Methods for controlling or preventing infestation of plants by a phytopathogenic microorganism of the genus alternaria

Abstract

The present invention relates to methods for controlling or preventing infestation of plants by a phytopathogenic microorganism of the genus Alternaria, comprising applying to a crop of plants, the locus thereof, or propagation material thereof, the compound of formula (I) or a pesticidal composition comprising the compound.

Description

[0001] Title

[0002] Methods for controlling or preventing infestation of plants by a phytopathogenic microorganism of the genus Altemaria

[0003] Technical Field

[0004] The present invention relates to methods for controlling or preventing infestation of plants by the phytopathogenic microorganism of the genus Alternaria.

[0005] Background

[0006] Tobacco brown spot disease represents a significant agricultural problem. This disease primarily targets lower or mature leaves of the tobacco plant, which are vital to the crop's commercial value. During the growing season, the brown spot disease populations proliferate at an exponential rate, imposing the greatest risk to plants with a prolonged presence in the field.

[0007] Altemaria alternata, the opportunistic pathogen responsible for brown spot, is known for its resilience and ability to survive on crop debris, from which it spreads its asexual spores, or conidia. These conidia can disperse widely and require moisture to facilitate germination and subsequent colonization of host plant tissues. The colonization phase leads to the formation of lesions on the host plants, within which a large number of conidia are produced and then dispersed, propagating the infection cycle.

[0008] The host range of Alternaria alternata is extensive, affecting not only tobacco but also other crops including pears, apples, wheat, tomatoes, beans, cotton, peppers, cucurbits, potatoes, strawberries, and beets, among others. Infection by A. alternata often necessitates a wound in the plant tissue, which underscores the opportunistic nature of this pathogen.

[0009] Current commercial standards for treating plants infected with Alternaria spp., particularly tobacco plants afflicted with brown spot disease, have been insufficient in providing effective control. This inadequacy has led to a pressing demand for the development of novel methods to manage this persistent phytopathogen and mitigate its impact on agriculture.

[0010] In light of these challenges, the current invention provides an improved method for controlling or preventing infestation by Alternaria spp., in particular Alternaria alternata. This method offers superior effectiveness in managing the pathogen, leading to healthier plants, higher crop yields, and enhanced quality, thereby providing tangible benefits to farmers.

[0011] Description of the embodiments

[0012] Cyclobutylcarboxamide compounds of formula (I) and processes for their preparation have been disclosed in WO2013 / 143811 and WO2015 / 003951 .

[0013] One cyclobutylcarboxamide, cyclobutrifluram (ISO name, CAS RN [1460292-16-3]), has been recently published as being under development as a nematicide

[0014] (http: / / pmonline.azurewebsites.net / _Main / Pesticide.aspx). The chemical structure of cyclobutrifluram is the compound of formula (1-1)

[0015] It was known that the compound of formula (I) (e.g., cyclobutrifluram) has activity against root-knot nematodes such as Meloidogyne genus and cyst-forming nematodes such as Heterodera genus. These nematode species are soil based and attack the root system of many plants. However, no data has been reported that the compound of formula (I) (e.g., cyclobutrifluram) has any fungicial activity against a fungi from the genus Alternaria, or on tobacco plants, and in particular no data has been reported that the compound of formula (I) (e.g., cyclobutrifluram), as a single active agent, has any activity against Alternaria altemata.

[0016] It has now been surprisingly found that the cyclobutylcarboxamide compound of formula (I) (e.g., cyclobutrifluram) is highly effective at controlling or preventing the infestation of plants by a phytopathogenic microorganism of the genus Alternaria. This highly effective compound thus represents an important new solution for farmers to control or prevent infestation of plants by a phytopathogenic microorganism of the genus Alternaria. It has been found that the compound of formula (I) (e.g., cyclobutrifluram) is highly effective when applied through foliar spraying on tobacco against the infestation by a phytopathogenic microorganism of the genus Alternaria. Testing has shown the compound of formula (I) (e.g., cyclobutrifluram) protects the plants far more effectively than any currently used commercial standards. Thus, the compound of formula (I) (e.g., cyclobutrifluram) presents an excellent tool for farmers for controlling or preventing infestation of plants by a phytopathogenic microorganism of the genus Alternaria.

