Enantiomer-enriched fungicides for controlling resistant plant pathogenic fungi

Abstract

The present invention relates to a composition suitable for controlling the phenotype of a 14 alpha-demethylase inhibitor resistant pathogenic fungi, comprising: (A) enantiomerically enriched or enantiomerically pure levorotatory compound of formula (I) wherein R1 and R2 are independently from each other halogen, cyano or C1-C3 haloalkyl, R3 is hydrogen, C1-C3 alkyl, C1-C3 alkenyl or C1-C3 alkynyl, A is CH or N, and R2 is hydrogen, C1-C3 alkyl, C1-C3 alkenyl or C1-C3 alkynyl; and X is CH2, C (= O), O or S; and at least one additional agrochemical active ingredient (B). # imgabs0 #

Description

[0001] The present invention relates to novel fungicidal compositions which are suitable for controlling diseases caused by plant pathogens, in particular phytopathogenic fungi which are resistant to sterol biosynthesis C14 α-demethylase inhibitor fungicides (DMI fungicides), and to a method for controlling these diseases on useful plants, in particular cereals, fruits and vegetables, which comprises treating the plants, their seeds or the soil with a fungicidally effective amount of an enantiomerically enriched compound of formula (I) or an enantiomerically pure or enantiomerically enriched compound of formula (I).

[0002] It is known from WO 2019 / 093522 that certain 2-hydroxypropionate derivatives and mixtures containing 2-hydroxypropionate derivatives have biological activity against plant pathogenic fungi, in particular against wheat leaf blight (septoria tritici blotch) (STB). WO 2021 / 230382 discloses a method for preparing certain 2-hydroxypropionate derivatives, wherein the left-handed (-)-methyl 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propionate with an enantiomeric excess of 90% ee, and its use for treating a variety of plant pathogenic fungi. Racemic mixtures of such compounds are also disclosed in US2022 / 217978 and WO2021 / 20936. Although the latter document claims various benefits of any enantiomer-enriched formulation, these benefits are not effectively disclosed in the text.

[0003] Wheat (Triticum aestivum L.) is a crop of global importance, with the EU representing the world's highest producer. Wheat is a major food and feed crop, a global commodity, and plays a key role in supporting world food security.

[0004] STB is the most devastating leaf disease of wheat and is caused by the ascomycete Zymoseptoriatritici. This fungal pathogen is most easily propagated under moist and mild conditions and may have several disease cycles each season. STB has been reported throughout Europe, but is prevalent in areas that provide favorable climatic conditions such as the British Isles or northern Germany. Infection with Zymoseptoriatritici usually results in necrotic areas on the leaves and may often also cause mixed infections with other co-pathogens.

[0005] To date, control of STB remains highly dependent on frequent and timely applications of fungicides, as yield losses can amount to up to 50% if the disease is not effectively controlled.One of the main groups of fungicides used are the sterol biosynthesis C14 α-demethylase inhibitors (DMIs).

[0006] In particular, azole (triazole) fungicides, which act as 14-alpha demethylase inhibitors, have become an essential component of field plant disease control because of their broad efficacy not only against STB but also against many agriculturally important diseases. However, the field efficacy of many azole fungicides in crop protection has been greatly reduced due to the emergence of resistance during their long-term and intensive agricultural use, and most populations of P. tritici now display mutations in the fungicide target genes.

[0007] Without wishing to be bound by any particular theory, it is believed that several molecular mechanisms play a role in reducing azole sensitivity. The most common mechanism is a change in the CYP51 gene, resulting in an amino acid change in the CYP51 enzyme. To date, more than 30 different amino acid changes have been identified in the CYP51 protein of modern wheat leaf blight populations, and more than 30 different genotypes have been registered to date.

[0008] WO 2020 / 078942 discloses that DMI-resistant Septoria tritici comprising at least one mutation in the CYP51 gene can be solved by a racemic mixture of a compound according to formula (X):

[0009]

[0010] Where A is CH or N; R 1 is selected from hydrogen, (C1-C6)-alkyl, C(O)CH3; R 2 is selected from hydrogen, (C1-C6)-alkyl or (C3-C6)-cycloalkyl; R 3 is selected from hydrogen, halogen, (C1-C6)-alkyl or (C1-C6)-haloalkyl; R 4 is selected from halogen, (C1-C6)-alkyl, (C1-C6)-haloalkyl, (C1-C6)-alkoxy or (C1-C6)-haloalkoxy; and n=0, 1, 2, 3.

[0011] However, it was found that the efficacy of these compounds was not sufficient to maintain efficacy against some strains that had developed higher resistance to this family of compounds. In particular, mutations that cause crossovers (L50S and I381V) and deletions or mutations at nucleotides 459-461 encoding amino acids are currently also considered to have the highest impact on azole sensitivity, while the presence of S524T in field populations of P. tritici is of particular concern because it limits the effective use of the remaining azole fungicides against STB. Thus, several point mutations in P. tritici populations are associated with high EC 50 Value related.

