Fungicidal mixtures comprising cyclothiazomycin C and malinomycin

Abstract

A composition comprising cyclothiazomycin C and 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 are disclosed.

Description

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

[0002] Cyclothiazolyl C is a known compound having formula I;

[0003]

[0004] The structure of cyclothiazomycin C is disclosed on page 3 of WO 2015191789. The disclosure also gives examples of the antimicrobial activity of cyclothiazomycin C in Table 6 on page 31. After Table 6 on page 31 in WO 2015191789, it is clearly stated that "the greatest inhibitory activity was observed against Bacillus. We also decided to evaluate whether cyclothiazomycin C exhibited growth inhibition against a variety of fungal strains, but none was observed."

[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] Malenomycin is a natural compound produced by a fermentation process. US 3 536 811 discloses malenomycin useful as an antibiotic and protozoan growth inhibitor. EP 1 860 939 describes malenomycin as an agricultural fungicide.

[0008] It has now surprisingly been found that mixtures comprising cyclothiazomycin C and malenomycin can exhibit an unexpected synergistic fungicidal effect.

[0009] According to a first aspect of the present invention, a mixture comprising cyclothiazolyl ampicillin C and malenomycin is provided.

[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 cyclothiazomycin C and malenomycin. 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 microbially produced compositions or non-natural compositions.

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

[0013] According to a third aspect of the present invention, there is provided a method for controlling or preventing plants from being infected by fungi, wherein a fungicidally effective amount of an agrochemical composition comprising a mixture of thiazolinyl and malenomycin is applied to the plants, parts thereof or a locus thereof.

[0014] According to a fourth aspect of the present invention, there is provided the use of a mixture comprising cyclothiazomycin C and malenomycin as a fungicide. According to this particular aspect of the present invention, the use may not involve a method of treating the human or animal body by surgery or therapy.

[0015] Cyclothiazolycin C can be obtained as disclosed in WO 2015191789. In particular, it is produced by NRRL strain WC-3908 and can be isolated as described in paragraph

[0178] of WO 2015191789. Strain WC-3908 is publicly available through the ARS Culture Collection (NRRL), 1815 N, University Street, Peoria, IL, 61604.

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

[0017] The mixture comprising thiazolyl and malenomycin can be used as an active ingredient, for example, for controlling fungal plant pests in the agricultural sector and related fields of use, or used on non-living materials to control corrupt fungi or fungi potentially harmful to humans. The mixture comprising thiazolyl and malenomycin has surprising activity at low application rates and is well tolerated by plants. It has very useful therapeutic and preventive properties and can be used to protect a wide range of cultivated plants. The mixture comprising thiazolyl and malenomycin has surprising synergy in addition. And the mixture can be used to suppress or destroy the fungi that occur on the 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 infection of plants or plant propagation materials and / or harvested food crops susceptible to fungal attack by treating plants or plant propagation materials and / or harvested food crops, wherein a fungicidally effective amount of a mixture comprising cyclothiazolin and malenomycin is applied to these plants, their parts or their loci.

[0019] Mixtures comprising cyclothiazolin and malenomycin can also be used more widely as fungicides. As used herein, the term "fungicide" means a compound that controls, modifies, or prevents fungal growth. The term "fungicide effective amount" when used means the amount of such a compound or a combination of such compounds that can have 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 in or on a plant to prevent fungal infection.

[0020] It is also possible to use a mixture comprising cyclothiazomycin C and malenomycin as a seed dressing for treating plant propagation materials (e.g., seeds, such as fruits, tubers or grains, or plant cuttings) for protection against fungal infections together with plant pathogenic fungi present in the soil. Propagation materials can be treated with a composition comprising cyclothiazomycin C and malenomycin before planting: for example, seed dressing can be used before sowing. Cyclothiazomycin C and malenomycin can also be applied to grains (coating) by dipping seeds in a liquid formulation or by coating them with a solid formulation. Compositions can also be applied to the planting site when planting propagation materials, such as being applied to the furrows of seeds during sowing. The present invention also relates to such methods for treating plant propagation materials, and to plant propagation materials so treated.

