Alcohol-type insect pheromone derivatives, preparation method therefor, and use thereof

Abstract

The present invention provides alcohol-type insect pheromone derivatives, wherein a compound containing at least one functional group such as a carboxyl group and an amide group acts as a carrier and is chemically reacted with an alcohol-type insect pheromone to form derivatives such as an ester derivative and an anhydride derivative. The present invention further provides a preparation method, a use, and a release method for the alcohol-type insect pheromone derivatives. The alcohol-type insect pheromone derivatives provided by the present invention, formed by means of chemically derivatizing an alcohol-type insect pheromone, significantly improve the stability of alcohol-type insect pheromones while also enabling the sustained release and controlled release of such pheromones. Carrier materials are widely available and offer a diverse range of options, providing convenience and cost-effectiveness. In addition, the alcohol-type insect pheromone derivatives provided by the present invention also enable the co-release of multiple pheromones, thereby allowing for a variety of insects to be trapped and managed.

Description

An alcohol-based insect pheromone derivative, its preparation method and uses Technical Field

[0001] This invention relates to the field of insect pheromone pesticides, specifically to an alcohol-based insect pheromone derivative, its preparation method, and its uses. Background Technology

[0002] Pheromones are a collective term for compounds that play a role in chemical communication between organisms. They are compounds used by insects to express various information such as gathering, foraging, mating, and alarm. In other words, they are the chemical molecular language of insect communication. Common pheromones include: altruistic pheromones, egoistic pheromones, synergistic pheromones, aggregation pheromones, tracking pheromones, alarm pheromones, dispersal pheromones, and sex pheromones.

[0003] In recent years, the overuse of pesticides has posed a serious threat to the environment, agricultural product safety, and human health. The increasing resistance of pests to pesticides has also presented new challenges to their control. With the improvement of people's environmental and ecological awareness, new pest control technologies that use sex pheromones to interfere with mating, such as sex mating techniques, to reduce the reproduction rate of pest populations and control pest damage are receiving more and more attention.

[0004] Insect sex pheromones are compounds that regulate the attraction behavior of male and female insects. They are both sensitive and specific, with a long range of action and strong attraction. Sex pheromones are biomimetic high-tech products that mimic natural insect sex pheromones and are released into the field through a releaser to lure and kill pests of the opposite sex. This technology kills pests without contacting plants or agricultural products, eliminating concerns about pesticide residues, and is one of the preferred methods for ecological pest control in modern agriculture.

[0005] Typically, insect sex pheromones used for pest monitoring and control are processed into slow-release formulations using physical methods. The carrier materials are often synthetic materials such as rubber, polyethylene, and polyvinyl chloride. These carriers are not easily degraded in the environment, easily becoming agricultural waste and causing farmland pollution. In recent years, researchers have also developed chemical methods to process insect sex pheromones. However, products obtained through chemical processing generally require light exposure for pheromone release, limiting their application.

[0006] For alcohol-based insect pheromones (such as cis-11-hexadecenol), their stability is generally poor, they evaporate quickly and are prone to deterioration. Physical processing alone is unlikely to significantly improve their stability. Existing chemical methods mainly achieve slow release through light, with ultraviolet light being the primary light source. This places high demands on the application environment. Furthermore, alcohol-based pheromones are inherently unstable under ultraviolet light, thus limiting their application.

[0007] Therefore, there is an urgent need to develop a chemical-based processing method for alcohol-based insect pheromones that is simple to process and has low application requirements, in order to improve their stability and expand their application range. Summary of the Invention

[0008] To overcome the shortcomings of the existing technology, one object of the present invention is to provide an alcohol-based insect pheromone derivative that improves the stability of alcohol-based insect pheromones through chemical reactions. Under certain conditions, this derivative can achieve the slow and controlled release of insect pheromones, and therefore has great potential as an insect trapping and control product.

[0009] Another object of the present invention is to provide a method for preparing, using and releasing the alcohol-based insect pheromone derivative.

[0010] The first aspect of the present invention provides an alcohol-based insect pheromone derivative, which uses a compound containing at least one carboxyl group as a carrier, with which the alcohol-based insect pheromone forms an ester derivative or a stereoisomer of the structure shown in formula (I).

[0011] Wherein, R represents the residues of the compound containing at least one carboxyl group after removing y carboxyl groups;

[0012] a represents an integer from 1 to 20 (for example, it can be any integer from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20);

[0013] b represents an integer from 0 to 20 (for example, it can be any integer from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20);

[0014] c represents an integer from 0 to 2 (for example, it can be any integer of 0, 1 or 2);

[0015] d represents an integer from 0 to 20 (for example, it can be any integer from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20);

[0016] y represents an integer that is at least 1.

[0017] Unlike existing physical processing methods, the alcohol-based insect pheromone derivatives provided by this invention use common compounds containing at least one carboxyl group as a carrier. The ester derivatives are generated through an esterification reaction between the carboxyl group and the hydroxyl group of the insect pheromone. This allows the alcohol-based insect pheromone to be attached to the carrier material, significantly improving its stability. Depending on the number of carboxyl groups involved in the reaction, one or more pheromones can be attached to the carrier, forming a novel "keychain"-like structure. The resulting ester derivatives can undergo controlled, slow hydrolysis under certain conditions (e.g., in air or water), thereby enabling the sustained release of the pheromone. The reaction route is shown below:

[0018] The alcohol-based insect pheromone derivatives provided by this invention can use any carboxyl-containing compound commonly found in the chemical field as a carrier material. Preferably, these are substances that are easily degradable under natural conditions, cause little pollution, and are inexpensive and readily available. They can be small molecules or large molecules such as polymers, polypeptides, and proteins. For example, the carrier materials that can be used in this invention include, but are not limited to, fatty acids, aromatic acids, amino acids, and polypeptides.

[0019] Furthermore, when the carrier material used contains other active reaction sites, other suitable pheromones can be linked to achieve the connection of multiple different insect pheromones on a single carrier, thereby enabling the combined application of pheromones to achieve the goal of controlling multiple insects simultaneously. For example, when amino acids and peptides are used as carrier materials, they also contain amino reaction sites, thus allowing the linking of aldehyde insect pheromones (imines can be formed through the reaction of aldehyde and amino groups), resulting in derivatives that can simultaneously release alcohol and aldehyde insect pheromones. If the combination of multiple pheromones is not required, they can be selectively protected depending on the actual situation. For example, common amino protecting groups such as Cbz, Boc, and Fmoc can be used, or no protection may be required.

[0020] In some implementations, y can represent an integer of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or larger.

[0021] In some embodiments, R may represent C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C3-C20 cycloalkyl, 3-20 heterocyclic, C6-C20 aryl, or 5-20 heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted by one or more substituents selected from deuterium, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkoxy, halogenated C1-C6 alkoxy, cyano, amino, nitro, hydroxyl, 3-8 heterocyclic, C3-C8 cycloalkyl, C6-C12 aryl, or 5-12 heteroaryl.

[0022] In some preferred embodiments, R may represent C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, 3-8 heterocyclic, C6-C12 aryl, or 5-12 heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted by one or more substituents selected from deuterium, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkoxy, halogenated C1-C6 alkoxy, cyano, amino, nitro, hydroxyl, 3-8 heterocyclic, C3-C8 cycloalkyl, C6-C12 aryl, or 5-12 heteroaryl.

[0023] In some preferred embodiments, R may represent phenyl, pyridyl, pyrazinyl or pyrimidinyl, and may optionally be substituted by one or more substituents selected from deuterium, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkoxy, cyano, amino, nitro, hydroxyl.

[0024] In some further preferred embodiments, the compound containing at least one carboxyl group (i.e., the support) may be one of the following compounds:

[0025] In some embodiments, the carrier used in the first aspect of the present invention can be a C2-C18 aliphatic monocarboxylic acid, dicarboxylic acid, tricarboxylic acid, or tetracarboxylic acid. In some preferred embodiments, the carrier can be a C2-C18 aliphatic α,ω-diacarboxylic acid, including but not limited to 1,3-malonic acid, 1,4-succinic acid, 1,5-glutaric acid, 1,6-adipic acid, 1,7-heptanenic acid, and 1,8-octanoic acid.

[0026] In other embodiments, the carrier used in the first aspect of the invention may be a natural amino acid or a non-natural amino acid. In some preferred embodiments, the carrier may be a natural amino acid, such as phenylalanine, alanine, glycine, leucine, γ-aminobutyric acid, etc.

[0027] In other embodiments, the carrier used in the first aspect of the invention can be a polypeptide formed from 2 to 20 (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) natural or non-natural amino acids. In some preferred embodiments, the carrier can be a polypeptide formed from 3 to 20 natural amino acids, for example, a polypeptide formed from 3 to 12 natural amino acids, and more specifically, a polypeptide formed from 3 to 8 natural amino acids. In some preferred embodiments, the carrier may be the polypeptide Ala-phe-leu-Trp-gly, Ala-Phe-Leu-Trp-Gly-Ala-Phe-Leu-Trp-Gly, Ala-Phe-Leu-Trp-Gly-Ala-Phe-Leu-Trp-Gly-Ala-Phe-Leu-Trp-Gly or Ala-Phe-Leu-Trp-Gly-Ala-Phe-Leu-Trp-Gly-Ala-Phe-Leu-Trp-Gly-Ala-Phe-Leu-Trp-Gly.

[0028] In some embodiments, the carrier used in the first aspect of the present invention can be a C3-C18 aliphatic α,ω-diacid, with which an alcoholic insect pheromone forms a monoester derivative with the structure shown in formula (I-1) or a diester derivative with the structure shown in formula (I-2), or a stereoisomer thereof.

[0029] Wherein, L represents a straight-chain or branched alkylene group of C1 to C16, for example, it can represent a straight-chain or branched alkylene group of C2 to C10, and further can represent a straight-chain alkylene group of C2 to C6;

[0030] R1 represents H, C1-C16 alkyl, C0-C8 alkylene, C6-C20 aryl or hydroxyl protecting group;

[0031] a, b, c, and d are each independently defined as in equation (Ⅰ).

[0032] When forming monoester derivatives, the remaining carboxyl group can be exposed or it can form esters with common alcohols, such as methyl ester, ethyl ester, n-propyl ester, isopropyl ester, n-butyl ester, isobutyl ester, tert-butyl ester, lauryl ester, benzyl ester, etc. The hydroxyl group can also be protected as needed, as long as it does not affect the release of alcohol-based insect pheromones.

[0033] In some embodiments, the carrier used in the first aspect of the invention can be an amino acid or a polypeptide, with which alcoholic insect pheromones form ester derivatives or stereoisomers of structures as shown in formula (I-3) or (I-4).

[0034] Wherein, R2 represents the amino acid residues after removing the carboxyl and amino groups;

[0035] P represents the polypeptide residues with the carboxyl and amino groups removed;

[0036] a, b, c, and d are each independently defined as in equation (Ⅰ);

[0037] R3 and R4 each independently represent H, C1-C16 alkyl, C0-C8 alkylene, C6-C20 aryl, R5-C(O)-, R5-NHC(O)-, R5-O-, or an amino protecting group, where R5 represents a C1-C6 alkyl or a halo-C1-C6 alkyl (e.g., trifluoromethyl), or -NR3R4 represents a structure as shown in formula (I-5).

[0038] Where a1 represents an integer from 1 to 20 (for example, it can be any integer from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20);

[0039] b1 represents an integer from 0 to 20 (for example, it can be any integer from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20);

[0040] c1 represents an integer from 0 to 2 (for example, it can be any integer of 0, 1 or 2);

[0041] d1 represents an integer from 0 to 20 (for example, it can be any integer from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20);

[0042] In some preferred embodiments, a1 represents an integer from 1 to 12, b1 represents an integer from 0 to 12, c1 represents an integer from 0 to 2, and d1 represents an integer from 0 to 10. In some more preferred embodiments, a1 represents an integer from 3 to 12, b1 represents an integer from 0 to 6, c1 represents an integer of 0 or 1, and d1 represents an integer from 0 to 8. In some even more preferred embodiments, a1 represents an integer from 6 to 10, b1 represents 0, c1 represents 0, and d1 represents an integer from 2 to 6.

[0043] In some preferred embodiments, the structure shown in formula (I-5) consists of amino acids and the amino group of polypeptides and the aldehyde insect pheromone CHO-(CH2). a1 -(CH=CH)-(CH2) b1 -(CH=CH) c1 -(CH2) d1 The -CH3 reaction forms a pheromone, at which point both aldehyde and alcohol insect pheromones are simultaneously attached to the carrier material. In some preferred embodiments, the aldehyde insect pheromone may be cis-9-hexadecenal, cis-11-hexadecenal, or cis-13-octadecenal.

[0044] In some embodiments, in formula (I), a represents an integer from 1 to 12, b represents an integer from 0 to 12, c represents an integer from 0 to 2, and d represents an integer from 0 to 10. In some preferred embodiments, a represents an integer from 3 to 12, b represents an integer from 0 to 6, c represents an integer of 0 or 1, and d represents an integer from 0 to 8. In some more preferred embodiments, a represents an integer from 6 to 10, b represents 0, c represents an integer of 0 or 1, and d represents an integer from 0 to 6. In some further preferred embodiments, the alcohol-based insect pheromone may be cis-9-hexadecenal or E8E10-dodecadien-1-ol.

[0045] A second aspect of the present invention provides a method for preparing an alcohol-based insect pheromone derivative as described in any of the above technical solutions, the method comprising: reacting a compound containing at least one carboxyl group of the structure shown in formula (III) with an alcohol-based insect pheromone of the structure shown in formula (IV) in an optional first organic solvent in the presence of an optional catalyst or condensing agent to prepare the ester derivative;

[0046] HO-CH2-(CH2) a -(CH=CH)-(CH2) b -(CH=CH) c -(CH2) d -CH3

[0047] Formula (Ⅳ)

[0048] Alternatively, a compound containing at least one carboxyl group, as shown in formula (III), is first formed in the presence of a halogenating agent into an acyl halide intermediate of formula (III-1), which is then reacted with an alcoholic insect pheromone of formula (IV) in an optional first organic solvent to prepare the ester derivative.

[0049] Wherein, R, a, b, c, d, and y are each independently defined as in any of the above technical solutions;

[0050] X1 represents a halogen (e.g., Cl or Br).

[0051] In the preparation method provided by the present invention, the reaction can be carried out in different reaction media (e.g., water, organic solvent or the reaction raw materials themselves) according to the different carrier materials selected, so as to prepare the ester derivatives. The reaction temperature and reaction time can also be adjusted by those skilled in the art according to different reaction media and in combination with the actual reaction conditions. The purification method of the product can also be selected by those skilled in the art according to different product types and in combination with the actual reaction conditions, such as extraction, crystallization, column chromatography, etc.

[0052] In some embodiments, the preparation method may further include: reacting a compound containing at least one carboxyl group of the structure shown in formula (III) with an alcoholic insect pheromone of the structure shown in formula (IV) in an optional first organic solvent at 10–150 °C in the presence of a protic acid catalyst or condensing agent to prepare the ester derivative.

[0053] In some embodiments, the reaction temperature can be about 10°C, about 20°C, about 30°C, about 40°C, about 50°C, about 60°C, about 70°C, about 80°C, about 90°C, about 100°C, about 110°C, about 120°C, about 130°C, about 140°C, about 150°C, or any temperature range. In some preferred embodiments, the reaction temperature can be 25–105°C.

