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WO2025019329A2 - Combinaisons d'ascaricides et d'insecticides et procédés d'utilisation - Google Patents

Combinaisons d'ascaricides et d'insecticides et procédés d'utilisation Download PDF

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Publication number
WO2025019329A2
WO2025019329A2 PCT/US2024/037825 US2024037825W WO2025019329A2 WO 2025019329 A2 WO2025019329 A2 WO 2025019329A2 US 2024037825 W US2024037825 W US 2024037825W WO 2025019329 A2 WO2025019329 A2 WO 2025019329A2
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Prior art keywords
optionally substituted
insecticide
group
ascaroside
peptide
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WO2025019329A3 (fr
Inventor
Murli MANOHAR
Edison Hidalgo
Gabriel WILMOTH
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Ascribe Bioscience Inc
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Ascribe Bioscience Inc
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Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/14—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings
    • A01N43/16—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings with oxygen as the ring hetero atom
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P7/00—Arthropodicides
    • A01P7/04—Insecticides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/02—Acyclic radicals, not substituted by cyclic structures
    • C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/02—Acyclic radicals, not substituted by cyclic structures
    • C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
    • C07H15/10—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical containing unsaturated carbon-to-carbon bonds

Definitions

  • the provided combinations comprise at least one ascaroside (or a derivative or analog of an ascaroside) with at least one insecticide.
  • the ascaroside can be combined with at least one insecticide to lessen the phytotoxic effects of the insecticide on the treated crop.
  • crop management can be made more efficient by simultaneously applying ascarosides (which can have value in controlling plant pathogens such as fungi, bacteria, viruses or nematodes, and/or in promoting plant health) with insecticides—this can minimize application passes, reduce fuel consumption, and lower crop production costs.
  • the ascarosides and insecticides may be provided in the same composition or may be applied together (i.e., substantially simultaneously) or sequentially.
  • the agents are applied in an effective amount, i.e., an amount sufficient to control or inhibit unwanted insects and also provide the desired benefits of ascaroside application (e.g., reduction of phytotoxic side effects of the insecticides, and/or control of pathogens on crop plants).
  • ascaroside application e.g., reduction of phytotoxic side effects of the insecticides, and/or control of pathogens on crop plants.
  • the disclosure provides compositions and methods relating to combinations of one or more ascarosides and one or more insecticides wherein the ascaroside(s) serve the purpose of a safener to lessen phytotoxic effects 2 BUSINESS.31669632.1 409753-016WO (210621) of the insecticide(s) on the treated crop.
  • the term “ascaroside” includes the ascaroside, a derivative or an analog of the ascaroside, or combinations thereof, as will be described in further detail herein.
  • the ascaroside can be used with any insecticide.
  • R c is an optionally substituted 3- and 8-membered saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R c is an optionally substituted 8- and 12-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R c is an optionally substituted aryl group. In some embodiments, R c is optionally substituted phenyl. In some embodiments, R 2 is phenyl. In some embodiments, R c is an optionally substituted heteroaryl group.
  • R 2 is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a glycoside, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule.
  • R 2 is -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, or an optionally substituted aromatic group, an optionally substituted heteroaryl group.
  • R 2 is selected from methyl, ethyl, n-propyl, i-propyl, n-butyl, sec- butyl, and t-butyl. In some embodiments, R 2 is an optionally substituted C 1-20 heteroaliphatic group. In some embodiments, R 2 is an optionally substituted C1-6 heteroaliphatic group. In some embodiments, R 2 is an optionally substituted 3- and 8-membered saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R 2 is an optionally substituted 8- and 12-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
  • neither R 3 is -H.
  • each R 3 is -H.
  • an occurrence of R 3 is an optionally substituted C1-20 aliphatic group.
  • an occurrence of R 3 is an optionally substituted C1-6 aliphatic group.
  • an occurrence of R 3 is an optionally substituted C 1-20 heteroaliphatic group.
  • an occurrence of R 3 is an optionally substituted C1-6 heteroaliphatic group.
  • R 3 is an optionally substituted 3- and 8-membered saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
  • R 3 is an optionally substituted 8- to 12-membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. [0040] In certain embodiments, at least one R 3 is -H. In certain embodiments, both R 3 groups are -H. In certain embodiments, at least one R 3 is an optionally substituted C 1-20 aliphatic group. In certain embodiments, both R 3 groups are an optionally substituted C1-20 aliphatic group which may be the same or different. In certain embodiments, at least one R 3 is an optionally substituted C1-12 aliphatic group. In certain embodiments, at least one R 3 is an optionally substituted C 1-8 aliphatic group.
  • At least one R 3 is an optionally substituted C1-6 aliphatic group. In certain embodiments, at least one R 3 is selected from methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, and t-butyl. In certain embodiments, at least one R 3 is -CH 2 CH 2 OH. In certain embodiments, at least one R 3 is -CH2CH2OR 2 . where R 2 is as defined in the genera and subgenera herein. In certain embodiments, at least one R 3 is an optionally substituted aromatic group. In certain embodiments, at least one R 3 comprises a glycoside.
  • At least one 15 BUSINESS.31669632.1 409753-016WO (210621) R 3 comprises an amino acid. In certain embodiments, at least one R 3 at least one R 3 comprises a peptide. In certain embodiments, at least one R 3 comprises a nucleotide. [0041] In certain embodiments, an ascaroside is selected from the group consisting of: CO 2 R 2 CO R 2 2 CO 2 R 2 O 2 CO x O x O 2 R O x x in the genera and subgenera herein.
  • an ascaroside is selected from the group consisting of: CO 2 H CO 2 H C CO 2 H O O x O x O 2 H O x x [0043] In certain embodiments, an ascaroside is selected from the group consisting of: CO O 2 R 2 y CO 2 R 2 CO 2 R 2 CO 2 R 2 in the genera and subgenera herein.
  • Specific ascarosides that are useful in the context of the present disclosure include, but are not limited to, ascr#7 and ascr#18.
  • an ascaroside used in the provided methods is selected from the group consisting of: ascr#9, ascr#14, ascr#10, and ascr#18. [0057] In certain embodiments, an ascaroside used in the provided methods and compositions is selected from the group consisting of: ascr#5, oscr#9, oscr#12, oscr#1, oscr#14, oscr#10, oscr#16, oscr#18, oscr#20, oscr#22, oscr#24, oscr#26, oscr#28, oscr#30, oscr#32, oscr#34, and oscr#36.
  • an ascaroside used in the provided methods is selected from the group consisting of: oscr#10, oscr#16, oscr#18, oscr#20, and oscr#22.
  • an ascaroside used in the provided methods is selected from the group consisting of: bhas#5, oscr#9, oscr#12, oscr#1, oscr#14, oscr#10, oscr#16, oscr#18, oscr#20, oscr#22, oscr#24, oscr#26, oscr#28, oscr#30, oscr#32, oscr#34, and oscr#36.
  • an ascaroside used in the provided methods is selected from the group consisting of: oscr#10, oscr#16, oscr#18, oscr#20, and oscr#22.
  • an ascaroside used in the provided methods and compositions is selected from the group consisting of: bhas#9, bhas#10, bhas#16, bhas#18, bhas#22, bhas#24, bhas#26, bhas#28, bhas#30, bhas#32, bhas#34, bhas#36, bhas#38, bhas#40, and bhas#42.
  • an ascaroside used in the provided methods and compositions is selected from the group consisting of: bhos#10, bhos#16, bhos#18, bhos#22, bhos#24, bhos#26, bhos#28, bhos#30, bhos#32, bhos#34, bhos#36, bhos#38, bhos#40, and bhos#42.
  • an ascaroside used in the provided methods and compositions is selected from the group consisting of: ascr#18, oscr#16, oscr#17, oscr#15, bhas#18, bhos#16, 19 BUSINESS.31669632.1 409753-016WO (210621) glas#18, dhas#18, ibha#18, ibho#16, icas#18, icos#15, icos#16, and any combination of two or more of these.
  • Ascarosides can be obtained from natural sources (e.g., nematodes) or they may be prepared synthetically.
  • Ascarosides can be prepared synthetically, for example, by converting 1- O-substituted rhamnose to 1-O-substituted ascarylose.
  • An exemplary method of preparing ascarosides includes: providing as a feedstock a 1-O-substituted rhamnose; forming a mono- sulfonate ester at the 3-OH group of the feedstock; and treating the mono-sulfonate ester with a hydride source to form a 1-O-substituted ascarylose.
  • forming the mono- sulfonate ester is conducted on a substrate without hydroxyl protecting groups at the 2- or 4- position of the rhamnose feedstock.
  • such methods comprise contacting the feedstock with a sulfonating agent (i.e., a sulfonyl halide, sulfonic anhydride, or similar reagent) in the presence of a Lewis acid.
  • a sulfonating agent i.e., a sulfonyl halide, sulfonic anhydride, or similar reagent
  • a Lewis acid i.e., a sulfonyl halide, sulfonic anhydride, or similar reagent
  • Insecticides whose phytotoxic side effects on crop plants can be reduced using ascarosides include, for example, insecticides from the chemical groups of: alkaloid insecticides; alkyl halide insecticides; aminopyrimidine insecticides; aminotriazene insecticides; antibiotic insecticides; aromatic hydrocarbon insecticides; arylpyrrole insecticides; benzimidazole insecticides; benzoylurea insecticides; beta-ketonitrile insecticides; botanical insecticides; carbamate insecticides; diacylhydrazine insecticides; diamide insecticides; dinitrophenol insecticides; dithiolane insecticides; formamidine insecticides; fumigant insecticides; inorganic insecticides; isoxazoline insecticides; juvenile hormone mimics; macrocyclic lactone insecticides; meta-diamide insecticides; methoxyacrylate insecticides; neonicotinoid insecticides; nereistoxin analogue insecticides; organochlor
  • Exemplary alkaloid insecticides include anabasine, matrine, nicotine, nornicotine, oxymatrine, ryania, ryanodine, sabadilla, and sanguinarine.
