Terpenoid ester compound, preparation method thereof and application of terpenoid ester compound in plant disease control

Abstract

The invention belongs to the technical field of chemical synthesis, and particularly relates to a terpenoid ester compound, a preparation method thereof and application of the terpenoid ester compound in plant disease control. The terpene ester compound provided by the invention has a structure as shown in a formula I or a formula II, wherein R4 is selected from or n is 0 or 1, and m is an integer from 0 to 5; r1 is selected from hydrogen or C1-C6 alkyl groups, R2 is selected from hydrogen or C1-C6 alkyl groups, and R3 is selected from one or more of hydrogen, C1-C6 saturated or unsaturated aliphatic groups, C1-C6 alkoxy groups, phenyl groups, halogen, cyano groups, hydroxyl groups, nitryl groups, benzyl groups, halogen-substituted C1-C6 alkyl groups and pyridyl groups. The terpene ester compound provided by the invention shows relatively good insecticidal activity and relatively good phytopathogen inhibition effect, and can be applied to prevention and control of agricultural diseases and insect pests and inhibition of phytopathogens; meanwhile, the preparation method is simple, feasible and suitable for industrial production and application. .

Description

A class of terpene ester compounds, their preparation methods, and their applications in plant disease control. Technical Field

[0001] This invention belongs to the field of chemical synthesis technology, specifically relating to a class of terpene ester compounds, their preparation methods, and their applications in the prevention and control of plant diseases. Background Technology

[0002] Pests, diseases, and weeds are major biological stresses facing crop production. Chemical pesticides, due to their high efficiency and convenience, play an irreplaceable role in pest and weed control. However, long-term and excessive use has also led to the following problems: continuous pesticide selection pressure has resulted in the widespread and increasingly severe development of pesticide resistance in pests, diseases, and weeds. The development of resistance not only reduces control efficiency but also leads to increased pesticide use, causing problems such as agricultural product quality and safety and ecological imbalance. Faced with the challenge of pesticide resistance and the needs of green agriculture development, there is an urgent need to develop new pesticide candidate compounds to provide new solutions for sustainable pest and weed management. Summary of the Invention

[0003] The purpose of this invention is to provide a class of terpene ester compounds, their preparation methods, and their applications in the prevention and control of plant diseases. The terpene ester compounds provided by this invention exhibit good insecticidal activity and good inhibitory effect on plant pathogens, and can be applied to the prevention and control of plant diseases. At the same time, the preparation method is simple and easy to implement, suitable for industrial production and application, and is of great significance for the discovery of novel candidate molecules with high selectivity and environmental compatibility.

[0004] To achieve the above objectives, the present invention provides the following technical solution: The present invention provides a class of terpene ester compounds having the structure shown in Formula I or Formula II: R4 is selected from or n is 0 or 1, m is an integer from 0 to 5; R1 is selected from hydrogen or C1 to C6 alkyl, R2 is selected from hydrogen or C1 to C6 alkyl, R3 is selected from one or more of hydrogen, C1 to C6 saturated or unsaturated aliphatic hydrocarbon group, C1 to C6 alkoxy group, phenyl group, halogen, cyano group, hydroxyl group, nitro group, benzyl group, halogen-substituted C1 to C6 alkyl group and pyridyl group, and the number of R3 is 1 to 5.

[0005] This invention provides terpene ester compounds, with structures shown in Formula I or Formula II. The terpene ester compounds provided by this invention exhibit insecticidal activity against cotton bollworm, with a mortality rate ranging from 3.33% to 59.81%. Among them, compound II-8 exhibits the most prominent insecticidal activity, with a mortality rate of 59.81%, comparable to the control agent lufenuron (60%); compound II-11 also shows good activity, with a mortality rate of 52.97%, exceeding 50%; in addition, compounds I-1 (46.67%), II-17 (46.33%), and II-6 (42.40%) also show moderate to high insecticidal effects. The terpene ester compounds provided by this invention exhibit insecticidal effects against cotton aphids, with a mortality rate ranging from 16.06% to 73.33%. Among them, compound I-25 showed the most significant activity, with a mortality rate of 73.33%. In addition, compounds I-18 (65.70%), I-26 (65.63%), I-7 (62.77%), I-24 (61.74%), I-35 (61.22%), I-17 (60.89%), and I-22 (60.16%) all showed mortality rates exceeding 60%, demonstrating good insecticidal potential. The terpene ester compounds provided by this invention exhibit significant inhibitory effects against *Fusarium graminearum* and *Fusarium oxysporum*, with compound I-25 showing excellent control effects against *Fusarium oxysporum*-induced root rot in peppers. Compound I-25 provided by this invention has the potential to be developed as a novel fungicide candidate compound, possessing high research value and application prospects.

[0006] This invention provides a method for preparing the terpene ester compounds described above. The synthetic route of the terpene ester compounds provided by this invention is simple, has a high yield, and the products are easy to separate, making it suitable for industrial production. Attached Figure Description

[0007] Figure 1 shows the potted plant control efficacy of compound I-25 against pepper root rot; Figure 2 is a flowchart of the synthesis of the compound with the structure shown in Formula I in this invention; Figure 3 is a flowchart of the synthesis of the compound with the structure shown in Formula II in this invention; Figure 4 shows the effects of compound I-25 on reactive oxygen species (A in Figure 4), ergosterol content (B in Figure 4), and cell membrane permeability (C in Figure 4) in Fusarium oxysporum; Figure 5 shows the results of cytoplasmic staining using the PI staining method; Figure 6 shows the effects of compound I-25 on the hyphal morphology and ultrastructure of Fusarium oxysporum; Figure 7 shows the two-dimensional interaction diagram of compound I-25 docking with ERG13 molecules (A in Figure 7) and the three-dimensional binding conformation diagram of compound I-25 (cyan) at the active site of ERG13 protein (B in Figure 7). Detailed Implementation

[0008] This invention provides a class of terpene ester compounds having the structure shown in Formula I or Formula II: R4 is selected from or n is 0 or 1, m is an integer from 0 to 5; R1 is selected from hydrogen or C1 to C6 alkyl, R2 is selected from hydrogen or C1 to C6 alkyl, R3 is selected from one or more of hydrogen, C1 to C6 saturated or unsaturated aliphatic hydrocarbon group, C1 to C6 alkoxy group, phenyl group, halogen, cyano group, hydroxyl group, nitro group, benzyl group, halogen-substituted C1 to C6 alkyl group and pyridinyl group, and the number of R3 is 1 to 5 (i.e. R3 is monosubstituted or polysubstituted).

[0009] In this invention, unless otherwise specified, all raw materials / components are commercially available products well-known to those skilled in the art. Compounds with the structure shown in Formula I are phenylaminooxyester compounds. Compounds with the structure shown in Formula II are phenylurea compounds. In this invention, R4 is selected from... When the terpene ester compound has the following structural formula: R4 is selected from When the terpene ester compound has the following structural formula: .