[0054] In some embodiments, the first organic solvent may be aliphatic hydrocarbons (such as n-pentane, n-hexane, etc.), alicyclic hydrocarbons (such as cyclopentane, cyclohexane, etc.), aromatic hydrocarbons (such as benzene, toluene, xylene, etc.), heterocyclic hydrocarbons (such as tetrahydrofuran, methyltetrahydrofuran, 1,4-dioxane, etc.), halogenated aliphatic hydrocarbons (such as dichloromethane, trichloromethane, dichloroethane, etc.), halogenated aromatic hydrocarbons (such as chlorobenzene, bromobenzene, chlorotoluene, bromotoluene, etc.), alcohols (such as methanol, ethanol, n-propanol, isopropanol, n-butanol, etc.), ketones (such as acetone, butanone, etc.), esters (such as methyl acetate, ethyl acetate, etc.), ethers (such as diethyl ether, diethyl ether, etc.), nitriles (such as acetonitrile, etc.), alkyl sulfoxides (such as dimethyl sulfoxide, etc.), alkyl amides (such as dimethyl imide, etc.), and other solvents commonly used in the art.

[0055] In some embodiments, the weight of the first organic solvent can be 1 to 100 times the weight of the alcohol-based insect pheromone, for example, about 2 times, about 5 times, about 8 times, about 10 times, about 12 times, about 15 times, about 18 times, about 20 times, about 22 times, about 25 times, about 28 times, about 30 times, about 35 times, about 40 times, about 45 times, about 50 times, about 60 times, about 70 times, about 80 times, about 90 times, about 100 times, or any multiple range.

[0056] In some embodiments, the protic acid catalyst can be any catalyst commonly used in the art capable of catalyzing the esterification of carboxyl and hydroxyl groups, including but not limited to one or more of toluenesulfonic acid, sulfuric acid, methanesulfonic acid, and trifluoromethanesulfonic acid.

[0057] In some embodiments, the molar ratio of the compound containing at least one carboxyl group, the alcoholic insect pheromone, and the protic acid catalyst can be 0.5–5:1:0.05–5.

[0058] In some embodiments, the condensing agent may be any condensing agent commonly used in the art for esterification reactions of carboxyl and hydroxyl groups, including but not limited to one or more of N,N-dicyclohexylcarbodiimide (DCC), 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (HATU), and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI).

[0059] A third aspect of the present invention provides an alcohol-based insect pheromone derivative, wherein a compound containing at least one carboxyl or amide group serves as a carrier, and the alcohol-based insect pheromone forms an anhydride derivative or an amide ester derivative, or a stereoisomer thereof, with the structure shown in formula (II).

[0060] Wherein, R' represents the compound containing at least one carboxyl or amide group, excluding y residues of the carboxyl or amide group moiety;

[0061] a represents an integer from 1 to 20 (for example, it can be any integer from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20);

[0062] b represents an integer from 0 to 20 (for example, it can be any integer from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20);

[0063] c represents an integer from 0 to 2 (for example, it can be any integer of 0, 1 or 2);

[0064] d represents an integer from 0 to 20 (for example, it can be any integer from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20);

[0065] X represents -O- or -NR0-;

[0066] R0 represents hydrogen or a C1-C16 alkyl group;

[0067] y represents an integer that is at least 1.

[0068] In some implementations, y can represent an integer of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or larger.

[0069] Compared to ester derivatives, acid anhydride derivatives are more easily hydrolyzed and do not require the presence of hydrolytic enzymes, thus making it easier to control the release of alcohol-based insect pheromones. The carrier used in the third aspect of this invention can be any carboxyl or amide-containing compound commonly found in the chemical field.

[0070] In some embodiments, R' may represent C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C3-C20 cycloalkyl, 3-20 heterocyclic, C6-C20 aryl, or 5-20 heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted by one or more substituents selected from deuterium, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkoxy, halogenated C1-C6 alkoxy, cyano, amino, nitro, hydroxyl, 3-8 heterocyclic, C3-C8 cycloalkyl, C6-C12 aryl, or 5-12 heteroaryl.

[0071] In some preferred embodiments, R' may represent C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, 3-8 heterocyclic, C6-C12 aryl, or 5-12 heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted by one or more substituents selected from deuterium, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkoxy, halogenated C1-C6 alkoxy, cyano, amino, nitro, hydroxyl, 3-8 heterocyclic, C3-C8 cycloalkyl, C6-C12 aryl, or 5-12 heteroaryl.

[0072] In some preferred embodiments, R' may represent a C2-C6 alkyl, C2-C6 alkenyl, C6-C12 aryl, or a 5-6 heteroaryl (e.g., phenyl, pyridyl, pyrazinyl, or pyrimidinyl), wherein the aryl and heteroaryl groups are optionally substituted by one or more substituents selected from deuterium, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkoxy, cyano, amino, nitro, and hydroxyl.

[0073] In some implementations, X may represent -O- or -NH-.

[0074] In some embodiments, the carrier used in the third aspect of the invention includes, but is not limited to, acetic acid, propionic acid, butyric acid, valeric acid, hexanoic acid, caprylic acid, and strawberry acid. wait.

[0075] In some embodiments, the carrier used in the third aspect of the present invention may also be one or more of fatty acids, aromatic acids, amino acids, and polypeptides containing at least one carboxyl group.

[0076] In some embodiments, the carrier used in the third aspect of the present invention can be a C2-C18 aliphatic monocarboxylic acid, dicarboxylic acid, tricarboxylic acid, or tetracarboxylic acid. In some preferred embodiments, the carrier can be a C2-C18 aliphatic monocarboxylic acid, including but not limited to acetic acid, propionic acid, butyric acid, valeric acid, hexanoic acid, octanoic acid, etc.

[0077] In other embodiments, the carrier used in the third aspect of the invention may be a natural amino acid or a non-natural amino acid. In some preferred embodiments, the carrier may be a natural amino acid, such as phenylalanine, alanine, glycine, leucine, γ-aminobutyric acid, etc.

[0078] In other embodiments, the carrier used in the third aspect of the invention may be a polypeptide formed from 2 to 20 natural amino acids or non-natural amino acids. In some preferred embodiments, the carrier may be a polypeptide formed from 3 to 20 natural amino acids, for example, a polypeptide formed from 3 to 12 natural amino acids, and more particularly, a polypeptide formed from 3 to 8 natural amino acids. In some most preferred embodiments, the carrier may be the polypeptide Ala-phe-leu-Trp-gly, Ala-Phe-Leu-Trp-Gly-Ala-Phe-Leu-Trp-Gly, Ala-Phe-Leu-Trp-Gly-Ala-Phe-Leu-Trp-Gly, or Ala-Phe-Leu-Trp-Gly-Ala-Phe-Leu-Trp-Gly-Ala-Phe-Leu-Trp-Gly.

[0079] In some embodiments, in formula (II), a represents an integer from 1 to 12, b represents an integer from 0 to 12, c represents an integer from 0 to 2, and d represents an integer from 0 to 10. In some preferred embodiments, a represents an integer from 3 to 12, b represents an integer from 0 to 6, c represents an integer of 0 or 1, and d represents an integer from 0 to 8. In some more preferred embodiments, a represents an integer from 6 to 10, b represents 0, c represents an integer of 0 or 1, and d represents an integer from 0 to 6. In some further preferred embodiments, the alcohol-based insect pheromone may be cis-9-hexadecenal or E8E10-dodecadien-1-ol.

[0080] A fourth aspect of the present invention provides a method for preparing the above-mentioned acid anhydride alcohol insect pheromone derivatives, the method comprising the following steps:

[0081] S1: Alcoholic insect pheromones with the structure shown in formula (Ⅳ) react to form intermediates with the structure shown in formula (Ⅳ-1); and

[0082] S2: In the presence of an optional basic reagent, a compound containing at least one carboxyl or amide group with the structure shown in formula (V) is reacted with an intermediate with the structure shown in formula (Ⅳ-1) in an optional second organic solvent to prepare the anhydride derivative.

[0083] HO-CH2-(CH2) a -(CH=CH)-(CH2) b -(CH=CH) c -(CH2) d -CH3

[0084] Formula (Ⅳ)

[0085] In this context, R', a, b, c, d, X, and y are each independently defined as in equation (II), and X1 represents a halogen, including F, Cl, Br, and I.

[0086] In the preparation method provided by the present invention, the reaction can be carried out in different reaction media (e.g., water, organic solvents, or the reaction raw materials themselves) according to the selected different carrier materials, and in the presence of optional catalysts or auxiliaries (e.g., alkaline reagents) to prepare the acid anhydride derivatives or amide ester derivatives. The reaction temperature and reaction time can also be adjusted by those skilled in the art according to different reaction media and actual reaction conditions. The purification method of the product can also be selected by those skilled in the art according to different product types and actual reaction conditions, such as extraction, crystallization, column chromatography, etc.

[0087] In some embodiments, alcoholic insect pheromones with the structure shown in formula (Ⅳ) can be reacted with phosgene or triphosgene in an optional third organic solvent to form an intermediate with the structure shown in formula (Ⅳ-1).

[0088] In some embodiments, the definitions (e.g., type, amount, etc.) of the second and third organic solvents are the same as those of the first organic solvent.

[0089] In some embodiments, the alkaline reagent can be of common types in the art, including but not limited to sodium hydride, sodium hydroxide, potassium hydroxide, diethylamine, triethylamine, N,N-diisopropylethylamine, DBU, pyridine, 2,6-dimethylpyridine, etc.

[0090] A fifth aspect of the present invention provides an alcohol-based insect pheromone derivative, wherein a compound containing at least one -O(CO)-Cl group serves as a carrier, and the alcohol-based insect pheromone forms an ester derivative or a stereoisomer thereof with the structure shown in formula (1).

[0091] Wherein, R” represents the residues of the compound containing at least one -O(CO)-Cl group, excluding y -O(CO)-Cl group portions;

[0092] a represents an integer from 1 to 20 (for example, it can be any integer from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20);

[0093] b represents an integer from 0 to 20 (for example, it can be any integer from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20);

[0094] c represents an integer from 0 to 2 (for example, it can be any integer of 0, 1 or 2);

[0095] d represents an integer from 0 to 20 (for example, it can be any integer from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20);

[0096] y represents an integer that is at least 1.

[0097] In some implementations, y can represent an integer of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or larger.

[0098] In some embodiments, "R" may represent C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C3-C20 cycloalkyl, 3-20 heterocyclic, C6-C20 aryl, or 5-20 heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted by one or more substituents selected from deuterium, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkoxy, halogenated C1-C6 alkoxy, cyano, amino, nitro, hydroxyl, 3-8 heterocyclic, C3-C8 cycloalkyl, C6-C12 aryl, or 5-12 heteroaryl.

[0099] In some preferred embodiments, R” may represent a C6-C12 aryl or a 5-6 heteroaryl (e.g., phenyl, pyridyl, pyrazinyl, or pyrimidinyl), wherein the aryl and heteroaryl groups are optionally substituted by one or more substituents selected from deuterium, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkoxy, cyano, amino, nitro, and hydroxyl.

[0100] In some further embodiments, the compound containing at least one -O(CO)-Cl group (i.e., the support) may be one of the following compounds:

[0101] In some embodiments, in formula (1), a represents an integer from 1 to 12, b represents an integer from 0 to 12, c represents an integer from 0 to 2, and d represents an integer from 0 to 10. In some preferred embodiments, a represents an integer from 3 to 12, b represents an integer from 0 to 6, c represents an integer of 0 or 1, and d represents an integer from 0 to 8. In some more preferred embodiments, a represents an integer from 6 to 10, b represents 0, c represents an integer of 0 or 1, and d represents an integer from 0 to 6. In some further preferred embodiments, the alcohol-based insect pheromone may be cis-9-hexadecenal or E8E10-dodecadien-1-ol.

[0102] In some embodiments, the alcohol-based insect pheromone derivatives provided by the present invention can be the following compounds:

[0103] A sixth aspect of the present invention provides the use of any of the alcohol-based insect pheromone derivatives described in the above-described technical solutions in the preparation of sustained-release and / or controlled-release formulations of insect pheromones. As described above, the alcohol-based insect pheromone derivatives provided by the present invention have the advantages of good stability and sustained-release and controlled-release capabilities, and are therefore very suitable for use in the preparation of sustained-release and controlled-release formulations of insect pheromones or other insect pheromone products with similar functions.

[0104] A seventh aspect of the present invention provides a method for releasing an alcohol-based insect pheromone derivative as described in any of the above technical solutions, wherein the method comprises: hydrolyzing the alcohol-based insect pheromone derivative in water or in air in the presence of an optional enzyme to release the alcohol-based insect pheromone.

[0105] In some embodiments, when the alcohol-based insect pheromone derivative is released into the air, the humidity of the air can be 1 to 100% (relative humidity, RH), for example, it can be about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 100%, or any humidity range.

[0106] In some embodiments, when the alcohol-based insect pheromone derivative is released into the air, the air temperature can be between 10 and 60°C, for example, about 10°C, about 15°C, about 20°C, about 25°C, about 30°C, about 35°C, about 40°C, about 45°C, about 50°C, about 55°C, about 60°C, or any temperature range.

[0107] In some embodiments, when the alcoholic insect pheromone derivative is released in water, its mass percentage concentration in water can be 0.1% to 50%, for example, it can be about 0.1%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, or any mass percentage range.

[0108] In some embodiments, when the alcohol-based insect pheromone derivative is released in water, the temperature of the water can be room temperature, i.e., 25±5℃.

[0109] In some embodiments, the enzyme may be a common enzyme in the art that promotes ester hydrolysis, including but not limited to Y200 enzyme, Novozym435, LVK-40G, etc.

[0110] In some preferred embodiments, the alcohol-based insect pheromone derivatives can be hydrolyzed in air at a temperature of 10–60°C (e.g., 25–50°C) and a relative humidity (RH) of 10–100% (e.g., 60–90%) to release the alcohol-based insect pheromone.

[0111] The release method provided by this invention can adjust the release rate and release amount of alcohol-based insect pheromones by various means such as adjusting the concentration of alcohol-based insect pheromone derivatives in water, air humidity, temperature, and using different enzymes, thereby achieving sustained release and controlled release.

[0112] The technical solution provided by this invention has the following advantages:

[0113] (1) The alcohol-based insect pheromone derivatives provided by the present invention can significantly improve the stability of alcohol-based insect pheromones by chemical reaction, and can also achieve sustained and controlled release of pheromones. The carrier materials are widely available, with many choices, convenient and economical. Some carrier materials are easily degraded in the environment after releasing pheromones, making them green and environmentally friendly.

[0114] (2) The alcohol-based insect pheromone derivatives provided by the present invention can also achieve the combined release of multiple pheromones and regulate the release rate and amount of different pheromones, thereby enabling the control of multiple insects in multiple scenarios.

[0115] (3) The preparation process of the alcohol-based insect pheromone derivatives provided by the present invention is simple, the carrier materials are widely available and inexpensive, the synthesis and release processes are mild and easy to control, and the operability is strong. Therefore, it has good industrial applicability and is suitable for large-scale production and application. Attached Figure Description

[0116] Figure 1 shows the experimental results of the hydrolysis experiment in Example 49;

[0117] Figure 2 shows the experimental results of the hydrolysis experiment in Example 50;

[0118] Figure 3 shows the experimental results of the hydrolysis experiment in Example 51;

[0119] Figure 4 shows the experimental results of the hydrolysis experiment in Example 52;

[0120] Figure 5 shows the experimental results of the hydrolysis experiment in Example 53;

[0121] Figure 6 is a graph showing the experimental results of the hydrolysis experiment in Example 54. Detailed Implementation

[0122] the term

[0123] Unless otherwise defined, the terminology used in this invention should be considered to have the ordinary meaning that can be understood by those skilled in the art. Some common terms are introduced and explained below:

[0124] The singular forms used in this article, such as “a,” “an,” “the,” “the,” “the above,” etc., contain both singular and plural referents.

