Ascarosides and insecticide combinations and methods for use

Abstract

Combinations of agents for preventing, treating, or controlling unwanted plants and methods of their use are provided. The combinations comprise at least one ascaroside (or a derivative or analog of an ascaroside) with at least one insecticide. The ascaroside can be combined with at least one insecticide to lessen the phytotoxic effects of the insecticide on the treated crop while simultaneously killing unwanted plants in the applied area. The ascarosides and insecticides may be provided in the same composition or may be applied together (i.e., substantially simultaneously) or sequentially.

Description

ASCAROSIDES AND INSECTICIDE COMBINATIONS AND METHODS FOR USE CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S. Provisional Appl. No. 63 / 513,860, filed on July 14, 2023, the entirety of which is hereby incorporated by reference. FIELD OF THE INVENTION

[0002] The invention is drawn to compositions and methods relating to use of an ascaroside and one or more insecticides. BACKGROUND OF THE INVENTION

[0003] Insecticides are well known to control undesired insects. Selective insecticides control specific insects, while non-selective insecticides kill most (if not all) insects that are contacted with or ingest the insecticide. A large percentage of insecticides are used for agricultural purposes to prevent unwanted insects from consuming crop-producing plants or products obtained from the plants.

[0004] In an effort to overcome increasing resistance of insect pests to insecticides, growers increasingly rely on products containing blends of multiple insecticidal ingredients, often with distinct modes of action. Such products typically contain a full dose of each component insecticide (e.g. when applied at label rate, such blends provide an amount of each active similar to the amount applied if that active were used at label rate as a solo product). This results in an overall increase in the amount of insecticide applied per acre and a correspondingly increased risk of phytotoxic effects on crops. Unfortunately, such multi-way products are harsher on plants, either due to additive or synergistic phytotoxic effects of the active ingredients, or as a result of the more complicated formulations necessary to compatibilize multiple insecticides, or due to the larger volume of adjuvants and inert formulation components applied to the crop with these multi-way products. With these higher levels of phytotoxicity, the benefits obtained in controlling insecticide- resistant pests can be undermined and can lead to poor perception of the products in the 1 BUSINESS.31669632.1 409753-016WO (210621)marketplace. While insecticides can be quite selective at reducing the unwanted insects in the field, insecticides can have phytotoxic side effects on the crop plants.

[0005] Additionally, there is increasing attention focused on the cost and environmental impacts of agricultural inputs. Strategies to minimize the number of times agrichemicals are applied to crops can lower costs and improve sustainability due to reduced fuel consumption. Minimizing application passes also prevents compaction of soil, physical damage to plants and reduces risk of undesired effects such as runoff and overspray.

[0006] The present invention provides solutions to these and related problems. SUMMARY OF THE INVENTION

[0007] Combinations of agents for preventing, treating, or controlling unwanted insects and / or plant pathogens and methods of their use are provided. The provided combinations comprise at least one ascaroside (or a derivative or analog of an ascaroside) with at least one insecticide. In some embodiments, the ascaroside can be combined with at least one insecticide to lessen the phytotoxic effects of the insecticide on the treated crop. In some embodiments, crop management can be made more efficient by simultaneously applying ascarosides (which can have value in controlling plant pathogens such as fungi, bacteria, viruses or nematodes, and / or in promoting plant health) with insecticides—this can minimize application passes, reduce fuel consumption, and lower crop production costs. The ascarosides and insecticides may be provided in the same composition or may be applied together (i.e., substantially simultaneously) or sequentially. The agents are applied in an effective amount, i.e., an amount sufficient to control or inhibit unwanted insects and also provide the desired benefits of ascaroside application (e.g., reduction of phytotoxic side effects of the insecticides, and / or control of pathogens on crop plants). DETAILED DESCRIPTION OF THE INVENTION

[0008] The disclosure provides compositions and methods relating to use of one or more ascarosides and one or more insecticides. In some embodiments, the disclosure provides compositions and methods relating to combinations of one or more ascarosides and one or more insecticides wherein the ascaroside(s) serve the purpose of a safener to lessen phytotoxic effects 2 BUSINESS.31669632.1 409753-016WO (210621)of the insecticide(s) on the treated crop. As used herein, the term “ascaroside” includes the ascaroside, a derivative or an analog of the ascaroside, or combinations thereof, as will be described in further detail herein. The ascaroside can be used with any insecticide.

[0009] The ascaroside(s) and the insecticide(s) may be used in the same composition (e.g., co- formulated or tank-mixed), or the ascaroside(s) and the insecticide(s) may be applied separately (e.g., in separate formulations), either simultaneously or sequentially. If applied sequentially, the applications are close enough in time such that they are able to work in combination to produce the beneficial results.

[0010] As noted, methods and compositions of the invention comprise ascarosides. Ascarosides are secondary metabolites produced by nematodes. Many structurally diverse ascarosides have been identified in nature and are believed to function as an evolutionarily conserved chemical language used by nematodes to control many aspects of their development.

[0011] Ascarosides are derivatives of the sugar ascarylose—a di-deoxy sugar lacking hydroxyl groups at its 3- and 6-positions. Ascarosides have the general structure shown in Formula I: OZwherein: Z is an optionally substituted C2-40 aliphatic group, and each of Raand Rbis independently -H, or an optionally substituted moiety selected from the group consisting of: C1-20aliphatic, C1-20acyl, C1-20heteroaliphatic, aryl, heteroaryl, a hydroxyl protecting group, a phosphorous-linked functional group, a sulfur-linked functional group, a silicon-linked functional group, a C2-20 carbonate (e.g. -a moiety -C(O)ORc), a C2-20 carbamate (e.g. -a moiety -C(O)N(Rc)2), a C2-20thioester (e.g. a moiety -C(S)Rc), a C2-20thiocarbonate (e.g. a moiety -C(S)ORc), a C2-20 dithiocarbonate (e.g. a moiety -C(S)SRc), a C1-20 thiocarbamate (e.g. a moiety -C(S)N(Rc)2), a sugar moiety, a peptide, a polymer chain, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; 3 BUSINESS.31669632.1 409753-016WO (210621)each Rcis independently at each occurrence selected from -H, optionally substituted C1-12aliphatic, optionally substituted C1-12 heteroaliphatic, optionally substituted aryl, optionally substituted heteroaryl, a polymer chain, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; and wherein Raand Rbmay be taken together to form an optionally substituted ring, optionally containing one or more heteroatoms, and optionally containing one or more sites of unsaturation.

[0012] In certain embodiments, Z is: (i) –CH(CH3)–R1, where R1is an optionally substituted C1-40 aliphatic group (ii) –CH(CH3)–(CH2)n–CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20aliphatic group, an optionally substituted C1-20heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a glycoside, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (iii) –CH(CH3)–(CH2)n–CH=CH-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a glycoside, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (iv) –CH(CH3)–(CH2)n–CH(OH)–CH2-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a glycoside, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (v) –CH(CH3)–(CH2)n–C(O)–CH2-CO2R2, where n is an integer from 1 to 40, and R2is - H, a metal cation, an optionally substituted C1-20aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a glycoside, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; 4 BUSINESS.31669632.1 409753-016WO (210621)(vi) –(CH2)n–CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a glycoside, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (vii) –(CH2)n–CH=CH-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20aliphatic group, an optionally substituted C1-20heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a glycoside, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (viii) –(CH2)n–CH(OH)–CH2-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a glycoside, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; or (ix) –(CH2)n–C(O)–CH2-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a glycoside, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule.

[0013] In certain embodiments, Z is: (x) –CH(CH3)–(CH2)n–CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xi) –CH(CH3)–(CH2)n–CH=CH-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20aliphatic group, an optionally substituted C1-20heteroaliphatic group, an optionally substituted aromatic group, an 5 BUSINESS.31669632.1 409753-016WO (210621)optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xii) –CH(CH3)–(CH2)n–CH(OH)–CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xiii) –CH(CH3)–(CH2)n–C(O)–CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xiv) –(CH2)n–CON(R3)2, where n is an integer from 1 to 40, and each R3is independently - H, an optionally substituted C1-20aliphatic group, an optionally substituted C1-20heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xv) –(CH2)n–CH=CH-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xvi) –(CH2)n–CH(OH)–CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a 6 BUSINESS.31669632.1 409753-016WO (210621)nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xvii) –(CH2)n–C(O)–CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; or (xviii) an optionally unsaturated, optionally substituted C2-40 sidechain terminating in a chain end comprising a nitrogen-, oxygen- or sulfur-containing functional group.

[0014] As defined above and described herein, in some embodiments, Z comprises a nitrogen-, oxygen-, or sulfur-containing functional group. It will be appreciated that “an oxygen-containing functional group” refers to moieties that comprise one or more oxygen atoms (e.g., carbonyl- containing groups such as esters, aldehydes, carboxylic acids, ortho esters, and ketones; ethers, hydroxyls, and heterocyclic rings comprising one or more oxygen atoms and / or one of the foregoing functional groups); “a nitrogen-containing functional group” refers to moieties that comprise one or more nitrogen atoms (e.g., amines, amides, carbamates, imines, ureas, oximes, amidines, guanidines, nitriles, azo groups, azides, and heterocyclic rings comprising one or more nitrogen atoms and / or one of the foregoing functional groups); and “a sulfur-containing functional group” refers to moieties that comprise one or more sulfur atoms (e.g., thioether, sulfone, sulfonic acid, sulfoxide, thiol, thiocyanate, or disulfide).

[0015] In some embodiments, Z is an optionally unsaturated, optionally substituted C2-40 sidechain terminating in a chain end comprising an oxygen-containing functional group. In certain embodiments, Z is an optionally unsaturated, optionally substituted C2-40sidechain terminating in a chain end comprising a carboxylic acid. In certain embodiments, Z is an optionally unsaturated, optionally substituted C2-40 sidechain terminating in a chain end comprising an aldehyde. In certain embodiments, Z is an optionally unsaturated, optionally substituted C2-40sidechain terminating in a chain end comprising an ester. In some embodiments, Z an optionally unsaturated, optionally substituted C2-40 sidechain terminating in a chain end comprising -CO2R2. In some embodiments, Z is an optionally unsaturated, optionally substituted C2-40sidechain terminating in a chain end comprising -CO2H. In some embodiments, Z is an optionally unsaturated, optionally substituted 7 BUSINESS.31669632.1 409753-016WO (210621)C2-40sidechain terminating in a chain end comprising -CO2CH3. In some embodiments, Z is an optionally unsaturated, optionally substituted C2-40 sidechain terminating in a chain end comprising -CON(R3)2. In some embodiments, Z is an optionally unsaturated, optionally substituted C2-40 sidechain terminating in a chain end comprising -N(R3)2. In some embodiments, Z is an optionally unsaturated, optionally substituted C2-40 sidechain terminating in a chain end comprising an ester comprising a linker moiety covalently attached to one or more additional ascaroside molecules.

[0016] As described above, the ascarylose sugar moiety in the provided compounds can be substituted or unsubstituted (i.e., there can be functional groups other than -OH at 2- and 4- positions of the sugar or, stated differently, variables Raand / or Rbcan be other than -H in any of the formulae herein).

[0017] As defined above and described herein, each of Raand Rbis independently -H, or an optionally substituted moiety selected from the group consisting of: C1-20 aliphatic, C1-20 acyl, C1- 20 heteroaliphatic, aryl, heteroaryl, a hydroxyl protecting group, a phosphorous-linked functional group, a sulfur-linked functional group, a silicon-linked functional group, a C2-20carbonate (e.g., -a moiety -C(O)ORc), a C2-20 carbamate (e.g., -a moiety -C(O)N(Rc)2), a C2-20 thioester (e.g. a moiety -C(S)Rc), a C2-20 thiocarbonate (e.g. a moiety -C(S)ORc), a C2-20 dithiocarbonate (e.g. a moiety -C(S)SRc), a C1-20thiocarbamate (e.g. a moiety -C(S)N(Rc)2), a sugar moiety, a peptide, a polymer chain, or a linkage via a bond or a carbon-containing linker moiety to an ascaroside molecule.

[0018] In certain embodiments, Rais -H. In certain embodiments, Rbis -H. In certain embodiments, Raand Rbare the same. In certain embodiments Raand Rbare both -H. In certain embodiments, Raand Rbare different. In certain embodiments, Rais -H, and Rbis other than -H. In certain embodiments, Rais other than -H and Rbis -H. In certain embodiments, Rais -H and Rbis p-hydroxybenzoate. In certain embodiments, Rais -H and Rbis indole-3-carboxylate. In certain embodiments, Rais -H and Rbis (E)-2-methyl-2-butenoate. In certain embodiments, Rais -H and Rbis picolinate. In certain embodiments, Rais -H and Rbis nicotinate. In certain embodiments, Rais -H and Rbis (R)-2-hydroxy-2-(4-hydroxyphenyl)ethyl)amino)-4-oxobutanoate. In certain embodiments, Rais -H and Rbis 4-((4-hydroxyphenethyl)amino)-4-oxobutanoate. In certain embodiments, Racomprises a glycoside, amino acid, a peptide, or nucleotide. In certain embodiments, Rbcomprises a glycoside, amino acid, a peptide, or nucleotide. In certain embodiments, Racomprises a linkage to a second ascaroside molecule. In certain embodiments, 8 BUSINESS.31669632.1 409753-016WO (210621)Rbcomprises a linkage to an ascaroside molecule. In certain embodiments, Racomprises a sugar. In certain embodiments, Rbcomprises a sugar.

[0019] In some embodiments, Rais an optionally substituted C1-20 aliphatic. In some embodiments, Rais an optionally substituted C1-6aliphatic. In some embodiments, Rais C1-20aliphatic. In some embodiments, Rais C1-6 aliphatic. In some embodiments, Rais methyl, ethyl, n-propyl, iso-propyl, n-butyl, isobutyl, sec-butyl, or t-butyl. In some embodiments, Rais C1-20 acyl. In some embodiments, Rais -C(O)Rc. In some embodiments, Rais -C(O)H. In some embodiments, Rais -C(O)CH3. In some embodiments, Rais an optionally substituted C1-20 heteroaliphatic. In some embodiments, Rais an optionally substituted C1-6 heteroaliphatic. In some embodiments, Rais C1-20heteroaliphatic. In some embodiments, Rais C1-6heteroaliphatic. In some embodiments, Rais an optionally substituted 3- and 8-membered saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Rais an optionally substituted 8- and 12-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Rais optionally substituted aryl. In some embodiments, Rais optionally substituted phenyl. In some embodiments, Rais phenyl. In some embodiments, Rais an optionally substituted heteroaryl group. In some embodiments, Rais an optionally substituted 5- to 6-membered heteroaryl having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Rais an optionally substituted 8- to 12- membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Rais an optionally substituted C2-20carbonate. In some embodiments, Rais -C(O)ORc. In some embodiments, Rais an optionally substituted C2-20 carbamate. In some embodiments, Rais -C(O)N(Rc)2. In some embodiments, Rais an optionally substituted C2-20thioester. In some embodiments, Rais -C(S)Rc. In some embodiments, Rais an optionally substituted C2-20 thiocarbonate. In some embodiments, Rais -C(S)ORc. In some embodiments, Rais an optionally substituted C2-20 dithiocarbonate. In some embodiments, Rais -C(S)SRc. In some embodiments, Rais an optionally substituted C1-20thiocarbamate. In some embodiments, Rais -C(S)N(Rc)2.

[0020] In some embodiments, Rais an optionally substituted hydroxyl protecting group. Suitable hydroxyl protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3rdedition, John 9 BUSINESS.31669632.1 409753-016WO (210621)Wiley & Sons, 1999. Examples of suitable oxygen protecting groups include, but are not limited to, acetyl, benzoyl benzyl, β-methoxyethoxymethyl ether (MEM), dimethoxytrityl (DMT), methoxymethyl ether (MOM), methoxytrityl (MMT), p-methoxybenzyl ether (PMB), methylthiomethyl ether, pivaloyl, tetrahydropyranyl (THP), tetrahydrofuran (THF), trityl, silyl ethers (e.g., trimethylsilyl (TMS), tert-butyldimethylsilyl (TBDMS), tri-iso-propylsilyloxymethyl (TOM), and triisopropylsilyl (TIPS) ethers), methyl ethers, and ethoxyethyl ethers. In some embodiments, Rais -ORc.