[0021] In addition, the mixture comprising cyclothiazomycin C and malenomycin can be used to control fungi in related fields, such as protection of industrial materials (including wood and wood-related industrial products), food storage, pharmaceutical applications, veterinary applications and hygiene management.

[0022] Furthermore, the invention can also be used to protect non-living materials such as wood, wallboard, wallpaper and paint from fungal attack.

[0023] Examples of important fungi that need to be controlled in agriculture and other areas 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 striiformis), 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, chive, 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" shall be understood to also include useful plants that are 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) as a result of 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" shall be understood to also include 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 those of the genus Bacillus.

[0030] A mixture containing cyclothiazomycin C and maridomycin can also be used, for example, for lawns, ornamental plants such as flowers, shrubs, broad-leaved trees or evergreen plants, such as conifers, and tree injection, pest management, etc.

[0031] Preferred crops on which a mixture containing cyclothiazomycin C and maridomycin can be used include bananas, cereals and legumes (such as peanuts or soybeans), and cereals (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, along with established vegetation.

[0033] The term "plant" refers to all 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 plant propagation, 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 will be transplanted after germination or after emergence can also be mentioned. These young plants can be protected before transplantation by being treated completely or partially by dipping. Preferably, "plant propagation material" shall be understood to mean seeds.

[0035] A mixture containing cyclothiazomycin C and maridomycin can be used in an unmodified form, or preferably, together with adjuvants conventionally used in the formulation field. For this purpose, it can be conveniently formulated in a known manner into emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions or suspensions, dilute emulsions, wettable powders, soluble powders, dust powders, granules, 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 that time, such as spraying, atomizing, dusting, sowing, coating, or irrigation. 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] In addition, when obtaining cyclothiazomycin C from a microorganism, it can be isolated from such a microorganism as described in WO 2015191789. Alternatively, a significant amount of cyclothiazomycin C may be present in the culture medium in which the microorganism grows, in which case the culture medium or broth can be used together with malinomycin to formulate a fungicidal composition. Malinomycin can also be produced by microorganisms disclosed in Examples IA and IB of EP 1860939. As another alternative, the microorganism can produce both cyclothiazomycin C and malinomycin, in which case the microorganism itself can be used to formulate the composition. Accordingly, a process for producing cyclothiazomycin C and malinomycin is disclosed, the process comprising fermenting a microorganism in a suitable fermentation medium under conditions allowing the production of cyclothiazomycin C and malinomycin. In such a case, the microorganism can be formulated as live cells actively producing cyclothiazomycin C and malinomycin, 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 defoamers and crystal growth inhibitors. In use, these concentrates are diluted in water and are generally 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 bleaching earth, kaolin, silica and other readily wettable organic or inorganic solids. Wettable powders generally 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 and a liquid or solid emulsifier, or can also contain a liquid carrier 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 generally 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 to the area to be treated without dilution. 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, glue, 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 from 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. Encapsulated particles are usually 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 granules. 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 active ingredients in solvents such as water, acetone, alkylated naphthalenes, xylene, and other organic solvents, in which the active ingredient is completely dissolved 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 oils, acetone, methyl ethyl ketone, cyclohexanone, acetic anhydride, acetonitrile, acetophenone, amyl acetate, 2-butanone, chlorobenzene, cyclohexane, cyclohexanol, alkyl acetates, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol 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 be advantageously 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 lauryltrimethylammonium 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] In addition, further, other agrochemical active ingredients or compositions can be combined with the compositions of the present invention and used in the methods of the present invention and applied simultaneously or sequentially with the compositions of the present invention. When applied sequentially, the compositions of the present invention can be applied to plants during different growth periods from other agrochemical active ingredients. When applied simultaneously, these additional active ingredients can be formulated together with the compositions of the present invention or mixed, for example, in a spray tank. These additional agrochemical active ingredients can be fungicides, herbicides, insecticides, bactericides, acaricides, nematicides, growth stimulants, systemic acquired resistance compounds 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] Mixtures comprising cirothiazoleomycin C and maridomycin can be used in the form of agrochemical compositions and can be applied to crop areas or plants to be treated either 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 auxiliaries customarily used in the formulation art.

