Ascaroside and insecticide combinations and methods of use

Abstract

Provided herein are combinations of agents for preventing, treating or controlling unwanted plants and methods of using the same. The combination comprises at least one ascaroside (or a derivative or analog of the ascaroside) and at least one pesticide. The ascaroside may be combined with at least one insecticide to mitigate the phytotoxic effect of the insecticide on the treated crop while killing unwanted plants in the application area. The ascaroside and insecticide may be provided in the same composition, or may be applied together (i.e., substantially simultaneously) or sequentially.

Description

[0001] Cross-reference to related applications

[0002] This application claims priority to U.S. Provisional Application No. 63 / 513,860, filed July 14, 2023, the entire contents of which are hereby incorporated by reference. Technical Field

[0003] This invention relates to compositions and methods related to the use of ascaroside and one or more insecticides. Background Technology

[0004] As is well known, pesticides control unwanted insects. Selective pesticides control specific insects, while non-selective pesticides kill most (if not all) insects that come into contact with or ingest the pesticide. Most pesticides are used for agricultural purposes to prevent harmful insects from consuming plants that produce crops or products obtained from those plants.

[0005] To overcome increasing insecticide resistance in pests, growers are increasingly relying on products containing blends of multiple insecticidal ingredients, often with different modes of action. These products typically contain the full dose of each insecticide ingredient (e.g., when applied at the label rate, the amount of each active ingredient provided by such a blend is similar to the amount applied when that active ingredient is used as a standalone product at the label rate). This results in an overall increase in the amount of insecticide applied per acre, and correspondingly, an increased risk of phytotoxicity to crops. Unfortunately, such pleiotropic products are more irritating to plants, either due to the additive or synergistic phytotoxicity of the active ingredients, the more complex formulations required to make multiple insecticides compatible, or the larger amounts of adjuvants and inert formulation components applied to crops with these pleiotropic products. The benefits gained from controlling insecticide-resistant pests may be compromised due to the higher levels of phytotoxicity, and this can lead to negative perceptions of the product in the market. While insecticides can very selectively reduce unwanted insects in the field, they can also have phytotoxic side effects on crop plants.

[0006] Furthermore, there is a growing concern about the cost and environmental impact of agricultural inputs. Strategies to minimize the frequency of agrochemical application to crops can reduce costs and improve sustainability by reducing fuel consumption. Minimizing application frequency can also prevent soil compaction, physical damage to plants, and reduce the risk of adverse effects such as runoff and overspraying.

[0007] This invention provides solutions to these and related problems. Summary of the Invention

[0008] This document provides combinations of agents for the prevention, treatment, or control of unwanted insects and / or plant pathogens, and methods of application thereof. The provided combinations comprise at least one ascaridin (or a derivative or analog of ascaridin) and at least one insecticide. In some embodiments, the ascaridin may be combined with at least one insecticide to mitigate the phytotoxic effects of the insecticide on the treated crop. In some embodiments, crop management can be made more efficient by simultaneously applying the ascaridin (which may be valuable in controlling plant pathogens such as fungi, bacteria, viruses, or nematodes and / or promoting plant health) and the insecticide, which can minimize the number of applications, reduce fuel consumption, and lower crop production costs. The ascaridin and the insecticide may be provided in the same composition, or may be applied together (i.e., substantially simultaneously) or sequentially. The agent is applied in an effective amount, sufficient to control or inhibit unwanted insects and also to provide the desired benefits of the ascaridin application (e.g., reducing the phytotoxic side effects of the insecticide and / or controlling pathogens on the crop plant). Detailed Implementation

[0009] This disclosure provides compositions and methods relating to the use of one or more ascarosides and one or more insecticides. In some embodiments, this disclosure provides compositions and methods relating to a combination of one or more ascarosides and one or more insecticides, wherein the one or more ascarosides act as a safener to mitigate the phytotoxic effects of the one or more insecticides on the treated crop. As used herein, the term "ascaroside" includes ascaroside, ascaroside derivatives or analogs, or combinations thereof, as will be described in further detail herein. Ascarosides can be used with any insecticide.

[0010] The one or more ascarosides and the one or more insecticides can be used in the same composition (e.g., co-formulated or canned), or the one or more ascarosides and the one or more insecticides can be applied simultaneously or sequentially (e.g., in separate formulations). If applied sequentially, these applications are close enough in time that they can work together to produce beneficial results.

[0011] As described above, the methods and compositions of the present invention comprise ascaroside. Ascaroside is a secondary metabolite produced by nematodes. Many structurally diverse ascarosides have been identified in nature, and these ascarosides are considered to function as an evolutionarily conserved chemical language used by nematodes to control many aspects of their development.

[0012] Ascaroside is a derivative of ascaroside, a dideoxysugar lacking hydroxyl groups at positions 3 and 6. Ascaroside has the general structure shown in Formula I:

[0013]

[0014] (Formula I),

[0015] in:

[0016] Z represents C, which is arbitrarily substituted. 2-40 Aliphatic groups, and

[0017] R a and R b Each of them is independently -H or an optionally substituted portion of a group consisting of the following: C 1-20 aliphatic, C 1-20 Acyl group, C 1-20 Heteroaliphatic, aryl, heteroaryl, hydroxyl protecting groups, phosphorus-linked functional groups, sulfur-linked functional groups, silicon-linked functional groups, C 2-20 Carbonates (e.g., partially -C(O)OR) c C 2-20 Carbamates (e.g., partially -C(O)N(R) c )2) C 2-20 Thioesters (e.g., partially -C(S)R) c C 2-20 Thiocarbonates (e.g., partially -C(S)OR) c C 2-20 Dithiocarbonates (e.g., partially -C(S)SR) c C 1-20 Thiocarbamates (e.g., partially -C(S)N(R) c )2) The sugar moiety, peptide, polymer chain, or the linking of the molecule to another ascaridin molecule via a bond or carbon-containing linker;

[0018] Each R c Each occurrence is independently selected from -H, optionally substituted C. 1-12 Aliphatic, optionally substituted C 1-12 Heteroaliphatic, optionally substituted aryl, optionally substituted heteroaryl, polymer chain or linkage to another ascaridin molecule via a bond or carbon-containing linker; and

[0019] Where R a and R b Together they can form an optionally substituted ring, which optionally contains one or more heteroatoms and optionally contains one or more unsaturated sites.

[0020] In some embodiments, Z is:

[0021] (i)–CH(CH3)–R 1 , where R 1 C is arbitrarily substituted 1-40 Aliphatic groups

[0022] (ii)–CH(CH3)–(CH2) n –CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, glycoside, amino acid, peptide, nucleotide, or linked to another ascaridone molecule via a bond or carbon-containing linker.

[0023] (iii)–CH(CH3)–(CH2) n –CH=CH-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, glycoside, amino acid, peptide, nucleotide, or linked to another ascaridone molecule via a bond or carbon-containing linker.

[0024] (iv)–CH(CH3)–(CH2) n –CH(OH)–CH2-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, glycoside, amino acid, peptide, nucleotide, or linked to another ascaridone molecule via a bond or carbon-containing linker.

[0025] (v)–CH(CH3)–(CH2) n –C(O)–CH2-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, glycoside, amino acid, peptide, nucleotide, or linked to another ascaridone molecule via a bond or carbon-containing linker.

[0026] (vi)–(CH2) n –CO2R 2, where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, glycoside, amino acid, peptide, nucleotide, or linked to another ascaridone molecule via a bond or carbon-containing linker.

[0027] (vii)–(CH2) n –CH=CH-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, glycoside, amino acid, peptide, nucleotide, or linked to another ascaridone molecule via a bond or carbon-containing linker.

[0028] (viii)–(CH2) n –CH(OH)–CH2-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 Heteroaliphatic groups, optionally substituted aromatic groups, optionally substituted heteroaryl groups, glycosides, amino acids, peptides, nucleotides, or linkage to another ascaridone molecule via a bond or carbon-containing linker; or

[0029] (ix)–(CH2) n –C(O)–CH2-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, glycoside, amino acid, peptide, nucleotide, or linked to another ascaridone molecule via a bond or carbon-containing linker.

[0030] In some embodiments, Z is:

[0031] (x)–CH(CH3)–(CH2) n –CON(R 3 )2, where n is an integer from 1 to 40, and each R 3Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linkage to another ascaridone molecule via a bond or carbon-containing linker.

[0032] (xi)–CH(CH3)–(CH2) n –CH=CH-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linkage to another ascaridone molecule via a bond or carbon-containing linker.

[0033] (xii)–CH(CH3)–(CH2) n –CH(OH)–CH2-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linkage to another ascaridone molecule via a bond or carbon-containing linker.

[0034] (xiii)–CH(CH3)–(CH2) n –C(O)–CH2-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linkage to another ascaridone molecule via a bond or carbon-containing linker.

[0035] (xiv)–(CH2) n –CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linkage to another ascaridone molecule via a bond or carbon-containing linker.

[0036] (xv)–(CH2) n –CH=CH-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linkage to another ascaridone molecule via a bond or carbon-containing linker.

[0037] (xvi)–(CH2) n –CH(OH)–CH2-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linkage to another ascaridone molecule via a bond or carbon-containing linker.

[0038] (xvii)–(CH2) n –C(O)–CH2-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 Heteroaliphatic groups, optionally substituted aromatic groups, optionally substituted heteroaryl groups, polymer chains, amino acids, peptides, nucleotides, or linkages to another ascaridone molecule via bonds or carbon-containing linker portions; or

[0039] (xviii) Optionally unsaturated, optional substituted C 2-40 Side chains terminate at chain ends containing functional groups of nitrogen, oxygen, or sulfur.

[0040] As defined above and described herein, in some embodiments, Z includes a nitrogen-, oxygen-, or sulfur-containing functional group. It will be understood that "oxygen-containing functional group" refers to a portion containing one or more oxygen atoms (e.g., carbonyl groups, such as esters, aldehydes, carboxylic acids, orthoesters, and ketones; ethers, hydroxyl groups, and heterocycles containing one or more oxygen atoms and / or one of the aforementioned functional groups); "nitrogen-containing functional group" refers to a portion containing one or more nitrogen atoms (e.g., amines, amides, carbamates, imines, ureas, oximes, amidines, guanidines, nitriles, azo groups, azides, and heterocycles containing one or more nitrogen atoms and / or one of the aforementioned functional groups); and "sulfur-containing functional group" refers to a portion containing one or more sulfur atoms (e.g., thioethers, sulfones, sulfonic acids, sulfoxides, thiols, thiocyanates, or disulfides).

[0041] In some embodiments, Z is optionally unsaturated, optionally substituted C. 2-40 Side chains terminate at chain ends containing oxygen-containing functional groups. In some embodiments, Z is optionally unsaturated, optionally substituted C. 2-40 Side chain, terminating at the end containing a carboxylic acid. In some embodiments, Z is optionally unsaturated, optionally substituted C. 2-40 Side chains that terminate at the aldehyde-containing chain end. In some embodiments, Z is optionally unsaturated, optionally substituted C. 2-40 Side chain, terminating at the end of the chain containing the ester. In some embodiments, Z is optionally unsaturated, optionally substituted C. 2-40 Side chain, which terminates at a point containing -CO2R 2 The chain end. In some embodiments, Z is optionally unsaturated, optionally substituted C 2-40 Side chains that terminate at a chain end containing -CO2H. In some embodiments, Z is optionally unsaturated, optionally substituted C 2-40 Side chains that terminate at a chain end containing -CO2CH3. In some embodiments, Z is optionally unsaturated, optionally substituted C 2-40 Sidechain, which terminates at a point containing -CON(R) 3 The chain end of )2. In some embodiments, Z is optionally unsaturated, optionally substituted C 2-40 Sidechains that terminate at points containing -N(R) 3 The chain end of )2. In some embodiments, Z is optionally unsaturated, optionally substituted C 2-40 Side chain, which terminates at the end of an ester containing a linker portion covalently attached to one or more other ascaroside molecules.

[0042] As stated above, the sucralose moiety in the provided compound can be substituted or unsubstituted (i.e., the 2 and 4 positions of the sugar can have functional groups other than -OH, or in other words, the variable R in any of the formulas herein).a and / or R b It can be omitted (-H).

[0043] As defined above and as described in this article, R a and R b Each of them is independently -H or an optionally substituted portion of a group consisting of the following: C 1-20 aliphatic, C 1-20 Acyl group, C 1-20 Heteroaliphatic, aryl, heteroaryl, hydroxyl protecting groups, phosphorus-linked functional groups, sulfur-linked functional groups, silicon-linked functional groups, C 2-20 Carbonates (e.g., partially -C(O)OR) c C 2-20 Carbamates (e.g., partially -C(O)N(R) c )2) C 2-20 Thioesters (e.g., partially -C(S)R) c C 2-20 Thiocarbonates (e.g., partially -C(S)OR) c C 2-20 Dithiocarbonates (e.g., partially -C(S)SR) c C 1-20 Thiocarbamates (e.g., partially -C(S)N(R) c )2) The sugar moiety, peptide, polymer chain or the ascaroside molecule is linked to the ascaroside molecule via a bond or carbon-containing linker.

[0044] In some embodiments, R a For -H. In some embodiments, R b For -H. In some embodiments, R a and R b They are the same. In some embodiments, R a and R b Both are -H. In some embodiments, R a and R b They are different. In some embodiments, R a It is -H, and R b Not -H. In some embodiments, R a Not -H and R b For -H. In some embodiments, R a -H and R b It is a para-hydroxybenzoic acid ester. In some embodiments, R a -H and R b It is an indole-3-carboxylate. In some embodiments, R a -H and R bIt is (E)-2-methyl-2-butenoate. In some embodiments, R a -H and R b It is a pyridine carboxylate. In some embodiments, R a -H and R b It is nicotinic acid ester. In some embodiments, R a -H and R b It is (R)-2-hydroxy-2-(4-hydroxyphenyl)ethyl)amino)-4-oxobutyrate. In some embodiments, R a -H and R b It is 4-((4-hydroxyphenylethyl)amino)-4-oxobutyrate. In some embodiments, R a It contains glycosides, amino acids, peptides, or nucleotides. In some embodiments, R b It contains glycosides, amino acids, peptides, or nucleotides. In some embodiments, R a It includes a link to a second ascaroside molecule. In some embodiments, R b It includes a link to an ascaroside molecule. In some embodiments, R a Contains sugar. In some embodiments, R b It contains sugar.

[0045] In some embodiments, R a C is arbitrarily substituted 1-20 Aliphatic. In some embodiments, R a C is arbitrarily substituted 1-6 Aliphatic. In some embodiments, R a C 1-20 Aliphatic. In some embodiments, R a C 1-6 Aliphatic. In some embodiments, R a It is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, or tert-butyl. In some embodiments, R a C 1-20 Acyl group. In some embodiments, R a -C(O)R c In some embodiments, R a It is -C(O)H. In some embodiments, R a It is -C(O)CH3. In some embodiments, R a C is arbitrarily substituted 1-20 Aliphatic. In some embodiments, R a C is arbitrarily substituted 1-6 Aliphatic. In some embodiments, R a C 1-20 Aliphatic. In some embodiments, Ra C 1-6 Aliphatic. In some embodiments, R a It is a optionally substituted 3- or 8-membered saturated or partially unsaturated heterocyclic group having 1 to 3 independently selected heteroatoms chosen from nitrogen, oxygen, or sulfur. In some embodiments, R a It is an optionally substituted 8- or 12-membered saturated or partially unsaturated bicyclic heterocyclic group having 1 to 4 independently selected heteroatoms chosen from nitrogen, oxygen, or sulfur. In some embodiments, R a The aryl group is optionally substituted. In some embodiments, R a Optionally substituted phenyl. In some embodiments, R a It is phenyl. In some embodiments, R a R is an optionally substituted heteroaryl group. In some embodiments, R a It is a optionally substituted 5- to 6-membered heteroaryl group having 1 to 3 independently selected heteroatoms chosen from nitrogen, oxygen, or sulfur. In some embodiments, R a It is an optionally substituted 8- to 12-membered heteroaryl group having 1 to 4 independently selected heteroatoms chosen from nitrogen, oxygen, or sulfur. In some embodiments, R a C is arbitrarily substituted 2-20 Carbonate. In some embodiments, R a -C(O)OR c In some embodiments, R a C is arbitrarily substituted 2-20 Carbamate. In some embodiments, R a -C(O)N(R) c )2. In some embodiments, R a C is arbitrarily substituted 2-20 Thioesters. In some embodiments, R a -C(S)R c In some embodiments, R a C is arbitrarily substituted 2-20 Thiocarbonates. In some embodiments, R a -C(S)OR c In some embodiments, R a C is arbitrarily substituted 2-20 Dithiocarbonate. In some embodiments, R a -C(S)SR c In some embodiments, R a C is arbitrarily substituted 1-20 Thiocarbamates. In some embodiments, R a -C(S)N(R) c )2.

[0046] In some embodiments, R a Optionally substituted hydroxyl protecting groups. Suitable hydroxyl protecting groups are well known in the art and include those described in Protecting Groups in Organic Synthesis, TWGreene and PGM Wuts, 3rd edition, John Wiley & Sons, 1999. Examples of suitable oxygen protecting groups include, but are not limited to, acetyl, benzoylbenzyl, β-methoxyethoxymethyl ether (MEM), dimethoxytriphenylmethyl (DMT), methoxymethyl ether (MOM), methoxytriphenylmethyl (MMT), p-methoxybenzyl ether (PMB), methyl thiomethyl ether, pivaloyl, tetrahydropyranyl (THP), tetrahydrofuranyl (THF), triphenylmethyl, silyl ethers (e.g., trimethylsilyl (TMS), tert-butyldimethylsilyl (TBDMS), triisopropylsilyloxymethyl (TOM), and triisopropylsilyl (TIPS) ether), methyl ethers, and ethoxyethyl ethers. In some embodiments, R a For -OR c .