[0021] In some embodiments, Rais an optionally substituted phosphorous-linked functional group. It will be appreciated that “phosphorous-linked functional group” as used herein refers to moieties that comprise one or more phosphorous atoms (e.g., phosphine, phosphodiester, phosphonic acid, phosphate). In some embodiments, Rais an optionally substituted sulfur-linked functional group. It will be appreciated that “sulfur-linked functional group” as used herein refers to moieties that comprise one or more sulfur atoms (e.g., thioether, sulfone, sulfonic acid, sulfoxide, thiol, thiocyanate, or disulfide). In some embodiments, Rais an optionally substituted silicon-linked functional group. It will be appreciated that “silicon-linked functional group” as used herein refers to moieties that comprise one or more silicon atoms (e.g., silanol, suloxides, siloxanes, silyl ethers, silyl chlorides, silyl hydrides, silenes, or siloles).

[0022] In some embodiments, Rais an optionally substituted sugar moiety. In some embodiments, Rais an optionally substituted peptide. In some embodiments, Rais an optionally substituted polymer chain. In some embodiments, Rais a linkage via a bond or a carbon-containing linker moiety to an ascaroside molecule. In some embodiments, Rais an optionally substituted C1-6aliphatic or heteroaliphatic comprising an ascaroside.

[0023] In some embodiments, Rbis an optionally substituted C1-20 aliphatic. In some embodiments, Rbis an optionally substituted C1-6aliphatic. In some embodiments, Rbis C1-20aliphatic. In some embodiments, Rbis C1-6 aliphatic. In some embodiments, Rbis methyl, ethyl, n-propyl, iso-propyl, n-butyl, isobutyl, sec-butyl, or t-butyl. In some embodiments, Rbis C1-20 acyl. In some embodiments, Rbis -C(O)Rc. In some embodiments, Rbis -C(O)H. In some embodiments, Rbis -C(O)CH3. In some embodiments, Rbis an optionally substituted C1-20 heteroaliphatic. In some embodiments, Rbis an optionally substituted C1-6 heteroaliphatic. In some embodiments, Rbis C1-20heteroaliphatic. In some embodiments, Rbis C1-6heteroaliphatic. In some embodiments, Rbis an optionally substituted 3- and 8-membered saturated or partially 10 BUSINESS.31669632.1 409753-016WO (210621)unsaturated heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Rbis an optionally substituted 8- and 12-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Rbis optionally substituted aryl. In some embodiments, Rbis optionally substituted phenyl. In some embodiments, Rbis phenyl. In some embodiments, Rbis an optionally substituted heteroaryl group. In some embodiments, Rbis an optionally substituted 5- to 6-membered heteroaryl having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Rbis an optionally substituted 8- to 12- membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Rbis an optionally substituted C2-20carbonate. In some embodiments, Rbis -C(O)ORc. In some embodiments, Rbis an optionally substituted C2-20carbamate. In some embodiments, Rbis -C(O)N(Rc)2. In some embodiments, Rbis an optionally substituted C2-20 thioester. In some embodiments, Rbis -C(S)Rc. In some embodiments, Rbis an optionally substituted C2-20thiocarbonate. In some embodiments, Rbis -C(S)ORc. In some embodiments, Rbis an optionally substituted C2-20 dithiocarbonate. In some embodiments, Rbis -C(S)SRc. In some embodiments, Rais an optionally substituted C1-20 thiocarbamate. In some embodiments, Rbis -C(S)N(Rc)2.

[0024] In some embodiments, Rbis an optionally substituted hydroxyl protecting group. In some embodiments, Rbis -ORc.

[0025] In some embodiments, Rbis an optionally substituted phosphorous-linked functional group. In some embodiments, Rbis an optionally substituted sulfur-linked functional group. In some embodiments, Rbis an optionally substituted silicon-linked functional group.

[0026] In some embodiments, Rbis an optionally substituted sugar moiety. In some embodiments, Rais an optionally substituted peptide. In some embodiments, Rbis an optionally substituted polymer chain. In some embodiments, Rbis a linkage via a bond or a carbon-containing linker moiety to an ascaroside molecule. In some embodiments, Rbis an optionally substituted C1-6 aliphatic or heteroaliphatic comprising an ascaroside.

[0027] In some embodiments, Raand Rbmay be taken together to form an optionally substituted ring, optionally containing one or more heteroatoms, and optionally containing one or more sites of unsaturation. In some embodiments, Raand Rbmay be taken together to form an optionally substituted 3- to 12- membered monocyclic or bicyclic saturated or partially unsaturated 11 BUSINESS.31669632.1 409753-016WO (210621)carbocyclyl or heterocyclyl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Raand Rbmay be taken together to form an optionally substituted 5- to 12-membered monocyclic or bicyclic aryl or heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0028] In certain embodiments, Rais -H and Rbis p-hydroxybenzoate. In certain embodiments, Rais -H and Rbis indole-3-carboxylate. In certain embodiments, Rais -H and Rbis (E)-2-methyl-2- butenoate. In certain embodiments, Rais -H and Rbis picolinate. In certain embodiments, Rais -H and Rbis nicotinate. In certain embodiments, Rais -H and Rbis (R)-2-hydroxy-2-(4- hydroxyphenyl)ethyl)amino)-4-oxobutanoate. In certain embodiments, Rais -H and Rbis 4-((4- hydroxyphenethyl)amino)-4-oxobutanoate.

[0029] In certain embodiments Raand Rbare both -H, and Z is selected from the formulae defined in (i) to (ix) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (i) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (ii) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (iii) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (iv) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (v) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (vi) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (vii) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (viii) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (ix) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (x) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (xi) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (xii) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (xiii) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (xiv) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (xv) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (xvi) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (xvii) above.

[0030] As defined above and described herein, each Rcis independently at each occurrence selected from -H, optionally substituted C1-12 aliphatic, optionally substituted C1-12 heteroaliphatic, 12 BUSINESS.31669632.1 409753-016WO (210621)optionally substituted aryl, optionally substituted heteroaryl, a polymer chain, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule.

[0031] In some embodiments, Rcis independently at each occurrence selected from -H, optionally substituted C1-12aliphatic, optionally substituted C1-12heteroaliphatic, optionally substituted aryl, optionally substituted heteroaryl.

[0032] In some embodiments, an occurrence of Rcis -H. In some embodiments, Rcis an optionally substituted C1-12aliphatic group. In some embodiments, Rcis an optionally substituted C1-6aliphatic group. In some embodiments, Rcis an optionally substituted C1-12 heteroaliphatic group. In some embodiments, Rcis an optionally substituted C1-6 heteroaliphatic group. In some embodiments, Rcis an optionally substituted 3- and 8-membered saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Rcis an optionally substituted 8- and 12-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Rcis an optionally substituted aryl group. In some embodiments, Rcis optionally substituted phenyl. In some embodiments, R2is phenyl. In some embodiments, Rcis an optionally substituted heteroaryl group. In some embodiments, Rcis an optionally substituted 5- to 6-membered heteroaryl having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Rcis an optionally substituted 8- to 12- membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0033] As defined above and described herein, R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a glycoside, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule. In some embodiments, R2is -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, or an optionally substituted aromatic group, an optionally substituted heteroaryl group.

[0034] In some embodiments, R2is -H. In some embodiments, R2is a metal cation. In certain embodiments, R2is an organic cation (e.g. a nitrogen or phosphorous centered cationic group). In some embodiments, R2is an optionally substituted C1-20aliphatic group. In certain embodiments, 13 BUSINESS.31669632.1 409753-016WO (210621)R2is an optionally substituted C1-12aliphatic group. In certain embodiments, R2is an optionally substituted C1-8 aliphatic group. In some embodiments, R2is an optionally substituted C1-6 aliphatic group. In certain embodiments, R2is selected from methyl, ethyl, n-propyl, i-propyl, n-butyl, sec- butyl, and t-butyl. In some embodiments, R2is an optionally substituted C1-20heteroaliphatic group. In some embodiments, R2is an optionally substituted C1-6 heteroaliphatic group. In some embodiments, R2is an optionally substituted 3- and 8-membered saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R2is an optionally substituted 8- and 12-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R2is an optionally substituted aromatic group. In some embodiments, R2is optionally substituted phenyl. In some embodiments, R2is phenyl. In some embodiments, R2is an optionally substituted heteroaryl group. In some embodiments, R2is an optionally substituted 5- to 6-membered heteroaryl having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R2is an optionally substituted 8- to 12- membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0035] In some embodiments, R2is a glycoside. It will be appreciated that a glycoside refers to a moiety comprising a sugar bound to another functional group via a glycosidic bond.

[0036] In some embodiments, R2is nucleotide. In some embodiments, R2is adenosine monophosphate, cytidine monophosphate, guanosine monophosphate, or uridine monophosphate. In some embodiments, R2is deoxyadenosine monophosphate, deoxycytidine monophosphate, deoxyguanosine monophosphate, or deoxythymidine monophosphate.

[0037] In some embodiments, R2is a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule. In some embodiments, R2is an optionally substituted C1-6aliphatic or heteroaliphatic comprising an ascaroside.

[0038] In certain embodiments, R2comprises an amino acid. In certain embodiments, R2comprises a peptide. In certain embodiments, R2comprises a nucleotide.

[0039] As defined above and described herein, each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, 14 BUSINESS.31669632.1 409753-016WO (210621)an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule. In some embodiments, each R3is independently selected from -H and C1-8 aliphatic. In some embodiments, one R3is -H and the other R3is other than -H. In some embodiments, neither R3is -H. In some embodiments, each R3is -H. In some embodiments, an occurrence of R3is an optionally substituted C1-20 aliphatic group. In some embodiments, an occurrence of R3is an optionally substituted C1-6 aliphatic group. In some embodiments, an occurrence of R3is an optionally substituted C1-20heteroaliphatic group. In some embodiments, an occurrence of R3is an optionally substituted C1-6 heteroaliphatic group. In some embodiments, R3is an optionally substituted 3- and 8-membered saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R3is an optionally substituted 8- and 12-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, occurrence of R3is an optionally substituted aryl group. In some embodiments, R3is optionally substituted phenyl. In some embodiments, R3is phenyl. In some embodiments, R3is an optionally substituted heteroaryl group. In some embodiments, R3is an optionally substituted 5- to 6-membered heteroaryl having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R3is an optionally substituted 8- to 12-membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0040] In certain embodiments, at least one R3is -H. In certain embodiments, both R3groups are -H. In certain embodiments, at least one R3is an optionally substituted C1-20aliphatic group. In certain embodiments, both R3groups are an optionally substituted C1-20 aliphatic group which may be the same or different. In certain embodiments, at least one R3is an optionally substituted C1-12 aliphatic group. In certain embodiments, at least one R3is an optionally substituted C1-8aliphatic group. In certain embodiments, at least one R3is an optionally substituted C1-6 aliphatic group. In certain embodiments, at least one R3is selected from methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, and t-butyl. In certain embodiments, at least one R3is -CH2CH2OH. In certain embodiments, at least one R3is -CH2CH2OR2. where R2is as defined in the genera and subgenera herein. In certain embodiments, at least one R3is an optionally substituted aromatic group. In certain embodiments, at least one R3comprises a glycoside. In certain embodiments, at least one 15 BUSINESS.31669632.1 409753-016WO (210621)R3comprises an amino acid. In certain embodiments, at least one R3at least one R3comprises a peptide. In certain embodiments, at least one R3comprises a nucleotide.

[0041] In certain embodiments, an ascaroside is selected from the group consisting of: CO2R2CO R2 2CO2R2O2CO x O x O2R O x x inthe genera and subgenera herein.

[0042] In certain embodiments, an ascaroside is selected from the group consisting of: CO2H CO2H C CO2H O O x O x O2H O x x

[0043] In certain embodiments, an ascaroside is selected from the group consisting of: CO O2R2y CO2R2CO2R2CO2R2in the genera and subgenera herein.

[0044] In certain embodiments, an ascaroside is selected from the group consisting of: CO2H CO2H CO2H

[0045] In certain embodiments, an ascaroside is selected from the group consisting of: 16 BUSINESS.31669632.1 409753-016WO (210621)CO2R2COR2 2CO2R2O2CO x O x O2R O x x

[0046] In certain embodiments, an ascaroside is selected from the group consisting of: COH C CO2H O2O2H CO x O x O2H O x x

[0047] In certain embodiments, an ascaroside is selected from the group consisting of: COR2O2y CO2R2CO2CO2R2O y2R O y

[0048] In certain embodiments, an ascaroside is selected from the group consisting of: CO O2H CO2H CO2H

[0049] In certain embodiments, an ascaroside is selected from the group consisting of:,

[0050] In certain embodiments, an ascaroside is selected from the group consisting of: 17 BUSINESS.31669632.1 409753-016WO (210621)

[0051] In certain embodiments, an ascaroside is selected from the group consisting of:

[0052] In certain embodiments, an ascaroside is selected from the group consisting of:

[0053] In an embodiment, ascarosides useful in the context of the present disclosure have the general structure (I), where Z is –CH(CH3)–(CH2)n–CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide.

[0054] In an embodiment, ascarosides useful in the context of the present disclosure have the general structure (I) where Z is –CH(CH3)–(CH2)n–CH=CH-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide.

[0055] Specific ascarosides that are useful in the context of the present disclosure include, but are not limited to, ascr#7 and ascr#18. 18 BUSINESS.31669632.1 409753-016WO (210621)O isselected from the group consisting of: ascr#9, ascr#12, ascr#14, ascr#1, ascr#10, ascr#16, ascr#18, ascr#20, ascr#22, ascr#24, ascr#26, ascr#28, ascr#30, ascr#32, ascr#34, and ascr#36. In certain embodiments, an ascaroside used in the provided methods is selected from the group consisting of: ascr#10, ascr#16, ascr#18, ascr#20, ascr#22, and ascr#24. In certain embodiments, an ascaroside used in the provided methods is selected from the group consisting of: ascr#9, ascr#14, ascr#10, and ascr#18.

[0057] In certain embodiments, an ascaroside used in the provided methods and compositions is selected from the group consisting of: ascr#5, oscr#9, oscr#12, oscr#1, oscr#14, oscr#10, oscr#16, oscr#18, oscr#20, oscr#22, oscr#24, oscr#26, oscr#28, oscr#30, oscr#32, oscr#34, and oscr#36. In certain embodiments, an ascaroside used in the provided methods is selected from the group consisting of: oscr#10, oscr#16, oscr#18, oscr#20, and oscr#22. In certain embodiments, an ascaroside used in the provided methods is selected from the group consisting of: bhas#5, oscr#9, oscr#12, oscr#1, oscr#14, oscr#10, oscr#16, oscr#18, oscr#20, oscr#22, oscr#24, oscr#26, oscr#28, oscr#30, oscr#32, oscr#34, and oscr#36. In certain embodiments, an ascaroside used in the provided methods is selected from the group consisting of: oscr#10, oscr#16, oscr#18, oscr#20, and oscr#22.

[0058] In certain embodiments, an ascaroside used in the provided methods and compositions is selected from the group consisting of: bhas#9, bhas#10, bhas#16, bhas#18, bhas#22, bhas#24, bhas#26, bhas#28, bhas#30, bhas#32, bhas#34, bhas#36, bhas#38, bhas#40, and bhas#42.

[0059] In certain embodiments, an ascaroside used in the provided methods and compositions is selected from the group consisting of: bhos#10, bhos#16, bhos#18, bhos#22, bhos#24, bhos#26, bhos#28, bhos#30, bhos#32, bhos#34, bhos#36, bhos#38, bhos#40, and bhos#42.

[0060] In certain embodiments, an ascaroside used in the provided methods and compositions is selected from the group consisting of: ascr#18, oscr#16, oscr#17, oscr#15, bhas#18, bhos#16, 19 BUSINESS.31669632.1 409753-016WO (210621)glas#18, dhas#18, ibha#18, ibho#16, icas#18, icos#15, icos#16, and any combination of two or more of these.

[0061] Ascarosides can be obtained from natural sources (e.g., nematodes) or they may be prepared synthetically. Ascarosides can be prepared synthetically, for example, by converting 1- O-substituted rhamnose to 1-O-substituted ascarylose. An exemplary method of preparing ascarosides includes: providing as a feedstock a 1-O-substituted rhamnose; forming a mono- sulfonate ester at the 3-OH group of the feedstock; and treating the mono-sulfonate ester with a hydride source to form a 1-O-substituted ascarylose. In certain embodiments, forming the mono- sulfonate ester is conducted on a substrate without hydroxyl protecting groups at the 2- or 4- position of the rhamnose feedstock. In certain embodiments, such methods comprise contacting the feedstock with a sulfonating agent (i.e., a sulfonyl halide, sulfonic anhydride, or similar reagent) in the presence of a Lewis acid. Specific details regarding the synthesis of 1-O-substituted ascarylose can be found in international publication No. WO 2022 / 024067, which is incorporated herein by reference.