[0054] Mixtures comprising cirothiazoleomycin C and maridomycin can be used in the form of (fungicidal) compositions for controlling or protecting against phytopathogenic microorganisms, these compositions comprising cirothiazoleomycin C and maridomycin as active ingredients and at least one of the abovementioned auxiliaries.

[0055] Accordingly, the present invention provides compositions, preferably fungicidal compositions, which comprise cirothiazoleomycin C, maridomycin, an agriculturally acceptable carrier and optionally auxiliaries. 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 cirothiazoleomycin C and maridomycin, the composition can comprise at least one or more pesticidally active compounds, for example further fungicidal active ingredients.

[0056] 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.

[0057] The compositions according to the invention are prepared in a manner known per se, in the absence of auxiliaries, for example by grinding, sieving 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 by 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 present invention.

[0058] Another aspect of the invention relates to the use of a composition comprising cyclothiazomycin C and maridamycin, or a fungicidal or insecticidal mixture comprising cyclothiazomycin C and maridamycin (mixed with other fungicides or insecticides as described above), for controlling or preventing plants (e.g., useful plants such as crop plants), their propagation materials (e.g., seeds), harvested crops (e.g., harvested food crops), or inanimate materials from being infested by insects or phytopathogenic microorganisms (preferably fungal organisms).

[0059] A further aspect of the invention relates to a method for controlling or preventing plants (e.g., useful plants such as crop plants), their propagation materials (e.g., seeds), harvested crops (e.g., harvested food crops), or inanimate materials from being infested by insects or phytopathogenic or spoilage microorganisms or organisms potentially harmful to humans (especially fungal organisms), which method comprises applying a mixture comprising cyclothiazomycin C and maridamycin as an active ingredient to these plants, parts of these plants or their sites, their propagation materials, or any part of these inanimate materials.

[0060] Controlling or preventing means reducing the infestation by phytopathogenic or spoilage microorganisms or organisms potentially harmful to humans (especially fungal organisms) to a proven improved level.

[0061] A preferred method for controlling or preventing crop plants from being infested 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 containing 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 roots through the soil by wetting the site of the plants with a liquid formulation or by applying the compounds in solid form, e.g., 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 coating them with a solid formulation.

[0062] Formulations (e.g., compositions containing 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)).

[0063] The weight / mole ratio of cyclothiazomycin C to maridamycin 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.

[0064] Preferred application rates are generally from 0.1 g to 6 kg of active ingredient (a.i.; combined weight of cicularin C and marinomycin) / 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.

[0065] When the combinations according to the invention are used for treating seeds, rates of from 0.001 to 100 g of active ingredient / kg of seeds, preferably from 0.01 to 10 g / kg of seeds, are generally sufficient.

[0066] Suitably, prophylactic (meaning before the development of the disease) or therapeutic (meaning after the development of the disease) applications are made of a composition comprising cicularin C and marinomycin according to the invention.

[0067] Certain mixtures of cicularin C and marinomycin can show 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 obeys 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):

[0068] ppm = milligrams of active ingredient (= a.i.) per liter of spray mixture

[0069] X = % action of active ingredient A), using p ppm of active ingredient

[0070] Y = % action of active ingredient B), using q ppm of active ingredient.

[0071] According to COLBY, the expected (additive) action of active ingredient A) + B), using p + q ppm of active ingredient, is:

[0072]

[0073] If the actually observed action (O) is greater than the expected action (E), then the action of the combination is superadditive, i.e., a synergistic effect exists. Mathematically, the synergistic effect corresponds to the positive value of the difference (O - E). In the case of 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.