[0047] In some embodiments, R a The phosphorus-linked functional group is optionally substituted. It will be understood that, as used herein, "phosphorus-linked functional group" refers to a moiety containing one or more phosphorus atoms (e.g., phosphine, phosphate diester, phosphonic acid, phosphate ester). In some embodiments, R a This is an optionally substituted sulfur-linked functional group. It will be understood that, as used herein, "sulfur-linked functional group" refers to a moiety containing one or more sulfur atoms (e.g., thioethers, sulfones, sulfonic acids, sulfoxides, thiols, thiocyanates, or disulfides). In some embodiments, R a The silicon-linked functional group is optionally substituted. It will be understood that, as used herein, "silicon-linked functional group" refers to a portion containing one or more silicon atoms (e.g., silanol, sulfoxide, siloxane, silyl ether, silyl chloride, silyl hydride, silene, or thiophene).

[0048] In some embodiments, R a For optionally substituted sugar portions. In some embodiments, R a The peptide is optionally substituted. In some embodiments, R a For optionally substituted polymer chains. In some embodiments, R a This is a connection to the ascaroside molecule via a bond or a carbon-containing linker. In some embodiments, R a C-type compounds containing ascaroside, optionally substituted 1-6 Aliphatic or mixed adipose.

[0049] In some embodiments, R b C is arbitrarily substituted 1-20 Aliphatic. In some embodiments, R b C is arbitrarily substituted 1-6 Aliphatic. In some embodiments, R b C 1-20 Aliphatic. In some embodiments, R b C 1-6 Aliphatic. In some embodiments, R b It is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, or tert-butyl. In some embodiments, R b C 1-20 Acyl group. In some embodiments, R b -C(O)R c In some embodiments, R b It is -C(O)H. In some embodiments, R b It is -C(O)CH3. In some embodiments, R b C is arbitrarily substituted 1-20 Aliphatic. In some embodiments, R b C is arbitrarily substituted 1-6 Aliphatic. In some embodiments, R b C 1-20 Aliphatic. In some embodiments, R b C 1-6 Aliphatic. In some embodiments, R b It is a optionally substituted 3- or 8-membered saturated or partially unsaturated heterocyclic group having 1 to 3 independently selected heteroatoms chosen from nitrogen, oxygen, or sulfur. In some embodiments, R b It is an optionally substituted 8- or 12-membered saturated or partially unsaturated bicyclic heterocyclic group having 1 to 4 independently selected heteroatoms chosen from nitrogen, oxygen, or sulfur. In some embodiments, R b The aryl group is optionally substituted. In some embodiments, R b Optionally substituted phenyl. In some embodiments, R b It is phenyl. In some embodiments, R b R is an optionally substituted heteroaryl group. In some embodiments, R b It is a optionally substituted 5- to 6-membered heteroaryl group having 1 to 3 independently selected heteroatoms chosen from nitrogen, oxygen, or sulfur. In some embodiments, R b It is an optionally substituted 8- to 12-membered heteroaryl group having 1 to 4 independently selected heteroatoms chosen from nitrogen, oxygen, or sulfur. In some embodiments, R b C is arbitrarily substituted2-20 Carbonate. In some embodiments, R b -C(O)OR c In some embodiments, R b C is arbitrarily substituted 2-20 Carbamate. In some embodiments, R b -C(O)N(R) c )2. In some embodiments, R b C is arbitrarily substituted 2-20 Thioesters. In some embodiments, R b -C(S)R c In some embodiments, R b C is arbitrarily substituted 2-20 Thiocarbonates. In some embodiments, R b -C(S)OR c In some embodiments, R b C is arbitrarily substituted 2-20 Dithiocarbonate. In some embodiments, R b -C(S)SR c In some embodiments, R a C is arbitrarily substituted 1-20 Thiocarbamates. In some embodiments, R b -C(S)N(R) c )2.

[0050] In some embodiments, R b The hydroxyl protecting group is optionally substituted. In some embodiments, R b For -OR c .

[0051] In some embodiments, R b R is an optionally substituted phosphorus-linked functional group. In some embodiments, R b R is an optionally substituted sulfur-linked functional group. In some embodiments, R b These are optional silicon-linked functional groups.

[0052] In some embodiments, R b For optionally substituted sugar portions. In some embodiments, R a The peptide is optionally substituted. In some embodiments, R b For optionally substituted polymer chains. In some embodiments, R b This is a connection to the ascaroside molecule via a bond or a carbon-containing linker. In some embodiments, R b C-type compounds containing ascaroside, optionally substituted 1-6Aliphatic or mixed adipose.

[0053] In some embodiments, R a and R b Together they can form optionally substituted rings, which optionally contain one or more heteroatoms and optionally one or more unsaturated sites. In some embodiments, R a and R b Together, they can form optionally substituted 3- to 12-membered monocyclic or bicyclic saturated or partially unsaturated carbocyclic or heterocyclic rings having 1 to 4 independently selected heteroatoms chosen from nitrogen, oxygen, or sulfur. In some embodiments, R a and R b They can be combined to form optional substituted 5- to 12-membered monocyclic or bicyclic aryl or heteroaryl rings having 1 to 4 independently selected heteroatoms chosen from nitrogen, oxygen or sulfur.

[0054] In some embodiments, R a -H and R b It is a para-hydroxybenzoic acid ester. In some embodiments, R a -H and R b It is an indole-3-carboxylate. In some embodiments, R a -H and R b It is (E)-2-methyl-2-butenoate. In some embodiments, R a -H and R b It is a pyridine carboxylate. In some embodiments, R a -H and R b It is nicotinic acid ester. In some embodiments, R a -H and R b It is (R)-2-hydroxy-2-(4-hydroxyphenyl)ethyl)amino)-4-oxobutyrate. In some embodiments, R a -H and R b It is 4-((4-hydroxyphenylethyl)amino)-4-oxobutyrate.

[0055] In some embodiments, R a and R b All are -H, and Z is selected from the formulas defined in (i) to (ix) above. In some embodiments, R a and R b Both are -H, and Z conforms to equation (i) above. In some embodiments, R a and R b Both are -H, and Z conforms to equation (ii) above. In some embodiments, R a and R b Both are -H, and Z conforms to equation (iii) above. In some embodiments, Ra and R b Both are -H, and Z conforms to equation (iv) above. In some embodiments, R a and R b Both are -H, and Z conforms to the above equation (v). In some embodiments, R a and R b Both are -H, and Z conforms to the above equation (vi). In some embodiments, R a and R b Both are -H, and Z conforms to the above equation (vii). In some embodiments, R a and R b Both are -H, and Z conforms to the above equation (viii). In some embodiments, R a and R b Both are -H, and Z conforms to the above equation (ix). In some embodiments, R a and R b Both are -H, and Z conforms to the above equation (x). In some embodiments, R a and R b Both are -H, and Z conforms to the above equation (xi). In some embodiments, R a and R b Both are -H, and Z conforms to the above equation (xii). In some embodiments, R a and R b Both are -H, and Z conforms to equation (xiii) above. In some embodiments, R a and R b Both are -H, and Z conforms to the above equation (xiv). In some embodiments, R a and R b Both are -H, and Z conforms to the above equation (xv). In some embodiments, R a and R b Both are -H, and Z conforms to the above equation (xvi). In some embodiments, R a and R b Both are -H, and Z satisfies the above formula (xvii).

[0056] As defined above and as described in this article, each R c Each occurrence is independently selected from -H, optionally substituted C. 1-12 Aliphatic, optionally substituted C 1-12 Heteroaliphatic, optionally substituted aryl, optionally substituted heteroaryl, polymer chain or linked to another ascaridin molecule via a bond or carbon-containing linker.

[0057] In some embodiments, R c Each occurrence is independently selected from -H, optionally substituted C. 1-12Aliphatic, optionally substituted C 1-12 Heteroaliphatic, optionally substituted aryl, optionally substituted heteroaryl.

[0058] In some embodiments, R c The occurrence is -H. In some embodiments, R c C is arbitrarily substituted 1-12 Aliphatic group. In some embodiments, R c C is arbitrarily substituted 1-6 Aliphatic group. In some embodiments, R c C is arbitrarily substituted 1-12 heteroaliphatic groups. In some embodiments, R c C is arbitrarily substituted 1-6 heteroaliphatic groups. In some embodiments, R c It is a optionally substituted 3- or 8-membered saturated or partially unsaturated heterocyclic group having 1 to 3 independently selected heteroatoms chosen from nitrogen, oxygen, or sulfur. In some embodiments, R c It is an optionally substituted 8- or 12-membered saturated or partially unsaturated bicyclic heterocyclic group having 1 to 4 independently selected heteroatoms chosen from nitrogen, oxygen, or sulfur. In some embodiments, R c Optionally substituted aryl groups. In some embodiments, R c Optionally substituted phenyl. In some embodiments, R 2 It is phenyl. In some embodiments, R c R is an optionally substituted heteroaryl group. In some embodiments, R c It is a optionally substituted 5- to 6-membered heteroaryl group having 1 to 3 independently selected heteroatoms chosen from nitrogen, oxygen, or sulfur. In some embodiments, R c It is an 8- to 12-membered heteroaryl group having 1 to 4 independently selected heteroatoms chosen from nitrogen, oxygen or sulfur, which are optionally substituted.

[0059] As defined above and as described in this article, R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 Heteroaliphatic groups, optionally substituted aromatic groups, optionally substituted heteroaryl groups, glycosides, amino acids, peptides, nucleotides, or linkage to another ascaridone molecule via a bond or carbon-containing linker. In some embodiments, R 2 -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 Heteroaliphatic groups or optionally substituted aromatic groups, optionally substituted heteroaryl groups.

[0060] In some embodiments, R 2 For -H. In some embodiments, R 2 It is a metal cation. In some embodiments, R 2 It is an organic cation (e.g., a cationic group centered on nitrogen or phosphorus). In some embodiments, R 2 C is arbitrarily substituted 1-20 Aliphatic groups. In some embodiments, R 2 C is arbitrarily substituted 1-12 Aliphatic groups. In some embodiments, R 2 C is arbitrarily substituted 1-8 Aliphatic group. In some embodiments, R 2 C is arbitrarily substituted 1-6 Aliphatic groups. In some embodiments, R 2 Selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, and tert-butyl. In some embodiments, R 2 C is arbitrarily substituted 1-20 heteroaliphatic groups. In some embodiments, R 2 C is arbitrarily substituted 1-6 heteroaliphatic groups. In some embodiments, R 2 It is a optionally substituted 3- or 8-membered saturated or partially unsaturated heterocyclic group having 1 to 3 independently selected heteroatoms chosen from nitrogen, oxygen, or sulfur. In some embodiments, R 2 It is an optionally substituted 8- or 12-membered saturated or partially unsaturated bicyclic heterocyclic group having 1 to 4 independently selected heteroatoms chosen from nitrogen, oxygen, or sulfur. In some embodiments, R 2 R is an optionally substituted aromatic group. In some embodiments, R 2 Optionally substituted phenyl. In some embodiments, R 2 It is phenyl. In some embodiments, R 2 R is an optionally substituted heteroaryl group. In some embodiments, R 2 It is a optionally substituted 5- to 6-membered heteroaryl group having 1 to 3 independently selected heteroatoms chosen from nitrogen, oxygen, or sulfur. In some embodiments, R 2 It is an 8- to 12-membered heteroaryl group having 1 to 4 independently selected heteroatoms chosen from nitrogen, oxygen or sulfur, which are optionally substituted.

[0061] In some embodiments, R 2 Glycosides. It will be understood that a glycoside is a portion of a sugar that is linked to another functional group via a glycosidic bond.

[0062] In some embodiments, R 2 It is a nucleotide. In some embodiments, R2 It is adenosine monophosphate, cytidine monophosphate, guanosine monophosphate, or uridine monophosphate. In some embodiments, R 2 It is deoxyadenosine monophosphate, deoxycytidine monophosphate, deoxyguanosine monophosphate, or deoxythymidine monophosphate.

[0063] In some embodiments, R 2 For linkage to another ascaroside molecule via a bond or carbon-containing linker. In some embodiments, R 2 C-type compounds containing ascaroside, optionally substituted 1-6 Aliphatic or mixed adipose.

[0064] In some embodiments, R 2 It contains amino acids. In some embodiments, R 2 Contains peptides. In some embodiments, R 2 It contains nucleotides.

[0065] As defined above and as described in this article, each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 Heteroaliphatic groups, optionally substituted aromatic groups, optionally substituted heteroaryl groups, polymer chains, amino acids, peptides, nucleotides, or linkages to another ascaridone molecule via bonds or carbon-containing linker portions. In some embodiments, each R 3 Independently selected from -H and C 1-8 Aliphatic. In some embodiments, an R 3 For -H and another R 3 Not -H. In some embodiments, R 3 None of them are -H. In some embodiments, each R 3 For -H. In some embodiments, R 3 The appearance of C is optionally substituted 1-20 Aliphatic group. In some embodiments, R 3 The appearance of C is optionally substituted 1-6 Aliphatic group. In some embodiments, R 3 The appearance of C is optionally substituted 1-20 heteroaliphatic groups. In some embodiments, R 3 The appearance of C is optionally substituted 1-6 heteroaliphatic groups. In some embodiments, R 3 It is a optionally substituted 3- or 8-membered saturated or partially unsaturated heterocyclic group having 1 to 3 independently selected heteroatoms chosen from nitrogen, oxygen, or sulfur. In some embodiments, R 3It is an optionally substituted 8- or 12-membered saturated or partially unsaturated bicyclic heterocyclic group having 1 to 4 independently selected heteroatoms chosen from nitrogen, oxygen, or sulfur. In some embodiments, R 3 The presence of is optionally a substituted aryl group. In some embodiments, R 3 Optionally substituted phenyl. In some embodiments, R 3 It is phenyl. In some embodiments, R 3 R is an optionally substituted heteroaryl group. In some embodiments, R 3 It is a optionally substituted 5- to 6-membered heteroaryl group having 1 to 3 independently selected heteroatoms chosen from nitrogen, oxygen, or sulfur. In some embodiments, R 3 It is an 8- to 12-membered heteroaryl group having 1 to 4 independently selected heteroatoms chosen from nitrogen, oxygen or sulfur, which are optionally substituted.

[0066] In some embodiments, at least one R 3 -H. In some embodiments, two R 3 All groups are -H. In some embodiments, at least one R 3 C is arbitrarily substituted 1-20 Aliphatic groups. In some embodiments, two R groups... 3 The group is an optionally substituted C 1-20 Aliphatic groups, which may be the same or different. In some embodiments, at least one R 3 C is arbitrarily substituted 1-12 Aliphatic group. In some embodiments, at least one R 3 C is arbitrarily substituted 1-8 Aliphatic group. In some embodiments, at least one R 3 C is arbitrarily substituted 1-6 Aliphatic group. In some embodiments, at least one R 3 The solvent is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, and tert-butyl. In some embodiments, at least one R 3 It is -CH2CH2OH. In some embodiments, at least one R 3 -CH2CH2OR 2 , where R 2 It is as defined in the genus and subgenus herein. In some embodiments, at least one R 3 Optionally substituted aromatic groups. In some embodiments, at least one R 3 Contains glycosides. In some embodiments, at least one R 3 Contains amino acids. In some embodiments, at least one R 3 At least one R 3Contains peptides. In some embodiments, at least one R 3 It contains nucleotides.

[0067] In some embodiments, ascaroside is selected from the group consisting of:

[0068]

[0069] Where x is an integer from 1 to 22, and R a R b and R 2 Each of them is as defined above and in this text as a genus and subgenus.

[0070] In some embodiments, ascaroside is selected from the group consisting of:

[0071]

[0072] Where x and R a and R b Each of them is as defined above and in this text as a genus and subgenus.

[0073] In some embodiments, ascaroside is selected from the group consisting of:

[0074]

[0075] Where y is an integer from 1 to 20, and R a R b and R 2 Each of them is as defined above and in this text as a genus and subgenus.

[0076] In some embodiments, ascaroside is selected from the group consisting of:

[0077]

[0078] Where y and R a and R b Each of them is as defined above and in this text as a genus and subgenus.

[0079] In some embodiments, ascaroside is selected from the group consisting of:

[0080]

[0081] Where x and R 2 Each of them is as defined above and in this text as a genus and subgenus.

[0082] In some embodiments, ascaroside is selected from the group consisting of:

[0083]

[0084] Where x is defined as above and as in this article as genus and subgenus.

[0085] In some embodiments, ascaroside is selected from the group consisting of:

[0086]

[0087] Where y and R 2 Each of them is as defined above and in this text as a genus and subgenus.

[0088] In some embodiments, ascaroside is selected from the group consisting of:

[0089]

[0090] Where y is defined as above and as in this article as genus and subgenus.

[0091] In some embodiments, ascaroside is selected from the group consisting of:

[0092]

[0093] Where x and R a R b and R 3 Each of them is as defined above and in this text as a genus and subgenus.

[0094] In some embodiments, ascaroside is selected from the group consisting of:

[0095]

[0096] Where x and R 3 Each of them is as defined above and in this text as a genus and subgenus.

[0097] In some embodiments, ascaroside is selected from the group consisting of:

[0098]

[0099] Where y and R a R b and R 2 Each of them is as defined above and in this text as a genus and subgenus.

[0100] In some embodiments, ascaroside is selected from the group consisting of:

[0101]

[0102] Where y and R 3 Each of them is as defined above and in this text as a genus and subgenus.

[0103] In the embodiments, the ascaroside available in the context of this disclosure has a universal structure (I), where Z is –CH(CH3)–(CH2). n –CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides, or nucleotides.