  • Exemplary alkyl halide insecticides include carbon tetrachloride, chloroform, 1,2- dichloropropane, ethylene dibromide, ethylene dichloride, methyl bromide, methyl iodide, methylchloroform, methylene chloride, and tetrachloroethane.
  • An exemplary aminopyrimidine insecticide is dicyclanil.
  • An exemplary aminotriazene insecticide is cyromazine.
  • An exemplary antibiotic insecticide is allosamidin.
  • Exemplary aromatic hydrocarbon insecticides include naphthalene and triarathene.
  • An exemplary arylpyrrole insecticide is chlorfenapyr.
  • An exemplary benzimidazole insecticide is fenazaflor.
  • An exemplary beta-ketonitrile insecticide is thiapronil.
  • Exemplary dinitrophenol insecticides include dinex, dinoprop, dinosam, and 4-6-dinitro-o-cresol (DNOC).
  • An exemplary dithiolane insecticide is isoprothiolane.
  • Exemplary formamidine insecticides include amitraz, chlordimeform, medimeform, and semiamitraz.
  • Exemplary benzoylurea insecticides include bistrifluron, chlorbenzuron, chlorfluazuron, dichlorbenzuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, penfluron, teflubenzuron, and triflumuron.
  • Exemplary botanical insecticides include allicin, azadirachtin, carvacrol, d-limonene, quassia, rhodojaponin-III, rotenone, and triptolide.
  • Exemplary carbamate insecticides include alanycarb, aldicarb, aldoxycarb, allyxycarb, aminocarb, bendiocarb, benfuracarb, bufencarb, butacarb, butocarboxim, butoxycarboxim, carbanolate, carbaryl, carbofuran, carbosulfan, cloethocarb, 2-chlorophenyl methylcarbamate (CPMC), decarbofuran, dicresyl, dimetan, dimethacarb, dimetilan, dioxacarb, p-(ethylthio)phenyl methylcarbamate (EMPC), ethiofencarb, fenethacarb, fenobucarb, formetanate, formparanate, furathiocarb, hyquincarb, isolan, isoprocarb, methiocarb, methomyl, metolcarb, is
  • Exemplary diacylhydrazine insecticides include chromafenozide, furan tebufenozide, halofenozide, methoxyfenozide, tebufenozide, and yishijing.
  • Exemplary diamide insecticide include chlorantraniliprole, cyantraniliprole, cyhalodiamide, cyclaniliprole, flubendiamide, fluchlordiniliprole, tetrachlorantraniliprole, tetraniliprole, and tiorantraniliprole.
  • Exemplary fumigant insecticides include acrylonitrile, allyl isothiocyanate, calcium cyanide, carbon disulfide, carbon tetrachloride, carbonyl sulfide, chloroform, chloropicrin, cyanogen, 1,2-dichloropropane, dimethyl disulfide, ethyl formate, ethylene dibromide, ethylene dichloride, ethylene oxide, hydrogen cyanide, methyl bromide, methyl iodide, methyl isothiocyanate, methylchloroform, methylene chloride, phosphine, sodium cyanide, sulfuryl fluoride, and tetrachloroethane.
  • Exemplary inorganic insecticides include barium hexafluorosilicate, borax, boric acid, calcium arsenate, calcium polysulfide, copper arsenate, copper naphthenate, copper oleate, cryolite, diatomaceous earth, lead arsenate, mercurous chloride, Paris green, potassium arsenite, potassium thiocyanate, silica gel, sodium arsenite, sodium fluoride, sodium silicofluoride, sodium thiocyanate, and sulfuryl fluoride.
  • Exemplary isoxazoline insecticides include afoxolaner, esafoxolaner, fluralaner, fluxametamide, isocycloseram, lotilaner, mivorilaner, sarolaner, tigolaner, and umifoxolaner.
  • Exemplary juvenile hormone mimics include dayoutong, diofenolan, epofenonane, fenoxycarb, hydroprene, juvenile hormone I, juvenile hormone II, juvenile hormone III, kinoprene, Methoprene, pyriproxyfen, and triprene.
  • Exemplary macrocyclic lactone insecticides include abamectin, doramectin, emamectin, eprinomectin, ivermectin, lepimectin, moxidectin, selamectin, spinetoram, and spinosad.
  • Exemplary meta-diamide insecticides include broflanilide, cyproflanilide, and modoflaner.
  • An exemplary methoxyacrylate insecticide is flupyroxystrobin.
  • An exemplary oxadiazine insecticide is indoxacarb.
  • An exemplary oxadiazolone insecticide is metoxadiazone.
  • Exempalry perfluoroalkyl sulfonamide insecticides are flursulamid and sulfluramid.
  • Exemplary pyridine 22 BUSINESS.31669632.1 409753-016WO (210621) azomethine insecticides include pymetrozine and pyrifluquinazon.
  • Exemplary pyrimidinamine insecticides include flufenerim and pyrimidifen.
  • An exemplary pyropene insecticide is afidopyropen.
  • An RNA1 insecticide is ledprona.
  • An exemplary salicylanilide insecticide is closantel.
  • An exemplary semicarbazone insecticide is metaflumizone.
  • Exemplary steroid insecticides include ⁇ -ecdysone and ecdysterone.
  • Exemplary tetramic acid insecticides include spidoxamat, spiropidion, and spirotetramat.
  • Exemplary tetronic acid insecticides include spirodiclofen and spiromesifen.
  • Exemplary thiocarbonate insecticides include O,O-diethyl dithiobis(thioformate) (EXD) and sodium tetrathiocarbonate.
  • An exemplary thiourea insecticide includes diafenthiuron.
  • Exemplary urea insecticides include flucofuron and sulcofuron.
  • Exemplary neonicotinoid insecticides include acetamiprid, clothianidin, cycloxaprid, dicloromezotiaz, dinotefuran, fenmezoditiaz, flupyradifurone, flupyrimin, imidacloprid, imidaclothiz, nitenpyram, nithiazine, paichongding, sulfoxaflor, thiacloprid, thiamethoxam, and triflumezopyrim.
  • Exemplary nereistoxin analogue insecticides include bensultap, cartap, polythialan, thiocyclam, and thiosultap.
  • organochlorine insecticides include aldrin, alpha-endosulfan, bromociclen, p,p- dibromo-diphenyl-1,1,1-trichloroethane (bromo-DDT), camphechlor, chlorbicyclen, chlordane, chlordecone, dichlorodiphenyltrichloroethane (DDT), difluorodiphenyltrichloroethane (DFDT), dieldrin, dilor, endosulfan, endrin, 1,1-dichloro-2,2-bis(4-ethylphenyl)ethane (ethyl-DDD), hexachlorocyclohexane (HCH), heptachlor, isobenzan, isodrin, kelevan, lindane, methoxychlor, mirex, p-dichlorobenzene, and tetrachlorodiphenylethane (TDE).
  • aldrin al
  • organophosphorus insecticides include acephate, acethion, acetophos, amidithion, amiton, athidathion, azamethiphos, azinphos-ethyl, azinphos-methyl, azothoate, bromfenvinfos, bromophos, bromophos-ethyl, butathiofos, butonate, cadusafos, calvinphos, carbophenothion, chloramine phosphorus, chlorethoxyfos, chlorfenvinphos, chlormephos, chlorphoxim, chlorprazophos, chlorpyrifos, chlorpyrifos-methyl, chlorthiophos, colophonate, coumaphos, coumithoate, crotoxyphos, crufomate, cyanofenphos, cyanophos, cyanthoate, cythioate, demephion, demeton, de
  • Exemplary phenol insecticides include pentachlorophenol, precocenes, precocene I, precocene II, and precocene III.
  • Exemplary pyrazole insecticides include acetoprole, dimpropyridaz, ethiprole, fipronil, flufiprole, pyrafluprole, pyriprole, tolfenpyrad, and vaniliprole.
  • Exemplary pyrethrin/pyrethroid insecticides include acrinathrin, allethrin, alpha- cypermethrin, barthrin, beta-cyfluthrin, beta-cypermethrin, bifenthrin, bioallethrin, bioethanomethrin, biopermethrin, bioresmethrin, brofenvalerate, brofluthrinate, bromethrin, butethrin, chlorempenthrin, chloroprallethrin, cinerin, cismethrin, cyclethrin, cycloprothrin, cyfluthrin, cyhalothrin, cypermethrin, cyphenothrin, deltamethrin, d-fanshiluquebingjuzhi, dimefluthrin, dimethrin, d-teflumethrin, emp
  • Additional unclassified insecticides that can be used in combination with ascarosides include benzpyrimoxan, buprofezin, crotamiton, fenoxacrim, fentrifanil, flometoquin, flonicamid, fluhexafon, hydramethylnon, indazapyroxamet, jiahuangchongzong, ledprona, malonoben, maltodextrin, nicofluprole, nifluprole, nifluprole, oxazosulfyl, plifenate, pyridaben, pyridalyl, rafoxanide, sulfiflumin, tartar emetic, thuringiensin, triazamate, trichlophenidine, and tyclopyrazoflor.