[0017] Hence, as embodiment 1 , there is provided a method for controlling or preventing infestation of plants by a phytopathogenic microorganism of the genus Alternaria, comprising applying to a crop of plants, the locus thereof, or propagation material thereof, the compound of formula (I) wherein

[0018] R11 and R12 are independently selected from halogen;

[0019] A is pyridyl which is substituted by one or two substituents independently selected from halogen, Ci- C4-alkyl and Ci-C4-haloalkyl.

[0020] In a preferred embodiment, R11 and R12 are independently selected from chloro and fluoro; and A is pyrid-2-yl or pyrid-3-yl, which is substituted by one or two Ci-C4-haloalkyl substituents. In a more preferred embodiment, A is selected from

[0021] R13 is Ci-C4-haloalkyl.

[0022] In an even more preferred embodiment, the compound is selected from any one of compounds 1 to 7 of formula (I) wherein R11 , R12 and A are as defined in the following table:

[0023] In the most preferred embodiment, the compound is cyclobutrifluram.

[0024] The compound of formula (I) represents the compound in cis configuration: the phenyl ring on the left hand side and the pyridyl-C(=O)-NH group on the right hand side are cis to each other on the cyclobutyl ring as illustrated for compound of formula (la) and (lb):

[0025] Particularly, Cyclobutrifluram as disclosed above represents the compound in cis configuration: the phenyl ring on the left hand side and the pyridyl-C(=O)-NH group on the right hand side are cis to each other on the cyclobutyl ring as illustrated for compound of formula (1-1 a) and (1-1 b):

[0026] The wedged bonds shown in the compounds of formula (la), (lb), (1-1 a) and (1-1 b) represent absolute stereochemistry, whereas the thick straight bonds such as those shown for compound of formula (I) and (1-1) represent relative stereochemistry.

[0027] It has also surprisingly been found that one enantiomer of the compound of formula (I) (e.g., cyclobutrifluram) is particularly useful in a method for controlling or preventing infestation of plants by a phytopathogenic microorganism of the genus Alternaria.

[0028] Thus, as embodiment 2, there is provided the method according to embodiment 1 wherein the compound of formula (I) (e.g., cyclobutrifluram) is in the form of the (1 S, 2S) stereoisomer, in which case the compound of formula (I) would have the structure of formula (la), and cyclobutrifluram would have the structure of formula (1-1 a):

[0029] In a method according to embodiment 3, the compound comprises both the (1S,2S) and (1 R,2R) stereoisomers, the ratio of the (1 S,2S) stereoisomer to its enantiomer (1 R,2R) is greater than 1 :1. Preferably, the ratio of the (1 S,2S) to (1 R,2R) is greater than 1.5:1 , more preferably greater than 2.5:1 , especially greater than 4:1 , advantageously greater than 9:1 , desirably greater than 20:1 , in particular greater than 35:1 .

[0030] A skilled person is aware that according to the method of embodiments 1 to 3, the compound of formula (I) (e.g., cyclobutrifluram) is generally applied as part of a pesticidal composition. Hence, as embodiment 4, there is provided a method for controlling or preventing infestation of plants by a phytopathogenic microorganism of the genus Alternaria comprising applying to a crop of plants, the locus thereof, or propagation material thereof a pesticidal composition comprising the compound of formula (I) (e.g., cyclobutrifluram) and one or more formulation adjuvants.

[0031] As embodiment 5, there is provided a method for controlling or preventing infestation of plants by a phytopathogenic microorganism of the genus Alternaria comprising applying to a crop of plants, the locus thereof, or propagation material thereof a pesticidal composition comprising a compound of formula (la) (e.g., a compound of formula (1-1 a)) and one or more formulation adjuvants.