[0074] However, in addition to the actual synergism 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 early germination.

[0075] The compositions according to the invention can be used in any conventional form, for example, in the form of a two-pack, a powder for dry seed treatment (DS), an emulsion for seed treatment (ES), a flowable concentrate for seed treatment (FS), a solution for seed treatment (LS), a water-dispersible powder for seed treatment (WS), a capsule suspension for seed treatment (CF), a gel for seed treatment (GF), an emulsion concentrate (EC), a suspension concentrate (SC), a suspo-emulsion (SE), a capsule suspension (CS), a water-dispersible granule (WG), an emulsifiable granule (EG), a water-in-oil emulsion (EO), an oil-in-water emulsion (EW), a microemulsion (ME), an oil dispersant (OD), an oil miscible flowable (OF), an oil-soluble concentrate (OL), a soluble concentrate (SL), an ultra-low volume suspension (SU), an ultra-low volume liquid (UL), a technical concentrate (TK), a dispersible concentrate (DC), a wettable powder (WP) or any technically feasible formulation in combination with agriculturally acceptable adjuvants.

[0076] 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-term sustained efficacy can also be used. In particular, formulations to be applied in spray form, such as water-dispersible concentrates (e.g. EC, SC, DC, OD, SE, EW, EO, etc.), wettable powders and granules, may contain surfactants such as wetting agents and dispersants and other compounds providing auxiliary effects, for example condensation products of formaldehyde with naphthalene sulfonates, alkylaryl sulfonates, lignin sulfonates, fatty alkyl sulfates, and ethoxylated alkyl phenols and ethoxylated fatty alcohols.

[0077] 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 may contain a single active ingredient or a combination of active ingredients in encapsulated form, such as as slow-release capsules or microcapsules.

[0078] Generally, these formulations contain 0.01% to 90% by weight of an active agent, 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, cyclothiazomycin C, malinomycin optionally together with other active agents (especially microbicides or preservatives, etc.). The concentrated form of the composition usually contains between about 2% and 80% by weight, preferably between about 5% and 70% by weight, of the active agent. The application form of the formulation may contain, for example, 0.01% to 20% by weight, preferably 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.

[0079] Examples

[0080] 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 [Calculating synergistic and antagonistic responses of herbicide combination]”. Weeds [Weeds], Volume 15, Pages 20 - 22; 1967 as discussed above.

[0081] 1. Fungicidal activity of mixtures with malinomycin in liquid culture assays

[0082] Method:

[0083] Cyclothiazomycin C was produced as disclosed in WO 2015191789. A stock solution of cyclothiazomycin C (up to 10 mg / ml) was produced in DMSO. Malinomycin was produced according to Law et al., 2018 (Nature Catalysis [Nature Catalysis] | Volume 1 | December 2018 | 977 - 984). A stock solution of malinomycin was produced in water plus 0.025% 20.

[0084] An assay for 96 - well plates was designed to test the control efficacy of mixtures of cyclothiazomycin C and malinomycin combinations against fungal pathogens in liquid culture assays.

[0085] Table 1: Overview of 96-well test plate (including concentration of compounds in each well). The upper number in the cell represents the concentration of maridomycin (ppm), and the lower number represents the concentration of cycloheximide C (ppm). (1) Column represents the dilution series of cycloheximide C, (H) row represents the dilution series of maridomycin, and (12) column represents the cell of untreated control.

