METHODS FOR CONTROLLING OR PREVENTING PLANT PATHOGENIC DISEASES OR FUNGAL DISEASES IN PLANT PROPAGATION MATERIALS

Abstract

The invention relates to a method for controlling or preventing disease caused by plant pathogens or plant-borne fungi on plant propagation material, which includes a step applied to plant propagation material, a composition containing at least one component (A), such that compound (A) contains jawsamycin according to the following formulation (IIa): preferably in a fungicide-effective amount. In addition, the invention relates to plant propagation material, specifically seeds, coated with this composition.

Description

[0001] METHOD OF CONTROLLING PHYTOPATHOGENIC FUNGI

[0002] The present invention relates to a method of controlling diseases caused by phytopathogenic fungi, especially of Fusarium Spp., on plant propagation material using fungicidal compositions.

[0003] Fusarium is a large cosmopolitan genus of imperfect fungi and contains numerous plant pathogens causing considerable economic losses. Fusarium species are often saprobic on plant debris and are therefore exposed to fungicides currently in use in agriculture. Due to the present fungicide pressure in the environment, resistance can increase in Fusarium species, although a main hypothesis is that resistance in Fusarium was already present prior to fungicide exposure and should, therefore, be considered as intrinsic resistance. In addition, resistance variation might occur due to chance mutations. Consequently, increasingly Fusarium species have emerged which exhibit resistance to known compounds exhibiting biological activity against phytopathogenic fungi, resulting in many customary fungicides being rendered increasingly less useful for controlling plant diseases caused by of Fusarium Spp.. Fusarium antifungal resistance thus represents a significant problem, and consequently there is an urgent need for novel fungicidal compounds and strategies.

[0004] Masaru et al, in The Journal of Antibiotics, 1990, Volume 43, Issue 7, Pages 748-754, as well as in US-A-4,803,074, disclose jawsamycin which exhibited antifungal activity against some filamentous fungi, and proposed its use for the treatment of patients.

[0005] A later publication by Fu, Y. et al., in Nat Commun 11, 3387 (2020), indicated that Jawsamycin appears to block a subunit of the fungal UDP-glycosyltransferase, which is involved in the first step in the biosynthesis of fungal glycosylphosphatidylinositol (GPI) anchors, and also show that it exhibits broad spectrum antifungal activity against several pathogenic fungi including a Fusarium oxysporuma species insensitive to voriconazole and echinocandin, and also provided a mouse model for medical infection treatment trials. The article also shows that even minor variations to the various structural portions of Jawsamycin may detrimentally affect the activity in particular versus fungi in a detrimental manner, while humans generally appear insensitive to Jawsamycin. This has also been described in a review article by Heard S. et al, Current Opinion in Biotechnology, Volume 69,2021, Pages 232-241. Accordingly, the use of this compound has been proposed as a pharmaceutical treatment against isolated fungal species, for use in pharmaceuticals. Despite disclosures of antifungal activities of jawsamycin, the activity thereof in agriculture is unknown. There is a need for improved methods for controlling phytopathogenic fungi in agriculture.

[0006] Brief Description of the Invention

[0007] Out of the above-mentioned needs of agricultural practice for increased activity against phytopathogenic fungi, in particular Fusarium Spp.and closely related species, there is therefore proposed in accordance with the present invention a novel 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 a component (A), wherein compound (A) comprises jawsamycin according to following formula (Ila):

[0008] , preferably in a fungicidally effective amount.

[0009] It has been found that the method of the invention is effective against a wide spectrum of

[0010] Fusarium Spp.

[0011] Detailed Description of the Invention

[0012] The present invention relates to a novel 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 a component (A), wherein component (A) comprises jawsamycin according to following formula (Ila):

[0013]

[0014] , preferably in a fungicidally effective amount.

[0015] The method of controlling or preventing phytopathogenic diseases or phytopathogenic fungi on plant propagation material, comprises applying to the plant propagation material a composition as disclosed herein which is effective against harmful microorganisms, such as microorganisms that cause phytopathogenic diseases, in particular against phytopathogenic fungi. The method according to the present invention comprises applying compositions effective especially against phytopathogenic fungi belonging to the following classes: Ascomycetes (e.g. Venturia, Podosphaera, Erysiphe, Monilinia, Mycosphaerella, Uncinula, Pyrenophora); more preferably against Fungi imperfecti (also known as Deuteromycetes; e.g. Botrytis, Helminthosporium, Rhynchosporium, Fusarium, Zymoseptoria, Cercospora, Alternaria, Pyricularia and Pseudocercosporella);