[0125] The use of "include" or "include" in this article is open-ended rather than restrictive, meaning that it does not exclude unlisted types, elements, or methods or steps.

[0126] As used herein, "one embodiment" specifically refers to the particular feature, structure, or property of the described subject when the phrase appears. Therefore, "one embodiment" appearing in different places herein does not necessarily refer to the same embodiment. On the other hand, some specific embodiments may include some features of other embodiments but not all features of other embodiments. In such cases, combinations of embodiments with different features, although not listed herein, should be assumed to be included in the claims and statements herein.

[0127] As used herein, "C1-Cn" includes C1-C2, C1-C3, ..., C1-Cn. For example, the term "C1-C16" refers to a group having 1 to 16 carbon atoms, meaning the group contains 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 carbon atoms. Therefore, for example, "C1-C16 alkyl" refers to an alkyl group containing 1 to 16 carbon atoms.

[0128] The term "alkyl" as used alone or in combination herein refers to a saturated aliphatic hydrocarbon with optional substituted straight or optional substituted branched chains. Preferably, it may have 1 to 16 carbon atoms, or 1 to 8 carbon atoms, or 1 to 6 carbon atoms. Non-limiting examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, 2-methyl-3-butyl, 2,2-dimethyl-1-propyl, 2-methyl-1-pentyl, 3-methyl-1-pentyl, 4-methyl-1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1-butyl, 3,3-dimethyl-1-butyl, 2-ethyl-1-butyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, and hexyl, as well as longer alkyl groups such as heptyl, octyl, nonyl, decyl, undecyl, dodecyl, etc.

[0129] As used alone or in combination herein, the term "alkylene" refers to an optionally substituted saturated straight-chain or branched aliphatic hydrocarbon group having two residues derived from the removal of two hydrogen atoms from the same carbon atom or two different carbon atoms of the parent alkane, preferably C1-C8 alkylene, more preferably C1-C6 alkylene. Non-limiting examples of alkylene include, but are not limited to, methylene, 1,1-ethylene, 1,2-ethylene, 1,1-propylene, 1,2-propylene, 1,3-propylene, 1,4-butylene, etc. Furthermore, when alkylene is "C0", it means that alkylene is absent.

[0130] As used alone or in combination herein, the term "alkenyl" refers to an alkyl group as defined above, consisting of at least two carbon atoms and at least one carbon-carbon double bond. It can be straight-chain or branched, preferably C2-C8 alkenyl, more preferably C2-C6 alkenyl. Non-limiting examples of alkenyl groups include, but are not limited to, vinyl, 1-propenyl, 2-propenyl, 1-, 2-, or 3-butenyl. wait.

[0131] The term "alkynyl" as used alone or in combination herein refers to an alkyl group as defined above, consisting of at least two carbon atoms and at least one carbon-carbon triple bond. It can be straight-chain or branched, preferably C2-C8 alkynyl, and more preferably C2-C6 alkynyl. Non-limiting examples of alkynyl groups include, but are not limited to, ethynyl, 1-propynyl, 2-propynyl, 1-, 2-, or 3-butynyl.

[0132] The term "cycloalkyl" as used alone or in combination herein refers to an optionally substituted non-aromatic saturated carbocyclic ring, which may include a monocyclic (having one ring), a bicyclic (having two rings), or a polycyclic (having more than two rings), and the ring type includes fused rings, bridged rings, and spirocyclic rings. Preferably, the cycloalkyl group may have 3 to 10 cyclic carbon atoms, for example, 3 to 6 cyclic carbon atoms. Non-limiting examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl.

[0133] The term "heterocyclic group" as used alone or in combination herein refers to a non-aromatic, 5- to 20-membered monocyclic, bicyclic, or polycyclic ring, including fused rings, bridged rings, and spirocyclic rings, wherein the cyclic atoms may comprise 1 to 4 (e.g., 1, 2, 3, or 4) atoms selected from nitrogen, oxygen, and / or sulfur. Preferably, the heterocyclic group may have 5 to 12 cyclic atoms, for example, 5 to 10 cyclic atoms, or 5 to 8 cyclic atoms, or 5 to 6 cyclic atoms. Non-limiting examples of heterocyclic groups include, but are not limited to, morpholino, oxobutyryl, thiomorpholino, tetrahydrofurano, tetrahydropyrano, 1,1-dioxo-thiomorpholino, piperidino, 2-oxo-piperidino, pyrrolyl, 2-oxo-pyrrolyl, piperazine-2-one, 8-oxa-3-aza-bicyclo[3.2.1]octyl, piperazine, hexahydropyrimidine, etc.

[0134] The term "aryl" as used alone or in combination herein refers to an optionally substituted aromatic hydrocarbon group having 6 to 20, such as 6 to 12 or 6 to 10 cyclic carbon atoms, which can be monocyclic, bicyclic, or polycyclic. Bicyclic or multiple cyclic aryl groups can be a monocyclic aryl group fused with other independent rings, such as alicyclic or aromatic rings. Non-limiting examples of monocyclic aryl groups include, but are not limited to, phenyl; non-limiting examples of bicyclic aryl groups include naphthyl; non-limiting examples of polycyclic aryl groups include, but are not limited to, phenanthryl, anthracene, fluorenyl, azulel, etc.

[0135] The term "heteroaryl" as used alone or in combination herein refers to an optionally substituted aromatic 5- to 20-membered monocyclic, bicyclic, or polycyclic ring, including fused rings, bridged rings, and spirocyclic rings, wherein the cyclic atoms may comprise 1 to 4 (e.g., 1, 2, 3, or 4) atoms selected from nitrogen, oxygen, and / or sulfur. Preferably, the heteroaryl group may have 5 to 12 cyclic atoms, for example, 5 to 10 cyclic atoms, 5 to 8 cyclic atoms, or 5 to 6 cyclic atoms. Non-limiting examples of heteroaryl groups include, but are not limited to, furanyl, pyridyl, 2-oxo-1,2-dihydropyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiopheneyl, isoxazolyl, oxazolyl, oxadiazolyl, imidazolyl, pyrroleyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, 1,2,3-thiadiazolyl, benzo[m]dioxacyclopentenyl, benzo[thiophene], benzimidazolyl, indoleyl, isoyindolyl, 1,3-dioxo-isoindolyl, quinolinyl, inzolyl, benzo[isothiazolyl], benzo[oxazolyl], benzo[isothiazolyl], isothiazolyl, 1H-1,2,4-triazolyl, 4H-1,2,4 - Triazolyl, pyridyl, pyrimidinyl, pyrazin-2(1H)-keto, pyrimidin-4(3H)-keto, pyridazin-3(2H)-keto, 1H-indolyl, 1H-benzo[d]imidazolyl, 1H-pyrrolo[2,3-c]pyridyl, 3H-imidazo[4,5-c]pyridyl, isoquinolinyl, quinazolinyl, 2H-isoindolyl, furan[3,2-b]pyridyl, furan[2,3-c]pyridyl, thieno[2,3-c]pyridyl, benzofuranyl, benzo[b]thienoyl, 1H-pyrrolo[3,2-b]pyridyl, 2H-pyrrolo[3,4-c]pyridyl, etc.

[0136] The term "alkoxy" as used alone or in combination herein refers to an "alkyl-O-" group. Alkyl groups are defined herein. Non-limiting examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, etc.

[0137] The term "nitro" as used alone or in combination in this article refers to the -NO2 group.

[0138] The term "hydroxyl group" as used alone or in combination in this article refers to the -OH group.

[0139] The term “halogen” as used alone or in combination in this article refers to fluorine (F), chlorine (Cl), bromine (Br) or iodine (I).

[0140] The term "amino" as used alone or in combination in this article refers to -NH2.

[0141] The term "cyano" as used alone or in combination in this article refers to -CN.

[0142] The term "carboxyl group" as used alone or in combination in this article refers to -COOH.

[0143] The term “benzyl” as used alone or in combination in this article refers to -CH2-phenyl.

[0144] The term “natural amino acid” as used alone or in combination herein includes the following amino acids having the α-configuration: glycine (Gly), alanine (Ala), valine (Val), leucine (Leu), isoleucine (Ile I), proline (Pro), phenylalanine (Phe), tyrosine (Tyr), tryptophan (Trp), serine (Ser), threonine (Thr), cysteine ​​(Cys), methionine (Met), asparagine (Asn), glutamine (Gln), aspartic acid (Asp), glutamic acid (Glu), lysine (Lys), arginine (Arg), and histidine (His), as well as non-protein natural amino acids such as γ-aminobutyric acid.

[0145] The term “non-natural amino acid” as used alone or in combination in this article refers to amino acids other than natural amino acids, such as citrulline.

[0146] The term "stereoisomer" as used alone or in combination herein includes all isomeric forms, such as R and S configurations arising from one or more asymmetric centers, (Z) and (E) double bond isomers (geometric isomers), (Z) and (E) conformational isomers, trans-restricted isomers, etc. Similarly, the invention can also exist as a mixture of two or more structurally different forms in rapid equilibrium (commonly referred to as tautomers), representative examples of which include keto-enol tautomers, phenol-keto tautomers, nitroso-oxime tautomers, imine-enamine tautomers, etc. It is contemplated that the scope of this invention covers all such isomers or mixtures thereof in any proportion.

[0147] The technical solution of the present invention will be further described in detail below with reference to specific embodiments.

[0148] Unless otherwise specified, all raw materials or reagents used in the embodiments of the present invention are commercially available products, and all percentages used are mass percentages unless otherwise specified.

[0149] In the embodiments of the present invention, room temperature (or normal temperature) refers to 25±5℃.

[0150] In embodiments of the present invention, the hydrolysis of the obtained derivatives is monitored by HPLC detection.

[0151] Example 1: Preparation of ester derivatives using succinic acid as a carrier

[0152] 22.4 g (95%, 2.2 eq) of cis-11-hexadecenol, 2.18 g (99%, 0.3 eq) of p-toluenesulfonic acid, 5 g (99%, 1 eq) of 1,4-succinic acid and 25 g of toluene were weighed and added to a reaction vessel. The mixture was refluxed at 120 °C for 8 h to remove water. The reaction was monitored by GC and the conversion rate was about 90%. The reaction solution was concentrated and purified by column chromatography (200-300 mesh silica gel, elution system: n-heptane: ethyl acetate = 20:1, v / v) to obtain 21.3 g of diester derivative 1.

[0153] 1 H NMR (400MHz, CDCl3) δ5.40–5.28(m,4H),4.07(t,J=6.1Hz,4H),2.64(s,4H),2.08–1.96(m,8H),1.49–1.20(m,41H),0.87(t,J=6.9Hz,6H).

[0154] Example 2: Preparation of ester derivatives using succinic acid as a carrier

[0155] 16.98 g (95%, 2.2 eq) of trans-8-trans-10-dodecadien-1-ol, 2.18 g (99%, 0.3 eq) of p-toluenesulfonic acid, 5 g (99%, 0.6 eq) of 1,4-succinic acid and 25 g of toluene were weighed and added to a reaction vessel. The mixture was refluxed at 120 °C for 8 h to remove water. The reaction was monitored by GC and the conversion rate was about 90%. The reaction solution was concentrated and purified by column chromatography (200-300 mesh silica gel, elution system: n-heptane: ethyl acetate = 20:1, v / v) to obtain 15.6 g of diester derivative 2.

[0156] 1 H NMR (400MHz, CDCl3) δ6.01–5.83(m,4H),5.64–5.47(m,4H),4.07(t,J=6.1Hz,3H),2. 64(s,4H),2.11(tdt,J=8.0,5.6,1.2Hz,4H),1.76–1.69(m,6H),1.49–1.26(m,21H).

[0157] Example 3: Preparation of ester derivatives using L-phenylalanine as a carrier

[0158] 10 g (95%, 1 eq) of cis-11-hexadecenol, 18.6 g (99%, 2.6 eq) of p-toluenesulfonic acid, 13.74 g (95%, 2 eq) of phenylalanine, and 100 g of toluene were weighed and added to a reaction vessel. The reaction was carried out at 120 °C for 6 h. The conversion rate was monitored by HPLC and found to be approximately 90%. After filtration, 130 g of DCM was added to the reaction solution. The organic phase was purified by rotary evaporation under reduced pressure and column chromatography (200-300 mesh silica gel, elution system: n-heptane: ethyl acetate = 20:1, v / v) to obtain 21.5 g of ester derivative 3.

[0159] 1 H NMR (400MHz, CDCl3) δ7.30(t,J=7.2Hz,2H),7.26–7.17(m,3H),5.35(t,J=4.9Hz,2H),4.09(t,J=6.7H z,2H),2.09-1.93(m,4H),1.79(s,3H),1.60(p,J=6.2Hz,2H),1.42-1.17(m,18H),0.92-0.87(m,3H).

[0160] Example 4: Preparation of ester derivatives using L-phenylalanine as a carrier

[0161] 10 g (95%, 1 eq) of trans-8-trans-10-dodecadien-1-ol, 24.5 g (99%, 2.6 eq) of p-toluenesulfonic acid, 18.12 g (95%, 2 eq) of phenylalanine, and 50 g of toluene were weighed and added to a reaction vessel. The reaction was carried out at 120 °C for 6 h. The conversion rate was monitored by HPLC and found to be approximately 90%. After filtration, 130 g of DCM was added to the reaction solution. The organic phase was purified by rotary evaporation under reduced pressure followed by column chromatography (200-300 mesh silica gel, elution system: n-heptane: ethyl acetate = 20:1, v / v) to obtain 16.8 g of ester derivative 4.

[0162] 1 H NMR(400MHz, CDCl3)δ7.29(d,J=7.4Hz,2H),7.20(d,J=7.3Hz,3H),6.08–5.92(m,2H),5.65-5.49(m,2H) ,4.09(t,J=6.6Hz,2H),2.15–1.96(m,4H),1.73(d,J=6.6Hz,1H),1.62-1.52(m,6H),1.44-1.23(m,9H).

[0163] Example 5: Preparation of ester derivatives using peptides as carriers.

[0164] 0.50 g (95%, 1 eq) of cis-11-hexadecenol, 0.46 g (99%, 1.2 eq) of p-toluenesulfonic acid, 1.48 g (95%, 1.2 eq) of the self-made peptide (Ala-phe-leu-Trp-gly) (peptide synthesis method referred to J.Am.Chem.Soc.2020,142,14201-14209.), and 20 g of THF were weighed and added to a reaction vessel. The reaction was carried out at 60 °C for 6 h. The conversion rate was monitored by HPLC and found to be approximately 74%. After the reaction solution was concentrated, 13 g of DCM was added, and the mixture was washed with 5% sodium bicarbonate (based on peptide, 1.2 eq) aqueous solution. After standing and separating, the organic phase was washed with water and separated again. The organic phase was then evaporated under reduced pressure to obtain 1.50 g of peptide esterification product.

[0165] 0.25 g (95%, 1 eq) of cis-9-hexadecenal and 1.4 g (95%, 1.2 eq) of the polypeptide esterification product were weighed into 5 g of DCM and reacted at 30 °C for 2 h. The reaction was monitored by HPLC and the conversion rate was approximately 70%. The reaction solution was washed with 5% sodium bicarbonate aqueous solution (1.0-1.1 eq based on the remaining amount of esterification product), allowed to stand and separated, and the organic phase was rotary evaporated under reduced pressure to obtain 1.1 g of ester derivative 5.