[0010] To provide a detailed description of the structure of the compounds described in Formula I or Formula II, the terminology used in this invention is explained in the context, but this explanation does not constitute a particular limitation on the scope of protection of this invention. The term "halogen" should represent fluorine, chlorine, bromine, or iodine. The term "cyano" should represent a -CN group. The term "hydroxyl" should represent a -OH group. The term "nitro" should represent a -NO2 group. The term "aliphatic hydrocarbon" refers to a chain hydrocarbon group that does not have a benzene ring. Hydrocarbons possessing the basic properties of aliphatic compounds are called aliphatic hydrocarbons. "C1~C5 saturated aliphatic hydrocarbon" refers to a C1~C5 "alkyl". The term "alkyl" should refer to a monovalent group derived by removing a hydrogen atom from any carbon atom of an alkane. The carbon atoms of an "alkyl" form a straight-chain or branched skeleton; therefore, "alkyl" can be divided into "straight-chain alkyl" and "branched alkyl". This terminology includes primary, secondary, and tertiary alkyl subgroups, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, and isohexyl. Specifically, the term "alkane" refers to a saturated hydrocarbon compound containing only carbon and hydrogen. "C1-C6 unsaturated aliphatic hydrocarbon group" refers to a chain hydrocarbon group with unsaturated bonds at C1-C6. The term "alkoxy group" refers to a group in which one hydrogen atom of an alkane is replaced by an oxygen atom. "C1-C6 alkoxy group" refers to a group in which one hydrogen atom of a C1-C6 alkane is replaced by an oxygen atom. The term "phenyl" should indicate a group in which the hydrogen atom on the benzene ring (C6) is substituted. "Substituted phenyl" refers to a phenyl group in which the hydrogen atom of one carbon atom is replaced by another group. "Substituted phenyl" can be divided into monosubstituted phenyl and polysubstituted phenyl. The term "monosubstituted phenyl" should be understood as a phenyl group in which the hydrogen atom of one carbon atom is replaced by another group. For example, this hydrogen can be replaced by a halogen (fluorine, chlorine, bromine, or iodine) to form ortho, meta, or para halophenyl; or replaced by a methyl group to form ortho-methylphenyl, meta-methylphenyl, or para-methylphenyl; or replaced by a methoxy group to form ortho-methoxyphenyl, meta-methoxyphenyl, or para-methoxyphenyl. The term "polysubstituted phenyl" refers to a phenyl group in which two or more carbon atoms have hydrogen atoms replaced by other groups. For example, two chlorine atoms, or two fluorine atoms, or one chlorine atom and one fluorine atom can replace hydrogen atoms on different carbon atoms; hydrogen atoms on the benzene ring can be replaced by methyl and fluorine atoms to form 2-fluoro-p-methylphenyl; or hydrogen atoms on the benzene ring can be replaced by methyl and chlorine to form 3-chloro-2-methylphenyl; or hydrogen atoms on the benzene ring can be replaced by two trifluoromethyl groups to form 3,5-trifluoromethylphenyl. The term "benzyl" is also known as benzyl, with the structure phenyl-methylene-. The term "pyridyl" should be understood as the group in which hydrogen atoms on pyridine are replaced.

[0011] In this invention, R1 and R2 are not both hydrogen, and R1 and R2 are not both C1-6 alkyl groups. R1 is preferably selected from hydrogen or C1-5 alkyl groups, more preferably from hydrogen or C1-3 alkyl groups. In the examples, it can be hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, or isohexyl. R2 is preferably selected from hydrogen or C1-5 alkyl groups, more preferably from hydrogen or C1-3 alkyl groups. In the examples, it can be hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, or isohexyl. R3 is selected from one, two, three, four, or five of the following: hydrogen, methyl, ethyl, C1, ethyl, tert-butyl, n-propyl, n-butyl, methoxy, phenyl, F, Br, I, trifluoromethyl, cyano, nitro, ethoxy, and benzyl.

[0012] In this invention, the terpene ester compound has any one of the structures shown in Formula I-1 to Formula I-46 and Formula II-1 to Formula II-18: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , .

[0013] This invention provides a method for preparing the terpene ester compound described in the above technical solution. The method for preparing the terpene ester compound of Formula I includes the following steps: reacting the compound of Formula III and oxaloyl chloride in an organic solvent (hereinafter referred to as the first reaction) to obtain an intermediate of Formula IV; reacting the intermediate of Formula IV and the compound of Formula V or Formula VII in an organic solvent (hereinafter referred to as the second reaction) to obtain the terpene ester compound of Formula I; the method for preparing the terpene ester compound of Formula II includes the following steps: reacting the compound of Formula III, bis(trichloromethyl) carbonate and sodium cyanate in an organic solvent (hereinafter referred to as the third reaction) to obtain an intermediate of Formula VI; reacting the intermediate of Formula VI and the compound of Formula V in an organic solvent (hereinafter referred to as the fourth reaction) to obtain the terpene ester compound of Formula II. , , , , .

[0014] In this invention, the compound with the structure shown in Formula III can be flavonol or borneol.

[0015] In this invention, when preparing the terpene ester compound of Formula I, the molar ratio of the compound of Formula III to oxaloyl chloride is 1:1.5. The first reaction is a nucleophilic reaction, and the organic solvent used in the first reaction can be 1,2-dichloroethane; the first reaction is carried out under reflux conditions. The first reaction is monitored by thin-layer chromatography (TLC), and the reaction is stopped after the starting material has completely disappeared. After the first reaction is completed, the oxaloyl chloride and solvent are preferably removed by vacuum distillation to obtain the intermediate of Formula VI. In this invention, the intermediate of Formula VI does not need to be purified and is directly used in the subsequent first reaction.

[0016] In this invention, the molar ratio of the compound with the structure shown in Formula III to the compound with the structure shown in Formula V or Formula VII is preferably 1:1.3. The organic solvent used in the second reaction can be acetonitrile. The second reaction is carried out at room temperature and under stirring. The second reaction is monitored by thin-layer chromatography (TLC). After the second reaction is completed, the solvent is preferably removed by vacuum distillation, followed by separation by column chromatography to obtain the terpene ester compound with the structure shown in Formula I. In this invention, the eluent used for the column chromatography is preferably petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is preferably 40:1.

[0017] In this invention, when preparing the terpene ester compound of Formula II, the molar ratio of the compound of Formula III to bis(trichloromethyl) carbonate is 1:1.5, and the molar ratio of the compound of Formula III to sodium cyanate is 1:1.5. In this invention, the organic solvent used in the third reaction can be 1,2-dichloroethane; the third reaction is carried out under reflux conditions. The third reaction is monitored by thin-layer chromatography (TLC). After the third reaction is completed, the solvent is preferably removed by vacuum distillation to obtain the intermediate of Formula IV. In this invention, the intermediate of Formula IV does not require purification and is directly used in the subsequent first reaction.

[0018] In this invention, the molar ratio of the compound with the structure shown in Formula III to the compound with the structure shown in Formula V is 1:1.5. In this invention, the organic solvent used in the fourth reaction can be acetonitrile. The fourth reaction is carried out at room temperature and under stirring. The fourth reaction is monitored by thin-layer chromatography (TLC). After the fourth reaction is completed, the solvent is preferably removed by vacuum distillation, followed by separation by column chromatography to obtain the terpene ester compound with the structure shown in Formula II. In this invention, the eluent used in the paper chromatography is preferably petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is preferably 40:1.

[0019] This invention provides the application of the terpene ester compounds described in the above-described technical solutions or their pharmaceutically acceptable salts, or the terpene ester compounds prepared by the preparation methods described in the above-described technical solutions, in the control of agricultural pests and diseases.

[0020] This invention provides the application of the terpene ester compounds described in the above-described technical solutions or their pharmaceutically acceptable salts, or the terpene ester compounds prepared by the preparation methods described in the above-described technical solutions, in the preparation of insecticides.

[0021] In this invention, the insecticide is a drug that kills cotton bollworms and / or cotton aphids.