[0062] As indicated, according to the present disclosure, ascarosides can be used in combination with insecticides as a safener to lessen phytotoxic effects of the insecticide on the treated crop. Insecticides work by affecting a variety of biological processes associated with insects. Insecticides can be classified by chemical class. Insecticides whose phytotoxic side effects on crop plants can be reduced using ascarosides include, for example, insecticides from the chemical groups of: alkaloid insecticides; alkyl halide insecticides; aminopyrimidine insecticides; aminotriazene insecticides; antibiotic insecticides; aromatic hydrocarbon insecticides; arylpyrrole insecticides; benzimidazole insecticides; benzoylurea insecticides; beta-ketonitrile insecticides; botanical insecticides; carbamate insecticides; diacylhydrazine insecticides; diamide insecticides; dinitrophenol insecticides; dithiolane insecticides; formamidine insecticides; fumigant insecticides; inorganic insecticides; isoxazoline insecticides; juvenile hormone mimics; macrocyclic lactone insecticides; meta-diamide insecticides; methoxyacrylate insecticides; neonicotinoid insecticides; nereistoxin analogue insecticides; organochlorine insecticides; organophosphorus insecticides; oxadiazine insecticides; oxadiazolone insecticides; perfluoroalkyl sulfonamide insecticides; phenol insecticides; pyrazole insecticides; pyrethrin insecticides; pyrethroid insecticides; pyridine azomethine insecticides; pyrimidinamine insecticides; pyropene 20 BUSINESS.31669632.1 409753-016WO (210621)insecticides; RNA1 insecticides; salicylanilide insecticides; semicarbazone insecticides; steroid insecticides; tetramic acid insecticides; tetronic acid insecticides; thiocarbonate insecticides; thiourea insecticides; and urea insecticides.

[0063] Exemplary alkaloid insecticides include anabasine, matrine, nicotine, nornicotine, oxymatrine, ryania, ryanodine, sabadilla, and sanguinarine.

[0064] Exemplary alkyl halide insecticides include carbon tetrachloride, chloroform, 1,2- dichloropropane, ethylene dibromide, ethylene dichloride, methyl bromide, methyl iodide, methylchloroform, methylene chloride, and tetrachloroethane.

[0065] An exemplary aminopyrimidine insecticide is dicyclanil. An exemplary aminotriazene insecticide is cyromazine. An exemplary antibiotic insecticide is allosamidin. Exemplary aromatic hydrocarbon insecticides include naphthalene and triarathene. An exemplary arylpyrrole insecticide is chlorfenapyr. An exemplary benzimidazole insecticide is fenazaflor. An exemplary beta-ketonitrile insecticide is thiapronil. Exemplary dinitrophenol insecticides include dinex, dinoprop, dinosam, and 4-6-dinitro-o-cresol (DNOC). An exemplary dithiolane insecticide is isoprothiolane. Exemplary formamidine insecticides include amitraz, chlordimeform, medimeform, and semiamitraz.

[0066] Exemplary benzoylurea insecticides include bistrifluron, chlorbenzuron, chlorfluazuron, dichlorbenzuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, penfluron, teflubenzuron, and triflumuron.

[0067] Exemplary botanical insecticides include allicin, azadirachtin, carvacrol, d-limonene, quassia, rhodojaponin-III, rotenone, and triptolide.

[0068] Exemplary carbamate insecticides include alanycarb, aldicarb, aldoxycarb, allyxycarb, aminocarb, bendiocarb, benfuracarb, bufencarb, butacarb, butocarboxim, butoxycarboxim, carbanolate, carbaryl, carbofuran, carbosulfan, cloethocarb, 2-chlorophenyl methylcarbamate (CPMC), decarbofuran, dicresyl, dimetan, dimethacarb, dimetilan, dioxacarb, p-(ethylthio)phenyl methylcarbamate (EMPC), ethiofencarb, fenethacarb, fenobucarb, formetanate, formparanate, furathiocarb, hyquincarb, isolan, isoprocarb, methiocarb, methomyl, metolcarb, mexacarbate, nitrilacarb, oxamyl, pirimicarb, promacyl, promecarb, propoxur, pyramat, pyrolan, tazimcarb, 21 BUSINESS.31669632.1 409753-016WO (210621)thiocarboxime, thiodicarb, thiofanox, trimethacarb, 3,5-xylyl methylcarbamate (XMC), and xylylcarb.

[0069] Exemplary diacylhydrazine insecticides include chromafenozide, furan tebufenozide, halofenozide, methoxyfenozide, tebufenozide, and yishijing.

[0070] Exemplary diamide insecticide include chlorantraniliprole, cyantraniliprole, cyhalodiamide, cyclaniliprole, flubendiamide, fluchlordiniliprole, tetrachlorantraniliprole, tetraniliprole, and tiorantraniliprole.

[0071] Exemplary fumigant insecticides include acrylonitrile, allyl isothiocyanate, calcium cyanide, carbon disulfide, carbon tetrachloride, carbonyl sulfide, chloroform, chloropicrin, cyanogen, 1,2-dichloropropane, dimethyl disulfide, ethyl formate, ethylene dibromide, ethylene dichloride, ethylene oxide, hydrogen cyanide, methyl bromide, methyl iodide, methyl isothiocyanate, methylchloroform, methylene chloride, phosphine, sodium cyanide, sulfuryl fluoride, and tetrachloroethane.

[0072] Exemplary inorganic insecticides include barium hexafluorosilicate, borax, boric acid, calcium arsenate, calcium polysulfide, copper arsenate, copper naphthenate, copper oleate, cryolite, diatomaceous earth, lead arsenate, mercurous chloride, Paris green, potassium arsenite, potassium thiocyanate, silica gel, sodium arsenite, sodium fluoride, sodium silicofluoride, sodium thiocyanate, and sulfuryl fluoride.

[0073] Exemplary isoxazoline insecticides include afoxolaner, esafoxolaner, fluralaner, fluxametamide, isocycloseram, lotilaner, mivorilaner, sarolaner, tigolaner, and umifoxolaner.

[0074] Exemplary juvenile hormone mimics include dayoutong, diofenolan, epofenonane, fenoxycarb, hydroprene, juvenile hormone I, juvenile hormone II, juvenile hormone III, kinoprene, Methoprene, pyriproxyfen, and triprene.

[0075] Exemplary macrocyclic lactone insecticides include abamectin, doramectin, emamectin, eprinomectin, ivermectin, lepimectin, moxidectin, selamectin, spinetoram, and spinosad.

[0076] Exemplary meta-diamide insecticides include broflanilide, cyproflanilide, and modoflaner. An exemplary methoxyacrylate insecticide is flupyroxystrobin. An exemplary oxadiazine insecticide is indoxacarb. An exemplary oxadiazolone insecticide is metoxadiazone. Exempalry perfluoroalkyl sulfonamide insecticides are flursulamid and sulfluramid. Exemplary pyridine 22 BUSINESS.31669632.1 409753-016WO (210621)azomethine insecticides include pymetrozine and pyrifluquinazon. Exemplary pyrimidinamine insecticides include flufenerim and pyrimidifen. An exemplary pyropene insecticide is afidopyropen. An exemplary RNA1 insecticide is ledprona. An exemplary salicylanilide insecticide is closantel. An exemplary semicarbazone insecticide is metaflumizone. Exemplary steroid insecticides include α-ecdysone and ecdysterone. Exemplary tetramic acid insecticides include spidoxamat, spiropidion, and spirotetramat. Exemplary tetronic acid insecticides include spirodiclofen and spiromesifen. Exemplary thiocarbonate insecticides include O,O-diethyl dithiobis(thioformate) (EXD) and sodium tetrathiocarbonate. An exemplary thiourea insecticide includes diafenthiuron. Exemplary urea insecticides include flucofuron and sulcofuron.

[0077] Exemplary neonicotinoid insecticides include acetamiprid, clothianidin, cycloxaprid, dicloromezotiaz, dinotefuran, fenmezoditiaz, flupyradifurone, flupyrimin, imidacloprid, imidaclothiz, nitenpyram, nithiazine, paichongding, sulfoxaflor, thiacloprid, thiamethoxam, and triflumezopyrim.

[0078] Exemplary nereistoxin analogue insecticides include bensultap, cartap, polythialan, thiocyclam, and thiosultap.

[0079] Exemplary organochlorine insecticides include aldrin, alpha-endosulfan, bromociclen, p,p- dibromo-diphenyl-1,1,1-trichloroethane (bromo-DDT), camphechlor, chlorbicyclen, chlordane, chlordecone, dichlorodiphenyltrichloroethane (DDT), difluorodiphenyltrichloroethane (DFDT), dieldrin, dilor, endosulfan, endrin, 1,1-dichloro-2,2-bis(4-ethylphenyl)ethane (ethyl-DDD), hexachlorocyclohexane (HCH), heptachlor, isobenzan, isodrin, kelevan, lindane, methoxychlor, mirex, p-dichlorobenzene, and tetrachlorodiphenylethane (TDE).

[0080] Exemplary organophosphorus insecticides include acephate, acethion, acetophos, amidithion, amiton, athidathion, azamethiphos, azinphos-ethyl, azinphos-methyl, azothoate, bromfenvinfos, bromophos, bromophos-ethyl, butathiofos, butonate, cadusafos, calvinphos, carbophenothion, chloramine phosphorus, chlorethoxyfos, chlorfenvinphos, chlormephos, chlorphoxim, chlorprazophos, chlorpyrifos, chlorpyrifos-methyl, chlorthiophos, colophonate, coumaphos, coumithoate, crotoxyphos, crufomate, cyanofenphos, cyanophos, cyanthoate, cythioate, demephion, demeton, demeton-methyl, demeton-S-methylsulphon, demephion-O, demephion-S, demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl, dialifos, diazinon, dicapthon, dichlofenthion, dichlorvos, dicrotophos, dimefox, dimethoate, dimethylvinphos, 23 BUSINESS.31669632.1 409753-016WO (210621)dioxabenzofos, dioxathion, disulfoton, dithicrofos, endothion, ethyl p-nitrophenyl phenylphosphorothioate (EPN), etaphos, ethion, ethoate-methyl, ethoprophos, S- [(ethylsulfinyl)methyl] O,O-diisopropyl phosphorodithioate (IPSP), etrimfos, famphur, fenamiphos, fenchlorphos, fenitrothion, fensulfothion, fenthion, fenthion-ethyl, flupyrazofos, fonofos, formothion, fosmethilan, fospirate, fosthietan, heptenophos, heterophos, , isazofos, isocarbophos, isofenphos, isofenphos-methyl, isothioate, isoxathion, jodfenphos, leptophos, lirimfos, lythidathion, malathion, mazidox, mecarbam, mecarphon, menazon, mephosfolan, mesulfenfos, methacrifos, methamidophos, methidathion, methocrotophos, methylacetophos, mevinphos, mipafox, monocrotophos, morphothion, naftalofos, naled, omethoate, oxydemeton- methyl, oxydeprofos, oxydisulfoton, parathion, parathion-methyl, phenkapton, phenthoate, phorate, phosalone, phosfolan, phosfolan-methyl, phosglycin, phosmet, phosnichlor, phosphamidon, phoxim, phoxim-methyl, pirimetaphos, pirimioxyphos, pirimiphos-ethyl, pirimiphos-methyl, primidophos, profenofos, propaphos, propetamphos, prothidathion, prothiofos, prothoate, pyraclofos, pyrazophos, pyrazothion, pyridaphenthion, pyrimitate, quinalphos, quinalphos-methyl, quinothion, schradan, sophamide, sulfotep, sulprofos, tebupirimfos, temephos, tetraethyl pyrophosphate (TEPP), terbufos, tetrachlorvinphos, thicrofos, thiometon, triamiphos, triazophos, trichlorfon, trichlormetaphos-3, trichloronat, trifenofos, xiaochongliulin, and zolaprofos.

[0081] Exemplary phenol insecticides include pentachlorophenol, precocenes, precocene I, precocene II, and precocene III.

[0082] Exemplary pyrazole insecticides include acetoprole, dimpropyridaz, ethiprole, fipronil, flufiprole, pyrafluprole, pyriprole, tolfenpyrad, and vaniliprole.

[0083] Exemplary pyrethrin / pyrethroid insecticides include acrinathrin, allethrin, alpha- cypermethrin, barthrin, beta-cyfluthrin, beta-cypermethrin, bifenthrin, bioallethrin, bioethanomethrin, biopermethrin, bioresmethrin, brofenvalerate, brofluthrinate, bromethrin, butethrin, chlorempenthrin, chloroprallethrin, cinerin, cismethrin, cyclethrin, cycloprothrin, cyfluthrin, cyhalothrin, cypermethrin, cyphenothrin, deltamethrin, d-fanshiluquebingjuzhi, dimefluthrin, dimethrin, d-teflumethrin, empenthrin, epsilon-metofluthrin, epsilon- momfluorothrin, esdépalléthrine, esfenvalerate, etofenprox, fenfluthrin, fenpirithrin, fenpropathrin, fenvalerate, flucythrinate, flufenprox, fluvalinate, furamethrin, furethrin, gamma- 24 BUSINESS.31669632.1 409753-016WO (210621)cyhalothrin, halfenprox, heptafluthrin, imiprothrin, japothrins, jasmolin, kadethrin, kappa- bifenthrin, kappa-tefluthrin, lambda-cyhalothrin, meperfluthrin, methothrin, metofluthrin, momfluorothrin, pentmethrin, permethrin, phenothrin, prallethrin, profluthrin, proparthrin, protrifenbute, pyrethrin, pyresmethrin, renofluthrin, resmethrin, silafluofen, sulfoxime, supermethrin, tau-fluvalinate, tefluthrin, terallethrin, tetramethrin, tetramethylfluthrin, theta- cypermethrin, thiofluoximate, tralocythrin, tralomethrin, transfluthrin, transpermethrin, valerate, and zeta-cypermethrin.

[0084] Additional unclassified insecticides that can be used in combination with ascarosides include benzpyrimoxan, buprofezin, crotamiton, fenoxacrim, fentrifanil, flometoquin, flonicamid, fluhexafon, hydramethylnon, indazapyroxamet, jiahuangchongzong, ledprona, malonoben, maltodextrin, nicofluprole, nifluridide, oxazosulfyl, plifenate, pyridaben, pyridalyl, rafoxanide, sulfiflumin, tartar emetic, thuringiensin, triazamate, trichlophenidine, and tyclopyrazoflor.

[0085] It is recognized that additional insecticides and other insect regulators may be included in the methods and compositions of the invention. Other additional active agents are known in the art that can be used with the combination described herein and include fungicides, herbicides, miticides, arthropodicides, bactericides, ectoparasiticides, and the like, that are compatible with the combination of the present invention and not antagonistic to the activity of the ascaroside(s) or the insecticide(s).

[0086] In some cases, the common names are mentioned in the insecticides lists disclosed herein. In such cases, the common name identifies the active ingredient in its commercially available form or forms including derivatives such as salts and esters, even if a specific salt or ester is not mentioned specifically (preferably in its usual commercial form).

[0087] The application of the one or more insecticides and the one or more ascarosides can be in pre- or post-emergence application. The preferred application method depends on the usual or optimal application time of the particular insecticide or insecticide combination.

[0088] The anti-pathogen activity of ascarosides provides additional benefits to the methods and composition. Advantageously, the one or more ascarosides can not only provide a reduction in the phytotoxic effects on plants commonly associated with insecticide application, but can also (or alternatively) provide long-lasting protection against fungi, mold, bacteria, viruses and / or nematodes. For example, although fungicides and antibacterials are generally applied at later time 25 BUSINESS.31669632.1 409753-016WO (210621)points in crop growth when such pathogens are present, the present disclosure provides methods and compositions which employ application of an ascaroside at a very early time point (i.e., a time point at which insecticides are traditionally applied to crops) and can impart resistance to pathogens in the crop plants so treated. In some embodiments, although applying the ascaroside at an early stage in the plant life cycle, it surprisingly exhibits a long-lasting effect, e.g., decreasing or preventing damage caused by fungi, bacteria, viruses and molds for a period of time exceeding 3 days after application, exceeding 5 days after application, exceeding one week after application, exceeding two weeks after application, exceeding one-month after application, exceeding two- months after application, or exceeding three-months after application.