[0012] Therefore, according to the present invention, a novel composition is provided, which is suitable for controlling the 14α-demethylase inhibitor-resistant pathogenic fungal phenotype, in particular the 14α-demethylase inhibitor-resistant wheat leaf blight phenotype comprising at least one mutation in the CYP51 gene, the L50S gene and / or the I381V gene, the composition comprising:

[0013] (A) an enantiomerically enriched or enantiomerically pure levorotatory compound of formula (I):

[0014]

[0015] Where R 1 and R 2 are independently halogen, cyano or C1-C3 haloalkyl, R 3 is hydrogen, C1-C3 alkyl, C1-C3 alkenyl or C1-C3 alkynyl, A is CH or N, and X is CH2, C(=O), O or S.

[0016] Advantageously, the enantiomerically enriched or enantiomerically pure levorotatory compound (A), if present as the only compound (A), is not a 90% enantiomeric excess of (-)-methyl 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoate enantiomer relative to the dextrorotatory (+)methyl 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoate of formula (I).

[0017] Preferably, the composition according to the present disclosure comprises at least one additional component (B), advantageously an agrochemically effective component or compound.

[0018] The presence of asymmetric carbon atoms in the compounds of formula I means that these compounds exist in the form of optical isomers (ie enantiomers). To date, these compounds have only been disclosed as racemic mixtures.

[0019] The compounds of the present invention contain at least one key chiral center and therefore exist as enantiomers. According to the present invention, the chemical structures depicted herein (including the compounds of the present invention) encompass all enantiomers of the corresponding compounds, i.e., both stereoisomerically pure form (i.e., enantiomerically pure) and enantiomerically enriched mixtures of the two enantiomers, wherein the weight ratio of the enantiomers is not 50:50.

[0020] Although it is known that enantiomers may have very different effects in biological systems, where usually one enantiomer has biological activity and the other has little or no biological activity, the applicant unexpectedly found that for controlling the 14α-demethylase inhibitor-resistant wheat leaf blight phenotype comprising at least one mutation in each of the CYP51 gene, the L50S gene and the I381V gene, particularly for those phenotypes comprising mutations in genes V136A, YG591, Y461S and S524T, the use of each enantiomer is more effective than the use of the racemate. Preferably, the composition can also be used to combat the wheat leaf blight phenotype comprising mutations in genes S188N, A379G and N513K. Without wishing to be bound by any particular theory, it is believed that the presence of the two enantiomers in the racemate results in an antagonistic effect, thereby reducing the efficiency of the single enantiomer, as shown by the experimental results.

[0021] Surprisingly, it has been found that the levorotatory enantiomer has superior activity compared to the racemic mixture when applied to plant pathogenic fungi with increased resistance to C14 alpha-demethylase inhibitor fungicides (also known as DMI fungicides). However, also surprisingly, the dextrorotatory enantiomer also shows some efficacy when compared to the racemate (although much less than its levorotatory enantiomer counterpart), but often appears to make the racemate less active than expected, resulting in an antagonistic effect.

[0022] By comparing the EC of the racemate 50 The EC values ​​of the pure enantiomers 50 The results also clearly show that there is no simple or linear relationship between enantiomers and their efficacy.

[0023] Thus, the present invention encompasses mixtures comprising enantiomerically enriched levorotatory compounds of formula (I) or enantiomerically pure levorotatory compounds of formula (I) and at least one additive for use in treating or controlling 14α-demethylase inhibitor-resistant wheat leaf blight phenotypes comprising at least one mutation in each of the CYP51 gene, the L50S gene and the I381V gene, in particular also for those phenotypes comprising mutations in genes V136A, YG591, Y461S and S524T. Preferably, the composition can also be used to combat wheat leaf blight phenotypes comprising mutations in genes S188N, A379G and N513K.

[0024] It has also been observed that the compounds according to formula (I) have not been able to crystallize, and therefore they are described as having the ability to rotate plane polarized light. The enantiomer that rotates plane polarized light in a positive (or clockwise) direction is called dextrorotatory [(+)], while the enantiomer that rotates light in a negative (or counterclockwise) direction is called levorotatory [(-)].

[0025] Preferred compositions are those comprising the levorotatory enantiomer of formula (I)

[0026]

[0027] Where R 1 represents halogen; more preferably chlorine; R 2 represents halogen or trifluoromethyl, R 3 represents methyl or ethyl, A represents N, and X represents C(═O) or O, more preferably O, the levorotatory enantiomer being in enantiomerically enriched or enantiomerically pure form.

[0028] Preferred compositions are those comprising a compound of formula I

[0029]

[0030] Where R 1 Represents halogen; R 2 Represents halogen, R 3 represents methyl or ethyl, A represents N, and X represents C(═O) or O, more preferably O, the compound is in enantiomerically enriched or enantiomerically pure levorotatory form.

[0031] Particularly preferred are levorotatory enantiomerically pure compounds of formula I in which R 1 Represents chlorine; R 2 Represents chlorine, R 3 represents methyl, A represents N, and X represents O, preferably wherein [α] D 20The value has been determined to be -97.26 [(-) enantiomer of compound 1-1].