  • insecticides and other insect regulators may be included in the methods and compositions of the invention.
  • additional active agents are known in the art that can be used with the combination described herein and include fungicides, herbicides, miticides, arthropodicides, bactericides, ectoparasiticides, and the like, that are compatible with the combination of the present invention and not antagonistic to the activity of the ascaroside(s) or the insecticide(s).
  • the common names are mentioned in the insecticides lists disclosed herein.
  • the common name identifies the active ingredient in its commercially available form or forms including derivatives such as salts and esters, even if a specific salt or ester is not mentioned specifically (preferably in its usual commercial form).
  • the application of the one or more insecticides and the one or more ascarosides can be in pre- or post-emergence application. The preferred application method depends on the usual or optimal application time of the particular insecticide or insecticide combination.
  • the anti-pathogen activity of ascarosides provides additional benefits to the methods and composition.
  • the ascaroside although applying the ascaroside at an early stage in the plant life cycle, it surprisingly exhibits a long-lasting effect, e.g., decreasing or preventing damage caused by fungi, bacteria, viruses and molds for a period of time exceeding 3 days after application, exceeding 5 days after application, exceeding one week after application, exceeding two weeks after application, exceeding one-month after application, exceeding two- months after application, or exceeding three-months after application.
  • the co-application of ascarosides and insecticides early in the season can also provide important economic advantages to growers and enhance the sustainability of crop production. Co- application of ascarosides with insecticide can prevent the need for a separate fungicide treatment later in the season.
  • the disclosure provides blends of one or more insecticides and one or more ascarosides. In certain embodiments, the disclosure provides blends of one or more insecticides and one or more ascarosides, characterized in that the blended product reduces the phytotoxic effects on the crops to which it is applied compared to application of the one or more insecticides alone. In certain embodiments, the blend is characterized in that one or more phytotoxicity symptoms in a treated crop is reduced by at least 10% relative to use of a comparable composition lacking ascaroside(s).
  • the blend is characterized in that one or more phytotoxicity symptoms in a treated crop is reduced by 10-90%, 10-70%, 10-50%, 10-30%, 30-90%, 50-90%, 70-90%, 30-70%, or 30-50% relative to use of a comparable composition lacking ascaroside(s).
  • phytotoxicity symptoms are measured by a phytotoxicity rating, e.g., as described by Example 1 herein.
  • the blend is characterized in that the phytotoxicity rating (e.g., as described in Example 1 herein) in a treated crop is reduced by at least 10% relative to use of a comparable composition lacking ascaroside(s).
  • phytotoxic effects that can be reduced by the use of ascarosides are selected from the group consisting of: poor germination; death of seedlings; death or damage to rapidly growing succulent tissues; stunting or delayed plant development; misshaped or distorted plants, fruits, or leaves; russeting or bronzing of leaves or fruit; dead spots or flecks on leaves; dead leaf tips or leaf margins; dead areas between the veins of the leaves; and combinations of any two or more of these.
  • the compounds described herein can be provided in a single formulation or agricultural composition or in separate formulations or agricultural compositions. Additionally, the components may be applied separately.
  • the one or more ascarosides and the one or more insecticides can be applied before or after the application of the one or more insecticides.
  • the components are co-applied at close points in time, e.g., substantially simultaneously or within about several minutes or hours, including within about 5 minutes, within about 10 minutes, within about 30 minutes, within about an hour, within about 2 hours, within about 3 hours, within about 4 hours, 27 BUSINESS.31669632.1 409753-016WO (210621) within about 6 hours, within about 7 hours, within about 8 hours, within about 24 hours, or within about 2 days of one another).
  • Co-application can, in some embodiments, involve combining the one or more ascarosides and the one or more insecticides before application (e.g., immediately prior to application) to the plants.
  • the one or more ascarosides and the one or more insecticides may be mixed in the field; for example, the one or more ascarosides can be added to a tank mix solution comprising the one or more insecticides.
  • the components to be co-applied can be combined at a timepoint further in advance of application.
  • an agricultural formulation is prepared comprising one or more ascarosides and the one or more insecticides in combination with one or more inert ingredients.
  • the one or more ascarosides and the one or more insecticides are compatible with one another, and the resulting formulations can demonstrate stability over long periods of time (e.g., about one week or more, about one month or more, about two months or more, about three months or more, about four months or more, about five months or more, or about six months or more).
  • the one or more ascarosides and the one or more insecticides can be formulated together in a combination formulation.
  • the formulations or methods can include other active ingredients and/or plant or plant product treatment compounds. Further, some of the compositions will be residual in that they do not easily wash off the leaves during rain, and thus can protect plants during and after rainy weather.
  • the disclosure provides blends of one or more insecticides and one or more ascarosides where a weight ratio of insecticide(s) to ascaroside is greater than 10:1, greater than 100:1, greater than 500:1 or greater than 1000:1.
  • the disclosure provides blends of an insecticide and an ascaroside where a weight ratio of an insecticide to ascaroside is greater than 1500:1, greater than 2000:1, greater than 3000:1, greater than 5000:1, greater than 7500:1, greater than 10,000:1, greater than 15,000:1, greater than 20,000:1, greater than 30,000:1, or greater than 50,000:1.
  • the formulations or compositions can be formulated as is conventional in the art and may be liquid or dry compositions.
  • Dry compositions include powders and the like.
  • the compositions can be utilized as liquid concentrates, Ready-To-Use (RTU) liquid sprays, dusts, or solids, 28 BUSINESS.31669632.1 409753-016WO (210621) depending upon the needs of the user.
  • the formulation chosen will depend on the use of the product. In use, the composition can be applied directly to the plant.
  • a formulation will include at least one ascaroside as described herein, or at least one ascaroside and one or more insecticides, and one or more agriculturally acceptable adjuvants (also referred to herein as “agriculturally suitable adjuvants”).
  • Agriculturally suitable adjuvants are used to enhance the effectiveness of the compounds described herein and include, but are not limited to, surfactants, emulsifiers, oils, salts, and the like.
  • the adjuvants may be added into the formulation or alternatively can be added separately at the time of application to the crops.
  • wetting agents, emulsifiers, spreaders, and the like may be used in the formulations.
  • Formulations include concentrated versions, in which the present active agent (a compound as described herein) is present in a concentration of from 0.001 to 98.0 percent, with the remaining content being physiologically acceptable carriers.
  • formulations especially those with less than 50 percent of the present compound, can sometimes be used directly, but these formulations can also be diluted with other physiologically acceptable carriers to form more dilute treating formulations. These latter formulations can include the compounds described herein in lesser concentrations of from 0.001 to 0.1 percent.
  • the formulations may additionally contain “adjuvant surfactants” to enhance deposition, wetting, and penetration of the compounds onto the target crop and organism. These “adjuvant surfactants” may optionally be employed as a component of the formulation or as a tank mix.
  • the amount of adjuvant surfactant will typically vary from 0.01 to 1.0 percent by volume, based on a spray-volume of water, preferably 0.05 to 0.5 volume percent.
  • Suitable adjuvant surfactants include, but are not limited to ethoxylated nonyl phenols, ethoxylated synthetic or natural alcohols, salts of the esters or sulfosuccinic acids, ethoxylated organosilicones, ethoxylated fatty amines, blends of surfactants with mineral or vegetable oils, crop oil concentrate (mineral oil (85%) + emulsifiers (15%)); nonylphenol ethoxylate; benzylcocoalkyldimethyl quaternary ammonium salt; blend of petroleum hydrocarbon, alkyl esters, organic acid, and anionic surfactant; C9- Cu alkylpolyglycoside; phosphated alcohol ethoxylate; natural primary alcohol (C12- Ci6) ethoxylate; di -sec-butylphenol EO-PO block copolymer; polysiloxane-methyl cap; nonylphenol ethoxylate + urea ammonium
  • the formulations may also include oil-in-water emulsions.
  • “Surfactants” comprise typically about 0.5% to about 10% of the wettable powder. “Surfactants” include sulfonated lignins, condensed naphthalene-sulfonates, the naphthalene- sulfonates, alkyl-benenesulfonates, alkysulfonates or nonionic surfactants such as ethylene oxide adducts of alkylphenols or mixtures thereof.
  • organic solvents which may be employed in preparing the emulsifiable concentrates of the disclosed ascaroside(s) and/or insecticide(s) are the aromatic liquids such as xylene, propyl benzene fractions; or mixed naphthalene fractions, mineral oils, substituted aromatic organic liquids such as dioctyl phthalate; kerosene; dialkyl amides of various fatty acids, particularly the dimethyl amides of fatty glycols and glycol derivatives such as the n-butyl ether, ethyl ether or methyl ether of diethylene glycol, the methyl ether of triethylene glycol, petroleum fractions or hydrocarbons such as mineral oil, aromatic solvents, paraffinic oils, and the like; terpenic solvents, rosin derivatives, aliphatic ketones such as cyclohexanone, complex aliphatic and aromatic alcohols such as 2-ethoxyethanol, vegetable oils such as soy bean oil,
  • Organic liquids include xylene, and propyl benzene fractions, with xylene being most preferred in some cases.
  • Surface-active dispersing agents are typically employed in liquid formulations and in an amount of from 0.1 to 20 percent by weight based on the combined weight of the dispersing agent with one or more of the compounds.
  • “Emulsifiers” for emulsifiable concentrates are typically mixed ionic and/or nonionic surfactants such as those mentioned herein or their equivalents.