[0016] The method according to the present invention comprises applying compositions in particular effective against Fusarium spp., such as Fusarium acacia, Fusarium fujikuroi, Fusarium acaciae-mearnsii, Fusarium acuminatum, Fusarium acutatum, Fusarium aderholdii, Fusarium acremoniopsis, Fusarium affine, Fusarium arthrosporioides, Fusarium avenaceum, Fusarium bubigeum, Fusarium circinatum, Fusarium crookwellense, Fusarium culmorum, Fusarium graminearum, Fusarium incarnatum, Fusarium langsethiae, Fusarium mangiferae, Fusarium merismoides, Fusarium moniliforme, Fusarium pallidoroseum, Fusarium poae, Fusarium proliferatum, Fusarium pseudograminearum, Fusarium redolens, Fusarium sacchari, Fusarium solani, Fusarium sporotrichioides, Fusarium sterilihyphosum, Fusarium subglutinans, Fusarium sulphureum, Fusarium tricinctum, Fusarium udum, Fusarium venenatum, Fusarium verticillioides, Fusarium virguliforme, and Fusarium xyroph. The method according to the present invention comprises applying compositions even more particularly effective against Fusarium solani, Fusarium culmorum, Fusarium avenaceum, Fusarium graminearum, Fusarium proliferatum Fusarium pseudograminearum, Fusarium langsethiae, Fusarium fujikuroi, Fusarium verticillioides, Fusarium virguliforme, Fusarium subglutinans, Fusarium oxysporum f. sp. Ubense, Fusarium oxysporum f. sp. Tuberosi, and Fusarium oxysporum f.sp. lycopersici.

[0017] The present method is in even more particularly effective against Fusarium culmorum, Fusarium graminearum, and Monographella nivalis and Sclerotinia sclerotiorum.

[0018] The method according to the present invention comprises applying compositions which may also be effective vis-a-vis members of the Fusarium oxysporum genus, in particular 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, 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 f.sp. koae, Fusarium oxysporum f.sp. lactucae, Fusarium oxysporum f.sp. lends, Fusarium oxysporum f.sp. lilli, Fusarium oxysporum f.sp. lini, Fusarium oxysporum f.sp. lycopersici, 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, Fusarium oxysporum f.sp. passiflorae, 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. tuberosi, and / or Fusarium oxysporum f.sp. tulipae.

[0019] Surprisingly, while a composition comprising Jawsamycin showed a high activity versus Fusarium oxysporum f.sp. vasinfectum in vitro, it failed to show the same activity in an in vivo experiment on cotton seeds in the experiments set out below. Accordingly, it appears the teaching of Fu, Y. et al. in Nat Commun 11, 3387 (2020) may not be applied for the entire species Fusarium oxysporum. It was surprisingly found that treatment of seeds with a composition comprising Jawsamycin was effective against Fusarium sp.. In contrast no activity against Fusarium sp. was found when the surrounding soil was treated with Jawsamycin.

[0020] Component A in disclosed herein may comprise further compounds of formula I:

[0021] Compounds according to formula I are in free form, in oxidized form as a N-oxide or in salt form, e.g., an agronomically usable salt form.

[0022] N-oxides are oxidized forms of tertiary amines or oxidized forms of nitrogen containing heteroaromatic compounds. They are described for instance in the book "Heterocyclic N- oxides" by A. Albini and S. Pietra, CRC Press, Boca Raton 1991.

[0023] The compounds of Formula I may have asymmetric centres, chiral axes, and chiral planes, as for instance described in E. L. Eliel and S. H. Wilen, Stereochemistry of Carbon Compounds, John Wiley & Sons, New York 1994, pages 1119-1190, and may occur as racemates, racemic mixtures, and as individual diastereomers, with all possible isomers and mixtures thereof, including optical isomers. In addition, the compounds disclosed herein may exist as tautomers and both tautomeric formsare intended to be encompassed , even though only one tautomeric structure is depicted.

[0024] The present disclosure includes all those possible isomeric forms and mixtures thereof for a compound of formula I. Likewise, formula I is intended to include all possible cogenerated metabolites, and tautomers. The present disclosure includes all possible tautomeric forms for a compound of formula I, and also racemic compounds, i.e., mixtures of at least two or more diastereomers or enantiomers in a substantially equal ratio.

[0025] In the compound according to Forumla I, R1preferably represents a Cio to Cis alkenyl chain comprising at least two adjacent cyclopropyl rings; more preferably at least three adjacent cyclopropyl rings, and most preferably at least four adjacent cyclopropyl rings.

[0026] In the compound according to Formula I, R1preferably represents one of the following substituents:

[0027] The components hence have the following structural formulae (II):

[0028] More preferably, R1essentially represents: such that component A has the following formula (Ila): i.e. representing Jawsamycin.

[0029] Preferably, component (A) is selected from (2E,4E)-N-[[(2R,3S,4R,5R)-5-(2,4-Dioxo-l,3- diazinan-l-yl)-3,4-dihydroxyoxolan-2-yl]methyl]-5-[(lS,2R)-2-[(lR,2R)-2-[(lR,2R)-2-[(lR,2S)-

[0030] 2-[(E)-2-[(lR,2R)-2-methylcyclopropyl]ethenyl]cyclopropyl]cyclopropyl]cyclopropyl]- cyclopropyl]penta-2,4-dienamide; N-{[(2R,3S,4R,5R)-5-(2,4-Dioxo-l,3,5,6-tetrahydro-l- pyrimidinyl)-3,4-dihydroxytetrahydro-2-furyl]methyl}-(2E,4E)-5-[(lR)-2-[(lR,2S)-2-[(lS)-2- [(lR,2S)-2-{(E)-2-[(lR,2R)-2-methylcyclopropyl]ethenyl}cyclopropyl]cyclopropyl]cyclopropyl]- cyclopropyl]-2,4-pentadienamide; and / or / V-{[(2 / ?,5 / ?)-5-(2,4-Dioxo-l,3,5,6-tetrahydro-l- pyrimidinyl)-3,4-dihydroxytetrahydro-2-furyl]methyl}-(2E,4E)-5-[(15,2S,l,S,2,S)-2,-[(Z)-2- [(15,2S)-2-{(f)-2-[(l / ?,2 / ?)-2-methylcyclopropyl]ethenyl}cyclopropyl]ethenyl]-l, - bi(cyclopropyl)-2-yl]-2,4-pentadienamide; or combinations thereof.