[0032] Mixtures containing up to 50%, preferably up to 40%, more preferably up to 30%, especially up to 20%, advantageously up to 10%, desirably up to 5%, in particular up to 3 %, of the trans stereoisomers of the compounds of formula (I) (i.e. wherein the phenyl and the pyridyl-C(=O)-NH groups are trans to each other) are also understood to be part of this invention. Preferably, the ratio of the cis isomer to its trans isomer is greater than 1.5:1 , more preferably greater than 2.5:1 , especially greater than 4:1 , advantageously greater than 9:1 , desirably greater than 20:1 , in particular greater than 35:1 .

[0033] As embodiment 6, there is provided the method according to any one of embodiments 1 to 5, wherein the pesticidal composition is a suspension composition.

[0034] As embodiment 7, there is provided the method according to any one of embodiments 1 to 6 comprising the steps providing the compound of formula (I) (e.g., cyclobutrifluram) or a pesticidal composition comprising the compound as defined in any one of embodiments 1 to 6; applying the composition to a propagation material (e.g., seed); and planting the propagation material.

[0035] As embodiment 8, there is provided the method according to any one of embodiments 1 to 6 comprising the steps providing the compound of formula (I) (e.g., cyclobutrifluram) or a pesticidal composition comprising the compound as defined in any one of embodiments 1 to 6; and applying the composition to a crop of plants or the locus thereof.

[0036] As embodiment 9, there is provided the use of the compound of formula (I) (e.g., cyclobutrifluram) or a pesticidal composition comprising the compound as defined in any one of embodiments 1 to 6 for controlling or preventing infestation of plants by a phytopathogenic microorganism of the genus Altemaria.

[0037] As embodiment 10, there is provided a method for growing a plant comprising applying or treating a propagation material thereof with the compound of formula (I) (e.g., cyclobutrifluram) or a pesticidal composition comprising the compound as defined in any one of embodiments 1 to 6.

[0038] As embodiment 11 , there is provided a method or use according to any one of embodiments 1 to 10 wherein the compound of formula (I) (e.g., cyclobutrifluram) or a pesticidal composition comprising the compound is applied on the leaves of the crop.

[0039] As embodiment 12, there is provided a method or use according to any one of embodiments 1 to 11 , wherein the compound of formula (I) (e.g., cyclobutrifluram) or a pesticidal composition comprising the compound is applied through foliar spraying.

[0040] As embodiment 13, there is provided a method or use according to any one of embodiments 1 to 12, wherein the compound of formula (I) (e.g., cyclobutrifluram) is applied at a rate of 0.05-100 mgai / plant, preferably, 0.1-50 mgai / plant, more preferably, 0.1-20 mgai / plant, especially 0.1-10 mgai / plant, in particular 0.1-5 mgai / plant.

[0041] As embodiment 14, there is provided a method or use according to any one of embodiments 1 to 13, wherein the phytopathogenic microorganism is Alternaria alternata.

[0042] As embodiment 15, there is provided a method or use according to any one of embodiments 1 to 14, wherein the plant is tobacco. As embodiment 16, there is provided a method or use according to any one of embodiments 1 to 15, wherein the phytopathogenic disease is tobacco brown spot.

[0043] As embodiment 17, there is provided a method or use according to any one of embodiments 1 to 16, wherein the compound of formula (I) (e.g., cyclobutrifluram) or the pesticidal composition is applied in the absence of difenoconazole.

[0044] As embodiment 18, there is provided a method or use according to any one of embodiments 1 to 17, wherein the compound of formula (I) (e.g., cyclobutrifluram) is applied as the single active ingredient or is comprised as the single active ingredient in the pesticidal composition.

[0045] The preparation of the compound of formula (I) (e.g., cyclobutrifluram) has been disclosed in WO2013 / 143811 and WO2015 / 003951 which are incorporated herein by reference.

[0046] The term “seed” embraces seeds and plant propagules of all kinds including but not limited to true seeds, seed pieces, suckers, corns, bulbs, fruit, tubers, grains, rhizomes, cuttings, cut shoots and the like and means in a preferred embodiment true seeds.

[0047] Application according to the methods or uses according to any one of embodiments 1 to 18 is preferably to a crop of plants, the locus thereof or propagation material thereof. Preferably application is to a crop of plants or propagation material thereof, e.g., leaves of the crop. Application of the compound of formula (I) (e.g., cyclobutrifluram) or a pesticidal composition comprising the compound can be performed according to any of the usual modes of application, e.g. foliar, drench, soil, in furrow etc, preferably through foliar spraying.