  • nonionic emulsifiers useful in preparing the emulsifiable concentrates include the polyalkylene glycol ethers and condensation products of alkyl and aryl phenols, aliphatic alcohols, aliphatic amines or fatty acids with ethylene oxide, propylene oxides such as the ethoxylated alkyl phenols and carboxylic esters solubilized with the polyol or polyoxyalkylene.
  • Cationic emulsifiers include quaternary ammonium compounds and fatty amine salts.
  • Anionic emulsifiers include the oil soluble salts (e.g., 30 BUSINESS.31669632.1 409753-016WO (210621) calcium) of alkylaryl sulphonic acids, oil-soluble salts or sulfated polyglycol ethers and appropriate salts of phosphated- polyglycol ether.
  • Dusts containing the ascaroside(s) and/or insecticide(s) may be prepared by intimately mixing one or more of the compounds in powdered form with a suitable dusty agricultural carrier, such as, for example, kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1 to about 10 weight percent of the compounds, based on the total weight of the dust.
  • Wettable powders may be agglomerated or compacted to form water dispersible granules.
  • These granules include mixtures of compounds, inert carriers suitable for granular applications, and surfactants.
  • concentration of the compound is typically between about 0.1% to about 90% by weight.
  • the “inert carrier suitable for granular applications” is typically prophyllite, talc, chalk, gypsum, Fuller's earth, bentonite, attapulgite, starch, casein, gluten, montmorillonite clays, diatomaceous earths, purified silicates, or the like.
  • the finely divided carrier and surfactants are typically blended with the compound(s) and milled.
  • Aqueous suspensions may be prepared where the one or more ascarosides and/or one or more insecticides are dispersed in an aqueous vehicle at a concentration typically in the range of between about 5% to about 50% by weight.
  • the suspensions are prepared by finely grinding the compound and vigorously mixing it into a vehicle of water, surfactants, and dispersants.
  • Inert ingredients such as inorganic salts and synthetic or natural gums may also be employed to increase the density and/or viscosity of the aqueous vehicle as is desired.
  • the compositions and methods of the invention are useful for lessening the phytotoxic effects of the insecticide on the treated crop.
  • the method comprises applying a combination of an effective amount of an ascaroside composition and an insecticide composition to a seed, a plant, plant foliage, or to the soil where the plant is grown.
  • the term “a” may be understood to mean “at least one.” 31 BUSINESS.31669632.1 409753-016WO (210621) [0110] As used in this application, the term “or” may be understood to mean “and/or.” In this application, the terms “comprising” and “including” may be understood to encompass itemized components or steps whether presented by themselves or together with one or more additional components or steps. As used in this application, the term “comprise” and variations of the term, such as “comprising” and “comprises,” are not intended to exclude other additives, components, integers, or steps. [0111] About, Approximately: As used herein, the terms “about” and “approximately” are used as equivalents.
  • the term “approximately” or “about” refers to a range of values that fall within 25 %, 20 %, 19 %, 18 %, 17 %, 16 %, 15 %, 14 %, 13 %, 12 %, 11 %, 10 %, 9 %, 8 %, 7 %, 6 %, 5 %, 4 %, 3 %, 2 %, 1 %, or less in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context (except where such number would exceed 100 % of a possible value).
  • Certain compounds provided herein can comprise one or more asymmetric centers, and thus can exist in various stereoisomeric forms, e.g., enantiomers and/or diastereomers.
  • inventive compounds and compositions thereof may be in the form of an individual enantiomer, 32 BUSINESS.31669632.1 409753-016WO (210621) diastereomer or geometric isomer, or may be in the form of a mixture of stereoisomers.
  • compounds described herein are enantiopure compounds.
  • mixtures of enantiomers or diastereomers are provided.
  • certain compounds as described herein may have one or more double bonds that can exist as either a Z or E isomer, unless otherwise indicated.
  • the compounds can be provided as individual isomers substantially free of other isomers and alternatively, as mixtures of various isomers, e.g., racemic mixtures of enantiomers.
  • isomers includes any and all geometric isomers and stereoisomers.
  • isomers include cis– and trans–isomers, E– and Z– isomers, R– and S–enantiomers, diastereomers, (D)–isomers, (L)–isomers, racemic mixtures thereof, and other mixtures thereof, as falling within the scope of the disclosure.
  • a compound may, in some embodiments, be provided substantially free of one or more corresponding stereoisomers, and may also be referred to as “stereochemically enriched.”
  • stereochemically enriched a particular enantiomer is preferred, it may, in some embodiments be provided substantially free of the opposite enantiomer, and may also be referred to as “optically enriched.”
  • Optically enriched means that the compound is made up of a significantly greater proportion of one enantiomer. In certain embodiments the compound is made up of at least about 90% by weight of an enantiomer.
  • the compound is made up of at least about 95%, 97%, 98%, 99%, 99.5%, 99.7%, 99.8%, or 99.9% by weight of an enantiomer.
  • the enantiomeric excess of provided compounds is at least about 90%, 95%, 97%, 98%, 99%, 99.5%, 99.7%, 99.8%, or 99.9%.
  • enantiomers may be isolated from racemic mixtures by any method known to those skilled in the art, including chiral high pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts or prepared by asymmetric syntheses.
  • halo and “halogen” as used herein refer to an atom selected from fluorine (fluoro, –F), chlorine (chloro, –Cl), bromine (bromo, –Br), and iodine (iodo, –I).
  • aliphatic or “aliphatic group”, as used herein, denotes a hydrocarbon moiety that may be straight–chain (i.e., unbranched), branched, or cyclic (including fused, bridging, and spiro–fused polycyclic) and may be completely saturated or may contain one or more units of unsaturation, but which is not aromatic. Unless otherwise specified, aliphatic groups contain 1– 30 carbon atoms. In certain embodiments, aliphatic groups contain 1–12 carbon atoms. In certain embodiments, aliphatic groups contain 1–8 carbon atoms.
  • aliphatic groups contain 1–6 carbon atoms. In some embodiments, aliphatic groups contain 1–5 carbon atoms, in some embodiments, aliphatic groups contain 1–4 carbon atoms, in yet other embodiments aliphatic groups contain 1–3 carbon atoms, and in yet other embodiments aliphatic groups contain 1–2 carbon atoms.
  • Suitable aliphatic groups include, but are not limited to, linear or branched, alkyl, alkenyl, and alkynyl groups, and hybrids thereof such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl.
  • heteroaliphatic or “heteroaliphatic group”, as used herein, denotes an aliphatic group where one or more carbon or hydrogen atoms are replaced by a heteroatom (e.g. oxygen, nitrogen, sulfur, phosphorous, boron, etc.). In some embodiments, a heteroaliphatic group is a heterocyclyl group.
  • unsaturated as used herein, means that a moiety has one or more double or triple bonds.
  • alkyl refers to saturated, straight– or branched–chain hydrocarbon radicals derived from an aliphatic moiety containing between one and six carbon atoms by removal of a single hydrogen atom. Unless otherwise specified, alkyl groups contain 1– 12 carbon atoms. In certain embodiments, alkyl groups contain 1–8 carbon atoms. In certain embodiments, alkyl groups contain 1–6 carbon atoms. In some embodiments, alkyl groups contain 1–5 carbon atoms, in some embodiments, alkyl groups contain 1–4 carbon atoms, in yet other embodiments alkyl groups contain 1–3 carbon atoms, and in yet other embodiments alkyl groups contain 1–2 carbon atoms.
  • alkyl radicals include, but are not limited to, methyl, ethyl, n–propyl, isopropyl, n–butyl, iso–butyl, sec–butyl, sec–pentyl, iso–pentyl, tert–butyl, n–pentyl, neopentyl, n–hexyl, sec–hexyl, n–heptyl, n–octyl, n–decyl, n–undecyl, dodecyl, and the like.
  • alkenyl denotes a monovalent group derived from a straight– or branched–chain aliphatic moiety having at least one carbon–carbon double bond by the removal 34 BUSINESS.31669632.1 409753-016WO (210621) of a single hydrogen atom. Unless otherwise specified, alkenyl groups contain 2–12 carbon atoms. In certain embodiments, alkenyl groups contain 2–8 carbon atoms. In certain embodiments, alkenyl groups contain 2–6 carbon atoms.
  • alkenyl groups contain 2–5 carbon atoms, in some embodiments, alkenyl groups contain 2–4 carbon atoms, in yet other embodiments alkenyl groups contain 2–3 carbon atoms, and in yet other embodiments alkenyl groups contain 2 carbon atoms.
  • Alkenyl groups include, for example, ethenyl, propenyl, butenyl, 1–methyl–2–buten–1–yl, and the like.
  • aryl used alone or as part of a larger moiety as in “aralkyl”, “aralkoxy”, or “aryloxyalkyl”, refers to monocyclic and polycyclic ring systems having a total of five to 20 ring members, wherein at least one ring in the system is aromatic and wherein each ring in the system contains three to twelve ring members.
  • aryl may be used interchangeably with the term “aryl ring”.
  • aryl refers to an aromatic ring system which includes, but is not limited to, phenyl, biphenyl, naphthyl, anthracyl and the like, which may bear one or more substituents.
  • heteroaryl and “heteroar—,” used alone or as part of a larger moiety, e.g., “heteroaralkyl,” or “heteroaralkoxy,” refer to groups having 5 to 10 ring atoms, preferably 5, 6, or 9 ring atoms; having 6, 10, or 14 pelectrons shared in a cyclic array; and having, in addition to carbon atoms, from one to five heteroatoms.