[0022] This invention provides the application of the terpene ester compounds described in the above-described technical solutions or their pharmaceutically acceptable salts, or the terpene ester compounds prepared by the preparation methods described in the above-described technical solutions, in the inhibition of plant pathogens, wherein the plant pathogens include one or more of Rhizoctonia solani, Cynotrophomonas chrysogenum, Fusarium graminearum, and Fusarium oxysporum.

[0023] This invention provides the application of the terpene ester compounds described in the above-described technical solutions or their pharmaceutically acceptable salts, or the terpene ester compounds prepared by the above-described technical solutions, in the preparation of drugs that inhibit plant pathogens, wherein the plant pathogens include one or more of Rhizoctonia solani, Cynotrophomonas chrysogenum, Fusarium graminearum, and Fusarium oxysporum.

[0024] This invention provides the application of the terpene ester compounds described in the above-described technical solutions or their pharmaceutically acceptable salts, or the terpene ester compounds prepared by the preparation methods described in the above-described technical solutions, in the prevention and control of pepper root rot caused by Fusarium oxysporum.

[0025] The present invention provides a pharmaceutical composition, wherein the terpene ester compound described in the above technical solution or its pharmaceutically acceptable salt or the terpene ester compound prepared by the preparation method described in the above technical solution is used as the active ingredient.

[0026] In this invention, the pharmaceutical composition may further comprise other insecticides. In this invention, the pharmaceutical composition may further comprise pharmaceutically acceptable excipients. The pharmaceutically acceptable excipients are selected from pharmaceutically acceptable carriers, diluents, or excipients. The dosage form of the pharmaceutical composition is selected from solid dosage forms, semi-solid dosage forms, or liquid dosage forms.

[0027] To further illustrate the present invention, the technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0028] Example 1: Synthesis of the compound with the structure shown in Formula I. This example uses commercially available reagents ferrous alcohol (or borneol) and oxalyl chloride as starting materials. After nucleophilic substitution, the compound is reacted with an aromatic amine (or an aromatic amine containing different substituents) to obtain the target compound. The synthetic route of the target product is shown in Figure 2.

[0029] Specific operating procedure: Accurately weigh 0.006 mol of borneol (or camphor) into a 250 mL three-necked flask, add 0.009 mol of oxaloyl chloride (1.5 times the borneol equivalent), add 10 mL of 1,2-dichloroethane, reflux the mixture, monitor the reaction by thin-layer chromatography (TLC), and stop the reaction after the starting material has completely disappeared. After the reaction is complete, remove the oxaloyl chloride and solvent by vacuum distillation to obtain intermediate IV. Intermediate IV does not require purification and can be used directly in subsequent reactions. Add 1.3 times the equivalent of aromatic amine V (or an aromatic amine containing different substituents) and 15 mL of acetonitrile to a 100 mL round-bottom flask containing intermediate IV, stir the mixture at room temperature, and monitor the reaction by TLC. After the reaction is complete, remove the solvent by vacuum distillation, and separate the target product by column chromatography (eluent: petroleum ether / ethyl acetate = 40:1, volume ratio).

[0030] Example 2: Synthesis of the compound with the structure shown in Formula II. This example uses commercially available reagents ferrous alcohol (or borneol) and urea as starting materials, reacting them with bis(trichloromethyl) carbonate and sodium cyanate to obtain intermediate VI, which is then reacted with the compound described in Formula V to obtain the target compound. The synthetic route of the target product is shown in Figure 3.

[0031] Specific procedures: Add 10 mL of 1,2-dichloroethane as a solvent to a 250 mL three-necked flask. Accurately weigh 0.9252 g (0.006 mol, 1.0 equiv.) of flavonol (or borneol), 2.6706 g of bis(trichloromethyl) carbonate (0.009 mol, 1.5 equiv.), and 0.5851 g of sodium cyanate (0.009 mol, 1.5 equiv.) and add them sequentially to the flask. Heat the reaction system to reflux and monitor the reaction progress by TLC. After the reaction is complete, remove the solvent by vacuum distillation to obtain intermediate VI. This intermediate does not require further purification and can be used directly in subsequent reactions. Add 15 mL of acetonitrile to a 100 mL round-bottom flask containing intermediate VI, followed by the addition of the corresponding aromatic amine V with different substituents (or aromatic amines containing different substituents) (1.5 equiv.), and stir the reaction at room temperature. The reaction was monitored by TLC. After the reaction was completed, the solvent was removed by vacuum distillation, and the target product was obtained by column chromatography (eluent: petroleum ether / ethyl acetate = 40:1, volume ratio).

[0032] Example 3: Structural characterization of several compounds with structures shown in Formula I. In this example, the compounds with structures shown in Formula I are designated with consecutive Arabic numerals as references in this invention.

[0033] I-1(1S,2R,4S)-1,3,3-trimethylbicyclo[2.2.1]heptane-2-yl-2-oxo-2-(phenylamino)acetic acid ester, colorless solid, yield 77%, melting point 86.9~87.4℃.

[0034] 1 H NMR (400 MHz, CDCl3) δ 8.87 (s, 1H), 7.65 (d,J= 7.5 Hz, 2H), 7.37(t,J= 7.1 Hz, 2H), 7.18 (t,J= 7.4 Hz, 1H), 4.53 (d,J= 2.1 Hz, 1H), 1.96 (td,J= 3.7, 1.8 Hz, 1H), 1.79 (d,J= 2.1 Hz, 1H), 1.76 (d,J= 2.9 Hz, 1H), 1.64 (d,J= 8.8 Hz, 1H), 1.54 – 1.48 (m, 1H), 1.28 (d,J= 8.8 Hz, 1H), 1.20 (d,J= 11.1Hz, 1H), 1.16 (s, 3H), 1.11 (s, 3H), 0.86 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.62, 153.96, 136.65, 129.35, 125.51,119.76, 119.67, 90.12, 48.78, 48.43, 41.60, 40.03, 29.96, 26.61, 25.92,20.36, 19.49.HRMS (ESI)m / zC 18 H 23 NO3Na + (M+Na + Theoretical value 324.15701, measured value 324.15689. I-21,3,3-trimethylbicyclo[2.2.1]heptane-2-yl-2-oxo-2-(o-toluidine)acetic acid ester, colorless solid, yield 73%, melting point 80.4~80.9 ℃.

[0035] 1H NMR (400 MHz, CDCl3) δ 8.83 (s, 1H), 7.52 (s, 1H), 7.42 (d,J= 5.5Hz, 1H), 7.23 (d,J= 7.8 Hz, 1H), 6.99 (d,J= 5.9 Hz, 1H), 4.53 (d,J= 2.1 Hz,1H), 2.36 (s, 3H), 1.96 (td,J= 5.3, 2.6 Hz, 1H), 1.78 (d,J= 2.2 Hz, 1H), 1.75(d,J= 6.4 Hz, 1H), 1.64 (d,J= 8.7 Hz, 1H), 1.53 – 1.49 (m, 1H), 1.27 (d,J=8.7 Hz, 1H), 1.20 (d,J= 11.1 Hz, 1H), 1.15 (s, 3H), 1.11 (s, 3H), 0.86 (s,3H). 13 C NMR (101 MHz, CDCl3) δ 161.44, 153.85, 134.81, 130.68, 127.24,125.68, 121.20, 90.13, 48.78, 48.43, 41.59, 40.02, 29.93, 26.68, 25.92,20.39, 19.52, 17.60.HRMS (ESI)m / zC 19 H 25 NO3Na + (M+Na) + Theoretical value 338.17266, measured value 338.17285. I-31,3,3-trimethylbicyclo[2.2.1]heptane-2-yl-2-oxo-2-(m-toluidine)acetic acid ester, white solid, yield 83%, melting point 87.9~88.4 ℃.