[0032] Particular preference is also given to levorotatory enantiomerically pure compounds of formula I in which R 1 Represents chlorine; R 2 represents trifluoromethyl, R 3 represents methyl, A represents N, and X represents O, preferably wherein the compound in CHCl3 [α] D 20 The value has been determined to be -20.54 [(-) enantiomer of compound 1-2].

[0033] Applicants have observed that in particular the levorotatory enantiomer unexpectedly and significantly enhances effectiveness against DMI-resistant fungi, especially when compared to the racemic mixture or the dextrorotatory enantiomer.

[0034] For comparison purposes, the right-hand enantiomerically pure compound of Formula I, wherein R 1 Represents chlorine; R 2 represents trifluoromethyl, R 3 represents methyl, A represents N, and X represents O, having an [α] of 20.78 in CHCl3 D 20 The value [(+) enantiomer of compound I-2], while the right-handed enantiomer is pure compound of formula I, wherein R 1 Represents chlorine; R 2 Represents chlorine, R 3 represents methyl, A represents N, and X represents O, having an [α] of 112.93 in CHCl3 D 20 Value [(+) enantiomer of compound I-1].

[0035] Another aspect of the invention is a method for controlling diseases on useful plants or their propagation materials caused by DMI-resistant Pseudomonas aeruginosa phenotypes comprising at least one mutation in each of the CYP51 gene, the L50S gene and the I381V gene, in particular also for those phenotypes comprising mutations in the genes V136A, YG591, Y461S and S524T, the method comprising applying a composition according to the invention to the useful plants, their loci or their propagation materials. Preferably, the composition can also be used against Pseudomonas aeruginosa phenotypes comprising mutations in the genes S188N, A379G and N513K.

[0036] In each case, the compounds of formula I according to the invention may be in free form, in oxidized form (such as N-oxides) or in salt form (e.g. agronomically acceptable salt forms). N-oxides are oxidized forms of tertiary amines or oxidized forms of nitrogen-containing heteroaromatic compounds. For example, they are described in the book "Heterocyclic N-oxides" by A. Albini and S. Pietra, published in 1991 by CRC Press, Boca Raton.

[0037] Preferred embodiments of the invention are represented by those compositions comprising a compound having formula (I) wherein A is N and X is O, and most preferably wherein R 1 is chlorine, R 2 is chlorine, R 3 is methyl, A is N, and X is O; or R 1 is chlorine, R 2 is chlorine, R 3 is ethyl, A is N, and X is O; or R 1 is chlorine, R 2 is trifluoromethyl, R 3 is methyl, A is N, and X is O. The preferred compounds of formula (I) are:

[0038] (-)-Methyl 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoate [the (-) enantiomer of compound I-1]; and (-)-methyl 2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoate [the (-) enantiomer of compound I-2].

[0039] The invention also relates to these compounds, or mixtures thereof, or enantiomerically enriched mixtures thereof with one or more corresponding dextrorotatory enantiomers.

[0040] For clarification, compound I-1 has the general structure (I-1)

[0041]

[0042] For clarification, compound I-2 has the general structure (I-2)

[0043]

[0044] Further preferred compounds I include the ethyl esters (I-3 and I4, respectively).

[0045] For clarification, compound I-3 has the general structure (I-3)

[0046]

[0047] For clarification, compound I-4 has the general structure (I-4)

[0048]

[0049] The present invention also relates to a composition comprising compounds 1-1, 1-2, 1-3 and 1-4 or mixtures thereof, or an enantiomerically enriched mixture of a levorotatory compound and one or more of its corresponding dextrorotatory enantiomers.

[0050] Compounds of formula (I) can be prepared in a similar manner to that outlined in WO 2019 / 093522 by chemical reactions known in the art and subsequently separated into enantiomers using preparative HPLC, separation using a chiral column.

[0051] Preference is given to a method which comprises applying the composition according to the invention to useful plants or their locus, more preferably to useful plants. Further preference is given to a method which comprises applying the composition according to the invention to propagation material of useful plants. The present invention encompasses all mixtures of compound I in any ratio.

[0052] Throughout this document, the expression "composition" represents various mixtures or combinations of component (A) and at least one additive (B), for example in a single "ready-to-use" form, in a combined spray mixture (which mixture consists of separate formulations of the single active ingredient components) (such as a "tank mix"), as well as the use of single active ingredient combinations when applied in a sequential manner (i.e., one after another within a reasonably short period of time, such as a few hours or days). For the implementation of the present invention, the order of applying components (A) and (B) is not important.

[0053] Further examples of compositions according to the invention comprising three active ingredients are defined as in Examples E1, E2 and E3:

[0054] The compositions according to the invention are effective against unwanted microorganisms, such as microorganisms which cause phytopathogenic diseases, in particular against phytopathogenic fungi and bacteria.

[0055] The compositions according to the invention can also be used to combat phytopathogenic fungi belonging to the following classes: Ascomycetes (e.g. Venturia, Psora, Erysiphe, Psora, Mycosphaeria, Uncinaria); Basidiomycetes (e.g. Hemileia, Rhizoctonia, Puccinia, Puccinia, Ustilago, Tilletia); Imperfect Fungi (also known as Deuteromycetes; e.g. Botrytis, Helminthosporium, Rhizoctonia, Fusarium, Zymoseptoria, Cercosporium, Alternaria, Pyrospora and Pseudocercosporium); Oomycetes (e.g. Phytophthora, Peronospora, Pseudocercospora, White Rust, Peronospora, Pythium, Pythium, Pseudocercospora, Monoparana), in particular those that have been made resistant to DMI.