  • heteroatom refers to nitrogen, oxygen, or sulfur, and includes any oxidized form of nitrogen or sulfur, and any quaternized form of a basic nitrogen.
  • Heteroaryl groups include, without limitation, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl, purinyl, naphthyridinyl, and pteridinyl.
  • heteroaryl and “heteroar—”, as used herein, also include groups in which a heteroaromatic ring is fused to one or more aryl, cycloaliphatic, or heterocyclyl rings, where the radical or point of attachment is on the heteroaromatic ring.
  • Nonlimiting examples include indolyl, isoindolyl, benzothienyl, benzofuranyl, dibenzofuranyl, indazolyl, benzimidazolyl, benzthiazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 4H–quinolizinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, tetrahydroquinolinyl, 35 BUSINESS.31669632.1 409753-016WO (210621) tetrahydroisoquinolinyl, and pyrido[2,3–b]–1,4–oxazin–3(4H)–one.
  • a heteroaryl group may be monocyclic, bicyclic, bridged bicyclic, or spirocyclic.
  • heteroaryl may be used interchangeably with the terms “heteroaryl ring,” “heteroaryl group,” or “heteroaromatic,” any of which terms include rings that are optionally substituted.
  • heteroarylkyl refers to an alkyl group substituted by a heteroaryl, wherein the alkyl and heteroaryl portions independently are optionally substituted.
  • heteroarylenyl refers to bivalent heteroaryl groups (e.g., pyridylenyl).
  • heterocycle As used herein, the terms “heterocycle,” “heterocyclyl,” “heterocyclic radical,” and “heterocyclic ring” are used interchangeably and refer to a stable 5– to 7–membered monocyclic or 7–10–membered bicyclic heterocyclic moiety that is either saturated or partially unsaturated, and having, in addition to carbon atoms, one or more, preferably one to four, heteroatoms, as defined above.
  • nitrogen includes a substituted nitrogen.
  • the nitrogen may be N (as in 3,4–dihydro– 2H–pyrrolyl), NH (as in pyrrolidinyl), or +NR (as in N–substituted pyrrolidinyl).
  • a heterocyclic ring can be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure and any of the ring atoms can be optionally substituted.
  • saturated or partially unsaturated heterocyclic radicals include, without limitation, tetrahydrofuranyl, tetrahydrothiophenyl pyrrolidinyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, and quinuclidinyl.
  • heterocycle used interchangeably herein, and also include groups in which a heterocyclyl ring is fused to one or more aryl, heteroaryl, or cycloaliphatic rings, such as indolinyl, 3H–indolyl, chromanyl, phenanthridinyl, or tetrahydroquinolinyl.
  • a heterocyclic ring may be a 5-12 membered bicyclic, bridged bicyclic, or spirocyclic ring.
  • heterocyclylalkyl refers to an alkyl group substituted by a heterocyclyl, wherein the alkyl and heterocyclyl portions independently are optionally substituted.
  • the term “partially unsaturated” refers to a ring moiety that includes at least one double or triple bond.
  • the term “partially unsaturated” is intended to encompass rings having multiple sites of unsaturation, but is not intended to include aryl or heteroaryl moieties, as herein defined.
  • compounds as provided herein may contain “optionally substituted” moieties.
  • substituted whether preceded by the term “optionally” or not, means that one or more hydrogens of the designated moiety are replaced with a suitable substituent.
  • an “optionally substituted” group may have a suitable substituent at each substitutable position of the group, and when more than one position in any given structure may be substituted with more than one substituent selected from a specified group, the substituent may be either the same or different at every position. Combinations of substituents envisioned are preferably those that result in the formation of stable or chemically feasible compounds.
  • Suitable monovalent substituents of R ⁇ together with their intervening atoms), are independently halogen, —(CH2)0–2R ⁇ , –(haloR ⁇ ), –(CH2)0–2OH, –(CH2)0–2OR ⁇ , –(CH2)0– 2 CH(OR ⁇ ) 2 ; -O(haloR ⁇ ), –CN, –N 3 , –(CH 2 ) 0–2 C(O)R ⁇ , –(CH 2 ) 0–2 C(O)OH, –(CH 2 ) 0– 2 C(O)OR ⁇ , -(CH 2 ) 0-4 C(O)N(R ⁇ ) 2 ; –(CH 2 ) 0–2 SR ⁇ , –(CH 2 ) 0–2 SH, –(CH 2 ) 0–2 NH 2 , –(CH 2 ) 0– 2 NHR
  • Suitable divalent substituents that are bound to vicinal substitutable carbons of an “optionally substituted” group include: –O(CR * 2)2– 3O–, wherein each independent occurrence of R * is selected from hydrogen, C1–6 aliphatic which may be substituted as defined below, or an unsubstituted 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
  • Suitable substituents on the aliphatic group of R * include halogen, –R ⁇ , -(haloR ⁇ ), –OH, – OR ⁇ , –O(haloR ⁇ ), –CN, –C(O)OH, –C(O)OR ⁇ , –NH 2 , –NHR ⁇ , –NR ⁇ 2 , or –NO 2 , wherein each R ⁇ is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is 38 BUSINESS.31669632.1 409753-016WO (210621) independently C 1–4 aliphatic, –CH 2 Ph, –O(CH 2 ) 0–1 Ph, or a 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
  • Suitable substituents on a substitutable nitrogen of an “optionally substituted” group include –R ⁇ , –NR ⁇ 2, –C(O)R ⁇ , –C(O)OR ⁇ , –C(O)C(O)R ⁇ , –C(O)CH2C(O)R ⁇ , – S(O)2R ⁇ , wherein each R ⁇ is below, unsubstituted –OPh, or an or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of R ⁇ , taken together with their intervening atom(s) form an unsubstituted 3–12–membered saturated, partially unsaturated, or aryl mono– or bicyclic ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
  • Suitable substituents on the aliphatic group of R ⁇ are independently halogen, –R ⁇ , – (haloR ⁇ ), –OH, –OR ⁇ , –O(haloR ⁇ ), –CN, –C(O)OH, –C(O)OR ⁇ , –NH 2 , –NHR ⁇ , –NR ⁇ 2 , or -NO 2 , wherein each R ⁇ is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently C1–4 aliphatic, –CH2Ph, –O(CH2)0–1Ph, or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
  • the term “substantially” refers to the qualitative condition of exhibiting total or near-total extent or degree of a characteristic or property of interest.
  • the convention of naming ascarosides by a several-letter prefix followed by a pound sign (#) and a number is sometimes used (for example ascr#18). This convention is used in the scientific literature and the skilled artisan will understand that each such name is associated with a specific chemical structure of known composition and will readily apprehend the structure of the molecule referred to using this naming convention. Unless otherwise indicated, all compound identifiers of this format used herein conform to the definitions described in the C.
  • Embodiments of the invention include: 39 BUSINESS.31669632.1 409753-016WO (210621) 1.
  • a method for reducing phytotoxic side effects on plants associated with application of an insecticide comprising contacting a plant or a plant part with an effective amount of a combination of agents, said agents comprising at least one ascaroside and at least one insecticide, wherein said effective amount reduces phytotoxic side effects on crop plants as compared to phytotoxic side effects on plants associated with application of the insecticide alone. 2.
  • said at least one insecticide is an alkaloid insecticide, an alkyl halide insecticide, an aminopyrimidine insecticide, an aminotriazene insecticide, an antibiotic insecticide, an aromatic hydrocarbon insecticide, an arylpyrrole insecticide, a benzimidazole insecticide, a benzoylurea insecticide, a beta-ketonitrile insecticide, a botanical insecticide, a carbamate insecticide, a diacylhydrazine insecticide, a diamide insecticide, a dinitrophenol insecticide, a dithiolane insecticide, a formamidine insecticide, a fumigant insecticide, an inorganic insecticide, an isoxazoline insecticide, a juvenile hormone mimic, a macrocyclic lactone insecticide, a meta-diamide insecticide, a methoxyacrylate insecticide, a neonicotinoid insecticide, a nereistoxin analogue insecticide, a organochlorine insecticide,
  • said at least one insecticide is an alkaloid insecticide selected from the group consisting of anabasine, matrine, nicotine, nornicotine, oxymatrine, ryania, ryanodine, sabadilla, and sanguinarine.
  • said at least one insecticide is an alkyl halide insecticide selected from the group consisting of carbon tetrachloride, chloroform, 1,2- dichloropropane, ethylene dibromide, ethylene dichloride, methyl bromide, methyl iodide, methylchloroform, methylene chloride, and tetrachloroethane. 5.
  • said at least one insecticide is dicyclanil, cyromazine, allosamidin, naphthalene, triarathene, chlorfenapyr, fenazaflor, thiapronil, dinex, 40 BUSINESS.31669632.1 409753-016WO (210621) dinoprop, dinosam, 4-6-dinitro-o-cresol (DNOC), isoprothiolane, amitraz, chlordimeform, medimeform, or semiamitraz. 6.
  • said at least one insecticide is a benzoylurea insecticide selected from the group consisting of bistrifluron, chlorbenzuron, chlorfluazuron, dichlorbenzuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, penfluron, teflubenzuron, and triflumuron. 7.
  • said at least one insecticide is a botanical insecticide selected from the allicin, azadirachtin, carvacrol, d-limonene, quassia, rhodojaponin-III, rotenone, and triptolide.