[0086] ppm (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) A 0 1000 500 250 125 62.5 31.25 15.63 7.81 3.00 1.00 0 100 100 100 100 100 100 100 100 100 100 100 0 B 0 1000 500 250 125 62.5 31.25 15.63 7.81 3.00 1.00 0 50 50 50 50 50 50 50 50 50 50 50 0 C 0 1000 500 250 125 62.5 31.25 15.63 7.81 3.00 1.00 0 25 25 25 25 25 25 25 25 25 25 25 0 D 0 1000 500 250 125 62.5 31.25 15.63 7.81 3.00 1.00 0 12.5 12.5 12.5 12.5 12.5 12.5 12.5 12.5 12.5 12.5 12.5 0 E 0 1000 500 250 125 62.5 31.25 15.63 7.81 3.00 1.00 0 6.25 6.25 6.25 6.25 6.25 6.25 6.25 6.25 6.25 6.25 6.25 0 F 0 1000 500 250 125 62.5 31.25 15.63 7.81 3.00 1.00 0 3.125 3.125 3.125 3.125 3.125 3.125 3.125 3.125 3.125 3.125 3.125 0 G 0 1000 500 250 125 62.5 31.25 15.63 7.81 3.00 1.00 0 1.56 1.56 1.56 1.56 1.56 1.56 1.56 1.56 1.56 1.56 1.56 0 H 0 1000 500 250 125 62.5 31.25 15.63 7.81 3.00 1.00 0 0 0 0 0 0 0 0 0 0 0 0 0

[0087] The 96-well plate design allows 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).

[0088] The same 96-well plate design can also evaluate whether 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.

[0089] Table 2: Mixing ratios of 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 maridomycin, and compound 2 is cycloheximide C. The plate design spans a wide range, from 641:1 to 1:100.

[0090] (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) A 10:1 5:1 2.5:1 1.25:1 1:1.6 1:3.2 1:6 1:13 1:33 1:100 B 20:1 10:1 5:1 2.5:1 1.25:1 1:1.6 1:3.2 1:6 1:17 1:50 C 40:1 20:1 10:1 5:1 2.5:1 1.25:1 1:1.6 1:3.2 1:8 1:25 D 80:1 40:1 20:1 10:1 5:1 2.5:1 1.25:1 1:1.6 1:4.2 1:13 E 160:1 80:1 40:1 20:1 10:1 5:1 2.5:1 1.25:1 1:2.1 1:6 F 320:1 160:1 80:1 40:1 20:1 10:1 5:1 2.5:1 1:1 1:3.1 G 641:1 321:1 160:1 80:1 40:1 20:1 10:1 5:1 1.9:1 1:1.6 H

[0091] A master plate with a 10x concentrated solution of the compound stock solution diluted in water plus 0.025% Tween20 was prepared. The concentrations of DMSO (from the stock solution of cycloheximide C) and Tween20 were kept constant in all wells of the master plate. 10 μl of the solution was transferred from the master plate to the 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 plate was 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 mixture was tested against the following different fungal species:

[0092] Septoria tritici (EPPO code: SEPTTR)

[0093] Fungal conidia from cryogenic storage were directly incorporated into nutrient broth (PDB: potato dextrose broth). These test plates were incubated at 24 °C and inhibition of growth was determined photometrically after 72 hr.

[0094] Fusarium culmorum (EPPO code: FUSACU)

[0095] Fungal conidia from cryogenic storage were directly incorporated into nutrient broth (PDB: potato dextrose broth). These test plates were incubated at 24 °C and inhibition of growth was determined photometrically after 72 hr.

[0096] Microdochium nivale (EPPO code: MONGNI)

[0097] Fungal conidia from cryogenic storage were directly incorporated into nutrient broth (PDB: potato dextrose broth). These test plates were incubated at 24 °C and inhibition of growth was determined photometrically after 72 hr.

[0098] Botrytis cinerea (EPPO code: BOTRCI)

[0099] Fungal conidia from cryogenic storage were directly incorporated into nutrient broth (Vogel's minimal medium). These test plates were incubated at 24 °C and inhibition of growth was determined photometrically after 72 hr.

[0100] Results:

[0101] Table 3: Control of Septoria tritici by single compounds and mixtures. Plate designs including concentrations of cyclosporin C and malonamycin are shown in Table 1. Values indicate control of fungal growth (% reduction in growth in test wells compared to untreated control).