[0056] Preferably, the (-)-enantiomer of compound I-1 in enantiomerically pure or enriched form can be suitably used to control genotypes K9020 wheat leaf blight CYP51 L50S V136AI381V Y461S S524T, K9026 wheat leaf blight CYP51 L50S S188N A379GI381V YG459 N513K and K9029 wheat leaf blight CYP51 L50S I381VYG459N513K. Similarly, the (-)-enantiomer of compound I-2 in enantiomerically pure or enriched form can be particularly used to control genotype K9029 wheat leaf blight CYP51 L50SI381V YG459 N513K.

[0057] The present invention also relates to a coated plant propagation material, wherein the coating of the plant propagation material comprises a composition comprising an enantiomerically enriched or enantiomerically pure levorotatory compound of formula (I):

[0058]

[0059] Where R 1 and R 2 are independently halogen, cyano or C1-C3 haloalkyl, R 3 is hydrogen, C1-C3 alkyl, C1-C3 alkenyl or C1-C3 alkynyl, A is CH or N, and X is CH2, C(=O), O or S; preferably, a composition as described above.

[0060] The present invention also advantageously relates to the use of enantiomerically enriched or enantiomerically pure levorotatory compounds of formula (I) for controlling the phenotype of pathogenic fungi resistant to 14α-demethylase inhibitors:

[0061]

[0062] Where R1 and R 2 are independently halogen, cyano or C1-C3 haloalkyl, R 3 is hydrogen, C1-C3 alkyl, C1-C3 alkenyl or C1-C3 alkynyl, A is CH or N, and X is CH2, C(=O), O or S; preferably, for controlling the 14α-demethylase inhibitor-resistant wheat leaf blight phenotype comprising at least one mutation in the CYP51 gene, the L50S gene and / or the I381V gene.

[0063] According to the invention, "useful plants" typically include the following plant species: grapevines; cereals, such as wheat, barley, rye or oats; beets, such as sugar beets or fodder beets; fruits, such as pome, stone or soft fruit, for example apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries or blackberries; leguminous plants, such as beans, lentils, peas or soybeans; oil crops, such as rapeseed, mustard, poppy, olives, sunflowers, coconuts, castor oil plants, cocoa beans or peanuts; cucumber plants, such as apples, gourds, cucumbers or melons; fiber plants such as cotton, flax, hemp or jute; citrus fruits such as oranges, lemons, grapefruits or mandarins; vegetables such as spinach, lettuce, asparagus, cabbage, carrots, onions, tomatoes, potatoes, gourds or peppers; lauraceae such as avocado, cinnamon or camphor; maize; tobacco; nuts; coffee; sugar cane; tea; vines; hops; durian; bananas; natural rubber plants; turf or ornamental plants such as flowers, shrubs, broadleaf trees or evergreens such as pines and cypresses. This list does not represent any limitation.

[0064] The term "useful plants" is to be understood as also including useful plants which have been rendered tolerant to herbicides such as bromoxynil or classes of herbicides such as, for example, HPPD inhibitors, ALS inhibitors such as primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5-enol-pyruvyl-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. Examples of crops which have been rendered tolerant to imidazolinones such as imazamox by conventional methods of breeding (mutagenesis) are Summer rapeseed (Canola). Examples of crops that have been rendered tolerant to herbicides or herbicides by genetic engineering methods include glyphosate-resistant and glufosinate-resistant maize varieties sold under the trade name Roundup®. Herculex and Commercially available.

[0065] The term "useful plants" is to be understood as also including useful plants which have been transformed by the use of recombinant DNA techniques in such a way that they are able to synthesize one or more selectively acting toxins, such as are known, for example, from toxigenic bacteria, in particular from the genus Bacillus.

[0066] The term "useful plants" is to be understood as also including useful plants which have been transformed by the use of recombinant DNA techniques so that they can synthesize selectively acting antipathogenic substances, such as, for example, so-called "pathogenesis-related proteins" (PRPs, see, for example, EP-A-0 392 225). Examples of such antipathogenic substances and transgenic plants which are able to synthesize such antipathogenic substances are known, for example, from EP-A-0 392 225, WO 95 / 33818 and EP-A-0 353 191. Methods for producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.

[0067] The term "location" of useful plants as used herein is intended to include places where useful plants grow, where plant propagation material of useful plants is sown or where plant propagation material of useful plants will be placed in the soil. Examples of such locations are fields where crop plants grow.

[0068] The term "plant propagation material" should be understood to mean the reproductive parts of a plant, such as seeds, which can be used for the propagation of a plant, and vegetative materials, such as cuttings or tubers (e.g., potatoes). For example, seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes and parts of plants can be mentioned. Germinated plants and young plants that will be transplanted after germination from the soil or after emergence can also be mentioned. These young plants can be protected before transplanting by being treated completely or partially via dipping. Preferably, "plant propagation material" should be understood to mean a seed.

