Methods of controlling phytopathogenic fungi

Abstract

The present disclosure relates to a method of controlling or preventing phytopathogenic diseases or phytopathogenic fungi on plant propagation material, the method comprising applying to the plant propagation material a composition comprising at least component (A) wherein Compound (A) comprises Jampmycin according to the following formula (IIa): [Formula IIa], preferably in a fungicidally effective amount. (IIa)

Description

[0001] This invention relates to a method for controlling diseases on plant propagation material caused by plant pathogenic fungi, especially Fusarium species, using a fungicidal composition.

[0002] Fusarium is a large, global genus of incomplete fungi, containing many plant pathogens that cause considerable economic losses. Fusarium species typically proliferate on plant debris and are thus exposed to fungicides currently used in agriculture. Resistance in Fusarium species may increase due to current environmental fungicide pressures, although the primary assumption is that resistance in Fusarium is pre-existing prior to exposure to fungicides and should therefore be considered inherent resistance. Furthermore, resistance variation can occur due to accidental mutations. Consequently, an increasing number of Fusarium species are exhibiting resistance to known compounds that demonstrate biological activity against plant pathogenic fungi, rendering many conventional fungicides increasingly ineffective in controlling plant diseases caused by Fusarium species. Therefore, Fusarium resistance is a significant problem, and thus, there is an urgent need for new fungicidal compounds and strategies.

[0003] Masaru et al. disclosed jassamycin, which exhibits antifungal activity against some filamentous fungi, in The Journal of Antibiotics, 1990, Vol. 43, No. 7, pp. 748-754, and in US-A-4,803,074, and proposed its use in treating patients.

[0004] A subsequent publication by Fu, Y. et al. in *Nature Communications* 11, 3387 (2020) demonstrated that jaxamycin appears to block a subunit of fungal UDP-glycosyltransferase involved in the first step of the biosynthesis of fungal glycosylphosphatidylinositol (GPI) anchors. It also showed broad-spectrum antifungal activity against several pathogenic fungi, including *Fusarium oxysporum* species, which are resistant to voriconazole and *Echinococcus*, and provided a mouse model for medical infection treatment trials. The article further showed that even minor changes in various structural motifs of jaxamycin can adversely affect its activity, particularly against fungi, which generally appear to be resistant in humans. This has also been described in a review article by Heard S. et al., *Current Opinion in Biotechnology*, Vol. 69, 2021, pp. 232-241. Therefore, the use of this compound as a pharmaceutical treatment against isolated fungal species has been proposed for use in pharmaceuticals. Although the antifungal activity of jasamcinol has been disclosed, its activity in agriculture remains unknown. Improved methods for controlling plant pathogenic fungi in agriculture are needed. Summary of the Invention

[0005] In light of the aforementioned agricultural practices' need to increase resistance to plant pathogenic fungi, particularly Fusarium species and closely related species, a novel method for controlling or preventing plant pathogenic diseases or fungi on plant propagation material is proposed according to the present invention. This method comprises applying to the plant propagation material a composition containing at least component (A), wherein compound (A) comprises jaxamycin according to formula (IIa):

[0006] (IIa),

[0007] Preferably, the effective amount for killing fungi is used.

[0008] It has been found that the method of the present invention is effective against a broad spectrum of Fusarium species. Detailed Implementation

[0009] This invention relates to a novel method for controlling or preventing plant pathogenic diseases or plant pathogenic fungi on plant propagation material, the method comprising applying to the plant propagation material a composition comprising at least component (A), wherein component (A) comprises jaxamycin according to formula (IIa):

[0010] (IIa),

[0011] Preferably, the effective amount for killing fungi is used.

[0012] A method for controlling or preventing plant pathogenic diseases or plant pathogenic fungi on plant propagation material includes applying to the plant propagation material a composition as disclosed herein, which is effective against harmful microorganisms (such as microorganisms that cause plant pathogenic diseases), particularly against plant pathogenic fungi. The method according to the invention includes applying a composition particularly effective against plant pathogenic fungi belonging to the following classes: Ascomycetes (e.g., *Aureobasidium*, *Cyclocarya*, *Erysiphe*, *Pseudomonas*, *Cyclocarya*, *Uncaria*, *Sclerotium*); more preferably against Incomplete Fungi (also known as Deuteromycetes; e.g., *Botrytis*, *Helicobacter*, *Rhizoctonia*, *Fusarium*, *Rhizoctonia*, *Cercospora*, *Alternaria*, *Pyreospora*, and *Pseudocercospora*).

[0013] The method according to the invention comprises applying a composition particularly effective against the following: Fusarium species, such as *Fusarium acacia*, *Fusarium fujikuro*, *Fusarium acuminatum*, *Fusarium scutatum*, *Fusarium aderholdii*, *Fusarium acremoniopsis*, *Fusarium affine*, *Fusarium arthrosporioides*, *Fusarium bubigeum*, *Fusarium circinatum*, *Fusarium crookwellense*, *Fusarium culmorum*, *Fusarium graminearum*, *Fusarium incarnatum*, *Fusarium langureni*, and *Fusarium mangoesense*. Fusarium species include mangiferae, filamentous Fusarium merismoides, beaded Fusarium, palm valley Fusarium, early-maturing Fusarium, proliferating Fusarium, false gramineous Fusarium, redolens Fusarium, sugarcane Fusarium, solanaceous Fusarium, pseudobranchial Fusarium, sterile Fusarium, colloidal Fusarium, sulfur-colored Fusarium, trilinear Fusarium, udum Fusarium, Venetian Fusarium, verticillate Fusarium, rod-shaped Fusarium, and Trichoderma (Fusarium xyroph).