[0102] (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) A 100 100 100 100 100 100 100 100 100 100 100 0 B 90 100 100 100 100 100 100 100 100 90 90 0 C 90 100 100 100 100 100 100 100 100 90 90 0 D 70 100 100 100 100 100 100 100 100 90 90 0 E 70 100 100 100 100 100 100 100 100 90 70 0 F 70 100 100 100 100 100 100 100 90 70 70 0 G 70 100 100 100 100 100 100 100 90 70 70 0 H 0 90 90 70 70 70 50 50 50 20 0 0

[0103] Table 4: Comparison of measured values of disease control of Septoria tritici (reported in Table 3) with values calculated for the same mixtures using the Colby formula. Numbers reported in the table represent the difference between measured efficacy (%) minus calculated efficacy (%). Values near 0 (zero) indicate additive activity, while positive values indicate synergistic activity.

[0104] (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) A 0 0 0 0 0 0 0 0 0 0 B 1 1 3 3 3 5 5 5 -2 0 C 1 1 3 3 3 5 5 5 -2 0 D 3 3 9 9 9 15 15 15 14 20 E 3 3 9 9 9 15 15 15 14 0 F 3 3 9 9 9 15 15 5 -6 0 G 3 3 9 9 9 15 15 5 -6 0 H

[0105] Table 5: Control of Fusarium culmorum by single compounds and mixtures. Plate designs including concentrations of cyclosporin C and malonamycin are shown in Table 1. Values indicate control of fungal growth (% reduction in growth in test wells compared to untreated control).

[0106] (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) A 20 100 100 70 50 50 50 20 20 20 20 0 B 20 100 90 70 50 50 50 20 20 20 20 0 C 20 100 90 50 50 50 20 20 20 20 20 0 D 20 100 90 50 50 20 20 20 20 20 20 0 E 20 100 90 50 20 20 20 20 20 20 20 0 F 20 100 90 50 20 20 20 20 20 20 20 0 G 20 100 70 50 20 20 20 20 20 20 20 0 H 0 20 20 20 20 20 0 0 0 0 0 0

[0107] Table 6: Comparison of measured values for the disease control of Fusarium culmorum (as reported in Table 5) 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 positive values indicate synergistic activity.

[0108] (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) A 64 64 34 14 14 30 0 0 0 0 B 64 54 34 14 14 30 0 0 0 0 C 64 54 14 14 14 0 0 0 0 0 D 64 54 14 14 -16 0 0 0 0 0 E 64 54 14 -16 -16 0 0 0 0 0 F 64 54 14 -16 -16 0 0 0 0 0 G 64 34 14 -16 -16 0 0 0 0 0 H

[0109] Table 7: Control of Microdochium nivale by single compounds and mixtures. The plate design including concentrations of cyproconazole C and malonamycin is shown in Table 1. The values indicate the control of fungal growth (reduction % of growth in the test wells compared to the untreated control).

[0110] (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) A 90 100 100 100 100 100 100 100 100 100 100 0 B 90 100 100 100 100 100 100 100 100 100 100 0 C 90 100 100 100 100 100 100 100 100 90 90 0 D 70 100 100 100 100 100 100 100 100 90 90 0 E 70 100 100 100 100 100 100 100 90 90 90 0 F 70 100 100 100 100 100 100 100 90 90 70 0 G 70 100 100 100 100 100 100 100 90 90 70 0 H 0 100 100 100 90 50 20 20 20 20 20 0

[0111] Table 8: Comparison of measured values for the disease control of Microdochium nivale (as reported in Table 7) 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 positive values indicate synergistic activity.

