Agricultural chemical adjuvants

Abstract

The present invention relates to a novel agrochemical formulation comprising a compound selected from hollybiocin and lamellicolic anhydride and an agrochemical active substance. A concentrate suitable for forming the formulation is also provided. Hollybiocin and lamellicolic anhydride provide adjuvants in the concentrate and the agrochemical formulation. The present invention also provides the use of the hollybiocin and lamellicolic anhydride as adjuvants in the agrochemical formulation. The present invention also provides a method for preparing the formulation and treating soil with the formulation. A method for obtaining hollybiocin and lamellicolic anhydride from the culture of the Erythrocortis strain RKD01747 is also described.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Application No. 63 / 004875, filed on April 3, 2020, entitled “AGROCHEMICAL ADJUVANTS,” which is incorporated herein by reference in its entirety.

[0003] The present invention generally relates to adjuvants for agrochemically active formulations obtainable from organisms, and methods for providing adjuvant synergy in agrochemical formulations comprising the adjuvants and one or more agrochemically active substances. The present invention also includes treating crops with the formulations.

[0004] Adjuvants are generally defined as chemicals or mixtures of chemicals that can enhance the biological activity or efficacy of pesticide active substances. Adjuvants themselves cannot control or kill pests. Instead, these additives may interact with molecular targets within the target organism (e.g., cell walls, ion channels, structural proteins, enzymes, etc.), or change certain properties of agricultural chemical formulations (e.g., diffusion, retention, penetration, droplet size), thereby enhancing the biological activity of pesticide active substances against organisms. Typical types of compounds used as adjuvants may include small molecules, surfactants, emulsifiers, oils, and salts. Adjuvants generally do not inhibit the transfer of active substances in treated plants. In addition, adjuvants should not produce harmful phytotoxic effects on plants.

[0005] Fungi are widespread in terrestrial environments and pose a major challenge to agricultural productivity. Unchecked fungal infections can result in pre-harvest and post-harvest crop losses of more than 80%. To help reduce such losses and meet growing food demands, the use of fungicides to control fungal agricultural pests is, and will continue to be, an important component of agricultural pest management systems.

[0006] There is a need to develop new strategies to control agricultural pests and diseases, especially fungal diseases. One strategy is to develop safe and non-toxic chemical adjuvants that enhance the efficacy of existing fungicides approved for use on field and greenhouse crops to prevent or reduce the impact of fungal pests and diseases on agricultural productivity. These adjuvants can improve pest and disease control in the field or after harvest, thereby increasing productivity. They can also reduce the amount of fungicide needed to achieve the desired level of disease control, thereby helping to achieve the goal of sustainable productivity improvements.

[0007] The present invention seeks to provide compounds for use in conjunction with agrochemical actives in agrochemical formulations, wherein the compounds can provide the desired adjuvant synergy, including improved efficacy of the actives. The present invention also seeks to provide the use of agrochemical concentrates and dilute formulations containing said adjuvants.

[0008] The present invention also seeks to provide compounds in agrochemical formulations where the compounds can provide adjuvant properties similar to or improved upon existing adjuvants.

[0009] The present invention also seeks to provide the use of the compounds as adjuvants, and formulations comprising the compounds for providing adjuvant properties in agrochemical formulations.

[0010] According to a first aspect of the present invention, there is provided an agricultural chemical formulation comprising:

[0011] i) an adjuvant selected from hollycolic acid H, hydroxyhollycolic acid H, hollycolic acid I or lamellicolic anhydride according to formula (I)

[0012]

[0013] in:

[0014] R 1 independently represents hydrogen or C1 to C4 alkyl;

[0015] R 2 independently represent hydrogen, C1 to C4 alkyl, hydroxyl or C1 to C4 alkoxy;

[0016] R 3 and R 4 independently represent hydrogen or C1 to C4 alkyl; and

[0017] R 5 and R 6 independently represent hydrogen, C1 to C4 alkyl, hydroxyl or C1 to C4 alkoxy; and

[0018] ii) at least one pesticidally active substance.

[0019] According to a second aspect of the present invention, there is provided a concentrate formulation suitable for preparing the agricultural chemical formulation of the first aspect, the concentrate comprising:

[0020] i) an adjuvant selected from hollycolic acid H, hydroxyhollycolic acid H, hollycolic acid I or lamellicolic anhydride according to formula (I)

[0021]

[0022] in:

[0023] R 1 independently represents hydrogen or C1 to C4 alkyl;

[0024] R 2 independently represent hydrogen, C1 to C4 alkyl, hydroxyl or C1 to C4 alkoxy;

[0025] R3 and R 4 independently represent hydrogen or C1 to C4 alkyl; and

[0026] R 5 and R 6 independently represent hydrogen, C1 to C4 alkyl, hydroxyl or C1 to C4 alkoxy; and

[0027] ii) at least one pesticidally active substance.

[0028] According to a third aspect of the present invention, there is provided the use of a compound selected from the group consisting of hollycolic acid H, hydroxyhollycolic acid H, hollycolic acid I or lamellicolic anhydride according to formula (I) as an adjuvant in an agrochemical formulation comprising at least one pesticide active substance.

[0029]

[0030] in:

[0031] R 1 independently represents hydrogen or C1 to C4 alkyl;

[0032] R 2 independently represent hydrogen, C1 to C4 alkyl, hydroxyl or C1 to C4 alkoxy;

[0033] R 3 and R 4 independently represent hydrogen or C1 to C4 alkyl; and

[0034] R 5 and R 6 and independently represent hydrogen, C1 to C4 alkyl, hydroxy or C1 to C4 alkoxy.

[0035] According to a fourth aspect of the present invention there is provided a method of treating plants to control pests, the method comprising applying the formulation of the first aspect or the diluted concentrate formulation of the second aspect to the plants or the immediate environment of the plants.

[0036] According to a fifth aspect of the present invention, there is provided a method for obtaining the adjuvant according to the first aspect, comprising the following steps:

[0037] Cultivating Cosmospora sp. RKDO1747 in a culture medium under conditions that promote metabolic synthesis of the fungicide adjuvant from Cosmospora sp. according to the first aspect, and

[0038] The synthetic adjuvant was purified from the culture medium.

[0039] According to a sixth aspect of the present invention, there is provided an organism consisting of the Erythrocrista strain RKDO1747, accession number NRRL-67910, of the Agricultural Research Service Culture Collection (NRRL).

[0040] According to a seventh aspect of the present invention, there is provided an extract obtained from an organism consisting of the Erythrocortis strain RKDO1747 with the registration number NRRL-67910 of the Agricultural Research Service Culture Collection (NRRL), the extract comprising at least one of hollycolic acid H, hydroxyhollycolic acid H, hollycolic acid I or lamellicolic anhydride according to the first aspect.

[0041] According to an eighth aspect of the present invention there is provided a method of treating plants to control pests, the method comprising applying an organism according to the sixth aspect to the plant or the direct environment of the plant.

[0042] According to a ninth aspect of the present invention, there is provided a seed coating composition comprising the adjuvant according to the first aspect or the organism according to the sixth aspect.

[0043] According to a tenth aspect of the present invention, there is provided a lamellicolic anhydride according to formula (I):

[0044]

[0045] in:

[0046] R 1 , R 3 , R 4 and R 6 All are hydrogen, R 5 is hydroxyl group, R 2 is methyl; or

[0047] R 1 , R 4 , R 5 and R 6 All are hydrogen, R 2 and R 3 is methyl; or

[0048] R 4 , R 5 and R 6 All are hydrogen, R 2 , R 3 and R 1 is methyl; or

[0049] R 3 , R 5 and R 6 All are hydrogen, R 2 , R 4 and R1 is methyl; or

[0050] R 4 and R 5 is hydrogen, R 2 , R 3 and R 1 is methyl, R 6 is hydroxyl; or

[0051] R 3 and R 5 is hydrogen, R 2 , R 4 and R 1 is methyl, R 6 It is hydroxyl.

[0052] It has been found that the compounds defined herein provide desirable adjuvant properties when used in agrochemical formulations having at least one pesticidal active substance. Importantly, the compounds of this class identified, lamellicolic anhydride and hollybiocin, do not exhibit inherent pesticidal activity.

[0053] As used herein, the terms "such as" or "including" are intended to introduce examples that further illustrate more general subject matter. Unless otherwise specified, these examples are provided only to aid in understanding the applications shown in the present invention and are not meant to be limiting in any way.

[0054] It should be understood that when describing the number of carbon atoms in a substituent (such as "C1 to C4 alkyl"), the number refers to the total number of carbon atoms present in the substituent, including any carbon atoms present in any branching groups. In addition, when describing the number of carbon atoms in, for example, a fatty acid, it refers to the total number of carbon atoms, including the carbon atoms on the carboxylic acid and any carbon atoms present in any branching groups.

[0055] The hollycin compound is selected from hollycin H, hydroxyhollycin H or hollycin I. Preferably, the hollycin compound is hollycin H.