[0104] In the embodiments, the ascaroside available in the context of this disclosure has a universal structure (I), where Z is –CH(CH3)–(CH2). n –CH=CH-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides, or nucleotides.

[0105] Specific ascarosides available in the context of this disclosure include, but are not limited to, ascr#7 and ascr#18.

[0106]

[0107] In some embodiments, the ascaroside used in the provided methods and compositions is selected from the group consisting of: ASCII#9, ASCII#12, ASCII#14, ASCII#1, ASCII#10, ASCII#16, ASCII#18, ASCII#20, ASCII#22, ASCII#24, ASCII#26, ASCII#28, ASCII#30, ASCII#32, ASCII#34, and ASCII#36. In some embodiments, the ascaroside used in the provided methods is selected from the group consisting of: ASCII#10, ASCII#16, ASCII#18, ASCII#20, ASCII#22, and ASCII#24. In some embodiments, the ascaroside used in the provided methods is selected from the group consisting of: ASCII#9, ASCII#14, ASCII#10, and ASCII#18.

[0108] In some embodiments, the ascaroside used in the provided methods and compositions is selected from the group consisting of: oscr#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. In some embodiments, the ascaroside used in the provided methods is selected from the group consisting of: oscr#10, oscr#16, oscr#18, oscr#20, and oscr#22. In some embodiments, the ascaroside used in the provided method 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. In some embodiments, the ascaroside used in the provided method is selected from the group consisting of: oscr#10, oscr#16, oscr#18, oscr#20, and oscr#22.

[0109] In some embodiments, the 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.

[0110] In some embodiments, the 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.

[0111] In some embodiments, the 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, glas#18, dhas#18, ibha#18, ibho#16, icas#18, icos#15, icos#16 and any combination of two or more of these.

[0112] Ascaroside can be obtained from natural sources (e.g., nematodes) or prepared synthetically. Ascaroside can be prepared synthetically, for example by converting 1-O-substituted rhamnose to 1-O-substituted ascaroside. Exemplary methods for preparing ascaroside include: providing 1-O-substituted rhamnose as a starting material; forming a monosulfonate ester on the 3-OH group of the starting material; and treating the monosulfonate ester with a hydride source to form the 1-O-substituted ascaroside. In some embodiments, the formation of the monosulfonate ester is carried out on a substrate without a hydroxyl protecting group at the 2 or 4 position of the rhamnose starting material. In some embodiments, such methods include contacting the starting material with a sulfonating agent (i.e., a sulfonyl halide, sulfonic anhydride, or a similar agent) in the presence of a Lewis acid. Specific details regarding the synthesis of 1-O-substituted ascaroside can be found in International Publication No. WO 2022 / 024067, which is incorporated herein by reference.

[0113] As indicated, according to this disclosure, ascaroside can be used as a safener in combination with insecticides to mitigate the phytotoxic effects of insecticides on the treated crops. Insecticides exert their effects by influencing a variety of biological processes associated with insects. Insecticides can be classified according to chemical categories. Insecticides that can use ascaroside to reduce their phytotoxic side effects on crops include, for example, insecticides from the following chemical groups: alkaloid insecticides; alkyl halide insecticides; aminopyrimidine insecticides; aminotriazine insecticides; antibiotic insecticides; aromatic hydrocarbon insecticides; arylpyrrole insecticides; benzimidazole insecticides; benzoylurea insecticides; β-ketonitrile insecticides; phytotoxicants; carbamate insecticides; dihydrazide insecticides; diamide insecticides; dinitrophenol insecticides; dithiopentane insecticides; formamid insecticides; fumigation insecticides; inorganic insecticides; isoxazoline insecticides; juvenile hormone mimics; macrolide insecticides. m-Diamide insecticides; methoxyacrylate insecticides; neonicotinoid insecticides; nereistoxin analog insecticides; organochlorine insecticides; organophosphate insecticides; oxadiazine insecticides; oxadiazon insecticides; perfluoroalkyl sulfonamide insecticides; phenol insecticides; pyrazole insecticides; pyrethroid insecticides; pyrethroid insecticides; pyridazine alkaloid insecticides; pyrimidine amine insecticides; pyropene insecticides; RNA1 insecticides; salicylaniline insecticides; azoxystrobin insecticides; steroid insecticides; tertranolic acid insecticides; terfenic acid insecticides; thiocarbonate insecticides; thiourea insecticides; and urea insecticides.

[0114] Exemplary alkaloid insecticides include neonicotinoids, matrine, nicotine, nornicotinoids, oxymatrine, ryanodine, rhodane, veratrum saba, and sanguisorbin.

[0115] Exemplary alkyl halide pesticides include carbon tetrachloride, chloroform, 1,2-dichloropropane, ethylene dibromide, ethylene dichloride, methyl bromide, iodomethane, methyl chloroform, dichloromethane, and tetrachloroethane.

[0116] Exemplary aminopyrimidine insecticides include desinil. Exemplary aminotriazine insecticides include cyclopropamide. Exemplary antibiotic insecticides include apromycin. Exemplary aromatic hydrocarbon insecticides include naphthalene and benzothiamethoxam. Exemplary arylpyrrole insecticides include bromfenac. Exemplary benzimidazole insecticides include fenbendazole. Exemplary β-ketonitrile insecticides include thiamethoxam. Exemplary dinitrophenol insecticides include fenbendazole, nitropropoxyphenate, pentylenetitol, and 4,6-dinitro-o-cresol (DNOC). Exemplary dithiopentane insecticides include isoprothiolane. Exemplary formamid insecticides include amitraz, chlorfenapyr, acaricide, and methylformamide.

[0117] Exemplary benzoylurea insecticides include bis(triflufenoxuron), chlorfenapyr, chlorofluorourea, dichlorofluorourea, diflubenzuron, flucyclopropionate, flufenoxuron, hexafluorourea, lufenuron, novaron, polyfluorourea, flufenoxuron, fenflurfen, and chlorfenapyr.

[0118] Exemplary plant-based insecticides include allicin, azadirachtin, carvacrol, d-limonene, quassardine, rhododendron toxin-III, rotenone, and triptolide.

[0119] Exemplary carbamate insecticides include carbaryl, aldicarb, oxydicarb, chlorpyrifos, thiamethoxam, carbaryl, thiamethoxam, chlorpyrifos, methylcarbamide, methylcarbamide sulfone, chlorpyrifos, carbamate, carbofuran, thiamethoxam, chlorpyrifos, 2-chlorophenylmethylcarbamate (CPMC), carbofuran, dimethylphenol, dimethoate, chlorpyrifos, dioxin, p-(ethylthio)phenylmethylamino Carbamate (EMPC), ethyl thiocarbamate, fenthiocarbamate, sec-butylcarbamate, chlorfenapyr, fenpropathrin, furazolidone, quinoxalic acid, isoxacarb, isopropylcarbamate, methyl thiocarbamate, methomyl, succinylcarbamate, acetamiprid, pyrimethanil, pyrazocarb, thiamethoxam, thiamethoxam, thiamethoxam, thiamethoxam, thiamethoxam, 3,5-xylylmethylcarbamate (XMC) and xylenecarbamate.

[0120] Exemplary dihydrazide insecticides include cyclotetracycline, furazolidone, chlorfenapyr, methoxyfenozide, tebufenozide, and acetamiprid.

[0121] Exemplary diamide insecticides include chlorantraniliprole, broflaniprole, chlorfluazuron, cyclobromhizobium, flufenoxuron, flufenoxuron, tetrachlorantraniliprole, and thiofenoxuron.

[0122] Exemplary fumigants include acrylonitrile, allyl isothiocyanate, calcium cyanide, carbon disulfide, carbon tetrachloride, carbonyl sulfide, chloroform, chloropicrin, cyanide, 1,2-dichloropropane, dimethyl disulfide, ethyl formate, ethylene dibromide, ethylene dichloride, ethylene oxide, hydrogen cyanide, methyl bromide, iodomethane, methyl isothiocyanate, methyl chloroform, dichloromethane, phosphine, sodium cyanide, thiocyanate fluoride, and tetrachloroethane.

[0123] Exemplary inorganic pesticides 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 fluorosilicate, sodium thiocyanate, and thioyl fluoride.

[0124] Exemplary isoxazoline insecticides include afolanar, esafolanar, fluranar, fluoxazolamide, isoxazolamide, lentilana, mivorana, salorana, ticorana, and yumivorana.

[0125] Exemplary juvenile hormone mimics include dextrin, benzyl ether, juvenile ether, phenoxycarb, acetamiprid, juvenile hormone I, juvenile hormone II, juvenile hormone III, acetamiprid, acetamiprid, pyriproxyfen, and acetamiprid thiocyanate.

[0126] Exemplary macrolide insecticides include abamectin, doramectin, emamectin, epromycin, ivermectin, rapamectin, moxicillin, cilamectin, ethyl spinosad, and spinosad.

[0127] Exemplary m-diamid insecticides include brofenoxam, cyclopropiconazole, and modorana. Exemplary methoxyacrylate insecticide is flupyradifurone. Exemplary oxadiazine insecticide is indoxacarb. Exemplary oxadiazonone insecticide is oxadiazon. Exemplary perfluoroalkyl sulfonamide insecticides are flusulfanilamide and fipronil. Exemplary pyridazine insecticides include pymetrozine and pyrifluquinazon. Exemplary pyrimidine amine insecticides include pyrimethanil and pyrimethanil. Exemplary propenyl insecticide is dipropionyl ester. Exemplary RNA1 insecticide is lepromazine. Exemplary salicylaniline insecticide is chlorfenapyr. Exemplary cyanamide insecticide is cyfluthrin. Exemplary steroid insecticides include α-ecdysone and ecdysterone. Exemplary tetramethrin insecticides include spirotetramat, methoxypiperidine ethyl ester, and spirotetramat. Exemplary terfenicol insecticides include spirodiclofen and spiromethrin. Exemplary thiocarbonate insecticides include O,O-diethyldithiobis(thiocarbamate) (EXD) and sodium tetrathiocarbonate. Exemplary thiourea insecticides include butylated urea. Exemplary urea insecticides include flufuran and sulfadiazine.

[0128] Exemplary neonicotinoid insecticides include acetamiprid, thiamethoxam, epoxiconazole, dichloromethazine, dinotefuran, fenmethazine, flupyrflufenone, flupyramide, imidacloprid, chlorpyrifos, acetamiprid, nitenpyram, piperam, flonicamid, thiamethoxam, thiamethoxam, and trifluorophenylpyrimidine.

[0129] Exemplary nereistoxin analog insecticides include chlorpyrifos, fenitrothion, polythiazide, cyclohexane, and dichlorvos.

[0130] Exemplary organochlorine insecticides include aldrin, α-endothelium, bromoxynil, p,p-dibromo-diphenyl-1,1,1-trichloroethane (bromo-DDT), toxaphene, borneol, chlordane, chlorpheniramine, dichlorodiphenyltrichloroethane (DDT), difluorodiphenyltrichloroethane (DFDT), dieldrin, dilor, endothelium, isodrin, 1,1-dichloro-2,2-bis(4-ethylphenyl)ethane (ethyl-DDD), hexachlorocyclohexane (HCH), heptachlorophen, carbapenem, isoaldrin, clenbuterol, lindane, methoxychloride, methylphenidate, p-dichlorobenzene, and tetrachlorodiphenylethane (TDE).

[0131] Exemplary organophosphorus insecticides include acephate, phosmet, ethyl phosmet, methamidophos, acephate, methyl pyridinium, ethyl phosmet, methyl phosmet, azophos, bromophenylenephos, bromothion, ethyl bromothion, butyl phosmet, thionyl phosmet, dichlorvos, trithion, chloramidophos, chlorpyrifos, chlorfenapyr, chlorpyrifos, methyl chlorpyrifos, chlorfenapyr, thiamethoxam, phosmet, phosmet, butenyl phosmet, phosmet, benzoylphos, fenitrothion, phosmet, phosmet, phosmet-S-methyl sulfone, phosmet-O, ​​phosmet-S Metophosphate-O, Metophosphate-O-methyl, Metophosphate-S, Methyl Metophosphate, Phosphorus chloride, Diazinon, Isochlorpyrifos, Phosphate dichlorvos, Dichlorvos, Methionol, Dimethoate, Methyl chlorpyrifos, Dichlorvos, Ethiophos, Phosphate dithiocarbamate, Ethiophos, Phosphate dichlorvos, Pyrimethanil, S-[(ethylsulfinyl)methyl]O,O-diisopropyl dithiophosphate (IPSP), Ethylpyrimethanil, Phosphate dichlorvos, Phosphate dichlorvos, Phosphate dichlorvos, Fenitrothion, Phosphate dichlorvos, Ethiophos dichlorvos, Ethiophos dichlorvos, Pyrimethanil, Dichlorvos dichlorvos, Ango, Butylbenzyl thiophanate Phosphorus, phosmet, thionyl phosphate, heptenyl phosphate, chlorpyrifos, methamidophos, isopropylamine phosphate, isopropylamine phosphate-methyl, isopropylthionyl phosphate, isoxazolyl phosphate, iodophos, bromobenzyl phosphate, liliphos, thiamethoxam, malathion, malathion, pymetrozine, methyl pymetrozine, pymetrozine, dithiamethoxam, fenthionyl sulfoxide, chlorfenapyr, methamidophos, chlorpyrifos, methoxyphos, methyl ethyl phosphate, phosmet, fenthionyl phosphate, malathion, phosmet, naphthalenephosphide, dibromophos, dimethoate, methyl sulfone phosphate, isosulfone phosphate, sulfone phosphate, parathion, methyl parathion, fenthion, phosmet, methamidophos, phosmet, thionyl phosphate, methyl thionyl phosphate, glycine Phosphorus, phosmet, parachlorpyrifos, phosphamidon, phorate, methyl phorate, pyrimidine phosphamidon, pyrimidine oxyphosphide, ethyl pyrimidine phosphide, methyl pyrimidine phosphide, pyrimidine carbendazim, profenofos, fenpyrophos, ethiophos, phenoxyphos, pyrazophos, pyrimidine phosphide, pyrimidine phosphide, pyrimidine phosphide, quinalphos, methyl quinalphos, phosphonium phosphate, octamethrin, thiophos, thiophos, thiophosprophos, butylpyrimidine phosphide, dithiophos, tetraethyl pyrophosphate (TEPP), terbufos, chlorpyrifos, thiophos, methyl ethiophos, phosphonium phosphate, triazophos, trichlorfon, methyl methiophos-3, phosphonium phosphate, trichlorfon, phosphonium oxyphos, phosphonium pyrophos and phosphonium phosphate.

[0132] Exemplary phenolic insecticides include pentachlorophenol, antijuvenile hormone, precocious hormone I, precocious hormone II, and precocious hormone III.

[0133] Exemplary pyrazole insecticides include acetamiprid, dipropionylpyridinium, acetamiprid, fipronil, tebufenozide, pyrfluthrin, pyrazosulfuron, oxadiazonamide, and vanillin.

[0134] Exemplary pyrethroid insecticides include flufenacet, allethrin, α-cypermethrin, propargyl, lambda-cyhalothrin, β-cypermethrin, bifenthrin, bio-allethrin, bio-ethoxyfen, bio-permethrin, bio-benzylfenoxuron, bromocypermethrin, bromoflufenoxuron, bromobenzylfenoxuron, benzylfenoxuron, chlorpyrifos, chlorpyrifos, cis-benzylfenoxuron. Cypermethrin, cypermethrin, deltamethrin, cypermethrin, fenflurfen, deltamethrin, d-trans-cypermethrin, tetrafluoromethoxyphen ... Pendimethalin, Trifluthrin, Flumethrin, Cypermethrin, Furazolidone, Gamma-triflumethrin, Benzylfentanyl, Heptamethrin, Dimethomorph, Azotocin, Jasminyl, Thiamethoxam, κ-Bifenthrin, κ-Hyperfluxrin, λ-Trifluthrin, Cyfluthrin, Methionyl, Methoxyfenozide, Cyfluthrin, Pendimethalin, Permethrin, Diphenoxy ... Pyrethroids, propargyl, methoxyfenozide, propargyl, pyrethroids, benzylfenozide, chlorfluazuron, benzylfenozide, flusilylfenozide, thiooxime ether, deltamethrin, flumethrin, heptamethrin, cyclopentenylfenozide, methoxyfenozide, tetramethylflumethrin, θ-cypermethrin, thiooxime ether, bromocypermethrin, tetrabromopyrethrin, tetrafluorobenzylfenozide, trans-benzylfenozide, valerate, and ζ-cypermethrin.

[0135] Other unclassified insecticides that can be used in combination with ascaridone include bensulfuron-methyl, thiamethoxam, clomiphene, fentriranil, flumetoquinone, flupyradifurone, fluhexenone, flufenoxuron, indoximetronidazole, mesotrione, leprona, mefenoxuron, maltodextrin, nicotinamide, flufenoxuron, oxazolidinyl, trichlorfon, pyridaben, acetamiprid, iodofensyl, thioflupyr, tartrate, thiophanate-methyl, azoxystrobin, pyridaben, trichlorfon, and chlorpyrifos.

[0136] It should be recognized that the methods and compositions of the present invention may include additional insecticides and other insect regulators. Other additional active agents that can be used with the combinations described herein are known in the art and include fungicides, herbicides, acaricides, arthropod cytokines, bactericides, ectoparasite cytokines, etc., which are compatible with the combinations of the present invention and do not antagonize the activity of one or more ascarosides or one or more insecticides.

[0137] In some cases, the pesticide lists disclosed herein refer to generic names. In such cases, even if a specific salt or ester is not specifically mentioned, the generic name identifies the active ingredient in one or more commercially available forms (preferably in their usual commercially available forms) including derivatives such as salts and esters.

