effect with respect to the fungicidal activity, the compositions according to the invention may also have further surprising advantageous properties. Examples of such advantageous properties that may be mentioned are: more favorable degradability; improved toxicological and / or ecotoxicological behavior; or improved characteristics of useful plants, including: emergence, crop yield, more developed root system, increased tillering, increased plant height, larger leaves, less basal leaf death, stronger tillering, greener leaf color, less fertilizer required, less seed required, more productive tillering, earlier flowering, earlier grain maturity, less plant lodging (lodging), enhanced bud growth, improved plant vigor, and earlier germination.

[0076] The compositions of the invention can be used in any conventional form, for example, in the form of a two-pack, powder for dry seed treatment (DS), emulsion for seed treatment (ES), flowable concentrate for seed treatment (FS), solution for seed treatment (LS), water dispersible powder for seed treatment (WS), capsule suspension for seed treatment (CF), gel for seed treatment (GF), emulsion concentrate (EC), suspension concentrate (SC), suspension emulsion (SE), capsule suspension (CS), water dispersible granule (WG), emulsifiable granule (EG), water-in-oil emulsion (EO), oil-in-water emulsion (EW), microemulsion (ME), oil dispersant (OD), oil miscible flowable (OF), oil soluble concentrate (OL), soluble concentrate (SL), ultra-low volume suspension (SU), ultra-low volume liquid (UL), technical concentrate (TK), dispersible concentrate (DC), wettable powder (WP) or any technically feasible formulation in combination with agriculturally acceptable adjuvants.

[0077] Such compositions can be produced in a conventional manner, for example by mixing the active ingredients with suitable formulation inert agents (diluents, solvents, fillers and optionally other formulation ingredients such as surfactants, biocides, antifreezes, adhesives, thickeners and compounds providing auxiliary effects). Conventional slow-release formulations intended for long-lasting efficacy can also be used. In particular, formulations to be applied in the form of sprays, such as water-dispersible concentrates (e.g. EC, SC, DC, OD, SE, EW, EO, etc.), wettable powders and granules, can contain surfactants such as wetting agents and dispersants and other compounds providing auxiliary effects, for example condensation products of formaldehyde with naphthalenesulfonates, alkylarylsulfonates, ligninsulfonates, fatty alkyl sulfates, and ethoxylated alkylphenols and ethoxylated fatty alcohols.

[0078] Using the combination and diluent of the present invention, in the form of a suitable seed dressing formulation, such as an aqueous suspension or a dry powder formulation having good adhesion to seeds, the seed dressing formulation is applied to the seeds in a manner known per se. Such seed dressing formulations are known in the art. The seed dressing formulation can contain a single active ingredient or a combination of active ingredients in encapsulated form, for example as slow-release capsules or microcapsules.

[0079] Generally, these formulations contain from 0.01% to 90% by weight of the active agent, from 0 to 20% of an agriculturally acceptable surfactant and 10% to 99.99% of a solid or liquid formulation inert agent and one or more adjuvants, streptimidone, marinomycin optionally together with other active agents (especially microbicides or preservatives, etc.). The concentrated form of the composition usually contains from about 2% to 80% by weight, preferably from about 5% to 70% by weight of the active agent. The application form of the formulation can contain, for example, from 0.01% to 20% by weight, preferably from 0.01% to 5% by weight of the active agent. However, commercial products will preferably be formulated as concentrates and the end user will generally use diluted formulations.

[0080] Examples

[0081] The following examples are used to illustrate the present invention. Temperatures are given in degrees Celsius (°C), rh means relative humidity, and ppm means parts per million by weight. Colby refers to COLBY, S.R. "Calculating synergistic and antagonistic responses of herbicide combination". Weeds, Vol. 15, pp. 20 - 22; 1967 as discussed above.

[0082] Examples

[0083] 1. Fungicidal Activity of a Mixture with Malonomycin in Liquid Culture Assays

[0084] Method:

[0085] Streptimidone (CAS: 738 - 72 - 7) was purchased from a commercial supplier. A stock solution of streptimidone (up to 10 mg / ml) was generated in DMSO. Malonomycin was generated according to Law et al., 2018 (Nature Catalysis | Volume 1 | December 2018 | 977 - 984). A stock solution of malonomycin was generated in water plus 0.025% Tween20.

[0086] An assay for 96 - well plates was designed to test the efficacy of mixtures of streptimidone and malonomycin in controlling fungal pathogens in liquid culture assays.

[0087] Table 1: Overview of the 96 - well test plate (including the concentration of compounds in each well). The upper number in the cell represents the malonomycin concentration (ppm), and the lower number represents the streptimidone concentration (ppm). Column (1) is the dilution series of streptimidone, row (H) is the dilution series of malonomycin, and column (12) is the cell for the untreated test substance.

[0088]

[0089] The 96 - well plate design allows for the comparison of the disease control of mixtures with that of the corresponding single compounds at the same rate. By comparing the evaluated efficacy of the mixture with the efficacy of the same mixture calculated according to Colby, it can be determined whether the mixture is additive (efficacy similar to that calculated by Colby), synergistic (efficacy better than that calculated by Colby), or antagonistic (efficacy lower than that calculated by Colby).