[0056] The hollybiocin compound is understood to be an adjuvant and will be referred to as such throughout the specification.

[0057] The structure of hollycin H is 5-(4-hydroxyphenyl)-2-pyridone with a bicyclic decahydronaphthalene system. It should be understood that the hollycin H compound refers to a compound having the structure of formula (A);

[0058]

[0059] The structure of hydroxyholicin H is the same as that of holicin H, except that there is one more hydroxyl group. It should be understood that the hydroxyholicin H compound refers to a compound having the structure of formula (B);

[0060]

[0061] The structure of hollycin I is a further variation on the bicyclic decalin system. It should be understood that the hollycin I compound refers to a compound having the structure of formula (C);

[0062]

[0063] The adjuvant of the present invention may also be selected from lamellicolic anhydride. It should be understood that the adjuvant is preferably selected from lamellicolic anhydride.

[0064] The lamellicolic anhydride is selected from compounds having the structure of formula (I):

[0065]

[0066] in:

[0067] R 1 independently represents hydrogen or C1 to C4 alkyl;

[0068] R 2 independently represent hydrogen, C1 to C4 alkyl, hydroxyl or C1 to C4 alkoxy;

[0069] R 3 and R 4 independently represent hydrogen or C1 to C4 alkyl; and

[0070] R 5 and R 6 and independently represent hydrogen, C1 to C4 alkyl, hydroxy or C1 to C4 alkoxy.

[0071] Unless otherwise defined, the term "C1 to C4 alkyl" as used herein refers to a straight or branched chain saturated hydrocarbon group containing 1 to 4 carbon atoms. 1 To R 6 Any one of represents a C1 to C4 alkyl group, the alkyl group may be independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, etc. Preferably, the C1 to C4 alkyl group is a methyl group or an ethyl group. More preferably, the C1 to C4 alkyl group is a methyl group.

[0072] Unless otherwise defined, the term “C1 to C4 alkoxy group” used herein refers to an alkyl group connected to oxygen to form an alkoxy group having a —O—Alk structure and bonded to an adjacent group through oxygen, wherein Alk represents a C1 to C4 alkyl group defined herein.

[0073] If R 2 , R 5 and R 6 Any one of represents a C1 to C4 alkoxy group, then the alkoxy group can be independently selected from methoxy, ethoxy, butoxy, propoxy, etc. Preferably, the C1 to C4 alkoxy group is a methoxy group or an ethoxy group. More preferably, the C1 to C4 alkoxy group is a methoxy group.

[0074] Preferably, the compound of formula (I) is selected from the following compounds, wherein:

[0075] R 1 independently represents hydrogen or methyl;

[0076] R 2 independently represents hydrogen or methyl, preferably methyl;

[0077] R 3 and R 4 independently represent hydrogen or methyl, preferably both are hydrogen or one is hydrogen and the other is methyl; and

[0078] R 5 and R 6 Each of them independently represents hydrogen or hydroxy, and preferably both of them are hydrogen or one of them is hydrogen and the other is hydroxy.

[0079] More preferably, the compound of formula (I) is selected from the following compounds, wherein:

[0080] R 1 , R 3 , R 4 , R 5 and R 6 All are hydrogen, R 2 is methyl; or

[0081] R 1 , R 3 , R 4 and R 6 All are hydrogen, R 5 is hydroxyl group, R 2 is methyl; or

[0082] R 1 , R 4 , R 5 and R 6 All are hydrogen, R 2 and R 3 is methyl; or

[0083] R 4 , R 5 and R 6 All are hydrogen, R 2 , R 3 and R 1 is methyl; or

[0084] R 3 , R 5 and R 6 All are hydrogen, R 2 , R 4 and R 1 is methyl; or

[0085] R 4 and R 5 is hydrogen, R 2 , R 3 and R 1 is methyl, R 6 is hydroxyl; or

[0086] R 3 and R 5 is hydrogen, R 2 , R 4 and R 1 is methyl, R 6 It is hydroxyl.

[0087] In particular, lamellicolic anhydrides selected from the following may be preferably used:

[0088]

[0089]

[0090] The organism used in the fermentation process is a filamentous fungus belonging to the genus Cosmospora sp. Certain strains of Cosmospora sp. RKDO1747 have been found to be particularly useful in the production of novel adjuvants and have been deposited with the Agricultural Research Service Culture Collection (NRRL) in Peoria, Illinois, USA, under the Budapest Treaty:

[0091]

[0092] NRRL-67910 is particularly preferred for providing bactericidal adjuvant activity in the present invention.

[0093] Hollycolic acid or lamellicolic anhydride can be formed and extracted from the culture of the genus Erythrocarp, in particular RKDO1747, respectively. The desired compound can be extracted and purified from the culture broth or fungal biomass by any method commonly used to collect biological metabolites. Examples include chromatography using adsorbents such as various ion exchange resins, nonionic adsorption resins, gel filtration chromatography, activated carbon, alumina and silica gel, or separation methods using high performance liquid chromatography, or crystallization, reduced pressure concentration or freeze drying, which can be used alone or in appropriate combination or repeatedly.

[0094] Cultures of Erythrocrista RKDO1747 can be obtained from natural sources or culture collections such as the Agricultural Research Service Culture Collection (NRRL). Isolates of Erythrocrista RKDO1747 can be cultured by methods known in the art of mycology.

[0095] As a method for producing the compounds of the present invention, the production organism can be grown on any suitable synthetic medium or natural medium as long as it contains a suitable carbon source, nitrogen source and inorganic salts. If necessary, the medium can be appropriately supplemented with vitamins and other nutrients.

[0096] Examples of general carbon sources include, but are not limited to, sugars such as glucose, maltose, fructose, sucrose and starch, alcohols such as glycerol and mannitol, amino acids such as glycine, alanine and asparagine, and oils and fats such as soybean oil and olive oil. Examples of nitrogen sources include organic nitrogen-containing compounds such as soybean meal, corn steep liquor, beef extract, peptone, yeast extract, amino acid mixtures and fish meal, and inorganic nitrogen compounds such as ammonium salts and nitrates. In addition, trace nutrients in the form of inorganic salts such as calcium carbonate, sodium chloride, potassium chloride, magnesium sulfate, copper sulfate, manganese chloride, zinc sulfate, cobalt chloride and various phosphates may also be used.

[0097] The organism can be grown at an appropriate culture temperature within the range that allows the microorganism to grow and effectively produce the compound of the present invention. The preferred culture temperature is 10° C. to 32° C., more preferably 20° C. to 25° C. The pH value at the start of culture is preferably about 4 to 6. The culture time is generally about one day to several weeks.

[0098] When the production amount of the compound of the present invention reaches an amount suitable for collection, preferably when it reaches a maximum amount, the culture may be terminated. As the culture method, any method may be appropriately used as long as the method is commonly used, such as solid culture and conventional stirring culture.

[0099] For example, the RKDO1747 isolate can be plated on agar containing nutrients such as YM (yeast malt extract) and incubated at room temperature for several days until visible colonies appear. A single RKDO1747 colony on the agar can be used to produce hollycolic acid or lamellicolic anhydride.

[0100] Those colonies that produce the desired molecule can be used to inoculate a broth medium (e.g., YM broth), which can be cultured under appropriate conditions (e.g., shaking at room temperature for several days) to produce a seed inoculum. The seed inoculum can be used to start a larger liquid medium (e.g., potato dextrose broth), which can be cultured at room temperature for several days (e.g., 4-28 days) to expand the Erythrocera culture.

[0101] Ilecithin or lamellicolic anhydride was found to be excreted into liquid culture media (e.g., potato dextrose broth). Ilecithin or lamellicolic anhydride can be isolated from the fermentation broth by liquid extraction using ethyl acetate and water, and by binding the compound to an adsorbent resin (e.g., Diaion TM HP20), washing the resin with water, and then eluting lamellicolic anhydride and hollycin using an appropriate solvent (e.g., methanol or ethanol). Due to the different polarities of hollycin and lamellicolic anhydride, the individual compounds can be easily separated using chromatography (e.g., flash chromatography) and a reversed phase stationary phase (e.g., C-18).

[0102] The hollycin and lamellicolic anhydride thus extracted can be purified and used as separate homogeneous compounds. In another embodiment, the extracted substances can be a combination of hollycin and lamellicolic anhydride according to the first aspect, and can be used in combination in agricultural chemical formulations.

[0103] In other embodiments, hollycolic acid and lamellicolic anhydride can be obtained from other available sources, typically other fungi.

[0104] Lamellic anhydride and lamellicolic anhydride can also be prepared by synthetic techniques. Lamellic anhydride and its derivatives can be prepared by chemical synthesis by those skilled in the art of organic chemistry using commercially available materials and synthetic methods described in the scientific literature. Commercially available materials that are structurally related to lamellicolic anhydride and can serve as starting materials include, but are not limited to, 1,8-naphthalene dicarboxylic acid, 1,8-naphthalene anhydride, acenaphthene, and 5-bromoacenaphthene. Using naphthyl starting materials, the carboxylic acid functional group can be protected using standard protecting groups as desired prior to completing the aromatic functionalization reaction.