[0069] In another aspect, the present application also relates to plant propagation material coated with the composition according to the invention.

[0070] Compositions of the present invention can also be used in the field of protecting stored goods from fungal attacks. According to the present invention, the term "stored goods" should be understood to represent natural substances and processed forms of plant and / or animal origin, which are taken from the natural life cycle and are expected to be protected for a long time. Stored goods of plant origin (such as plants or parts thereof (for example, stalks, leaves, tubers, seeds, fruits or grains)) can be protected in a freshly harvested state or in a processed form (such as pre-dried, moistened, crushed, ground, pressed or baked). Also falling under the definition of stored goods is wood, whether it is wood in the form of logs, such as building timber, transmission towers and fences, or wood in the form of finished products, such as wooden furniture or objects. Stored goods of animal origin are raw hides, leather, fur, hair, etc. Compositions according to the present invention can prevent adverse effects, such as corruption, fading or mildew. Preferably, "stored goods" should be understood to represent natural substances and / or processed forms of plant origin, more preferably fruit and processed forms thereof (such as pears, stone fruits, berries and citrus and processed forms thereof). In another preferred embodiment of the present invention, "stored goods" is understood to mean wood.

[0071] Therefore, another aspect of the present invention is a method for protecting stored goods, which method comprises applying a composition according to the present invention to the stored goods.

[0072] The composition according to the invention can also be used in the field of protecting technical materials from fungal attack. According to the invention, the term "technical material" includes paper; carpets; buildings; cooling and heating systems; wallboards; ventilation and air conditioning systems, etc.; preferably, "technical material" is understood to mean wallboards. The composition according to the invention can prevent adverse effects such as decay, discoloration or mold.

[0073] Furthermore, the compositions according to the invention are particularly effective against seedborne and soilborne diseases, such as Alternaria spp., Ascochyta spp., Botrytis cinerea, Cercospora spp., Claviceps purpurogenum, Cochliobolus graminearum, Colletotrichum spp., Epicoccum spp., Fusarium graminearum, Fusarium moniliforme, Fusarium oxysporum, Fusarium proliferatum, Fusarium solani, Fusarium gloeosporium, Gaimanella graminearum, graminis, Helminthosporium spp., Leaf blight, Phoma spp., Pyrenophora graminea, Pyrithosporium spp., Rhizoctonia cerealis, Sclerotinia spp., Zymoseptoria spp., Ustilago spp., Tilletia spp., Typhula incarnata, Ustilago spp., Ustilago spp. or Verticillium spp.; in particular against cereals, such as wheat, barley, rye or oats; maize; rice; cotton; soybeans; turf; sugar beet; rapeseed; potato; pulse crops (pulse crops), such as peas, lentils or chickpeas; and sunflower.

[0074] Furthermore, the compositions according to the invention can be particularly effective against post-harvest diseases such as Botrytis cinerea, Colletotrichum lunulata, Fusarium seminatum, Geotrichum candidum, Psoralea corylifolia, Psoralea sclerotiorum, Mucor pyriformis, Penicillium italicum, Penicillium sepium, Penicillium digitatum or Penicillium expansum; in particular against pathogens of fruits such as pome fruits (e.g. apples and pears), stone fruits (e.g. peaches and plums), citrus, melon, papaya, kiwi, mango, berries (e.g. strawberries), avocados, pomegranates and bananas, and nuts.

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

[0076] Some compositions according to the invention have a systemic effect and can be

[0077] Used as a foliar, soil and seed treatment fungicide.

[0078] With the compositions according to the invention it is possible to inhibit or destroy phytopathogenic microorganisms which are present on plants or plant parts (fruits, flowers, leaves, stems, tubers, roots) of various useful plants, while also protecting later growing plant parts from attack by phytopathogenic microorganisms.

[0079] The compositions according to the invention can be applied to phytopathogenic microorganisms, to useful plants threatened by attack by microorganisms, to the locus thereof, to their propagation material, to stored goods or to technological material.

[0080] The compositions according to the invention can be applied before or after the useful plants, their propagation material, stored goods or technical material have been infected with the microorganisms.

[0081] The amount of the composition according to the invention to be applied will depend on various factors, such as the compound used; the object of treatment, such as, for example, plants, soil or seeds; the type of treatment, such as, for example, spraying, dusting or seed dressing; the purpose of the treatment, such as, for example, prevention or treatment; the type of fungus to be controlled or the time of application.

[0082] When applied to useful plants, component (I) is typically applied at a rate of 5 to 2000 g ai / ha, especially 10 to 1000 g ai / ha, for example 50, 75, 100 or 200 g ai / ha.

[0083] In agricultural practice, the application rates of the compositions according to the invention depend on the type of action desired and typically range from 20 to 4000 g of total composition per hectare.

[0084] When the compositions according to the invention are used to treat seed, a rate of 0.001 to 50 g of compound (I) per kg of seed, preferably 0.01 to 10 g per kg of seed, is generally sufficient.