[0166] Calculated Mass [M+H] + :1034.75(100%); Mass Found(ESI+); 1034.74[M+H] + .

[0167] Example 6: Preparation of ester derivatives using polypeptides as carriers.

[0168] 0.45 g (95%, 1 eq) of trans-8-trans-10-dodecadien-1-ol, 0.46 g (99%, 1.2 eq) of p-toluenesulfonic acid, 1.48 g (95%, 1.2 eq) of the self-made polypeptide (Ala-phe-leu-Trp-gly) (polypeptide synthesis method referred to J.Am.Chem.Soc.2020,142,14201-14209.), and 5 g of THF were weighed and added to a reaction vessel. The reaction was carried out at 90 °C for 6 h. The conversion rate was monitored by HPLC and found to be approximately 74%. After the reaction solution was concentrated, 10 ml of DCM was added, and the mixture was washed with 5% sodium bicarbonate (based on the polypeptide, 1.2 eq) aqueous solution. After standing and separating, the organic phase was washed with water and separated again. The organic phase was then evaporated under reduced pressure to obtain 1.30 g of the polypeptide esterification product.

[0169] 0.25 g (95%, 1 eq) of cis-9-hexadecenal and 1.03 g (95%, 1.2 eq) of the polypeptide esterification product were weighed into 5 g of DCM and reacted at 60 °C for 2 h. The reaction was monitored by HPLC and the conversion rate was approximately 73%. The reaction solution was washed with 5% sodium bicarbonate aqueous solution (1.0-1.1 eq based on the remaining amount of esterification product), allowed to stand and separated, and the organic phase was rotary evaporated under reduced pressure to obtain 0.83 g of ester derivative 6.

[0170] Calculated Mass [M+H] + :976.68(100%); Mass Found(ESI+); 976.65[M+H] + .

[0171] Example 7: Preparation of ester derivatives using γ-aminobutyric acid as a carrier 7

[0172] 10 g (95%, 1 eq) of trans-8-trans-10-dodecadien-1-ol, 24.5 g (99%, 2.6 eq) of p-toluenesulfonic acid, 11.4 g (99%, 2 eq) of γ-aminobutyric acid, and 50 g of toluene were weighed and added to a reaction vessel. The reaction was carried out at 120 °C for 6 h. The conversion rate was monitored by HPLC and found to be approximately 90%. After filtration, 130 g of DCM was added to the reaction solution. The organic phase was purified by rotary evaporation under reduced pressure followed by column chromatography (200-300 mesh silica gel, elution system: n-heptane: ethyl acetate = 10:1, v / v) to obtain 17.6 g of ester derivative 7.

[0173] 1 H NMR (400MHz, CDCl3) δ6.01–5.83(m,2H),5.63–5.47(m,2H),3.99–3.91(m,2H),2.87(tt,J=6.5,5.5Hz,2H),2.43–2 .33(m,4H),2.11(tdt,J=8.0,5.6,1.2Hz,2H),1.87(tt,J=8.0,5.5Hz,2H),1.76–1.69(m,3H),1.49–1.26(m,10H).

[0174] Example 8: Preparation of ester derivatives using γ-aminobutyric acid as a carrier.

[0175] 10 g (95%, 1 eq) of cis-11-hexadecenol, 18.6 g (99%, 2.6 eq) of p-toluenesulfonic acid, 8.6 g (99%, 2 eq) of γ-aminobutyric acid, and 50 g of toluene were weighed and added to a reaction vessel. The reaction was carried out at 120 °C for 6 h. The conversion rate was monitored by HPLC and found to be approximately 90%. After filtration, 130 g of DCM was added to the reaction solution. The organic phase was purified by rotary evaporation under reduced pressure followed by column chromatography (200-300 mesh silica gel, elution system: n-heptane: ethyl acetate = 10:1, v / v) to obtain 15.6 g of ester derivative 8.

[0176] 1 H NMR (400MHz, CDCl3) δ5.43–5.31(m,2H),3.95(t,J=6.1Hz,2H),2.87(tt,J=6.5,5.6Hz,2H),2.43–2.33(m,4H),2.07–1.93(m,4H ),1.87(tt,J=8.0,5.5Hz,2H),1.49–1.38(m,2H),1.42–1.33(m,3H),1.37–1.27(m,4H),1.31–1.20(m,11H),0.92–0.81(m,3H).

[0177] Example 9: Preparation of chloroformate derivatives

[0178] 53.36 g (95%, 1 eq) of trans-8-trans-10-dodecadien-1-ol, 62 g (99%, 0.7 eq) of triphosgene, and 736 g of toluene were weighed and added to a reaction vessel. The reaction was carried out at 10 °C for 24 h. The conversion rate was approximately 90% as monitored by GC. The reaction solution was concentrated by rotary evaporation under reduced pressure to obtain 76.50 g of the target product 9.

[0179] 1 H NMR (400MHz, CDCl3) δ5.42–5.31(m,2H),4.27(t,J=6.1Hz,2H),2.07–1.94(m,4H),1. 70(tt,J=7.6,6.1Hz,2H),1.45–1.27(m,7H),1.31–1.20(m,11H),0.91–0.81(m,3H).

[0180] Example 10 Preparation of chloroformate derivative 10

[0181] 52g (95%, 1 eq) of cis-11-hexadecenol, 53.8g (99%, 0.7 eq) of triphosgene, and 717g of toluene were weighed and added to a reaction vessel. The reaction was carried out at 10°C for 24 hours. The conversion rate was approximately 90% as monitored by GC. The reaction solution was concentrated by rotary evaporation under reduced pressure to obtain 73.50g of the target product 10.

[0182] 1 H NMR (400MHz, CDCl3) δ5.42–5.31(m,2H),4.27(t,J=6.1Hz,2H),2.07–1.94(m,4H),1. 70(tt,J=7.6,6.1Hz,2H),1.45–1.27(m,7H),1.31–1.20(m,11H),0.91–0.81(m,3H).

[0183] Example 11: Preparation of amide ester derivatives using nicotinamide as a carrier.

[0184] 3.1 g (99%, 1.6 eq) of nicotinamide, 0.8 g (99%, 2 eq) of sodium hydride, and 25 g of THF were weighed and added to a reaction vessel. Under ice bath conditions, 5 g (80%, 1 eq) of the target product prepared in Example 9 was slowly added dropwise to the reaction vessel. The reaction was carried out at room temperature for 2 h. The conversion rate was monitored by GC and found to be approximately 90%. The reaction solution was concentrated by rotary evaporation under reduced pressure and then purified by column chromatography (200-300 mesh silica gel, elution system: n-heptane: ethyl acetate = 10:1, v / v) to obtain 4.80 g of target product 11.

[0185] 1 H NMR (400MHz, CDCl3) δ8.91(s,1H),8.84(d,J=3.8Hz,1H),7.98(dt,J=8.0,1.9Hz,1H),7.45(dd,J=7.8,5.1Hz,1H),6.04-5.9 6(m,2H),5.65-5.51(m,2H),3.64(t,J=6.6Hz,2H),2.09(s,1H),1.72(d,J=6.5Hz,4H),1.60–1.48(m,2H),1.43–1.20(m,9H).

[0186] Example 12: Preparation of amide ester derivatives using nicotinamide as a carrier.

[0187] 2.58 g (99%, 1.6 eq) of nicotinamide, 0.63 g (99%, 2 eq) of sodium hydride, and 25 g of THF were weighed and added to a reaction vessel. Under ice bath conditions, 5 g (80%, 1 eq) of the target product prepared in Example 10 was slowly added dropwise to the reaction vessel. The reaction was carried out at room temperature for 2 h. The conversion rate was monitored by GC and found to be approximately 90%. The reaction solution was concentrated by rotary evaporation under reduced pressure and then purified by column chromatography (200-300 mesh silica gel, elution system: n-heptane: ethyl acetate = 10:1, v / v) to obtain 4.10 g of the target product 12.

[0188] 1 H NMR (400MHz, CDCl3) δ8.91(s,1H),8.84(d,J=3.8Hz,1H),7.98(dt,J=8.0,1.9Hz,1H),7.45(dd,J=7.8,5.1Hz,1H),5.35( t,J=4.9Hz,2H),4.09(t,J=6.7Hz,2H),2.09-1.93(m,4H),1.60(p,J=6.2Hz,2H),1.42-1.17(m,17H),0.92-0.87(m,3H).

[0189] Example 13: Preparation of acid anhydride derivatives using strawberry acid as a carrier.

[0190] 2.3 g (99%, 1.3 eq) of strawberry acid, 0.8 g (99%, 2 eq) of sodium hydride, and 25 g of THF were weighed and added to a reaction vessel. Under ice bath conditions, 5 g (80%, 1 eq) of the target product prepared in Example 9 was slowly added dropwise to the reaction vessel. The reaction was carried out at room temperature for 2 h. The conversion rate was monitored by GC and found to be approximately 90%. The reaction solution was concentrated by rotary evaporation under reduced pressure and then purified by column chromatography (200-300 mesh silica gel, elution system: n-heptane: ethyl acetate = 20:1, v / v) to obtain 3.90 g of target product 13.

[0191] 1 H NMR (400MHz, CDCl3) δ6.07-5.92(m,2H),5.62-5.48(m,2H),3.64(t,J=6.6Hz,2H),2.06-1.96(m,2 H),1.73(d,J=6.4Hz,3H),1.65-1.51(m,4H),1.39-1.28(m,11H),1.26(s,3H),0.91-0.80(m,3H).

[0192] Example 14: Preparation of acid anhydride derivatives using strawberry acid as a carrier.

[0193] 1.96 g (99%, 1.3 eq) of strawberry acid, 0.63 g (99%, 2 eq) of sodium hydride, and 25 g of THF were weighed and added to a reaction vessel. Under ice bath conditions, 5 g (80%, 1 eq) of the target product prepared in Example 10 was slowly added dropwise to the reaction vessel. The reaction was carried out at room temperature for 2 h. The conversion rate was monitored by GC and found to be approximately 90%. The reaction solution was concentrated by rotary evaporation under reduced pressure and then purified by column chromatography (200-300 mesh silica gel, elution system: n-heptane: ethyl acetate = 20:1, v / v) to obtain 4.20 g of target product 14.

[0194] 1 H NMR (400MHz, CDCl3) δ6.91(td,J=7.4,1.4Hz,1H),5.39(t,J=4.6Hz,2H),3.68(t,J=6. 7Hz,2H),2.03–1.95(m,4H),1.61–1.51(m,2H),1.35–1.27(m,18H),0.90–0.79(m,3H).

[0195] Example 15: Preparation of anhydride derivatives using glacial acetic acid as a carrier.

[0196] 1.5 g (99%, 1.5 eq) of glacial acetic acid, 0.8 g (99%, 2 eq) of sodium hydride, and 25 g of THF were weighed and added to a reaction vessel. Under ice bath conditions, 5 g (80%, 1 eq) of the target product prepared in Example 9 was slowly added dropwise to the reaction vessel. The reaction was carried out at room temperature for 2 h. The reaction was monitored by GC and the conversion rate was about 90%. The reaction solution was concentrated by rotary evaporation under reduced pressure and then purified by column chromatography (200-300 mesh silica gel, elution system: n-heptane: ethyl acetate = 20:1, v / v) to obtain 3.70 g of the target product 15.

[0197] 1 H NMR (400MHz, CDCl3) δ6.82(td,J=7.4,1.4Hz,1H),6.06-5.92(m,2H),5.63-5.49(m,2H),3.64(t,J=6.6Hz,2 H),2.07-2.01(m,2H),1.73(d,J=6.5Hz,2H),1.56(dt,J=13.7,6.8Hz,2H),1.36-1.27(m,8H),1.25(s,3H).

[0198] Example 16: Preparation of anhydride derivatives using glacial acetic acid as a carrier.

[0199] 1.19 g (99%, 1.5 eq) of glacial acetic acid, 0.63 g (99%, 2 eq) of sodium hydride, and 25 g of THF were weighed and added to a reaction vessel. Under ice bath conditions, 5 g (80%, 1 eq) of the target product prepared in Example 10 was slowly added dropwise to the reaction vessel. The reaction was carried out at room temperature for 2 h. The reaction was monitored by GC and the conversion rate was about 90%. The reaction solution was concentrated by rotary evaporation under reduced pressure and then purified by column chromatography (200-300 mesh silica gel, elution system: n-heptane: ethyl acetate = 20:1, v / v) to obtain 3.10 g of target product 16.

[0200] 1 H NMR (400MHz, CDCl3) δ6.91(t,J=7.3Hz,1H),5.4-5.29(m,2H),3.68(t,J=6.7Hz,2H),2.35– 2.19(m,2H),1.97-2.07(m,4H),1.73–1.54(m,4H),1.49–1.16(m,19H),0.99–0.81(m,6H).

[0201] Example 17: Preparation of amide ester derivatives using benzamide as a carrier.

[0202] 0.38 g (99%, 1.2 eq) of benzamide, 0.13 g (99%, 2 eq) of sodium hydride, and 25 g of THF were weighed and added to a reaction vessel. Under ice bath conditions, 1 g (80%, 1 eq) of the target product from Example 9 was slowly added dropwise to the reaction vessel. The reaction was carried out at room temperature for 2 h. The conversion rate was monitored by GC and found to be approximately 90%. The reaction solution was concentrated by rotary evaporation under reduced pressure and then purified by column chromatography (200-300 mesh silica gel, elution system: n-heptane: ethyl acetate = 2:1, v / v) to obtain 0.82 g of the target product 17.

[0203] 1 H NMR(400MHz, CDCl3)δ9.01(s,1H),7.74(dd,J=7.9,1.7Hz,1H),7.42–7.23(m,3H),5.43–5.31(m,2H) ,3.74(t,J=6.3Hz,2H),2.07–1.94(m,4H),1.70–1.58(m,2H),1.43–1.20(m,18H),0.92–0.81(m,3H).

[0204] Example 18: Preparation of amide ester derivatives using benzamide as a carrier.

[0205] 0.48 g (99%, 1.2 eq) of benzamide, 0.16 g (99%, 2 eq) of sodium hydride, and 25 g of THF were weighed and added to a reaction vessel. Under ice bath conditions, 1 g (80%, 1 eq) of the target product from Example 10 was slowly added dropwise to the reaction vessel. The reaction was carried out at room temperature for 2 h. The conversion rate was monitored by GC and found to be approximately 90%. The reaction solution was concentrated by rotary evaporation under reduced pressure and then purified by column chromatography (200-300 mesh silica gel, elution system: n-heptane: ethyl acetate = 2:1, v / v) to obtain 1.03 g of the target product 18.

[0206] 1 H NMR(400MHz, CDCl3)δ9.01(s,1H),7.74(dd,J=7.9,1.7Hz,1H),7.42–7.23(m,3H),6.01–5.83(m,2H),5.63–5.47(m,2H),3.74(t, J=6.3Hz,2H),2.44(d,J=0.7Hz,3H),2.11(tdt,J=8.0,5.6,1.2Hz,2H),1.76–1.70(m,3H),1.70–1.58(m,2H),1.45–1.26(m,9H).

[0207] Example 19: Preparation of amide ester derivatives using 4-(trifluoromethyl)nicotinamide as a carrier.

[0208] 3.76 g (99%, 1.2 eq) of 4-(trifluoromethyl)nicotinamide, 0.8 g (99%, 2 eq) of sodium hydride, and 25 g of THF were weighed and added to a reaction vessel. Under ice bath conditions, 5 g (80%, 1 eq) of the target product from Example 9 was slowly added dropwise to the reaction vessel. The reaction was carried out at room temperature for 2 h. The conversion rate was monitored by GC and found to be approximately 90%. The reaction solution was concentrated by rotary evaporation under reduced pressure and then purified by column chromatography (200-300 mesh silica gel, elution system: n-heptane: ethyl acetate = 2:1, v / v) to obtain 6.50 g of the target product 19.