[0105] The arylmethyl groups of the lamellicolic anhydride can be introduced by electrophilic aromatic substitution, such as Friedel-Crafts alkylation. The phenolic group can then be introduced by electrophilic aromatic halogenation using, for example, chlorine or bromine, followed by nucleophilic aromatic substitution using sodium hydroxide. To introduce arylmethoxy groups, such as those found in lamellic anhydrides Ib and Ic, nucleophilic aromatic substitution can be performed using sodium methoxide. Protection and deprotection of the hydroxyl and carboxylic acid functional groups can be completed as desired to allow the anhydride moiety to be generated, which can be performed, for example, by dehydrating the 1,8-dicarboxylic acid reaction intermediate using acetic anhydride. It is also conceivable to synthesize the lamellic anhydride using acenaphthene or one of its derivatives as a starting material. In this method, the anhydride moiety can be introduced by oxidizing the ethylene bridge. Prior to this oxidation, the methyl, methoxy and / or hydroxyl functional groups can be introduced by different available synthetic methods, including but not limited to electrophilic and nucleophilic aromatic substitution as described above. However, depending on the desired results of the aromatic functionalization reaction, these reactions can also be completed after the oxidation of the ethylene bridge to adjust the aromatic directing effect.

[0106] The aromatic positions of acenaphthene can also be functionalized using biocatalytic or chemoenzymatic methods prior to the synthesis of the anhydride moiety by oxidation. These reaction steps can result in lamellicolic anhydrides Ia-Ic or other derivatives with altered positions of the methyl, methoxy and / or hydroxyl functional groups.

[0107] The properties of the adjuvant itself are understood to provide the same advantages to the agrochemical formulation comprising the adjuvant. Thus, when comprising an adjuvant of the present invention, an agrochemical formulation is provided which has the advantages of the properties of the adjuvant itself.

[0108] Agrochemical active compounds, including pesticides and fungicides, require formulations that allow for uptake of the active compound by the plant / target organism.

[0109] The term "agricultural chemical formulation" used herein refers to a composition including active agricultural chemicals, and is intended to include all forms of compositions (including concentrates and sprayable formulations). If not specifically stated, the agricultural chemical formulation of the present invention may be in the form of a concentrate, a diluted concentrate or a sprayable formulation.

[0110] The adjuvants of the present invention can be combined with other components to form an agrochemical formulation comprising at least one pesticidally active substance.

[0111] Thus, the agrochemically active compound may be formulated as an emulsifiable concentrate (EC), an emulsion (EW), a suspension concentrate (SC), a soluble liquid (SL), an oil-based suspension concentrate (OD) and / or a suspoemulsion (SE).

[0112] In EC and SL formulations, the active compound may be present in dissolved form, whereas in OD, SC, EW or SE formulations, the active compound may be present in solid or emulsified liquid form.

[0113] It is envisaged that the adjuvants of the invention will be particularly useful in EC, EW, SC, SL, OD or SE formulations.

[0114] Agrochemical concentrates are agrochemical compositions, which may be aqueous or non-aqueous, designed to be diluted with water (or a water-based liquid) to form a corresponding spray formulation. Such compositions include compositions in liquid form (such as solutions, emulsions or dispersions) and solid form (especially water-dispersible solid form) such as granules or powders.

[0115] Spray formulations are aqueous agricultural chemical formulations that include all the components that are desired to be applied to plants or their environment. Spray formulations can be prepared by simply diluting a concentrate containing the desired components (except water), or by mixing the individual components, or by diluting the concentrate and adding other individual components or a combination of component mixtures. Typically, this final use mixing is carried out in a barrel of the spray formulation, or in a storage barrel that fills the spray barrel. Such mixing and mixtures are commonly referred to as barrel mixes and barrel mixes.

[0116] Thus, adjuvants can be added to the formulation of the agrochemical active compound (in-tank / in-line formulation) or added after dilution of the concentrated formulation of the spray liquid (tank mix). In order to avoid dosage errors and increase user safety during the application of agrochemical products, it is advantageous to add adjuvants to the formulation. This also avoids the unnecessary use of additional packaging materials for tank-mix products.

[0117] Depending on the needs of the customer, the concentrate thus formed may generally contain up to 95% by weight of the pesticide active substance. The concentrate may be diluted for use to obtain a diluted composition having a concentration of about 0.5% by weight to about 1% by weight of the agrochemical active substance. In the diluted composition (e.g., a spray formulation, wherein the spray application rate may be 10 to 500 l.ha -1 ), the concentration of the agricultural chemical active substance may be from about 0.001 wt % to about 1 wt % of the total spray formulation.

[0118] The amount of adjuvant of the present invention is generally proportional to the amount of active agricultural chemicals in the formulation. In the agricultural chemical formulation concentrate, the proportion of the adjuvant depends on the solubility of each component in the liquid carrier. Generally, the concentration of the adjuvant in such a concentrate is 1% to 99% by weight. Preferably, the concentration of the adjuvant in such a concentrate is 1% to 70% by weight. More preferably, the concentration of the adjuvant in such a concentrate is 3% to 50% by weight.

[0119] When diluted to form, for example, a spray formulation, the concentration of the adjuvant is typically 0.01% to 2% by weight of the spray formulation, more typically 0.03% to 0.5% by weight. It is further preferred that the concentration of the adjuvant is 0.12% to 0.4% by weight of the spray formulation.

[0120] The ratio of adjuvant to active agrochemical in the agrochemical formulation is preferably from about 1:40 to about 1:1. More preferably, the ratio of adjuvant to active agrochemical in the agrochemical formulation is from about 1:20 to about 1:1. Further preferably, the ratio of adjuvant to active agrochemical in the agrochemical formulation is from about 1:5 to about 1:1. For concentrated forms of formulations (e.g., adjuvants are included in dispersible liquid concentrates or dispersible solid granule formulations) and in spray formulations, this ratio range generally remains the same.

[0121] When a concentrate (solid or liquid) is used as a source of active agricultural chemicals and / or adjuvants, the concentrate is usually diluted to form a spray formulation. The concentrate can be diluted with water at 1 to 10,000, especially 10 to 1,000 times the total weight of the concentrate to form a spray formulation.

[0122] If the pesticide active material is present in the aqueous final use formulation in the form of solid particles, it is usually present primarily in the form of active agrochemical particles. However, if desired, the active agrochemical can be supported on a solid carrier, such as silica or diatomaceous earth, which can be a solid carrier, filler or diluent material as described above.

[0123] The pH of aerosol formulations is generally moderately acidic (e.g., about 3) to moderately alkaline (e.g., about 10), particularly close to neutral (e.g., about 5-8). More concentrated formulations have similar acidity / alkalinity, but since they may be largely free of water, pH is not necessarily an appropriate metric.

[0124] The agrochemical formulation may include solvents (other than water), such as monopropylene glycol, oils which may be vegetable oils or mineral oils, such as spray oils (oils included in the spray formulation as non-surfactant adjuvants), associated with the first adjuvant and the co-adjuvant. Such solvents may be included as solvents for the adjuvant and / or as humectants, such as, in particular, propylene glycol. When used, such solvents are typically present in an amount of 5% to 500% by weight, preferably 10% to 100% by weight, based on the weight of the adjuvant. Such combinations may also include salts, such as ammonium chloride and / or sodium benzoate, and / or urea, in particular as gel inhibition aids.

[0125] In an alternative embodiment, the adjuvant of the invention or the organism according to the sixth aspect may be comprised in a seed coating composition suitable for use with seeds. Preferably, the adjuvant of the invention may be comprised in a seed coating composition.

[0126] The concentration of the adjuvant in the seed coating composition is suitably 0.5 to 25 wt%, preferably 2 to 18 wt%, more preferably 5 to 15 wt%, especially 8 to 12 wt%, based on the total weight of the composition.

[0127] Coating may include film coating, granulation and encapsulation or a combination of those techniques known in the art. It is envisaged that the present invention is applicable to all such coating types, preferably to film coating.

[0128] The seed coating composition of the present invention can be applied to seeds in a conventional manner.

[0129] The seeds may be pretreated (treated to increase germination, such as osmotic priming, water uptake, matrix priming) or not.

[0130] In one embodiment, the seed does not have an artificial layer, such as a primer comprising a binder (e.g., a polymer), prior to application of the seed coating composition of the present invention. Thus, the seed coating composition is preferably applied directly onto the natural outer surface of the seed. Nevertheless, the seed surface may have been surface treated prior to application of the seed coating composition.

[0131] Preferably, the seed coating composition is applied in the form of a liquid composition and / or an emulsion and / or a dispersion and / or a latex composition, and then solidified (including solidification and / or drying) to form a seed coating. The term "liquid coating composition" used in this application means a coating composition in the form of a suspension, an emulsion and / or a dispersion, preferably a dispersion.