[0036] 1H NMR (400 MHz, CDCl3) δ 8.84 (s, 1H), 8.16 (d,J= 8.2 Hz, 1H), 7.26(t,J= 6.8 Hz, 1H), 7.21 (d,J= 5.9 Hz, 1H), 7.13 – 7.09 (m, 1H), 4.55 (d,J=2.0 Hz, 1H), 2.34 (s, 3H), 1.94 (dd,J= 12.3, 6.3 Hz, 1H), 1.80 (d,J= 3.7 Hz,1H), 1.78 (d,J= 3.4 Hz, 1H), 1.65 (d,J= 12.2 Hz, 1H), 1.56 – 1.49 (m, 1H), 1.28 (dd,J= 10.5, 1.7 Hz, 1H), 1.22 (d,J= 14.1 Hz, 1H), 1.17 (s, 3H), 1.13(s, 3H), 0.88 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.39, 153.80, 134.76, 130.63, 127.63,127.17, 125.63, 121.17, 90.05, 48.73, 48.38, 41.53, 39.97, 29.88, 26.63,25.87, 20.34, 19.48, 17.55.HRMS (ESI)m / zC 19 H 25 NO3Na + (M+Na) + Theoretical value 338.17267, measured value 338.17288. I-41,3,3-trimethylbicyclo[2.2.1]heptane-2-yl-2-oxo-2-(p-toluidine)acetic acid ester, white solid, yield 80%, melting point 127.5~128.0 ℃.

[0037] 1H NMR (400 MHz, CDCl3) δ 8.83 (s, 1H), 7.54 (d,J= 8.4 Hz, 2H), 7.17(d,J= 8.4 Hz, 2H), 4.52 (s, 1H), 2.33 (s, 3H), 1.99 – 1.92 (m, 1H), 1.78 (d,J= 3.9 Hz, 1H), 1.75 (d,J= 8.9 Hz, 1H), 1.62 (s, 1H), 1.54 – 1.46 (m, 1H), 1.27 (d,J= 10.4 Hz, 1H), 1.19 (d,J= 12.7 Hz, 1H),1.15 (s, 3H), 1.11 (s, 3H), 0.86 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.54, 161.51, 153.67, 153.58, 135.06,133.99, 133.90, 129.66, 119.54, 119.46, 89.84, 77.32, 77.20, 77.00, 76.68,48.60, 48.27, 41.43, 39.85, 29.78, 26.44, 25.75, 20.92, 20.20, 19.33.HRMS (ESI)m / zC 19 H 25 NO3Na + (M+Na) + Theoretical value 338.17267, measured value 338.17294. I-51,3,3-trimethylbicyclo[2.2.1]heptane-2-yl 2-((2,4-dimethylphenyl)amino)-2-oxoacetic acid ester, white solid, yield 85%, melting point 60.5~61.0 ℃.

[0038] 1H NMR (400 MHz, CDCl3) δ 8.76 (s, 1H), 8.00 (d,J= 8.2 Hz, 1H), 7.06(d,J= 8.2 Hz, 1H), 7.03 (s, 1H), 4.54 (d,J= 2.0 Hz, 1H), 2.31 (s, 3H), 2.30(s, 3H), 1.98 – 1.90 (m, 1H), 1.79 (d,J= 3.7 Hz, 1H), 1.77 (d,J= 3.3 Hz, 1H), 1.65 (d,J= 12.1 Hz, 1H), 1.55 – 1.47 (m, 1H), 1.28 (d,J= 10.4 Hz, 1H), 1.21(d,J= 12.6 Hz, 1H), 1.17 (s, 3H), 1.12 (s, 3H), 0.87 (s, 3H).

[0039] 13 C NMR (101 MHz, CDCl3) δ 161.52, 153.79, 135.43, 132.23, 131.34,127.73, 127.70, 121.31, 90.03, 48.78, 48.44, 41.59, 40.01, 29.93, 26.68,25.92, 21.05, 20.39, 19.53, 17.56.

[0040] HRMS theoretical value C 20 H 27 NO3Na + (M+Na) + 352.1883149, measured value 352.18835.I-61,3,3-trimethylbicyclo[2.2.1]heptane-2-yl-2-((2-chloro-4-methylphenyl)amino)-2-oxoacetic acid ester, white solid, yield 85%, melting point 82.3~82.8 ℃.

[0041] 1H NMR (400 MHz, CDCl3) δ 9.41 (s, 1H), 8.36 (d,J= 8.3 Hz, 1H), 7.24(s, 1H), 7.12 (d,J= 8.3 Hz, 1H), 4.56 (d,J= 2.1 Hz, 1H), 2.33 (s, 3H). 1.95 –1.92 (m, 1H), 1.80 (d,J= 3.5 Hz, 1H), 1.77 (d,J= 2.9 Hz, 1H), 1.65 (d,J= 8.8Hz, 1H), 1.53 – 1.49 (m, 1H), 1.28 (d,J= 8.9 Hz, 1H), 1.22 (d,J= 10.5 Hz,1H,), 1.17 (s, 3H), 1.12 (s, 3H), 0.88 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 160.61, 153.81, 136.12, 131.03, 129.69,128.69, 123.08, 120.90, 90.21, 48.80, 48.43, 41.57, 40.03, 29.91, 26.71,25.92, 20.91, 20.40, 19.51.HRMS (ESI)m / zC 16 H 22 N2O3Na + (M+Na) + Theoretical value 313.15226, measured value 313.15222. I-71,3,3-trimethylbicyclo[2.2.1]heptane-2-yl 2-((2-ethylphenyl)amino)-2-oxoacetic acid ester, white solid, yield 76%, melting point 92.4~92.9 ℃.

[0042] 1H NMR (400 MHz, CDCl3) δ 8.91 (s, 1H), 8.16 (s, 1H), 7.23 (d,J= 7.6Hz, 2H), 7.15 (s, 1H), 4.55 (d,J= 2.1 Hz, 1H), 2.68 (d,J= 7.7 Hz, 2H), 1.93(d,J= 5.9 Hz, 1H), 1.80 (s, 1H), 1.78 – 1.75 (m, 1H), 1.67 (s, 1H), 1.55 –1.50 (m, 1H),1.30 (d,J= 1.6 Hz, 1H), 1.28 (d,J= 4.4 Hz, 3H), 1.21 (s, 1H), 1.17 (s, 3H), 1.13 (s, 3H), 0.88 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.37, 153.88, 134.10, 133.48, 128.85,127.13, 125.89, 121.52, 90.11, 48.74, 48.41, 41.56, 39.98, 29.89, 26.66,25.90, 24.44, 20.34, 19.49, 14.06.HRMS(ESI)m / zC 20 H 27 NO3Na + (M+Na) + Theoretical value 352.18831, measured value 352.18820. I-81,3,3-trimethylbicyclo[2.2.1]heptane-2-yl-2-((3-ethylphenyl)amino)-2-oxoacetic acid ester, yellow liquid, yield 78%.