[0138] The application of one or more insecticides and one or more ascaridins can be done before or after emergence. The preferred application method depends on the usual or optimal application time of the particular insecticide or combination of insecticides.

[0139] The antipathogenic activity of ascaroside provides additional benefits to the method and composition. Advantageously, one or more ascarosides can not only reduce the phytotoxic effects on plants typically associated with pesticide application, but can also (or alternatively) provide durable protection against fungi, molds, bacteria, viruses, and / or nematodes. For example, while fungicides and antibacterial agents are typically applied at later points in crop growth when such pathogens are present, this disclosure provides methods and compositions for applying ascaroside at very early points in time (i.e., the points at which pesticides are conventionally applied to crops), and can confer resistance to pathogens in crops treated in this way. In some embodiments, ascaroside surprisingly exhibits durable effects, such as reducing or preventing damage caused by fungi, bacteria, viruses, and molds for periods exceeding 3 days, 5 days, 1 week, 2 weeks, 1 month, 2 months, or 3 months after application, despite being applied at an early stage of the plant life cycle.

[0140] Co-application of ascaridone and insecticides at the beginning of the season can also provide growers with significant economic advantages and enhance the sustainability of crop production. Co-application of ascaridone with insecticides avoids the need for separate fungicide treatments later in the season. This saves fuel and labor, and may avoid the need for additional toxic pathogen control products, as ascaridone treatment can act as a preventative control to enhance crop tolerance to a wide range of pathogens. Another, or alternative, benefit of combining ascaridone with insecticide treatment is the control of early-season plant pathogens such as fungi, bacteria, viruses, and nematodes. Co-application of ascaridone with insecticides avoids the need for separate early-season disease control applications (such as fungicides, antimicrobials, or nematicides), thus saving fuel and labor, and may avoid the need for additional toxic pathogen control products, as ascaridone treatment can act as a preventative control to enhance crop tolerance to a variety of pathogens.

[0141] In some embodiments, this disclosure provides a blend of one or more insecticides and one or more ascaridosin. In some embodiments, this disclosure provides a blend of one or more insecticides and one or more ascaridosin, characterized in that the blend reduces phytotoxicity to the applied crop compared to the application of the one or more insecticides alone. In some embodiments, the blend is characterized in that one or more phytotoxic symptoms in the treated crop are reduced by at least 10% relative to a comparable composition lacking one or more ascaridosin. In some embodiments, the provided method is characterized in that one or more phytotoxic symptoms are reduced by at least 15%, at least 20%, at least 25%, at least 35%, at least 50%, at least 75%, or at least 90% relative to a comparable composition lacking one or more ascaridosin. In some embodiments, the provided blend is characterized in that one or more phytotoxic symptoms are substantially absent relative to a comparable composition lacking one or more ascaridosin.

[0142] In some embodiments, the blend is characterized in that, relative to a comparable composition lacking one or more ascorbic acid glycosides, the symptoms of one or more phytotoxicities in the treated crop are reduced by 10% to 90%, 10% to 70%, 10% to 50%, 10% to 30%, 30% to 90%, 50% to 90%, 70% to 90%, 30% to 70%, or 30% to 50%.

[0143] In some embodiments, phytotoxicity symptoms are measured by a phytotoxicity rating, for example, as described in Example 1 herein. In some embodiments, the blend is characterized in that the phytotoxicity rating in the treated crop (e.g., as described in Example 1 herein) is reduced by at least 10% relative to a comparable composition lacking one or more ascarosides. In some embodiments, the provided method is characterized in that the phytotoxicity rating (e.g., as described in Example 1 herein) is reduced by at least 15%, at least 20%, at least 25%, at least 35%, at least 50%, at least 75%, or at least 90% relative to a comparable composition lacking one or more ascarosides. In some embodiments, the blend is characterized in that the phytotoxicity rating in the treated crop (e.g., as described in Example 1 herein) is reduced by 10% to 90%, 10% to 70%, 10% to 50%, 10% to 30%, 30% to 90%, 50% to 90%, 70% to 90%, 30% to 70%, or 30% to 50% relative to a comparable composition lacking one or more ascarosides.

[0144] In some embodiments, the phytotoxic effects that can be reduced by using ascaroside are selected from the group consisting of: poor germination; seedling death; death or damage to rapidly growing fleshy tissue; slow or delayed plant development; malformation or deformity of plant, fruit, or leaf; rust spots or bronze discoloration of leaves or fruit; necrotic spots or patches on leaves; necrosis of leaf tips or leaf margins; necrosis of interveinal areas of leaves; and any combination of two or more of these.

[0145] The compounds described herein may be provided as a single formulation or agricultural composition, or as separate formulations or agricultural compositions. Alternatively, these components may be applied separately. When one or more ascarosides and one or more insecticides are applied separately, the one or more ascarosides may be applied before or after the application of the one or more insecticides. Typically, when applied separately, the components are applied together at close points in time, for example substantially simultaneously or within about a few minutes or hours (including within about 5 minutes, about 10 minutes, about 30 minutes, about one hour, about 2 hours, about 3 hours, about 4 hours, about 6 hours, about 7 hours, about 8 hours, about 24 hours, or about 2 days).

[0146] In some embodiments, co-application may involve combining one or more ascarosides and one or more insecticides before application to the plants (e.g., just before application). One or more ascarosides and one or more insecticides may be mixed in the field; for example, one or more ascarosides may be added to a tank mixture containing one or more insecticides.

[0147] In other embodiments, the components to be applied together can be combined at a point in time prior to application. In such embodiments, an agricultural formulation is prepared comprising a combination of one or more ascarosides and one or more insecticides with one or more inert ingredients. Advantageously, in such combinations, one or more ascarosides and one or more insecticides are compatible with each other, and the resulting formulation can exhibit stability over long periods of time (e.g., about one week or longer, about one month or longer, about two months or longer, about three months or longer, about four months or longer, about five months or longer, or about six months or longer).

[0148] One or more ascarosides and one or more insecticides can be formulated together in a combination formulation. As mentioned above, the formulation or method may include other active ingredients and / or plant or plant product treatment compounds. Furthermore, some compositions may leave residues because they are not easily washed off the leaves during rain, thus protecting the plants during and after rain.

[0149] In some embodiments, this disclosure provides blends of one or more insecticides and one or more ascarosides, wherein the weight ratio of the one or more insecticides to ascarosides is greater than 10:1, greater than 100:1, greater than 500:1, or greater than 1000:1. In some embodiments, this disclosure provides blends of insecticides and ascarosides, wherein the weight ratio of the insecticides to ascarosides 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.

[0150] The formulation or composition can be formulated according to conventional methods in the art and can be a liquid or dry composition. Dry compositions include powders, etc. The composition can be used as a liquid concentrate, a ready-to-use (RTU) liquid spray, a powder, or a solid, depending on the user's needs. The selected formulation will depend on the intended use of the product. When in use, the composition can be applied directly to the plant.

[0151] Generally, formulations will include at least one ascaridin as described herein, or at least one ascaridin 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, etc. Adjuvants may be added to formulations or, alternatively, may be added separately when applied to crops. In some embodiments, wetting agents, emulsifiers, spreading agents, etc., may be used in formulations. Formulations include concentrated forms in which the active agents of the invention (compounds as described herein) are present at a concentration of 0.001% to 98.0%, with the remainder being a physiologically acceptable carrier. Such formulations (especially those containing less than 50% of the compounds of the invention) can sometimes be used directly, but these formulations may also be diluted with other physiologically acceptable carriers to form more diluted treatment formulations. These subsequent formulations may contain a lower concentration of 0.001% to 0.1% of the compounds described herein.

[0152] The formulation may additionally contain "adjuvant surfactants" to enhance the deposition, wetting, and penetration of the compound on target crops and organisms. These "adjuvant surfactants" may optionally be used as components of the formulation or as canister mixtures. The amount of adjuvant surfactant is typically 0.01 to 1.0% by volume, preferably 0.05 to 0.5% by volume, based on the water spray volume. Suitable adjuvant surfactants include, but are not limited to, ethoxylated nonylphenol, ethoxylated synthetic or natural alcohols, esters or sulfosuccinic acid salts, ethoxylated silicones, ethoxylated fatty amines, blends of surfactants with mineral or vegetable oils, crop oil concentrates (mineral oil (85%) + emulsifier (15%)); nonylphenol ethoxylates; benzyl coconut oil alkyl dimethyl quaternary ammonium salts; blends of petroleum hydrocarbons, alkyl esters, organic acids and anionic surfactants; C9-Cu alkyl polysaccharides; phosphorylated alcohol ethoxylates; natural primary alcohols (C12 to Ci6) ethoxylates; di-sec-butylphenol EO-PO block copolymers; polysiloxane-methyl caps; nonylphenol ethoxylates + urea ammonium nitrate; emulsified methylated seed oils; tridecanol (synthetic) ethoxylates (8EO); animal fat amine ethoxylates (15EO); PEG (400) dioleate-99. Formulations may also include oil-in-water emulsions.

[0153] "Surfactant" typically constitutes about 0.5% to about 10% of the wettable powder. "Surfactant" includes sulfonated lignin, condensed naphthalene sulfonate, naphthalene sulfonate, alkylbenzene sulfonate, alkyl sulfonate, or nonionic surfactants such as ethylene oxide adducts of alkylphenols or mixtures thereof.

[0154] Representative organic solvents that can be used to prepare emulsifiable concentrates of one or more of the disclosed ascarosides and / or one or more insecticides are aromatic liquids, such as xylene, propylbenzene fractions; or mixed naphthalene fractions, mineral oils, substituted aromatic organic liquids such as dioctyl phthalate; kerosene; dialkylamides of various fatty acids, especially dimethylamides of fatty glycols and their derivatives, such as butyl ether, ethyl ether, or methyl ether of diethylene glycol, methyl ether of triethylene glycol, petroleum fractions or hydrocarbons such as mineral oils, aromatic solvents, paraffin oils, etc.; terpene solvents, rosin derivatives, aliphatic ketones such as cyclohexanone, complex aliphatic and aromatic alcohols such as 2-ethoxyethanol, vegetable oils such as soybean oil, rapeseed oil, olive oil, castor oil, sunflower oil, coconut oil, corn oil, cottonseed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil, etc.; esters of the above vegetable oils; etc. Mixtures of two or more organic liquids can also be used to prepare emulsifiable concentrates. Organic liquids include xylene and propylbenzene fractions, with xylene being the preferred choice in some cases. Surfactant dispersants are commonly used in liquid formulations, and their dosage ranges from 0.1 to 20% by weight, based on the combined weight of the dispersant with one or more compounds.

[0155] "Emulsifiers" used for emulsifiable concentrates are typically mixtures of ionic and / or nonionic surfactants, such as those mentioned herein or their equivalents. Examples of nonionic emulsifiers that can be used to prepare emulsifiable concentrates include polyalkylene glycol ethers and condensation products of alkyl and aryl phenols, fatty alcohols, fatty amines, or fatty acids with ethylene oxide or propylene oxide, such as ethoxylated alkylphenols and carboxylic acid esters solubilized with polyols or polyoxyethylenes. Cationic emulsifiers include quaternary ammonium salts and fatty amine salts. Anionic emulsifiers include oil-soluble salts of alkyl aryl sulfonic acids (e.g., calcium), oil-soluble salts, or suitable salts of sulfated and phosphorylated polyethylene glycol ethers.

[0156] Powders containing one or more ascarosides and / or one or more insecticides can be prepared by tightly mixing one or more powdered compounds with a suitable powdered agricultural carrier (such as, for example, kaolin, ground volcanic rock, etc.). Based on the total weight of the powder, the powder may suitably contain about 1 to about 10% by weight of the compound.

[0157] Wettable powders can be formed into clumps or compacted to form water-dispersible particles. These particles comprise a mixture of compounds, an inert carrier suitable for particle application, and a surfactant. The concentration of the compound is typically between about 0.1% by weight and about 90% by weight. "Inert carriers suitable for particle application" are typically wax stone, talc, chalk, gypsum, bleaching clay, bentonite, palygorskite, starch, casein, gluten, montmorillonite clay, diatomaceous earth, purified silicates, etc. In such operations, the finely chopped carrier and surfactant are typically blended with one or more compounds and ground.

[0158] An "aqueous suspension" can be prepared in which one or more ascarosides and / or one or more insecticides are dispersed in an aqueous medium at a concentration typically ranging from about 5% to about 50% by weight. The suspension is prepared by finely grinding the compound and vigorously mixing it into a medium of water, surfactants, and dispersants. Inert components such as inorganic salts and synthetic or natural gums can also be used to increase the density and / or viscosity of the aqueous medium as needed.

[0159] As described herein, the compositions and methods of the present invention can be used to mitigate the phytotoxic effects of insecticides on treated crops. The method comprises applying an effective amount of a combination of an ascaridin composition and an insecticide composition to seeds, plants, plant leaves, or the soil in which the plants grow.

[0160] definition

[0161] To facilitate understanding of this disclosure, certain terms are defined below. Further definitions for these and other terms are set forth throughout the specification. In this application, unless clearly apparent from the context, the term "an" or "a" may be understood to mean "at least one / a kind".

[0162] As used in this application, the term "or" can be understood to mean "and / or". In this application, the terms "comprising" and "including" can be understood to cover the listed components or steps, whether presented alone or together with one or more other components or steps. As used in this application, the term "comprise" and variations thereof (such as "comprising" and "comprises") are not intended to exclude other additives, components, wholes, or steps.

[0163] About, approximately: As used herein, the terms “about” and “approximately” are used equivalently. Unless otherwise stated, the terms “about” and “approximately” are to be understood as allowing for standard variations as would be understood by one of ordinary skill in the art. Where the scope provided herein includes endpoints. Any numbers used in this application with or without “about” are intended to cover any normal fluctuations as understood by one of ordinary skill in the relevant art. In some embodiments, the terms “about” or “approximately” refer to a range of values ​​of 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 of the specified reference value, unless otherwise stated or clearly apparent from the context (except where such a number would exceed 100% of the possible value).

[0164] The definitions of specific functional groups and chemical terms are described in more detail below. For the purposes of this invention, chemical elements are identified according to the Periodic Table of the Elements, CAS edition, Handbook of Chemistry and Physics, 75th edition, inner cover, and specific functional groups are generally defined as described herein. Furthermore, general principles of organic chemistry, as well as specific functional groups and reactivity, are described in the following references: Organic Chemistry, Thomas Sorrell, University Science Books, Sausalito, 1999; Smith and March March's Advanced Organic Chemistry, 5th edition, John Wiley & Sons, Inc., New York, 2001; Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989; Carruthers, Some Modern Methods of Organic Synthesis, 3rd edition, Cambridge University Press, Cambridge, 1987; the entire contents of each reference are incorporated herein by reference.

[0165] Some of the compounds provided herein may include one or more asymmetric centers and therefore may exist in a variety of stereoisomeric forms, such as enantiomers and / or diastereomers. Thus, the compounds and compositions thereof of the present invention may be in the form of individual enantiomers, diastereomers, or geometric isomers, or may be in the form of mixtures of stereoisomers. In some embodiments, the compounds described herein are enantiomerically pure compounds. In some other embodiments, mixtures of enantiomers or diastereomers are provided.

[0166] Furthermore, unless otherwise indicated, some compounds described herein may have one or more double bonds that can exist as Z or E isomers. Compounds may be provided as single isomers substantially free of other isomers, and alternatively as mixtures of various isomers, such as racemic mixtures of enantiomers.

[0167] As used herein, the term "isomer" includes any and all geometric and stereoisomers. For example, "isomer" includes cis- and trans-isomers, E- and Z-isomers, R- and S-enantiomers, diastereomers, (D)- and (L)-isomers, racemic mixtures thereof, and other mixtures thereof, all of which fall within the scope of this disclosure. For example, in some embodiments, the compound may be provided substantially free of one or more corresponding stereoisomers and may also be referred to as "stereochemically enriched".

[0168] When a particular enantiomer is preferred, in some embodiments it may be provided substantially free of the opposite enantiomer and may also be referred to as “optically enriched.” As used herein, “optically enriched” means that the compound consists of a significantly larger proportion of one enantiomer. In some embodiments, the compound consists of at least about 90% enantiomers by weight. In some embodiments, the compound consists of at least about 95%, 97%, 98%, 99%, 99.5%, 99.7%, 99.8%, or 99.9% enantiomers by weight. In some embodiments, the enantiomer excess of the provided compound is at least about 90%, 95%, 97%, 98%, 99%, 99.5%, 99.7%, 99.8%, or 99.9%. In some embodiments, the enantiomers may be isolated from a racemic mixture or prepared by any method known to those skilled in the art, including chiral high-performance liquid chromatography (HPLC) and the formation and crystallization of chiral salts. See, for example, Jacques et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen, SH et al., Tetrahedron 33:2725 (1977); Eliel, ELStereochemistry of Carbon Compounds (McGraw–Hill, New York, 1962); Wilen, SH Tables of Resolving Agents and Optical Resolutions, p. 268 (edited by Eliel, Univ. of Notre Dame Press, Notre Dame, IN 1972).

[0169] As used herein, the terms “halo” and “halogen” refer to atoms selected from fluorine (fluorinated, -F), chlorine (chlorinated, -Cl), bromine (brominated, -Br), and iodine (iodinated, -I).

[0170] As used herein, the term "aliphatic" or "aliphatic group" means a hydrocarbon moiety that can be linear (i.e., unbranched), branched, or cyclic (including fused, bridged, and spirofused polycyclic rings) and can be fully saturated or may contain one or more unsaturated units but is not aromatic. Unless otherwise stated, an aliphatic group contains 1 to 30 carbon atoms. In some embodiments, the aliphatic group contains 1 to 12 carbon atoms. In some embodiments, the aliphatic group contains 1 to 8 carbon atoms. In some embodiments, the aliphatic group contains 1 to 6 carbon atoms. In some embodiments, the aliphatic group contains 1 to 5 carbon atoms; in some embodiments, the aliphatic group contains 1 to 4 carbon atoms; in still other embodiments, the aliphatic group contains 1 to 3 carbon atoms; and in still other embodiments, the aliphatic group contains 1 to 2 carbon atoms. Suitable aliphatic groups include, but are not limited to, linear or branched alkyl, alkenyl, and alkynyl groups and their hybrids, such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl, or (cycloalkyl)alkenyl.