[0089] The co-application of ascarosides and insecticides early in the season can also provide important economic advantages to growers and enhance the sustainability of crop production. Co- application of ascarosides with insecticide can prevent the need for a separate fungicide treatment later in the season. This saves fuel and labor and potentially avoids the need to apply more toxic pathogen control products since ascaroside treatments can act as a preventative control that enhances crops’ tolerance to a broad range of pathogens. An additional or alternate benefit of combining ascarosides with insecticide treatments is the control of early season plant pathogens such as fungi, bacteria, viruses and nematodes. Co-application of ascarosides with insecticides can prevent the need for a separate early season disease control application (e.g. of a fungicide, antimicrobial, or nematicide) which saves fuel and labor and potentially avoids the need to apply more toxic pathogen control products since ascaroside treatments can act as a preventative control that enhances crops’ tolerance to a broad range of pathogens.

[0090] In certain embodiments, the disclosure provides blends of one or more insecticides and one or more ascarosides. In certain embodiments, the disclosure provides blends of one or more insecticides and one or more ascarosides, characterized in that the blended product reduces the phytotoxic effects on the crops to which it is applied compared to application of the one or more insecticides alone. In certain embodiments, the blend is characterized in that one or more phytotoxicity symptoms in a treated crop is reduced by at least 10% relative to use of a comparable composition lacking ascaroside(s). In certain embodiments, provided methods are characterized in that one or more phytotoxicity symptoms is reduced by at least 15%, by at least 20%, by at least 25%, by at least 35%, by at least 50%, by at least 75%, or by at least 90% relative to use of a comparable composition lacking ascaroside(s). In certain embodiments, provided blends are 26 BUSINESS.31669632.1 409753-016WO (210621)characterized in that one or more phytotoxicity symptoms are substantially absent relative to use of a comparable composition lacking ascaroside(s).

[0091] In some embodiments, the blend is characterized in that one or more phytotoxicity symptoms in a treated crop is reduced by 10-90%, 10-70%, 10-50%, 10-30%, 30-90%, 50-90%, 70-90%, 30-70%, or 30-50% relative to use of a comparable composition lacking ascaroside(s).

[0092] In some embodiments, phytotoxicity symptoms are measured by a phytotoxicity rating, e.g., as described by Example 1 herein. In some embodiments, the blend is characterized in that the phytotoxicity rating (e.g., as described in Example 1 herein) in a treated crop is reduced by at least 10% relative to use of a comparable composition lacking ascaroside(s). In certain embodiments, provided methods are characterized in that the phytotoxicity rating (e.g., as described in Example 1 herein) is reduced by at least 15%, by at least 20%, by at least 25%, by at least 35%, by at least 50%, by at least 75%, or by at least 90% relative to use of a comparable composition lacking ascaroside(s). In some embodiments, the blend is characterized in that the phytotoxicity rating (e.g., as described in Example 1 herein) in a treated crop is reduced by 10- 90%, 10-70%, 10-50%, 10-30%, 30-90%, 50-90%, 70-90%, 30-70%, or 30-50% relative to use of a comparable composition lacking ascaroside(s).

[0093] In certain embodiments, phytotoxic effects that can be reduced by the use of ascarosides are selected from the group consisting of: poor germination; death of seedlings; death or damage to rapidly growing succulent tissues; stunting or delayed plant development; misshaped or distorted plants, fruits, or leaves; russeting or bronzing of leaves or fruit; dead spots or flecks on leaves; dead leaf tips or leaf margins; dead areas between the veins of the leaves; and combinations of any two or more of these.

[0094] The compounds described herein can be provided in a single formulation or agricultural composition or in separate formulations or agricultural compositions. Additionally, the components may be applied separately. When the one or more ascarosides and the one or more insecticides are applied separately, the one or more ascarosides can be applied before or after the application of the one or more insecticides. Generally, when applied separately, the components are co-applied at close points in time, e.g., substantially simultaneously or within about several minutes or hours, including within about 5 minutes, within about 10 minutes, within about 30 minutes, within about an hour, within about 2 hours, within about 3 hours, within about 4 hours, 27 BUSINESS.31669632.1 409753-016WO (210621)within about 6 hours, within about 7 hours, within about 8 hours, within about 24 hours, or within about 2 days of one another).

[0095] Co-application, can, in some embodiments, involve combining the one or more ascarosides and the one or more insecticides before application (e.g., immediately prior to application) to the plants. The one or more ascarosides and the one or more insecticides may be mixed in the field; for example, the one or more ascarosides can be added to a tank mix solution comprising the one or more insecticides.

[0096] In other embodiments, the components to be co-applied can be combined at a timepoint further in advance of application. In such embodiments, an agricultural formulation is prepared comprising one or more ascarosides and the one or more insecticides in combination with one or more inert ingredients. Advantageously, in such combinations, the one or more ascarosides and the one or more insecticides are compatible with one another, and the resulting formulations can demonstrate stability over long periods of time (e.g., about one week or more, about one month or more, about two months or more, about three months or more, about four months or more, about five months or more, or about six months or more).

[0097] The one or more ascarosides and the one or more insecticides can be formulated together in a combination formulation. As noted above, the formulations or methods can include other active ingredients and / or plant or plant product treatment compounds. Further, some of the compositions will be residual in that they do not easily wash off the leaves during rain, and thus can protect plants during and after rainy weather.

[0098] In certain embodiments, the disclosure provides blends of one or more insecticides and one or more ascarosides where a weight ratio of insecticide(s) to ascaroside is greater than 10:1, greater than 100:1, greater than 500:1 or greater than 1000:1. In certain embodiments, the disclosure provides blends of an insecticide and an ascaroside where a weight ratio of an insecticide to ascaroside is greater than 1500:1, greater than 2000:1, greater than 3000:1, greater than 5000:1, greater than 7500:1, greater than 10,000:1, greater than 15,000:1, greater than 20,000:1, greater than 30,000:1, or greater than 50,000:1.

[0099] The formulations or compositions can be formulated as is conventional in the art and may be liquid or dry compositions. Dry compositions include powders and the like. The compositions can be utilized as liquid concentrates, Ready-To-Use (RTU) liquid sprays, dusts, or solids, 28 BUSINESS.31669632.1 409753-016WO (210621)depending upon the needs of the user. The formulation chosen will depend on the use of the product. In use, the composition can be applied directly to the plant.

[0100] In general, a formulation will include at least one ascaroside as described herein, or at least one ascaroside and one or more insecticides, and one or more agriculturally acceptable adjuvants (also referred to herein as “agriculturally suitable adjuvants”). Agriculturally suitable adjuvants are used to enhance the effectiveness of the compounds described herein and include, but are not limited to, surfactants, emulsifiers, oils, salts, and the like. The adjuvants may be added into the formulation or alternatively can be added separately at the time of application to the crops. In some embodiments, wetting agents, emulsifiers, spreaders, and the like may be used in the formulations. Formulations include concentrated versions, in which the present active agent (a compound as described herein) is present in a concentration of from 0.001 to 98.0 percent, with the remaining content being physiologically acceptable carriers. Such formulations, especially those with less than 50 percent of the present compound, can sometimes be used directly, but these formulations can also be diluted with other physiologically acceptable carriers to form more dilute treating formulations. These latter formulations can include the compounds described herein in lesser concentrations of from 0.001 to 0.1 percent.

[0101] The formulations may additionally contain “adjuvant surfactants” to enhance deposition, wetting, and penetration of the compounds onto the target crop and organism. These “adjuvant surfactants” may optionally be employed as a component of the formulation or as a tank mix. The amount of adjuvant surfactant will typically vary from 0.01 to 1.0 percent by volume, based on a spray-volume of water, preferably 0.05 to 0.5 volume percent. Suitable adjuvant surfactants include, but are not limited to ethoxylated nonyl phenols, ethoxylated synthetic or natural alcohols, salts of the esters or sulfosuccinic acids, ethoxylated organosilicones, ethoxylated fatty amines, blends of surfactants with mineral or vegetable oils, crop oil concentrate (mineral oil (85%) + emulsifiers (15%)); nonylphenol ethoxylate; benzylcocoalkyldimethyl quaternary ammonium salt; blend of petroleum hydrocarbon, alkyl esters, organic acid, and anionic surfactant; C9- Cu alkylpolyglycoside; phosphated alcohol ethoxylate; natural primary alcohol (C12- Ci6) ethoxylate; di -sec-butylphenol EO-PO block copolymer; polysiloxane-methyl cap; nonylphenol ethoxylate + urea ammonium nitrate; emulsified methylated seed oil; tridecyl alcohol (synthetic) ethoxylate 29 BUSINESS.31669632.1 409753-016WO (210621)(8EO); tallow amine ethoxylate (15 EO); PEG(400) dioleate-99. The formulations may also include oil-in-water emulsions.

[0102] “Surfactants” comprise typically about 0.5% to about 10% of the wettable powder. “Surfactants” include sulfonated lignins, condensed naphthalene-sulfonates, the naphthalene- sulfonates, alkyl-benenesulfonates, alkysulfonates or nonionic surfactants such as ethylene oxide adducts of alkylphenols or mixtures thereof.

[0103] Representative organic solvents which may be employed in preparing the emulsifiable concentrates of the disclosed ascaroside(s) and / or insecticide(s) are the aromatic liquids such as xylene, propyl benzene fractions; or mixed naphthalene fractions, mineral oils, substituted aromatic organic liquids such as dioctyl phthalate; kerosene; dialkyl amides of various fatty acids, particularly the dimethyl amides of fatty glycols and glycol derivatives such as the n-butyl ether, ethyl ether or methyl ether of diethylene glycol, the methyl ether of triethylene glycol, petroleum fractions or hydrocarbons such as mineral oil, aromatic solvents, paraffinic oils, and the like; terpenic solvents, rosin derivatives, aliphatic ketones such as cyclohexanone, complex aliphatic and aromatic alcohols such as 2-ethoxyethanol, vegetable oils such as soy bean oil, rape seed oil, olive oil, castor oil, sunflower seed oil, coconut oil, com oil, cotton seed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and the like; esters of the above vegetable oils; and the like. Mixtures of two or more organic liquids may also be employed in the preparation of the emulsifiable concentrate. Organic liquids include xylene, and propyl benzene fractions, with xylene being most preferred in some cases. Surface-active dispersing agents are typically employed in liquid formulations and in an amount of from 0.1 to 20 percent by weight based on the combined weight of the dispersing agent with one or more of the compounds.

[0104] “Emulsifiers” for emulsifiable concentrates are typically mixed ionic and / or nonionic surfactants such as those mentioned herein or their equivalents. Examples of nonionic emulsifiers useful in preparing the emulsifiable concentrates include the polyalkylene glycol ethers and condensation products of alkyl and aryl phenols, aliphatic alcohols, aliphatic amines or fatty acids with ethylene oxide, propylene oxides such as the ethoxylated alkyl phenols and carboxylic esters solubilized with the polyol or polyoxyalkylene. Cationic emulsifiers include quaternary ammonium compounds and fatty amine salts. Anionic emulsifiers include the oil soluble salts (e.g., 30 BUSINESS.31669632.1 409753-016WO (210621)calcium) of alkylaryl sulphonic acids, oil-soluble salts or sulfated polyglycol ethers and appropriate salts of phosphated- polyglycol ether.

[0105] Dusts containing the ascaroside(s) and / or insecticide(s) may be prepared by intimately mixing one or more of the compounds in powdered form with a suitable dusty agricultural carrier, such as, for example, kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1 to about 10 weight percent of the compounds, based on the total weight of the dust.

[0106] Wettable powders may be agglomerated or compacted to form water dispersible granules. These granules include mixtures of compounds, inert carriers suitable for granular applications, and surfactants. The concentration of the compound is typically between about 0.1% to about 90% by weight. The “inert carrier suitable for granular applications” is typically prophyllite, talc, chalk, gypsum, Fuller's earth, bentonite, attapulgite, starch, casein, gluten, montmorillonite clays, diatomaceous earths, purified silicates, or the like. In such operations, the finely divided carrier and surfactants are typically blended with the compound(s) and milled.

[0107] “Aqueous suspensions” may be prepared where the one or more ascarosides and / or one or more insecticides are dispersed in an aqueous vehicle at a concentration typically in the range of between about 5% to about 50% by weight. The suspensions are prepared by finely grinding the compound and vigorously mixing it into a vehicle of water, surfactants, and dispersants. Inert ingredients such as inorganic salts and synthetic or natural gums may also be employed to increase the density and / or viscosity of the aqueous vehicle as is desired.

[0108] As described herein, the compositions and methods of the invention are useful for lessening the phytotoxic effects of the insecticide on the treated crop. The method comprises applying a combination of an effective amount of an ascaroside composition and an insecticide composition to a seed, a plant, plant foliage, or to the soil where the plant is grown. DEFINITIONS

[0109] In order for the present disclosure to be more readily understood, certain terms are defined below. Additional definitions for the following terms and other terms are set forth throughout the specification. In this application, unless otherwise clear from context, the term “a” may be understood to mean “at least one.” 31 BUSINESS.31669632.1 409753-016WO (210621)

[0110] As used in this application, the term “or” may be understood to mean “and / or.” In this application, the terms “comprising” and “including” may be understood to encompass itemized components or steps whether presented by themselves or together with one or more additional components or steps. As used in this application, the term “comprise” and variations of the term, such as “comprising” and “comprises,” are not intended to exclude other additives, components, integers, or steps.

[0111] About, Approximately: As used herein, the terms “about” and “approximately” are used as equivalents. Unless otherwise stated, the terms “about” and “approximately” may be understood to permit standard variation as would be understood by those of ordinary skill in the art. Where ranges are provided herein, the endpoints are included. Any numerals used in this application with or without about / approximately are meant to cover any normal fluctuations appreciated by one of ordinary skill in the relevant art. In some embodiments, the term “approximately” or “about” refers to a range of values that fall within 25 %, 20 %, 19 %, 18 %, 17 %, 16 %, 15 %, 14 %, 13 %, 12 %, 11 %, 10 %, 9 %, 8 %, 7 %, 6 %, 5 %, 4 %, 3 %, 2 %, 1 %, or less in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context (except where such number would exceed 100 % of a possible value).

[0112] Definitions of specific functional groups and chemical terms are described in more detail below. For purposes of this invention, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75th Ed., inside cover, and specific functional groups are generally defined as described therein. Additionally, general principles of organic chemistry, as well as specific functional moieties and reactivity, are described in 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 of which are incorporated herein by reference.

[0113] Certain compounds provided herein can comprise one or more asymmetric centers, and thus can exist in various stereoisomeric forms, e.g., enantiomers and / or diastereomers. Thus, inventive compounds and compositions thereof may be in the form of an individual enantiomer, 32 BUSINESS.31669632.1 409753-016WO (210621)diastereomer or geometric isomer, or may be in the form of a mixture of stereoisomers. In certain embodiments, compounds described herein are enantiopure compounds. In certain other embodiments, mixtures of enantiomers or diastereomers are provided.

[0114] Furthermore, certain compounds as described herein may have one or more double bonds that can exist as either a Z or E isomer, unless otherwise indicated. The compounds can be provided as individual isomers substantially free of other isomers and alternatively, as mixtures of various isomers, e.g., racemic mixtures of enantiomers.

[0115] As used herein, the term “isomers” includes any and all geometric isomers and stereoisomers. For example, “isomers” include cis– and trans–isomers, E– and Z– isomers, R– and S–enantiomers, diastereomers, (D)–isomers, (L)–isomers, racemic mixtures thereof, and other mixtures thereof, as falling within the scope of the disclosure. For instance, a compound may, in some embodiments, be provided substantially free of one or more corresponding stereoisomers, and may also be referred to as “stereochemically enriched.”

[0116] Where a particular enantiomer is preferred, it may, in some embodiments be provided substantially free of the opposite enantiomer, and may also be referred to as “optically enriched.” “Optically enriched,” as used herein, means that the compound is made up of a significantly greater proportion of one enantiomer. In certain embodiments the compound is made up of at least about 90% by weight of an enantiomer. In some embodiments the compound is made up of at least about 95%, 97%, 98%, 99%, 99.5%, 99.7%, 99.8%, or 99.9% by weight of an enantiomer. In some embodiments the enantiomeric excess of provided compounds is at least about 90%, 95%, 97%, 98%, 99%, 99.5%, 99.7%, 99.8%, or 99.9%. In some embodiments, enantiomers may be isolated from racemic mixtures by any method known to those skilled in the art, including chiral high pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts or prepared by asymmetric syntheses. See, for example, Jacques, et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen, S.H., et al., Tetrahedron 33:2725 (1977); Eliel, E.L. Stereochemistry of Carbon Compounds (McGraw–Hill, NY, 1962); Wilen, S.H. Tables of Resolving Agents and Optical Resolutions p.268 (E.L. Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN 1972).