[0048] The methods or uses as defined in any one of embodiments 1 to 18 are suitable for use on any plant, including those that have been genetically modified to be resistant to active ingredients such as herbicides, or to produce biologically active compounds that control infestation by plant pests.

[0049] Generally, the compound of formula (I) (e.g., cyclobutrifluram) is used in the form of a composition (e.g. formulation) containing a carrier. The compound of formula (I) (e.g., Cyclobutrifluram) and compositions comprising the compound as defined in any one of embodiments 1 to 18 can be used in various forms such as aerosol dispenser, capsule suspension, cold fogging concentrate, dustable powder, emulsifiable concentrate, emulsion oil in water, emulsion water in oil, encapsulated granule, fine granule, flowable concentrate for seed treatment, gas (under pressure), gas generating product, granule, hot fogging concentrate, macrogranule, microgranule, oil dispersible powder, oil miscible flowable concentrate, oil miscible liquid, paste, plant rodlet, powder for dry seed treatment, seed coated with a pesticide, soluble concentrate, soluble powder, solution for seed treatment, suspension concentrate (flowable concentrate), ultra low volume (ulv) liquid, ultra low volume (ulv) suspension, water dispersible granules or tablets, water dispersible powder for slurry treatment, water soluble granules or tablets, water soluble powder for seed treatment and wettable powder.

[0050] A formulation typically comprises a liquid or solid carrier and optionally one or more customary formulation auxiliaries, which may be solid or liquid auxiliaries, for example unepoxidized or epoxidized vegetable oils (for example epoxidized coconut oil, rapeseed oil or soya oil), antifoams, for example silicone oil, preservatives, clays, inorganic compounds, viscosity regulators, surfactant, binders and / or tackifiers. The composition may also further comprise a fertilizer, a micronutrient donor or other preparations which influence the growth of plants as well as comprising a combination containing the compound of the invention with one or more other biologically active agents, such as bactericides, fungicides, nematicides, plant activators, acaricides, and insecticides.

[0051] The compositions are prepared in a manner known per se, in the absence of auxiliaries for example by grinding, screening and / or compressing a solid compound of the present invention and in the presence of at least one auxiliary for example by intimately mixing and / or grinding the compound of the present invention with the auxiliary (auxiliaries). In the case of solid compounds of the invention, the grinding / milling of the compounds is to ensure specific particle size.

[0052] Examples of compositions for use in agriculture are emulsifiable concentrates, suspension concentrates, microemulsions, oil dispersibles, directly sprayable or dilutable solutions, spreadable pastes, dilute emulsions, soluble powders, dispersible powders, wettable powders, dusts, granules or encapsulations in polymeric substances, which comprise - at least - the compound of formula (I) (e.g., cyclobutrifluram) and the type of composition is to be selected to suit the intended aims and the prevailing circumstances.

[0053] As a rule, the compositions comprise 0.1 to 99%, especially 0.1 to 95%, of the compound of formula (I) (e.g., cyclobutrifluram) and 1 to 99.9%, especially 5 to 99.9%, of at least one solid or liquid carrier, it being possible as a rule for 0 to 25%, especially 0.1 to 20%, of the composition to be surfactants (% in each case meaning percent by weight). Whereas concentrated compositions tend to be preferred for commercial goods, the end consumer as a rule uses dilute compositions which have substantially lower concentrations of active ingredient.

[0054] Examples of foliar formulation types for pre-mix compositions are: GR: Granules

[0055] WP: wettable powders

[0056] WG: water dispersable granules (powders)

[0057] SG: water soluble granules

[0058] SL: soluble concentrates

[0059] EC: emulsifiable concentrate

[0060] EW: emulsions, oil in water ME: micro-emulsion

[0061] SC: aqueous suspension concentrate

[0062] CS: aqueous capsule suspension

[0063] OD: oil-based suspension concentrate, and

[0064] SE: aqueous suspo-emulsion.