[0014] The method according to the invention includes the application of compositions effective against, and more particularly against, the following: Fusarium solani, Fusarium xanthoides, Fusarium oatum, Fusarium graminearum, Fusarium flocculationii, Fusarium pseudograminearum, Fusarium langureni, Fusarium fusiforme, Fusarium tumefaciens, Fusarium rod-shaped, Fusarium collodionii, Fusarium oxysporum f. sp. Ubense, Fusarium oxysporum f. sp. Tuberosi, and Fusarium oxysporum f. sp. lycopersici.

[0015] The method of the present invention is even more effective against Fusarium oxysporum, Fusarium graminearum, as well as Clostridium nivale and Sclerotinia sclerotiorum.

[0016] The method according to the invention includes the application of a composition that is also effective against: members of the genus *Fusarium*, particularly *Fusarium oxysporum* f.sp. albedinis, *Fusarium oxysporum* f.sp. asparagi, *Fusarium oxysporum* f.sp. batatas, *Fusarium oxysporum* f.sp. betae, *Fusarium oxysporum* f.sp. cattleyae, *Fusarium oxysporum* f.sp. cannabis, *Fusarium oxysporum* f.sp. cepae, and *Fusarium oxysporum* f.sp. chickpea. *Fusarium oxysporum f.sp. ciceris*, *Fusarium oxysporum f.sp. citri*, *Fusarium oxysporum f.sp. coffea*, *Fusarium oxysporum f.sp. cubense*, *Fusarium oxysporum f.sp. cyclaminis*, *Fusarium oxysporum f.sp. herbemontis*, *Fusarium oxysporum f.sp. dianthi*, *Fusarium oxysporum f.sp. Fragariae*, *Fusarium oxysporum f.sp. gladioli*, *Fusarium oxysporum* Coa... *Fusarium oxysporum f.sp.koae*, *Fusarium oxysporum f.sp. lactucae*, *Fusarium oxysporum f.sp. lentis*, *Fusarium oxysporum f.sp. lilli*, and *Fusarium oxysporum f.sp. linimentum*.*Fusarium oxysporum* f.sp. medicaginis, *Fusarium oxysporum* f.sp. melonis, *Fusarium oxysporum* f.sp. momordicae, *Fusarium oxysporum* f.sp. narcissi, *Fusarium oxysporum* f.sp. nicotianae, *Fusarium oxysporum* f.sp. niveum, *Fusarium oxysporum* f.sp. palmarum, and *Fusarium oxysporum* f.sp. passionflower. *Fusarium oxysporum* f.sp. perniciosum, *Fusarium oxysporum* f.sp. phaseoli, *Fusarium oxysporum* f.sp. pisi, *Fusarium oxysporum* f.sp. radicis-lycopersici, *Fusarium oxysporum* f.sp. ricini, *Fusarium oxysporum* f.sp. strigae, *Fusarium oxysporum* f.sp. potato, and / or *Fusarium oxysporum* f.sp. tulipae.

[0017] Surprisingly, while the composition containing jaxamycin showed high activity in vitro compared to *Fusarium oxysporum* f.sp. vasinfectum, it failed to show the same activity in in vivo in cotton seeds in the experiments listed below. Therefore, it appears that the teachings of Fu, Y. et al. in *NatCommun* [Nature Communications] 11, 3387 (2020) may not apply to the entire species *Fusarium oxysporum*. Surprisingly, treatment of seeds with the jaxamycin-containing composition was found to be effective against *Fusarium* species. In contrast, no activity against *Fusarium* was observed when the surrounding soil was treated with jaxamycin.

[0018] Component A disclosed herein may include other compounds having formula I:

[0019] (I).

[0020] The compound according to Formula I is in a free form, an oxidized form such as an N-oxide, or a salt form (e.g., a salt form available in agronomical terms).

[0021] N-oxides are the oxidized forms of tertiary amines or nitrogen-containing heteroaromatic compounds. For example, they are described by A. Albini and S. Pietra in their 1991 book, "Heterocyclic N-oxides," published by CRC Press in Boca Raton.

[0022] Compounds having Formula I can have an asymmetry center, a chiral axis, and a chiral plane, as described, for example, in ELEliel and S.H. Wilen, Stereochemistry of Carbon Compounds, John Wiley & Sons, New York, 1994, pp. 1119-1190, and can exist as racemates, racemic mixtures, and individual diastereomers and all possible isomers and mixtures thereof (including optical isomers). Furthermore, the compounds disclosed herein can exist as tautomers, and both tautomer forms are intended to be covered, even if only one tautomer structure is described.

[0023] This disclosure includes all possible isomers of compounds having Formula I and mixtures thereof. Similarly, Formula I is intended to include all possible co-generated metabolites and tautomers. This disclosure includes all possible tautomers of compounds having Formula I, as well as racemic compounds, i.e., mixtures of at least two or more diastereomers or enantiomers in substantially equal ratios.

[0024] In the compound according to formula I, R 1 Preferably, it represents a C-type ring containing at least two adjacent cyclopropyl rings; more preferably, at least three adjacent cyclopropyl rings; and most preferably, at least four adjacent cyclopropyl rings. 10 To C 18 Alkenyl chain.

[0025] In the compound according to formula I, R 1 Preferably, it represents one of the following substituents:

[0026] ,

[0027] ,

[0028] or

[0029] ,

[0030] Therefore, these components have the following structural formula (II):

[0031] (IIa);

[0032] (IIb); and

[0033] (IIc).

[0034] More preferably, R 1 Basically, it means: ,

[0035] This makes component A have the following formula (IIa):

[0036] (IIa),

[0037] This refers to jasamicin.