[0171] As used herein, the term "heteroaliphatic" or "heteroaliphatic group" refers to an aliphatic group in which one or more carbon or hydrogen atoms are replaced by heteroatoms (e.g., oxygen, nitrogen, sulfur, phosphorus, boron, etc.). In some embodiments, the heteroaliphatic group is a heterocyclic group.

[0172] As used in this article, the term "unsaturated" means that a portion of the material has one or more double or triple bonds.

[0173] As used herein, the term "alkyl" refers to a saturated straight-chain or branched hydrocarbon group derived by removing a single hydrogen atom from an aliphatic portion containing one to six carbon atoms. Unless otherwise stated, an alkyl group contains 1 to 12 carbon atoms. In some embodiments, the alkyl group contains 1 to 8 carbon atoms. In some embodiments, the alkyl group contains 1 to 6 carbon atoms. In some embodiments, the alkyl group contains 1 to 5 carbon atoms; in some embodiments, the alkyl group contains 1 to 4 carbon atoms; in still other embodiments, the alkyl group contains 1 to 3 carbon atoms; and in still other embodiments, the alkyl group contains 1 to 2 carbon atoms. Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, sec-pentyl, isopentyl, tert-butyl, n-pentyl, neopentyl, n-hexyl, sec-hexyl, n-heptyl, n-octyl, n-decyl, n-undecyl, dodecyl, etc.

[0174] As used herein, the term "alkenyl" refers to a monovalent group derived by removing a single hydrogen atom from a straight-chain or branched aliphatic moiety having at least one carbon-carbon double bond. Unless otherwise stated, an alkenyl group contains 2 to 12 carbon atoms. In some embodiments, the alkenyl group contains 2 to 8 carbon atoms. In some embodiments, the alkenyl group contains 2 to 6 carbon atoms. In some embodiments, the alkenyl group contains 2 to 5 carbon atoms; in some embodiments, the alkenyl group contains 2 to 4 carbon atoms; in still other embodiments, the alkenyl group contains 2 to 3 carbon atoms; and in still other embodiments, the alkenyl group contains 2 carbon atoms. Alkenyl groups include, for example, vinyl, propenyl, butenyl, 1-methyl-2-buten-1-yl, etc.

[0175] The term "aryl," used alone or as part of a larger part such as in "aralkyl," "arylalkoxy," or "aryloxyalkyl," refers to a monocyclic or polycyclic system 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. The term "aryl" may be used interchangeably with the term "aryl ring." In some embodiments, "aryl" refers to an aromatic ring system including, but not limited to, phenyl, biphenyl, naphthyl, anthracene, etc., which may have one or more substituents. As used herein, the term "aryl" also includes groups within its scope where the aromatic ring is fused to one or more additional rings, such as benzofuranyl, indanyl, phthalimide, naphthimide, phenanthridine, or tetrahydronaphthyl.

[0176] The terms "heteroaryl" and "heteroary-" used alone or as part of a larger portion, such as "heteroarylalkyl" or "heteroarylalkoxy," refer to groups having 5 to 10 ring atoms, preferably 5, 6, or 9 ring atoms; groups sharing 6, 10, or 14 p electrons in a cyclic array; and groups having one to five heteroatoms in addition to a carbon atom. The term "heteroatom" refers to nitrogen, oxygen, or sulfur, and includes any oxidized form of nitrogen or sulfur, and any quaternized form of basic nitrogen. Heteroaryl groups include, but are not limited to, thienyl, furanyl, pyrroleyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indoleazinyl, purine, naphridinyl, and pteridinyl. As used herein, the terms “heteroaryl” and “heteroary-” also include groups fused to one or more aryl, alicyclic, or heterocyclic rings, wherein the group or connecting point is located on the heteroaryl ring. Non-limiting examples include indolyl, isoindolyl, benzothiopheneyl, benzofuranyl, dibenzofuranyl, indazoleyl, benzimidazolyl, phenthiazolyl, quinolinyl, isoquinolinyl, cenolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 4H-quinazinyl, carbazolyl, acridineyl, phenazinyl, phenothiazinyl, phenotoxazinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and pyrido[2,3–b]–1,4–oxazin–3(4H)–one. Heteroaryl groups can be monocyclic, bicyclic, bridged bicyclic, or spirocyclic. The term "heteroaryl" may be used interchangeably with the terms "heteroaryl ring," "heteroaryl group," or "heteroaromatic," any of which includes optionally substituted rings. The term "heteroarylalkyl" refers to an alkyl group substituted with a heteroaryl group, wherein the alkyl and heteroaryl portions are independently optionally substituted. The term "heteroarylenyl" refers to a divalent heteroaryl group (e.g., pyridinylenyl).

[0177] As used herein, the terms “heterocycle,” “heterocyclic group,” “heterocyclic group,” and “heterocyclic ring” are used interchangeably and refer to a stable 5- to 7-membered monocyclic or 7- to 10-membered bicyclic heterocyclic portion that is saturated or partially unsaturated and has one or more, preferably one to four, heteroatoms as defined above, in addition to a carbon atom. When referring to the ring atom of the heterocycle, the term “nitrogen” includes substituted nitrogen. As an example, in a saturated or partially unsaturated ring having 0 to 3 heteroatoms selected from oxygen, sulfur, or nitrogen, nitrogen can be N (as in 3,4-dihydro-2H-pyrrole), NH (as in pyrrolidinyl), or +NR (as in N-substituted pyrrolidinyl).

[0178] Heterocycles can be attached to their side groups at any heteroatom or carbon atom to produce a stable structure, and any ring atom can optionally be substituted. Examples of such saturated or partially unsaturated heterocyclic groups include, but are not limited to, tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolyl, piperidinyl, pyrrololinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazine, dioxalyl, dioxopentyl, diazazyl, oxonitrile, thioazazyl, morpholinyl, and quininecycloyl. The terms “heterocycle,” “heterocyclic group,” “heterocyclic ring,” “heterocyclic moiety,” and “heterocyclic group” are used interchangeably herein and also include groups fused with one or more aryl, heteroaryl, or alicyclic rings, such as dihydroindolyl, 3H-indolyl, benzodihydropyranyl, phenanthridine, or tetrahydroquinolinyl. In some embodiments, the heterocycle may be a 5- to 12-membered bicyclic, bridged bicyclic, or spirocyclic. The heterocycle may contain one or more oxo (=O) or thio (=S) substituents. The term "heterocyclic alkyl" refers to an alkyl group substituted with a heterocyclic group, wherein the alkyl and heterocyclic portions are optionally substituted independently.

[0179] As used herein, the term "partially unsaturated" refers to a ring moiety containing at least one double or triple bond. The term "partially unsaturated" is intended to cover rings having multiple unsaturated sites, but not to include aryl or heteroaryl moiety as defined herein.

[0180] As described herein, compounds provided herein may contain an "optionally substituted" moiety. Generally, the term "substituted," whether or not preceded by the term "optionally," means that one or more hydrogen atoms of the specified moiety are replaced by suitable substituents. Unless otherwise indicated, the "optionally substituted" group may have suitable substituents at each substituted position of the group, and the substituents at each position may be the same or different when more than one position in any given structure is substituted by more than one substituent selected from the specified group. The contemplated combinations of substituents are preferably those that result in the formation of stable or chemically viable compounds. The term "stable" as used herein means that the compound remains substantially unchanged when subjected to conditions that allow it to be generated, detected, and, in some embodiments, recovered, purified, and used for one or more purposes disclosed herein.

[0181] The suitable monovalent substituent on the substituted carbon atom of the "optionally substituted" group is independently a halogen; –(CH2) 0–4 R°;–(CH2) 0–4 OR°;-O-(CH2) 0-4 C(O)OR°;–(CH2) 0–4 CH(OR°)2;–(CH2) 0–4 SR°;–(CH2)0– 4Ph, which can be substituted via R°; –(CH2) 0–4 O(CH2) 0–1 Ph, which can be substituted by R°; –CH=CHPh, which can be substituted by R°; –NO2; -CN; –N3; –(CH2) 0–4 N(R°)2;–(CH2) 0–4 N(R°)C(O)R°; –N(R°)C(S)R°; –(CH2) 0-4 N(R°)C(O)NR°2; –N(R°)C(S)NR°2; –(CH2) 0–4 N(R°)C(O)OR°; -N(R°)N(R°)C(O)R°; –N(R°)N(R°)C(O)NR°2; –N(R°)N(R°)C(O)OR°; –(CH2) 0–4 C(O)R°;-C(S)R°;–(CH2) 0–4 C(O)OR°;–(CH2) 0–4 C(O)N(R°)2;–(CH2) 0–4 C(O)SR°;–(CH2) 0–4 C(O)OSiR°3;–(CH2) 0–4 OC(O)R°;–OC(O)(CH2) 0–4 SR–, SC(S)SR°; –(CH2) 0–4 SC(O)R°;–(CH2) 0–4 C(O)NR°2; -C(S)NR°2; –C(S)SR°; –SC(S)SR°, –(CH2) 0–4 OC(O)NR°2; –C(O)N(OR°)R°; –C(O)C(O)R°; –C(O)CH2C(O)R°; –C(NOR°)R°; –(CH2) 0–4 SSR°;–(CH2) 0– 4S(O)2R°;–(CH2) 0–4 S(O)₂OR°;-(CH₂) 0–4 OS(O)2R°; –S(O)2NR°2; –(CH2) 0–4 S(O)R°; –N(R°)S(O)2NR°2; –N(R°)S(O)2R°; –N(OR°)R°; –C(NH)NR°2; –P(O)2R°; –P(O)R°2; –OP(O)R°2; –OP(O)(OR°)2; SiR°3; –(C 1–4 (linear or branched alkylene)O–N(R°)2; or –(C 1–4(straight-chain or branched alkylene)C(O)O–N(R°)2, wherein each R° can be substituted as defined below and is independently hydrogen, C 1-8 Aliphatic, –CH2Ph, –O(CH2) 0–1 Ph or a 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 independent heteroatoms selected from nitrogen, oxygen, or sulfur; or, in addition to the above definitions, two independently occurring R° together with one or more intermediate atoms to form a 3- to 12-membered saturated, partially saturated, or aryl monocyclic or polycyclic ring having 0 to 4 independent heteroatoms selected from nitrogen, oxygen, or sulfur, which may be substituted as defined below.

[0182] The appropriate monovalent substituent of R° is independently a halogen, –(CH2), along with its intermediate atom. 0–2 R –(halogenated R) ), –(CH2) 0–2 OH, –(CH2) 0–2 OR –(CH2) 0–2 CH(OR )2;-O(halogenated R –CN, –N3, –(CH2) 0–2 C(O)R –(CH2) 0–2 C(O)OH, –(CH2) 0–2 C(O)OR -(CH2) 0-4 C(O)N(R°)2;–(CH2) 0–2 SR –(CH2) 0–2 SH, –(CH2) 0–2 NH2、–(CH2) 0–2 NHR -(CH2) 0-2 NR 2, –NO2, –SiR 3. –OSiR 3. –C(O)SR 、–(C 1–4 (straight-chain or branched alkylene)C(O)OR Or –SSR , where each R It is either unsubstituted or, in the case of the prefix "halogenated", substituted with only one or more halogens, and independently selected from C. 1–4 Aliphatic, -CH2Ph, –O(CH2) 0–1Ph or a 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents on the saturated carbon atom of R° include =O and =S.

[0183] Suitable divalent substituents on the saturated carbon atom of the "optionally substituted" group include the following: =O, =S, =NNR. * 2、=NNHC(O)R * =NNHC(O)OR * =NNHS(O)2R * =NR * =NOR * 、 –O(C(R) * 2)) 2–3 O – or –S(C(R) * 2)) 2– 3S–, where R appears independently each time * Selected from hydrogen, and C that can be substituted as defined below. 1–6 Aliphatic or unsubstituted 5- to 6-membered saturated, partially unsaturated, or aryl rings having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents bonded to the ortho-substituted carbon of the "optionally substituted" group include: –O(CR * 2) 2–3 O–, where each independently occurring R * Selected from hydrogen, C can be substituted as defined below. 1–6 Aliphatic, or having 0 to 4 unsubstituted 5 to 6 saturated, partially unsaturated or aryl rings independently selected from nitrogen, oxygen or sulfur.

[0184] R * Suitable substituents on aliphatic groups include halogens, -R -(halogenated R) –OH, –OR –O (halogenated R) ), –CN, –C(O)OH, –C(O)OR –NH2, –NHR –NR 2 or –NO2, where each R It is either unsubstituted or, in the case of the prefix "halogenated", substituted with only one or more halogens, and is independently C. 1–4 Aliphatic, –CH2Ph, –O(CH2) 0–1 Ph or a 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0185] Suitable substituents on the substituted nitrogen of the "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 † -S(O)2NR † 2. –C(S)NR † 2. –C(NH)NR † 2 or –N(R) † )S(O)2R † ; where each R † Independently, hydrogen can be substituted C as defined below. 1-6 Aliphatic, unsubstituted -OPh, or an unsubstituted 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0-4 independently selected heteroatoms chosen from nitrogen, oxygen, or sulfur; or, in addition to the above definitions, two independently occurring R... † Together with its intermediate atom, it forms an unsubstituted 3 to 12-membered saturated, partially unsaturated, or aryl monocyclic or bicyclic ring with 0 to 4 independent heteroatoms selected from nitrogen, oxygen, or sulfur.

[0186] R † Suitable substituents on the aliphatic group can be halogens, -R –(halogenated R) –OH, –OR –O (halogenated R) ), –CN, –C(O)OH, –C(O)OR –NH2, –NHR –NR 2 or -NO2, where each R It is either unsubstituted or, in the case of the prefix "halogenated", substituted with only one or more halogens, and is independently C. 1–4 Aliphatic, –CH2Ph, –O(CH2) 0–1 Ph or a 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0187] As used in this article, the term “substantially” refers to a qualitative condition that exhibits all or nearly all of the scope or degree of the intended characteristics or properties.

[0188] Sometimes, a convention is used to name ascarosides with a few letters prefixed followed by a hash symbol (#) and a number (e.g., ascr#18). This convention is used in scientific literature, and those skilled in the art will understand that each such name relates to a specific chemical structure of known composition and will readily understand the structure of the molecule referred to using this naming convention. Unless otherwise indicated, all compound identifiers in this format used herein conform to the definitions described in the Small Molecule Identifiers Database for Caenorhabditis elegans (SMID-DB) maintained on the World Wide Web smid-db.org.

[0189] Embodiments of the present invention include:

[0190] 1. A method for reducing phytotoxic side effects on plants associated with the application of an insecticide, the method comprising contacting a plant or plant part with an effective amount of a combination of agents comprising at least one ascaridin and at least one insecticide, wherein the effective amount reduces phytotoxic side effects on the crop plant compared to phytotoxic side effects associated with the application of the insecticide alone.

[0191] 2. According to the method described in Example 1, wherein the at least one insecticide is an alkaloid insecticide, an alkyl halide insecticide, an aminopyrimidine insecticide, an aminotriazine insecticide, an antibiotic insecticide, an aromatic hydrocarbon insecticide, an arylpyrrole insecticide, a benzimidazole insecticide, a benzoylurea insecticide, a β-ketonitrile insecticide, a plant insecticide, a carbamate insecticide, a dihydrazide insecticide, a diamide insecticide, a dinitrophenol insecticide, a dithiopentane insecticide, a formamid insecticide, a fumigant insecticide, an inorganic insecticide, an isoxazoline insecticide, a juvenile hormone mimic, a macrolide insecticide, or a meta-dioxazoline insecticide. Amide insecticides, methoxyacrylate insecticides, neonicotinoid insecticides, nereistoxin analog insecticides, organochlorine insecticides, organophosphorus insecticides, oxadiazine insecticides, oxadiazon insecticides, perfluoroalkyl sulfonamide insecticides, phenol insecticides, pyrethroid insecticides, pyrethroid insecticides, pyridazine insecticides, pyridine azomethyl insecticides, pyrimidine amine insecticides, propylene insecticides, RNA1 insecticides, salicylaniline insecticides, amine urea insecticides, steroid insecticides, tertran acid insecticides, terfenic acid insecticides, thiocarbonate insecticides, thiourea insecticides, or urea insecticides.

[0192] 3. The method according to Example 1, wherein the at least one insecticide is an alkaloid insecticide selected from the group consisting of: neonicotinoids, matrine, nicotine, nornicotinoids, oxymatrine, ryanodine, rhodane, veratrum saba, and sanguisorbin.

[0193] 4. The method according to Example 1, wherein the 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, iodomethane, methyl chloroform, dichloromethane, and tetrachloroethane.

[0194] 5. The method according to Example 1, wherein the at least one insecticide is desinil, cyprofen, acyclovir, naphthalene, benzothiamethoxam, bromonitrile, fenproxazole, thiamethoxam, nitropropoxyphenate, pendimethalin, 4-6-dinitro-o-cresol (DNOC), isoprothiolane, amitraz, chlorfenapyr, amitraz, or methyl amitraz.

[0195] 6. The method according to Example 1, wherein the at least one insecticide is a benzoylurea insecticide selected from the group consisting of: bis(triflufenoxuron), chlorfenapyr, chlorofluorourea, dichlorofluorourea, diflubenzuron, flucyclobenzamide, flufenoxuron, hexafluorourea, lufenuron, novaron, polyfluorourea, flufenoxuron, fenflurfen, and chlorfenapyr.