[0117] The terms “halo” and “halogen” as used herein refer to an atom selected from fluorine (fluoro, –F), chlorine (chloro, –Cl), bromine (bromo, –Br), and iodine (iodo, –I). 33 BUSINESS.31669632.1 409753-016WO (210621)

[0118] The term “aliphatic” or “aliphatic group”, as used herein, denotes a hydrocarbon moiety that may be straight–chain (i.e., unbranched), branched, or cyclic (including fused, bridging, and spiro–fused polycyclic) and may be completely saturated or may contain one or more units of unsaturation, but which is not aromatic. Unless otherwise specified, aliphatic groups contain 1– 30 carbon atoms. In certain embodiments, aliphatic groups contain 1–12 carbon atoms. In certain embodiments, aliphatic groups contain 1–8 carbon atoms. In certain embodiments, aliphatic groups contain 1–6 carbon atoms. In some embodiments, aliphatic groups contain 1–5 carbon atoms, in some embodiments, aliphatic groups contain 1–4 carbon atoms, in yet other embodiments aliphatic groups contain 1–3 carbon atoms, and in yet other embodiments aliphatic groups contain 1–2 carbon atoms. Suitable aliphatic groups include, but are not limited to, linear or branched, alkyl, alkenyl, and alkynyl groups, and hybrids thereof such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl.

[0119] The term “heteroaliphatic” or “heteroaliphatic group”, as used herein, denotes an aliphatic group where one or more carbon or hydrogen atoms are replaced by a heteroatom (e.g. oxygen, nitrogen, sulfur, phosphorous, boron, etc.). In some embodiments, a heteroaliphatic group is a heterocyclyl group.

[0120] The term "unsaturated", as used herein, means that a moiety has one or more double or triple bonds.

[0121] The term “alkyl,” as used herein, refers to saturated, straight– or branched–chain hydrocarbon radicals derived from an aliphatic moiety containing between one and six carbon atoms by removal of a single hydrogen atom. Unless otherwise specified, alkyl groups contain 1– 12 carbon atoms. In certain embodiments, alkyl groups contain 1–8 carbon atoms. In certain embodiments, alkyl groups contain 1–6 carbon atoms. In some embodiments, alkyl groups contain 1–5 carbon atoms, in some embodiments, alkyl groups contain 1–4 carbon atoms, in yet other embodiments alkyl groups contain 1–3 carbon atoms, and in yet other embodiments alkyl groups contain 1–2 carbon atoms. Examples of alkyl radicals include, but are not limited to, methyl, ethyl, n–propyl, isopropyl, n–butyl, iso–butyl, sec–butyl, sec–pentyl, iso–pentyl, tert–butyl, n–pentyl, neopentyl, n–hexyl, sec–hexyl, n–heptyl, n–octyl, n–decyl, n–undecyl, dodecyl, and the like.

[0122] The term “alkenyl,” as used herein, denotes a monovalent group derived from a straight– or branched–chain aliphatic moiety having at least one carbon–carbon double bond by the removal 34 BUSINESS.31669632.1 409753-016WO (210621)of a single hydrogen atom. Unless otherwise specified, alkenyl groups contain 2–12 carbon atoms. In certain embodiments, alkenyl groups contain 2–8 carbon atoms. In certain embodiments, alkenyl groups contain 2–6 carbon atoms. In some embodiments, alkenyl groups contain 2–5 carbon atoms, in some embodiments, alkenyl groups contain 2–4 carbon atoms, in yet other embodiments alkenyl groups contain 2–3 carbon atoms, and in yet other embodiments alkenyl groups contain 2 carbon atoms. Alkenyl groups include, for example, ethenyl, propenyl, butenyl, 1–methyl–2–buten–1–yl, and the like.

[0123] The term “aryl” used alone or as part of a larger moiety as in “aralkyl”, “aralkoxy”, or “aryloxyalkyl”, refers to monocyclic and polycyclic ring systems having a total of five to 20 ring members, wherein at least one ring in the system is aromatic and wherein each ring in the system contains three to twelve ring members. The term “aryl” may be used interchangeably with the term “aryl ring”. In certain embodiments, “aryl” refers to an aromatic ring system which includes, but is not limited to, phenyl, biphenyl, naphthyl, anthracyl and the like, which may bear one or more substituents. Also included within the scope of the term “aryl”, as it is used herein, is a group in which an aromatic ring is fused to one or more additional rings, such as benzofuranyl, indanyl, phthalimidyl, naphthimidyl, phenantriidinyl, or tetrahydronaphthyl, and the like.

[0124] The terms “heteroaryl” and “heteroar–,” used alone or as part of a larger moiety, e.g., “heteroaralkyl,” or “heteroaralkoxy,” refer to groups having 5 to 10 ring atoms, preferably 5, 6, or 9 ring atoms; having 6, 10, or 14 pelectrons shared in a cyclic array; and having, in addition to carbon atoms, from one to five heteroatoms. The term “heteroatom” refers to nitrogen, oxygen, or sulfur, and includes any oxidized form of nitrogen or sulfur, and any quaternized form of a basic nitrogen. Heteroaryl groups include, without limitation, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl, purinyl, naphthyridinyl, and pteridinyl. The terms “heteroaryl” and “heteroar–”, as used herein, also include groups in which a heteroaromatic ring is fused to one or more aryl, cycloaliphatic, or heterocyclyl rings, where the radical or point of attachment is on the heteroaromatic ring. Nonlimiting examples include indolyl, isoindolyl, benzothienyl, benzofuranyl, dibenzofuranyl, indazolyl, benzimidazolyl, benzthiazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 4H–quinolizinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, tetrahydroquinolinyl, 35 BUSINESS.31669632.1 409753-016WO (210621)tetrahydroisoquinolinyl, and pyrido[2,3–b]–1,4–oxazin–3(4H)–one. A heteroaryl group may be monocyclic, bicyclic, bridged bicyclic, or spirocyclic. The term “heteroaryl” may be used interchangeably with the terms “heteroaryl ring,” “heteroaryl group,” or “heteroaromatic,” any of which terms include rings that are optionally substituted. The term “heteroaralkyl” refers to an alkyl group substituted by a heteroaryl, wherein the alkyl and heteroaryl portions independently are optionally substituted. The term “heteroarylenyl” refers to bivalent heteroaryl groups (e.g., pyridylenyl).

[0125] As used herein, the terms “heterocycle,” “heterocyclyl,” “heterocyclic radical,” and “heterocyclic ring” are used interchangeably and refer to a stable 5– to 7–membered monocyclic or 7–10–membered bicyclic heterocyclic moiety that is either saturated or partially unsaturated, and having, in addition to carbon atoms, one or more, preferably one to four, heteroatoms, as defined above. When used in reference to a ring atom of a heterocycle, the term "nitrogen" includes a substituted nitrogen. As an example, in a saturated or partially unsaturated ring having 0–3 heteroatoms selected from oxygen, sulfur or nitrogen, the nitrogen may be N (as in 3,4–dihydro– 2H–pyrrolyl), NH (as in pyrrolidinyl), or +NR (as in N–substituted pyrrolidinyl).

[0126] A heterocyclic ring can be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure and any of the ring atoms can be optionally substituted. Examples of such saturated or partially unsaturated heterocyclic radicals include, without limitation, tetrahydrofuranyl, tetrahydrothiophenyl pyrrolidinyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, and quinuclidinyl. The terms “heterocycle,” “heterocyclyl,” “heterocyclyl ring,” “heterocyclic group,” “heterocyclic moiety,” and “heterocyclic radical,” are used interchangeably herein, and also include groups in which a heterocyclyl ring is fused to one or more aryl, heteroaryl, or cycloaliphatic rings, such as indolinyl, 3H–indolyl, chromanyl, phenanthridinyl, or tetrahydroquinolinyl. In some embodiments, a heterocyclic ring may be a 5-12 membered bicyclic, bridged bicyclic, or spirocyclic ring. A heterocyclic ring may include one or more oxo (=O) or thioxo (=S) substituent. The term “heterocyclylalkyl” refers to an alkyl group substituted by a heterocyclyl, wherein the alkyl and heterocyclyl portions independently are optionally substituted. 36 BUSINESS.31669632.1 409753-016WO (210621)

[0127] As used herein, the term “partially unsaturated” refers to a ring moiety that includes at least one double or triple bond. The term “partially unsaturated” is intended to encompass rings having multiple sites of unsaturation, but is not intended to include aryl or heteroaryl moieties, as herein defined.

[0128] As described herein, compounds as provided herein may contain “optionally substituted” moieties. In general, the term “substituted”, whether preceded by the term “optionally” or not, means that one or more hydrogens of the designated moiety are replaced with a suitable substituent. Unless otherwise indicated, an “optionally substituted” group may have a suitable substituent at each substitutable position of the group, and when more than one position in any given structure may be substituted with more than one substituent selected from a specified group, the substituent may be either the same or different at every position. Combinations of substituents envisioned are preferably those that result in the formation of stable or chemically feasible compounds. The term “stable,” as used herein, refers to compounds that are not substantially altered when subjected to conditions to allow for their production, detection, and, in certain embodiments, their recovery, purification, and use for one or more of the purposes disclosed herein.

[0129] Suitable monovalent substituents on a substitutable carbon atom of an “optionally substituted” group are independently halogen; –(CH2)0–4R ^; –(CH2)0–4OR ^; -O-(CH2)0-4C(O)OR°; –(CH2)0–4CH(OR ^)2; –(CH2)0–4SR ^; –(CH2)0–4Ph, which may be substituted with R°; –(CH2)0–4O(CH2)0–1Ph which may be substituted with R°; –CH=CHPh, which may be substituted with R°; –NO2; –CN; –N3; –(CH2)0–4N(R ^)2; –(CH2)0–4N(R ^)C(O)R ^; –N(R ^)C(S)R ^; – (CH2)0-4N(R ^)C(O)NR ^2; –N(R ^)C(S)NR ^2; –(CH2)0–4N(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)0–4C(O)R ^; -C(S)R ^; –(CH2)0–4C(O)OR ^; –(CH2)0–4C(O)N(R ^)2; –(CH2)0–4C(O)SR ^; –(CH2)0–4C(O)OSiR ^3; –(CH2)0–4OC(O)R ^; – OC(O)(CH2)0–4SR–, SC(S)SR°; –(CH2)0–4SC(O)R ^; –(CH2)0–4C(O)NR ^2; -C(S)NR ^2; –C(S)SR°; –SC(S)SR°, –(CH2)0–4OC(O)NR ^2; –C(O)N(OR ^)R ^; –C(O)C(O)R ^; -C(O)CH2C(O)R ^; – C(NOR ^)R ^; –(CH2)0–4SSR ^; –(CH2)0–4S(O)2R ^; –(CH2)0–4S(O)2OR ^; -(CH2)0–4OS(O)2R ^; – S(O)2NR ^2; –(CH2)0–4S(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; –(C1–4 straight or branched alkylene)O– N(R ^)2; or –(C1–4 straight or branched alkylene)C(O)O–N(R ^)2, wherein each R ^ may be substituted as defined below and is independently hydrogen, C1-8 aliphatic, –CH2Ph, –O(CH2)0– 37 BUSINESS.31669632.1 409753-016WO (210621)1Ph, or a 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of R ^, taken together with their intervening atom(s), form a 3–12– membered saturated, partially unsaturated, or aryl mono– or polycyclic ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, which may be substituted as defined below.

[0130] Suitable monovalent substituents of R ^ together with their intervening atoms), are independently halogen, –(CH2)0–2R^, –(haloR^), –(CH2)0–2OH, –(CH2)0–2OR^, –(CH2)0–2CH(OR^)2; -O(haloR^), –CN, –N3, –(CH2)0–2C(O)R^, –(CH2)0–2C(O)OH, –(CH2)0–2C(O)OR^, -(CH2)0-4C(O)N(R ^)2; –(CH2)0–2SR^, –(CH2)0–2SH, –(CH2)0–2NH2, –(CH2)0–2NHR^, -(CH2)0-2NR^2, –NO2, –SiR^3, –OSiR^3, –C(O)SR^,–(C1–4straight or branched alkylene)C(O)OR^, or –SSR^wherein each R^is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently selected from C1–4aliphatic, -CH2Ph, –O(CH2)0–1Ph, or a 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents on a saturated carbon atom of R ^ include =O and =S.

[0131] Suitable divalent substituents on a saturated carbon atom of an “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))2–3O–, or –S(C(R*2))2–3S–, wherein each independent occurrence of R*is selected from hydrogen, C1–6 aliphatic which may be substituted as defined below, or an unsubstituted 5–6–membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents that are bound to vicinal substitutable carbons of an “optionally substituted” group include: –O(CR*2)2– 3O–, wherein each independent occurrence of R*is selected from hydrogen, C1–6 aliphatic which may be substituted as defined below, or an unsubstituted 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0132] Suitable substituents on the aliphatic group of R*include halogen, –R^, -(haloR^), –OH, – OR^, –O(haloR^), –CN, –C(O)OH, –C(O)OR^, –NH2, –NHR^, –NR^2, or –NO2, wherein each R^is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is 38 BUSINESS.31669632.1 409753-016WO (210621)independently C1–4aliphatic, –CH2Ph, –O(CH2)0–1Ph, or a 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0133] Suitable substituents on a substitutable nitrogen of an “optionally substituted” group include –R†, –NR†2, –C(O)R†, –C(O)OR†, –C(O)C(O)R†, –C(O)CH2C(O)R†, – S(O)2R†, wherein each R†is below, unsubstituted–OPh, or an or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of R†, taken together with their intervening atom(s) form an unsubstituted 3–12–membered saturated, partially unsaturated, or aryl mono– or bicyclic ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0134] Suitable substituents on the aliphatic group of R†are independently halogen, –R^, – (haloR^), –OH, –OR^, –O(haloR^), –CN, –C(O)OH, –C(O)OR^, –NH2, –NHR^, –NR^2, or -NO2, wherein each R^is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently C1–4 aliphatic, –CH2Ph, –O(CH2)0–1Ph, or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0135] As used herein, the term “substantially” refers to the qualitative condition of exhibiting total or near-total extent or degree of a characteristic or property of interest.

[0136] The convention of naming ascarosides by a several-letter prefix followed by a pound sign (#) and a number is sometimes used (for example ascr#18). This convention is used in the scientific literature and the skilled artisan will understand that each such name is associated with a specific chemical structure of known composition and will readily apprehend the structure of the molecule referred to using this naming convention. Unless otherwise indicated, all compound identifiers of this format used herein conform to the definitions described in the C. elegans Small Molecule Identifier Database (SMID-DB) maintained on the World Wide Web at smid-db.org.