[0038] Preferably, component (A) is selected from (2E,4E)-N-[[(2R,3S,4R,5R)-5-(2,4-dioxo-1,3-hexahydropyridazin-1-yl)-3,4-dihydroxyoxacyclopentan-2-yl]methyl]-5-[(1S,2R)-2-[(1R,2R)-2-[(1R,2R)-2-[(1R,2S)-2-[(E)-2-[(1R) [(2R)-2-methylcyclopropyl]vinyl]cyclopropyl]cyclopropyl]cyclopropyl]cyclopropyl]cyclopropyl]pent-2,4-dieneamide; N-{[(2R,3S,4R,5R)-5-(2,4-dioxo-1,3,5,6-tetrahydro-1-pyrimidinyl)-3,4-dihydroxytetrahydro-2-furanyl]methyl}-(2E,4E)-5-[(1R)-2-[(1 R,2S)-2-[(1S)-2-[(1R,2S)-2-{(E)-2-[(1R,2R)-2-methylcyclopropyl]vinyl}cyclopropyl]cyclopropyl]cyclopropyl]cyclopropyl]cyclopropyl]cyclopropyl]-2,4-pentadienamide; and / or N-{[(2R,5R)-5-(2,4-dioxo-1,3,5,6-tetrahydro-1-pyrimidinyl)-3,4-dioxo-1,3,5,6-tetrahydro-1-pyrimidinyl)-3,4-dioxo-1,3,5,6-tetrahydro-1-pyrimidinyl]cyclopropyl]cyclopropyl]cyclopropyl]-2,4-pentadienamide; and / or N-{(2R,5R)-5-(2,4-dioxo-1,3,5,6-tetrahydro-1-pyrimidinyl)-3,4-dioxo-1 ... Hydroxytetrahydro-2-furanyl]methyl}-(2E,4E)-5-[(1S,2S,1'S,2'S)-2'-[(Z)-2-[(1S,2S)-2-{(E)-2-[(1R,2R)-2-methylcyclopropyl]vinyl}cyclopropyl]vinyl]-1,1'-bis(cyclopropane)-2-yl]-2,4-pentadienamide; or combinations thereof.

[0039] The microorganisms expressing compounds according to formula (II) can be *Streptoverticillium* and / or *Streptomyces*, preferably fermenting *Streptoverticillium fervens* and / or *Streptomyces luteoverticillatus*, or their spores, because these microorganisms express compounds having formula (II) as metabolites. Preferably, the microorganisms include fermenting *Streptoverticillium* and / or *Streptomyces luteoverticillatus* expressing jassamycin.

[0040] The compositions disclosed herein comprise at least one compound having formula IIa:

[0041] (IIa);

[0042] as well as

[0043] (B) At least one additive, carrier and / or auxiliary compound.

[0044] The compound with chemical formula (IIa) is called jassamycin, a natural product containing an oligocyclopropyl group, also known as FR-900848, and is a metabolite isolated from cultures of *Streptococcus fermentans* or *Streptococcus faecium*. Jassamycin is a polyketide containing 5'-amino-5'-deoxy-3,4,5,6-tetrahydrouridine, wherein one hydrogen atom of the amino group is replaced by a (1E,3E)-1-[(1R,1'R,1''R,1'''R,2S,2'R,2''R,2'''S)-2'''-{(E)-2-[(1R,2R)-2-methylcyclopropyl]vinyl}[1,1':2',1'':2'',1'''-tetra(cyclopropane)]-2-yl]-5-oxopent-1,3-diene-5-yl group.

[0045] The structure of jasamicin is C. 32 H 43 N3O6 contains 5'-amino-5'-deoxy-5,6-dihydrouridine and an unsaturated fatty acid comprising four tandem and one separate cyclopropane ring.

[0046] The IUPAC name for jasamicin is (2E,4E)-N-[[(2R,3S,4R,5R)-5-(2,4-dioxo-1,3-hexahydropyridazin-1-yl)-3,4-dihydroxyoxacyclopentan-2-yl]methyl]-5-[(1S,2R)-2-[(1R,2R)-2-[(1R,2R)-2-[(1R,2S)-2-[(E)-2-[(1R,2R)-2-methylcyclopropyl]vinyl]cyclopropyl]cyclopropyl]cyclopropyl]cyclopropyl]cyclopropyl]cyclopropyl]pent-2,4-dieneamide.

[0047] Based on the following formulas, compounds IIb and IIc:

[0048] (IIb); and

[0049] (IIc),

[0050] It is a homologue of jassamycin and is expressed in different but usually small or negligible amounts by the aforementioned microbial cultures.

[0051] Although A. Barrett et al., J. Am. Chem. Soc. [Journal of the American Chemical Society] 1996, 118, 45, 11030-11037 disclosed a method for the total synthesis of jasamcinol entitled "pentacyclopropane antifungal agent FR-900848", the compound that can be accessed and used is preferably a metabolite obtained or isolated from bacteria of the genus *Streptomyces* or *Streptomyces*, preferably fermented *Streptomyces* or *Streptomyces glaucus*, or their cultures.

[0052] A particularly suitable approach could be, for example, the production of jaxamycin by culturing fermented Cyclospora and isolating jaxamycin, as disclosed by Masaru et al., as described above.

[0053] Alternatively, a mixture of metabolites and microbacterial cells or spores can be used as component A, provided that jaxamycin is present in an appropriate amount.

[0054] Component (A) can be advantageously prepared in a manner similar to that outlined in US-A-4,803,074 or any procedure listed in the literature.