  • said at least one insecticide is a carbamate insecticide selected from the group consisting of alanycarb, aldicarb, aldoxycarb, allyxycarb, aminocarb, bendiocarb, benfuracarb, bufencarb, butacarb, butocarboxim, butoxycarboxim, carbanolate, carbaryl, carbofuran, carbosulfan, cloethocarb, 2-chlorophenyl methylcarbamate (CPMC), decarbofuran, dicresyl, dimetan, dimethacarb, dimetilan, dioxacarb, p-(ethylthio)phenyl methylcarbamate (EMPC), ethiofencarb, fenethacarb, fenobucarb, formetanate, formparanate, furathiocarb, hyquincarb, isolan, isoprocarb,
  • said at least one insecticide is a diamide insecticide selected from the group consisting of chlorantraniliprole, cyantraniliprole, cyhalodiamide, cyclaniliprole, flubendiamide, fluchlordiniliprole, tetrachlorantraniliprole, tetraniliprole, and tiorantraniliprole. 10.
  • said at least one insecticide is a fumigant insecticide selected from the group consisting of acrylonitrile, allyl isothiocyanate, calcium cyanide, carbon disulfide, carbon tetrachloride, carbonyl sulfide, chloroform, chloropicrin, cyanogen, 1,2- dichloropropane, dimethyl disulfide, ethyl formate, ethylene dibromide, ethylene dichloride, ethylene oxide, hydrogen cyanide, methyl bromide, methyl iodide, methyl isothiocyanate, methylchloroform, methylene chloride, phosphine, sodium cyanide, sulfuryl fluoride, and tetrachloroethane.
  • a fumigant insecticide selected from the group consisting of acrylonitrile, allyl isothiocyanate, calcium cyanide, carbon disulfide, carbon tetrachloride, carbonyl sulfide, chloro
  • said at least one insecticide is an inorganic insecticide selected from the group consisting of barium hexafluorosilicate, borax, boric acid, calcium arsenate, calcium polysulfide, copper arsenate, copper naphthenate, copper oleate, cryolite, diatomaceous earth, lead arsenate, mercurous chloride, Paris green, potassium arsenite, potassium thiocyanate, silica gel, sodium arsenite, sodium fluoride, sodium silicofluoride, sodium thiocyanate, and sulfuryl fluoride. 12.
  • said at least one insecticide is an isoxazoline insecticide selected from the group consisting of afoxolaner, esafoxolaner, fluralaner, fluxametamide, isocycloseram, lotilaner, mivorilaner, sarolaner, tigolaner, and umifoxolaner.
  • said at least one insecticide is a juvenile hormone mimic selected from the group consisting of dayoutong, diofenolan, epofenonane, fenoxycarb, hydroprene, juvenile hormone I, juvenile hormone II, juvenile hormone III, kinoprene, Methoprene, pyriproxyfen, and triprene.
  • said at least one insecticide is a macrocyclic lactone insecticide selected from the group consisting of abamectin, doramectin, emamectin, eprinomectin, ivermectin, lepimectin, moxidectin, selamectin, spinetoram, and spinosad. 15.
  • said at least one insecticide is broflanilide, cyproflanilide, modoflaner, flupyroxystrobin, indoxacarb, metoxadiazone, flursulamid, sulfluramid, pymetrozine, pyrifluquinazon, flufenerim, pyrimidifen, ledprona, closantel, metaflumizone, ⁇ -ecdysone, ecdysterone, spidoxamat, spiropidion, spirotetramat, spirodiclofen, spiromesifen, O,O-diethyl dithiobisthioformate (EXD), sodium tetrathiocarbonate, diafenthiuron, flucofuron and sulcofuron.
  • said at least one insecticide is broflanilide, cyproflanilide, modoflaner, flupyroxystrobin, indoxacarb, metoxadiazone
  • said at least one insecticide is a neonicotinoid insecticide selected from the group consisting of acetamiprid, clothianidin, cycloxaprid, dicloromezotiaz, dinotefuran, fenmezoditiaz, flupyradifurone, flupyrimin, imidacloprid, imidaclothiz, nitenpyram, nithiazine, paichongding, sulfoxaflor, thiacloprid, thiamethoxam, and triflumezopyrim. 42 BUSINESS.31669632.1 409753-016WO (210621) 17.
  • said at least one insecticide is a nereistoxin analogue insecticide selected from the group consisting of bensultap, cartap, polythialan, thiocyclam, and thiosultap. 18.
  • said at least one insecticide is an organochlorine insecticide selected from the group consisting of aldrin, alpha-endosulfan, bromociclen, p,p- dibromo-diphenyl-1,1,1-trichloroethane (bromo-DDT), camphechlor, chlorbicyclen, chlordane, chlordecone, dichlorodiphenyltrichloroethane (DDT), difluorodiphenyltrichloroethane (DFDT), dieldrin, dilor, endosulfan, endrin, 1,1-dichloro-2,2-bis(4-ethylphenyl)ethane (ethyl-DDD), he
  • said at least one insecticide is an organophosphorus insecticide selected from the group consisting of acephate, acethion, acetophos, amidithion, amiton, athidathion, azamethiphos, azinphos-ethyl, azinphos-methyl, azothoate, bromfenvinfos, bromophos, bromophos-ethyl, butathiofos, butonate, cadusafos, calvinphos, carbophenothion, chloramine phosphorus, chlorethoxyfos, chlorfenvinphos, chlormephos, chlorphoxim, chlorprazophos, chlorpyrifos, chlorpyrifos-methyl, chlorthiophos, colophonate, coumaphos, coumithoate, crotoxyphos, crufomate, cyanofenphos, cyanophos, cyanthoate, c
  • said at least one insecticide is a phenol insecticide selected from the group consisting of pentachlorophenol, precocenes, precocene I, precocene II, and precocene III.
  • said at least one insecticide is a pyrazole insecticide selected from the group consisting of acetoprole, dimpropyridaz, ethiprole, fipronil, flufiprole, pyrafluprole, pyriprole, tolfenpyrad, and vaniliprole. 22.
  • said at least one insecticide is a pyrethrin/pyrethroid insecticide selected from the group consisting of acrinathrin, allethrin, alpha-cypermethrin, barthrin, beta-cyfluthrin, beta-cypermethrin, bifenthrin, bioallethrin, bioethanomethrin, biopermethrin, bioresmethrin, brofenvalerate, brofluthrinate, bromethrin, butethrin, chlorempenthrin, chloroprallethrin, cinerin, cismethrin, cyclethrin, cycloprothrin, cyfluthrin, cyhalothrin, cypermethrin, cyphenothrin, deltamethrin, d-fanshiluquebingjuzhi, dimefluthrin, dimethr
  • said at least one ascaroside comprises an ascaroside having the structure (I): OZ where: Z is an optionally substituted C3-40 aliphatic group, and each of R a and R b is independently -H, or an optionally substituted moiety selected from the group consisting of: C 1-20 aliphatic, C 1-20 acyl, C 1-20 heteroaliphatic, aryl, heteroaryl, a hydroxyl protecting group, a phosphorous-linked functional group , a sulfur-linked functional group, a silicon-linked functional group, a C2-20 carbonate (e.g.
  • a C2-20 carbamate e.g. -a moiety -C(O)N(R c ) 2
  • a C 2-20 thioester e.g. a moiety -C(S)R c
  • a C 2-20 thiocarbonate e.g. a moiety -C(S)OR c
  • a C2-20 dithiocarbonate e.g. a moiety -C(S)SR c
  • a C1-20 thiocarbamate e.g.
  • a moiety -C(S)N(R c )2) a sugar moiety, a peptide, a polymer chain, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule.
  • R c is independently at each occurrence selected from -H, optionally substituted C 1-12 aliphatic, optionally substituted C1-12 heteroaliphatic, optionally substituted aryl, optionally substituted heteroaryl, a polymer chain, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule, and where R a and R b may be taken together to form an optionally substituted ring, optionally containing one or more heteroatoms, and optionally containing one or more sites of unsaturation.
  • Z is selected from the group consisting of: i. –CH(CH3)–R 1 , where R 1 is an optionally substituted C1-40 aliphatic group ii.
  • n is an integer from 1 to 40, and R 2 is -H, a metal cation, an optionally substituted C 1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; 45 BUSINESS.31669632.1 409753-016WO (210621) iii.
  • n is an integer from 1 to 40, and R 2 is - H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; iv.
  • n is an integer from 1 to 40, and R 2 is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; v.
  • n is an integer from 1 to 40, and R 2 is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; vi. –(CH 2 ) n –CO 2 R 2 , where n is an integer from 1 to 40, and R 2 is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; vii.
  • n is an integer from 1 to 40, and R 2 is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; viii.
  • n is an integer from 1 to 40, and R 2 is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; and ix.
  • n is an integer from 1 to 40, and R 2 is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide.
  • any one of embodiments 1-28 wherein said at least one ascaroside comprises an ascaroside selected from the group consisting of ascr#9, ascr#10, ascr#16, ascr#18, ascr#20, ascr#22, and ascr#24.
  • 30 The method of any one of embodiments 1-29, wherein said at least one ascaroside comprises ascr#18.
  • 31. The method of any one of embodiments 1-30, wherein said at least one ascaroside and said at least one insecticide are applied simultaneously.