[0137] Embodiments of the invention include: 39 BUSINESS.31669632.1 409753-016WO (210621)1. A method for reducing phytotoxic side effects on plants associated with application of an insecticide, said method comprising contacting a plant or a plant part with an effective amount of a combination of agents, said agents comprising at least one ascaroside and at least one insecticide, wherein said effective amount reduces phytotoxic side effects on crop plants as compared to phytotoxic side effects on plants associated with application of the insecticide alone. 2. The method of embodiment 1, wherein said at least one insecticide is an alkaloid insecticide, an alkyl halide insecticide, an aminopyrimidine insecticide, an aminotriazene insecticide, an antibiotic insecticide, an aromatic hydrocarbon insecticide, an arylpyrrole insecticide, a benzimidazole insecticide, a benzoylurea insecticide, a beta-ketonitrile insecticide, a botanical insecticide, a carbamate insecticide, a diacylhydrazine insecticide, a diamide insecticide, a dinitrophenol insecticide, a dithiolane insecticide, a formamidine insecticide, a fumigant insecticide, an inorganic insecticide, an isoxazoline insecticide, a juvenile hormone mimic, a macrocyclic lactone insecticide, a meta-diamide insecticide, a methoxyacrylate insecticide, a neonicotinoid insecticide, a nereistoxin analogue insecticide, a organochlorine insecticide, an organophosphorus insecticide, an oxadiazine insecticide, an oxadiazolone insecticide, a perfluoroalkyl sulfonamide insecticide, a phenol insecticide, a pyrazole insecticide, a pyrethrin insecticide, a pyrethroid insecticide, a pyridine azomethine insecticide, a pyrimidinamine insecticide, a pyropene insecticide, an RNA1 insecticide, a salicylanilide insecticide, a semicarbazone insecticide, a steroid insecticide, a tetramic acid insecticide, a tetronic acid insecticide, a thiocarbonate insecticide, a thiourea insecticide, or a urea insecticide. 3. The method of embodiment 1, wherein said at least one insecticide is an alkaloid insecticide selected from the group consisting of anabasine, matrine, nicotine, nornicotine, oxymatrine, ryania, ryanodine, sabadilla, and sanguinarine. 4. The method of embodiment 1, wherein said at least one insecticide is an alkyl halide insecticide selected from the group consisting of carbon tetrachloride, chloroform, 1,2- dichloropropane, ethylene dibromide, ethylene dichloride, methyl bromide, methyl iodide, methylchloroform, methylene chloride, and tetrachloroethane. 5. The method of embodiment 1, wherein said at least one insecticide is dicyclanil, cyromazine, allosamidin, naphthalene, triarathene, chlorfenapyr, fenazaflor, thiapronil, dinex, 40 BUSINESS.31669632.1 409753-016WO (210621)dinoprop, dinosam, 4-6-dinitro-o-cresol (DNOC), isoprothiolane, amitraz, chlordimeform, medimeform, or semiamitraz. 6. The method of embodiment 1, wherein said at least one insecticide is a benzoylurea insecticide selected from the group consisting of bistrifluron, chlorbenzuron, chlorfluazuron, dichlorbenzuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, penfluron, teflubenzuron, and triflumuron. 7. The method of embodiment 1, wherein said at least one insecticide is a botanical insecticide selected from the allicin, azadirachtin, carvacrol, d-limonene, quassia, rhodojaponin-III, rotenone, and triptolide. 8. The method of embodiment 1, wherein said at least one insecticide is a carbamate insecticide selected from the group consisting of alanycarb, aldicarb, aldoxycarb, allyxycarb, aminocarb, bendiocarb, benfuracarb, bufencarb, butacarb, butocarboxim, butoxycarboxim, carbanolate, carbaryl, carbofuran, carbosulfan, cloethocarb, 2-chlorophenyl methylcarbamate (CPMC), decarbofuran, dicresyl, dimetan, dimethacarb, dimetilan, dioxacarb, p-(ethylthio)phenyl methylcarbamate (EMPC), ethiofencarb, fenethacarb, fenobucarb, formetanate, formparanate, furathiocarb, hyquincarb, isolan, isoprocarb, methiocarb, methomyl, metolcarb, mexacarbate, nitrilacarb, oxamyl, pirimicarb, promacyl, promecarb, propoxur, pyramat, pyrolan, tazimcarb, thiocarboxime, thiodicarb, thiofanox, trimethacarb, 3,5-xylyl methylcarbamate (XMC), and xylylcarb. 9. The method of embodiment 1, wherein said at least one insecticide is a diamide insecticide selected from the group consisting of chlorantraniliprole, cyantraniliprole, cyhalodiamide, cyclaniliprole, flubendiamide, fluchlordiniliprole, tetrachlorantraniliprole, tetraniliprole, and tiorantraniliprole. 10. The method of embodiment 1, wherein said at least one insecticide is a fumigant insecticide selected from the group consisting of acrylonitrile, allyl isothiocyanate, calcium cyanide, carbon disulfide, carbon tetrachloride, carbonyl sulfide, chloroform, chloropicrin, cyanogen, 1,2- dichloropropane, dimethyl disulfide, ethyl formate, ethylene dibromide, ethylene dichloride, ethylene oxide, hydrogen cyanide, methyl bromide, methyl iodide, methyl isothiocyanate, methylchloroform, methylene chloride, phosphine, sodium cyanide, sulfuryl fluoride, and tetrachloroethane. 41 BUSINESS.31669632.1 409753-016WO (210621)11. The method of embodiment 1, wherein said at least one insecticide is an inorganic insecticide selected from the group consisting of barium hexafluorosilicate, borax, boric acid, calcium arsenate, calcium polysulfide, copper arsenate, copper naphthenate, copper oleate, cryolite, diatomaceous earth, lead arsenate, mercurous chloride, Paris green, potassium arsenite, potassium thiocyanate, silica gel, sodium arsenite, sodium fluoride, sodium silicofluoride, sodium thiocyanate, and sulfuryl fluoride. 12. The method of embodiment 1, wherein said at least one insecticide is an isoxazoline insecticide selected from the group consisting of afoxolaner, esafoxolaner, fluralaner, fluxametamide, isocycloseram, lotilaner, mivorilaner, sarolaner, tigolaner, and umifoxolaner. 13. The method of embodiment 1, wherein said at least one insecticide is a juvenile hormone mimic selected from the group consisting of dayoutong, diofenolan, epofenonane, fenoxycarb, hydroprene, juvenile hormone I, juvenile hormone II, juvenile hormone III, kinoprene, Methoprene, pyriproxyfen, and triprene. 14. The method of embodiment 1, wherein said at least one insecticide is a macrocyclic lactone insecticide selected from the group consisting of abamectin, doramectin, emamectin, eprinomectin, ivermectin, lepimectin, moxidectin, selamectin, spinetoram, and spinosad. 15. The method of embodiment 1, wherein said at least one insecticide is broflanilide, cyproflanilide, modoflaner, flupyroxystrobin, indoxacarb, metoxadiazone, flursulamid, sulfluramid, pymetrozine, pyrifluquinazon, flufenerim, pyrimidifen, ledprona, closantel, metaflumizone, α-ecdysone, ecdysterone, spidoxamat, spiropidion, spirotetramat, spirodiclofen, spiromesifen, O,O-diethyl dithiobisthioformate (EXD), sodium tetrathiocarbonate, diafenthiuron, flucofuron and sulcofuron. 16. The method of embodiment 1, wherein said at least one insecticide is a neonicotinoid insecticide selected from the group consisting of acetamiprid, clothianidin, cycloxaprid, dicloromezotiaz, dinotefuran, fenmezoditiaz, flupyradifurone, flupyrimin, imidacloprid, imidaclothiz, nitenpyram, nithiazine, paichongding, sulfoxaflor, thiacloprid, thiamethoxam, and triflumezopyrim. 42 BUSINESS.31669632.1 409753-016WO (210621)17. The method of embodiment 1, wherein said at least one insecticide is a nereistoxin analogue insecticide selected from the group consisting of bensultap, cartap, polythialan, thiocyclam, and thiosultap. 18. The method of embodiment 1, wherein said at least one insecticide is an organochlorine insecticide selected from the group consisting of aldrin, alpha-endosulfan, bromociclen, p,p- dibromo-diphenyl-1,1,1-trichloroethane (bromo-DDT), camphechlor, chlorbicyclen, chlordane, chlordecone, dichlorodiphenyltrichloroethane (DDT), difluorodiphenyltrichloroethane (DFDT), dieldrin, dilor, endosulfan, endrin, 1,1-dichloro-2,2-bis(4-ethylphenyl)ethane (ethyl-DDD), hexachlorocyclohexane (HCH), heptachlor, isobenzan, isodrin, kelevan, lindane, methoxychlor, mirex, p-dichlorobenzene, and tetrachlorodiphenylethane (TDE). 19. The method of embodiment 1, wherein said at least one insecticide is an organophosphorus insecticide selected from the group consisting of acephate, acethion, acetophos, amidithion, amiton, athidathion, azamethiphos, azinphos-ethyl, azinphos-methyl, azothoate, bromfenvinfos, bromophos, bromophos-ethyl, butathiofos, butonate, cadusafos, calvinphos, carbophenothion, chloramine phosphorus, chlorethoxyfos, chlorfenvinphos, chlormephos, chlorphoxim, chlorprazophos, chlorpyrifos, chlorpyrifos-methyl, chlorthiophos, colophonate, coumaphos, coumithoate, crotoxyphos, crufomate, cyanofenphos, cyanophos, cyanthoate, cythioate, demephion, demeton, demeton-methyl, demeton-S-methylsulphon, demephion-O, demephion-S, demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl, dialifos, diazinon, dicapthon, dichlofenthion, dichlorvos, dicrotophos, dimefox, dimethoate, dimethylvinphos, dioxabenzofos, dioxathion, disulfoton, dithicrofos, endothion, ethyl p-nitrophenyl phenylphosphorothioate (EPN), etaphos, ethion, ethoate-methyl, ethoprophos, S-[(ethylsulfinyl)methyl] O,O-diisopropyl phosphorodithioate (IPSP), etrimfos, famphur, fenamiphos, fenchlorphos, fenitrothion, fensulfothion, fenthion, fenthion-ethyl, flupyrazofos, fonofos, formothion, fosmethilan, fospirate, fosthietan, heptenophos, heterophos, , isazofos, isocarbophos, isofenphos, isofenphos-methyl, isothioate, isoxathion, jodfenphos, leptophos, lirimfos, lythidathion, malathion, mazidox, mecarbam, mecarphon, menazon, mephosfolan, mesulfenfos, methacrifos, methamidophos, methidathion, methocrotophos, methylacetophos, mevinphos, mipafox, monocrotophos, morphothion, naftalofos, naled, omethoate, oxydemeton-methyl, oxydeprofos, oxydisulfoton, parathion, parathion-methyl, phenkapton, phenthoate, phorate, phosalone, phosfolan, phosfolan- 43 BUSINESS.31669632.1 409753-016WO (210621)methyl, phosglycin, phosmet, phosnichlor, phosphamidon, phoxim, phoxim-methyl, pirimetaphos, pirimioxyphos, pirimiphos-ethyl, pirimiphos-methyl, primidophos, profenofos, propaphos, propetamphos, prothidathion, prothiofos, prothoate, pyraclofos, pyrazophos, pyrazothion, pyridaphenthion, pyrimitate, quinalphos, quinalphos-methyl, quinothion, schradan, sophamide, sulfotep, sulprofos, tebupirimfos, temephos, tetraethyl pyrophosphate (TEPP), terbufos, tetrachlorvinphos, thicrofos, thiometon, triamiphos, triazophos, trichlorfon, trichlormetaphos-3, trichloronat, trifenofos, xiaochongliulin, and zolaprofos. 20. The method of embodiment 1, wherein said at least one insecticide is a phenol insecticide selected from the group consisting of pentachlorophenol, precocenes, precocene I, precocene II, and precocene III. 21. The method of embodiment 1, wherein said at least one insecticide is a pyrazole insecticide selected from the group consisting of acetoprole, dimpropyridaz, ethiprole, fipronil, flufiprole, pyrafluprole, pyriprole, tolfenpyrad, and vaniliprole. 22. The method of embodiment 1, wherein said at least one insecticide is a pyrethrin / pyrethroid insecticide selected from the group consisting of acrinathrin, allethrin, alpha-cypermethrin, barthrin, beta-cyfluthrin, beta-cypermethrin, bifenthrin, bioallethrin, bioethanomethrin, biopermethrin, bioresmethrin, brofenvalerate, brofluthrinate, bromethrin, butethrin, chlorempenthrin, chloroprallethrin, cinerin, cismethrin, cyclethrin, cycloprothrin, cyfluthrin, cyhalothrin, cypermethrin, cyphenothrin, deltamethrin, d-fanshiluquebingjuzhi, dimefluthrin, dimethrin, d-teflumethrin, empenthrin, epsilon-metofluthrin, epsilon-momfluorothrin, esdépalléthrine, esfenvalerate, etofenprox, fenfluthrin, fenpirithrin, fenpropathrin, fenvalerate, flucythrinate, flufenprox, fluvalinate, furamethrin, furethrin, gamma-cyhalothrin, halfenprox, heptafluthrin, imiprothrin, japothrins, jasmolin, kadethrin, kappa-bifenthrin, kappa-tefluthrin, lambda-cyhalothrin, meperfluthrin, methothrin, metofluthrin, momfluorothrin, pentmethrin, permethrin, phenothrin, prallethrin, profluthrin, proparthrin, protrifenbute, pyrethrin, pyresmethrin, renofluthrin, resmethrin, silafluofen, sulfoxime, supermethrin, tau-fluvalinate, tefluthrin, terallethrin, tetramethrin, tetramethylfluthrin, theta-cypermethrin, thiofluoximate, tralocythrin, tralomethrin, transfluthrin, transpermethrin, valerate, and zeta-cypermethrin. 23. The method of embodiment 1, wherein said at least one insecticide is benzpyrimoxan, buprofezin, crotamiton, fenoxacrim, fentrifanil, flometoquin, flonicamid, fluhexafon, 44 BUSINESS.31669632.1 409753-016WO (210621)hydramethylnon, indazapyroxamet, jiahuangchongzong, ledprona, malonoben, maltodextrin, nicofluprole, nifluridide, oxazosulfyl, plifenate, pyridaben, pyridalyl, rafoxanide, sulfiflumin, tartar emetic, thuringiensin, triazamate, trichlophenidine, or tyclopyrazoflor. 24. The method of any one of embodiments 1-23, wherein said at least one ascaroside comprises an ascaroside having the structure (I): OZ where:Z is an optionally substituted C3-40 aliphatic group, and each of Raand Rbis independently -H, or an optionally substituted moiety selected from the group consisting of: C1-20aliphatic, C1-20acyl, C1-20heteroaliphatic, aryl, heteroaryl, a hydroxyl protecting group, a phosphorous-linked functional group , a sulfur-linked functional group, a silicon-linked functional group, a C2-20 carbonate (e.g. -a moiety -C(O)ORc), a C2-20 carbamate (e.g. -a moiety -C(O)N(Rc)2), a C2-20thioester (e.g. a moiety -C(S)Rc), a C2-20thiocarbonate (e.g. a moiety -C(S)ORc), a C2-20 dithiocarbonate (e.g. a moiety -C(S)SRc), a C1-20 thiocarbamate (e.g. a moiety -C(S)N(Rc)2), a sugar moiety, a peptide, a polymer chain, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule. Where Rcis independently at each occurrence selected from -H, optionally substituted C1-12aliphatic, optionally substituted C1-12 heteroaliphatic, optionally substituted aryl, optionally substituted heteroaryl, a polymer chain, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule, and where Raand Rbmay be taken together to form an optionally substituted ring, optionally containing one or more heteroatoms, and optionally containing one or more sites of unsaturation. 25. The method of embodiment 24, wherein Z is selected from the group consisting of: i. –CH(CH3)–R1, where R1is an optionally substituted C1-40 aliphatic group ii. –CH(CH3)–(CH2)n–CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; 45 BUSINESS.31669632.1 409753-016WO (210621)iii. –CH(CH3)–(CH2)n–CH=CH-CO2R2, where n is an integer from 1 to 40, and R2is - H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; iv. –CH(CH3)–(CH2)n–CH(OH)–CH2-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; v. –CH(CH3)–(CH2)n–C(O)–CH2-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; vi. –(CH2)n–CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; vii. –(CH2)n–CH=CH-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; viii. –(CH2)n–CH(OH)–CH2-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; and ix. –(CH2)n–C(O)–CH2-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide. 26. The method of embodiment 24, wherein Z is selected from the group consisting of: (x) –CH(CH3)–(CH2)n–CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; 46 BUSINESS.31669632.1 409753-016WO (210621)(xi) –CH(CH3)–(CH2)n–CH=CH-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xii) –CH(CH3)–(CH2)n–CH(OH)–CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xiii) –CH(CH3)–(CH2)n–C(O)–CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xiv) –(CH2)n–CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20aliphatic group, an optionally substituted C1-20heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xv) –(CH2)n–CH=CH-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; 47 BUSINESS.31669632.1 409753-016WO (210621)(xvi) –(CH2)n–CH(OH)–CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; or (xvii) –(CH2)n–C(O)–CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule. 27. The method of any one of embodiments 24-26, wherein Raand Rbare each -H. 28. The method of any one of embodiments 24-27, wherein Z is –CH(CH3)–(CH2)n–CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide. 29. The method of any one of embodiments 1-28, wherein said at least one ascaroside comprises an ascaroside selected from the group consisting of ascr#9, ascr#10, ascr#16, ascr#18, ascr#20, ascr#22, and ascr#24. 30. The method of any one of embodiments 1-29, wherein said at least one ascaroside comprises ascr#18. 31. The method of any one of embodiments 1-30, wherein said at least one ascaroside and said at least one insecticide are applied simultaneously. 32. The method of embodiment 31, wherein said at least one ascaroside and said at least one insecticide are combined together in a tank mix. 33. The method of any one of embodiments 1-30, wherein said at least one ascaroside and said at least one insecticide are applied sequentially. 48 BUSINESS.31669632.1 409753-016WO (210621)34. The method of any one of embodiments 1-33, wherein said combination is used as a seed coating. 35. A composition comprising at least one ascaroside and at least one insecticide. 36. The composition of embodiment 35, wherein said at least one ascaroside and said at least one insecticide are present in effective amounts. 