[0055] Salts of compounds having formula I, preferably compounds having formula IIa), are advantageously included using pK. a Conventional salts formed from inorganic and organic acids of less than approximately 4. These salts include, for example, those derived from inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, aminosulfonic acid, phosphoric acid, nitric acid, hexafluorophosphate, perchloric acid, tetrafluoroboric acid, hexafluoroantimonyic acid, tetraarylboric acid, etc., and those prepared from organic acids such as acetic acid, propionic acid, succinic acid, glycolic acid, stearic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, maleic acid, hydroxymaleic acid, phenylacetic acid, glutamic acid, benzoic acid, salicylic acid, p-aminobenzenesulfonic acid, 2-acetoxybenzoic acid, fumaric acid, toluenesulfonic acid, methanesulfonic acid, ethanedisulfonic acid, oxalic acid, hydroxyethylsulfonic acid, trifluoroacetic acid, etc. Chemically acceptable salts of the compounds disclosed herein include conventional, non-toxic salts of compounds formed from inorganic or organic acids. For example, conventional non-toxic salts include those derived from inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, aminosulfonic acid, phosphoric acid, and nitric acid, as well as salts prepared from organic acids such as acetic acid, propionic acid, succinic acid, glycolic acid, stearic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, pamoic acid, maleic acid, hydroxymaleic acid, phenylacetic acid, glutamic acid, benzoic acid, salicylic acid, p-aminobenzenesulfonic acid, 2-acetoxybenzoic acid, fumaric acid, toluenesulfonic acid, methanesulfonic acid, ethanedisulfonic acid, oxalic acid, hydroxyethylsulfonic acid, and trifluoroacetic acid.

[0056] Agrochemically acceptable salts of the compounds disclosed herein can be prepared from the compounds containing basic or acidic moieties using conventional chemical methods. Typically, salts of basic compounds are prepared by ion-exchange chromatography or by reacting a free base with a stoichiometric amount or excess of the desired salt-forming inorganic or organic acid in a suitable solvent or various combinations of solvents. Similarly, salts of acidic compounds are formed by reaction with a suitable inorganic or organic base.

[0057] Throughout this document, the term "composition" refers to various mixtures or combinations of components (A) and (B), for example, in a single "ready-to-use with water" form, in a combined spray mixture (consisting of formulations of separate single active ingredient components) (such as a "tank mix"), and when used in a sequential manner (i.e., one after another over a suitably short period of time, such as hours or days). For the purposes of this invention, the order in which components (A) and (B) are applied is not critical.

[0058] These compositions may also contain one or more other pest-killing components, which are known and referred to above by their so-called ISO common names or their IUPAC names. Typical pest-killing components are included in the UK Crop Production Council's online Pesticide Manual Online ("E-pesticide Manual") and Alan Wood's Compendium of Pesticide Common Names.

[0059] As used herein, plants include useful plants. "Useful plants" typically include the following plant species: grapevines; cereals such as wheat, barley, corn, maize, rye, or oats; beets such as sugar beets or forage beets; fruits such as pome, drupes, or soft fruits, such as apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries, or blackberries; legumes such as beans, lentils, peas, or soybeans; oil crops such as rapeseed, mustard, poppies, olives, sunflowers, coconuts, castor oil plants, cocoa beans, or peanuts; and cucumbers, such as… Zucchini, cucumber, or cantaloupe; fiber plants such as cotton, flax, hemp, or jute; citrus fruits such as oranges, lemons, grapefruits, or tangerines; vegetables such as spinach, lettuce, asparagus, cabbage, carrots, onions, tomatoes, potatoes, melons, or peppers; Lauraceae, such as avocados, cinnamon, or camphor; corn; tobacco; nuts; coffee; sugarcane; tea; vines; hops; durian; bananas; natural rubber plants; turf or ornamental plants such as flowering plants, shrubs, broadleaf trees, or evergreens, such as conifers. This list does not represent any restrictions.

[0060] The term "useful plants" should be understood to also include useful plants that have developed tolerance to herbicides (like bromobenzonitrile) or herbicide classes (such as HPPD inhibitors, ALS inhibitors like flusulfuron, flusulfuron, and triflusulfuron, EPSPS (5-enol-pyruvyl-shikimate-3-phosphate synthase) inhibitors, GS (glutamine synthase) inhibitors, or PPO (protoporphyrinogen oxidase) inhibitors) through conventional breeding or genetic engineering methods. An example of a crop that has been induced to tolerate imidazolinones (such as methoxymethyl) through conventional breeding methods (mutation) is Clearfield. ® Summer rapeseed (canola). Clearfield is a registered trademark of BASF Agrochemical Products BV. Examples of crops genetically engineered to be resistant to herbicides or herbicide classes include glyphosate- and glufosinate-resistant corn varieties, marketed under the trade name RoundupReady. ® Herculex I® and LibertyLink ® Available for commercial purchase. RoundupReady is a registered trademark of Monsanto Technology LLC; Herculex is a registered trademark of Corteva Agriscience LLC; and LibertyLink is a registered trademark of BASF AgriculturalSolutions Seed US LLC.

[0061] The term "useful plant" should also be understood to include useful plants that have been transformed using recombinant DNA technology to enable them to synthesize one or more selectively acting toxins, such as those known to come from toxin-producing bacteria, especially those of the genus Bacillus.

[0062] The term "useful plant" should also be understood to include useful plants that have been transformed using recombinant DNA technology to enable them to synthesize selectively active antipathogenic substances, such as so-called "pathogenesis-associated proteins" (PRPs, see, for example, EP-A-0 392 225). Examples of such antipathogenic substances and transgenic plants capable of synthesizing such antipathogenic substances are known, for example, from EP-A-0 392 225, WO 95 / 33818, and EP-A-0 353 191. Methods for producing such transgenic plants are generally known to those skilled in the art and are described in, for example, the disclosures mentioned above.