  • composition of embodiment 35 wherein said at least one insecticide is an alkaloid insecticide, an alkyl halide insecticide, an aminopyrimidine insecticide, an aminotriazene insecticide, an antibiotic insecticide, an aromatic hydrocarbon insecticide, an arylpyrrole insecticide, a benzimidazole insecticide, a benzoylurea insecticide, a beta-ketonitrile insecticide, a botanical insecticide, a carbamate insecticide, a diacylhydrazine insecticide, a diamide insecticide, a dinitrophenol insecticide, a dithiolane insecticide, a formamidine insecticide, a fumigant insecticide, an inorganic insecticide, an isoxazoline insecticide, a juvenile hormone mimic, a macrocyclic lactone insecticide, a meta-diamide insecticide, a methoxyacrylate insecticide, a neonicotinoid insecticide, a nereistoxin analogue insecticide, a organochlorine insecticide
  • composition of embodiment 35 wherein said at least one insecticide is an alkaloid insecticide selected from the group consisting of anabasine, matrine, nicotine, nornicotine, oxymatrine, ryania, ryanodine, sabadilla, and sanguinarine.
  • said at least one insecticide is an alkyl halide insecticide selected from the group consisting of carbon tetrachloride, chloroform, 1,2- dichloropropane, ethylene dibromide, ethylene dichloride, methyl bromide, methyl iodide, methylchloroform, methylene chloride, and tetrachloroethane. 40.
  • composition of embodiment 35 wherein said at least one insecticide is dicyclanil, cyromazine, allosamidin, naphthalene, triarathene, chlorfenapyr, fenazaflor, thiapronil, dinex, 49 BUSINESS.31669632.1 409753-016WO (210621) dinoprop, dinosam, 4-6-dinitro-o-cresol (DNOC), isoprothiolane, amitraz, chlordimeform, medimeform, or semiamitraz. 41.
  • composition of embodiment 35 wherein said at least one insecticide is a benzoylurea insecticide selected from the group consisting of bistrifluron, chlorbenzuron, chlorfluazuron, dichlorbenzuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, penfluron, teflubenzuron, and triflumuron. 42.
  • a benzoylurea insecticide selected from the group consisting of bistrifluron, chlorbenzuron, chlorfluazuron, dichlorbenzuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, penfluron, teflubenzuron, and triflumuron.
  • composition of embodiment 35 wherein said at least one insecticide is a botanical insecticide selected from the allicin, azadirachtin, carvacrol, d-limonene, quassia, rhodojaponin- III, rotenone, and triptolide. 43.
  • composition of embodiment 35 wherein said at least one insecticide is a carbamate insecticide selected from the group consisting of alanycarb, aldicarb, aldoxycarb, allyxycarb, aminocarb, bendiocarb, benfuracarb, bufencarb, butacarb, butocarboxim, butoxycarboxim, carbanolate, carbaryl, carbofuran, carbosulfan, cloethocarb, 2-chlorophenyl methylcarbamate (CPMC), decarbofuran, dicresyl, dimetan, dimethacarb, dimetilan, dioxacarb, p-(ethylthio)phenyl methylcarbamate (EMPC), ethiofencarb, fenethacarb, fenobucarb, formetanate, formparanate, furathiocarb, hyquincarb, isolan, isoprocarb
  • composition of embodiment 35, wherein said at least one insecticide is a diamide insecticide selected from the group consisting of chlorantraniliprole, cyantraniliprole, cyhalodiamide, cyclaniliprole, flubendiamide, fluchlordiniliprole, tetrachlorantraniliprole, tetraniliprole, and tiorantraniliprole. 45.
  • composition of embodiment 35 wherein said at least one insecticide is a fumigant insecticide selected from the group consisting of acrylonitrile, allyl isothiocyanate, calcium cyanide, carbon disulfide, carbon tetrachloride, carbonyl sulfide, chloroform, chloropicrin, cyanogen, 1,2-dichloropropane, dimethyl disulfide, ethyl formate, ethylene dibromide, ethylene dichloride, ethylene oxide, hydrogen cyanide, methyl bromide, methyl iodide, methyl isothiocyanate, methylchloroform, methylene chloride, phosphine, sodium cyanide, sulfuryl fluoride, and tetrachloroethane.
  • a fumigant insecticide selected from the group consisting of acrylonitrile, allyl isothiocyanate, calcium cyanide, carbon disulfide, carbon tetrachloride, carbonyl
  • composition of embodiment 35 wherein said at least one insecticide is an inorganic insecticide selected from the group consisting of barium hexafluorosilicate, borax, boric acid, calcium arsenate, calcium polysulfide, copper arsenate, copper naphthenate, copper oleate, cryolite, diatomaceous earth, lead arsenate, mercurous chloride, Paris green, potassium arsenite, potassium thiocyanate, silica gel, sodium arsenite, sodium fluoride, sodium silicofluoride, sodium thiocyanate, and sulfuryl fluoride. 47.
  • inorganic insecticide selected from the group consisting of barium hexafluorosilicate, borax, boric acid, calcium arsenate, calcium polysulfide, copper arsenate, copper naphthenate, copper oleate, cryolite, diatomaceous earth, lead arsenate, mercurous chloride, Paris green, potassium arsenite,
  • composition of embodiment 35 wherein said at least one insecticide is an isoxazoline insecticide selected from the group consisting of afoxolaner, esafoxolaner, fluralaner, fluxametamide, isocycloseram, lotilaner, mivorilaner, sarolaner, tigolaner, and umifoxolaner. 48.
  • isoxazoline insecticide selected from the group consisting of afoxolaner, esafoxolaner, fluralaner, fluxametamide, isocycloseram, lotilaner, mivorilaner, sarolaner, tigolaner, and umifoxolaner.
  • composition of embodiment 35 wherein said at least one insecticide is a juvenile hormone mimic selected from the group consisting of dayoutong, diofenolan, epofenonane, fenoxycarb, hydroprene, juvenile hormone I, juvenile hormone II, juvenile hormone III, kinoprene, Methoprene, pyriproxyfen, and triprene. 49.
  • a juvenile hormone mimic selected from the group consisting of dayoutong, diofenolan, epofenonane, fenoxycarb, hydroprene, juvenile hormone I, juvenile hormone II, juvenile hormone III, kinoprene, Methoprene, pyriproxyfen, and triprene. 49.
  • composition of embodiment 35 wherein said at least one insecticide is a macrocyclic lactone insecticide selected from the group consisting of abamectin, doramectin, emamectin, eprinomectin, ivermectin, lepimectin, moxidectin, selamectin, spinetoram, and spinosad. 50.
  • a macrocyclic lactone insecticide selected from the group consisting of abamectin, doramectin, emamectin, eprinomectin, ivermectin, lepimectin, moxidectin, selamectin, spinetoram, and spinosad. 50.
  • composition of embodiment 35 wherein said at least one insecticide is broflanilide, cyproflanilide, modoflaner, flupyroxystrobin, indoxacarb, metoxadiazone, flursulamid, sulfluramid, pymetrozine, pyrifluquinazon, flufenerim, pyrimidifen, ledprona, closantel, metaflumizone, ⁇ -ecdysone, ecdysterone, spidoxamat, spiropidion, spirotetramat, spirodiclofen, spiromesifen, O,O-diethyl dithiobisthioformate (EXD), sodium tetrathiocarbonate, diafenthiuron, flucofuron and sulcofuron.
  • said at least one insecticide is broflanilide, cyproflanilide, modoflaner, flupyroxystrobin, indoxacarb
  • composition of embodiment 35 wherein said at least one insecticide is a neonicotinoid insecticide selected from the group consisting of acetamiprid, clothianidin, cycloxaprid, dicloromezotiaz, dinotefuran, fenmezoditiaz, flupyradifurone, flupyrimin, imidacloprid, imidaclothiz, nitenpyram, nithiazine, paichongding, sulfoxaflor, thiacloprid, thiamethoxam, and triflumezopyrim. 51 BUSINESS.31669632.1 409753-016WO (210621) 52.
  • composition of embodiment 35 wherein said at least one insecticide is a nereistoxin analogue insecticide selected from the group consisting of bensultap, cartap, polythialan, thiocyclam, and thiosultap. 53.
  • composition of embodiment 35 wherein said at least one insecticide is an organochlorine insecticide selected from the group consisting of aldrin, alpha-endosulfan, bromociclen, p,p-dibromo-diphenyl-1,1,1-trichloroethane (bromo-DDT), camphechlor, chlorbicyclen, chlordane, chlordecone, dichlorodiphenyltrichloroethane (DDT), difluorodiphenyltrichloroethane (DFDT), dieldrin, dilor, endosulfan, endrin, 1,1-dichloro-2,2- bis(4-ethylphenyl)ethane (ethyl-DDD), hexachlorocyclohexane (HCH), heptachlor, isobenzan, isodrin, kelevan, lindane, methoxychlor, mirex, p-dichlorobenzene, and
  • composition of embodiment 35 wherein said at least one insecticide is an organophosphorus insecticide selected from the group consisting of acephate, acethion, acetophos, amidithion, amiton, athidathion, azamethiphos, azinphos-ethyl, azinphos-methyl, azothoate, bromfenvinfos, bromophos, bromophos-ethyl, butathiofos, butonate, cadusafos, calvinphos, carbophenothion, chloramine phosphorus, chlorethoxyfos, chlorfenvinphos, chlormephos, chlorphoxim, chlorprazophos, chlorpyrifos, chlorpyrifos-methyl, chlorthiophos, colophonate, coumaphos, coumithoate, crotoxyphos, crufomate, cyanofenphos, cyanophos, cyanthoate,
  • composition of embodiment 35 wherein said at least one insecticide is a phenol insecticide selected from the group consisting of pentachlorophenol, precocenes, precocene I, precocene II, and precocene III.