[0043] 1H NMR (400 MHz, CDCl3) δ 8.83 (s, 1H), 7.56 (s, 1H), 7.42 (d,J= 7.0Hz, 1H), 7.29 (d,J= 7.8 Hz, 1H), 7.02 (d,J= 7.6 Hz, 1H), 4.53 (d,J= 2.1 Hz,1H), 2.66 (d,J= 7.6 Hz, 2H), 1.97 (t,J= 2.9 Hz, 1H), 1.79 (s, 1H), 1.77 –1.73 (m, 1H), 1.64 (d,J= 10.6 Hz, 1H), 1.52 (d,J= 5.9 Hz, 1H), 1.29 (d,J= 1.7Hz, 1H), 1.24 (s, 3H), 1.20 (d,J= 12.7 Hz, 1H), 1.16 (s, 3H), 1.11 (s, 3H), 0.86 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.68, 153.94, 145.76, 136.63, 129.23,125.17, 119.26, 117.08, 90.06, 48.79, 48.45, 41.61, 40.05, 29.97, 29.01,26.62, 25.93, 20.37, 15.58.HRMS (ESI)m / zC 20 H 27 NO3Na + (M+Na) + Theoretical value 352.18831, measured value 352.18820. I-91,3,3-trimethylbicyclo[2.2.1]heptane-2-yl-2-((4-ethylphenyl)amino)-2-oxoacetic acid ester, white solid, yield 65%, melting point 124.8~125.3℃.

[0044] 1H NMR (400 MHz, CDCl3) δ 8.82 (s, 1H), 7.56 (d,J= 8.6 Hz, 2H), 7.19 (d,J= 8.7 Hz, 2H), 4.53 (d,J= 2.0 Hz, 1H), 2.63 (q,J= 7.6 Hz, 2H), 2.00 –1.92 (m, 1H), 1.78 (d,J= 3.5 Hz, 1H), 1.75 (d,J= 9.2 Hz, 1H), 1.62 (d,J= 11.2Hz, 1H), 1.54 – 1.46 (m, 1H), 1.27 (d,J= 8.8 Hz, 1H), 1.24 (d,J= 7.6 Hz, 3H), 1.18 (d,J= 5.5 Hz, 1H), 1.15 (s, 3H), 1.11 (s, 3H), 0.86 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.71, 153.81, 140.34, 134.29, 129.20,119.70, 90.01, 89.04, 48.76, 48.44, 41.60, 40.02, 35.24, 33.69, 29.95, 26.61,25.92, 22.39, 20.35, 19.49, 14.05.HRMS (ESI) m / z C 20 H 27 NO3Na + (M+Na) + Theoretical value 352.18831, measured value 352.18823. I-101,3,3-trimethylbicyclo[2.2.1]heptane-2-yl 2-((4-(tert-butyl)phenyl)amino)-2-oxoacetic acid ester, white solid, yield 71%, melting point 129.3~130.2℃.

[0045] 1H NMR (400 MHz, CDCl3) δ 8.83 (s, 1H), 7.57 (d,J= 8.7 Hz, 2H), 7.38 (d,J= 8.8 Hz, 2H), 4.53 (d,J= 2.1 Hz, 1H), 1.96 (dd,J= 5.9, 3.7 Hz, 1H), 1.79(s, 1H), 1.77 – 1.74 (m, 1H), 1.66 – 1.63 (m, 1H), 1.60 (s, 1H), 1.53 – 1.48(m, 1H), 1.31 (s, 9H), 1.27 (d,J= 8.8 Hz, 1H), 1.20 (d,J= 12.7 Hz, 1H), 1.16(s, 3H), 1.11(s, 3H), 0.86(s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.73, 153.84, 148.60, 134.06, 126.18,119.48, 90.05, 48.78, 48.45, 41.62, 40.04, 34.64, 31.45, 29.96, 26.62, 25.93,20.36, 19.51.HRMS (ESI)m / zC 22 H 31 NO3Na + (M+Na) +理论值 380.21962, the measured value is 380.21982.I-111,3,3-trimethylbicyclo[2.2.1]heptane-2-yl-2-oxo-2-((4-propylphenyl)amino)acetic acid ester, yellow solid, yield 67%, melting point 72.0~72.5℃.

[0046] 1H NMR (400 MHz, CDCl3) δ 8.82 (s, 1H), 7.55 (d,J= 8.6 Hz, 2H), 7.17(d,J= 8.6 Hz, 2H), 4.53 (d,J= 2.1 Hz, 1H), 2.59 (t,J= 7.7 Hz, 2H), 1.96 (s,1H), 1.79 (s, 1H), 1.75 (d,J= 9.2 Hz, 1H), 1.61 (s, 1H), 1.52 – 1.48 (m, 1H), 1.34 (d,J= 7.7 Hz, 2H), 1.26 (s, 1H), 1.20 (dd,J= 9.1, 2.0 Hz, 1H), 1.15 (s, 3H), 1.11 (s, 3H), 0.92 (s, 3H), 0.86 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.70, 153.82, 140.11, 134.33, 129.26,119.69, 90.02, 48.77, 48.44, 41.60, 40.02, 37.61, 29.95, 26.61, 25.92, 24.62,20.35, 19.49, 13.85.HRMS (ESI)m / zC 21 H 29 NO3Na + (M+Na) + Theoretical value 366.20396, measured value 366.20358. I-121,3,3-trimethylbicyclo[2.2.1]heptane-2-yl-2-((4-butylphenyl)amino)-2-oxoacetic acid ester, brown liquid, yield 76%.

[0047] 1H NMR (400 MHz, CDCl3) δ 8.83 (s, 1H), 7.55 (d,J= 8.4 Hz, 2H), 7.17(d,J= 8.6 Hz, 2H), 4.53 (d,J= 2.0 Hz, 1H), 2.61 – 2.57 (m, 2H), 1.97 – 1.93(m, 1H), 1.79 (s, 1H), 1.76 – 1.73 (m, 1H), 1.63 (s, 1H), 1.58 (td,J= 5.4,2.6 Hz, 2H), 1.52 – 1.48 (m, 1H), 1.34 (d,J= 7.6 Hz, 2H), 1.27 (d,J= 9.4 Hz,1H), 1.19 (d,J= 12.7 Hz, 1H), 1.15 (s, 3H), 1.11 (s, 3H), 0.92 (t,J= 7.3 Hz,3H), 0.86 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.71, 153.81, 140.34, 134.29, 129.20,119.70, 90.01, 48.76, 48.44, 41.60, 40.02, 35.24, 33.69, 29.95, 26.61, 25.92,22.39, 20.35, 19.49, 14.05.HRMS (ESI)m / zC 22 H 31 NO3Na + (M+Na) + Theoretical value 380.22016, measured value 380.21962.I-131,3,3-trimethylbicyclo[2.2.1]heptane-2-yl 2-((4-methoxyphenyl)amino)-2-oxoacetic acid ester, white solid, yield 73%, melting point 92.0~92.5℃.

[0048] 1H NMR (400 MHz, CDCl3) δ 8.78 (s, 1H), 7.57 (d,J= 9.2 Hz, 2H), 6.90 (d,J= 9.0 Hz, 2H), 4.52 (d,J= 2.1 Hz, 1H), 3.81 (s, 3H), 1.98 – 1.93 (m, 1H),1.79 (s, 1H), 1.77 – 1.73 (m, 1H), 1.64 (d,J= 10.5 Hz, 1H), 1.54 – 1.49 (m,1H), 1.27 (d,J= 8.8 Hz, 1H), 1.18 (s, 1H), 1.15 (s, 3H), 1.11 (s, 3H), 0.86 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.78, 157.20, 153.71, 129.89, 121.27,114.47, 90.01, 55.62, 48.78, 48.45, 41.62, 40.03, 29.96, 26.62, 25.93, 20.38,19.50.HRMS (ESI)m / zC 19 H 25 NO4K + (M+K) + Theoretical value 370.14152, measured value 370.14194. I-141,3,3-trimethylbicyclo[2.2.1]heptane-2-yl-2-([1,1'-biphenyl]-4-ylamino)-2-oxoacetic acid ester, yellow solid, yield 83%, melting point 108.5~109.0℃.