[0063] As used herein, the term "site" for useful plants is intended to include places on which useful plants grow, where plant propagating material of useful plants is sown, or where plant propagating material of useful plants will be placed in the soil. An example of such a site is a field on which crop plants grow.

[0064] The term "plant propagation material" should be understood to refer to the reproductive parts of a plant, such as seeds, which can be used for plant propagation, as well as vegetarian material, such as cuttings or tubers (e.g., potatoes). As used herein, plant propagation material includes the propagation material of plants (such as useful plants). References may include, for example, plant seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes, and parts of the plant. References may also include germinating plants and young plants that will be transplanted after germination or emergence. These young plants can be protected prior to transplanting by complete or partial treatment via maceration. Preferably, "plant propagation material" should be understood to mean seeds.

[0065] In another aspect, this application also relates to plant propagation material coated with the compositions disclosed herein.

[0066] By applying these compositions in the method according to the invention, it is possible to inhibit or destroy plant pathogenic microorganisms that appear on the plant propagation material of various useful plants, while also protecting later-growing plant parts from attack by plant pathogenic microorganisms.

[0067] The composition of the method according to the invention can be applied before or after the plant's propagation material is infected by microorganisms.

[0068] The amount of the composition to be applied will depend on various factors, such as the compound used; the target organism, such as the type of seed; the type of treatment, such as a seed dressing agent; the purpose of the treatment, such as the type of fungus to be controlled; or the timing of application. When applied to beneficial plants, component (A) can typically be applied at a rate of 5 to 2000 g ai / ha, particularly 10 to 1000 g ai / ha, for example, at a ratio of 50, 75, 100, or 200 g ai / ha.

[0069] The method for treating seeds according to the invention comprises applying the composition disclosed herein at a ratio of 0.001 to 50 g of component (A) compound / kg seed, preferably 0.01 to 10 g / kg seed, which is generally sufficient.

[0070] The method according to the invention includes applying a composition, wherein the composition may be used in any conventional form, for example, as a double-packaged 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 suspension emulsion (SE), a capsule suspension (CS), water-dispersible particles (WG), emulsifiable particles (EG), a water-in-oil emulsion (EO), an oil-in-water emulsion (EW), a microemulsion (ME), an oil dispersant (OD), an oil suspension (OF), an oil-soluble liquid (OL), a soluble concentrate (SL), an ultra-low volume suspension (SU), an ultra-low volume liquid (UL), a technical grade (TK), a dispersible concentrate (DC), a wettable powder (WP), or any technically feasible formulation in combination with agriculturally acceptable adjuvants. Such compositions can be produced in conventional ways, for example by mixing the active ingredient with at least one suitable inert formulation adjuvant (e.g., diluent, solvent, filler, and optionally, other formulation ingredients such as surfactants, biocides, antifreeze agents, adhesives, thickeners, and compounds that provide adjuvant effects). Conventional sustained-release formulations designed for long-term sustained efficacy can also be used. In particular, formulations intended for spray application, 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 that provide adjuvant effects, such as condensation products of formaldehyde and naphthalene sulfonates, alkyl aryl sulfonates, lignin sulfonates, fatty alkyl sulfates, and ethoxylated alkylphenols and ethoxylated fatty alcohols.

[0071] The method according to the invention includes applying compositions, wherein these compositions may also contain additional pest control agents, such as fungicides, insecticides, or herbicides. The compositions disclosed herein are agricultural chemical compositions.

[0072] Using the combinations and diluents disclosed herein, the seed dressing formulation is applied to the seeds in a suitable seed dressing formulation form, such as an aqueous suspension or dry powder having good adhesion to the seeds, in a manner known per se. Such seed dressing formulations are known in the art. Seed dressing formulations may contain a single active ingredient or a combination of active ingredients in an encapsulated form, such as as a sustained-release capsule or microcapsule; and also include precise application to the seeds or propagation material, for example, as disclosed in EP 3755137.

[0073] Typically, a formulation comprises, by weight, 0.01% to 90% 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, wherein the active agent is composed of at least a compound of component (A) together with a compound of component (B), and optionally other active agents (particularly microbial agents or preservatives, etc.).

[0074] The concentrated form of the composition typically contains between about 2% and 80% by weight, preferably between about 5% and 70% of an active agent. The formulation may, for example, contain 0.01% to 20% by weight, preferably 0.01% to 5% by weight of an active agent. However, commercial products will preferably be formulated as concentrates, and end users will typically use diluted formulations. Further characteristics of compositions comprising compounds of formula (I) (such as compounds of formula IIa), the method of application thereto to plant propagating material, and the ratio of their application are as described for compositions comprising compounds of formula (I) (such as compounds of formula IIa) and additionally at least one component (B) as described above. Their application can be performed before and after fungal infection of these plant propagating materials. Preferably, treatment is performed before infection.

[0075] Therefore, the present invention provides a method for applying a composition suitable for applying a fungicide to plant propagation material, the composition being a blend of the following components:

[0076] Component B: a surfactant; at least one water-dispersible or water-soluble film-forming polymer; at least one inorganic solid carrier; and optionally, at least one antifreeze agent; and at least one fungicide-effective amount of component A.

[0077] In another embodiment, the method according to the invention includes the application of a composition, wherein the composition provides an aqueous composition suitable for applying a fungicide to plant propagation material, the aqueous composition comprising at least three fungicide active compounds as active ingredients, water, and a blend of these active ingredients.