[0085] The composition of the present invention can be used in any conventional form, for example, in the form of a twin pack, a dry powder for 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 suspoemulsion (SE), a capsule suspension (CS), a water-dispersible granule (WG), an emulsifiable granule (EG), an oil-in-water emulsion (EO), an oil-in-water emulsion (EW), a microemulsion (ME), a dispersible oil suspension (OD), an oil suspension (OF), an oil-soluble liquid (OL), a soluble concentrate (SL), an ultra-low volume suspension (SU), an ultra-low volume liquid (UL), a master batch (TK), a dispersible concentrate (DC), a wettable powder (WP) or any technically feasible formulation in combination with an agriculturally acceptable adjuvant.

[0086] Such compositions can be produced in a conventional manner, for example by mixing the active ingredient with at least one suitable inert formulation adjuvant (e.g., diluent, solvent, filler and optionally other formulation ingredients, such as surfactants, biocides, antifreeze agents, adhesives, thickeners and compounds providing auxiliary effects). Conventional slow-release formulations intended to last for a long time can also be used. In particular, formulations to be applied in a spray form, such as water-dispersible concentrates (e.g., EC, SC, DC, OD, SE, EW, EO, etc.), wettable powders and granules can contain surfactants such as wetting agents and dispersants and other compounds providing auxiliary effects, such as condensation products of formaldehyde and naphthalene sulfonates, alkylaryl sulfonates, lignin sulfonates, fatty alkyl sulfates and ethoxylated alkylphenols and ethoxylated fatty alcohols.

[0087] The compositions according to the invention may also comprise additional pesticides, such as, for example, fungicides, insecticides or herbicides.

[0088] The composition according to the invention and the diluent are used in the form of a suitable seed dressing formulation, for example an aqueous suspension or dry powder with good adhesion to the seeds, in a manner known per se. Such seed dressing formulations are known in the art. The seed dressing formulations may contain a single active ingredient or a combination of active ingredients in encapsulated form, for example as slow-release capsules or microcapsules.

[0089] Typically, these formulations comprise by weight 0.01% to 90% active agent, 0 to 20% agriculturally acceptable surfactant and 10% to 99.99% solid or liquid formulation inert agent and one or more adjuvants, the active agent being composed of at least compound (I) and optionally other active agents (particularly microbicides or preservatives, etc.). The concentrated form of the composition typically contains by weight between about 2% and 80%, preferably between about 5% and 70% active agent. The application form of the formulation can, for example, contain by weight 0.01% to 20%, preferably by weight 0.01% to 5% active agent. However, commercial products will preferably be formulated as concentrates, and end users will typically use diluted formulations.

[0090] The other features of the composition comprising the compound of formula (I), the method for applying it to plants and its use ratio are as described for the composition comprising the compound of formula (I) and additionally at least one component (B) as described above. Their application can be before and after these plants or their parts are infected by fungi. Preferably, the treatment is carried out before infection. When the compound of formula (I) is used by itself, the application ratio in the method according to the present invention is as described above, for example, typically 5 to 2000 g ai. / ha, especially 10 to 1000 g ai / ha, for example 50, 75, 100 or 200 g ai / ha. During the growing season, the compound of formula (I) can be applied to these plants once or more than once. In order to be used in the method according to the present invention, the compound of formula (I) can be converted into the conventional formulation described above, such as solution, emulsion, suspension, dust, powder, paste and granule. The use form will depend on the particular intended purpose; in each case, it should ensure a fine and uniform distribution of the compound of formula (I).

[0091] The term "plants" as used herein includes seedlings, bushes and crops of fruits and vegetables.

[0092] The following examples are used to illustrate the present invention, "active ingredient" means a mixture of component (I).

[0093] The same formulation can be used for compositions containing only the compound of formula (I) as active ingredient, as described in the table below.

[0094] Preparation Examples

[0095] Table 1

[0096]

[0097] The active ingredient is mixed thoroughly with the other formulation components and the mixture is thoroughly ground in a suitable grinder to give wettable powders which can be diluted with water to provide a suspension having the desired concentration.

[0098] Table 2

[0099]

[0100] The active ingredient is thoroughly mixed with other formulation components and the mixture is thoroughly ground in a suitable grinder to obtain a dust that can be used directly for seed treatment.

[0101] Table 3

[0102]

[0103]

[0104] Emulsions of any desired dilution which can be used for plant protection can be obtained from these concentrates by dilution with water.

[0105] Table 4

[0106]

[0107] Ready-to-use dusts are obtained by mixing the active ingredient with a carrier and grinding the mixture in a suitable grinder. Such dusts can also be used for dry seed dressing of seeds.

[0108] Table 5

[0109]

[0110] 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.

[0111] Suspension concentrates

[0112] Table 6

[0113]

[0114] The finely ground active ingredient is mixed thoroughly with the other formulation components to give a suspension concentrate which can be diluted in water in any desired ratio. Using such a dilution, living plants and plant propagation materials can be treated and protected from microbial infestation by spraying, pouring or immersion.