[0049] 1 H NMR (400 MHz, CDCl3) δ 8.93 (s, 1H), 7.74 (s, 2H), 7.60 (s, 2H), 7.44 (s, 3H), 7.35 (t,J= 7.3 Hz, 2H), 4.55 (d,J= 1.9 Hz, 1H), 1.97 (d,J= 6.0Hz, 1H), 1.80 (s, 1H), 1.78 (d,J= 3.2 Hz, 1H), 1.65 (s, 1H), 1.52 (d,J= 5.9Hz, 1H), 1.30 (s, 1H), 1.23 (s, 1H), 1.17 (s, 3H), 1.13 (s, 3H), 0.88 (s,3H). 13C NMR (101 MHz, CDCl3) δ 161.62, 153.94, 140.35, 138.39, 135.91, 128.98, 127.95, 127.50, 127.03, 120.07, 119.99, 90.19, 48.81, 48.45, 41.62, 40.07, 29.98, 26.63, 25.94, 20.40, 19.52. HRMS (ESI) m / z theoretical value C 24 H 27 NO3Na + (M+Na) + Theoretical value 400.18831, measured value 400.18845. I-151,3,3-trimethylbicyclo[2.2.1]heptane-2-yl 2-((4-fluorophenyl)amino)-2-oxoacetic acid ester, white solid, yield 73%, melting point 166.5~167.0℃.

[0050] 1 H NMR (400 MHz, CDCl3) δ 8.91 (s, 1H), 7.65 – 7.62 (m, 2H), 7.05 (d,J= 9.0 Hz, 2H), 4.52 (d,J= 2.1 Hz, 1H), 1.96 – 1.91 (m, 1H), 1.78 (d,J= 4.2Hz, 1H), 1.75 (d,J= 3.4 Hz, 1H), 1.63 (d,J= 10.5 Hz, 1H), 1.54 – 1.48 (m,1H), 1.27 (d,J= 10.5 Hz, 1H), 1.19 (d,J= 12.6 Hz, 1H), 1.14 (s, 3H), 1.10 (s, 3H), 0.85 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.55, 158.79, 153.97, 132.78, 121.47,116.18, 90.18, 48.75, 48.40, 41.57, 40.01, 29.93, 26.57, 25.89, 20.34, 19.46.HRMS (ESI)m / zC 18 H 23 FNO3 + (M+H) +Theoretical value 320.16565, measured value 320.16599. I-161,3,3-trimethylbicyclo[2.2.1]heptane-2-yl-2-((4-chlorophenyl)amino)-2-oxoacetic acid ester, white solid, yield 76%, melting point 115.5~116.0℃.

[0051] 1 H NMR (400 MHz, CDCl3) δ 8.88 (s, 1H), 7.61 (d,J= 8.9 Hz, 2H), 7.34(d,J= 8.9 Hz, 2H), 4.53 (d,J= 2.0 Hz, 1H), 1.96 – 1.93 (m, 1H), 1.78 (s, 1H), 1.76 (s, 1H), 1.64 (d,J= 10.4 Hz, 1H), 1.51 (dd,J= 5.9, 4.0 Hz, 1H), 1.26 (s,1H), 1.20 (d,J= 12.7 Hz, 1H), 1.15 (s, 3H), 1.11 (s, 3H), 0.85 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.43, 153.96, 135.22, 130.61, 129.43,120.98, 90.30, 48.79, 48.42, 41.59, 40.04, 29.96, 26.59, 25.91, 20.37, 19.49.HRMS (ESI)m / zC 18 H 22 ClNO3Na + (M+Na) +理论值 358.11804, the measured value is 358.11810.I-171,3,3-trimethylbicyclo[2.2.1]heptane-2-yl 2-((4-bromophenyl)amino)-2-oxoacetic acid ester, colorless oily liquid, yield 66%.

[0052] 1H NMR (400 MHz, CDCl3) δ 8.87 (s, 1H), 7.56 (d,J= 8.9 Hz, 2H), 7.49 (d,J= 9.0 Hz, 2H), 4.53 (d,J= 2.1 Hz, 1H), 1.93 (d,J= 6.1 Hz, 1H), 1.79 (s,1H), 1.75 (d,J= 9.0 Hz, 1H), 1.62 (s, 1H), 1.53 – 1.49 (m, 1H), 1.26 (s, 1H),1.19 (s, 1H), 1.15 (s, 3H), 1.11 (s, 3H), 0.85 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.27, 153.82, 135.56, 132.24, 121.14,118.14, 90.17, 48.64, 48.27, 41.44, 39.89, 29.80, 26.44, 25.75, 20.22, 19.33.HRMS (ESI)m / zC 18 H 22 BrNO3Na + (M+Na) + Theoretical values ​​402.06753 and 404.06603, measured values ​​402.06787 and 404.06561. I-181,3,3-trimethylbicyclo[2.2.1]heptane-2-yl 2-((4-iodophenyl)amino)-2-oxoacetic acid ester, white solid, yield 81%, melting point 120.0~120.5℃.

[0053] 1 H NMR (400 MHz, CDCl3) δ 8.87 (s, 1H), 7.68 (d,J= 8.9 Hz, 2H), 7.43(d,J= 8.9 Hz, 2H), 4.52 (d,J= 2.0 Hz, 1H), 1.96 – 1.91 (m, 1H), 1.79 (s, 1H), 1.76 (s, 1H), 1.63 (d,J= 10.5 Hz, 1H), 1.54 – 1.49 (m, 1H), 1.27 (d,J= 8.8Hz, 1H), 1.20 (d,J= 11.1 Hz, 1H), 1.15 (s, 3H), 1.10 (s, 3H), 0.85 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 161.41, 153.99, 138.33, 136.41, 121.54,90.31, 89.05, 48.78, 48.41, 41.59, 40.04, 29.95, 26.58, 25.91, 20.37, 19.49.HRMS (ESI)m / zC 18 H 22 INO3Na + (M+Na) + Theoretical value 450.05366, measured value 450.05374. I-191,3,3-trimethylbicyclo[2.2.1]heptane-2-yl-2-oxo-2-((4-(trifluoromethyl)phenyl)amino)acetic acid ester, white solid, yield 62%, melting point 99.5~100℃.

[0054] 1 H NMR (400 MHz, CDCl3) δ 8.87 (s, 1H), 7.56 (d,J= 9.0 Hz, 2H), 7.49 (d,J= 8.9 Hz, 2H), 4.53 (s, 1H), 1.93 (d,J= 6.4 Hz, 1H), 1.79 (s, 1H), 1.75(d,J= 9.0 Hz, 1H), 1.64 (d,J= 8.4 Hz, 1H), 1.52 (d,J= 4.0 Hz, 1H), 1.28 (d,J=8.8 Hz, 1H), 1.20 (d,J= 11.4 Hz, 1H), 1.15 (s, 3H), 1.11 (s, 3H), 0.85 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.42, 153.96, 136.47, 129.19, 125.36,19.66, 83.87, 49.26, 48.10, 44.84, 36.27, 27.88, 26.97, 19.66, 18.83, 13.49.HRMS (ESI)m / zC 19 H 22 F3NO3Na + (M+Na) + Theoretical value 392.14434, measured value 392.14432.I-201,3,3-trimethylbicyclo[2.2.1]heptane-2-yl 2-((4-cyanophenyl)amino)-2-oxoacetic acid ester, white solid, yield 73%, melting point 156.2~156.7℃.