  • said at least one insecticide is a pyrazole insecticide selected from the group consisting of acetoprole, dimpropyridaz, ethiprole, fipronil, flufiprole, pyrafluprole, pyriprole, tolfenpyrad, and vaniliprole. 57.
  • composition of embodiment 35 wherein said at least one insecticide is a pyrethrin/pyrethroid insecticide selected from the group consisting of acrinathrin, allethrin, alpha- cypermethrin, barthrin, beta-cyfluthrin, beta-cypermethrin, bifenthrin, bioallethrin, bioethanomethrin, biopermethrin, bioresmethrin, brofenvalerate, brofluthrinate, bromethrin, butethrin, chlorempenthrin, chloroprallethrin, cinerin, cismethrin, cyclethrin, cycloprothrin, cyfluthrin, cyhalothrin, cypermethrin, cyphenothrin, deltamethrin, d-fanshiluquebingjuzhi, dimefluthrin, dime
  • composition of embodiment 35 wherein said at least one insecticide is benzpyrimoxan, buprofezin, crotamiton, fenoxacrim, fentrifanil, flometoquin, flonicamid, fluhexafon, hydramethylnon, indazapyroxamet, jiahuangchongzong, ledprona, malonoben, maltodextrin, nicofluprole, nifluprole, nifluprole, oxazosulfyl, plifenate, pyridaben, pyridalyl, rafoxanide, sulfiflumin, tartar emetic, thuringiensin, triazamate, trichlophenidine, or tyclopyrazoflor.
  • said at least one insecticide is benzpyrimoxan, buprofezin, crotamiton, fenoxacrim, fen
  • composition of any one of embodiments 35-58 wherein said at least one ascaroside comprises an ascaroside having the structure (I): OZ where: Z is an optionally substituted C3-40 aliphatic group, and each of R a and R b is independently -H, or an optionally substituted moiety selected from the group consisting of: C1-20 aliphatic, C1-20 acyl, C1-20 heteroaliphatic, aryl, heteroaryl, a hydroxyl protecting group, a phosphorous-linked functional group , a sulfur-linked functional group, a silicon-linked functional group, a C 2-20 carbonate (e.g.
  • -a moiety -C(O)OR c a C 2-20 carbamate (e.g. -a moiety -C(O)N(R c ) 2 ), a C 2-20 thioester (e.g. a moiety -C(S)R c ), a C 2-20 thiocarbonate (e.g. a moiety -C(S)OR c ), a C2-20 dithiocarbonate (e.g. a moiety -C(S)SR c ), a C 1-20 thiocarbamate (e.g.
  • a moiety -C(S)N(R c ) 2 a sugar moiety, a peptide, a polymer chain, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule.
  • R c is independently at each occurrence selected from -H, optionally substituted C1-12 aliphatic, optionally substituted C1-12 heteroaliphatic, optionally substituted aryl, optionally substituted heteroaryl, a polymer chain, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule, and where R a and R b may be taken together to form an optionally substituted ring, optionally containing one or more heteroatoms, and optionally containing one or more sites of unsaturation.
  • BUSINESS.31669632.1 409753-016WO (210621) 60.
  • Z is selected from the group consisting of: i.
  • R 1 is an optionally substituted C1-40 aliphatic group ii. –CH(CH3)–(CH2)n–CO2R 2 , where n is an integer from 1 to 40, and R 2 is -H, a metal cation, an optionally substituted C 1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; iii.
  • n is an integer from 1 to 40, and R 2 is - H, a metal cation, an optionally substituted C 1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; iv.
  • n is an integer from 1 to 40, and R 2 is -H, a metal cation, an optionally substituted C 1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; v.
  • n is an integer from 1 to 40, and R 2 is -H, a metal cation, an optionally substituted C 1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; vi. –(CH2)n–CO2R 2 , where n is an integer from 1 to 40, and R 2 is -H, a metal cation, an optionally substituted C 1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; vii.
  • n is an integer from 1 to 40, and R 2 is -H, a metal cation, an optionally substituted C 1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; viii. –(CH2)n–CH(OH)–CH2-CO2R 2 , where n is an integer from 1 to 40, and R 2 is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; and ix.
  • n is an integer from 1 to 40, and R 2 is -H, a metal cation, an optionally substituted C 1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide. 61.
  • composition of any one of embodiments 35-63, wherein said at least one ascaroside comprises an ascaroside selected from the group consisting of ascr#9, ascr#10, ascr#16, ascr#18, ascr#20, ascr#22, and ascr#24.
  • 66. The composition of any one of embodiments 35-63, wherein said at least one ascaroside comprises ascr#18.
  • composition of any one of embodiments 35-66, wherein said composition is part of a tank mix.
  • composition of any one of embodiments 35-66, wherein said composition is in a solid form.
  • the composition of embodiment 68, wherein said solid form comprises powder or granules.
  • the composition of any one of embodiments 35-66, wherein said composition is in liquid form.
  • the composition of embodiment 70, wherein said liquid form is a sprayable formulation.
  • 72. The composition of any one of embodiments 35-71, wherein the composition is stable for a period of greater than 6 months. 73.
  • composition of any one of embodiments 35-72 wherein said composition further comprises one or more additional components selected from the group consisting of surfactants, including emulsifiers, dispersants, foam-formers, colorants, processing aids, lubricants, fillers, reinforcements, flame retardants, light stabilizers, ultraviolet radiation absorbers, weather stabilizers, plasticizers, release agents, perfumes, heat-retaining additives (e.g., silica), cross- linking agents, antioxidants, anti-foaming agents, buffers, pH modifiers, compatibility agents, drift control additives, extenders/stickers, tackifiers, plant penetrants, safeners, spreaders, and wetting agents.
  • surfactants including emulsifiers, dispersants, foam-formers, colorants, processing aids, lubricants, fillers, reinforcements, flame retardants, light stabilizers, ultraviolet radiation absorbers, weather stabilizers, plasticizers, release agents, perfumes, heat-retaining additives (e.g., si
  • Example 1 Ascaroside tank mix trial with insectiside.
  • a trial is performed to evaluate the application of Phytalix® (a formulation containing ascarosides) in combination with one or more insecticides. The trial is organized in a randomized complete block design with four replications per treatment and a plot size of 10 ft by 30 ft. The trial is replicated at three separate field sites.
  • Tank mixes are created with different insecticides from a range of different molecular classes and modes of actions along with an effective amount of Phytalix® or a similar ascaroside formulation. Untreated controls and control groups with each insecticide only and no added Phytalix® are included for comparison.
  • Example 1 The plots in Example 1 are evaluated as follows: Insect control in each plot is rated as % control 7 and 14 days after application. A Phytotoxicity rating of each plot is also measured at 7 and 14 days after application. Disease ratings (e.g. for fungal, bacterial, and/or viral diseases) are 58 BUSINESS.31669632.1 409753-016WO (210621) collected when the crop reaches the appropriate growth stage, or whenever routine monitoring reveals the presence of a measurable disease in the control plots. The disease evaluation includes % disease incidence and severity. The plots are harvested separately and the yield measured and reported as bushel/acre.
  • Disease ratings e.g. for fungal, bacterial, and/or viral diseases
  • Disease ratings are 58 BUSINESS.31669632.1 409753-016WO (210621) collected when the crop reaches the appropriate growth stage, or whenever routine monitoring reveals the presence of a measurable disease in the control plots.
  • the disease evaluation includes % disease incidence and severity. The plots are harvested separately and the yield measured
  • Insect control levels, phytotoxicity ratings, disease incidence and severity and yield are averaged for the plots for each treatment group and compared to appropriate controls to assess the impact of ascarosides.
  • compounds, compositions, and methods of the present application encompass variations and adaptations developed using information from the embodiments described in the present disclosure. Adaptation or modification of the methods and processes described in this specification may be performed by those of ordinary skill in the relevant art.
  • headers in the present disclosure are provided for the convenience of the reader. The presence and/or placement of a header is not intended to limit the scope of the subject matter described herein. Unless otherwise specified, embodiments located in one section of the application apply throughout the application to other embodiments, both singly and in combination.
  • compositions, compounds, or products are described as having, including, or comprising specific components, or where processes and methods are described as having, including, or comprising specific steps, it is contemplated that, additionally, there are articles, devices, and systems of the present application that consist essentially of, or consist of, the recited components, and that there are processes and methods according to the present application that consist essentially of, or consist of, the recited processing steps.
  • articles, devices, and systems of the present application that consist essentially of, or consist of, the recited components, and that there are processes and methods according to the present application that consist essentially of, or consist of, the recited processing steps.

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Abstract

L'invention concerne des combinaisons d'agents pour prévenir, traiter ou lutter contre des plantes indésirables et des procédés d'utilisation de celles-ci. Les combinaisons comprennent au moins un ascaricide (ou un dérivé ou un analogue d'un ascaricide) et au moins un insecticide. L'ascaricide peut être combiné à au moins un insecticide pour réduire les effets phytotoxiques de l'insecticide sur la culture traitée tout en éliminant simultanément des plantes indésirables dans la zone d'application. Les ascaricides et les insecticides peuvent être contenus dans la même composition ou être appliqués ensemble (c'est-à-dire, sensiblement simultanément) ou encore l'un à la suite de l'autre.
PCT/US2024/037825 2023-07-14 2024-07-12 Combinaisons d'ascaricides et d'insecticides et procédés d'utilisation Pending WO2025019329A2 (fr)

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