[0132] Conventional coating methods can be used to coat seeds. Various coating machines can be used by those skilled in the art. Some well-known technologies include the use of drum coaters, fluidized bed technology, rotary coaters (with or without integrated drying) and spouted beds. Suitably, the seed coating composition is applied to the seeds by a rotary coater, a rotary drying coater, a pan coater or a continuous processor.

[0133] The seed coating composition can be applied, for example, by film coating, spraying, dipping or brushing the seed coating composition. Preferably, the method comprises applying the seed coating composition to form a film or seed coating layer. Seed coating generally comprises forming a firmly adhered, moisture permeable coating on the seed surface. The method generally comprises applying a liquid seed coating composition to the seed before planting.

[0134] Additional film coating layers may optionally be applied over the coating of the present invention to provide additional benefits including, but not limited to, modification, coverage, actives, nutrients, and processing improvements such as faster drying, seed flowability, durability, and the like.

[0135] The agricultural chemical formulation or seed coating composition may also contain other components as required. Those other components may be selected from the following:

[0136] ■ Binders, particularly those that are readily soluble in water to provide low viscosity solutions at high binder concentrations, such as polyvinyl pyrrolidone; polyvinyl alcohol; carboxymethyl cellulose; gum arabic; sugars such as sucrose or sorbitol; starch; ethylene vinyl acetate copolymers, sucrose and alginates;

[0137] ■ diluents, absorbents or carriers, such as carbon black; talc; diatomaceous earth; kaolin; aluminum, calcium or magnesium stearate; sodium tripolyphosphate; sodium tetraborate; sodium sulfate; sodium, aluminum and mixed sodium-aluminum silicates; and sodium benzoate;

[0138] ■ disintegrants, such as surfactants, substances that swell in water such as carboxymethylcellulose, cotton gum, polyvinyl pyrrolidone and microcrystalline cellulose swelling agents; salts such as sodium or potassium acetate, sodium carbonate, sodium bicarbonate or sodium sesquicarbonate, ammonium sulfate and dipotassium hydrogen phosphate;

[0139] ■ Wetting agents, such as alcohol ethoxylates and alcohol ethoxylate / propoxylate wetting agents;

[0140] ■ dispersants, such as sulfonated naphthalene formaldehyde condensates and acrylic acid copolymers, such as comb copolymers having end-capped polyethylene glycol side chains on a polyacrylic acid backbone;

[0141] ■ Emulsifiers, such as alcohol ethoxylates, ABA block copolymers, or castor oil ethoxylates;

[0142] ■Antifoaming agents, such as polysiloxane antifoaming agents, usually in an amount of 0.005-10 wt % of the formulation;

[0143] ■ viscosity modifiers, such as commercially available water-soluble or miscible gums, such as xanthan gum, and / or celluloses, such as carboxy-methyl, ethyl or propyl cellulose; and / or

[0144] ■ Preservatives and / or antimicrobial agents, such as organic acids or their esters or salts, such as ascorbic acid such as ascorbic acid palmitate, sorbic acid such as potassium sorbate, benzoic acid such as benzoic acid and methyl 4-hydroxybenzoate and propyl 4-hydroxybenzoate, propionic acid such as sodium propionate, phenols such as sodium 2-phenylphenol, 1,2-benzisothiazolin-3-one; or formaldehyde itself or paraformaldehyde; or inorganic materials such as sulfite and its salts, usually in an amount of 0.01-1 wt % of the preparation.

[0145] The agrochemical formulation or seed coating composition according to the present invention may also contain a component forming part of an emulsifier system, such as a surfactant substance. The surfactant may include a surfactant dispersant. Other adjuvants, such as surfactant adjuvants, which are not within the scope of the present invention, may be included in the compositions and formulations of the present invention and used in the present invention. Examples include alkyl polysaccharides (more properly referred to as alkyl oligosaccharides); fatty amine ethoxylates, such as coconut oil alkylamine 2EO; and derivatives of alk(en)yl succinic anhydrides, particularly those described in PCT applications WO94 / 00508 and WO 96 / 16930.

[0146] The formulation / composition may comprise one or more biologically active ingredients (including plant enhancers, in particular plant protection products (also referred to as PPP)). Suitable examples of active ingredients (in particular plant enhancers) are fungicides, bactericides, insecticides, nematicides, molluscicides, biological agents, acaricides or miticides, insecticides and biocides. Other possible active ingredients include disinfectants, microorganisms, rodenticides, herbicides (weed killers), attractants, (bird) repellents, plant growth regulators (such as gibberellins, auxins or cytokinins), nutrients (such as potassium nitrate, magnesium sulfate, iron chelates), plant hormones, minerals, plant extracts, germination agents, pheromones, biological agents, etc.

[0147] Suitable pesticidal active substances for use in the formulations or seed coating compositions of the invention are all agrochemically active compounds which may be solid or liquid at room temperature. It is envisaged that the adjuvants of the invention will be broadly applicable to all types of pesticidal active substances.

[0148] Pesticide active substances are biocides, which in the context of the present invention are plant protection agents, more particularly chemical substances which are used in the fields of medicine, agriculture, forestry and mosquito control and are able to kill different forms of organisms. In this group of biocides, so-called plant growth regulators are also included.

[0149] Biocides used in the agrochemical formulations or seed coating compositions of the present invention are generally divided into two subgroups:

[0150] ■ Pesticides, including fungicides, herbicides, insecticides, algaecides, molluscicides, miticides and rodenticides, and

[0151] ■ Antimicrobial agents, including antiseptics, antibiotics, antibacterials, antivirals, antifungals, antiprotozoals and antiparasitics.

[0152] In particular, biocides selected from insecticides, fungicides or herbicides may be particularly preferred.

[0153] The term 'pesticide' is understood to mean any substance or mixture of substances which is intended for use in preventing, destroying, repelling or mitigating any pest. Pesticides may be chemical substances or biological agents (such as viruses or bacteria) used to combat pests, including insects, plant pathogens, weeds, molluscs, birds, mammals, fish, nematodes (roundworms) and microorganisms that compete with humans for food, destroy goods, spread disease or become a nuisance. In the following examples, pesticides suitable for the agricultural chemical compositions of the present invention are provided.

[0154] Fungicides are chemical control agents for fungi. Fungicides are compounds used to prevent the spread of fungi in gardens and crops. Fungicides are also used to combat fungal infections. Fungicides can be contact or systemic. Contact fungicides kill fungi when they come into contact with the fungicide, which remains on the leaf surface. Systemic fungicides are absorbed into plant tissues and kill the fungi as they try to invade their host.