[0209] 1 H NMR(400MHz, CDCl3)δ9.82(s,1H),8.97(d,J=1.3Hz,1H),8.77(dd,J=3.7,1.4Hz,1H),7.66(dq,J=4.2,2.1Hz,1H),6.01–5.84(m,2H), 5.63–5.47(m,2H),3.74(t,J=6.3Hz,2H),2.11(tdt,J=8.0,5.6,1.2Hz,2H),1.76–1.70(m,3H),1.70–1.58(m,2H),1.45–1.26(m,9H).

[0210] Example 20: Preparation of amide ester derivatives using 4-(trifluoromethyl)nicotinamide as a carrier.

[0211] 3.0 g (99%, 1.2 eq) of 4-(trifluoromethyl)nicotinamide, 0.63 g (99%, 2 eq) of sodium hydride, and 25 g of THF were weighed and added to a reaction vessel. Under ice bath conditions, 5 g (80%, 1 eq) of the target product from Example 10 was slowly added dropwise to the reaction vessel. The reaction was carried out at room temperature for 2 h. The conversion rate was monitored by GC and found to be approximately 90%. The reaction solution was concentrated by rotary evaporation under reduced pressure and then purified by column chromatography (200-300 mesh silica gel, elution system: n-heptane: ethyl acetate = 2:1, v / v) to obtain 6.10 g of the target product 20.

[0212] 1 H NMR (400MHz, CDCl3) δ9.82(s,1H),8.97(d,J=1.4Hz,1H),8.77(dd,J=3.7,1.3Hz,1H),7.66(dq,J=4.2,2.1Hz,1H),5.42–5.31(m ,2H),3.74(t,J=6.3Hz,2H),2.07–1.94(m,4H),1.70–1.58(m,2H),1.43–1.24(m,12H),1.26(d,J=1.6Hz,6H),0.92–0.81(m,3H).

[0213] Example 21: Preparation of ester derivatives using N-Boc-γ-aminobutyric acid as a support

[0214] 3.5 g (95%, 1 eq) E-8-E-10-dodecadienol, 3.5 g (99%, 1.1 eq) N,N-dicyclohexylcarbodiimide, 3 g (99%, 1 eq) N-Boc-γ-aminobutyric acid, 0.36 g (99%, 0.2 eq) 4-dimethylaminopyridine, and 30 g dichloromethane were weighed and added to a reaction vessel. The mixture was stirred at room temperature for 12 h. The reaction was monitored by HPLC, and the conversion rate was approximately 90%. The reaction solution was filtered, and the organic phase was purified by rotary evaporation under reduced pressure followed by column chromatography (200-300 mesh silica gel, elution system: n-heptane: ethyl acetate = 1:1, v / v) to obtain 5.70 g of ester derivative 21.

[0215] 1H NMR (400MHz, CDCl3) δ6.06-5.93(m,2H),5.62-5.49(m,2H),4.06(t,J=6.7Hz,2H),3.16(dd,J=12.4,6.1Hz,2H),2.34(t,J=7.4 Hz,2H),2.04(q,J=7.0Hz,2H),1.81(p,J=7.1Hz,2H),1.73(d,J=6.6Hz,3H),1.65-1.56(m,3H),1.44(s,9H),1.38-1.28(m,8H).

[0216] Example 22: Preparation of ester derivatives using N-Boc-γ-aminobutyric acid as a support.

[0217] 3.6 g (95%, 1 eq) cis-11-hexadecenol, 3.5 g (99%, 1.1 eq) N,N-dicyclohexylcarbodiimide, 3 g (99%, 1 eq) N-Boc-γ-aminobutyric acid, 0.36 g (99%, 0.2 eq) 4-dimethylaminopyridine, and 30 g dichloromethane were weighed and added to a reaction vessel. The mixture was stirred at room temperature for 12 h. The reaction was monitored by HPLC and the conversion rate was approximately 90%. The reaction solution was filtered, and the organic phase was purified by rotary evaporation under reduced pressure followed by column chromatography (200-300 mesh silica gel, elution system: n-heptane: ethyl acetate = 1:1, v / v) to obtain 5.90 g of ester derivative 22.

[0218] 1 H NMR (400MHz, CDCl3) δ5.40-5.29(m,2H),4.06(t,J=6.7Hz,2H),3.74(t,J=6.3Hz,2H),2.34(t,J=7.4Hz,2H),2.04(q,J=7.0H z,2H),1.81(p,J=7.1Hz,2H),1.73(d,J=6.6Hz,3H),1.65-1.56(m,5H),1.44(s,9H),1.38-1.28(m,15H),0.92-0.81(m,3H).

[0219] Example 23: Preparation of ester derivatives using N-Fmoc-γ-aminobutyric acid as a carrier.

[0220] 3.5 g (90%, 1 eq) of the target product prepared in Example 7, 3.3 g (99%, 1.0 eq) of Fmoc-OSu, 1 g (99%, 1.2 eq) of sodium bicarbonate, 30 g of dichloromethane, and 6 g of water were weighed and added to a reaction vessel. The mixture was stirred at room temperature for 12 h. The reaction was monitored by HPLC and the conversion rate was approximately 90%. The reaction solution was washed with water, separated into layers, and the organic phase was dried. The solution was purified by column chromatography after rotary evaporation under reduced pressure (200-300 mesh silica gel, elution system: n-heptane: ethyl acetate = 1:1, v / v) to obtain 5.80 g of ester derivative 23.

[0221] 1 H NMR (400MHz, CDCl3) δ7.76(d,J=7.5Hz,2H),7.59(d,J=7.5Hz,2H),7.39(t,J=7.4Hz,2H),7.34–7.29(m,2H),6.04-5.95(m,2H),5.61-5. 48(m,2H),4.06(t,J=6.7Hz,2H),3.24(q,J=6.4Hz,2H),2.11-1.98(m,2H),1.72(d,J=6.6Hz,2H),1.65-1.54(m,3H),1.42-1.22(m,16H).

[0222] Example 24: Preparation of ester derivatives using N-Fmoc-γ-aminobutyric acid as a support.

[0223] 3.7 g (90%, 1 eq) of the target product prepared in Example 8, 3.5 g (99%, 1.1 eq) of N,N-dicyclohexylcarbodiimide, 5.0 g (99%, 1 eq) of Fmoc-OSu, 0.36 g (99%, 0.2 eq) of 4-dimethylaminopyridine, and 30 g of dichloromethane were weighed and added to a reaction vessel. The mixture was stirred at room temperature for 12 h. The reaction was monitored by HPLC and the conversion rate was approximately 90%. The reaction solution was filtered, and the organic phase was purified by rotary evaporation under reduced pressure followed by column chromatography (200-300 mesh silica gel, elution system: n-heptane: ethyl acetate = 1:1, v / v) to obtain 7.40 g of ester derivative 24.

[0224] 1H NMR (400MHz, CDCl3) δ7.76(d,J=7.5Hz,2H),7.59(d,J=7.5Hz,2H),7.39(t,J=7.4Hz,2H),7.34-7.29(m,2H),5.40-5.29(m,2H),4.06(t,J=6.7Hz, 2H),3.24(q,J=6.4Hz,2H),2.11-1.98(m,4H),1.72(d,J=6.6Hz,2H),1.6 5-1.54(m,3H),1.49-1.38(m,2H),1.42-1.22(m,21H),0.92-0.81(m,3H).

[0225] Example 25: Preparation of ester derivatives using N-acetylglycine as a carrier.

[0226] N-acetylglycine (10.0 g, 85.5 mmol, 1.00 eq) was placed in a 250 mL single-necked flask, followed by 100 mL of dichloromethane. Then, HATU (37.3 g, 98.2 mmol, 1.15 eq) and DIEA (22.0 g, 171 mmol, 2.00 eq) were added sequentially. The reaction mixture was stirred at 30–35 °C for 0.5 h. Then, trans-8-trans-10-dodecadien-1-ol (12.4 g, 68.4 mmol, 0.80 eq) was added to the reaction mixture, and the mixture was stirred overnight (16 h). LC-MS monitoring showed the formation of the target product. The reaction mixture was transferred to a separatory funnel, and the reaction was quenched by slowly adding 200 mL of saturated sodium bicarbonate solution. The mixture was extracted twice with DCM (200 mL), and the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated to obtain the crude product. The crude product was purified by column chromatography using 100-200 mesh silica gel (200 g) and dichloromethane and methanol as eluents. The ratio of DCM:MeOH was 100:1 to 50:1 (1.5 L, v / v). The purified product yielded 7.2 g of pure product (white solid, LC-MS purity: 97.8%, yield: 37.5%), namely ester derivative 25.

[0227] 1 H NMR (400MHz, CDCl3) δ6.07-5.93(m,3H),5.63-5.48(m,2H),4.14(t,J=6.8Hz,2H),4.02(d,J =5.2Hz,2H),2.06-2.01(m,5H),1.72(d,J=6.8Hz,3H),1.66-1.59(m,2H),1.38-1.28(m,8H).

[0228] Example 26: Preparation of ester derivatives using N-trifluoroacetylglycine as a carrier.

[0229] N-Trifluoroacetylglycine (5.0 g, 29.2 mmol, 1.00 eq) was placed in a 100 mL single-necked flask, followed by dichloromethane (50 mL). Then, HATU (14.4 g, 37.9 mmol, 1.30 eq) and DIEA (7.51 g, 58.4 mmol, 2.00 eq) were added sequentially. The reaction mixture was stirred at 23–27 °C for 0.5 h. Then, trans-8-trans-10-dodecadien-1-ol (4.26 g, 23.4 mmol, 0.80 eq) was added to the reaction mixture, and the mixture was stirred overnight (16 h). LC-MS monitoring showed the formation of the target product. The reaction mixture was transferred to a separatory funnel, and the reaction was quenched by slowly adding 200 mL of saturated sodium bicarbonate solution. The mixture was extracted twice with DCM (50 mL), and the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated to obtain the crude product. The crude product was purified by column chromatography: 200-300 mesh silica gel was used, and petroleum ether and dichloromethane were used as eluents. The ratio of PE:DCM was 2:1 to 0:1 (1.0 L, v / v). The purified product was 730 mg (white solid, LC-MS purity: 92.1%, yield: 9.20%), namely ester derivative 26. In addition, 2.05 g of cross-crude product was also obtained.

[0230] 1 H NMR (400MHz, CDCl3) δ6.85 (s, 1H), 6.07-5.93 (m, 2H), 5.56 (ddt, J=20.0, 13.6, 6.8Hz, 2H), 4.20 (t, J=6.8Hz, 2H), 4.12(d,J=5.2Hz,2H),2.09-2.01(m,2H),1.73(d,J=6.8Hz,3H),1.65(dd,J=14.0,6.8Hz,2H),1.39-1.29(m,8H).

[0231] Example 27: Preparation of ester derivatives using nicotinic acid as a carrier.

[0232] Nicotinic acid (1.00 g, 8.13 mmol, 1.00 eq) was placed in a 25 mL single-necked flask, and anhydrous dichloromethane (10 mL) was added to the flask. Then, one drop of DMF was added as a catalyst. Oxaloyl chloride (1.55 g, 12.2 mmol, 1.50 eq) was slowly added to the reaction solution under ice bath conditions. The flask was sealed and stirred at 30–35 °C for 2 h. LC-MS was used to confirm the complete reaction of the starting materials. The reaction solution was concentrated to remove excess oxaloyl chloride and hydrochloric acid. Anhydrous dichloromethane (30 mL) was then added to the crude product. Triethylamine (1.64 g, 16.3 mmol, 2.00 eq) and trans-8-trans-10-dodecadien-1-ol (1.48 g, 8.13 mmol, 1.00 eq) were slowly added sequentially to the reaction solution under ice bath conditions. The reaction solution was stirred at 30–35 °C for 16 h. LC-MS was used to confirm the formation of the product. The reaction mixture was transferred to a separatory funnel, and water (10 mL) was slowly added to quench the reaction. Extraction was performed twice with DCM (20 mL), the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated to obtain the crude product. The crude product was purified by column chromatography using 200–300 mesh silica gel (25 g) as the eluent, with petroleum ether and ethyl acetate as the eluents. The PE:EA ratio was 100:1 (300 mL, v / v), yielding 1.56 g of pure product (white solid, LC-MS purity: 98.7%, yield: 67.2%), i.e., ester derivative 27.

[0233] 1 H NMR(400MHz, CDCl3)9.22(d,J=1.6Hz,1H),8.76(dd,J=4.8,1.6Hz,1H),8.29(dt,J=8.0,1.9Hz,1H),7.38(dd,J=8.0,4.8Hz,1 H),6.06-5.92(m,2H),5.62-5.47(m,2H),4.34(t,J=6.8Hz,2H),2.04(q,J=6.8Hz,2H),1.80-1.70(m,6H),1.45-1.30(m,8H).

[0234] Example 28: Preparation of ester derivatives using salicylic acid as a carrier.

[0235] Salicylic acid (568 mg, 4.11 mmol, 1.50 eq) and anhydrous DCM (15 mL) were added to a 100 mL three-necked flask. After purging with nitrogen three times, the mixture was cooled to 0 °C. At 0 °C, trans-8-trans-10-dodecadien-1-ol (500 mg, 2.74 mmol, 1.00 eq), DMAP (268 mg, 2.19 mmol, 0.80 eq), and EDCI (946 mg, 4.94 mmol, 1.80 eq) were added to the above reaction solution. The reaction solution was stirred at 0 °C for 1 h, then heated to room temperature (27–30 °C) and stirred for 16 h. LC-MS showed the formation of new peaks. The reaction solution was diluted with DCM (10 mL), washed successively with water (10 mL × 3) and saturated NaHCO3 (10 mL × 2), and the organic phase was dried over anhydrous Na2SO4, filtered, and concentrated to obtain 2.4 g of crude product. The crude product was slurried with MTBE (10 mL), the insoluble matter was filtered off, and the product was concentrated and purified by column chromatography. It was dissolved in petroleum ether (1 mL) and a 12 g silica gel column was used. The eluent system was petroleum ether and ethyl acetate. When the eluent volume ratio was 100% petroleum ether, the product was flushed out. The product was combined and concentrated to obtain 510 mg of pure product (colorless liquid, LCMS purity: 95.1%, yield: 61.5%), namely ester derivative 28.

[0236] 1 H NMR (400MHz, CDCl3) δ10.84 (s, 1H), 7.84 (dd, J = 8.0, 1.6Hz, 1H), 7.49–7.41 ( m,1H),6.98(d,J=8.0Hz,1H),6.88(t,J=7.6Hz,1H),5.99(dt,J=19.6,6.8Hz ,2H),5.56(tt,J=13.6,6.8Hz,2H),4.34(t,J=6.8Hz,2H),2.05(q,J=6.8Hz, 2H), 1.79 (dd, J=14.0, 7.2Hz, 2H), 1.73 (d, J=6.4Hz, 3H), 1.45–1.31 (m, 8H).

[0237] Example 29: Preparation of ester derivatives using 4-pyridinecarboxylic acid as a carrier.