[0031] A microorganism expressing a compound according to formula II may be a Streptoverticillium and / or a Streptomyces, preferably Streptoverticillium fervens, and / or Streptomyces luteoverticillatus, or their spores, as these microorganisms express the compounds of formula (II) as metabolites. Preferably, the microorganisms comprise Streptoverticillium fervens, and / or Streptomyces luteoverticillatus that express jawsamycin.

[0032] The composition disclosed hereincomprises at a least a compound of formula Ila:

[0033] (B) at least one additive, carrier and / or adjuvant compound.

[0034] The compound of formula (Ila) is known as Jawsamycin, an oligocyclopropyl-containing natural product, also noted as FR-900848, and is a metabolite isolated from Streptoverticillium fervens or Streptomyces luteoverticillatus cultures. Jawsamycin is a polyketide comprising a 5'-amino-5'-deoxy-3,4,5,6-tetrahydrouridine in which one of the hydrogens of the amino group is substituted by a (lE,3E)-l-[(lR,l'R,l"R,l"'R,2S,2'R,2"R,2"'S)-2"'-{(E)-2-[(lR,2R)-2- methylcyclopropyl]ethenyl}[l,l':2',l":2",l"'-quater(cyclopropan)]-2-yl]-5-oxopenta-l,3-dien- 5-y I group.

[0035] Its structure is C32H43N3O6, comprising a 5'-amino-5'-deoxy-5, 6-dihydrouridine with an unsaturated fatty acid comprising four serial and one isolated cyclopropane rings. Its IUPAC name is (2E,4E)-N-[[(2R,3S,4R,5R)-5-(2,4-dioxo-l,3-diazinan-l-yl)-3,4- dihydroxyoxolan-2-yl]methyl]-5-[(lS,2R)-2-[(lR,2R)-2-[(lR,2R)-2-[(lR,2S)-2-[(E)-2-[(lR,2R)-2- methylcyclopropyl]ethenyl]cyclopropyl]cyclopropyl]cyclopropyl]cyclopropyl]penta-2,4- dienamide. formulae: are congeners of jawsamycin, and are expressed by the above microbial cultures in varying, but usually small or negligible amounts.

[0036] While the total synthesis of jawsamycin, entitled "pentacyclopropane antifungal agent FR- 900848" has been disclosed by A. Barrett et al., J. Am. Chem. Soc. 1996, 118, 45, 11030-11037, the compound is preferably accessible, and employed, as the metabolite obtained from, or isolated from Streptoverticillium or Streptomyces bacteria, preferably Streptoverticillium fervens bacteria or Streptomyces luteoverticillatus bacteria, or their cultures.

[0037] A particularly suitable route may be to produce jawsamycin, by cultivating Streptoverticillium fervens and isolatingjawsamycin, for instance according to the methods disclosed in Masaru et al, as set out herein above. Alternatively, mixtures of metabolites and microbacterial cells or spores may be employed as component A, provided Jawsamycin is present in a suitable amount.

[0038] Component (A) may advantageously be prepared in analogous manner as outlined in US-A- 4,803,074, or any of the procedures set out in the literature.

[0039] The salts of compounds of formula I, preferably a compound of formula Ila) advantageously include conventional salts of the compounds that may be formed using inorganic and organic acids that have a pKaless than about 4. For example, the salts include those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric, hexafluorophosphate, perchlorate, tetrafluoroborate, hexafluroroantimonate, tetraarylborates and the like, as well as salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, sulfanilic, 2-acetoxy-benzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionic, trifluoroacetic and the like. Agrochemically acceptable salts of the compounds disclosed herein include the conventional non-toxic salts of the compounds as formed inorganic or organic acids. For example, conventional non-toxic salts include those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric and the like, as well as salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, sulfanilic, 2-acetoxy-benzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionic, trifluoroacetic and the like.

[0040] Agrochemically acceptable salts of the compounds disclosed herein can be prepared from the compounds disclosed herein which contain a basic or acidic moiety by conventional chemical methods. Generally, the salts of the basic compounds are prepared either by ion exchange chromatography or by reacting the free base with stoichiometric amounts or with an excess of the desired salt-forming inorganic or organic acid in a suitable solvent or various combinations of solvents. Similarly, the salts of the acidic compounds are formed by reactions with the appropriate inorganic or organic base.

[0041] Throughout this document the expression "composition" stands for the various mixtures or combinations of components (A) and (B), for example in a single "ready-mix" form, in a combined spray mixture composed from separate formulations of the single active ingredient components, such as a "tank-mix", and in a combined use of the single active ingredients when applied in a sequential manner, i.e. one after the other with a reasonably short period, such as a few hours or days. The order of applying the components (A) and (B) is not essential for working the present invention.