[0155] According to the present invention, examples of suitable fungicides include the following: (3-ethoxypropyl) mercuric bromide, 2-methoxyethyl mercuric chloride, 2-phenylphenol, 8-hydroxyquinoline sulfate, 8-phenylmercuric hydroxyquinoline, activated acid (acibenzolar), acyl amino acid fungicides, acypetacs, aldimorph, aliphatic nitrogen fungicides, allyl alcohol, amide fungicides, ampropylfos, dithiocarb, acylanilide fungicides, antibiotic fungicides, aromatic fungicides, aureofungin, oxepiconazole, azithiram, pyrimidine esters, barium polysulfide, bensulfuron, malpighiam, benomyl, quinone oxime hydrazone, bentaluron, benthiavalicarb, benzalkonium chloride, benzamacril, benzamide fungicides, benzamorf, benzanilide fungicides, benzimidazole fungicides, benzimidazole precursor fungicides, benzimidazolyl carbamate fungicides, benzohydroxamic acid, benzothiazole fungicides, bethoxazin, binapacryl, biphenyl, triadimefon, thiochlorophenol, blasticidin, Bordeaux mixture, boscalid, bridged diphenyl fungicides, fuconazole, pyrimidine sulfonate, soda bordeaux liquid, butylthiocarb, butylamine, calcium polysulfide, captol, captan, carbamate fungicides, morphine, phenylcarbamate / ester fungicides, carbendazim, carboxin, cyproconazole, carvone, Cheshunt mixture, mite-killing agent, chlobenthiazone, chloraniformethan, tetrachloroquinone, chlorfenazole, chlorodinitronaphthalene, chloroanisole, chloropicrin, thiophanate-methyl, tetrachloroquinoxaline, ethoxyconazole, ciclopirox, imidacloprid, clotrimazole, conazole fungicides, conazole fungicides fungicides (imidazoles), conazole fungicides (triazoles), copper (II) acetate, basic copper (II) carbonate, copper fungicides, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper (II) sulfate, basic copper sulfate, copper zinc chromate, cresol, cufraneb, cuprobam, cuprous oxide, cyazofamid, cyclamic acid amide, cyclic dithiocarbamate fungicides, cycloheximide, cycloheximide, cymoxanil, cyanamide, cyproconazole, cyprodinil, dazomethanil, dibromochloropropane, imidacloprid, decafentin, dehydroacetic acid acid), dicarboximide fungicides, benzene flusulfamide, dichloronaphthoquinone, dichlorophen, dichlorophenyl, dicarboximide fungicides, sclerotin, benzyltriadol, dichlorocyanamide, pyrochloranil, chloranil, ethochlor, diethyl pyrocarbonate, fenpropimorph, fluazifop, dimethomorph,dimethomorph, diniconazole, dinitrophenol fungicide, chloranil, dinitrocrotonate, dinocton, dinopenton, dinosulphon, dinoterbon, diphenylamine, dipyrithione, disulfiram, dimethoate, dicyanoanthraquinone, dithiocarbamate fungicide, dinitrophenol, dodecanol, dodecyl morpholine, dodecyl morpholine, dodecyl morpholine, donatidine, DONATODINE, cyclohexanone, dichlorvos, fluopicolide, ethyl Cyproconazole, mancozeb, ethaboxam, ethoxyquin, 2,3-dihydroxypropylmercury ethylmercury, ethylmercury acetate, ethylmercury bromide, ethylmercury chloride, ethylmercury phosphate, thiabendazole, famoxadone, imidacloprid, sodium sulfamethoxam, imidacloprid, chlorfenapyr, fenthiocarb, furamide, cyclamoxadone, seed coat ester, rice blastamide, fenpropathrin, fenpropidin, fenbutamide, triphenyltin, ferbam, pyrimidine, fluazinam, fludioxonil, fluoxamidopyram, fluclorac, trifloxystrobin, fluoxastrobin, fluquinconazole, flusilazole, sulfamethoxam, flutolanil, flutriafol , foltan, formaldehyde, phosphonic acid, wheat spike, furalaxyl, furazolidone, furamide fungicide, furanilide fungicide, dimethylfuran, furconazole, furconazole, furfural, seed dressing amine, furthiophanate-methyl, fruit green pyridine, griseofulvin, biguanide, quinoline acrylate, hexachlorobenzene, hexachlorobutadiene, toxic fungol, hexaconazole, hexylthiofos, mercury plus phenanthate, oxadiazine, imazalil, imidoazole, imidazole fungicide, biguanide, inorganic fungicide, inorganic mercury fungicide, iodomethane, imidoconazole, isopyruvate Bifungin, isoprodinil, valproic acid, pyraclostrobin, isovaledione, kasugamycin, kresoxim-methyl, lime sulfur, mancozeb, mancozeb, maneb, o-amide, mecarbinzid, pyraclostrobin, sulfamethoxam, mercuric chloride, mercuric oxide, mercurous chloride, mercuric fungicide, metalaxyl, metalaxyl-M, metam, metazoxolon, metconazole, sulfamethoxam, furazolidone, methyl bromide, methyl isothiocyanate, methyl mercuric benzoate, methyl mercury dicyandiamide dicyandiamide), pentachlorophenol methylmercuric salt, mesamiprole, metrafenone, metrafenone, mesamiprole, mesamiprole, morpholine fungicides, myclobutanil, meclofenoxate, N-(ethylmercury)-p-toluenesulfonylanilide, manson sodium, natamycin, nitrostyrene, phthalocyanine, flufenoxanol, OCH, octhilamide, furamide, organic mercury fungicides, organophosphorus fungicides, organotin fungicides, oxamoxadone, oxaloxane, oxathiapiprolin fungicides, oxazole fungicides, quinoline copper, oxpoconazole, oxycarboxin, pyralidone, penconazole, pencuron, pentachlorophenol,Penthiopyrad, phenylmercury urea, phenylmercury acetate, phenylmercury chloride, pyrocatechol phenylmercury derivatives, phenylmercury nitrate, phenylmercury salicylate, phenylsulfonamide fungicides, chlorpyrifos, tetrachlorophthalide, phthalimide fungicides, picoxystrobin, pyraclostrobin, mancozeb zinc, polymer dithiocarbamate fungicides, polyoxin, polyoxorim, polysulfide fungicides, potassium azide, potassium polysulfide, potassium thiocyanate, allylbenzazole, prochloraz Amine, Procymidone, Cyproconazole, Propiconazole, Propineb, Propoxyquin, Thiophanate, Prothioconazole, Pyraclostrobin, Pyraclostrobin, Pyrazole fungicides, Pyraclofos, Pyridine fungicides, Pyraclostrobin, Pyrimidine fungicides, Pyroxychlor, Pyroxypyralid, Pyrrole fungicides, Quinacetol, Quinazamid, Quinconazole, Quinoline fungicides, Quinones fungicides, quinoxaline fungicides, quinoxyfen, pentachloronitrobenzene, rabenzazole, salicylanilide, silthiopyrad, siloxane, sodium azide, sodium o-phenylphenol, sodium pentachlorophenol, sodium polysulfide, spiroxane, streptomycin, strobilurin fungicides, sulfonylanilide fungicides, sulfur, sultropen, TCMTB, tebuconazole, foliar thiophene fungicide, tetrachloronitrobenzene, tecoram, tetrafluconazole, thiabendazole, thiadifluor, thiazole fungicide, thiodimethoate, thiofluanid, thiocarbamate fungicide, thiochlorfenphim, thimerosal, thiophanate, methyl thiophanate, thiophene fungicide, cypermethrin, thiram, thiabendazole, tioxymid, tivedo, methyl tolclofos, tolnaftate, tolylfluanid, tolylmercury acetate acetate), triadimefon, triadimenol, cypermethrin, triarimol, oxadiazine, triazine fungicide, triazole fungicide, imidazobacter, tributyltin oxide, salicylate, tricyclazole, trifloxystrobin, triflumizole, triaminate, trichlorfon, unclassified fungicide, undecylenic acid, uniconazole, urea fungicide, validamycin, valinamide fungicide, vinclozolin, cyanamide, zinc cyclohexaneate, mancozeb, ziram, zoxamide and mixtures thereof.

[0156] Herbicides are pesticides used to kill unwanted plants. Selective herbicides kill specific targets while leaving desired crops relatively unharmed. Some of them work by interfering with weed growth and are usually based on plant hormones. Herbicides used to clear wasteland are non-selective and kill all plant material that comes into contact with them. Herbicides are widely used in agriculture and landscape turf management. They are used in total vegetation control (TVC) programs for highway and rail maintenance. Small amounts are used in forestry, pasture systems, and the management of areas reserved for wildlife habitat.

[0157] Suitable herbicides can be selected from the group comprising: aryloxycarboxylic acids, such as 2-methyl-4-chloro-4-nitropropionic acids, such as clodinafop, cyclohexanedione oximes, such as sethoxydim, hydroxybenzonitriles, such as bromoxynil, sulfonylureas, such as nicosulfuron, triazolopyrimidines, such as penoxsulam, triketones, such as mesotrione, triazine herbicides, such as metribuzin, hexaxinone, atrazine; sulfonylurea herbicides, such as chlorsulfuron; uracils, such as cypermethrin, cypermethrin or terbacil; urea herbicides, such as linuron, diuron, cypermethrin or chloranil; acetanilide herbicides herbicides such as alachlor or isopropyl metolachlor; thiocarbamate herbicides such as cypermethrin and cypermethrin; oxadiazole herbicides such as oxadiazon, isoxazole herbicides, phenoxyacetic acid; diphenyl ether herbicides such as fluazifop-butyl, cypermethrin, carbamate or oxyfluorfen; dinitroaniline herbicides such as trifluralin; organic phosphonate herbicides such as glufosinate salts and esters and glyphosate salts and esters; and / or dihalobenzonitrile herbicides such as bromoxynil or ioxynil, benzoic acid herbicides, dipyridilium herbicides such as paraquat; and other herbicides such as clomazone, triadimefon, benzylsulfuron and pyroxasulphone.

[0158] Particularly preferred herbicides may be selected from 2,4-dichlorophenoxyacetic acid (2,4-D), atrazine, dicamba (benzoic acid class), glyphosate, glufosinate, imazapic (imidazolinone class), isopropylamine (chloroacetamide class), picloram, clopyralid, and triclopyr (pyridine carboxylic acid class or synthetic auxin), their respective water-soluble salts and esters, and mixtures thereof.

[0159] Insecticides are pesticides used against all developmental forms of insects and include ovicides and larvicides used against eggs and larvae of insects. Insecticides are used in agriculture, medicine, industry and in the home.