[0090] The same 96 - well plate design can also evaluate whether the two compounds can be mixed at different application rates and mixing ratios. The plate design outlined in Table 1 will provide the following mixing ratios, as shown in Table 2.

[0091] Table 2: Mixing ratios of the two compounds in the 96 - well plate assay design as outlined in Table 1. The numbers represent the ratio of compound 1: compound 2. Compound 1 is malonomycin and compound 2 is streptimidone. The plate design spans a wide range, from 641:1 to 1:100.

[0092]

[0093] A master plate of 10x concentrated solution with a compound stock solution diluted in water plus 0.025% Tween20 was prepared. The concentrations of DMSO (stock solution from streptolydigin) and Tween20 were kept constant in all wells of the master plate. 10 μl was transferred from the master plate to a 96-well test plate. Then nutrient broth containing fungal spores / hyphal fragments was added to the test plate to obtain a 1x final concentration of the test compound (as outlined in Table 1). The test plates were incubated in the dark at 24 °C and 96% rh. After about 3 days, the inhibition of fungal growth was determined photometrically, and the percentage reduction in fungal growth relative to the untreated control was calculated. The efficacy of the mixtures was tested on the following fungal species:

[0094] Botrytis cinerea (EPPO code: BOTRCI)

[0095] Fungal conidia from cryogenic storage were directly incorporated into nutrient broth (Vogel's minimal medium). These test plates were incubated at 24 °C and after 72 hr, the inhibition of growth was determined photometrically.

[0096] Results

[0097] Table 3: Control of Botrytis cinerea by single compounds and mixtures. The plate design including the concentrations of streptolydigin and malonomycin is shown in Table 1. Values indicate the control of fungal growth (percent reduction in growth in the test wells compared to the untreated control).

[0098]

[0099] Table 4: Comparison of measured values of disease control of Botrytis cinerea (reported in Table 3) with values calculated for the same mixtures using the Colby formula. The numbers reported in the table represent the difference between the measured efficacy (in %) and the calculated efficacy (in %). Values near 0 (zero) indicate additive activity, while values above zero indicate synergistic activity.

[0100]

[0101] Conclusion:

[0102] Streptolydigin and malonomycin can be mixed to obtain complete or partial control of fungal pathogens. The mixing ratios of the two compounds in the mixtures can vary widely, but still produce 50% or more control of fungal growth. Surprisingly, the efficacy of many mixtures is better than that predicted by Colby-based calculations, indicating a synergistic effect in the control of fungal pathogens by the mixture of streptolydigin and malonomycin. This surprising synergistic effect was observed in the tests for the control of Botrytis cinerea.

[0103] 2. Fungicidal Activity of the Mixture with Malonomycin in the Leaf Disc Assay

[0104] Method:

[0105] Streptimidone (CAS: 738 - 72 - 7) was purchased from a commercial supplier. A stock solution of streptimidone (up to 10 mg / ml) was generated in DMSO. Malonomycin was generated according to Law et al., 2018 (Nature Catalysis | Volume 1 | December 2018 | 977 - 984). A stock solution of malonomycin was generated in water plus 0.025% Tween 20.

[0106] An assay targeting two 24 - well plates was designed to test the control efficacy of the mixture of streptimidone and malonomycin against fungal pathogens in the leaf disc assay.

[0107] Table 5 and Table 6: Overview of 24 - well test plates (1) and (2) (including the concentrations of the compounds sprayed into each well). The upper number in the cell represents the streptimidone concentration (ppm), and the lower number represents the malonomycin concentration (ppm). Column (1) is the dilution series of streptimidone, and rows (2 - D) are the dilution series of malonomycin. Well 2 - D-(1) represents the untreated test item. This design has been applied to tests including Puccinia recondita (EPPO code: PUCCRE) with prophylactic and therapeutic spray times.

[0108] 24 - well plate (1)

[0109]

[0110] 24 - well plate (2)

[0111]

[0112] Table 7: The mixing ratios of the compounds sprayed in the 24 - well plate assay are as outlined in Table 5 and Table 6. The numbers represent the ratio of Compound 1:Compound 2. Compound 1 is malonomycin, and Compound 2 is streptimidone. The plate designs of the two 24 - well plates span a wide range, from 64:1 to 1:270.

[0113]

[0114] A first set of master plates of 1x concentrated spray solutions with streptimidone stock solutions diluted in water according to Table 5 or Table 6, respectively, were prepared. Each well contained 2% DMSO and 0.025% Tween20. Correspondingly, a second set of master plates with 1x concentrated marinomycin stock solutions diluted in water were prepared. Each well of the second set contained 0.025% Tween20. Leaf segments placed on agar in a 24-well plate were sprayed with 8 μl of the solution from the master plate containing streptimidone, allowed to dry, and then sprayed with 8 μl of the solution from the master plate containing marinomycin after 2 hours. After the second spray and drying, the leaf segments were infected with fungal spores to obtain the prophylactic application time. Alternatively, leaf segments infected one day prior to spraying with the compound were used to determine the therapeutic spray time. Additionally, several plates were made where leaf segments were sprayed 2x in the absence of the test compound (containing only DMSO and Tween20), representing untreated test samples. The leaf coverage of disease symptoms of each leaf segment was evaluated. The percentage reduction in leaf coverage relative to the untreated test was calculated. The efficacy of the test mixtures was tested in duplicate on different fungal species. The reported efficacy values are the average of the results of two replicates.