[0042] The compositions may also comprise one or more other pesticidal components that are known and are referred to hereinabove by their so-called ISO common name or their IUPAC name. Typical pesticidal components are included in the Pesticide Manual Online ("E-pesticide Manual") by the British Crop Production Council and in the Compendium of Pesticide Common Names by Alan Wood.

[0043] As used herein, a plant includes a useful plant. "Useful plants" typically comprise the following species of plants: grape vines; cereals, such as wheat, barley, corn or maize, rye or oats; beet, such as sugar beet or fodder beet; fruits, such as pomes, stone fruits or soft fruits, for example apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries or blackberries; leguminous plants, such as beans, lentils, peas or soybeans; oil plants, such as rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans or groundnuts; cucumber plants, such as marrows, cucumbers or melons; fibre plants, such as cotton, flax, hemp or jute; citrus fruit, such as oranges, lemons, grapefruit or mandarins; vegetables, such as spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, cucurbits or paprika; lauraceae, such as avocados, cinnamon or camphor; maize; tobacco; nuts; coffee; sugar cane; tea; vines; hops; durian; bananas; natural rubber plants; turf or ornamentals, such as flowers, shrubs, broad-leaved trees or evergreens, for example conifers. This list does not represent any limitation. The term "useful plants" is to be understood as including also useful plants that have been rendered tolerant to herbicides like bromoxynil or classes of herbicides (such as, for example, HPPD inhibitors, ALS inhibitors, for example primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5-enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors, GS (glutamine synthetase) inhibitors or PPO (protoporphyrinogen-oxidase) inhibitors) as a result of conventional methods of breeding or genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g., imazamox, by conventional methods of breeding (mutagenesis) is Clearfield® summer rape (Canola). Clearfield is a trademark registered to BASF Agrochemical Products B.V.. Examples of crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® , Herculex I® and LibertyLink®. 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 Agricultural Solutions Seed US LLC.

[0044] The term "useful plants" is also to be understood as including also useful plants which have been so transformed using recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.

[0045] The term "useful plants" is also to be understood as including also useful plants which have been so transformed using recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for example, the so-called "pathogenesis-related proteins" (PRPs, see e.g., EP-A-0 392 225). Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-0 392 225, WO 95 / 33818, and EP-A-0 353 191. The methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.

[0046] The term "locus" of a useful plant as used herein is intended to embrace the place on which the useful plants are growing, where the plant propagation materials of the useful plants are sown or where the plant propagation materials of the useful plants will be placed into the soil. An example for such a locus is a field, on which crop plants are growing.

[0047] The term "plant propagation material" is understood to denote generative parts of the plant, such as seeds, which can be used for the multiplication of the latter, and vegetative material, such as cuttings or tubers, for example potatoes. Plant propagation material as used herein comprises plant propagation material of a plant, such as a useful plant. There may be mentioned for example seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes of plants and parts of plants. Germinated plants and young plants which are to be transplanted after germination or after emergence from the soil, may also be mentioned. These young plants may be protected before transplantation by total or partial treatment by immersion. Preferably "plant propagation material" is understood to denote seeds.

[0048] In a further aspect, the present application also relates to plant propagation material coated with the compositions disclosed herein.

[0049] By applying the compositions in a method according to the present invention it is possible to inhibit or destroy the phytopathogenic microorganisms which occur on plant propagation material of different useful plants, while at the same time the parts of plants which grow later are also protected from attack by phytopathogenic microorganisms.

[0050] The compositions in a method according to the invention may be applied before or after infection of the propagation material of plants, by the microorganisms.

[0051] The amount of a composition to be applied will depend on various factors, such as the compounds employed; the subject of the treatment, such as, type of seeds; the type of treatment, for instance seed dressing; the purpose of the treatment, such as the type of fungi to be controlled, or the application time. When applied to the useful plants, component (A) may typically be applied at a rate of 5 to 2000 g a .i . / ha, particularly 10 to 1000 g a .i . / ha, e.g., 50, 75, 100 or 200 g a.i. / ha.

[0052] The method according to the present invention for treating seeds comprises applying a composition as disclosed herein at rates of 0.001 to 50 g of a compound of component (A) per kg of seed, preferably from 0.01 to 10g per kg of seed, are generally sufficient. The method according to the present invention comprises applying compositions, wherein the composition may be employed in any conventional form, for example in the form of a twin 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), an emulsion, water in oil (EO), an emulsion, oil in water (EW), a micro-emulsion (ME), an oil dispersion (OD), an oil miscible flowable (OF), an oil miscible liquid (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. Such compositions may be produced in conventional manner, e.g., by mixing the active ingredients with at least one appropriate inert formulation adjuvant (for example, diluents, solvents, fillers, and optionally other formulating ingredients such as surfactants, biocides, anti-freeze, stickers, thickeners, and compounds that provide adjuvancy effects). Also, conventional slow- release formulations may be employed where long lasting efficacy is intended. Particularly formulations to be applied in spraying forms, such as water dispersible concentrates (e.g. EC, SC, DC, OD, SE, EW, EO and the like), wettable powders and granules, may contain surfactants such as wetting and dispersing agents and other compounds that provide adjuvancy effects, e.g. the condensation product of formaldehyde with naphthalene sulphonate, an alkylarylsulphonate, a lignin sulphonate, a fatty alkyl sulphate, and ethoxylated alkylphenol and an ethoxylated fatty alcohol.