[0160] Suitable insecticides may include those selected from the group consisting of chlorinated insecticides such as toxaphene, DDT, hexachlorocyclohexane, gamma-hexachlorocyclohexane, methoxychlor, pentachlorophenol, TDE, aldrin, chlordane, chlorphen, dieldrin, endosulfan, endrin, heptachlor, mirex and mixtures thereof; organophosphorus compounds such as acephate, azinphos, benzylphos, chloroxyfos, chlorpyrifos, chlorpyrifos-methyl, diazinon, dichlorvos (DDVP), dicrotophos, dimethoate, ethsulfate, chlorpyrifos, fenamiphos, fenitrothion, fenthion, thiothion, malathion, methamidophos, methidathion, methyl-parathion, mefenphos, dibromophos, omethoate, sulfoxide, parathion, phorate, phosalone, phosmet, Phostebupirim, methyl pirimiphos, propanphos Bromophos, Terbufos, Chlorpyrifos, Tribufos, Trichlorfon and mixtures thereof; Carbamates such as aldicarb, carbofuran, carbaryl, methomyl, 2-(l-methylpropyl)phenylmethylcarbamate and mixtures thereof; Pyrethroids such as allethrin, bifenthrin, deltamethrin, permethrin, resmethrin, sumithrin, tetramethrin, tralomethrin, transfluthrin and mixtures thereof; Plant toxin derived compounds such as rotenone, pyrethrum, Neem, nicotine, caffeine and mixtures thereof; Neonicotinoids such as imidacloprid; Avermectins such as avermectin; Oxadiazines such as indoxacarb; Anthranilic acid diamides such as rynaxypyr.

[0161] Acaricides are insecticides that kill mites. Antibiotic acaricides, carbamate acaricides, formamidine acaricides, mite growth regulators, organochlorines, permethrins, and organophosphate acaricides all belong to this category. Molluscicides are pesticides used to control mollusks such as moths, slugs, and snails. These substances include metaldehyde, methiocarb, and aluminum sulfate. Nematicides are chemical pesticides used to kill parasitic nematodes (worms).

[0162] Most preferably, the active substance present in the agrochemical formulation or seed coating composition of the present invention is selected from triazole fungicides, strobilurin fungicides or combinations thereof, in particular tebuconazole, flutriafol, carbendazim, azoxystrobin, kresoxim-methyl, cyproconazole or pyraclostrobin.

[0163] In addition to or as a substitute for agrochemical active substances, nutrients may also be present. In such preparations, the nutrients are usually in dry form.

[0164] The nutrients may preferably be solid nutrients. Solid nutrients are understood in the present invention to mean substances with a melting point above 20° C. (at standard pressure). Solid nutrients will also include insoluble nutrient ingredients, i.e. nutrient ingredients whose solubility in water is such that after addition there is a significant solid content in the concentrate.

[0165] Nutrients refer to chemical elements and compounds which are required or essential to promote or improve plant growth. Suitable nutrients are usually described as macronutrients or micronutrients. Suitable nutrients for the concentrates according to the invention are all nutritional compounds.

[0166] Micronutrients generally refer to trace metals or trace elements, and are generally administered in lower doses. Suitable micronutrients include trace elements selected from zinc, boron, chlorine, copper, iron, molybdenum and manganese. Micronutrients may be in soluble form or included as insoluble solids, and may be salts or chelated.

[0167] Macronutrients generally refer to those containing nitrogen, phosphorus and potassium, and include fertilizers such as ammonium sulfate and water conditioners. Suitable macronutrients include fertilizers and other compounds containing nitrogen, phosphorus, potassium, calcium, magnesium, sulfur and water conditioners.

[0168] Suitable fertilizers include inorganic fertilizers that provide nutrients such as nitrogen, phosphorus, potassium or sulfur. Fertilizers may be included in dilute formulations at relatively low concentrations or as more concentrated solutions, and at very high levels may include solid fertilizers as well as solutions.

[0169] It is contemplated that the inclusion of nutrients will depend on the specific nutrient, with micronutrients generally included in lower concentrations and macronutrients generally included in higher concentrations.

[0170] The biostimulant component can be added to a formulation or seed coating composition to promote the growth of crop plants. The biostimulant component can include or consist of one or more biostimulants.

[0171] Examples of useful biostimulants include, but are not limited to, plant growth hormones and plant growth regulators, such as cytokinins, auxins, gibberellins, ethylene, abscisic acid. Other biostimulants include protein hydrolysate derivatives, seaweed extracts, amino acids, plant extracts, chitosan derivatives, biopolymers, inorganic compounds, humic substances, microbial inoculants and microbial products or mixtures thereof.

[0172] The adjuvants of the present invention will provide adjuvancy to agricultural chemical formulations containing them, and are particularly useful for providing adjuvants for fungicides.

[0173] As used herein, the term "adjuvant" or "adjuvant" refers to a compound that, when added to an agrochemical formulation, will improve the desired effect of the agrochemical. An adjuvant can affect a diluent, a mixture, an active substance, or a target by its improved performance of the active substance. Adjuvants can be used to adhere the pesticide to the area where the pesticide acts, to change the leaf surface epidermis to allow the pesticide to enter, and / or to sensitize target pests to the active pesticide in the agrochemical formulation.

[0174] Specific adjuvant effects may include surfactants, emulsifiers (dispersants and suspending agents), oils, emulsified oils, compatibilizers, buffers and regulators, defoamers, sedimentation agents, drift control agents, thickeners, spreaders (wetting agents), stickers (thickeners and extenders), plant penetrants, translocating molecules, soil penetrants, stabilizers (UV filters) and / or sensitization of pests to active pesticides.

[0175] Preferably, the adjuvant of the present invention can be used as the sole ingredient or the main functional agent in an adjuvant formulated for tank addition use or directly formulated into a pesticide concentrate.

[0176] As a measure of the relationship between the activity of the adjuvant and the activity of a fungicide alone (e.g. pyraclostrobin) against Botrytis cinerea, a value of Inhibition Rate (Adjuvant and Fungicide) divided by Inhibition Rate (Fungicide) can be defined, with higher values ​​being desirable. Thus, a value of 1 means that the activity of the adjuvant / fungicide combination is equal to that of the fungicide alone, while a value greater than 1 means that the activity of the adjuvant / fungicide combination is greater than that of the fungicide alone. The activity values ​​of the present invention may be greater than 1. Preferably, the activity values ​​of the present invention are greater than 1.5, most preferably greater than 2.

[0177] All features described herein may be combined with any of the above aspects in any combination. Example

[0178] In order that the invention may be more readily understood, reference will now be made to the following description by way of example.

[0179] It is to be understood that all tests and physical properties listed are measured at atmospheric pressure and room temperature (ie, 20-25°C) unless otherwise stated herein or unless otherwise stated in the referenced test methods and procedures.

[0180] Formation and extraction

[0181] Activity tracking of culture extracts of the fungus Erythrocarpus sp. RKDO 1747 was performed to isolate lamellicolic anhydride and hollybiocin. The isolate RKDO 1747 was cultured on YM (yeast extract-malt extract) agar and incubated at 22°C for 14 days. Eight colony explants (approximately 3 mm) were used in sterile 50 mL test tubes. 3 ) was inoculated with 15 mL YM broth and shaken at 200 RPM, 22° C. for 5 days to produce seed inoculum. The seed culture was used to inoculate sterilized rice fermentation medium (1% brown rice and 2.5% mL YNB broth (0.67% g YNB powder, 0.5% sucrose)) prepared in Erlenmeyer flasks.

[0182] After 21 days at 22°C, the fermentation was extracted with 1 volume of ethyl acetate and shaken at 175 RPM for 60 minutes. The extract was clarified by filtration through Whatman #3 filter paper and the solvent removed in vacuo prior to chemical purification.

[0183] RKDO1747 fermentation extract was purified on a Silasep C18 flash chromatography column (43 g C-18) using a gradient of 10% MeOH:90% H2O to 100% MeOH on a Teledyne Nextgen 300 + Combiflash for 20 minutes. Fractions were analyzed on a Thermo Scientific Accela UHPLC coupled to a Thermo Exactive electrospray mass spectrometer (ESI-MS) with a SEDEX 80LT ELSD and a Thermo photodiode array (PDA) detector. Fractions containing lamellicolic anhydride or hollysin were purified on a Waters HPLC system with an evaporative light scattering detector (Waters 2424) and a mass spectrometer (Waters 3100) using a reverse phase C-18 HPLC (Kinetex 5 μm C18 column, 10x250 mm). Initial purification of lamellicolic anhydride was performed with an isocratic elution of 60% MeCN in water at a flow rate of 3 mL / min. Elution of hollysin H was performed with an isocratic elution of 80% MeCN in water.

[0184] The structures of lamellicolic anhydride and hollycosin H were elucidated by combined mass spectrometry and NMR analysis. NMR spectra were recorded on a Bruker Avance III 400 MHz NMR spectrometer. 1 H and 13 C, operated at 400 and 150 MHz, respectively. Spectra were referenced to the residual undeuterated solvent peak.

[0185] Corresponds to m / z 261.0396 [M+H] + and m / z 434.2327[M+H] + The NMR analysis of the metabolites matched the literature data and confirmed their structures as lamellic anhydride (Ia) and hollybiocin H (A). The remaining four metabolites (m / z 275.0553 (Ic), 277.0342 (Ib), 289.0707 (Id&Ie) and 305.0657 (If&Ig) [M+H] + ) corresponds to a further substituted lamellicolic anhydride containing additional hydroxyl and / or methoxy substitutions.