[0065] Whereas, examples of seed treatment formulation types for pre-mix compositions are:

[0066] WS: wettable powders for seed treatment slurry

[0067] LS: solution for seed treatment

[0068] ES: emulsions for seed treatment

[0069] FS: suspension concentrate for seed treatment

[0070] WG: water dispersible granules, and

[0071] CS: aqueous capsule suspension.

[0072] Examples of formulation types suitable for tank-mix compositions are solutions, dilute emulsions, suspensions, or a mixture thereof, and dusts.

[0073] As with the nature of the formulations, the methods of application, such as foliar, drench, spraying, atomizing, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances.

[0074] The tank-mix compositions are generally prepared by diluting with a solvent (for example, water) the one or more pre-mix compositions containing different pesticides, and optionally further auxiliaries.

[0075] Suitable carriers and adjuvants can be solid or liquid and are the substances ordinarily employed in formulation technology, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers.

[0076] Generally, a tank-mix formulation for foliar or soil application comprises 0.1 to 20%, especially 0.1 to 15 %, of the desired ingredients, and 99.9 to 80 %, especially 99.9 to 85 %, of a solid or liquid auxiliaries (including, for example, a solvent such as water), where the auxiliaries can be a surfactant in an amount of 0 to 20 %, especially 0.1 to 15 %, based on the tank-mix formulation.

[0077] Typically, a pre-mix formulation for foliar application comprises 0.1 to 99.9 %, especially 1 to 95 %, of the desired ingredients, and 99.9 to 0.1 %, especially 99 to 5 %, of a solid or liquid adjuvant (including, for example, a solvent such as water), where the auxiliaries can be a surfactant in an amount of 0 to 50 %, especially 0.5 to 40 %, based on the pre-mix formulation.

[0078] Normally, a tank-mix formulation for seed treatment application comprises 0.25 to 80 %, especially 1 to 75 %, of the desired ingredients, and 99.75 to 20 %, especially 99 to 25 %, of a solid or liquid auxiliaries (including, for example, a solvent such as water), where the auxiliaries can be a surfactant in an amount of 0 to 40 %, especially 0.5 to 30 %, based on the tank-mix formulation.

[0079] Typically, a pre-mix formulation for seed treatment application comprises 0.5 to 99.9 %, especially 1 to 95 %, of the desired ingredients, and 99.5 to 0.1 %, especially 99 to 5 %, of a solid or liquid adjuvant (including, for example, a solvent such as water), where the auxiliaries can be a surfactant in an amount of 0 to 50 %, especially 0.5 to 40 %, based on the pre-mix formulation.

[0080] Whereas commercial products will preferably be formulated as concentrates (e.g., pre-mix composition (formulation)), the end user will normally employ dilute formulations (e.g., tank mix composition).

[0081] Seed treatment pre-mix formulations are aqueous suspension concentrates. The formulation can be applied to the seeds using conventional treating techniques and machines, such as fluidized bed techniques, the roller mill method, rotostatic seed treaters, and drum coaters. Other methods, such as spouted beds may also be useful. The seeds may be presized before coating. After coating, the seeds are typically dried and then transferred to a sizing machine for sizing. Such procedures are known in the art. The compound of formula (I) (e.g., Cyclobutrifluram) is particularly suited for use in soil and seed treatment applications.

[0082] The invention will now be illustrated by the following non-limiting Examples. All citations are incorporated by reference.

[0083] Biological example

[0084] Example 1 : Pot trial of Cyclobutrifluram against tobacco brown spot

[0085] Methods:

[0086] Tobacco culture: tobacco seedlings were cultured in a greenhouse at 18-28°C until 8-10 leaves stage. Pathogen propagate: an isolate of Alternaria alternata, which causes tobacco brown spot, was incubated on potato-dextrose-agar (PDA) medium at 25°C for 10 days for use.

[0087] Fungicides application: applied by foliar spraying once 70 days after sowing.

[0088] Inoculation: 24h after application of the fungicide, a mycelial plug with 5 mm was taken from isolate culture and transferred upside down to the surface of tobacco leaves.

[0089] Incubation: seedlings incubated at 20-26°C, 12h light per day.