[0115] Puccinia recondita (EPPO code: PUCCRE), using prophylactic spray time.

[0116] Leaf segments of wheat (cultivar Kanzler) were placed on agar in a multi-well plate (24-well format) and sprayed with the test solution (8 μl / well). After drying, the leaf discs were inoculated with a spore suspension of the fungus. After appropriate incubation, the compound activity at 8 days post inoculation (8 dpi) was evaluated as prophylactic fungicidal activity.

[0117] Puccinia recondita (EPPO code: PUCCRE), using therapeutic spray time.

[0118] Leaf segments of wheat (cultivar Kanzler) were placed on agar in a multi-well plate (24-well format). These leaf discs were then inoculated with a spore suspension of the fungus. One day after inoculation, they were sprayed with the test solution (8 μl / well). After appropriate incubation, the compound activity at 8 days post inoculation (8 dpi) was evaluated as prophylactic fungicidal activity.

[0119] Results

[0120] Table 8: Control of Puccinia recondita (prophylactic) by single compounds and mixtures. The plate designs including streptimidone and marinomycin concentrations are shown in Tables 5 and 6. Values indicate control of fungal growth (% reduction in symptoms on leaf segments compared to untreated test).

[0121]

[0122] Table 9: Comparison of measured values of disease control of Puccinia recondita (preventive) (as reported in Table 8) with values calculated for the same mixtures using the Colby formula. The numbers reported in the table represent the difference between the measured efficacy (%) minus the calculated efficacy (%). Values near 0 (zero) indicate additive activity, while values above zero indicate synergistic activity.

[0123]

[0124] Table 10: Control of Puccinia recondita (curative) by single compounds and mixtures. The plate designs including concentrations of streptimidone and malonamycin are shown in Tables 5 and 6. The values indicate control of fungal growth (% reduction in symptoms on leaf segments compared to untreated assays).

[0125]

[0126] Table 11: Comparison of measured values of disease control of Puccinia recondita (curative) (as reported in Table 10) with values calculated for the same mixtures using the Colby formula. The numbers reported in the table represent the difference between the measured efficacy (%) minus the calculated efficacy (%). Values near 0 (zero) indicate additive activity, while values above zero indicate synergistic activity.

[0127]

[0128]

[0129] Conclusion:

[0130] Streptimidone and malonamycin can be mixed to obtain complete or partial control of fungal pathogens. The mixing ratio of the two compounds in the mixture can vary widely, but still produces 50% or more control of fungal growth when sprayed on leaves. Surprisingly, the efficacy of many mixtures is better than that predicted by Colby-based calculations, indicating a synergistic effect in the control of fungal pathogens when the mixture of streptimidone and malonamycin is sprayed on leaves. This surprising synergistic effect was observed in the tests for controlling Puccinia recondita.

Claims

1. A composition comprising streptimidone and malinomycin.

2. The composition according to claim 1, wherein the ratio of streptimidone to malinomycin is from 10:1 to 1:500 by weight.

3. The composition according to claim 2, wherein the ratio of streptimidone to malinomycin is from 1:1 to 1:300 by weight.

4. An agrochemical composition comprising a fungicidally effective amount of a mixture comprising streptimidone and malinomycin.

5. The agrochemical composition according to claim 4, further comprising an agrochemically acceptable diluent or carrier.

6. The agrochemical composition according to claim 4 or 5, comprising the composition according to any one of claims 1 to 3.

7. A method for controlling or preventing fungal infection of plants, wherein a fungicidally effective amount of the composition according to any one of claims 1 to 6 is applied to the plants, parts thereof or the places where they are located.

8. The method according to claim 7, wherein the composition is applied to the plants at a rate of from 0.1 g to 6 kg per hectare of the combined weight of streptimidone and malinomycin.

9. The method according to claim 7, wherein the composition is applied to the seeds at a rate of from 0.001 to 100 g per kg of seeds of the combined weight of streptimidone and malinomycin.

10. The method according to any one of claims 7 to 9, wherein the plants are selected from the group consisting of cereals and legumes.

11. The method according to any one of claims 7 to 10, wherein the fungi are selected from the group consisting of Fusarium avenaceum, Fusarium culmorum, Fusarium langsethiae, Fusarium poae, Fusarium sporotrichioides, Fusarium tricinctum, Fusarium xyrophilum, Fusarium verticillioides, Fusarium subglutinans, Septoria tritici, Puccinia recondita (=Puccinia striiformis), Mycosphaerella fijiensis, Puccinia striiformis, Magnaporthe oryzae and Rhizoctonia solani.

12. Use of the composition comprising streptimidone and malinomycin according to any one of claims 1 to 3 as an antifungal agent or as a fungicide.

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