37. The composition of embodiment 35, wherein said at least one insecticide is an alkaloid insecticide, an alkyl halide insecticide, an aminopyrimidine insecticide, an aminotriazene insecticide, an antibiotic insecticide, an aromatic hydrocarbon insecticide, an arylpyrrole insecticide, a benzimidazole insecticide, a benzoylurea insecticide, a beta-ketonitrile insecticide, a botanical insecticide, a carbamate insecticide, a diacylhydrazine insecticide, a diamide insecticide, a dinitrophenol insecticide, a dithiolane insecticide, a formamidine insecticide, a fumigant insecticide, an inorganic insecticide, an isoxazoline insecticide, a juvenile hormone mimic, a macrocyclic lactone insecticide, a meta-diamide insecticide, a methoxyacrylate insecticide, a neonicotinoid insecticide, a nereistoxin analogue insecticide, a organochlorine insecticide, an organophosphorus insecticide, an oxadiazine insecticide, an oxadiazolone insecticide, a perfluoroalkyl sulfonamide insecticide, a phenol insecticide, a pyrazole insecticide, a pyrethrin insecticide, a pyrethroid insecticide, a pyridine azomethine insecticide, a pyrimidinamine insecticide, a pyropene insecticide, an RNA1 insecticide, a salicylanilide insecticide, a semicarbazone insecticide, a steroid insecticide, a tetramic acid insecticide, a tetronic acid insecticide, a thiocarbonate insecticide, a thiourea insecticide, or a urea insecticide. 38. The composition of embodiment 35, wherein said at least one insecticide is an alkaloid insecticide selected from the group consisting of anabasine, matrine, nicotine, nornicotine, oxymatrine, ryania, ryanodine, sabadilla, and sanguinarine. 39. The composition of embodiment 35, wherein said at least one insecticide is an alkyl halide insecticide selected from the group consisting of carbon tetrachloride, chloroform, 1,2- dichloropropane, ethylene dibromide, ethylene dichloride, methyl bromide, methyl iodide, methylchloroform, methylene chloride, and tetrachloroethane. 40. The composition of embodiment 35, wherein said at least one insecticide is dicyclanil, cyromazine, allosamidin, naphthalene, triarathene, chlorfenapyr, fenazaflor, thiapronil, dinex, 49 BUSINESS.31669632.1 409753-016WO (210621)dinoprop, dinosam, 4-6-dinitro-o-cresol (DNOC), isoprothiolane, amitraz, chlordimeform, medimeform, or semiamitraz. 41. The composition of embodiment 35, wherein said at least one insecticide is a benzoylurea insecticide selected from the group consisting of bistrifluron, chlorbenzuron, chlorfluazuron, dichlorbenzuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, penfluron, teflubenzuron, and triflumuron. 42. The composition of embodiment 35, wherein said at least one insecticide is a botanical insecticide selected from the allicin, azadirachtin, carvacrol, d-limonene, quassia, rhodojaponin- III, rotenone, and triptolide. 43. The composition of embodiment 35, wherein said at least one insecticide is a carbamate insecticide selected from the group consisting of alanycarb, aldicarb, aldoxycarb, allyxycarb, aminocarb, bendiocarb, benfuracarb, bufencarb, butacarb, butocarboxim, butoxycarboxim, carbanolate, carbaryl, carbofuran, carbosulfan, cloethocarb, 2-chlorophenyl methylcarbamate (CPMC), decarbofuran, dicresyl, dimetan, dimethacarb, dimetilan, dioxacarb, p-(ethylthio)phenyl methylcarbamate (EMPC), ethiofencarb, fenethacarb, fenobucarb, formetanate, formparanate, furathiocarb, hyquincarb, isolan, isoprocarb, methiocarb, methomyl, metolcarb, mexacarbate, nitrilacarb, oxamyl, pirimicarb, promacyl, promecarb, propoxur, pyramat, pyrolan, tazimcarb, thiocarboxime, thiodicarb, thiofanox, trimethacarb, 3,5-xylyl methylcarbamate (XMC), and xylylcarb. 44. The composition of embodiment 35, wherein said at least one insecticide is a diamide insecticide selected from the group consisting of chlorantraniliprole, cyantraniliprole, cyhalodiamide, cyclaniliprole, flubendiamide, fluchlordiniliprole, tetrachlorantraniliprole, tetraniliprole, and tiorantraniliprole. 45. The composition of embodiment 35, wherein said at least one insecticide is a fumigant insecticide selected from the group consisting of acrylonitrile, allyl isothiocyanate, calcium cyanide, carbon disulfide, carbon tetrachloride, carbonyl sulfide, chloroform, chloropicrin, cyanogen, 1,2-dichloropropane, dimethyl disulfide, ethyl formate, ethylene dibromide, ethylene dichloride, ethylene oxide, hydrogen cyanide, methyl bromide, methyl iodide, methyl isothiocyanate, methylchloroform, methylene chloride, phosphine, sodium cyanide, sulfuryl fluoride, and tetrachloroethane. 50 BUSINESS.31669632.1 409753-016WO (210621)46. The composition of embodiment 35, wherein said at least one insecticide is an inorganic insecticide selected from the group consisting of barium hexafluorosilicate, borax, boric acid, calcium arsenate, calcium polysulfide, copper arsenate, copper naphthenate, copper oleate, cryolite, diatomaceous earth, lead arsenate, mercurous chloride, Paris green, potassium arsenite, potassium thiocyanate, silica gel, sodium arsenite, sodium fluoride, sodium silicofluoride, sodium thiocyanate, and sulfuryl fluoride. 47. The composition of embodiment 35, wherein said at least one insecticide is an isoxazoline insecticide selected from the group consisting of afoxolaner, esafoxolaner, fluralaner, fluxametamide, isocycloseram, lotilaner, mivorilaner, sarolaner, tigolaner, and umifoxolaner. 48. The composition of embodiment 35, wherein said at least one insecticide is a juvenile hormone mimic selected from the group consisting of dayoutong, diofenolan, epofenonane, fenoxycarb, hydroprene, juvenile hormone I, juvenile hormone II, juvenile hormone III, kinoprene, Methoprene, pyriproxyfen, and triprene. 49. The composition of embodiment 35, wherein said at least one insecticide is a macrocyclic lactone insecticide selected from the group consisting of abamectin, doramectin, emamectin, eprinomectin, ivermectin, lepimectin, moxidectin, selamectin, spinetoram, and spinosad. 50. The composition of embodiment 35, wherein said at least one insecticide is broflanilide, cyproflanilide, modoflaner, flupyroxystrobin, indoxacarb, metoxadiazone, flursulamid, sulfluramid, pymetrozine, pyrifluquinazon, flufenerim, pyrimidifen, ledprona, closantel, metaflumizone, α-ecdysone, ecdysterone, spidoxamat, spiropidion, spirotetramat, spirodiclofen, spiromesifen, O,O-diethyl dithiobisthioformate (EXD), sodium tetrathiocarbonate, diafenthiuron, flucofuron and sulcofuron. 51. The composition of embodiment 35, wherein said at least one insecticide is a neonicotinoid insecticide selected from the group consisting of acetamiprid, clothianidin, cycloxaprid, dicloromezotiaz, dinotefuran, fenmezoditiaz, flupyradifurone, flupyrimin, imidacloprid, imidaclothiz, nitenpyram, nithiazine, paichongding, sulfoxaflor, thiacloprid, thiamethoxam, and triflumezopyrim. 51 BUSINESS.31669632.1 409753-016WO (210621)52. The composition of embodiment 35, wherein said at least one insecticide is a nereistoxin analogue insecticide selected from the group consisting of bensultap, cartap, polythialan, thiocyclam, and thiosultap. 53. The composition of embodiment 35, wherein said at least one insecticide is an organochlorine insecticide selected from the group consisting of aldrin, alpha-endosulfan, bromociclen, p,p-dibromo-diphenyl-1,1,1-trichloroethane (bromo-DDT), camphechlor, chlorbicyclen, chlordane, chlordecone, dichlorodiphenyltrichloroethane (DDT), difluorodiphenyltrichloroethane (DFDT), dieldrin, dilor, endosulfan, endrin, 1,1-dichloro-2,2- bis(4-ethylphenyl)ethane (ethyl-DDD), hexachlorocyclohexane (HCH), heptachlor, isobenzan, isodrin, kelevan, lindane, methoxychlor, mirex, p-dichlorobenzene, and tetrachlorodiphenylethane (TDE). 54. The composition of embodiment 35, wherein said at least one insecticide is an organophosphorus insecticide selected from the group consisting of acephate, acethion, acetophos, amidithion, amiton, athidathion, azamethiphos, azinphos-ethyl, azinphos-methyl, azothoate, bromfenvinfos, bromophos, bromophos-ethyl, butathiofos, butonate, cadusafos, calvinphos, carbophenothion, chloramine phosphorus, chlorethoxyfos, chlorfenvinphos, chlormephos, chlorphoxim, chlorprazophos, chlorpyrifos, chlorpyrifos-methyl, chlorthiophos, colophonate, coumaphos, coumithoate, crotoxyphos, crufomate, cyanofenphos, cyanophos, cyanthoate, cythioate, demephion, demeton, demeton-methyl, demeton-S-methylsulphon, demephion-O, demephion-S, demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl, dialifos, diazinon, dicapthon, dichlofenthion, dichlorvos, dicrotophos, dimefox, dimethoate, dimethylvinphos, dioxabenzofos, dioxathion, disulfoton, dithicrofos, endothion, ethyl p-nitrophenyl phenylphosphorothioate (EPN), etaphos, ethion, ethoate-methyl, ethoprophos, S- [(ethylsulfinyl)methyl] O,O-diisopropyl phosphorodithioate (IPSP), etrimfos, famphur, fenamiphos, fenchlorphos, fenitrothion, fensulfothion, fenthion, fenthion-ethyl, flupyrazofos, fonofos, formothion, fosmethilan, fospirate, fosthietan, heptenophos, heterophos, , isazofos, isocarbophos, isofenphos, isofenphos-methyl, isothioate, isoxathion, jodfenphos, leptophos, lirimfos, lythidathion, malathion, mazidox, mecarbam, mecarphon, menazon, mephosfolan, mesulfenfos, methacrifos, methamidophos, methidathion, methocrotophos, methylacetophos, mevinphos, mipafox, monocrotophos, morphothion, naftalofos, naled, omethoate, oxydemeton- 52 BUSINESS.31669632.1 409753-016WO (210621)methyl, oxydeprofos, oxydisulfoton, parathion, parathion-methyl, phenkapton, phenthoate, phorate, phosalone, phosfolan, phosfolan-methyl, phosglycin, phosmet, phosnichlor, phosphamidon, phoxim, phoxim-methyl, pirimetaphos, pirimioxyphos, pirimiphos-ethyl, pirimiphos-methyl, primidophos, profenofos, propaphos, propetamphos, prothidathion, prothiofos, prothoate, pyraclofos, pyrazophos, pyrazothion, pyridaphenthion, pyrimitate, quinalphos, quinalphos-methyl, quinothion, schradan, sophamide, sulfotep, sulprofos, tebupirimfos, temephos, tetraethyl pyrophosphate (TEPP), terbufos, tetrachlorvinphos, thicrofos, thiometon, triamiphos, triazophos, trichlorfon, trichlormetaphos-3, trichloronat, trifenofos, xiaochongliulin, and zolaprofos. 55. The composition of embodiment 35, wherein said at least one insecticide is a phenol insecticide selected from the group consisting of pentachlorophenol, precocenes, precocene I, precocene II, and precocene III. 56. The composition of embodiment 35, wherein said at least one insecticide is a pyrazole insecticide selected from the group consisting of acetoprole, dimpropyridaz, ethiprole, fipronil, flufiprole, pyrafluprole, pyriprole, tolfenpyrad, and vaniliprole. 57. The composition of embodiment 35, wherein said at least one insecticide is a pyrethrin / pyrethroid insecticide selected from the group consisting of acrinathrin, allethrin, alpha- cypermethrin, barthrin, beta-cyfluthrin, beta-cypermethrin, bifenthrin, bioallethrin, bioethanomethrin, biopermethrin, bioresmethrin, brofenvalerate, brofluthrinate, bromethrin, butethrin, chlorempenthrin, chloroprallethrin, cinerin, cismethrin, cyclethrin, cycloprothrin, cyfluthrin, cyhalothrin, cypermethrin, cyphenothrin, deltamethrin, d-fanshiluquebingjuzhi, dimefluthrin, dimethrin, d-teflumethrin, empenthrin, epsilon-metofluthrin, epsilon- momfluorothrin, esdépalléthrine, esfenvalerate, etofenprox, fenfluthrin, fenpirithrin, fenpropathrin, fenvalerate, flucythrinate, flufenprox, fluvalinate, furamethrin, furethrin, gamma- cyhalothrin, halfenprox, heptafluthrin, imiprothrin, japothrins, jasmolin, kadethrin, kappa- bifenthrin, kappa-tefluthrin, lambda-cyhalothrin, meperfluthrin, methothrin, metofluthrin, momfluorothrin, pentmethrin, permethrin, phenothrin, prallethrin, profluthrin, proparthrin, protrifenbute, pyrethrin, pyresmethrin, renofluthrin, resmethrin, silafluofen, sulfoxime, supermethrin, tau-fluvalinate, tefluthrin, terallethrin, tetramethrin, tetramethylfluthrin, theta- 53 BUSINESS.31669632.1 409753-016WO (210621)cypermethrin, thiofluoximate, tralocythrin, tralomethrin, transfluthrin, transpermethrin, valerate, and zeta-cypermethrin. 58. The composition of embodiment 35, wherein said at least one insecticide is benzpyrimoxan, buprofezin, crotamiton, fenoxacrim, fentrifanil, flometoquin, flonicamid, fluhexafon, hydramethylnon, indazapyroxamet, jiahuangchongzong, ledprona, malonoben, maltodextrin, nicofluprole, nifluridide, oxazosulfyl, plifenate, pyridaben, pyridalyl, rafoxanide, sulfiflumin, tartar emetic, thuringiensin, triazamate, trichlophenidine, or tyclopyrazoflor. 59. The composition of any one of embodiments 35-58 wherein said at least one ascaroside comprises an ascaroside having the structure (I): OZ where:Z is an optionally substituted C3-40 aliphatic group, and each of Raand Rbis independently -H, or an optionally substituted moiety selected from the group consisting of: C1-20 aliphatic, C1-20 acyl, C1-20 heteroaliphatic, aryl, heteroaryl, a hydroxyl protecting group, a phosphorous-linked functional group , a sulfur-linked functional group, a silicon-linked functional group, a C2-20carbonate (e.g. -a moiety -C(O)ORc), a C2-20carbamate (e.g. -a moiety -C(O)N(Rc)2), a C2-20thioester (e.g. a moiety -C(S)Rc), a C2-20thiocarbonate (e.g. a moiety -C(S)ORc), a C2-20 dithiocarbonate (e.g. a moiety -C(S)SRc), a C1-20thiocarbamate (e.g. a moiety -C(S)N(Rc)2), a sugar moiety, a peptide, a polymer chain, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule. Where Rcis independently at each occurrence selected from -H, optionally substituted C1-12 aliphatic, optionally substituted C1-12 heteroaliphatic, optionally substituted aryl, optionally substituted heteroaryl, a polymer chain, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule, and where Raand Rbmay be taken together to form an optionally substituted ring, optionally containing one or more heteroatoms, and optionally containing one or more sites of unsaturation. 54 BUSINESS.31669632.1 409753-016WO (210621)60. The composition of embodiment 59, wherein Z is selected from the group consisting of: i. –CH(CH3)–R1, where R1is an optionally substituted C1-40 aliphatic group ii. –CH(CH3)–(CH2)n–CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; iii. –CH(CH3)–(CH2)n–CH=CH-CO2R2, where n is an integer from 1 to 40, and R2is - H, a metal cation, an optionally substituted C1-20aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; iv. –CH(CH3)–(CH2)n–CH(OH)–CH2-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; v. –CH(CH3)–(CH2)n–C(O)–CH2-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; vi. –(CH2)n–CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; vii. –(CH2)n–CH=CH-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; viii. –(CH2)n–CH(OH)–CH2-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; and ix. –(CH2)n–C(O)–CH2-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide. 61. The composition of embodiment 47, wherein Z is: (x) –CH(CH3)–(CH2)n–CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20aliphatic group, an optionally 55 BUSINESS.31669632.1 409753-016WO (210621)substituted C1-20heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xi) –CH(CH3)–(CH2)n–CH=CH-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xii) –CH(CH3)–(CH2)n–CH(OH)–CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xiii) –CH(CH3)–(CH2)n–C(O)–CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xiv) –(CH2)n–CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xv) –(CH2)n–CH=CH-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20aliphatic group, an optionally substituted C1-20heteroaliphatic group, an optionally substituted aromatic group, an 56 BUSINESS.31669632.1 409753-016WO (210621)optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xvi) –(CH2)n–CH(OH)–CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; or (xvii) –(CH2)n–C(O)–CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule. 62. The composition of embodiment 60 or 61, wherein Raand Rbare each -H. 63. The composition of any one of embodiments 59-62, wherein Z is –CH(CH3)–(CH2)n– CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide. 64. The composition of any one of embodiments 35-63, wherein said at least one ascaroside comprises an ascaroside selected from the group consisting of ascr#9, ascr#10, ascr#16, ascr#18, ascr#20, ascr#22, and ascr#24. 65. The composition of any one of embodiments 35-63, wherein said at least one ascaroside comprises ascr#18, or wherein wherein said at least one ascaroside comprises oscr#16. 66. The composition of any one of embodiments 35-63, wherein said at least one ascaroside comprises ascr#18. 67. The composition of any one of embodiments 35-66, wherein said composition is part of a tank mix. 57 BUSINESS.31669632.1 409753-016WO (210621)68. The composition of any one of embodiments 35-66, wherein said composition is in a solid form. 69. The composition of embodiment 68, wherein said solid form comprises powder or granules. 70. The composition of any one of embodiments 35-66, wherein said composition is in liquid form. 71. The composition of embodiment 70, wherein said liquid form is a sprayable formulation. 72. The composition of any one of embodiments 35-71, wherein the composition is stable for a period of greater than 6 months. 73. The composition of any one of embodiments 35-72, wherein said composition further comprises one or more additional components selected from the group consisting of surfactants, including emulsifiers, dispersants, foam-formers, colorants, processing aids, lubricants, fillers, reinforcements, flame retardants, light stabilizers, ultraviolet radiation absorbers, weather stabilizers, plasticizers, release agents, perfumes, heat-retaining additives (e.g., silica), cross- linking agents, antioxidants, anti-foaming agents, buffers, pH modifiers, compatibility agents, drift control additives, extenders / stickers, tackifiers, plant penetrants, safeners, spreaders, and wetting agents. EXAMPLES