[0090] Evaluation: 9 days after application of the fungicide, the disease index was recorded based on the size of the disease lesion.

[0091] Based on the size of the infected lesion, each plant was evaluated using a 0-9 scale, wherein 0 = no infection, 1 = lesion diameter < 1 cm, 3 = lesion diameter between 1 -1.49 cm, 5 = lesion diameter between 1 .5-1 .99 cm, 7 = lesion diameter between 2-2.5 cm, 9 = lesion diameter > 2.5 cm. The disease index was calculated according to the following formula: Disease index = 100* (Number of infected leaves at each level x value of the respective level) / (sum of evaluated leaves x 9)

[0092] The control efficacy was calculated according to the following formula:

[0093] Control efficacy (%) = (Disease index of untreated control - disease index of treated group by chemical) / disease index of untreated control x 100

[0094] Table 1 : Control efficacy of different products

[0095] As is well known in the art, Cyclobutrifluram, Fluopyram, Boscalid, Penthiopyrad and Thifluzamide may share the same mode of action (see e.g., FRAC Code List ®* 2022: Fungal control agents sorted by cross-resistance pattern and mode of action (including coding for FRAC Groups on product labels)). However, the above test data show that Cyclobutrifluram surprisingly provides the best control efficacy against tobacco brown spot compared to other products even at the lowest rate.

Claims

Claims1 . A method for controlling or preventing infestation of plants by a phytopathogenic microorganism of the genus Alternaria, comprising applying to a crop of plants, the locus thereof, or propagation material thereof, the compound of formula (I)whereinR11 and R12 are independently selected from halogen;A is pyridyl which is substituted by one or two substituents independently selected from halogen, C1- C4-alkyl and Ci-C4-haloalkyl.

2. The method according to claim 1 , whereinR11 and R12 are independently selected from chloro and fluoro;A is pyrid-2-yl or pyrid-3-yl, which is substituted by one or two Ci-C4-haloalkyl substituents.

3. The method according to claim 1 or 2 whereinA is selected fromR13 is Ci-C4-haloalkyl.

4. The method according to claim 1 wherein the compound is selected from any one of compounds 1 to 7 of formula (I)wherein Rn, R12 and A are as defined in the following table:

5. The method according to claim 1 , wherein the compound is cyclobutrifluram.

6. The method according to any one of claims 1 to 5, wherein the compound comprises (1 S,2S) and (1 R,2R) stereoisomers, the ratio of the (1 S,2S) stereoisomer to its enantiomer (1 R,2R) is greater than 1 :1 , preferably, the ratio of the (1 S,2S) to (1 R,2R) is greater than 1.5:1 , more preferably greater than 2.5:1 , especially greater than 4:1 , advantageously greater than 9:1 , desirably greater than 20:1 , in particular greater than 35:1 .

7. The method according to any one of claims 1 to 6, wherein the compound is applied as a pesticidal composition comprising the compound and one or more formulation adjuvants.

8. The method according to claim 7, wherein the pesticidal composition is a suspension composition.

9. The method according to any one of claims 1 to 8, wherein the compound or a pesticidal composition comprising the compound is applied on the leaves of the crop.

10. The method according to any one of claims 1 to 9, wherein the compound is applied at a rate of 0.05-100 mgai / plant, preferably, 0.1-50 mgai / plant, more preferably, 0.1-20 mgai / plant, especially 0.1- 10 mgai / plant, in particular 0.1-5 mgai / plant.

11. Use of the compound as defined in any one of claims 1 to 6 or a pesticidal composition comprising the compound for controlling or preventing infestation of plants by a phytopathogenic microorganism Alternaria.

12. The method or use according to any one of claims 1 to 11 , wherein the phytopathogenic microorganism is Alternaria alternata.

13. The method or use according to any one of claims 1 to 12, wherein the plant is tobacco.

14. The method or use according to any one of claims 1 to 13, wherein the phytopathogenic disease is tobacco brown spot.

15. The method or use according to any one of claims 1 to 14, wherein the compound or the pesticidal composition is applied in the absence of difenoconazole; preferably, the compound is applied as the single active ingredient or is comprised as the single active ingredient in the pesticidal composition.

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