[0053] The method according to the present invention comprises applying compositions wherein the compositions may also comprise further pesticides, such as, for example, fungicides, insecticides or herbicides. A composition as disclosed herein is an agrochemical composition. A seed dressing formulation is applied in a manner known per se to the seeds employing the compositions as disclosed herein and a diluent in suitable seed dressing formulation form, e.g., as an aqueous suspension or in a dry powder form having good adherence to the seeds. 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 encapsulated form, e.g., as slow-release capsules, or microcapsules; and also include precision applications on seeds or propagation materials, e.g. as disclosed in EP3755137.

[0054] In general, the formulations include from 0.01 to 90% by weight of active agent, from O to 20% agriculturally acceptable surfactant and 10 to 99.99% solid or liquid formulation inerts and adjuvant(s), the active agent consisting of at least a compound of component (A) together with a compound of component (B), and optionally other active agents, particularly microbiocides or conservatives or the like.

[0055] Concentrated forms of compositions generally contain between about 2 and 80%, preferably between about 5 and 70% by weight of active agent. Application forms of formulation may for example contain from 0.01 to 20% by weight, preferably from 0.01 to 5% by weight of active agent. Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ diluted formulations. Further characteristics of compositions comprising compounds of formula (I), such as compounds of formula Ila), their application methods to plant propagation material and their use rates are as described for compositions comprising compounds of formula (I), such as compounds of formula Ila), and additionally at least one component (B) as described above. Their application can be both before and after the infection of the plant propagation material with the fungi. The treatment is preferably carried out prior to the infection.

[0056] The present invention thus provides a method for applying for a composition suitable for applying fungicides to plant propagation materials a blend of the following components:

[0057] As component B: a surface-active agent; at least one water-dispersible or water-soluble filmforming polymer; at least one inorganic solid carrier; and optionally, at least one antifreeze agent; as well as a fu ngicida I ly effective amount of at least one component A. In another embodiment, the method according to the present invention comprises applying compositions wherein the composition provides for an aqueous composition suitable for applying fungicides to plant propagation materials comprising at least three fu ngicida I ly active compounds, as active ingredients, water and a blend of the active components.

[0058] In still another embodiment, the method according to the present invention comprises applying compositions wherein the composition provides for a composition suitable for applying fungicides to plant propagation materials comprising at least one f ungicida I ly active component A. Such compositions are typically described as "seed treatments". For the purposes of this invention, seed treatments are defined as agrochemically active substances that are applied to seeds or vegetative plant propagation materials to control disease organisms, insects, or other pests. The seed treatment composition of as disclosed herein includes fungicides, but can also include other pesticides such as bactericides and insecticides. Most seed treatments are applied to true seeds, which have a seed coat surrounding an embryo. However, some seed treatments can be applied to vegetative plant propagation materials such as rhizomes, bulbs, corms or tubers.

[0059] There is provided a seed treatment composition suitable for applying a composition according to the disclosure to plant propagation materials comprising as active ingredient a compound of Formula 11(a), a carrier, such as water, and a blend of the following components: at least one surface-active agent; at least one polymer selected from water dispersible and water- soluble film-forming polymers; and at least one antifreeze agent.

[0060] There is also provided a use of the composition described herein for rendering plant propagation material fungus-resistant.

[0061] There is also provided a method of protecting plant propagation material against attack by phytopathogenic fungi which comprises treating said plant propagation material with a fungicidally effective amount of the composition described herein. The compositions are prepared by intimately mixing the components with a solvent, for instance water, optionally using a concentrated premix prepared by wet milling the solid components, until an evenly dispersed phase is achieved.

[0062] Also provided herein are plant propagation materials treated with a composition disclosed herein and for a method for reducing fungal infestation of plant propagation materials such as seeds. The method comprises contacting the seeds with an aqueous fungicidal composition described above.

[0063] Also disclosed herein is the use of a composition for the control of diseases caused by phytopathogens, in particular root, wilt or rust diseases on useful plants, more particularly comprising soybeans and / or cereals, and / or or the enhancement of growth of such useful plants, in particular for the control of Fusarium Spp., more preferably on plant propagation material, in particular seeds. The invention also provides for the use of a composition for rendering plant propagation material fungus-resistant. Preferably, the composition is used for a plant seed selected from potatoes, wheat, barley, rye, oats, rice, maize, sugar beet, cotton, sorghum, sun flowers, beans, peas, canola, rape, soybeans, cabbages, tomatoes, eggplants and pepper. Advantageously, this includes transgenic plant seeds. Preferably, the plant or plant propagation material, such as plant seed, is selected from wheat, corn, soybean, cotton, barley, and sunflower.

[0064] The invention also provides for a method of protecting plant propagation material against attack by phytopathogenic fungi which comprises treating the plant propagation material with a fungicidally effective amount of the composition. Preferably, the plant propagation material is a plant seed selected from potatoes, wheat, barley, rye, oats, rice, maize, sugar beet, cotton, sorghum, sun flowers, beans, peas, canola, rape, soybeans, cabbages, tomatoes, eggplants and pepper, preferably wheat, corn, soybean, cotton, barley, and sunflower. The term "plant" as used herein also includes seedlings, bushes and crops of fruits and vegetables.