[0078] In another embodiment, the method according to the invention includes applying a composition suitable for applying a fungicide to plant propagation material containing at least one fungicide active ingredient A. Such compositions are typically described as “seed treatments.” For the purposes of this invention, a seed treatment is defined as an agriculturally active chemical substance applied to seeds or vegetative plant propagation material to control diseased organisms, insects, or other harmful organisms. Seed treatment compositions disclosed herein contain fungicides, but may also contain other pest control agents, such as bactericides and insecticides. Most seed treatments are applied to true seeds, which have a seed coat enclosing the embryo. However, some seed treatments can be applied to vegetative plant propagation material, such as rhizomes, bulbs, corms, or tubers.

[0079] A seed treatment composition is provided that is suitable for applying the composition according to the present disclosure to plant propagation material, the seed treatment composition comprising a compound having formula II(a) as an active ingredient, a carrier (such as water), and a blend of the following components: at least one surfactant; at least one polymer selected from water-dispersible and water-soluble film-forming polymers; and at least one antifreeze agent.

[0080] The use of the compositions described herein for making plant propagation material resistant to fungi is also provided.

[0081] A method for protecting plant propagation material from plant pathogenic fungi is also provided, the method comprising treating the plant propagation material with a fungicide-effective amount of the composition described herein.

[0082] The composition is prepared by tightly mixing the components with a solvent (e.g., water), optionally using a concentrated premix prepared by wet milling of solid components, until a uniformly dispersed phase is achieved.

[0083] This document also provides methods for treating plant propagating material with the compositions disclosed herein and for reducing fungal contamination of plant propagating material, such as seeds. The method involves contacting the seeds with the aforementioned aqueous fungicidal composition.

[0084] This document also discloses the use of the composition for controlling diseases caused by plant pathogens, particularly root rot, wilting, or rust on useful plants (more particularly including soybeans and / or cereals), and / or enhancing the growth of such useful plants, especially for controlling Fusarium species on more preferably plant propagation material (particularly seeds). The invention also provides the use of the composition for making plant propagation material resistant to fungi. Preferably, the composition is used for plant seeds selected from potatoes, wheat, barley, rye, oats, rice, corn, sugar beets, cotton, sorghum, sunflowers, beans, peas, canola, rapeseed, soybeans, cabbage, tomatoes, eggplants, and peppers. Advantageously, this includes transgenic plant seeds. Preferably, the plant or plant propagation material, such as plant seeds, is selected from wheat, corn, soybeans, cotton, barley, and sunflowers.

[0085] This invention also provides a method for protecting plant propagation material from plant pathogenic fungi, the method comprising treating the plant propagation material with a fungicide-effective amount of a composition. Preferably, the plant propagation material is a seed selected from potatoes, wheat, barley, rye, oats, rice, corn, sugar beets, cotton, sorghum, sunflowers, beans, peas, canola, rapeseed, soybeans, cabbage, tomatoes, eggplants, and peppers, with wheat, corn, soybeans, cotton, barley, and sunflowers being more preferred. As used herein, the term "plant" also includes seedlings, shrubs, and crops of fruits and vegetables.

[0086] The following examples illustrate the invention.

[0087] Examples of preparations

[0088]

[0089] Component A is thoroughly mixed with other formulation components (component B) and the mixture is thoroughly ground in a suitable grinder to obtain a wettable powder, which can be diluted with water to provide a suspension with the desired concentration.

[0090]

[0091] The active ingredient is thoroughly mixed with other formulation components and the mixture is thoroughly ground in a suitable grinder to provide a powder that can be used directly for seed treatment.

[0092]

[0093] Emulsions with any required dilution that can be used in plant protection can be obtained by diluting such concentrates with water.

[0094]

[0095] A ready-to-use dust is obtained by mixing the active ingredient with a carrier and grinding the mixture in a suitable grinder. Such powders can also be used for dry seed dressing.

[0096]

[0097] The active ingredient is mixed and ground with other formulation components, and the mixture is moistened with water. The mixture is then extruded and dried in an air stream.

[0098] suspension concentrate

[0099]

[0100] The finely ground active ingredient is thoroughly mixed with other formulation components to obtain a suspension concentrate, which can be diluted in water at any desired ratio. Using such a dilution, living plants and plant propagation material can be treated and protected from microbial contamination by spraying, watering, or immersion.

[0101] Flowable concentrate for seed treatment

[0102]

[0103] The finely ground active ingredient is thoroughly mixed with other formulation components to obtain a suspension concentrate, which can be further diluted in water for application to seeds. Using such a dilution, propagation material can be treated and protected from microbial contamination by spraying, watering, or soaking.

[0104] Therefore, this document provides a method for controlling diseases on plants, comprising applying to plant propagation material a composition containing a compound having formula (IIa) as disclosed herein. This method does not include methods for treating human or animal bodies via surgery or therapy.

[0105] This method can also be used specifically for grain crops, including rice, wheat, rye, oats, barley, millet, and corn or maize.

[0106] This method can also be used specifically against Fusarium graminearum on cereals (especially wheat); Fusarium graminearum on cereals (especially corn or maize); and Monographella nivalis (also known as Fusarium nivale or Fusarium nivale f.sp. graminicola) on cereals (especially barley).

[0107] This method can also be used specifically for fungi of the genus Sclerotium, especially Sclerotium sclerotium, and even more specifically Sclerotium sclerotium on sunflowers.

[0108] Preferred methods are those for controlling pathogens, particularly in cereals such as wheat, barley, rye, or oats; corn or maize; rice; cotton; soybeans; turf; sugar beets; rapeseed; potatoes; pulse crops such as peas, lentils, or chickpeas; and sunflowers.

[0109] The method according to the invention also allows for effective control of other harmful fungi frequently encountered in plants. This disclosure also relates to the use of component (A) or compositions comprising component A according to this disclosure for treating plant propagation material.