[0196] 7. The method according to Example 1, wherein the at least one insecticide is a plant insecticide selected from the following: allicin, azadirachtin, carvacrol, d-limonene, quassula, rhododendron toxin-III, rotenone and triptolide.

[0197] 8. The method according to Example 1, wherein the at least one insecticide is a carbamate insecticide selected from the group consisting of: carbaryl, aldicarb, oxydicarb, chlorpyrifos, chlorpyrifos, thiamethoxam, carbaryl, chlorpyrifos, methylcarbide, methylcarbide, chlorpyrifos, carbamate, carbofuran, thiamethoxam, chlorpyrifos, 2-chlorophenylmethylcarbamate (CPMC), carbofuran, dimethylphenol, dimethoate, methylcarbide, and chlorpyrifos. Dioxane, p-(ethylthio)phenylmethylcarbamate (EMPC), ethyl thiocarbamate, fenthiocarbamate, sec-butylcarbamate, chlorfenapyr, fenpropathrin, furazolidone, quinoxalic acid, isoxacarb, isopropylcarbamate, methyl thiocarbamate, methomyl, fenpropathrin, acetamiprid, pyrimethanil, pyrazocarb, thiamethoxam, thiamethoxam, thiamethoxam, thiamethoxam, thiamethoxam, 3,5-xylylmethylcarbamate (XMC) and xylenecarbamate.

[0198] 9. The method according to Example 1, wherein the at least one insecticide is a diamide insecticide selected from the group consisting of: chlorantraniliprole, broflaniprole, chlorfluazuron, cyclobromhizometamide, flufenoxuron, flufenoxuron, tetrachlorantraniliprole, flufenoxuron, and thiofenoxuron.

[0199] 10. The method according to Example 1, wherein the at least one insecticide is a fumigant selected from the group consisting of: acrylonitrile, allyl isothiocyanate, calcium cyanide, carbon disulfide, carbon tetrachloride, carbonyl sulfide, chloroform, chloropicrin, cyanide, 1,2-dichloropropane, dimethyl disulfide, ethyl formate, ethylene dibromide, ethylene dichloride, ethylene oxide, hydrogen cyanide, methyl bromide, iodomethane, methyl isothiocyanate, methyl chloroform, dichloromethane, phosphine, sodium cyanide, thiocyanate fluoride, and tetrachloroethane.

[0200] 11. The method according to Example 1, wherein the 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 fluorosilicate, sodium thiocyanate, and thioyl fluoride.

[0201] 12. The method according to Example 1, wherein the at least one insecticide is an isoxazoline insecticide selected from the group consisting of: afolanar, esafolanar, flerolanar, fluoxazolamide, isoxazolamide, lentilana, mivorana, salorana, ticorana, and yumivola.

[0202] 13. The method according to Example 1, wherein the at least one insecticide is a juvenile hormone mimic selected from the group consisting of: tebufenozide, benzyl ether, juvenile ether, phenoxycarb, tebufenozide, juvenile hormone I, juvenile hormone II, juvenile hormone III, tebufenozide, tebufenozide, pyriproxyfen, and tebufenozide thiophanate-methyl.

[0203] 14. The method according to Example 1, wherein the at least one insecticide is a macrolide insecticide selected from the group consisting of: abamectin, doramectin, emamectin, epramycin, ivermectin, rapamectin, moxicillin, cilamectin, ethyl spinosad and spinosad.

[0204] 15. The method according to Example 1, wherein the at least one insecticide is bromfenac, cyprodinil, modorana, flupyridine, indoxacarb, oxadiazon, flusulfanilamide, flufenoxuron, pymetrozine, pyrimethanil, pyrimethanil, lepromazine, chlorfenapyr, cyfluthrin, α-ecdysone, ecdysterone, spirotetramat, methoxypiperidine ethyl ester, spirotetramat, spirodiclofen, spirodiclofen, O,O-diethyldithiocarbamate (EXD), sodium tetrathiocarbonate, bufenozide, flufuran, and sulfadiazine.

[0205] 16. The method according to Example 1, wherein the at least one insecticide is a neonicotinoid insecticide selected from the group consisting of: acetamiprid, thiamethoxam, epoxiconazole, dichloromethazine, dinotefuran, fenmethazine, flupyrflufenoxam, flupyramide, imidacloprid, chlorpyrifos, acetamiprid, nitenpyram, piperazine, flonicamid, thiamethoxam, thiamethoxam, and trifluralin.

[0206] 17. The method according to Example 1, wherein the at least one insecticide is a nereistoxin analog insecticide selected from the group consisting of: chlorpyrifos, fenitrothion, polythiazide, cyclohexane, and dichlorvos.

[0207] 18. The method according to Example 1, wherein the at least one insecticide is an organochlorine insecticide selected from the group consisting of: aldrin, α-endosulfan, bromoxynil, p,p-dibromo-diphenyl-1,1,1-trichloroethane (bromo-DDT), toxaphene, borneol, chlordane, chlorpheniramine, dichlorodiphenyltrichloroethane (DDT), difluorodiphenyltrichloroethane (DFDT), dieldrin, dilor, endosulfan, isodrin, 1,1-dichloro-2,2-bis(4-ethylphenyl)ethane (ethyl-DDD), hexachlorocyclohexane (HCH), heptachlorophen, carbapenem, isoaldrin, clenbuterol, lindane, methoxychloride, methylphenidate, p-dichlorobenzene, and tetrachlorodiphenylethane (TDE).

[0208] 19. The method according to Example 1, wherein the at least one insecticide is an organophosphorus insecticide selected from the group consisting of: acephate, housefly phosmet, ethyl phosmet, methamidophos, acephate, ethyl phosmet, methyl pyridinium phosphate, ethyl phosmet, methyl phosmet, azophos, bromophenylenephos, bromothion, ethyl bromothion, butyl phosmet, thionyl phosmet, dichlorvos, trisulfite, chloramidophos, chlorpyrifos, chlorfenapyr, chlorpyrifos, chlorpyrifos, methyl chlorpyrifos, chlorfenapyr, thiamethoxam, fly phosmet, phosmet, phosmet, phosmet, benzoylphos, pyridaben, fruit phosmet, phosmet, phosmet, phosmet, demeton-methyl, demeton-methyl -Methyl, Methionine-S-methyl sulfone, Tebuconazole-O, Tebuconazole-S, Methionine-O, Methionine-O-methyl, Methionine-S, Methyl Methionine, Phosphine chloride, Diazinon, Isochlorpyrifos, Phosphate dichlorvos, Dichlorvos, Phosphate sulfadiazine, Methionol, Methyl chlorpyrifos, Dichlorvos, Ethyl methamidophos, Dithiophos, Indomethacin, Ethyl methamidophos, Propylthion ethyl phosphate (EPN), Propylthion oxychloride analog, Ethyl methamidophos, Ethyl methamidophos, Methionol, S-[(ethyl sulfinyl)methyl]O,O-diisopropyl dithiophosphate (IPSP), Ethyl methamidophos, Valdex, Phosphate dichlorvos, Phosphate dichlorvos, Fenitrothion, Phosphate dichlorvos, Ethyl methamidophos Phosphorus, pyrimethanil, terbufos, fenvalerate, phosmet, phosmet, phosmet, heptenylphos, phosmet, chlorpyrifos, methamidophos, isopropylamine, isopropylamine-methyl, isopropylamine, isoxazophos, phosmet, bromobenzylphos, liliphos, thiamethoxam, malathion, malathion, phosmet, methyl phosmet, phosmet, dithiamethoxam, phosmet sulfoxide, chlorpyrifos, methamidophos, chlorpyrifos, methoxyphos, methyl ethyl phosmet, phosmet, phosmet, phosmet, phosmet, phosmet, naphthalenephos, dibromophos, dimethoate, methyl sulfone, isosulfoxide, sulfone, parathion, methyl parathion, fenthion, phosmet, methamidophos, phosmet, phosmet, phosmet, phosmet, phosmet, phosmet, phosmet Methyl thiophanate, glyphosate, imidacloprid, parachlorothiazoline, phosphamidon, phorate, methyl phorate, pyrimidine phosphamidon, pyrimidine oxyphosphamidon, ethyl pyrimidine phosphamidon, methyl pyrimidine phosphamidon, pyrimidine carbendazim, profenofos, fenpyrophos, ethiophanate-methyl, pyrimidine phosphamidon, pyrimidine phosphamidon, quinalphos, methyl quinalphos, phosphamidon, octamethrin, thiophanate-methyl, thiophanate-methyl, thiophanate-methyl, thiophanate-methyl, thiophanate-methyl, thiophanate-methyl, thiophanate-methyl, butyl pyrimidine phosphamidon, dithion, tetraethyl pyrophosphate (TEPP), terbufos, chlorpyrifos, methyl ethoxyphos, phosphamidon, triazophos, trichlorfon, trichloromethyl phosphamidon-3, phosphonophosphorus, trichloropropoxyphosphorus, pyrimidine phosphamidon, and zopyridine.

[0209] 20. The method according to Example 1, wherein the at least one insecticide is a phenolic insecticide selected from the group consisting of: pentachlorophenol, antijuvenile hormone, precocious hormone I, precocious hormone II and precocious hormone III.

[0210] 21. The method according to Example 1, wherein the at least one insecticide is a pyrazole insecticide selected from the group consisting of: acetamiprid, dipropionylpyridinium, acetamiprid, fipronil, tebufenozide, pyrifluquinazon, pyrazosulfuron, acetamiprid, and vanillin.

[0211] 22. The method according to Example 1, wherein the at least one insecticide is a pyrethroid / pyrethroid insecticide selected from the group consisting of: flufenacet, allethrin, α-cypermethrin, propargyl, lambda-cyhalothrin, β-cypermethrin, bifenthrin, bio-allethrin, bio-ethoxyfen, bio-permethrin, bio-benzylfenoxuron, bromocypermethrin, bromoflumethrin, bromobenzylfenoxuron, benzylene. Pyrethroids, chlorpyrifos, cypermethrin, cis-benzylfuran, pyrethrum, cypermethrin, deltamethrin, cypermethrin, cypermethrin, deltamethrin, deltamethrin, d-trans-chlorpyrifos, tetrafluoromethoxyphen ... Cypermethrin, cypermethrin, fenvalerate, deltamethrin, trifluralin, flufenoxuron, cypermethrin, cypermethrin, γ-trifluorocypermethrin, benzylpyr, heptamethrin, cypermethrin, cypermethrin, jasminylpyr, thiamethoxam, κ-bifenthrin, κ-heptamethrin, λ-trifluorocypermethrin, cypermethrin, methoxyfenozide, cypermethrin, pendimethalin, benzylpyr. Esters, fenpyroxene, propargyl, propargyl, propargyl, propargyl, pyrethrin, benzylfuran, chlorfluazuron, benzylfuran, flusilyl, thiooxime, deltamethrin, cypermethrin, heptamethrin, cyclopentenylpyrethrin, pyrethrin, tetramethylflumethrin, θ-cypermethrin, thiooxime, bromocypermethrin, tetrabromopyrethrin, tetrafluorobenzylpyrethrin, trans-benzylcypermethrin, valerate, and ζ-cypermethrin.

[0212] 23. The method according to Example 1, wherein the at least one insecticide is benzimidazole, thiamethoxam, clomiphene, fentriranil, flumetoquinone, flupyradifurone, fluhexenone, flufenoxuron, indoximetronidazole, mesotrione, lepromazine, mefenoxuron, maltodextrin, nicotinamide, flufenoxuron, oxazolidinyl, trichlorfon, pyridaben, acetamiprid, iodofensyl, thioflupyr, tartaric acid, thiophanate-methyl, azoxystrobin, trichlorfon, or chlorpyrifos.

[0213] 24. The method according to any one of Examples 1 to 23, wherein the at least one ascaroside comprises an ascaroside having structure (I):

[0214]

[0215] in:

[0216] Z represents C, which is arbitrarily substituted. 3-40 Aliphatic groups, and

[0217] R a and R b Each of them is independently -H or an optionally substituted portion of a group consisting of the following: C 1-20 aliphatic, C 1-20 Acyl group, C 1-20 Heteroaliphatic, aryl, heteroaryl, hydroxyl protecting groups, phosphorus-linked functional groups, sulfur-linked functional groups, silicon-linked functional groups, C 2-20 Carbonates (e.g., partially -C(O)OR) c C 2-20 Carbamates (e.g., partially -C(O)N(R) c )2) C 2-20 Thioesters (e.g., partially -C(S)R) c C 2-20 Thiocarbonates (e.g., partially -C(S)OR) c C 2-20 Dithiocarbonates (e.g., partially -C(S)SR) c C 1-20 Thiocarbamates (e.g., partially -C(S)N(R) c 2) The sugar moiety, peptide, polymer chain, or linker to another ascaridin molecule via a bond or carbon-containing linker. Among them, R... c Each occurrence is independently selected from -H, optionally substituted C. 1-12 Aliphatic, optionally substituted C 1-12 Heteroaliphatic, optionally substituted aryl, optionally substituted heteroaryl, polymer chain or linkage to another ascaridin molecule via a bond or carbon-containing linker, wherein R a and R b Together they can form an optionally substituted ring, which optionally contains one or more heteroatoms and optionally contains one or more unsaturated sites.

[0218] 25. The method according to embodiment 24, wherein Z is selected from the group consisting of:

[0219] i.–CH(CH3)–R 1 , where R 1 C is arbitrarily substituted 1-40 Aliphatic groups

[0220] ii.–CH(CH3)–(CH2) n –CO2R 2, where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides;

[0221] iii.–CH(CH3)–(CH2) n –CH=CH-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides;

[0222] iv.–CH(CH3)–(CH2) n –CH(OH)–CH2-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides;

[0223] v.–CH(CH3)–(CH2) n –C(O)–CH2-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides;

[0224] vi. –(CH2) n –CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides;

[0225] vii.–(CH2) n –CH=CH-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides;

[0226] viii.–(CH2) n–CH(OH)–CH2-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides, or nucleotides; and

[0227] ix.–(CH2) n –C(O)–CH2-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides, or nucleotides.

[0228] 26. The method according to embodiment 24, wherein Z is selected from the group consisting of:

[0229] (x)–CH(CH3)–(CH2) n –CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linkage to another ascaridone molecule via a bond or carbon-containing linker.

[0230] (xi)–CH(CH3)–(CH2) n –CH=CH-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linkage to another ascaridone molecule via a bond or carbon-containing linker.

[0231] (xii)–CH(CH3)–(CH2) n –CH(OH)–CH2-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linkage to another ascaridone molecule via a bond or carbon-containing linker.

[0232] (xiii)–CH(CH3)–(CH2) n –C(O)–CH2-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linkage to another ascaridone molecule via a bond or carbon-containing linker.

[0233] (xiv)–(CH2) n –CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linkage to another ascaridone molecule via a bond or carbon-containing linker.

[0234] (xv)–(CH2) n –CH=CH-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linkage to another ascaridone molecule via a bond or carbon-containing linker.

[0235] (xvi)–(CH2) n –CH(OH)–CH2-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20Heteroaliphatic groups, optionally substituted aromatic groups, optionally substituted heteroaryl groups, polymer chains, amino acids, peptides, nucleotides, or linkages to another ascaridone molecule via bonds or carbon-containing linker portions; or

[0236] (xvii)–(CH2) n –C(O)–CH2-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linked to another ascaroside molecule via a bond or carbon-containing linker.

[0237] 27. The method according to any one of Examples 24 to 26, wherein R a and R b Each is -H.

[0238] 28. The method according to any one of Examples 24 to 27, wherein Z is –CH(CH3)–(CH2). n –CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides, or nucleotides.

[0239] 29. The method according to any one of Examples 1 to 28, wherein the at least one ascaroside comprises ascaroside selected from the group consisting of: ascr#9, ascr#10, ascr#16, ascr#18, ascr#20, ascr#22 and ascr#24.

[0240] 30. The method according to any one of Examples 1 to 29, wherein the at least one ascaroside comprises ascr#18.

[0241] 31. The method according to any one of Examples 1 to 30, wherein the at least one ascaroside and the at least one insecticide are applied simultaneously.

[0242] 32. The method according to Example 31, wherein the at least one ascaroside and the at least one insecticide are combined together in a can mixture.

[0243] 33. The method according to any one of Examples 1 to 30, wherein the at least one ascaroside and the at least one insecticide are applied sequentially.

[0244] 34. The method according to any one of Examples 1 to 33, wherein the combination is used as a seed coating.

[0245] 35. A composition comprising at least one ascaroside and at least one insecticide.

[0246] 36. The composition according to Example 35, wherein the at least one ascaroside and the at least one insecticide are present in an effective amount.

[0247] 37. The composition according to Example 35, wherein the at least one insecticide is an alkaloid insecticide, an alkyl halide insecticide, an aminopyrimidine insecticide, an aminotriazine insecticide, an antibiotic insecticide, an aromatic hydrocarbon insecticide, an arylpyrrole insecticide, a benzimidazole insecticide, a benzoylurea insecticide, a β-ketonitrile insecticide, a phytotoxicant, a carbamate insecticide, a dihydrazide insecticide, a diamide insecticide, a dinitrophenol insecticide, a dithiopentane insecticide, a formamid insecticide, a fumigant insecticide, an inorganic insecticide, an isoxazoline insecticide, a juvenile hormone mimic, a macrolide insecticide, or a metabolite. Diamide insecticides, methoxyacrylate insecticides, neonicotinoid insecticides, nereistoxin analog insecticides, organochlorine insecticides, organophosphate insecticides, oxadiazine insecticides, oxadiazon insecticides, perfluoroalkyl sulfonamide insecticides, phenol insecticides, pyrazole insecticides, pyrethroid insecticides, pyrethroid insecticides, pyridazine insecticides, pyridinium chloride insecticides, propylene insecticides, RNA1 insecticides, salicylaniline insecticides, amine urea insecticides, steroid insecticides, tertran acid insecticides, terfenic acid insecticides, thiocarbonate insecticides, thiourea insecticides, or urea insecticides.