[0055] 1 H NMR (400 MHz, CDCl3) δ 9.09 (s, 1H), 7.79 (d,J= 8.9 Hz, 2H), 7.67(d,J= 8.9 Hz, 2H), 4.53 (d,J= 2.1 Hz, 1H), 1.94 – 1.89 (m, 1H), 1.79 (d,J=4.3 Hz, 1H), 1.75 (d,J= 3.3 Hz, 1H), 1.62 (s, 1H), 1.54 – 1.47 (m, 1H), 1.28 (d,J= 10.4 Hz, 1H), 1.20 (d,J= 11.1 Hz, 1H), 1.14 (s, 3H), 1.10 (s, 3H), 0.84(s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.05, 154.26, 140.48, 133.58, 119.89,118.59, 108.68, 90.66, 48.78, 48.38, 41.56, 40.05, 29.93, 26.55, 25.87,20.34, 19.46.HRMS (ESI)m / zC 19 H 22 N2O3Na + (M+Na) + Theoretical value 349.15226, measured value 349.15225. I-211,3,3-trimethylbicyclo[2.2.1]heptane-2-yl 2-((4-nitrophenyl)amino)-2-oxoacetic acid ester, white solid, yield 73%, melting point 140.2~140.7℃.

[0056] 1H NMR (400 MHz, CDCl3) δ 9.18 (s, 1H), 8.27 (d,J= 9.2 Hz, 2H), 7.84(d,J= 9.2 Hz, 2H), 4.54 (d,J= 2.1 Hz, 1H), 1.92 (d,J= 9.2 Hz, 1H), 1.80 (s,1H), 1.76 (d,J= 3.3 Hz, 1H), 1.65 (s, 1H), 1.52 (d,J= 9.9 Hz, 1H), 1.28 (s,1H), 1.21 (d,J= 12.6 Hz, 1H), 1.15 (s, 3H), 1.11 (s, 3H), 0.86 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.01, 154.28, 144.58, 142.15, 125.36,119.58, 90.78, 48.82, 48.40, 41.57, 40.09, 29.96, 26.57, 25.89, 20.37, 19.48.HRMS (ESI) m / z C 18 H 22 N2O5Na + (M+Na) + Theoretical value 369.14209, measured value 369.14209. I-221,3,3-trimethylbicyclo[2.2.1]heptane-2-yl 2-((2-chloro-4-nitrophenyl)amino)-2-oxoacetic acid ester, white solid, yield 75%, melting point 99.5~100.0℃.

[0057] 1 H NMR (400 MHz, CDCl3) δ 9.73 (s, 1H), 8.73 (d,J= 9.2 Hz, 1H), 8.34(s, 1H), 8.22 (d,J= 9.2 Hz, 1H), 4.57 (s, 1H), 1.92 (d,J= 6.5 Hz, 1H), 1.81(s, 1H), 1.77 (d,J= 3.3 Hz, 1H), 1.66 (d,J= 10.5 Hz, 1H), 1.53 (t,J= 4.9 Hz,1H), 1.31 (s, 1H), 1.23 (d,J= 14.3 Hz, 1H), 1.16 (s, 3H), 1.12 (s, 3H), 0.87(s, 3H). 13C NMR (101 MHz, CDCl3) δ 161.71, 153.81, 140.11, 134.34, 129.27,119.68, 90.02, 48.78, 48.44, 41.61, 40.03, 37.62, 29.96, 26.62, 25.93, 24.63,20.37, 19.50, 13.86.HRMS (ESI)m / zC 18 H 21 ClN2O5Na + (M+Na) + Theoretical value 403.10312, measured value 403.10324. I-231,3,3-trimethylbicyclo[2.2.1]heptane-2-yl-2-(benzylamino)-2-oxoacetic acid ester, white solid, yield 43%, melting point 101.7~102.2℃.

[0058] 1 H NMR (400 MHz, CDCl3) δ 7.38 (s, 1H), 7.34 (d,J= 0.9 Hz, 2H), 7.32(d,J= 2.8 Hz, 2H), 7.30 (d,J= 1.7 Hz, 1H), 4.52 (d,J= 3.8 Hz, 2H), 4.48 (d,J=2.1 Hz, 1H), 1.93 – 1.87 (m, 1H), 1.76 (d,J= 4.0 Hz, 1H), 1.74 (d,J= 6.2 Hz,1H), 1.62 (dt,J= 10.5, 2.1 Hz, 1H), 1.49 (tdd,J= 12.6, 5.8, 4.1 Hz, 1H), 1.25(d, J = 8.8 Hz, 1H), 1.17 (d,J= 12.7 Hz, 1H), 1.12 (s, 3H), 1.08 (s, 3H,10), 0.83 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.30, 156.62, 137.02, 129.03, 128.11,128.07, 89.61, 48.71, 48.43, 44.09, 41.61, 39.96, 29.93, 26.65, 25.94, 20.38,19.52.HRMS (ESI) m / z C 19 H 25 NO3Na + (M+Na)+理论值 338.17266, measured value 338.17270.I-241,3,3-trimethylbicyclo[2.2.1]heptane-2-yl-2-((4-methylbenzyl)amino)-2-oxoacetic acid ester, white solid, yield 78%, melting point 91.5~92.0℃.

[0059] 1 H NMR (400 MHz, CDCl3) δ 7.31 (s, 1H), 7.19 (s, 2H), 7.15 (s, 2H), 4.48 (s, 1H), 4.47 (d,J= 2.1 Hz), 2.34 (s, 3H), 1.92 – 1.88 (m, 1H), 1.76 (s,1H), 1.72 (d,J= 9.2 Hz, 1H), 1.60 (d,J= 3.3 Hz, 1H), 1.51 – 1.47 (m, 1H), 1.26 (s, 1H), 1.16 (d,J= 12.6 Hz, 1H), 1.12 (s, 3H), 1.08 (s, 3H), 0.82 (s,3H). 13 C NMR (101 MHz, CDCl3) δ 161.28, 156.53, 137.79, 133.98, 129.64,128.08, 89.51, 48.67, 48.40, 43.82, 41.58, 39.92, 29.89, 26.61, 25.91, 21.24,20.34, 19.48.HRMS (ESI)m / zC 20 H 27 NO3Na + (M+Na) + Theoretical value 352.18831, measured value 352.18817.I-251,3,3-trimethylbicyclo[2.2.1]heptane-2-yl 2-((1H-pyrrolo-1-yl)amino)-2-oxoacetate, white solid, yield 79%, melting point 123.5~124.0℃.

[0060] 1H NMR (400 MHz, CDCl3) δ 9.39 (s, 1H), 6.70 (t,J= 2.3 Hz, 2H), 6.22(t,J= 2.3 Hz, 2H), 4.55 (d,J= 2.1 Hz, 1H), 1.90 – 1.86 (m, 1H), 1.79 (d,J=3.8 Hz, 1H), 1.75 (d,J= 3.3 Hz, 1H), 1.64 (d,J= 8.8 Hz, 1H), 1.53 – 1.48 (m,1H), 1.28 (d,J= 8.8 Hz, 1H), 1.19 (d,J= 11.2 Hz, 1H), 1.15 (s, 3H), 1.12 (s, 3H), 0.87 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 159.86, 155.25, 121.21, 108.47, 90.45,48.78, 48.38, 41.57, 40.04, 29.91, 26.58, 25.88, 20.42, 19.50.HRMS (ESI) m / z C 16 H 23 N3O3Na + (M+Na) + Theoretical value 328.16316, measured value 328.16336. I-26(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl-2-oxo-2-(phenylamino)oxoacetic acid ester, white solid, yield 72%, melting point 67.9~68.4℃.