[0110] Preferably, the plant propagation material is selected from seeds of plants such as potatoes, wheat, barley, rye, oats, rice, corn, sugar beets, cotton, sorghum, sunflowers, beans, peas, canola, rapeseed, soybeans, cabbage, tomatoes, eggplants, and peppers. Advantageously, the plant propagation material may be genetically modified plant seeds.

[0111] This disclosure also relates to a method for protecting plant propagation material from attack by plant pathogenic fungi, the method comprising treating the plant propagation material with a fungicide-effective amount of component A, wherein component A comprises jaxamycin or a composition comprising component A according to this disclosure, preferably wherein component A comprises jaxamycin. Preferably, in this method, the plant propagation material is a seed selected from plants such as potato, wheat, barley, rye, oats, rice, corn, sugar beet, cotton, sorghum, sunflower, legumes, peas, canola, rapeseed, soybean, cabbage, tomato, eggplant, and pepper; it may include one or more transgenic plant seeds.

[0112] Biological examples

[0113] The jaxamycin used in this example was produced by culturing fermented *Streptococcus* and isolating jaxamycin according to the method disclosed by Masaru et al., *The Journal of Antibiotics*, 1990, Vol. 43, No. 7, pp. 748-754.

[0114] Example 1: In vitro bioassay of various Fusarium species using Jassarmycin

[0115] In vitro bioassay methods for various Fusarium species The inhibition of mycelial growth of various Fusarium species was evaluated in an in vitro bioassay using Piper dishes (9 cm in diameter). The Piper dishes contained a free-flowing concentrate of PDA and jaxamycin as seed treatment at concentrations of 0.01, 0.1, 1, and 10 ppm.

[0116] Each treatment concentration and for the control included three replicates (Pietrochlear plates). Agar plugs were removed from fresh Fusarium colonies using a cork burr and one plug was placed in the center of each plate. The fungus was incubated in the dark at 22°C. To calculate the half-maximum effective concentration (EC50) of jassarmycin, mycelial growth (diameter) was measured after 6 to 13 days of incubation, depending on the Fusarium species.

[0117] Table 1: In vitro results

[0118]

[0119] As shown in Table 1 below, jasamcinol was active against all tested Fusarium species, with EC50% (in ppm) being the highest among them. 50 The value is in the range of < 0.01 to 2.050.

[0120] Example 2: In vivo seed treatment tests using jasamicin against various disease targets

[0121] Various useful plants were infected with specific pathogens, and the effects of the compositions according to this disclosure were tested, as shown in Table 2 below.

[0122] Method for treating Fusarium oxysporum on wheat :

[0123] The aim of this study was to investigate the activity of jaxamycin, formulated as a seed treatment water-dispersible powder, against soil-borne infection of wheat by *Fusarium oxysporum* under controlled conditions. Wheat seeds were treated with a slurry of 10 g / kg of seeds using a Turbula mixer. Three replicates (soil trays) were used, each containing 50 seeds. The soil substrate was infected with an inoculum containing the test pathogen (*Fusarium oxysporum*) prior to sowing. Two control treatments were included in this test: an infected control and an uninfected control. Activity (%) was calculated based on the final seedling emergence rate (%).

[0124] Method for treating Fusarium graminearum on corn :

[0125] The aim of this study was to investigate the activity of jaxamycin, formulated as a seed treatment water-dispersible powder, under controlled conditions, against soil-borne infection of maize by *Fusarium graminearum*. Maize seeds were treated with a slurry of 5 g / kg of seeds using a Turbula mixer. Three replicates (soil trays) were used, each containing 50 seeds. The soil substrate was infected with an inoculum of the test pathogen (*Fusarium graminearum*) before sowing. Two control treatments were included in this test: an infected control and an uninfected control. Activity (%) was calculated based on the final seedling emergence rate (%).

[0126] Method for treating Fusarium moniliforme on soybeans :

[0127] The aim of this study was to investigate the activity of jaxamycin, formulated as a seed treatment water-dispersible powder, against soil-borne infection of soybean by *Fusarium oxysporum* under controlled conditions. Soybean seeds were treated with a slurry at a dose of 5 g / kg of seed using a Turbula mixer. Four replicates (pots) were used, each containing 5 seeds. The soil substrate was infected with an inoculum containing the test pathogen (*Fusarium oxysporum*) prior to sowing. Two control treatments were included in this test: an infected control and an uninfected control. Activity (%) was calculated based on the disease index (severity of symptoms on leaves).

[0128] Methods for treating Fusarium oxysporum cotton-specific strains on cotton. :

[0129] The aim of this study was to investigate the activity of jaxamycin, formulated as a seed treatment concentrate and applied via seed application, against soil-borne infection of cotton by *Fusarium oxysporum* var. *cottonense* under controlled conditions. Cotton seeds were treated with a slurry containing 5 g / kg of the test compound using a Turbula mixer. Four replicates (pots) were used, each containing 5 seeds. The soil substrate was infected with an inoculum of the test pathogen (i.e., *Fusarium oxysporum* var. *cottonense*) prior to sowing. Two control treatments were included in this test: an infected control and an uninfected control. Activity (%) was calculated based on the disease index (severity of symptoms on leaves).

[0130] Methods for using *Clostridium nivale* on barley :

[0131] The aim of this study was to investigate the activity of jaxamycin, formulated as a seed-treatment free-flowing concentrate, applied by seed under controlled conditions, against seed-borne infection of barley caused by *Clostridium nivale*. Barley seeds were treated with a slurry of 10 g / kg of seeds using a Turbula mixer. Two replicates (soil trays) were used, each containing 100 seeds. An infected control treatment was included in this test. Activity (%) was calculated based on the number of infected plants.