[0248] 38. The composition according to Example 35, wherein the at least one insecticide is an alkaloid insecticide selected from the group consisting of: neonicotinoids, matrine, nicotine, nornicotinoids, oxymatrine, ryanodine, rhodane, veratrum salsa and sanguisorbin.

[0249] 39. The composition according to Example 35, wherein the 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, iodomethane, methyl chloroform, dichloromethane, and tetrachloroethane.

[0250] 40. The composition according to Example 35, wherein the at least one insecticide is desinil, cyprofen, acyclovir, naphthalene, benzothiamethoxam, bromonitrile, fenproxil, thiamethoxam, nitropropoxyphenate, pentylnitrophenol, 4-6-dinitro-o-cresol (DNOC), isoprothiolane, amitraz, chlorpyrifos, amitraz, or methyl amitraz.

[0251] 41. The composition according to Example 35, wherein the at least one insecticide is a benzoylurea insecticide selected from the group consisting of: bis(triflufenoxuron), chlorfenapyr, chlorofluorourea, dichlorofluorourea, diflubenzuron, flufenoxuron, flufenoxuron, hexafluorourea, lufenuron, novaron, polyfluorourea, flufenoxuron, fenflurfen, and chlorfenapyr.

[0252] 42. The composition according to Example 35, wherein the at least one insecticide is a plant insecticide selected from the following: allicin, azadirachtin, carvacrol, d-limonene, quassodeoxycholic acid, rhododendron toxin-III, rotenone and triptolide.

[0253] 43. The composition according to Example 35, wherein the at least one insecticide is a carbamate insecticide selected from the group consisting of: carbaryl, aldicarb, oxydicarb, chlorpyrifos, chlorpyrifos, pyridaben, carbofuran, thiamethoxam, chlorpyrifos, methylcarbide, methylcarbide, chlorpyrifos, carbamate, carbofuran, thiamethoxam, chlorpyrifos, 2-chlorophenylmethylcarbamate (CPMC), carbofuran, dimethylphenol, dimethoate, chlorpyrifos, chlorpyrifos Dan, dioxin, p-(ethylthio)phenylmethylcarbamate (EMPC), ethyl thiocarbamate, fenthiocarbamate, sec-butylcarbamate, chlorfenapyr, chlorfenapyr, furazolidone, quinoxalic acid, isoxacarb, isopropylcarbamate, methyl thiocarbamate, methomyl, fenpropathrin, cypermethrin, fenpropathrin, pirimicarb, pyrimethanil, pyrazocarb, thiamethoxam, thiamethoxam, thiamethoxam, thiamethoxam, thiamethoxam, 3,5-xylylmethylcarbamate (XMC) and xylenecarbamate.

[0254] 44. The composition according to Example 35, wherein the at least one insecticide is a diamide insecticide selected from the group consisting of: chlorantraniliprole, broflaniprole, chlorfluazuron, cyclobromhizometamide, flufenoxuron, flufenoxuron, tetrachlorantraniliprole, flufenoxuron, and thiofenoxuron.

[0255] 45. The composition according to Example 35, wherein the at least one insecticide is a fumigant selected from the group consisting of: acrylonitrile, allyl isothiocyanate, calcium cyanide, carbon disulfide, carbon tetrachloride, carbonyl sulfide, chloroform, chloropicrin, cyanide, 1,2-dichloropropane, dimethyl disulfide, ethyl formate, ethylene dibromide, ethylene dichloride, ethylene oxide, hydrogen cyanide, methyl bromide, iodomethane, methyl isothiocyanate, methyl chloroform, dichloromethane, phosphine, sodium cyanide, thiocyanate fluoride, and tetrachloroethane.

[0256] 46. ​​The composition according to Example 35, wherein the 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 fluorosilicate, sodium thiocyanate, and thioyl fluoride.

[0257] 47. The composition according to Example 35, wherein the at least one insecticide is an isoxazoline insecticide selected from the group consisting of: afolanar, esafolanar, flerolanar, fluoxazolamide, isoxazolamide, lentilana, mivorana, salorana, ticorana, and yumivola.

[0258] 48. The composition according to Example 35, wherein the at least one insecticide is a juvenile hormone mimic selected from the group consisting of: tebufenozide, benzyl ether, juvenile ether, phenoxycarb, tebufenozide, juvenile hormone I, juvenile hormone II, juvenile hormone III, tebufenozide, tebufenozide, pyriproxyfen, and tebufenozide thiophanate.

[0259] 49. The composition according to Example 35, wherein the at least one insecticide is a macrolide insecticide selected from the group consisting of: abamectin, doramectin, emamectin, epramycin, ivermectin, rapamectin, moxicillin, cilamectin, ethyl spinosad and spinosad.

[0260] 50. The composition according to Example 35, wherein the at least one insecticide is bromfenac, cyprodinil, modorana, flupyridine, indoxacarb, oxadiazon, flusulfanilamide, flufenoxuron, pymetrozine, pyrimethanil, pyrimethanil, lepromazine, chlorfenapyr, cyfluthrin, α-ecdysone, ecdysterone, spirotetramat, methoxypiperidine ethyl ester, spirotetramat, spirodiclofen, spirodiclofen, O,O-diethyldithiocarbamate (EXD), sodium tetrathiocarbonate, bufenozide, flufuran, and sulfadiazine.

[0261] 51. The composition according to Example 35, wherein the at least one insecticide is a neonicotinoid insecticide selected from the group consisting of: acetamiprid, thiamethoxam, epoxiconazole, dichloromethazine, dinotefuran, fenmethazine, flupyrflurane, flupyramide, imidacloprid, chlorpyrifos, acetamiprid, nitenpyram, piperazine, flonicamid, thiamethoxam, thiamethoxam, and trifluralin.

[0262] 52. The composition according to Example 35, wherein the at least one insecticide is a nereistoxin analog insecticide selected from the group consisting of: chlorpyrifos, fenitrothion, polythiazide, cyclohexane, and dichlorvos.

[0263] 53. The composition according to Example 35, wherein the at least one insecticide is an organochlorine insecticide selected from the group consisting of: aldrin, α-endosulfan, bromoxynil, p,p-dibromo-diphenyl-1,1,1-trichloroethane (bromo-DDT), toxaphene, borneol, chlordane, chlorpheniramine, dichlorodiphenyltrichloroethane (DDT), difluorodiphenyltrichloroethane (DFDT), dieldrin, dilor, endosulfan, isodrin, 1,1-dichloro-2,2-bis(4-ethylphenyl)ethane (ethyl-DDD), hexachlorocyclohexane (HCH), heptachlorophen, carbapenem, isoaldrin, clenbuterol, lindane, methoxychloride, methylphenidate, p-dichlorobenzene, and tetrachlorodiphenylethane (TDE).

[0264] 54. The composition according to Example 35, wherein the at least one insecticide is an organophosphorus insecticide selected from the group consisting of: acephate, housefly phosmet, ethyl phosmet, methamidophos, acephate, ethyl phosmet, methyl pyridinium phosphate, ethyl phosmet, methyl phosmet, azophos, bromophenylenephos, bromothion, ethyl bromothion, butyl phosmet, thionyl phosmet, dichlorvos, trisulfite, chloramidophos, chlorpyrifos, chlorfenapyr, chlorpyrifos, chlorpyrifos, methyl chlorpyrifos, chlorfenapyr, thiamethoxam, fly phosmet, phosmet, phosmet, phosmet, benzoylphos, pyridaben, fruit phosmet, phosmet, phosmet, phosmet, systemic phosmet, systemic phosmet Phosphorus-methyl, Methion-S-methyl sulfone, Tebuphos-O, Tebuphos-S, Methion-O, Methion-O-methyl, Methion-S, Methyl Methion, Phosphine chloride, Diazinon, Isochlorpyrifos, Phosphate dichlorvos, Dichlorvos, Phosphate sulfadiazine, Methionol, Dimethoate, Methyl chlorpyrifos, Dichlorvos, Ethiophos, Phosphate dithiocarbamate, Ethiophos oxychloride, Phosphate dichlorvos, Ethiophos dichlorvos, S-[(ethyl sulfinyl)methyl]O,O-diisopropyl dithiophosphate (IPSP), Ethylpyridinium phosphate, Valdex, Phosphate dichlorvos, Phosphate dichlorvos, Fenitrothion, Phosphate dichlorvos, Phosphate dichlorvos, Phosphate dichlorvos, Phosphate dichlorvos, Ethiophos dichlorvos Phosphine, pyrimethanil, terbufos, fenvalerate, phosmet, phosmet, phosmet, phosmet, chlorpyrifos, methamidophos, isopropylamine, isopropylamine-methyl, isopropylamine, isoxazophos, phosmet, bromobenzylphos, lyephos, thiamethoxam, malathion, malathion, phosmet, methyl phosmet, phosmet, dithiamethoxam, phosmet sulfoxide, chlorfenapyr, methamidophos, chlorpyrifos, methoxyphos, methyl ethyl phosmet, phosmet, phosmet, phosmet, phosmet, phosmet, phosmet, dimethoate, methyl sulfoxide, isosulfoxide, phosmet, parathion, methyl parathion, fenthion, phosmet, phosmet, phosmet, phosmet, phosmet, phosmet, phosmet, phosmet, phosmet Methyl thiophanate, glyphosate, imidacloprid, parachlorothiazoline, phosphamidon, phorate, methyl phorate, pyrimidine phosphamidon, pyrimidine oxyphosphamidon, ethyl pyrimidine phosphamidon, methyl pyrimidine phosphamidon, pyrimidine carbendazim, profenofos, fenpyrophos, ethiophanate, phenanthrenephos, pyrazophos, pyrimidine phosphamidon, quinalphos, methyl quinalphos, phosphamidon, octophos, thiophanate, thiophanate, thiophanate-methyl, thiophanate, butyl pyrimidine phosphamidon, dithion, tetraethyl pyrophosphate (TEPP), terbufos, chlorpyrifos, methyl ethoxyphos, phosphamidon, triazophos, trichlorfon, methyl methiophos-3, phosphonophosphorus, trichlorfon, phosphamidon, phosphamidon, and zopyridine.

[0265] 55. The composition according to Example 35, wherein the at least one insecticide is a phenolic insecticide selected from the group consisting of: pentachlorophenol, antijuvenile hormone, precocious hormone I, precocious hormone II and precocious hormone III.

[0266] 56. The composition according to Example 35, wherein the at least one insecticide is a pyrazole insecticide selected from the group consisting of: acetamiprid, dipropionylpyridinium, acetamiprid, fipronil, tebufenozide, pyrifluquinazon, pyrazosulfuron, pyrazosulfuron, and vanillin.

[0267] 57. The composition according to Example 35, wherein the at least one insecticide is a pyrethroid / pyrethroid insecticide selected from the group consisting of: flufenacet, allethrin, α-cypermethrin, propargyl, lambda-cyhalothrin, β-cypermethrin, bifenthrin, bio-allethrin, bio-ethoxyfen, bio-permethrin, bio-benzylfenoxamyl, bromocypermethrin ... Benzylpyrethrin, Chlorpyrifos, Chlorpyrifos, Ciprofloxacin, Ciprofloxacin, Cypermethrin, Cypermethrin, Lambda-cyhalothrin, Trifluralin, Cypermethrin, Lambda-cyhalothrin, Delcypermethrin, d-trans-Cypermethrin, Tetrafluoromethoxyphen ... Cypermethrin, cypermethrin, fenvalerate, deltamethrin, trifluralin, flufenoxuron, cypermethrin, cypermethrin, γ-cypermethrin, benzylpyr, heptamethrin, cypermethrin, cypermethrin, jasminylpyr, thiamethoxam, κ-bifenthrin, κ-heptamethrin, λ-cypermethrin, chlorfluazuron, methoxyfenozide, cypermethrin, pendimethalin, benzylpyr. Esters, fenpyroxene, propargyl, propargyl, propargyl, propargyl, pyrethrin, benzylfuran, chlorfluazuron, benzylfuran, flusilyl, thiooxime, deltamethrin, cypermethrin, heptamethrin, cyclopentenylpyrethrin, pyrethrin, tetramethylflumethrin, θ-cypermethrin, thiooxime, bromocypermethrin, tetrabromopyrethrin, tetrafluorobenzylpyrethrin, trans-benzylcypermethrin, valerate, and ζ-cypermethrin.

[0268] 58. The composition according to Example 35, wherein the at least one insecticide is benzimidazole, thiamethoxam, clomiphene, fentriranil, flumetoquinone, flupyradifurone, fluhexenone, fipronil, indoximetronidazole, mesotrione, lepromazine, mefenoxam, maltodextrin, nicotinamide, flufenoxuron, oxazolidinyl, trichlorfon, pyridaben, acetamiprid, iodofensyl, thioflupyr, tartaric acid, thiophanate-methyl, azoxystrobin, trichlorfon, or chlorpyrifos.

[0269] 59. The composition according to any one of Examples 35 to 58, wherein the at least one ascaroside comprises an ascaroside having structure (I):

[0270]

[0271] in:

[0272] Z represents C, which is arbitrarily substituted. 3-40 Aliphatic groups, and

[0273] R a and R b Each of them is independently -H or an optionally substituted portion of a group consisting of the following: C 1-20 aliphatic, C 1-20 Acyl group, C 1-20 Heteroaliphatic, aryl, heteroaryl, hydroxyl protecting groups, phosphorus-linked functional groups, sulfur-linked functional groups, silicon-linked functional groups, C 2-20 Carbonates (e.g., partially -C(O)OR) c C 2-20 Carbamates (e.g., partially -C(O)N(R) c )2) C 2-20 Thioesters (e.g., partially -C(S)R) c C 2-20 Thiocarbonates (e.g., partially -C(S)OR) c C 2-20 Dithiocarbonates (e.g., partially -C(S)SR) c C 1-20 Thiocarbamates (e.g., partially -C(S)N(R) c 2) The sugar moiety, peptide, polymer chain, or linker to another ascaridin molecule via a bond or carbon-containing linker. Among them, R... c Each occurrence is independently selected from -H, optionally substituted C. 1-12 Aliphatic, optionally substituted C 1-12 Heteroaliphatic, optionally substituted aryl, optionally substituted heteroaryl, polymer chain or linkage to another ascaridin molecule via a bond or carbon-containing linker, wherein R a and R b Together they can form an optionally substituted ring, which optionally contains one or more heteroatoms and optionally contains one or more unsaturated sites.

[0274] 60. The composition according to Example 59, wherein Z is selected from the group consisting of:

[0275] i.–CH(CH3)–R 1 , where R 1 C is arbitrarily substituted 1-40 Aliphatic groups

[0276] ii.–CH(CH3)–(CH2) n –CO2R 2, where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides;

[0277] iii.–CH(CH3)–(CH2) n –CH=CH-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides;

[0278] iv.–CH(CH3)–(CH2) n –CH(OH)–CH2-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides;

[0279] v.–CH(CH3)–(CH2) n –C(O)–CH2-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides;

[0280] vi. –(CH2) n –CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides;

[0281] vii.–(CH2) n –CH=CH-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides;

[0282] viii.–(CH2) n–CH(OH)–CH2-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides, or nucleotides; and

[0283] ix.–(CH2) n –C(O)–CH2-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides, or nucleotides.

[0284] 61. The composition according to Example 47, wherein Z is:

[0285] (x)–CH(CH3)–(CH2) n –CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linkage to another ascaridone molecule via a bond or carbon-containing linker.

[0286] (xi)–CH(CH3)–(CH2) n –CH=CH-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linkage to another ascaridone molecule via a bond or carbon-containing linker.

[0287] (xii)–CH(CH3)–(CH2) n –CH(OH)–CH2-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linkage to another ascaridone molecule via a bond or carbon-containing linker.

[0288] (xiii)–CH(CH3)–(CH2) n –C(O)–CH2-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linkage to another ascaridone molecule via a bond or carbon-containing linker.

[0289] (xiv)–(CH2) n –CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linkage to another ascaridone molecule via a bond or carbon-containing linker.

[0290] (xv)–(CH2) n –CH=CH-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linkage to another ascaridone molecule via a bond or carbon-containing linker.

[0291] (xvi)–(CH2) n –CH(OH)–CH2-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20Heteroaliphatic groups, optionally substituted aromatic groups, optionally substituted heteroaryl groups, polymer chains, amino acids, peptides, nucleotides, or linkages to another ascaridone molecule via bonds or carbon-containing linker portions; or

[0292] (xvii)–(CH2) n –C(O)–CH2-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linked to another ascaroside molecule via a bond or carbon-containing linker.

[0293] 62. The composition according to Example 60 or 61, wherein R a and R b Each is -H.

[0294] 63. The composition according to any one of Examples 59 to 62, wherein Z is –CH(CH3)–(CH2). n –CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides, or nucleotides.

[0295] 64. The composition according to any one of Examples 35 to 63, wherein the at least one ascaroside comprises ascaroside selected from the group consisting of: ascr#9, ascr#10, ascr#16, ascr#18, ascr#20, ascr#22 and ascr#24.

[0296] 65. The composition according to any one of Examples 35 to 63, wherein the at least one ascaroside comprises ascr#18, or wherein the at least one ascaroside comprises oscr#16.

[0297] 66. The composition according to any one of Examples 35 to 63, wherein the at least one ascaroside comprises ascr#18.

[0298] 67. The composition according to any one of Examples 35 to 66, wherein the composition is part of a canned mixture.