[0238] 4-Pyridinecarboxylic acid (1.00 g, 8.13 mmol, 1.00 eq) was placed in a 25 mL single-necked flask, and anhydrous dichloromethane (10 mL) was added to the flask. Then, 1 drop of DMF was added as a catalyst, and oxalyl chloride (1.54 g, 12.2 mmol, 1.50 eq) was slowly added to the reaction solution under ice bath conditions. The flask was sealed and stirred at 30–35 °C for 1 h. LC-MS was used to confirm that the starting material had reacted completely. The reaction solution was concentrated to dryness, and excess oxalyl chloride and hydrochloric acid were removed. Anhydrous dichloromethane (20 mL) was then added to the crude product. Under ice bath conditions, triethylamine (2.46 g, 24.6 mmol, 3.00 eq) and trans-8-trans-10-dodecadien-1-ol (1.48 g, 8.13 mmol, 1.00 eq) were slowly added sequentially to the reaction solution. The reaction solution was stirred at 30–35 °C for 4 h, and LC-MS was used to confirm the formation of the product. The reaction mixture was transferred to a separatory funnel, and water (20 mL) was slowly added to quench the reaction. Extraction was performed twice with DCM (20 mL), the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated to obtain the crude product. The crude product was purified by column chromatography using 200–300 mesh silica gel (25 g) as the eluent, with petroleum ether and ethyl acetate as the eluents. The PE:EA ratios were 50:1 (200 mL, v / v) and 20:1 (200 mL, v / v) to obtain 1.56 g of pure product (white solid, LC-MS purity: 99.6%, yield: 67.0%), i.e., ester derivative 29.

[0239] 1 H NMR (400MHz, CDCl3) δ8.77(d,J=6.0Hz,2H),7.84(dd,J=4.8,1.4Hz,2H),6.05-5.93(m,2H),5.62-5.48(m,2H),4. 34(t,J=6.8Hz,2H),2.04(q,J=6.8Hz,2H),1.78(dd,J=14.0,7.2Hz,2H),1.72(d,J=6.8Hz,3H),1.45-1.32(m,8H).

[0240] Example 30: Preparation of ester derivatives using 2-pyridinecarboxylic acid as a support.

[0241] 2-Pyridinecarboxylic acid (500 mg, 4.07 mmol, 1.00 eq) was placed in a 25 mL single-necked flask, and anhydrous dichloromethane (5 mL) was added to the flask. Then, 1 drop of DMF was added as a catalyst, and oxalyl chloride (773 mg, 6.10 mmol, 1.50 eq) was slowly added to the reaction solution under ice bath conditions. After sealing the flask, the mixture was stirred at 30–35 °C for 1 h. LC-MS was used to confirm the complete reaction of the starting materials. The reaction solution was concentrated to dryness, and excess oxalyl chloride and hydrochloric acid were removed. Anhydrous dichloromethane (15 mL) was then added to the crude product. Under ice bath conditions, triethylamine (1.23 g, 12.2 mmol, 3.00 eq) and trans-8-trans-10-dodecadien-1-ol (740 mg, 4.07 mmol, 1.00 eq) were slowly added sequentially to the reaction solution. The reaction solution was stirred at 30–35 °C for 4 h, and LC-MS was used to confirm the formation of the product. The reaction mixture was transferred to a separatory funnel, and water (20 mL) was slowly added to quench the reaction. Extraction was performed twice with DCM (20 mL), the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated to obtain the crude product. The crude product was purified by column chromatography using 200–300 mesh silica gel (12 g) as the eluent, with petroleum ether and ethyl acetate as the eluents. The eluent ratios were PE:EA = 50:1 (200 mL, v / v), PE:EA = 20:1 (200 mL, v / v), and PE:EA = 10:1 (200 mL, v / v). 550 mg of pure product (colorless, transparent oily liquid, LC-MS purity: 97.6%, yield: 49.7%), i.e., ester derivative 330, was obtained.

[0242] 1 H NMR (400MHz, CDCl3) δ8.75(d,J=4.4Hz,1H),8.11(d,J=7.6Hz,1H),7.83(td,J=7.6,1.6Hz,1H),7.46(dd,J=7.6,4.8Hz,1H),6.06-5.9 1(m,2H),5.61-5.47(m,2H),4.40(t,J=6.8Hz,2H),2.02(q,J=6.8Hz,2H),1.84-1.77(m,2H),1.71(d,J=6.8Hz,3H),1.44-1.28(m,8H).

[0243] Example 31: Preparation of ester derivatives using o-nitrobenzoic acid as a support

[0244] In a 40 mL glass bottle, o-nitrobenzoic acid (458 mg, 2.74 mmol, 1.00 eq) and dichloromethane (5 mL) were added, and the reaction mixture was cooled to 0 °C. Oxaloyl chloride (522 mg, 4.11 mmol, 1.50 eq) was added dropwise to the reaction mixture at 0 °C, and the mixture was reacted at 28–32 °C for 1 h. Excess oxaloyl chloride was removed by vacuum concentration, and the residue was dissolved in dichloromethane (5 mL). Then, trans-8-trans-10-dodecadien-1-ol (500 mg, 2.74 mmol, 1.00 eq) was added, followed by the dropwise addition of triethylamine (555 mg, 5.48 mmol, 2.00 eq) at 0 °C. After the addition was complete, the reaction mixture was stirred at 28–32 °C for 3 h. LC-MS showed the reaction was complete. Water (10 mL) was added to the reaction solution, and the mixture was separated. The organic phase was dried over anhydrous Na₂SO₄, filtered, and concentrated to obtain 940 mg of crude product. The crude product was dissolved in petroleum ether:dichloromethane = 20:1 (1 mL, v / v), and purified by column chromatography using a 12 g silica gel column. The eluents were petroleum ether and ethyl acetate. When the eluent volume ratio was 4% ethyl acetate, the product was flushed out. The eluents were combined and concentrated to obtain 670 mg of pure product (colorless oil, LC-MS purity: 97.6%, yield: 73.7%), i.e., ester derivative 31.

[0245] 1 H NMR(400MHz, CDCl3)δ7.89(d,J=7.8Hz,1H),7.75(dd,J=7.6,1.2Hz,1H),7.70–7.59(m,2H),6.07–5.93(m,2H),5 .64–5.48(m,2H),4.32(t,J=6.8Hz,2H),2.04(q,J=6.8Hz,2H),1.71(dd,J=14.0,6.8Hz,5H),1.39–1.29(m,8H).

[0246] Example 32: Preparation of ester derivatives using 2-fluoronicotinic acid as a carrier.

[0247] In a 40 mL glass bottle, 2-fluoronicotinic acid (387 mg, 2.74 mmol, 1.00 eq) and dichloromethane (5 mL) were added. The reaction mixture was cooled to 0 °C. Oxaloyl chloride (522 mg, 4.11 mmol, 1.50 eq) was added dropwise to the reaction mixture at 0 °C. The mixture was reacted at 28–32 °C for 1.0 h. Excess oxaloyl chloride was removed by concentration under reduced pressure. Dichloromethane (5 mL) was added to the residue to dissolve it. Then, trans-8-trans-10-dodecadien-1-ol (500 mg, 2.74 mmol, 1.00 eq) was added. Triethylamine (555 mg, 5.48 mmol, 2.00 eq) was added dropwise at 0 °C. After the addition was complete, the reaction mixture was stirred at 28–32 °C for 3 h. LC-MS showed that the reaction was complete. Water (10 mL) was added to the reaction solution for dilution, and the mixture was separated. The organic phase was washed with saturated brine (10 mL), dried over anhydrous Na2SO4, filtered, and concentrated to obtain 910 mg of crude product. The crude product was dissolved in petroleum ether:dichloromethane = 20:1 (1 mL, v / v), and purified by column chromatography using a 12 g silica gel column. The eluents were petroleum ether and ethyl acetate. When the eluent volume ratio was 4% ethyl acetate, the product was flushed out. The product was combined and concentrated to obtain 548 mg of pure product (colorless oil, LC-MS purity: 96.0%, yield: 65.4%), i.e., ester derivative 33.

[0248] 1 H NMR (400MHz, CDCl3) δ8.42–8.33(m,2H),7.33–7.27(m,1H),6.06–5.93(m,2H),5.62–5.49( m,2H),4.35(t,J=6.8Hz,2H),2.04(q,J=6.8Hz,2H),1.79–1.70(m,5H),1.46–1.31(m,8H).

[0249] Example 33: Preparation of ester derivatives using 2-chloronicotinic acid as a carrier.

[0250] In a 40 mL glass bottle, 2-chloronicotinic acid (432 mg, 2.74 mmol, 1.00 eq) and dichloromethane (5 mL) were added. The reaction mixture was cooled to 0 °C. Oxaloyl chloride (522 mg, 4.11 mmol, 1.50 eq) was added dropwise to the reaction mixture at 0 °C. The mixture was reacted at 28–32 °C for 1 h. Excess oxaloyl chloride was removed by concentration under reduced pressure. The residue was dissolved in dichloromethane (5 mL), followed by the addition of trans-8-trans-10-dodecadien-1-ol (500 mg, 2.74 mmol, 1.00 eq). Triethylamine (555 mg, 5.48 mmol, 2.00 eq) was added dropwise at 0 °C. After the addition was complete, the reaction mixture was stirred at 28–32 °C for 3 h. LCMS showed that the reaction was complete. Water (10 mL) was added to the reaction solution, and the mixture was separated. The organic phase was washed with saturated brine (10 mL), dried over anhydrous Na2SO4, filtered, and concentrated to obtain 812 mg of crude product. The crude product was dissolved in petroleum ether:dichloromethane = 20:1 (1 mL, v / v), and purified by column chromatography using a 12 g silica gel column. The eluents were petroleum ether and ethyl acetate. When the eluent ratio was 4% ethyl acetate, the product was flushed out. The product was combined and concentrated to obtain 530 mg of pure product (colorless oil, LC-MS purity: 96.6%, yield: 60.2%), i.e., ester derivative 33.

[0251] 1 H NMR (400MHz, CDCl3) δ8.50(dd,J=4.8,2.0Hz,1H),8.14(dd,J=7.6,2.0Hz,1H),7.32(dd,J=7.6,4.8Hz,1H),6.06–5.93(m,2H),5.63 –5.47(m,2H),4.35(t,J=6.8Hz,2H),2.04(q,J=6.8Hz,2H),1.77(dd,J=14.4,7.2Hz,2H),1.72(d,J=6.8Hz,3H),1.45–1.31(m,8H).

[0252] Example 34: Preparation of anhydride derivatives using salicylic acid as a carrier.

[0253] Trans-8-trans-10-dodecadien-1-ol (4.00 g, 22.0 mmol, 1.00 eq) was dissolved in DCM (40 mL, 10 V), followed by the addition of triphosgene (8.66 g, 29.3 mmol, 1.33 eq). The reaction mixture was stirred at room temperature for 16 h, then water (50 mL) was added. The mixture was separated, and the organic phase was concentrated and used directly in the next step of the reaction. In a 100 mL round-bottom flask, salicylic acid (758 mg, 5.48 mmol, 1.00 eq), THF (15 mL), and N-methylmorpholine (554 mg, 5.48 mmol, 1.00 eq) were added. After stirring the reaction mixture for 10 minutes, the above-mentioned concentrated organic phase solution (1.34 g, 5.48 mmol, 1.00 eq) was added. The reaction mixture was stirred at room temperature (26–30 °C) for 2 hours. TLC showed that the starting materials had reacted completely (PE:EA = 1:1, v / v, UV, Rf = 0.3). The reaction solution was concentrated to remove tetrahydrofuran. The residue was diluted with methyl tert-butyl ether (20 mL) and filtered through a triangular funnel. The filter cake was washed twice with methyl tert-butyl ether (10 mL). The filtrate was concentrated under reduced pressure to obtain 2.59 g of crude product. The crude product was dissolved in dichloromethane (2 mL) and purified by column chromatography using a 25 g silica gel column. The eluent system was petroleum ether and ethyl acetate. The product was obtained when the eluent ratio was petroleum ether:ethyl acetate = 3:1 (v / v). The product was combined and concentrated to obtain 670 mg of pure product (white solid, LC-MS purity: 92.0%, yield: 35.2%), i.e., acid anhydride derivative 34.

[0254] 1 H NMR (400MHz, CDCl3) δ8.10 (dd, J=7.6, 1.6Hz, 1H), 7.62 (td, J=8.0, 1.6Hz, 1H), 7.39–7.34 (m, 1H), 7.23 (d, J=7.2Hz, 1H), 6.00 (tt ,J=14.8,10.4Hz,2H),5.63–5.46(m,2H),4.27(t,J=6.8Hz,2H),2.03(q,J=6.8Hz,2H),1.72(d,J=6.8Hz,3H),1.45–1.27(m,10H).

[0255] Example 35: Preparation of ester derivatives using phenyl chloroformate as a carrier.

[0256] At 0 °C, phenyl chloroformate (1.72 g, 10.9 mmol, 2.00 eq) was added dropwise to a mixture of trans-8-trans-10-dodecadien-1-ol (1.00 g, 5.49 mmol, 1.00 eq) and pyridine (868 mg, 10.9 mmol, 2.00 eq) in diethyl ether (20 mL). The reaction mixture was stirred at room temperature (23–26 °C) for 16 h. LC-MS was used to monitor the reaction until it was complete. Water (20 mL) was then slowly added. L) Quenching reaction, extraction twice with methyl tert-butyl ether (20 mL), combining organic phases, drying with anhydrous sodium sulfate and concentrating to obtain 2.37 g crude product (colorless liquid), crude product dissolved in petroleum ether (2 mL), purified by column chromatography using a 25 g silica gel column, with petroleum ether and ethyl acetate as eluents, product obtained when 100% petroleum ether was used as eluent, combined and concentrated to obtain 1.12 g pure product (colorless liquid, HPLC purity: 94.1%, yield: 67.4%), i.e. ester derivative 35.

[0257] 1 H NMR (400MHz, CDCl3) δ7.43(dd,J=15.2,7.2Hz,2H),7.29(d,J=8.8Hz,1H),7.22(d,J=7.6Hz,2H),6.12–5.97(m,2H),5.60(tt, J=13.6,6.8Hz,2H),4.28(t,J=6.8Hz,2H),2.09(q,J=6.8Hz,2H),1.83–1.77(m,3H),1.75(d,J=6.8Hz,2H),1.49–1.33(m,8H).

[0258] Example 36: Preparation of ester derivatives using phenyl p-nitrochloroformate as a carrier.

[0259] Trans-8-trans-10-dodecadien-1-ol (1.00 g, 5.48 mmol, 1.00 eq) was dissolved in dichloromethane (10 mL). Pyridine (867 mg, 10.9 mmol, 2.00 eq) and phenyl p-nitrochloroformate (1.96 g, 9.75 mmol, 1.78 eq) were slowly added sequentially with stirring. The reaction mixture was stirred at room temperature for 16 h (observation: after the addition was complete, it was a pure white turbid liquid; after stirring overnight, it became a pink turbid liquid). LC- MS monitoring showed the reaction was complete. The reaction was quenched by slowly adding water (10 mL), and extracted twice with DCM (20 mL). The organic phases were combined, dried with anhydrous sodium sulfate, and concentrated to obtain the crude product. The crude product was purified by column chromatography using 200-300 mesh silica gel (25 g) as the eluent and petroleum ether and ethyl acetate as the eluent. The PE:EA ratio was 100:1 (approximately 500 mL, v / v). The purified product yielded 1.45 g of pure product (white solid, LCMS purity: 96.3%, yield: 63.4%), namely ester derivative 36.

[0260] 1 H NMR (400MHz, CDCl3) δ8.28 (d, J = 9.2Hz, 2H), 7.38 (d, J = 9.2Hz, 2H), 6.07-5.94 (m, 2H), 5.55 (ddd, J = 17. 6,13.6,6.8Hz,2H),4.28(t,J=6.8Hz,2H),2.05(q,J=6.8Hz,2H),1.79-1.71(m,5H),1.44-1.31(m,8H).