[0132] Method for using *Sclerotinia sclerotiorum* on sunflowers :

[0133] The aim of this study was to investigate the activity of jaxamycin, formulated as a flowable concentrate for seed treatment, under controlled conditions, against soil-borne infection of sunflower by *Sclerotinia sclerotiorum*. Sunflower seeds were treated with a slurry of 10 g / kg of seeds using a Turbula mixer. Three replicates (soil trays) were used, each containing 50 seeds. The soil substrate was inoculated with the fungus of the tested pathogen (i.e., *Sclerotinia sclerotiorum*) before sowing. Two control treatments were included in this test: an infected control and an uninfected control. Activity (%) was calculated based on the final seedling emergence rate (%).

[0134] Table 2: Seed treatment tests using jaxamycin against various disease targets

[0135]

[0136] Example 3. Seed-applied jaxamycin versus soil-applied jaxamycin in controlling corn sickle. The effects of Knife Fungus

[0137] The aim of this study was to compare the efficacy of seed-applied jaxamycin versus soil-applied jaxamycin against soil-borne infections of maize caused by Fusarium graminearum under controlled conditions.

[0138] Jaxamycin was applied at a rate of 5 g / 100 kg of seed, with the same application rate used for both seed and soil application treatments on each soil surface to allow for comparison. Maize cultivar Andromeda seeds were treated with a slurry of 5 g / kg of seed using a Turbula mixer according to standard procedures. Four replicates (soil trays) were used, each containing 25 seeds. Jaxamycin was formulated as WS10 (a water-dispersible powder containing 10% of the active ingredient). The soil was inoculated with an inoculum of the fungus testing the pathogen (i.e., Fusarium graminearum) before sowing. This test included two controls: an infected control and an uninfected control. The efficacy (%) of the treatment was calculated based on the final seedling emergence rate (%) compared to the control.

[0139] The efficacy of jaxamycin applied through seeds was 36%, while the efficacy of jaxamycin applied through soil was 0%.

Claims

1. A method for controlling or preventing plant pathogenic diseases or plant pathogenic fungi on plant propagation material, the method comprising applying to the plant propagation material a composition comprising at least component (A), wherein compound (A) comprises jasamicin according to formula (IIa): (IIa), Preferably, the effective amount for killing fungi is used.

2. The method according to claim 1, wherein, The composition further comprises compound (B), wherein compound (B) further comprises at least one agriculturally acceptable carrier, additive and / or formulation adjuvant, and optionally a surfactant.

3. The method according to claim 1 or 2, wherein, The composition further comprises microorganisms capable of expressing compounds having formula IIa as metabolites.

4. The method according to claim 3, wherein, The microorganisms include Streptomyces or Streptomyces, preferably fermenting Streptomyces or Streptomyces gambogey.

5. The method according to any one of claims 2 to 4, wherein, The composition comprises 10% to 99.9% by weight, preferably 20% to 99.9% by weight, more preferably 40% to 99.9% by weight, of a compound having formula (IIa), and 0.1% to 90% by weight, preferably 0.1% to 80% by weight, more preferably 0.1% to 60% by weight, of component (B).

6. The method according to any one of claims 2 to 5, wherein, The weight ratio of component (A) to component (B) is in the range of 100:1 to 1:5000.

7. The method according to any one of claims 1 to 6, wherein, The composition contains one or more other bioactive compounds, preferably one or more other pest control agents, such as fungicides, insecticides, or herbicides.

8. The method according to any one of claims 1 to 7, wherein, The plant pathogenic fungi are selected from species of the genera *Fusarium*, *Sclerotinia*, and *Gerberis*, preferably from *Fusarium solanum*, *Fusarium chrysogenum*, *Fusarium oatum*, *Fusarium graminearum*, *Fusarium proliferatorum*, *Fusarium pseudograminearum*, *Fusarium roninii*, *Fusarium fusiforme*, *Fusarium tumefaciens*, *Fusarium graminearum*, *Fusarium graminearum*, *Fusarium graminearum*, *Fusarium graminearum*, *Fusarium graminearum*, *Fusarium graminearum*, *Fusarium graminearum*, *Fusarium graminearum*, *Fusarium graminearum*, *Fusarium graminearum*, and *Sclerotinia sclerotiorum*, preferably from *Fusarium chrysogenum*, *Fusarium graminearum*, and *Sclerotinia sclerotiorum*.

9. The method according to any one of claims 1 to 8, wherein, The plant propagation material includes seeds.

10. The method according to any one of claims 1 to 9, wherein, Plant propagation material is derived from useful plants selected from the following: cereals, fruits and tree nuts, vegetables, field crops, oil crops, forage crops, forest plants, horticultural crops, floriculture, greenhouse and nursery plants, propagation material, edible herbs and spices, and medicinal herbs, preferably wherein said useful plants are selected from: fruits and tree nuts, vegetables, horticultural crops and floriculture.

11. The method according to claim 10, wherein, The plant propagation material is derived from fruits, soybeans, cereals, and / or sunflowers; preferably, the plant propagation material is derived from plants including wheat, corn, soybeans, barley, sunflowers, and / or cotton.

12. The method according to any one of claims 1 to 11, wherein the method comprises applying 0.001 to 50 g of at least one compound of component (A) per kg of plant propagation material, particularly per kg of seeds.

13. A plant propagation material, particularly seeds, said plant propagation material being coated with a composition comprising component A, wherein compound (A) comprises jaxamycin according to formula (IIa): (IIa)。 14. A composition comprising component A for the protection of plant propagation material, particularly seeds of useful plants, against fungal invasion, especially against Fusarium species, wherein compound (A) comprises jasamicin according to formula (IIa): (IIa) The useful plants mentioned include fruits, soybeans, cereals, especially wheat, corn, soybeans, barley, sunflowers and / or cotton.

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