[0112] (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) A 0 0 0 1 5 8 8 8 8 8 B 0 0 0 1 5 8 8 8 8 8 C 0 0 0 1 5 8 8 8 -2 -2 D 0 0 0 3 15 24 24 24 14 14 E 0 0 0 3 15 24 24 14 14 14 F 0 0 0 3 15 24 24 14 14 -6 G 0 0 0 3 15 24 24 14 14 -6 H

[0113] Table 9: Control of Botrytis cinerea by single compounds and mixtures. The plate design including concentrations of cyproconazole C and malonamycin is shown in Table 1. The values indicate the control of fungal growth (reduction % of growth in the test wells compared to the untreated control).

[0114] (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) A 20 90 90 90 90 90 90 70 70 70 50 0 B 20 90 90 90 90 90 70 70 70 70 50 0 C 20 90 90 90 90 90 70 70 50 50 50 0 D 20 90 90 90 90 90 70 70 50 50 50 0 E 20 90 90 90 90 70 70 70 50 50 50 0 F 20 90 90 90 70 70 70 50 50 20 20 0 G 20 90 90 70 70 70 70 50 20 20 20 0 H 0 70 70 70 70 50 20 0 0 0 0 0

[0115] Table 10: Comparison of measured values for the disease control of Botrytis cinerea (as reported in Table 9) 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 positive values indicate synergistic activity.

[0116] (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) A 14 14 14 14 30 54 50 50 50 30 B 14 14 14 14 30 34 50 50 50 30 C 14 14 14 14 30 34 50 30 30 30 D 14 14 14 14 30 34 50 30 30 30 E 14 14 14 14 10 34 50 30 30 30 F 14 14 14 -6 10 34 30 30 0 0 G 14 14 -6 -6 10 34 30 0 0 0 H

[0117] Conclusion:

[0118] Cyclothiazomycin C and malenomycin can be mixed to obtain complete or partial control of various fungal pathogens. The mixing ratio of the two compounds in the mixture 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 of the mixture of cyclothiazomycin C and malenomycin on the control of fungal pathogens. This surprising synergistic effect was observed in tests for controlling Septoria tritici, Fusarium culmorum, Microdochium nivale, and Botrytis cinerea.

[0119] 2. Fungicidal Activity of the Mixture of Cyclothiazomycin C and Malenomycin in Leaf Disc Assays

[0120] Method:

[0121] Cyclothiazomycin C was produced as disclosed in WO 2015191789. A stock solution of cyclothiazomycin C (up to 10 mg / ml) was produced in DMSO. Malenomycin was produced according to Law et al., 2018 (Nature Catalysis | Volume 1 | December 2018 | 977 - 984). A stock solution of malenomycin was produced in water plus 0.025% Tween 20.

[0122] An assay for two plates was designed to test the control efficacy of the mixture of cyclothiazomycin C and malenomycin in combination against fungal pathogens in leaf disc assays.

[0123] Tables 11 and 12: Overview of test plate (1) and test plate (2) (including the concentrations of the compounds sprayed in each well). The upper number in the cell represents the cyclothiazomycin C concentration (ppm), and the lower number represents the malenomycin concentration (ppm). Column (1) is the dilution series of cyclothiazomycin C, and rows (2 - D) are the dilution series of malenomycin. Well 2 - D-(1) represents the untreated control. This design has been applied to tests including Puccinia recondita (EPPO code: PUCCRE) with prophylactic and therapeutic spray timings.

[0124] Plate (1)

[0125]

[0126] Plate (2)

[0127]

[0128] Table 13: The mixing ratios of the compounds sprayed in the on-plate assays are outlined in Tables 11 and 12. The numbers represent the ratio of Compound 1:Compound 2. Compound 1 is marinomycin, and Compound 2 is cyclothiazomycin C. The plate designs of the two plates span a wide range, from 2:1 to 1:270.