[0115] Flowable concentrate for seed treatment

[0116] Table 7

[0117]

[0118] The finely ground active ingredient is thoroughly mixed with the other formulation components to give a suspension concentrate which can be further diluted in water for application to seeds. Using such a dilution, the propagation material can be treated and protected from microbial infestation by spraying, pouring or dipping.

[0119] Therefore, another aspect of the invention is a method of controlling leaf spot on plants, which method comprises applying to the plants, the locus thereof or their propagation material a composition comprising a compound of formula (I).

[0120] Preferred is a method where plant pathogens are attacking plants and causing diseases like leaf spot, powdery mildew and fungal wilt.

[0121] Preference is given to a method which comprises applying a composition comprising a compound of formula (I) to plants or the locus thereof, preferably to these plants.

[0122] Further preferred is a method which comprises applying a composition comprising a compound of formula (I) to propagation material of a plant. Still further, the present invention also relates to the use of a composition according to the invention for controlling leaf spot on plants.

[0123] The method according to the invention, in particular when a compound of formula (I) is used in combination with at least one compound (B) as described above, also allows good control of other frequently encountered harmful fungi in plants.

[0124] Preference is given to a method of controlling diseases on oilseeds and cereals, in particular diseases caused by leaf spot, which method comprises applying a composition comprising an enantiomerically pure or enriched compound of formula (I) to useful plants, their locus or their propagation material

[0125]

[0126] Where R 1 and R 2 are independently fluorine, chlorine or trifluoromethyl, R 3 is methyl or ethyl, A is N and X is C(═O) or O.

[0127] It has surprisingly been found that enantiomerically pure or enriched compounds (I), in particular levorotatory ones, are capable of producing higher activities compared to the racemic mixture.

[0128] Efficacy by comparing the EC of the racemate 50 The EC values ​​of the pure enantiomers 50 The activity of the enantiomers was tested by comparing the enantiomers to the racemates and then calculating the following values:

[0129] (EC 50 (Enantiomer) / EC 50 (racemate))-0.5=M(measured value).

[0130] A measurement M of 0 indicates a situation in which the racemate and the enantiomer show no difference in efficacy. An M value greater than 0 indicates that the racemate is more effective, while a value less than 0 indicates that the enantiomer is superior to the racemate.

[0131] Assuming that the active enantiomer of DMI contributes fully to the activity of the racemate, it should be twice as active. Therefore, the quotient of EC enantiomer / EC racemate should be 0.5. Subtracting 0.5 from this quotient should give 0. If the active enantiomer does not contribute fully, the result will be positive, but if the enantiomer is much more active than expected, the result will be negative.

[0132] It was shown that the (-)-enantiomers of the compound of formula (I) showed reproducible and unexpectedly enhanced activity at least against the DMI-tolerant genotypes of Pseudomonas aeruginosa, showing that these enantiomers showed significant and stable activity against the following DMI-tolerant genotypes: Pseudomonas aeruginosa having mutations in genes CYP51, L50S, I381V, YG459 and N513K; Pseudomonas aeruginosa having mutations in genes CYP51, L50S, V136A, I381V, Y461S and S524T; and Pseudomonas aeruginosa having mutations in genes CYP51, L50S, S188N, A379G, I381V, YG459 and N513K.

[0133] Biological Examples

[0134] A set of 16 P. tritici isolates were tested for in vitro antifungal activity. Spore suspensions of P. tritici isolates were prepared in potato dextrose nutrient broth (PDB) and exposed to a defined range of inhibitor concentrations (20 ppm starting concentration, dilution step of 3). Sensitive wild-type isolates were used together with a set of strains containing variants of the P. tritici CYP51 gene that confer resistance to the DMI fungicide. The DMI-resistant isolates were isolated from wheat in the UK, Ireland, Germany and Russia in 2020. The determination of CYP51 gene variants was achieved using targeted gene sequencing. The half-maximal effective concentration (EC50) of the inhibitor was calculated using linear regression based on the growth response of P. tritici after exposure to different concentrations of agonists for 3 days. Tables A and B show the average values ​​(in ppm) of the EC50 values ​​from two replicates, and M=(EC50 (enantiomer) / EC50 (racemate))-0.5.

[0135] Table A .*M = (EC50 (enantiomer) / EC50 (racemate)) - 0.5. An M value greater than 0 indicates that the racemate is more effective, while a value less than 0 indicates that the enantiomer is superior to the racemate.

[0136]

[0137]

[0138]

[0139] Table B *M = (EC50 (enantiomer) / EC50 (racemate)) - 0.5. M values ​​greater than 0 indicate that the racemate is more effective, while values ​​less than 0 indicate that the enantiomer is superior to the racemate.

[0140]

[0141]

[0142] As shown in Table A, the (-)-enantiomer of compound I-1 was superior to the racemate of compound I-1 in several cases and was more effective against K9020 Pseudomonas aeruginosa CYP51 L50S V136AI381V Y461S S524T, K9026 Pseudomonas aeruginosa CYP51 L50S S188N A379GI381V YG459 N513K and K9029 Pseudomonas aeruginosa CYP51 L50S I381VYG459N513K. Similarly, as shown in Table B, the (-)-enantiomer of compound I-2 was superior to the racemate of compound I-2 and was more effective against isolate K9029 Pseudomonas aeruginosa CYP51 L50S I381V YG459 N513K.