[0299] 68. The composition according to any one of Examples 35 to 66, wherein the composition is in solid form.

[0300] 69. The composition according to Example 68, wherein the solid form comprises powder or granules.

[0301] 70. The composition according to any one of Examples 35 to 66, wherein the composition is in liquid form.

[0302] 71. The composition according to Example 70, wherein the liquid form is a sprayable formulation.

[0303] 72. The composition according to any one of Examples 35 to 71, wherein the composition is stable for a period of time greater than 6 months.

[0304] 73. The composition according to any one of Examples 35 to 72, wherein the composition further comprises one or more additional components selected from the group consisting of: surfactants including emulsifiers, dispersants, foaming agents, colorants, processing aids, lubricants, fillers, reinforcing agents, flame retardants, light stabilizers, ultraviolet radiation absorbers, climate stabilizers, plasticizers, release agents, fragrances, heat-insulating additives (e.g., silica), crosslinking agents, antioxidants, defoamers, buffers, pH adjusters, compatibilizers, drift control additives, expanders / adhesives, tackifiers, plant penetrants, safeners, spreading agents, and wetting agents.

[0305] Example

[0306] Example 1: Canning test of ascaroside and insecticide.

[0307] A trial was conducted to evaluate the combined application of Phytalix® (a formulation containing ascaroside) with one or more insecticides. The trial was organized in a randomized, complete block design, with each treatment replicated four times, and plots measuring 10 ft by 30 ft. The trial was replicated at three different locations. The tank mixtures consisted of different insecticides with different molecular classes and modes of action, along with an effective amount of Phytalix® or a similar ascaroside formulation. Comparisons included an untreated control and a control group treated with only each insecticide without the addition of Phytalix®.

[0308] In the following evaluation of the plots in Example 1: Insect control in each plot was assessed as control % at 7 and 14 days post-application. Phytotoxicity ratings were also measured for each plot at 7 and 14 days post-application. Disease ratings (e.g., fungal, bacterial, and / or viral diseases) were collected when the crop reached an appropriate growth stage, or whenever routine monitoring showed measurable disease in control plots. Disease assessments included disease incidence % and severity. Plots were harvested separately and yields were measured and reported in bushels per acre. Insect control levels, phytotoxicity ratings, disease incidence and severity, and yields for each treatment group were averaged and compared to appropriate controls to assess the impact of ascaridone.

[0309] The compounds, compositions, and methods of this application are intended to cover variations and adaptations developed using information from the embodiments described in this disclosure. Those skilled in the art can adjust or modify the methods and processes described in this specification.

[0310] It will be understood that the use of headings in this disclosure is for the reader's convenience. The presence and / or placement of headings are not intended to limit the scope of the subject matter described herein. Unless otherwise stated, embodiments located in one part of this application are applicable, individually or in combination, to other embodiments throughout the application.

[0311] Throughout this specification, where a composition, compound, or product is described as having, including, or containing specific components, or where a process or method is described as having, including, or containing specific steps, it is contemplated that the articles, apparatus, and systems of this application are also substantially composed of, or consist of, the said components, and that the processes and methods according to this application are also substantially composed of, or consist of, the said process steps.

[0312] It should be understood that the order of steps or the order in which an action is performed is irrelevant as long as the method remains operational. Furthermore, two or more steps or actions can be performed simultaneously.

[0313] All publications and patent applications mentioned in this specification are intended to be of the skill of a person skilled in the art to which this invention pertains. All publications and patent applications are incorporated herein by reference as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference.

[0314] Although the invention has been described in detail by way of illustrations and examples for clarity, it will be apparent that certain changes and modifications may be made within the scope of the appended claims.

Claims

1. A method for controlling insect infestation of plants, the method comprising applying ascaroside to a plant, a plant part, or the soil surrounding the plant or plant part, wherein the plant, plant part, or the soil surrounding the plant or plant part is being or has been treated with an insecticide (e.g., via application to the plant, plant part, or the soil surrounding the plant or plant part).

2. A method for controlling insect infestation of plants, the method comprising applying an insecticide to a plant, a plant part, or the soil surrounding the plant or plant part, wherein the plant, plant part, or the soil surrounding the plant or plant part is being or has been treated with ascaroside (e.g., via application to the plant, plant part, or the soil surrounding the plant or plant part).

3. A method for reducing phytotoxic side effects on plants associated with the application of insecticides, the method comprising contacting a plant or plant part with an effective amount of a combination of agents, said agents comprising at least one ascaroside and at least one insecticide.

4. The method of claim 3, wherein the effective amount reduces the phytotoxic side effects on the crop plant compared to the phytotoxic side effects associated with applying the insecticide alone.

5. The method of claim 3 or 4, wherein the effective amount reduces the phytotoxicity rating of the crop plant compared to the phytotoxicity rating associated with applying the insecticide alone.

6. The method according to any one of claims 1 to 5, wherein the at least one insecticide is an alkaloid insecticide, an alkyl halide insecticide, an aminopyrimidine insecticide, an aminotriazine insecticide, an antibiotic insecticide, an aromatic hydrocarbon insecticide, an arylpyrrole insecticide, a benzimidazole insecticide, a benzoylurea insecticide, a β-ketonitrile insecticide, a phytotoxicant, a carbamate insecticide, a dihydrazide insecticide, a diamide insecticide, a dinitrophenol insecticide, a dithiopentane insecticide, a formamid insecticide, a fumigant insecticide, an inorganic insecticide, an isoxazoline insecticide, a juvenile hormone mimic, or a macrolide insecticide. , m-diamide insecticides, methoxyacrylate insecticides, neonicotinoid insecticides, nereistoxin analog insecticides, organochlorine insecticides, organophosphorus insecticides, oxadiazine insecticides, oxadiazon insecticides, perfluoroalkyl sulfonamide insecticides, phenol insecticides, pyrethroid insecticides, pyrethroid insecticides, pyridazine insecticides, pyridine azomethyl insecticides, pyrimidine amine insecticides, propylene insecticides, RNA1 insecticides, salicylaniline insecticides, amine urea insecticides, steroid insecticides, tertran acid insecticides, terfenic acid insecticides, thiocarbonate insecticides, thiourea insecticides, or urea insecticides.

7. The method according to any one of claims 1 to 6, wherein the at least one ascaroside comprises an ascaroside having structure (I): in: Z represents C, which is arbitrarily substituted. 3-40 Aliphatic groups, and R a and R b Each of them is independently -H or an optionally substituted portion of a group consisting of the following: C 1-20 aliphatic, C 1-20 Acyl group, C 1-20 Heteroaliphatic, aryl, heteroaryl, hydroxyl protecting groups, phosphorus-linked functional groups, sulfur-linked functional groups, silicon-linked functional groups, C 2-20 Carbonates (e.g., partially -C(O)OR) c C 2-20 Carbamates (e.g., partially -C(O)N(R) c )2) C 2-20 Thioesters (e.g., partially -C(S)R) c C 2-20 Thiocarbonates (e.g., partially -C(S)OR) c C 2-20 Dithiocarbonates (e.g., partially -C(S)SR) c C 1-20 Thiocarbamates (e.g., partially -C(S)N(R) c 2) The sugar moiety, peptide, polymer chain, or linker to another ascaridin molecule via a bond or carbon-containing linker. Where R c Each occurrence is independently selected from -H, optionally substituted C. 1-12 Aliphatic, optionally substituted C 1-12 Heteroaliphatic, optionally substituted aryl, optionally substituted heteroaryl, polymer chain or linkage to another ascaridin molecule via a bond or carbon-containing linker, and Where R a and R b Together they can form optionally substituted rings, which optionally contain one or more heteroatoms and optionally one or more unsaturated sites.

8. The method of claim 7, wherein Z is selected from the group consisting of: i.–CH(CH3)–R 1 , where R 1 C is arbitrarily substituted 1-40 Aliphatic groups ii.–CH(CH3)–(CH2) n –CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides; iii.–CH(CH3)–(CH2) n –CH=CH-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides; iv.–CH(CH3)–(CH2) n –CH(OH)–CH2-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides; v.–CH(CH3)–(CH2) n –C(O)–CH2-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides; vi. –(CH2) n –CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides; vii.–(CH2) n –CH=CH-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides; viii.–(CH2) n –CH(OH)–CH2-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides, or nucleotides; and ix.–(CH2) n –C(O)–CH2-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides, or nucleotides.

9. The method of claim 7, wherein Z is selected from the group consisting of: (x)–CH(CH3)–(CH2) n –CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linked to another ascaridone molecule via a bond or carbon-containing linker. (xi)–CH(CH3)–(CH2) n –CH=CH-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linked to another ascaridone molecule via a bond or carbon-containing linker. (xii)–CH(CH3)–(CH2) n –CH(OH)–CH2-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linked to another ascaridone molecule via a bond or carbon-containing linker. (xiii)–CH(CH3)–(CH2) n –C(O)–CH2-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linked to another ascaridone molecule via a bond or carbon-containing linker. (xiv)–(CH2) n –CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linked to another ascaridone molecule via a bond or carbon-containing linker. (xv)–(CH2) n –CH=CH-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linked to another ascaridone molecule via a bond or carbon-containing linker. (xvi)–(CH2) n –CH(OH)–CH2-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linked to another ascaridone molecule via a bond or carbon-containing linker. (xvii)–(CH2) n –C(O)–CH2-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 Heteroaliphatic groups, optionally substituted aromatic groups, optionally substituted heteroaryl groups, polymer chains, amino acids, peptides, nucleotides, or linkages to another ascaridone molecule via bonds or carbon-containing linker portions; and (xix) optionally unsaturated optionally substituted C 2-40 Side chains terminate at chain ends containing functional groups of nitrogen, oxygen, or sulfur.

10. The method according to any one of claims 1 to 9, wherein the at least one ascaroside comprises ascaroside selected from the group consisting of: ascr#9, ascr#10, ascr#16, ascr#18, ascr#20, ascr#22 and ascr#24.

11. The method according to any one of claims 1 to 10, wherein the at least one ascaroside comprises ascr#18.

12. The method according to any one of claims 1 to 11, wherein the at least one ascaroside and the at least one insecticide are applied simultaneously.

13. The method of claim 12, wherein the at least one ascaroside and the at least one insecticide are combined together in a can mixture.

14. The method according to any one of claims 1 to 11, wherein the at least one ascaroside and the at least one insecticide are applied sequentially.

15. The method according to any one of claims 1 to 14, wherein the combination is used as a seed coating.

16. A composition comprising at least one ascaroside and at least one insecticide.

17. The composition according to claim 16, wherein the at least one ascaroside and the at least one insecticide are present in an effective amount.

18. The composition of claim 17, wherein the effective amount reduces phytotoxic side effects on the crop plant compared to the phytotoxic side effects associated with applying the insecticide alone.

19. The composition according to claim 17 or 18, wherein the effective amount reduces the phytotoxicity rating of the crop plant compared to the phytotoxicity rating associated with applying the insecticide alone.

20. The composition according to any one of claims 16 to 19, wherein the at least one insecticide is an alkaloid insecticide, an alkyl halide insecticide, an aminopyrimidine insecticide, an aminotriazine insecticide, an antibiotic insecticide, an aromatic hydrocarbon insecticide, an arylpyrrole insecticide, a benzimidazole insecticide, a benzoylurea insecticide, a β-ketonitrile insecticide, a phytotoxicant, a carbamate insecticide, a dihydrazide insecticide, a diamide insecticide, a dinitrophenol insecticide, a dithiopentane insecticide, a formamid insecticide, a fumigant insecticide, an inorganic insecticide, an isoxazoline insecticide, a juvenile hormone mimic, or a macrolide insecticide. Insecticides, m-diamide insecticides, methoxyacrylate insecticides, neonicotinoid insecticides, nereistoxin analog insecticides, organochlorine insecticides, organophosphate insecticides, oxadiazine insecticides, oxadiazon insecticides, perfluoroalkyl sulfonamide insecticides, phenol insecticides, pyrethroid insecticides, pyrethroid insecticides, pyridazine insecticides, pyridinium chloride insecticides, propylene insecticides, RNA1 insecticides, salicylaniline insecticides, urea insecticides, steroid insecticides, tertran acid insecticides, terfenic acid insecticides, thiocarbonate insecticides, thiourea insecticides, or urea insecticides.

21. The composition according to any one of claims 16 to 20, wherein the at least one ascaroside comprises an ascaroside having structure (I): in: Z represents C, which is arbitrarily substituted. 3-40 Aliphatic groups, and R a and R b Each of them is independently -H or an optionally substituted portion of a group consisting of the following: C 1-20 aliphatic, C 1-20 Acyl group, C 1-20 Heteroaliphatic, aryl, heteroaryl, hydroxyl protecting groups, phosphorus-linked functional groups, sulfur-linked functional groups, silicon-linked functional groups, C 2-20 Carbonates (e.g., partially -C(O)OR) c C 2-20 Carbamates (e.g., partially -C(O)N(R) c )2) C 2-20 Thioesters (e.g., partially -C(S)R) c C 2-20 Thiocarbonates (e.g., partially -C(S)OR) c C 2-20 Dithiocarbonates (e.g., partially -C(S)SR) c C 1-20 Thiocarbamates (e.g., partially -C(S)N(R) c )2) The sugar moiety, peptide, polymer chain, or the linking of the molecule to another ascaridin molecule via a bond or carbon-containing linker; Where R c Each occurrence is independently selected from -H, optionally substituted C. 1-12 Aliphatic, optionally substituted C 1-12 Heteroaliphatic, optionally substituted aryl, optionally substituted heteroaryl, polymer chain or linkage to another ascaridin molecule via a bond or carbon-containing linker, and Where R a and R b Together they can form optionally substituted rings, which optionally contain one or more heteroatoms and optionally one or more unsaturated sites.

22. The composition of claim 21, wherein Z is selected from the group consisting of: i.–CH(CH3)–R 1 , where R 1 C is arbitrarily substituted 1-40 Aliphatic groups ii.–CH(CH3)–(CH2) n –CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides; iii.–CH(CH3)–(CH2) n –CH=CH-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides; iv.–CH(CH3)–(CH2) n –CH(OH)–CH2-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides; v.–CH(CH3)–(CH2) n –C(O)–CH2-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides; vi. –(CH2) n –CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides; vii.–(CH2) n –CH=CH-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides or nucleotides; viii.–(CH2) n –CH(OH)–CH2-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides, or nucleotides; and ix.–(CH2) n –C(O)–CH2-CO2R 2 , where n is an integer from 1 to 40, and R 2 -H, metal cation, or optionally substituted C 1-20 Aliphatic groups, optionally substituted aromatic groups, glycosides, amino acids, peptides, or nucleotides.

23. The composition according to claim 21, wherein Z is: (x)–CH(CH3)–(CH2) n –CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linked to another ascaridone molecule via a bond or carbon-containing linker. (xi)–CH(CH3)–(CH2) n –CH=CH-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linked to another ascaridone molecule via a bond or carbon-containing linker. (xii)–CH(CH3)–(CH2) n –CH(OH)–CH2-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linked to another ascaridone molecule via a bond or carbon-containing linker. (xiii)–CH(CH3)–(CH2) n –C(O)–CH2-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linked to another ascaridone molecule via a bond or carbon-containing linker. (xiv)–(CH2) n –CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linked to another ascaridone molecule via a bond or carbon-containing linker. (xv)–(CH2) n –CH=CH-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linked to another ascaridone molecule via a bond or carbon-containing linker. (xvi)–(CH2) n –CH(OH)–CH2-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 The heteroaliphatic group, optionally substituted aromatic group, optionally substituted heteroaryl group, polymer chain, amino acid, peptide, nucleotide, or linked to another ascaridone molecule via a bond or carbon-containing linker. (xvii)–(CH2) n –C(O)–CH2-CON(R 3 )2, where n is an integer from 1 to 40, and each R 3 Independently -H, optionally substituted C 1-20 Aliphatic groups, optionally substituted C 1-20 Heteroaliphatic groups, optionally substituted aromatic groups, optionally substituted heteroaryl groups, polymer chains, amino acids, peptides, nucleotides, or linkages to another ascaridone molecule via bonds or carbon-containing linker portions; or (xviii) Optionally unsaturated, optional substituted C 2-40 Side chains terminate at chain ends containing functional groups of nitrogen, oxygen, or sulfur.

24. The composition according to any one of claims 16 to 23, wherein the at least one ascaroside comprises ascaroside selected from the group consisting of: ascr#9, ascr#10, ascr#16, ascr#18, ascr#20, ascr#22 and ascr#24.

25. The composition according to any one of claims 16 to 23, wherein the at least one ascaroside comprises ascr#18.

26. The composition according to any one of claims 16 to 24, wherein the composition is part of a canned mixture.

27. The composition according to any one of claims 16 to 25, wherein the composition is in solid form.

28. The composition of claim 25, wherein the solid form comprises powder or granules.

29. The composition according to any one of claims 16 to 25, wherein the composition is in liquid form.

30. The composition of claim 29, wherein the liquid form is a sprayable formulation.

31. The composition according to any one of claims 16 to 30, wherein the composition is stable for a period of time greater than 6 months.

32. The composition according to any one of claims 16 to 31, wherein the composition further comprises one or more additional components selected from the group consisting of: surfactants including emulsifiers, dispersants, foaming agents, colorants, processing aids, lubricants, fillers, reinforcing agents, flame retardants, light stabilizers, ultraviolet radiation absorbers, climate stabilizers, plasticizers, release agents, fragrances, heat-insulating additives (e.g., silica), crosslinking agents, antioxidants, defoamers, buffers, pH adjusters, compatibilizers, drift control additives, expanders / adhesives, tackifiers, plant penetrants, safeners, spreading agents, and wetting agents.

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