[0186] Lamellicolic anhydride (Ia): 1 H NMR (MeOD, 400 MHz): δ 2.78 (s, 3H), 6.35 (s, H), 6.78 (s) ppm; HRMS (ESI) m / z: calculated value C 13 H8O6[M+H]+261.0394, found value 261.0396.

[0187] Lamellicolic anhydride 277(Ib): 1 H NMR (MeOD, 400 MHz): δ 2.84 (s, 3H), 6.78 (s, H) ppm; HRMS (ESI) m / z: calculated value C 13 H8O7[M+H]+277.0343, found 277.0342.

[0188] Lamellicolic anhydride 275(Ic): 1 H NMR (MeOD, 400 MHz): δ 2.67 (s, 3H), 3.96 (s, H), 6.35 (s, H), 6.62 (s, H) ppm; HRMS (ESI) m / z: calculated value C 14 H 10 O6[M+H]+275.0550, found 275.0553.

[0189] Lamellicolic anhydride 289(Id&Ie): 1 H NMR (MeOD, 400 MHz): δ 2.96 (s, 3H), 3.82 (s, 3H), 3.90 (s, 3H), 6.79 (s, H), 6.34 (s, H) ppm; HRMS (ESI) m / z: calculated value C 15 H 12 O6[M+H]+289.0707, found 289.0708.

[0190] Lamellicolic anhydride 305(If&Ig): 1 H NMR (MeOD, 400 MHz): δ 2.66 (s, 3H), 3.77 (s, 3H), 3.96 (s, 3H), 6.37 (s, H) ppm; m / z: calculated value C 15 H 12 O7[M+H]+305.0656, found 305.0657.

[0191] Adjuvant Examples

[0192] The parameters "inhibition rate" and "fold change" should be understood to mean the following calculation:

[0193] Inhibition rate - Inhibition rate is understood to mean the amount of bactericide and / or adjuvant that inhibits visible microbial growth relative to vehicle-treated controls after incubation for 48 hours at 22°C. It is calculated using the following formula:

[0194]

[0195] in:

[0196] (i.e., vehicle-treated controls), and

[0197] The diameter of colonies grown on agar containing fungicides and / or adjuvants (i.e., solvents such as water, EtOH, MeOH, MeCN, DMSO).

[0198] Fold Change - Fold change is a measure of how well an adjuvant / bactericide combination inhibits a microorganism compared to the bactericide alone. This indicates how well the adjuvant performs relative to the bactericide alone. It is calculated using the following formula:

[0199] INH AF / INH F

[0200] in:

[0201] INH AF = inhibition of fungal growth when treated with fungicide and adjuvant, and

[0202] INH F = The inhibition rate of fungal growth when treated with fungicide alone.

[0203] Example - Combination of adjuvant and pyraclostrobin

[0204] Botrytis cinerea (ATCC 90479) was cultured on potato dextrose agar (PDA) for 7 days with daily UV cycles (12 hours UV light and 12 hours dark). Spores were harvested in a buffered sterile saline solution (0.9% saline and 1% Tween 80) and counted using a hemocytometer. The spore suspension was adjusted to 8.5 x 10 6 The final concentration of spores / mL was determined to form a standardized inoculum.

[0205] To prepare mycelial fragments for adjuvant testing, 8.5 x 10 4The spores were inoculated into 10 mL of potato dextrose broth. The tubes were incubated at 220 RPM, 22°C for 48 hours. To generate hyphal fragments from the culture, the culture was transferred to a 50 mL plastic conical tube containing approximately 20 sterile 5 mm diameter glass beads and vortexed for 5 minutes. After vortexing, the tubes were left to stand for 5 minutes to allow large hyphal masses to settle, and then the top layer containing the hyphal fragments was removed and used as inoculum for the growth inhibition assay.

[0206] The bactericide and adjuvant were dissolved in methanol and added to molten PDA (~50°C), and then agar was distributed in the wells of a 12-well multiwell plate (1 mL / well). The plates were cooled to room temperature and 10 μL of mycelial inoculum was added to the center of each well. The plates were incubated at 22°C for 48 hours and then the colony diameters were measured using a digital caliper. The biological growth control consisted of mycelium and carrier (0.07% methanol), and the negative control was culture medium and carrier (0.07% methanol).

[0207] The results of the adjuvant activity of the present invention are shown in Table 1. In each of the tested compounds, the activity of the adjuvant and pyraclostrobin in combination against Botrytis cinerea was observed, most notably lamellicolic anhydride 289 (Id & Ie) and 305 (If & Ig), which showed a 7.59 and 6.10-fold increase in fungicidal activity over pyraclostrobin alone at 0.1 μg / mL, respectively. Lamellic anhydride 289 (Id & Ie), lamellic anhydride 305 (If & Ig) and hollybiocin H (A) themselves did not show any inherent fungicidal activity at any tested concentration.

[0208] Table 1. Effect of adjuvants on the fungicidal activity of pyraclostrobin

[0209]

[0210]

[0211] The effect of adjuvant on bactericidal activity is expressed as an increase in the fold inhibition of growth. A value of 1 indicates no increase in bactericidal activity. A value less than 1 indicates a decrease in bactericidal activity, and a value greater than 1 indicates an increase in bactericidal activity.

[0212] Example - Cytotoxicity

[0213] The cytotoxicity of lamellic anhydride and hollybiocin H against African green monkey Vero kidney cells (ATCC CCL-81) was evaluated in vitro. 2Cells were cultured and maintained in 15 mL Eagle's minimally invasive medium (Sigma M5650) supplemented with 10% fetal bovine serum (VWR #CA95043-976), 100 μU penicillin and 0.1 mg / mL streptomycin in a cell culture flask. Cells were incubated at 37°C in a humidified atmosphere of 5% CO2 for 24 hours. The medium was changed every 2-3 days, and the cell confluency was not allowed to exceed 80%.

[0214] At 80% confluence, cells were counted, diluted and plated in 96-well cell culture plates (VWR#29442-054) at a cell density of 10,000 cells per well in 90 μL of growth medium. The plates were incubated at 37°C in a humidified atmosphere of 5% CO2 for 24 hours to allow cells to adhere to the plates before treatment. After 24 hours, adjuvants were dissolved in DMSO, serially diluted and added to the wells at a final concentration of 1 μg / mL to 128 μg / mL. DMSO was used as a vehicle at a final concentration of 1% in the wells.

[0215] The plates were incubated at 37°C, 5% CO2 in a humidified atmosphere for 24 hours, and then alamarBlue (Invitrogen) was added to each well at 10% of the culture volume. The fluorescence was monitored at 560 / 12 excitation, 590nm emission at time 0 and 4 hours after the addition of alamarBlue using a Thermo Scientific VarioskanFlash plate reader. After subtracting the time zero emission 590nm measurement from the final reading, the percentage of cell survival inference relative to the vehicle control well was calculated.

[0216] At the highest tested concentration (128 mg / mL), lamellicolic anhydride 289 (Id & Ie), lamellicolic anhydride 305 (If & Ig) and hollybiocin H (A) did not show any cytotoxicity towards Vero cells, indicating that the adjuvants were non-toxic to mammalian cells at the tested concentrations.

[0217] Example - Activity of adjuvants in combination with other fungicides against Botrytis cinerea

[0218] To expand the functional properties of lamellicolic anhydride, adjuvant (Ia) was tested in combination with seven fungicides belonging to six different fungicide groups classified by the Fungicide Resistance Committee (FRAC Code List 2018). The effects of the adjuvant-fungicide combinations on the fungicidal activity against Botrytis cinerea are shown in Table 2.

[0219] Table 2. Effect of (Ia) on the fungicidal activity of seven fungicides

[0220]

[0221] Fungicide codes are based on the Fungicide Resistance Action Committee Mode of Action Codes (FRAC Code List 2018).

[0222] Numbers indicate fold change improvement in fungal growth inhibition compared to the fungal test organism treated with fungicide and adjuvant vehicle alone. nt indicates not tested.

[0223] Adjuvant (Ia) and six of the seven fungicides showed a 16- to 45-fold increase in fungicidal activity against Botrytis cinerea. Mancozeb was the least effective, although in this case the fungicidal effect was still increased by 1.9 to 3.1 times.

[0224] These results clearly demonstrate that lamellicolic anhydride adjuvant (Ia) provides an adjuvant effect for a variety of fungicides from different chemical classes with different modes of action.

[0225] The improved control was not due to an additive fungicidal effect, as the adjuvant alone did not inhibit the growth of B. cinerea, as shown by a fold change value of 1, indicating no effect on fungal growth.

[0226] Example - Effects of adjuvants combined with other fungicides on other fungi

[0227] To evaluate the biological spectrum of activity, lamellicolic anhydride adjuvant (Ia) was tested in combination with seven fungicides against six different fungal test organisms from five different genera.