[0129]

[0130]

[0131] A first set of master plates of 1x concentrated spray solutions with cyclothiazomycin C stock solutions diluted in water according to the concentrations in Table 11 or Table 12, 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. 8 μl of the solution from the master plate containing cyclothiazomycin C was sprayed onto the leaf segments placed on the agar in the plates, the leaf segments were dried, and 2 hours later, 8 μl of the solution from the master plate containing marinomycin was sprayed again. After the second spray drying, the leaf segments were infected with fungal spores to obtain the prophylactic application time. Alternatively, leaf segments infected one day before spraying with the compounds were used to determine the therapeutic spray time. Additionally, several plates were made where the leaf segments were sprayed twice in the absence of the test compounds (containing only DMSO and Tween20), representing untreated control samples. The leaf coverage of the disease symptoms of each leaf segment was evaluated. The percentage reduction in leaf coverage relative to the untreated control was calculated. The efficacy of the test mixtures was tested in duplicate. The reported efficacy values are the average of the results of two replicates.

[0132] Puccinia recondita (EPPO code: PUCCRE), using the prophylactic spray time.

[0133] Leaf segments of wheat (cultivar Kanzler) were placed on the agar in a multi-well plate 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.

[0134] Puccinia recondita (EPPO code: PUCCRE), using the therapeutic spray time.

[0135] Leaf segments of wheat (cultivar Kanzler) were placed on the agar in a multi-well plate. Then these leaf discs were inoculated with a spore suspension of the fungus. One day after inoculation, the test solution (8 μl / well) was sprayed. After appropriate incubation, the compound activity at 8 days post-inoculation (8 dpi) was evaluated as therapeutic fungicidal activity.

[0136] Results:

[0137] Table 14: Control of Puccinia recondita (preventive) by single compounds and mixtures. The plate designs including concentrations of cicosazolomycin C and marinomycin are shown in Tables 11 and 12. Values indicate control of fungal growth (% reduction in symptoms on leaf segments compared to untreated control).

[0138]

[0139] Table 15: Comparison of measured values of disease control of Puccinia recondita (preventive) (as reported in Table 14) with values calculated for the same mixtures using the Colby formula. Numbers reported in the table represent the difference between measured efficacy (%) minus calculated efficacy (%). Values near 0 (zero) indicate additive activity, while positive values indicate synergistic activity.

[0140]

[0141] Table 16: Control of Puccinia recondita (curative) by single compounds and mixtures. The plate designs including concentrations of cicosazolomycin C and marinomycin are shown in Tables 11 and 12. Values indicate control of fungal growth (% reduction in symptoms on leaf segments compared to untreated control).

[0142]

[0143]

[0144] Table 17: Comparison of measured values of disease control of Puccinia recondita (curative) (as reported in Table 16) with values calculated for the same mixtures using the Colby formula. Numbers reported in the table represent the difference between measured efficacy (%) minus calculated efficacy (%). Values near 0 (zero) indicate additive activity, while positive values indicate synergistic activity.

[0145]

[0146] Conclusion:

[0147] Cicosazolomycin C and marinomycin 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 cicosazolomycin C and marinomycin is sprayed on leaves. This surprising synergistic effect was observed in tests for controlling Puccinia recondita.

Claims

1. A composition comprising cyclothiazomycin C and maridomycin.

2. The composition according to claim 1, wherein the ratio of cyclothiazomycin C to maridomycin by weight is from 10:1 to 1:

500.

3. The composition according to claim 2, wherein the ratio of cyclothiazomycin C to maridomycin by weight is from 1:1 to 1:

300.

4. An agrochemical composition comprising a fungicidally effective amount of a mixture comprising cyclothiazomycin C and streptomaridomycin.

5. The agrochemical composition according to claim 4, further comprising an agrichemically 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 infestation 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 locus thereof.

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 (ha) of the combined weight of cyclothiazomycin C and maridomycin.

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 cyclothiazomycin C and maridomycin.

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, Mycosphaerella graminicola, Puccinia recondita (= Puccinia triticina), Mycosphaerella fijiensis, Puccinia striiformis, Magnaporthe oryzae and Rhizoctonia solani.

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

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