[0261] Example 37: Preparation of ester derivatives using phenyl o-nitrochloroformate as a carrier.

[0262] o-Nitrophenol (1.00 g, 7.19 mmol, 1.00 eq) was dissolved in dichloromethane (8 mL), and triphosgene (3.33 g, 11.3 mmol, 1.57 eq) was slowly added under stirring. The reaction mixture was stirred in an ice bath for 10 min, followed by the dropwise addition of pyridine (678 μL, 8.40 mmol, 1.17 eq). The mixture was reacted at 28 °C–35 °C for 18 h. Water (10 mL) was slowly added to the reaction mixture, and the mixture was extracted twice with DCM (20 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated to obtain crude chloroformate. The crude chloroformate was dissolved in dichloromethane (8 mL, 8V), and pyridine (1.99 g, 25.2 mmol, 3.50 eq) was slowly added dropwise in an ice bath. (Observation: Dropwise addition...) The reaction mixture was subjected to a violent exothermic reaction upon addition of pyridine and trans-8-trans-10-dodecadien-1-ol (1.53 g, 8.40 mmol, 1.17 eq). The reaction solution was then heated to 28 °C–35 °C for 3 h. The reaction was monitored by LC-MS until it was complete. The reaction was quenched by slowly adding water (10 mL). The mixture was extracted twice with DCM (20 mL). The organic phases were combined, dried with anhydrous sodium sulfate, and concentrated to obtain the crude product. The crude product was purified by column chromatography using 200–300 mesh silica gel (20 g) as the eluent and petroleum ether and ethyl acetate as the eluent. The PE:EA ratio was 50:1 (approximately 500 mL, v / v). The purified product yielded 640 mg of product (yellow oil, LC-MS purity: 87.4%, yield: 22.0%), namely ester derivative 37.

[0263] 1 H NMR (400MHz, CDCl3) δ8.12(dd,J=8.0,1.6Hz,1H),7.71-7.62(m,1H),7.47-7.37(m,1H),7.33(dd,J=8.0,1.2Hz,1H),6.06-5.94(m,2H),5.55 (td,J=13.6,6.8Hz,2H),4.29(t,J=6.8Hz,2H),2.05(q,J=6.8Hz,2H),1.77(dd,J=14.4,7.2Hz,2H),1.72(d,J=6.4Hz,3H),1.45-1.30(m,8H).

[0264] Example 38: Preparation of ester derivatives using phenyl 4-trifluoromethylchloroformate as a carrier.

[0265] 4-Trifluoromethylphenol (1.00 g, 6.17 mmol, 1.00 eq) was dissolved in dichloromethane (10 mL, 10 V), and triphosgene (2.43 g, 8.20 mmol, 1.33 eq) was slowly added under stirring. The reaction mixture was stirred in an ice bath for 10 min, followed by the dropwise addition of pyridine (487 mg, 6.17 mmol, 1.00 eq). The mixture was reacted at 28 °C–35 °C for 16 h. Water (10 mL) was slowly added to the reaction mixture, and the mixture was extracted twice with DCM (20 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated to obtain crude chloroformate. The crude chloroformate was dissolved in dichloromethane (10 mL, 10 V), and pyridine (974 mg, 12.3 mmol, 2.00 eq) was slowly added sequentially in an ice bath. (Observation: Dropwise addition...) The reaction mixture was subjected to a violent exothermic reaction upon addition of pyridine and trans-8-trans-10-dodecadien-1-ol (2.24 g, 12.3 mmol, 2.00 eq). The reaction solution was then heated to 28-35 °C for 3 h. The reaction was monitored by TLC until it was complete. Water (10 mL) was slowly added to quench the reaction. The mixture was extracted twice with DCM (20 mL). The organic phases were combined, dried with anhydrous sodium sulfate, and concentrated to obtain the crude product. The crude product was purified by column chromatography using 200-300 mesh silica gel (20 g) as the eluent and petroleum ether and ethyl acetate as the eluent. PE (approximately 500 mL) and PE:EA = 100:1 (approximately 500 mL, v / v) were used to obtain 1.03 g of product (white solid, LC-MS purity: 91.3%, yield: 45.1%), namely ester derivative 38.

[0266] 1 H NMR (400MHz, CDCl3) δ7.66 (d, J = 8.4Hz, 2H), 7.32 (d, J = 8.4Hz, 2H), 6.08-5.94 (m, 2H), 5.64-5. 49(m,2H),4.27(t,J=6.8Hz,2H),2.05(q,J=6.8Hz,2H),1.79-1.70(m,5H),1.44-1.30(m,8H).

[0267] Example 39 Sustained release of ester derivatives with succinic acid as a carrier

[0268] 125 mg of substrate (diester derivative 1 with succinic acid as a carrier prepared in Example 1) was placed in 4 mL of pure water, and 2.5 mg of immobilized enzyme named Y 200 (Anhui Lvweikang Biotechnology Co., Ltd.) was weighed into the above solution. The mixture was allowed to stand naturally at 25 °C. Under these conditions, the substrate hydrolyzed by about 84% in 20 days.

[0269] 125 mg of substrate (diester derivative 2 with succinic acid as a carrier prepared in Example 2) was placed in 4 mL of pure water, and 2.5 mg of immobilized enzyme named Y 200 was weighed into the above solution. The mixture was allowed to stand naturally at 25 °C. Under these conditions, the substrate hydrolyzed by about 67% after 20 days.

[0270] Example 40: Sustained release of L-phenylalanine-based ester derivatives

[0271] 125 mg of substrate (ester derivative 3 with phenylalanine as a carrier prepared in Example 3) was placed in 4 mL of pure water, and 2.5 mg of immobilized enzyme named Y 200 was weighed into the above solution. The mixture was allowed to stand naturally at 25 °C. Under these conditions, the substrate was hydrolyzed by about 73% after 20 days.

[0272] 125 mg of substrate (ester derivative 4 with phenylalanine as a carrier prepared in Example 4) was placed in 4 mL of pure water, and 2.5 mg of immobilized enzyme named Y 200 was weighed into the above solution. The mixture was allowed to stand naturally at 25 °C. Under these conditions, the substrate was hydrolyzed by about 52% after 20 days.

[0273] Example 41: Sustained release of peptide-based ester derivatives as carriers

[0274] 125 mg of substrate (ester derivative 5 with polypeptide as carrier prepared in Example 5) was placed in 4 mL of pure water, and 2.5 mg of immobilized enzyme named Y 200 was weighed into the above solution. The mixture was allowed to stand naturally at 25 °C. Under these conditions, the substrate was hydrolyzed by about 60% after 20 days.

[0275] 125 mg of substrate (ester derivative 6 with polypeptide as carrier prepared in Example 6) was placed in 4 mL of pure water, and 2.5 mg of immobilized enzyme named Y 200 was weighed into the above solution. The mixture was allowed to stand naturally at 25 °C. Under these conditions, the substrate was hydrolyzed by about 65% after 20 days.

[0276] Example 42: Sustained release of γ-aminobutyric acid (GABA) as a carrier ester derivative

[0277] 125 mg of substrate (ester derivative 7 with γ-aminobutyric acid as a carrier prepared in Example 7) was placed in mL of pure water and allowed to stand naturally at 25°C. Under these conditions, the substrate was hydrolyzed by about 72% after 20 days.

[0278] 125 mg of substrate (ester derivative 8 with γ-aminobutyric acid as a carrier prepared in Example 8) was placed in 4 mL of pure water and allowed to stand naturally at 25 °C. Under these conditions, the substrate hydrolyzed by about 78% after 20 days.

[0279] Example 43 Sustained release of nicotinamide as a carrier amide derivative

[0280] 125 mg of substrate (acid anhydride derivative 11 with nicotinamide as a carrier prepared in Example 11) was placed in 4 mL of pure water and allowed to stand naturally at 25 °C. Under these conditions, the substrate hydrolyzed by approximately 8.124% after 20 days.

[0281] 125 mg of substrate (acid anhydride derivative 12 with nicotinamide as a carrier prepared in Example 12) was placed in 4 mL of pure water and allowed to stand naturally at 25 °C. Under these conditions, the substrate hydrolyzed by approximately 20.734% after 20 days.

[0282] Example 44: Sustained release of anhydride derivatives with strawberry acid as the carrier

[0283] 125 mg of substrate (ester derivative 13 with strawberry acid as a carrier prepared in Example 13) was placed in 4 mL of pure water and allowed to stand naturally at 25 °C. Under these conditions, the substrate hydrolyzed by about 84% after 20 days.

[0284] 125 mg of substrate (ester derivative 14 with strawberry acid as a carrier prepared in Example 14) was placed in 4 mL of pure water and allowed to stand naturally at 25 °C. Under these conditions, the substrate hydrolyzed by about 91% after 20 days.

[0285] Example 45: Sustained release of anhydride derivatives using glacial acetic acid as a carrier

[0286] 125 mg of substrate (ester derivative 15 with glacial acetic acid as a carrier prepared in Example 15) was placed in 4 mL of pure water and allowed to stand naturally at 25 °C. Under these conditions, the substrate hydrolyzed by about 81% after 20 days.

[0287] 125 mg of substrate (ester derivative 16 with glacial acetic acid as a carrier prepared in Example 16) was placed in 4 mL of pure water and allowed to stand naturally at 25 °C. Under these conditions, the substrate was hydrolyzed by about 90% after 20 days.

[0288] Example 46: Sustained-release preparation of amide ester derivatives using benzamide as a carrier

[0289] 125 mg of substrate (amide ester derivative 17 with benzamide as a carrier prepared in Example 17) was placed in 4 mL of pure water and allowed to stand naturally at 25 °C. Under these conditions, the substrate was hydrolyzed by about 75% after 20 days.

[0290] 125 mg of substrate (amide ester derivative 18 with benzamide as a carrier prepared in Example 18) was placed in 4 mL of pure water and allowed to stand naturally at 25 °C. Under these conditions, the substrate hydrolyzed by about 71% after 20 days.

[0291] Example 47: Sustained-release preparation of amide ester derivatives using 4-(trifluoromethyl)nicotinamide as a carrier

[0292] 125 mg of substrate (amide ester derivative 19 with 4-(trifluoromethyl)nicotinamide as a carrier prepared in Example 19) was placed in 4 mL of pure water and allowed to stand naturally at 25 °C. Under these conditions, the substrate hydrolyzed by about 73% after 20 days.

[0293] 125 mg of substrate (4-(trifluoromethyl)nicotinamide-based amide ester derivative 20 prepared in Example 20) was placed in 4 mL of pure water and allowed to stand naturally at 25 °C. Under these conditions, the substrate hydrolyzed by approximately 76% after 20 days.

[0294] Example 48: Sustained-release preparation of ester derivatives using N-Fmoc-γ-aminobutyric acid as a carrier

[0295] 125 mg of substrate (ester derivative 23 with N-Fmoc-γ-aminobutyric acid as a carrier prepared in Example 23) was placed in 4 mL of pure water and allowed to stand naturally at 25 °C. Under these conditions, the substrate hydrolyzed by about 57% after 20 days.

[0296] 125 mg of substrate (ester derivative 24 with N-Fmoc-γ-aminobutyric acid as a carrier prepared in Example 24) was placed in 4 mL of pure water and allowed to stand naturally at 25 °C. Under these conditions, the substrate hydrolyzed by about 71% after 20 days.

[0297] Example 49: Sustained-release preparation of ester derivatives using nicotinic acid as a carrier

[0298] Five mg of the product prepared in Example 27 was placed in 10 mL centrifuge tubes, resulting in three groups. Each group was allowed to stand naturally at different temperatures / relative humidity levels (25℃ / 60%, 40℃ / 75%, and 50℃ / 90%). Samples were taken at 0, 1, 4, 7, 11, and 14 days to monitor the hydrolysis process. The results are shown in Figure 1.

[0299] Example 50: Sustained-release preparation of ester derivatives using 4-pyridinecarboxylic acid (isonicotinic acid) as a carrier

[0300] Five mg of the product prepared in Example 29 was placed in 10 mL centrifuge tubes, resulting in three groups. Each group was placed naturally at different temperatures / relative humidity levels (25℃ / 60%, 40℃ / 75%, and 50℃ / 90%). Samples were taken at 0, 1, 4, 7, 11, and 14 days to monitor the hydrolysis process. The results are shown in Figure 2.

[0301] Example 51: Sustained-release preparation of ester derivatives using o-nitrobenzoic acid as a carrier

[0302] Five mg of the product prepared in Example 31 was placed in 10 mL centrifuge tubes, resulting in three groups. Each group was placed naturally at different temperatures / relative humidity levels (25℃ / 60%, 40℃ / 75%, and 50℃ / 90%). Samples were taken at 0, 1, 4, 7, 11, and 14 days to monitor the hydrolysis process. The results are shown in Figure 3.

[0303] Example 52: Sustained-release preparation of ester derivatives using 2-fluoronicotinic acid as a carrier

[0304] Five mg of the product prepared in Example 32 was placed in 10 mL centrifuge tubes, resulting in three groups. Each group was placed naturally at different temperatures / relative humidity levels (25℃ / 60%, 40℃ / 75%, and 50℃ / 90%). Samples were taken at 0, 1, 4, 7, 11, and 14 days to monitor the hydrolysis process. The results are shown in Figure 4.

[0305] Example 53: Sustained-release preparation of ester derivatives using salicylic acid as a carrier

[0306] Five mg of the product prepared in Example 34 was placed in 10 mL centrifuge tubes, resulting in three groups. Each group was placed naturally at different temperatures / relative humidity levels (25℃ / 60%, 40℃ / 75%, and 50℃ / 90%). Samples were taken at 0, 1, 4, 7, 11, and 14 days to monitor the hydrolysis process. The results are shown in Figure 5.

[0307] Example 54: Sustained-release preparation of ester derivatives using phenyl p-nitrochloroformate as a carrier

[0308] Five mg of the product prepared in Example 36 was placed in 10 mL centrifuge tubes, resulting in four groups. Each group was placed naturally at different temperatures / relative humidity levels (25℃ / 60%, 25℃ / 90%, 50℃ / 60%, 50℃ / 90%). Samples were taken at 0, 1, 4, 7, 11, and 15 days to monitor hydrolysis. The results are shown in Figure 6.

[0309] As can be seen from the above embodiments, the ester derivatives, acid anhydride derivatives, and other derivatives provided by the present invention improve the stability of alcohol pheromones by reacting them with carriers containing active groups such as carboxyl and amide groups, such as amino acids, polypeptides, amides, fatty acids, and chloroformates, through chemical methods, thus preventing their volatilization and deterioration. The resulting derivatives can be slowly released in air or water, and therefore have great potential as sustained-release formulations of insect pheromones. Compared with conventional physical methods, the derivative carriers provided by the present invention have a wide range of sources and high selectivity, thus being more economical. Some carriers are also more environmentally friendly because they are easily degraded after releasing pheromones.

[0310] Unless otherwise specified, the terms used in this invention have the meanings commonly understood by those skilled in the art.

[0311] The embodiments described in this invention are for illustrative purposes only and are not intended to limit the scope of protection of this invention. Those skilled in the art can make various other substitutions, changes and improvements within the scope of this invention. Therefore, this invention is not limited to the above embodiments, but is only defined by the claims.