[0065] The Examples which follow serve to illustrate the invention. Formulation Examples

[0066] Wettable powders i ) i i )

[0067] Component [A]: 25 % 75 %

[0068] Component [B]: sodium lignosulfonate 5 % sodium lauryl sulfate 3 % 5 % sodium diisobutylnaphthalenesulfonate - 10 %

[0069] (7-8 mol of ethylene oxide) highly dispersed silicic acid 5 % 10 %

[0070] Kaolin 62 %

[0071] Component A is thoroughly mixed with the other formulation components (Component B), and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with water to give suspensions of the desired concentration.

[0072] Powders for dry seed treatment i) ii)

[0073] Component [A]: 25 % 75 %

[0074] Component [B]: light mineral oil 5 % 5 % highly dispersed silicic acid 5 % Kaolin 65 %

[0075] Talc 20

[0076] The active ingredient is thoroughly mixed with the other formulation components and the mixture is thoroughly ground in a suitable mill, providing powders that can be used directly for seed treatment.

[0077] Emulsifiable concentrate

[0078] Component (A): 10 %

[0079] Component [B]: octylphenol polyethylene glycol ether 3 %

[0080] (4-5 mol of ethylene oxide) calcium dodecylbenzenesulfonate 3 % castor oil polyglycol ether (35 mol of ethylene oxide) 4 %

[0081] Cyclohexanone 30 % xylene mixture 50 %

[0082] Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water.

[0083] Dustable powders a) b)

[0084] Component [A]: 5 % 6 %

[0085] -Component [B]:

[0086] Talcum 95 %

[0087] Kaolin - 94 %

[0088] Ready-for-use dusts are obtained by mixing the active ingredient with the carriers and grinding the mixture in a suitable mill. Such powders can also be used for dry dressings for seed.

[0089] Extruded granules % w / w

[0090] Component (A): 15 %

[0091] Component [B]: sodium lignosulfonate 2 % sodium alkyl naphthalene sulfonate 1 %

[0092] Kaolin 82 %

[0093] The active ingredient is mixed and ground with the other formulation components, and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air.

[0094] Suspension concentrate

[0095] Component [A]: 40 %

[0096] Component [B]: propylene glycol 10 % nonylphenol polyethylene glycol ether (15 mol of ethylene oxide) 6 % sodium lignosulfonate 10 %

[0097] Carboxymethylcellulose 1 % silicone oil (in the form of a 75 % emulsion in water) 1 %

[0098] Water 32 %

[0099] The finely ground active ingredient is intimately mixed with the other formulation components, giving a suspension concentrate which can be diluted in water at any desired rate. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.

[0100] Flowable concentrate for seed treatment

[0101] Component [A]: 40 %

[0102] Component [B]: propylene glycol 5 % copolymer butanol PO / EO 2 % tristyrenephenole ethoxylate (with 10-20 moles EO) 2 % l,2-benzisothiazolin-3-one 0.5 % monoazo-pigment calcium salt 5 % silicone oil (in the form of a 75 % emulsion in water) 0.2 %

[0103] Water 45.3 %

[0104] The finely ground active ingredient is intimately mixed with the other formulation components, giving a suspension concentrate which can be diluted further in water to be applied to seeds. Using such dilutions, propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.

[0105] Accordingly, provided herein is a method of controlling diseases on plants which comprises applying to plant propagation material, a composition comprising a compound of formula (Ila) as disclosed herein. The method excludes methods for the treatment of the human or animal body by surgery or therapy.

[0106] The method may also be in particular employed vis-a-vis cereal grain crops including rice, wheat, rye, oats, barley, millet, and maize or corn.

[0107] The present method may also be in particular employed vis-a-vis Fusarium culmorum on cereals, in particular on wheat; vis-a-vis Fusarium graminearum on cereals, in particular on maize or corn; vis-a-vis Monographella nivalis (also known as Fusarium nivale or Fusarium nivalef.sp. graminicola) on cereals, in particular on barley.

[0108] The present method may also be in particular employed vis-a-vis fungi of the genus Sclerotinia, in particular Sclerotinia sclerotiorum, more particularly Sclerotinia sclerotiorum on sunflowers. Preferred is a method for controlling in particular pathogens of cereals, such as wheat, barley, rye or oats; maize or corn; rice; cotton; soybean; turf; sugarbeet; oil seed rape; potatoes; pulse crops, such as peas, lentils or chickpea; and sunflower.

[0109] The methods according to the invention also allows good control of other harmful fungi frequently encountered in plants. The present disclosure also relates to the use of component (A), or a composition according to the disclosure comprising component A, for the treatment of plant propagation material.

[0110] Preferably, the plant propagation material is a plant seed selected from potatoes, wheat, barley, rye, oats, rice, maize, sugar beet, cotton, sorghum, sun flowers, beans, peas, canola, rape, soybeans, cabbages, tomatoes, eggplants and pepper. Advantageously, said plant propagation material may be a transgenic plant seed.