[0228] Prior to evaluating the adjuvant effect of (Ia), the minimum inhibitory concentration (MIC) of each fungicide against each test organism was determined by measuring growth on agar plates containing decreasing concentrations of the fungicide.

[0229] After determining the MIC, an adjuvant test was performed, with the concentration of (Ia) fixed at 4 μg / mL, and the concentration of each fungicide inhibiting fungal growth by 10-20%.

[0230] The results are shown in Table 3.

[0231] Table 3. Adjuvant Effects of 4 μg / mL of Ia on the Fungicidal Activity of Seven Fungicides Against Six Fungal Target Organisms

[0232]

[0233]

[0234] Fungicide codes are based on the Fungicide Resistance Action Committee Mode of Action Codes (FRAC Code List 2018).

[0235] The fungal targets are: FT1-Fusarium solani, FT2-Fusarium oxysporum, FT3-Alternaria infectorium, FT4-Penicillium roqueforti, FT5-Aspergillus flavus, FT6-Cladosporium sp.

[0236] These numbers indicate the fold change improvement in fungal growth inhibition compared to the fungal test organism treated with the fungicide alone and the adjuvant vehicle. A value of 1 indicates no effect on fungicidal activity, while a value > 1 indicates an improvement in fungicidal activity. nt indicates not tested.

[0237] It was observed that the activity of the adjuvant in combination with dimethomorph against Fusarium solani (increased by 1.63 times), in combination with pyraclostrobin against Fusarium oxysporum (increased by 1.63 times), in combination with mancozeb, dimethomorph, prothioconazole and pyraclostrobin against infectious Neurospora (increased by 2.45 times, 1.25 times, 1.50 times and 1.18 times, respectively), and in combination with pyrimethanil, mancozeb, dimethomorph, prothioconazole, iprodione, The activity of pyraclostrobin in combination with captan against Penicillium roqueforti (increased by 1.31, 1.63, 1.85, 1.52, 1.65, 1.27 and 1.17 times, respectively), the activity of pyraclostrobin in combination with mancozeb, dimethomorph, prothioconazole and iprodione against Aspergillus flavus (increased by 2.01, 1.27 and 1.28, 1.72 times, respectively), and the activity of pyrimethanil in combination with pyrimethanil against Cladosporium (increased by 1.67 times).

[0238] These results suggest that the combination of lamellicolic anhydride adjuvant (Ia) with a variety of fungicides having different chemical structures and modes of action can improve the control of a variety of fungi, further broadening the practical applications of the adjuvants described herein.

[0239] Example - Phytotoxicity

[0240] Phytotoxicity testing on soybean (Glycine max, cv Alexa) was performed to determine the safe use level of lamellicolic anhydride.

[0241] Soybean plants were grown by sowing a single seed inoculated with Bradyrhizobium japonicum (Novozymes GlyciMax) in Levington's M3 compost in 9 cm x 9 cm plastic pots. The greenhouse temperature was set to maintain 22°C ± 2 during the day and 19°C ± 2 at night. The photoperiod was set to 14 h day.

[0242] Soybean plants received supplemental lighting from SON-T bulbs. Biocontrol was used to prevent thrips damage (Bioline – Amblyseius cucumeris).

[0243] All plants were kept well watered. Adjuvant treatments were applied to soybean plants once they reached the V4 stage (6 weeks). To maintain the treatment on the leaf surface immediately after application, leaves were placed on a platform made of potting frames. The frames were stacked high enough to allow leaves to spread out on top. Laminated cardstock was taped to the top of the frames to provide support for the leaves.

[0244] For soybean plants, the central leaf of a fully expanded trifoliate leaf was held flat by carefully taping along the edges with microporous tape.

[0245] The phytotoxicity of two preparations was evaluated, a crude fermentation extract containing hollycolic acid and lamellicolic anhydride prepared by extraction of solid rice ferment with ethyl acetate, and a purified fraction containing lamellicolic anhydride 305 (If & Ig). These materials were prepared as described above.

[0246] The test substance was dissolved in 20% (v / v) DMSO at a concentration of 10 mg / mL, and then a dilution series of 0.05-1 g / L was prepared while maintaining the DMSO concentration at 2% (v / v).

[0247] The positive phytotoxicity control was Synpronic A11 (1 g / L; obtained from Croda), and the negative control was AtplusUEP-100 (1 g / L; obtained from Croda).

[0248] The treatments were randomly assigned to leaf sites and marked using a fine tip marker. For any given dilution rate, all treatments fit on one leaf. A total of eight replicate leaves on separate plants were used for each treatment dilution. Treatments were applied to leaves as 10 μL drops. During treatment application, the lights above the plants were turned off and not turned back on until the drops were completely dry.

[0249] Phytotoxicity was scored and plants were evaluated for phytotoxic tissue damage 1 day after treatment (DAT), 7 days, and 14 days after treatment.

[0250] The results are shown in Table 4.

[0251] Table 4. Phytotoxicity evaluation on soybean (Glycine max, cv Alexa).

[0252]

[0253] The phytotoxicity rating ranges from 0 to 3, where:

[0254] 0 – no damage / necrosis; 1 – slight spotty necrosis in the area wetted by the droplet; 2 – ring-shaped necrosis; 3 – extensive necrosis.

[0255] Phytotoxicity was observed for the crude extract and lamellicolic anhydride 305 at less than 0.4 when tested up to 0.25 mg / L per point. This indicates that the phytotoxic effects were minimal and limited to the sites wetted by the droplets. At 0.1 mg / mL and below, no phytotoxic effects were observed for either test sample. As expected, Atplus UEP-100 showed only mild phytotoxic effects, which occurred in just 14 days.

[0256] These results show that the application of the adjuvant formulation prepared by RKDO1747 does not damage soybean tissue when applied at a concentration below 0.25 g / L, and there is no phytotoxic effect when the crude extract and lamellicolic anhydride 305 samples are applied at 0.1 or 0.05 g / L, respectively. Since the adjuvant activity of lamellicolic anhydride can generally be obtained at a concentration below 0.01 g / L, the ratio required to obtain adjuvant activity is much lower than the ratio at which phytotoxic effects are observed. It should be understood that the present invention is not limited to the details of the above-described embodiments, which are described by way of example only. Many variations are possible.

Claims

1. An agricultural chemical preparation comprising: i) an adjuvant which is a lamellicolic anhydride according to formula (I) in: R 1 independently represents hydrogen or methyl; R 2 independently represents hydrogen or methyl; R 3 and R 4 independently represent hydrogen or methyl; and R 5 and R 6 independently represent hydrogen or hydroxy; and ii) at least one pesticide active substance; The ratio of the adjuvant to the pesticide active substance is 1:20 to 1:

1.

2. The formulation according to claim 1, wherein the compound of formula (I) is selected from the group consisting of: R 1 , R 3 , R 4 , R 5 and R 6 are hydrogen, and R 2 is methyl; or R 1 , R 3 , R 4 and R 6 All are hydrogen, R 5 is a hydroxyl group, and R 2 is methyl; or R 1 , R 4 , R 5 and R 6 are hydrogen, and R 2 and R 3 is methyl; or R 4 , R 5 and R 6 are hydrogen, and R 2 , R 3 and R 1 is methyl; or R 3 , R 5 and R 6 are hydrogen, and R 2 , R 4 and R 1 is methyl; or R 4 and R 5 is hydrogen, R 2 , R 3 and R 1 is methyl, and R 6 is hydroxyl; or R 3 and R 5 is hydrogen, R 2 , R 4 and R 1 is methyl, and R 6 It is hydroxyl.

3. The formulation of claim 1 or claim 2, wherein the lamellicolic anhydride is selected from the following:

4. A concentrated formulation suitable for preparing an agricultural chemical formulation according to any one of claims 1 to 3, the concentrated formulation comprising: i) an adjuvant which is a lamellicolic anhydride according to formula (I) in: R 1 independently represents hydrogen or methyl; R 2 independently represents hydrogen or methyl; R 3 and R 4 independently represent hydrogen or methyl; and R 5 and R 6 independently represent hydrogen or hydroxy; and ii) at least one pesticide active substance; The ratio of the adjuvant to the pesticide active substance is 1:20 to 1:

1.

5. Use of a compound of lamellicolic anhydride according to formula (I) as an adjuvant in an agrochemical formulation comprising at least one pesticide active substance in: R 1 independently represents hydrogen or methyl; R 2 independently represents hydrogen or methyl; R 3 and R 4 independently represent hydrogen or methyl; and R 5 and R 6 independently represents hydrogen or hydroxyl; The ratio of the adjuvant to the pesticide active substance is 1:20 to 1:

1.

6. A method of treating plants to control pests, the method comprising applying a formulation according to any one of claims 1 to 3 or a diluted concentrated formulation according to claim 4 to the plants or to the immediate environment of the plants.

7. A seed coating composition comprising the adjuvant of any one of claims 1 to 3.

8. A lamellicolic anhydride selected from the group consisting of:

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