Claims

1. An alcohol-based insect pheromone derivative, characterized in that, Using a compound containing at least one carboxyl group as a carrier, alcohol-based insect pheromones form ester derivatives or stereoisomers with the structure shown in formula (I). Wherein, R represents the residues of the compound containing at least one carboxyl group after removing y carboxyl groups; a represents an integer from 1 to 20; b represents an integer from 0 to 20; c represents an integer from 0 to 2; d represents an integer from 0 to 20; y represents an integer that is at least 1.

2. The alcohol-based insect pheromone derivative according to claim 1, characterized in that, R represents C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C3-C20 cycloalkyl, 3-20 heterocyclic, C6-C20 aryl, or 5-20 heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted by one or more substituents selected from deuterium, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, halogenated C1-C6 alkoxy, cyano, amino, nitro, hydroxyl, 3-8 heterocyclic, C3-C8 cycloalkyl, C6-C12 aryl, or 5-12 heteroaryl groups; Preferably, R represents C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, 3-8 heterocyclic, C6-C12 aryl, or 5-12 heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted by one or more substituents selected from deuterium, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkoxy, halogenated C1-C6 alkoxy, cyano, amino, nitro, hydroxyl, 3-8 heterocyclic, C3-C8 cycloalkyl, C6-C12 aryl, or 5-12 heteroaryl groups; More preferably, R represents phenyl, pyridyl, pyrazinyl or pyrimidinyl, and is optionally substituted by one or more substituents selected from deuterium, halogen, C1-C6 alkyl, halo-C1-C6 alkyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, cyano, amino, nitro, hydroxyl; More preferably, the compound containing at least one carboxyl group is one of the following compounds:

3. The alcohol-based insect pheromone derivative according to claim 1, characterized in that, The carrier is one or more of the following: fatty acids, aromatic acids, amino acids, and polypeptides containing at least one carboxyl group; Preferably, the carrier is an aliphatic monocarboxylic acid, dicarboxylic acid, tricarboxylic acid or tetracarboxylic acid of C2 to C18, more preferably an aliphatic α,ω-dicarboxylic acid of C2 to C18; Alternatively, the carrier may be a natural amino acid or a non-natural amino acid, preferably a natural amino acid, and more preferably one or more of phenylalanine, alanine, glycine, leucine, and γ-aminobutyric acid. Alternatively, the carrier is a polypeptide formed from 2 to 20 natural amino acids or non-natural amino acids, preferably a polypeptide formed from 3 to 20 natural amino acids, more preferably a polypeptide formed from 3 to 16 natural amino acids, and most preferably Ala-phe-leu-Trp-gly, Ala-Phe-Leu-Trp-Gly-Ala-Phe-Leu-Trp-Gly, Ala-Phe-Leu-Trp-Gly-Ala-Phe-Leu-Trp-Gly-Ala-Phe-Leu-Trp-Gly or Ala-Phe-Leu-Trp-Gly-Ala-Phe-Leu-Trp-Gly-Ala-Phe-Leu-Trp-Gly; More preferably, the carrier is a C3-C18 aliphatic α,ω-diacarboxylic acid, with which alcoholic insect pheromones form monoester derivatives with the structure shown in formula (I-1) or diester derivatives with the structure shown in formula (I-2), or their stereoisomers. Wherein, L represents a straight-chain or branched alkylene group of C1 to C16, preferably a straight-chain or branched alkylene group of C2 to C10; R1 represents H, C1-C16 alkyl, C0-C8 alkylene, C6-C20 aryl or hydroxyl protecting group; a, b, c, and d are each independently defined as in claim 1 or 2; Alternatively, the carrier may be an amino acid or a polypeptide, with which alcohol-based insect pheromones form ester derivatives or stereoisomers of structures as shown in formula (I-3) or (I-4). Wherein, R2 represents the amino acid residues after removing the carboxyl and amino groups; P represents the polypeptide residues with the carboxyl and amino groups removed; a, b, c, and d are each independently defined as in claim 1 or 2; R3 and R4 each independently represent H, C1-C16 alkyl, C0-C8 alkylene-C6-C20 aryl, R5-C(O)-, R5-NHC(O)-, R5-O- or amino protecting group, and R5 represents C1-C6 alkyl or halo-C1-C6 alkyl; Alternatively, -NR3R4 represents the structure shown in equation (Ⅰ-5). Wherein, a1 represents an integer from 1 to 20, b1 represents an integer from 0 to 20, c1 represents an integer from 0 to 2, and d1 represents an integer from 0 to 20; preferably, a1 represents an integer from 1 to 12, b1 represents an integer from 0 to 12, c1 represents an integer from 0 to 2, and d1 represents an integer from 0 to 10; more preferably, a1 represents an integer from 3 to 12, b1 represents an integer from 0 to 6, c1 represents an integer of 0 or 1, and d1 represents an integer from 0 to 8; even more preferably, a1 represents an integer from 6 to 10, b1 represents 0, c1 represents 0, and d1 represents an integer from 2 to 6; preferably, the structure shown in formula (Ⅰ-5) is composed of amino and aldehyde insect pheromones CHO-(CH2). a1 -(CH=CH)-(CH2) b1 -(CH=CH) c1 -(CH2) d1 The aldehyde insect pheromone is formed by a -CH3 reaction. More preferably, the aldehyde insect pheromone is cis-9-hexadecenal, cis-11-hexadecenal, or cis-13-octadecenal.

4. The alcohol-based insect pheromone derivative according to any one of claims 1-3, characterized in that, In formula (Ⅰ), a represents an integer from 1 to 12, b represents an integer from 0 to 12, c represents an integer from 0 to 2, and d represents an integer from 0 to 10; preferably, a represents an integer from 3 to 12, b represents an integer from 0 to 6, c represents an integer of 0 or 1, and d represents an integer from 0 to 8; more preferably, a represents an integer from 6 to 10, b represents 0, c represents an integer of 0 or 1, and d represents an integer from 0 to 6; most preferably, the alcohol insect pheromone is cis-11-hexadecenol or E8E10-dodecadien-1-ol.

5. The method for preparing the alcohol-based insect pheromone derivative according to any one of claims 1-4, characterized in that, The preparation method includes: reacting a compound containing at least one carboxyl group of the structure shown in formula (III) with an alcohol insect pheromone of the structure shown in formula (IV) in an optional first organic solvent in the presence of an optional catalyst or condensing agent to prepare the ester derivative; HO-CH2-(CH2) a -(CH=CH)-(CH2) b -(CH=CH) c -(CH2) d -CH3 Formula (Ⅳ) Alternatively, a compound containing at least one carboxyl group, as shown in formula (III), is first formed in the presence of a halogenating agent into an acyl halide intermediate of formula (III-1), which is then reacted with an alcoholic insect pheromone of formula (IV) in an optional first organic solvent to prepare the ester derivative. Wherein, R, a, b, c, d, and y are each independently defined as in any one of claims 1-4; X1 represents halogen; Preferably, the preparation method comprises: reacting a compound containing at least one carboxyl group of the structure shown in formula (III) with an alcohol insect pheromone of the structure shown in formula (IV) in an optional first organic solvent at 10-150°C in the presence of a protic acid catalyst or condensing agent to prepare the ester derivative; Preferably, the first organic solvent is one or more of the following: aliphatic hydrocarbons, alicyclic hydrocarbons, aromatic hydrocarbons, heterocyclic hydrocarbons, halogenated aliphatic hydrocarbons, halogenated aromatic hydrocarbons, alcohols, ketones, esters, ethers, nitriles, alkyl sulfoxides, and alkyl amides. Preferably, the protic acid catalyst is one or more of p-toluenesulfonic acid, sulfuric acid, methanesulfonic acid, and trifluoromethanesulfonic acid; Preferably, the condensing agent is one or more of N,N-dicyclohexylcarbodiimide (DCC), 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (HATU), and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI).

6. An alcohol-based insect pheromone derivative, characterized in that, Using a compound containing at least one carboxyl or amide group as a carrier, alcoholic insect pheromones form anhydride or amide ester derivatives or their stereoisomers with the structure shown in formula (II). Wherein, R' represents the compound containing at least one carboxyl or amide group, excluding y residues of the carboxyl or amide group moiety; a represents an integer from 1 to 20; b represents an integer from 0 to 20; c represents an integer from 0 to 2; d represents an integer from 0 to 20; X represents -O- or -NR0-; R0 represents hydrogen or a C1-C16 alkyl group; y represents an integer that is at least 1.

7. The alcohol-based insect pheromone derivative according to claim 6, characterized in that, R' represents C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C3-C20 cycloalkyl, 3-20 heterocyclic, C6-C20 aryl, or 5-20 heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted by one or more substituents selected from deuterium, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, halogenated C1-C6 alkoxy, cyano, amino, nitro, hydroxyl, 3-8 heterocyclic, C3-C8 cycloalkyl, C6-C12 aryl, or 5-12 heteroaryl groups; Preferably, R' represents C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, 3-8 heterocyclic, C6-C12 aryl, or 5-12 heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted by one or more substituents selected from deuterium, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkoxy, halogenated C1-C6 alkoxy, cyano, amino, nitro, hydroxyl, 3-8 heterocyclic, C3-C8 cycloalkyl, C6-C12 aryl, or 5-12 heteroaryl groups; More preferably, R' represents a C2-C6 alkyl, C2-C6 alkenyl, C6-C12 aryl or a 5-6 heteroaryl (e.g., phenyl, pyridyl, pyrazinyl or pyrimidinyl), wherein the aryl and heteroaryl are optionally substituted by one or more substituents selected from deuterium, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkoxy, cyano, amino, nitro, hydroxyl; X represents -O- or -NH-; Most preferably, the compound containing at least one carboxyl or amide group is one of the following compounds: acetic acid, propionic acid, butyric acid, valeric acid, hexanoic acid, octanoic acid, strawberry acid, etc.

8. The alcohol-based insect pheromone derivative according to claim 6, characterized in that, The carrier is one or more of the following: fatty acids, aromatic acids, amino acids, and polypeptides containing at least one carboxyl group; Preferably, the carrier is an aliphatic monocarboxylic acid, dicarboxylic acid, tricarboxylic acid or tetracarboxylic acid of C2 to C18, more preferably an aliphatic monocarboxylic acid of C2 to C18; Alternatively, the carrier may be a natural amino acid or a non-natural amino acid, preferably a natural amino acid, and more preferably one or more of phenylalanine, alanine, glycine, leucine, and γ-aminobutyric acid. Alternatively, the carrier is a polypeptide formed from 2 to 20 natural amino acids or non-natural amino acids, preferably a polypeptide formed from 3 to 20 natural amino acids, more preferably a polypeptide formed from 3 to 16 natural amino acids, and most preferably Ala-phe-leu-Trp-gly, Ala-Phe-Leu-Trp-Gly-Ala-Phe-Leu-Trp-Gly, Ala-Phe-Leu-Trp-Gly-Ala-Phe-Leu-Trp-Gly or Ala-Phe-Leu-Trp-Gly-Ala-Phe-Leu-Trp-Gly-Ala-Phe-Leu-Trp-Gly.

9. The alcohol-based insect pheromone derivative according to any one of claims 6-8, characterized in that, In formula (II), a represents an integer from 1 to 12, b represents an integer from 0 to 12, c represents an integer from 0 to 2, and d represents an integer from 0 to 10; preferably, a represents an integer from 3 to 12, b represents an integer from 0 to 6, c represents an integer of 0 or 1, and d represents an integer from 0 to 8; more preferably, a represents an integer from 6 to 10, b represents 0, c represents an integer of 0 or 1, and d represents an integer from 0 to 6; most preferably, the alcohol insect pheromone is cis-11-hexadecenol or E8E10-dodecadien-1-ol.

10. The method for preparing the alcohol-based insect pheromone derivative according to any one of claims 6-9, characterized in that, The preparation method includes the following steps: S1: Alcoholic insect pheromones with the structure shown in formula (Ⅳ) react to form intermediates with the structure shown in formula (Ⅳ-1); and S2: In the presence of an optional basic reagent, a compound containing at least one carboxyl or amide group with the structure shown in formula (V) is reacted with an intermediate with the structure shown in formula (Ⅳ-1) in an optional second organic solvent to prepare the anhydride derivative. HO-CH2-(CH2) a -(CH=CH)-(CH2) b -(CH=CH) c -(CH2) d -CH3 Formula (Ⅳ) Wherein, R', a, b, c, d, X, and y are each independently defined as in any one of claims 6-9, and X1 represents a halogen; Preferably, the second organic solvent is one or more of the following: aliphatic hydrocarbons, alicyclic hydrocarbons, aromatic hydrocarbons, heterocyclic hydrocarbons, halogenated aliphatic hydrocarbons, halogenated aromatic hydrocarbons, alcohols, ketones, esters, ethers, nitriles, alkyl sulfoxides, and alkyl amides. The alkaline reagent is one or more of sodium hydride, sodium hydroxide, potassium hydroxide, diethylamine, triethylamine, N,N-diisopropylethylamine, DBU, pyridine, and 2,6-dimethylpyridine.

11. An alcohol-based insect pheromone derivative, characterized in that, Using a compound containing at least one -O(CO)-Cl group as a carrier, alcoholic insect pheromones form ester derivatives or stereoisomers with the structure shown in formula (1). Wherein, R” represents the residues of the compound containing at least one -O(CO)-Cl group, excluding y -O(CO)-Cl group portions; a represents an integer from 1 to 20; b represents an integer from 0 to 20; c represents an integer from 0 to 2; d represents an integer from 0 to 20; y represents an integer that is at least 1; Preferably, "R" represents C1-C16 alkyl, C2-C16 alkenyl, C2-C16 alkynyl, C3-C20 cycloalkyl, 3-20 heterocyclic, C6-C20 aryl, or 5-20 heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, and heteroaryl groups are optionally substituted by one or more substituents selected from deuterium, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkoxy, halogenated C1-C6 alkoxy, cyano, amino, nitro, hydroxyl, 3-8 heterocyclic, C3-C8 cycloalkyl, C6-C12 aryl, or 5-12 heteroaryl groups; More preferably, R” represents a C6-C12 aryl or a 5-6 heteroaryl (e.g., phenyl, pyridyl, pyrazinyl or pyrimidinyl), wherein the aryl and heteroaryl are optionally substituted by one or more substituents selected from deuterium, halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkoxy, cyano, amino, nitro, hydroxyl; More preferably, the compound containing at least one -O(CO)-Cl group is one of the following compounds: Preferably, in formula (1), a represents an integer from 1 to 12, b represents an integer from 0 to 12, c represents an integer from 0 to 2, and d represents an integer from 0 to 10; preferably, a represents an integer from 3 to 12, b represents an integer from 0 to 6, c represents an integer of 0 or 1, and d represents an integer from 0 to 8; more preferably, a represents an integer from 6 to 10, b represents 0, c represents an integer of 0 or 1, and d represents an integer from 0 to 6; most preferably, the alcohol insect pheromone is cis-11-hexadecenol or E8E10-dodecadien-1-ol.

12. The alcohol-based insect pheromone derivative according to any one of claims 1-4, 6-9, and 11, characterized in that, The alcohol-based insect pheromone derivatives are the following compounds:

13. Use of the alcohol-based insect pheromone derivatives according to any one of claims 1-4, 6-9, 11-12 in the preparation of sustained-release insect pheromone formulations.

14. The method for releasing the alcohol-based insect pheromone derivative according to any one of claims 1-4, 6-9, and 11-12, characterized in that, In the presence of an optional enzyme, the alcohol-based insect pheromone derivative is hydrolyzed in water or in air to release the alcohol-based insect pheromone. Preferably, the alcohol-based insect pheromone derivative is hydrolyzed in air at a temperature of 10–60°C and a relative humidity of 10–100% to release the alcohol-based insect pheromone.

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