[0111] The present disclosure also relates to a method of protecting plant propagation material against attack by phytopathogenic fungi, which comprises treating the plant propagation material with a fungicidally effective amount of component A, wherein component A comprises jawsamycin or a composition according to the disclosure comprising component A, preferably wherein component A comprises jawsamycin. Preferably, in this method, wherein the plant propagation material is a plant seed selected from potatoes, wheat, barley, rye, oats, rice, maize, sugar beet, cotton, sorghum, sun flowers, beans, peas, canola, rape, soybeans, cabbages, tomatoes, eggplants and pepper; which may include one or more transgenic plant seed(s).

[0112] Biological Examples

[0113] Jawsamycin employed in the examples was produced by cultivating Streptoverticillium fervens and isolating jawsamycin according to the methods disclosed in Masaru et al, The Journal of Antibiotics, 1990, Volume 43, Issue 7, Pages 748-754.

[0114] Example 1: In vitro bioassay with jawsamycin against various Fusarium species

[0115] Methodology for in vitro bioassay against various Fusarium species: The mycelium growth inhibition of various Fusarium species was assessed in an in vitro bioassay using petri dishes (9 cm diameter) which contained PDA and jawsamycin composition as a flowable concentrate for seed treatment at the following concentrations in ppm: 0.01, 0.1, 1 and 10.

[0116] Three replicates (petri dishes) were included per treatment concentration and for the control. Agar plugs were taken from fresh colonies of Fusarium with a cork borer and one plug was placed in the center of each petri dish. The fungi were incubated at 22°C in the dark. In order to calculate the half maximal effective concentration of jawsamycin (i.e., EC50), the mycelium growth (diameter) was measured after 6 to 13 days of incubation depending on the Fusarium species.

[0117] Table 1: In vitro results

[0118] As shown in table 1 below, jawsamycin was active against all tested Fusarium species with EC50 values in ppm in the range of from <0.01 to 2.050. Example 2: In vivo Seed treatment tests with jawsamycin against various disease targets Various useful plants were infected with specific pathogens, and the effect of the compositions according to the present disclosure was tested, as set out in Table 2 below.

[0119] Methodology for Fusarium culmorum on wheat: The objective of this study was to investigate the activity of seed applied jawsamycin formulated as a water dispersible powder for seed treatment against soilborne infection by Fusarium culmorum on wheat under controlled conditions. Wheat seeds were treated with a slurry amount of 10 g per kg seeds using a Turbula mixer. Three replicates (soil trays) were used, each containing 50 seeds. Before sowing, the soil substrate was infected with fungal inoculum of the test pathogen, i.e., Fusarium culmorum. Two control treatments were included in this test, i.e., an infected and a non-infected control. The activity (%) was calculated based on the plant emergence (%) at the final plant stand. Methodology for Fusarium graminearum on corn:

[0120] The objective of this study was to investigate the activity of seed applied jawsamycin formulated as water dispersible powder for seed treatment against soilborne infection by Fusarium graminearum on corn under controlled conditions. Corn seeds were treated with a slurry amount of 5 g per kg seeds using a Turbula mixer. Three replicates (soil trays) were used, each containing 50 seeds. Before sowing, the soil substrate was infected with fungal inoculum of the test pathogen, i.e., Fusarium graminearum. Two control treatments were included in this test, i.e., an infected and a non-infected control. The activity (%) was calculated based on the plant emergence (%) at the final plant stand.

[0121] Methodology for Fusarium virquliforme on soybean:

[0122] The objective of this study was to investigate the activity of seed applied jawsamycin formulated as water dispersible powder for seed treatment against soilborne infection by Fusarium virguliforme on soybean under controlled conditions. Soybean seeds were treated with a slurry amount of 5 g per kg seeds using a Turbula mixer. Four replicates (pots) were used, each containing 5 seeds. Before sowing, the soil substrate was infected with fungal inoculum of the test pathogen, i.e., Fusarium virguliforme. Two control treatments were included in this test, i.e., an infected and a non-infected control. The activity (%) was calculated based on the disease index (severity of the symptoms on leaves).

[0123] Methodology for Fusarium oxysporum f.sp. vasinfectum on cotton:

[0124] The objective of this study was to investigate the activity of seed applied jawsamycin formulated as flowable concentrate for seed treatment against soilborne infection by Fusarium oxysporum f.sp. vasinfectum on cotton under controlled conditions. Cotton seeds were treated with a slurry amount, containing the test compound, of 5 g per kg seeds using a Turbula mixer. Four replicates (pots) were used, each containing 5 seeds. Before sowing, the soil substrate was infected with fungal inoculum of the test pathogen, i.e., Fusarium oxysporum f.sp. vasinfectum. Two control treatments were included in this test, i.e., an infected and a non-infected control. The activity (%) was calculated based on the disease index (severity of the symptoms on the leaves).

[0125] Methodology for Monoqraphella nivalis on barley:

[0126] The objective of this study was to investigate the activity of seed applied jawsamycin formulated as flowable concentrate for seed treatment against seedborne infection by Monographella nivalis on barley under controlled conditions. Barley seeds were treated with a slurry amount of 10 g per kg seeds using a Turbula mixer. Two replicates (soil trays) were used, each containing 100 seeds. An infected control treatment was included in this test. The activity (%) was calculated based on the number of diseased plants.