[0138] Example 1: Ascaroside tank mix trial with insectiside.

[0139] A trial is performed to evaluate the application of Phytalix® (a formulation containing ascarosides) in combination with one or more insecticides. The trial is organized in a randomized complete block design with four replications per treatment and a plot size of 10 ft by 30 ft. The trial is replicated at three separate field sites. Tank mixes are created with different insecticides from a range of different molecular classes and modes of actions along with an effective amount of Phytalix® or a similar ascaroside formulation. Untreated controls and control groups with each insecticide only and no added Phytalix® are included for comparison.

[0140] The plots in Example 1 are evaluated as follows: Insect control in each plot is rated as % control 7 and 14 days after application. A Phytotoxicity rating of each plot is also measured at 7 and 14 days after application. Disease ratings (e.g. for fungal, bacterial, and / or viral diseases) are 58 BUSINESS.31669632.1 409753-016WO (210621)collected when the crop reaches the appropriate growth stage, or whenever routine monitoring reveals the presence of a measurable disease in the control plots. The disease evaluation includes % disease incidence and severity. The plots are harvested separately and the yield measured and reported as bushel / acre. Insect control levels, phytotoxicity ratings, disease incidence and severity and yield are averaged for the plots for each treatment group and compared to appropriate controls to assess the impact of ascarosides.

[0141] It is contemplated that compounds, compositions, and methods of the present application encompass variations and adaptations developed using information from the embodiments described in the present disclosure. Adaptation or modification of the methods and processes described in this specification may be performed by those of ordinary skill in the relevant art.

[0142] It will be appreciated that use of headers in the present disclosure are provided for the convenience of the reader. The presence and / or placement of a header is not intended to limit the scope of the subject matter described herein. Unless otherwise specified, embodiments located in one section of the application apply throughout the application to other embodiments, both singly and in combination.

[0143] Throughout the description, where compositions, compounds, or products are described as having, including, or comprising specific components, or where processes and methods are described as having, including, or comprising specific steps, it is contemplated that, additionally, there are articles, devices, and systems of the present application that consist essentially of, or consist of, the recited components, and that there are processes and methods according to the present application that consist essentially of, or consist of, the recited processing steps.

[0144] It should be understood that the order of steps or order for performing certain action is immaterial so long as the described method remains operable. Moreover, two or more steps or actions may be conducted simultaneously.

[0145] All publications and patent applications mentioned in the specification are indicative of the level of those skilled in the art to which this invention pertains. All publications and patent applications are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. 59 BUSINESS.31669632.1 409753-016WO (210621)

[0146] Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it will be obvious that certain changes and modifications may be practiced within the scope of the appended claims. 60 BUSINESS.31669632.1 409753-016WO (210621)

Claims

CLAIMS What is claimed is:

1. A method for controlling insect infestation of a plant, the method comprising administering an ascaroside to a plant, plant part, or soil surrounding the plant or plant part, wherein the plant, plant part, or soil surrounding the plant or plant part is receiving or has received an insecticide (e.g., via administration to the plant, plant part, or soil surrounding the plant or plant part).

2. A method for controlling insect infestation of a plant, the method comprising administering an insecticide to a plant, plant part, or soil surrounding the plant or plant part, wherein the plant, plant part, or soil surrounding the plant or plant part is receiving or has received an ascaroside (e.g., via administration to the plant, plant part, or soil surrounding the plant or plant part).

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

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

5. The method of claim 3 or 4, wherein said effective amount reduces the phytotoxicity rating on crop plants as compared to the phytotoxicity rating on plants associated with application of the insecticide alone.

6. The method of any one of claims 1-5, wherein said at least one insecticide is an alkaloid insecticide, an alkyl halide insecticide, an aminopyrimidine insecticide, an aminotriazene insecticide, an antibiotic insecticide, an aromatic hydrocarbon insecticide, an arylpyrrole insecticide, a benzimidazole insecticide, a benzoylurea insecticide, a beta-ketonitrile insecticide, a botanical insecticide, a carbamate insecticide, a diacylhydrazine insecticide, a diamide insecticide, a dinitrophenol insecticide, a dithiolane insecticide, a formamidine insecticide, a fumigant insecticide, an inorganic insecticide, an isoxazoline insecticide, a juvenile hormone mimic, a macrocyclic lactone insecticide, a meta-diamide insecticide, a methoxyacrylate insecticide, a neonicotinoid insecticide, a nereistoxin analogue insecticide, a 61 BUSINESS.31669632.1 409753-016WO (210621)organochlorine insecticide, an organophosphorus insecticide, an oxadiazine insecticide, an oxadiazolone insecticide, a perfluoroalkyl sulfonamide insecticide, a phenol insecticide, a pyrazole insecticide, a pyrethrin insecticide, a pyrethroid insecticide, a pyridine azomethine insecticide, a pyrimidinamine insecticide, a pyropene insecticide, an RNA1 insecticide, a salicylanilide insecticide, a semicarbazone insecticide, a steroid insecticide, a tetramic acid insecticide, a tetronic acid insecticide, a thiocarbonate insecticide, a thiourea insecticide, or a urea insecticide.

7. The method of any one of claims 1-6, wherein said at least one ascaroside comprises an ascaroside having the structure (I): OZ where:Z is an optionally substituted C3-40 aliphatic group, and each of Raand Rbis independently -H, or an optionally substituted moiety selected from the group consisting of: C1-20 aliphatic, C1-20 acyl, C1-20 heteroaliphatic, aryl, heteroaryl, a hydroxyl protecting group, a phosphorous-linked functional group , a sulfur-linked functional group, a silicon-linked functional group, a C2-20carbonate (e.g. -a moiety -C(O)ORc), a C2-20carbamate (e.g. -a moiety -C(O)N(Rc)2), a C2-20thioester (e.g. a moiety -C(S)Rc), a C2-20thiocarbonate (e.g. a moiety -C(S)ORc), a C2-20 dithiocarbonate (e.g. a moiety -C(S)SRc), a C1-20thiocarbamate (e.g. a moiety -C(S)N(Rc)2), a sugar moiety, a peptide, a polymer chain, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule. wherein Rcis independently at each occurrence selected from -H, optionally substituted C1-12 aliphatic, optionally substituted C1-12 heteroaliphatic, optionally substituted aryl, optionally substituted heteroaryl, a polymer chain, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule, and wherein Raand Rbmay be taken together to form an optionally substituted ring, optionally containing one or more heteroatoms, and optionally containing one or more sites of unsaturation.

8. The method of claim 7, wherein Z is selected from the group consisting of: 62 BUSINESS.31669632.1 409753-016WO (210621)i. –CH(CH3)–R1, where R1is an optionally substituted C1-40aliphatic group ii. –CH(CH3)–(CH2)n–CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; iii. –CH(CH3)–(CH2)n–CH=CH-CO2R2, where n is an integer from 1 to 40, and R2is - H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; iv. –CH(CH3)–(CH2)n–CH(OH)–CH2-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; v. –CH(CH3)–(CH2)n–C(O)–CH2-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; vi. –(CH2)n–CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; vii. –(CH2)n–CH=CH-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; viii. –(CH2)n–CH(OH)–CH2-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; and ix. –(CH2)n–C(O)–CH2-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide.

9. The method of claim 7, wherein Z is selected from the group consisting of: (x) –CH(CH3)–(CH2)n–CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20aliphatic group, an optionally substituted C1-20heteroaliphatic group, an optionally substituted aromatic group, an 63 BUSINESS.31669632.1 409753-016WO (210621)optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xi) –CH(CH3)–(CH2)n–CH=CH-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xii) –CH(CH3)–(CH2)n–CH(OH)–CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xiii) –CH(CH3)–(CH2)n–C(O)–CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xiv) –(CH2)n–CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xv) –(CH2)n–CH=CH-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, 64 BUSINESS.31669632.1 409753-016WO (210621)a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xvi) –(CH2)n–CH(OH)–CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xvii) –(CH2)n–C(O)–CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20aliphatic group, an optionally substituted C1-20heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; and (xix) an optionally unsaturated, optionally substituted C2-40 sidechain terminating in a chain end comprising a nitrogen-, oxygen- or sulfur-containing functional group.

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

11. The method of any one of claims 1-10, wherein said at least one ascaroside comprises ascr#18.

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

13. The method of claim 12, wherein said at least one ascaroside and said at least one insecticide are combined together in a tank mix.

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

15. The method of any one of claims 1-14, wherein said combination is used as a seed coating.

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

17. The composition of claim 16, wherein said at least one ascaroside and said at least one insecticide are present in effective amounts. 65 BUSINESS.31669632.1 409753-016WO (210621)18. The composition of claim 17, wherein said effective amount reduces phytotoxic side effects on crop plants as compared to phytotoxic side effects on plants associated with application of the insecticide alone.

19. The composition of claim 17 or 18, wherein said effective amount reduces the phytotoxicity rating on crop plants as compared to the phytotoxicity rating on plants associated with application of the insecticide alone.

20. The composition of any one of claims 16-19, wherein said at least one insecticide is an alkaloid insecticide, an alkyl halide insecticide, an aminopyrimidine insecticide, an aminotriazene insecticide, an antibiotic insecticide, an aromatic hydrocarbon insecticide, an arylpyrrole insecticide, a benzimidazole insecticide, a benzoylurea insecticide, a beta-ketonitrile insecticide, a botanical insecticide, a carbamate insecticide, a diacylhydrazine insecticide, a diamide insecticide, a dinitrophenol insecticide, a dithiolane insecticide, a formamidine insecticide, a fumigant insecticide, an inorganic insecticide, an isoxazoline insecticide, a juvenile hormone mimic, a macrocyclic lactone insecticide, a meta-diamide insecticide, a methoxyacrylate insecticide, a neonicotinoid insecticide, a nereistoxin analogue insecticide, a organochlorine insecticide, an organophosphorus insecticide, an oxadiazine insecticide, an oxadiazolone insecticide, a perfluoroalkyl sulfonamide insecticide, a phenol insecticide, a pyrazole insecticide, a pyrethrin insecticide, a pyrethroid insecticide, a pyridine azomethine insecticide, a pyrimidinamine insecticide, a pyropene insecticide, an RNA1 insecticide, a salicylanilide insecticide, a semicarbazone insecticide, a steroid insecticide, a tetramic acid insecticide, a tetronic acid insecticide, a thiocarbonate insecticide, a thiourea insecticide, or a urea insecticide.

21. The composition of any one of claims 16-20 wherein said at least one ascaroside comprises an ascaroside having the structure (I): OZ where:Z is an optionally substituted C3-40 aliphatic group, and 66 BUSINESS.31669632.1 409753-016WO (210621)each of Raand Rbis independently -H, or an optionally substituted moiety selected from the group consisting of: C1-20 aliphatic, C1-20 acyl, C1-20 heteroaliphatic, aryl, heteroaryl, a hydroxyl protecting group, a phosphorous-linked functional group , a sulfur-linked functional group, a silicon-linked functional group, a C2-20carbonate (e.g. -a moiety -C(O)ORc), a C2-20carbamate (e.g. -a moiety -C(O)N(Rc)2), a C2-20 thioester (e.g. a moiety -C(S)Rc), a C2-20 thiocarbonate (e.g. a moiety -C(S)ORc), a C2-20 dithiocarbonate (e.g. a moiety -C(S)SRc), a C1-20thiocarbamate (e.g. a moiety -C(S)N(Rc)2), a sugar moiety, a peptide, a polymer chain, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; wherein Rcis independently at each occurrence selected from -H, optionally substituted C1-12 aliphatic, optionally substituted C1-12heteroaliphatic, optionally substituted aryl, optionally substituted heteroaryl, a polymer chain, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule, and where Raand Rbmay be taken together to form an optionally substituted ring, optionally containing one or more heteroatoms, and optionally containing one or more sites of unsaturation.

22. The composition of claim 21, wherein Z is selected from the group consisting of: i. –CH(CH3)–R1, where R1is an optionally substituted C1-40 aliphatic group ii. –CH(CH3)–(CH2)n–CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; iii. –CH(CH3)–(CH2)n–CH=CH-CO2R2, where n is an integer from 1 to 40, and R2is - H, a metal cation, an optionally substituted C1-20aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; iv. –CH(CH3)–(CH2)n–CH(OH)–CH2-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; v. –CH(CH3)–(CH2)n–C(O)–CH2-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; 67 BUSINESS.31669632.1 409753-016WO (210621)vi. –(CH2)n–CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; vii. –(CH2)n–CH=CH-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; viii. –(CH2)n–CH(OH)–CH2-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide; and ix. –(CH2)n–C(O)–CH2-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide.

23. The composition of claim 21, wherein Z is: (x) –CH(CH3)–(CH2)n–CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xi) –CH(CH3)–(CH2)n–CH=CH-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xii) –CH(CH3)–(CH2)n–CH(OH)–CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an 68 BUSINESS.31669632.1 409753-016WO (210621)amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xiii) –CH(CH3)–(CH2)n–C(O)–CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xiv) –(CH2)n–CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20aliphatic group, an optionally substituted C1-20heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xv) –(CH2)n–CH=CH-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xvi) –(CH2)n–CH(OH)–CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; (xvii) –(CH2)n–C(O)–CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, 69 BUSINESS.31669632.1 409753-016WO (210621)a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; or (xviii) an optionally unsaturated, optionally substituted C2-40 sidechain terminating in a chain end comprising a nitrogen-, oxygen- or sulfur-containing functional group.

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

25. The composition of any one of claims 16-23, wherein said at least one ascaroside comprises ascr#18.

26. The composition of any one of claims 16-24, wherein said composition is part of a tank mix.

27. The composition of any one of claims 16-25, wherein said composition is in a solid form.

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

29. The composition of any one of claims 16-25, wherein said composition is in liquid form.

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

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

32. The composition of any one of claims 16-31, wherein said composition further comprises one or more additional components selected from the group consisting of surfactants, including emulsifiers, dispersants, foam-formers, colorants, processing aids, lubricants, fillers, reinforcements, flame retardants, light stabilizers, ultraviolet radiation absorbers, weather stabilizers, plasticizers, release agents, perfumes, heat-retaining additives (e.g., silica), cross- linking agents, antioxidants, anti-foaming agents, buffers, pH modifiers, compatibility agents, drift control additives, extenders / stickers, tackifiers, plant penetrants, safeners, spreaders, and wetting agents. 70 BUSINESS.31669632.1 409753-016WO (210621)

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