Claims

1. A composition for controlling a 14α-demethylase inhibitor-resistant wheat leaf blight phenotype comprising at least one mutation in a CYP51 gene, a L50S gene and / or an I381V gene, the composition comprising: (A) an enantiomerically enriched or enantiomerically pure levorotatory compound of formula (I): Where R 1 and R 2 are independently halogen, cyano or C1-C3 haloalkyl, R 3 is hydrogen, C1-C3 alkyl, C1-C3 alkenyl or C1-C3 alkynyl, A is CH or N, and X is CH2, C(=O), O or S, wherein compound (A), if present as the only compound (A) having formula (I), is not 90% ee enantiomeric excess of levorotatory (-)-methyl 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoate relative to dextrorotatory (+)-methyl 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoate.

2. The composition according to claim 1, further comprising at least one additional agrochemical active component (B).

3. The composition according to claim 1 or claim 2, wherein In compound (A), R 1 and R 2 are independently fluorine, chlorine or trifluoromethyl, R 3 is methyl or ethyl, A is N, and X is C(═O) or O, or an agrochemically acceptable salt or N-oxide thereof.

4. The composition according to any one of claims 1 to 3, wherein In component (A), R 1 and R 2 are independently chloro or trifluoromethyl, and wherein R 3 It is methyl or ethyl.

5. A composition according to any one of the preceding claims, wherein In component (A), A is N.

6. A composition according to any one of the preceding claims, wherein In component (A), X is C(═O) or O.

7. The composition according to any one of claims 1 to 6, wherein Component (A) is an enantiomerically enriched or enantiomerically pure composition comprising essentially levorotatory methyl 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoate; levorotatory ethyl 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoate, levorotatory methyl 2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoate, or levorotatory ethyl 2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoate, or a combination or mixture thereof.

8. The composition according to any one of claims 1 to 7, wherein Component (B) is at least one or more additional insecticidal, acaricidal, nematicidal and / or fungicidal active agents, wherein component B is not the dextrorotatory enantiomer according to formula (I).

9. A composition according to any one of the preceding claims, wherein The weight ratio of (A) to (B) is in the range of 2000:1 to 1:2000.

10. The composition according to any one of claims 1 to 9, wherein The weight ratio of (A) to (B) is in the range of 100:1 to 1:100; preferably 40:1 to 1:40; more preferably 25:1 to 1:25; still more preferably 5:1 to 1:5; and again more preferably 2:1 to 1:

2.

11. A composition according to any one of claims 1 to 10, further comprising an agriculturally acceptable carrier and optionally a surfactant, an uptake enhancer and / or one or more formulation adjuvants.

12. A method for controlling the 14α-demethylase inhibitor-resistant Pseudomonas aeruginosa phenotype caused by a plant pathogen in useful plants or their propagation material, preferably a phenotype comprising at least one mutation in the CYP51 gene, the L50S gene and / or the I381V gene, said method comprising applying to said useful plants, their locus or their propagation material a composition comprising (A) an enantiomerically enriched or enantiomerically pure levorotatory compound of formula (I): Where R 1 and R 2 are independently halogen, cyano or C1-C3 haloalkyl, R 3 is hydrogen, C1-C3 alkyl, C1-C3 alkenyl or C1-C3 alkynyl, A is CH or N, and X is CH2, C(=O), O or S.

13. The method according to claim 12, wherein: Component (A) comprises an enantiomerically enriched or enantiomerically pure composition comprising essentially levorotatory methyl 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoate; levorotatory ethyl 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoate, levorotatory methyl 2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoate, or levorotatory ethyl 2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoate, or a combination or mixture thereof.

14. The method according to claim 12 or claim 13, wherein: The composition is a composition according to any one of claims 1 to 11.

15. The method according to claim 14, wherein: Component (A) and, if applicable, component (B) are applied simultaneously, intermittently or sequentially.

16. A coated plant propagation material, wherein the coating of the plant propagation material comprises a composition comprising an enantiomerically enriched or enantiomerically pure levorotatory compound of formula (I): Where R 1 and R 2 are independently halogen, cyano or C1-C3 haloalkyl, R 3 is hydrogen, C1-C3 alkyl, C1-C3 alkenyl or C1-C3 alkynyl, A is CH or N, and X is CH2, C(=O), O or S; preferably, a composition according to any one of claims 1 to 11.

17. Use of an enantiomerically enriched or enantiomerically pure levorotatory compound of formula (I) for controlling the phenotype of pathogenic fungi resistant to 14α-demethylase inhibitors: Where R 1 and R 2 are independently halogen, cyano or C1-C3 haloalkyl, R 3 is hydrogen, C1-C3 alkyl, C1-C3 alkenyl or C1-C3 alkynyl, A is CH or N, and X is CH2, C(=O), O or S.

18. The use according to claim 17, for controlling the 14α-demethylase inhibitor-resistant Pseudomonas aeruginosa phenotype comprising at least one mutation in the CYP51 gene, the L50S gene and / or the I381V gene.

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