[0127] Methodology for Sclerotinia sclerotiorum on sunflower:

[0128] The objective of this study was to investigate the activity of seed applied jawsamycin formulated as flowable concentrate for seed treatment against soilborne infection by Sclerotinia sclerotiorum on sunflower under controlled conditions. Sunflower seeds were treated with a slurry amount of 10 g per kg seeds using a Turbula mixer. Three replicates (soil trays) were used, each containing 50 seeds. Before sowing, the soil substrate was infected with fungal inoculum of the test pathogen, i.e., Sclerotinia sclerotiorum. Two control treatments were included in this test, i.e., an infected and a non-infected control. The activity (%) was calculated based on the plant emergence (%) at the final plant stand.

[0129] Table 2: Seed treatment tests with jawsamycin against various disease targets

[0130] Example 3. Efficacy of seed applied jawsamycin in comparison to soil applied jawsamycin against Fusarium graminearum on corn The objective of this study was to compare the efficacy of seed applied jawsamycin compared to soil applied jawsamycin against soilborne infection by Fusarium graminearum on corn under controlled conditions.

[0131] Jawsamycin was applied at 5 g per 100 kg seeds, and same application rate was used for both seed applied and soil applied treatments per soil surface to allow a comparison. Corn seeds cv. Andromeda were treated according to standard procedures with a slurry amount of 5 g per kg seeds using a Turbula mixer. Four replicates (soil trays) were used, each containing 25 seeds. Jawsamycin was formulated as WS10 (water dispersible powder containing 10% active ingredient). Before sowing, the soil was infected with fungal inoculum of the test pathogen, i.e. Fusarium graminearum. Two controls were included in this test, i.e., an infected and a non- infected control. The efficacy (%) of the treatments was calculated based on the plant emergence (%) at final plant stand in comparison to the controls.

[0132] The efficacy of seed applied jawsamycin was 36% while the efficacy of soil applied jawsamycin was 0%.

Claims

Claims1. 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 a component (A), wherein compound (A) comprises jawsamycin according to following formula (Ila):, preferably in a fungicidally effective amount.

2. The method according to claim 1, wherein the composition further comprises a 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 a microorganism capable of expressing a compound of formula Ila as metabolite.

4. The method according to claim 3, wherein the microorganism comprises Streptoverticillium or Streptomyces , preferably Streptoverticillium fervens bacteria or Streptomyces luteoverticillatus bacteria5. The method according to any one of the claims 2 to 4 wherein the composition comprises of from 10% to 99.9% by weight, preferably of from 20% to 99.9% by weight, more preferably of from 40% to 99.9% by weight of a compound of formula (Ila), and of from 0.1% to 90% by weight, preferably of from 0.1% to 80% by weight, more preferably of from 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 from 100:1 to 1:5000.

7. The method according to any one of the claims 1 to 6, wherein the composition comprises one or more further biologically active compound(s), preferably one or more further pesticide, such as fungicides, insecticides, or herbicides.

8. The method according to any one of the claims 1 to 7, wherein the phytopathogenic fungi are selected from Fusarium Spp. , Sclerotinia spp, and Monographella Spp, preferably wherein the phytopathogenic fungi are selected from Fusarium solani Fusarium culmorum Fusarium avenaceum, Fusarium graminearum, Fusarium proliferatum, Fusarium pseudograminearum, Fusarium langsethiae, Fusarium fujikuroi, Fusarium verticillioides, Fusarium virguliforme, Fusarium subglutinans, Fusarium oxysporum f. sp. Cubense, Fusarium oxysporum f. sp. Tuberosi, Fusarium oxysporum f.sp. lycopersici, Monographella nivalis, and Sclerotinia sclerotiorum, preferably selected from Fusarium culmorum, Fusarium graminearum, Monographella nivalis, and Sclerotinia sclerotiorum.

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

10. The method according to any one of the claims 1 to 9, wherein plant propagation material is from a useful plant selected from: grains, fruits and tree nuts, vegetables, field crops, oil seed crops, forage crops, forest plants, horticulture crops, floriculture, greenhouse and nursery plants, propagative materials, culinary herbs and spices, and medicinal herbs, preferably wherein the useful plant is selected from: fruits and tree nuts, vegetables, horticulture crops, and floriculture.

11. The method according to claim 10, wherein the plant propagation material is from fruit, soybean, cereals, and / or sunflowers; preferably, wherein the plant propagation material is from a plant comprising wheat, corn, soybean, barley, sunflower and / or cotton.

12. The method according to any one of claims 1 to 11, comprising applying 0.001 to 50 g of at least a compound of component (A) per kg of plant propagation material, in particular per kg of seeds.

13. A plant propagation material, in particular seeds, coated with a composition comprising Component A, wherein compound (A) comprises jawsamycin according to14. Use of a composition comprising Component A, wherein compound (A) comprises jawsamycin according to following formula (Ila):for protecting plant propagation material, in particular seeds of useful plants, wherein the useful plants comprise fruit, soybean, cereals, in particular wheat, corn, soybean, barley, sunflower and / or cotton against fungal attacks, in particular against Fusarium spp.