[0061] 1 H NMR (400 MHz, CDCl3) δ 8.94 (s, 1H), 7.66 (d,J= 7.6 Hz, 2H), 7.38 –7.34 (m, 2H), 7.17 (t,J= 7.5 Hz, 1H), 5.06 (ddd,J= 10.0, 3.5, 2.1 Hz, 1H),2.43 – 2.39 (m, 1H), 2.14 (q,J= 3.4 Hz, 1H), 1.79 (d,J= 3.3 Hz, 1H), 1.74 (s,1H), 1.42 (s, 1H), 1.36 (s, 1H), 1.15 (d,J= 10.4 Hz, 1H), 0.94 (s, 2H), 0.91(s, 2H), 0.90 (s, 2H).13 C NMR (101 MHz, CDCl3) δ 161.56, 154.13, 136.64, 129.30, 125.47,119.83, 119.75, 83.96, 49.38, 48.22, 44.96, 36.39, 28.01, 27.09, 19.79,18.95, 13.61.HRMS (ESI)m / zC 18 H 23 NO3Na + (M+Na) + Theoretical value 324.15701, measured value 324.15701. I-27(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl-2-oxo-2-(o-toluidine)oxoacetate, white solid, yield 83%, melting point 70.9~71.4℃.

[0062] 1 H NMR (400 MHz, CDCl3) δ 8.85 (s, 1H), 8.12 (d,J= 6.7 Hz, 1H), 7.26 (d,J= 7.6 Hz, 1H), 7.23 – 7.20 (m, 1H), 7.12 (d,J= 8.9 Hz, 1H), 5.08 (ddd,J=10.0, 3.5, 2.1 Hz, 1H), 2.48 – 2.41 (m, 1H), 2.33 (s, 3H), 2.16 – 2.09 (m,1H), 1.81 (d,J= 3.3 Hz, 1H), 1.76 (t,J= 4.5 Hz, 1H), 1.42 (d,J= 15.7 Hz, 1H), 1.34 (d,J= 4.3 Hz, 1H), 1.18 (dd,J= 13.9, 3.5 Hz, 1H), 0.95 (s, 3H), 0.92 (s,3H), 0.92 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.51, 153.98, 134.74, 130.66, 127.86,127.19, 125.71, 121.32, 84.02, 49.38, 48.22, 44.98, 36.46, 28.04, 27.15,19.80, 18.95, 17.56, 13.65.HRMS (ESI)m / zC 19 H 25 NO3Na+ (M+Na) + Theoretical value 338.17266, measured value 338.17322. I-28(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl-2-oxo-2-(m-toluidine)oxoacetate, pale yellow solid, yield 88%, melting point 113.4~113.9℃.

[0063] 1 H NMR (400 MHz, CDCl3) δ 8.84 (s, 1H), 7.50 (s, 1H), 7.43 (d,J= 5.5Hz, 1H), 7.25 (t,J= 7.8 Hz, 1H), 6.99 (d,J= 6.7 Hz, 1H), 5.06 (ddd,J= 9.9,3.5, 2.1 Hz, 1H), 2.46 – 2.40 (m, 1H), 2.36 (s, 3H), 2.17 – 2.10 (m, 1H),1.79 (d,J= 3.3 Hz, 1H), 1.75 (t,J= 4.5 Hz, 1H), 1.40 (d,J= 13.2 Hz, 1H), 1.36– 1.32 (m, 1H), 1.15 (dd,J= 13.9, 3.4 Hz, 1H), 0.94 (s, 3H), 0.91 (s, 3H), 0.91 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.58, 154.09, 139.30, 136.54, 129.13,126.31, 120.45, 116.92, 83.92, 49.40, 48.23, 44.99, 36.43, 28.02, 27.11,21.59, 19.80, 18.98, 13.62.HRMS (ESI)m / zC 19 H 25 NO3Na + (M+Na) + Theoretical value 338.17266, measured value 338.17270. I-29(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl-2-oxo-2-(p-toluidine)oxoacetate, white solid, yield 83%, melting point 99.6~100.1℃.

[0064] 1H NMR (400 MHz, CDCl3) δ 8.81 (s, 1H), 7.53 (d,J= 8.4 Hz, 2H), 7.17(d,J= 8.3 Hz, 2H), 5.08 – 5.05 (m, 1H), 2.46 – 2.41 (m, 1H), 2.34 (s, 3H),2.17 – 2.11 (m, 1H), 1.79 (s, 1H), 1.75 (d,J= 4.5 Hz, 1H), 1.36 (d,J= 6.6 Hz,1H), 1.16 (dd,J= 13.9, 3.5 Hz, 1H), 0.95 (s, 3H), 0.91 (s, 3H), 0.91 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.67, 153.98, 135.27, 134.13, 129.85,119.77, 83.93, 49.41, 48.25, 45.01, 36.44, 28.05, 27.13, 21.10, 19.83, 19.00,13.65.HRMS (ESI)m / zC 19 H 25 NO3Na + (M+Na) + Theoretical value 338.17266, measured value 338.17297. I-30(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl-2-((2-ethylphenyl)amino)-2-oxoacetic acid ester, pale red solid, yield 82%, melting point 112.5~113.0℃.

[0065] 1H NMR (400 MHz, CDCl3) δ 8.93 (s, 1H), 8.11 (s, 1H), 7.28 (s, 1H), 7.19 (s, 1H), 7.17 (s, 1H), 5.09 (dt,J= 9.9, 2.6 Hz, 1H), 2.73 (s, 2H), 2.67(s, 1H), 2.50 – 2.42 (m, 1H), 2.17 – 2.08 (m, 1H), 1.81 (d,J= 3.9 Hz, 1H), 1.76 (t,J= 4.5 Hz, 1H), 1.58 (s, 1H), 1.31 (s, 3H), 1.16 (d,J= 3.4 Hz, 1H), 0.95 (s, 3H), 0.93 (s, 3H), 0.92 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 157.91, 134.41, 133.87, 129.08, 127.10,126.20, 121.62, 84.11, 49.40, 48.26, 45.01, 41.61, 36.52, 28.08, 27.20,24.44, 19.83, 18.98, 14.13, 14.10, 13.69.HRMS (ESI)m / zC 20 H 27 NO3Na + (M+Na) + Theoretical value 352.18831, measured value 352.18823. I-31(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl-2-((4-ethylphenyl)amino)-2-oxoacetic acid ester, white solid, yield 73%, melting point 70.9~71.4℃.

[0066] 1H NMR (400 MHz, CDCl3) δ 8.84 (s, 1H), 7.56 (d,J= 8.6 Hz, 2H), 7.20 (d,J= 7.8 Hz, 2H), 5.06 (ddd,J= 10.2, 3.5, 2.4 Hz, 1H), 2.63 (q,J= 7.6 Hz,2H), 2.47 – 2.39 (m, 1H), 2.16 – 2.09 (m, 1H), 1.79 (d,J= 3.3 Hz, 1H), 1.74(d,J= 4.4 Hz, 1H), 1.38 (s, 1H), 1.34 (s, 1H), 1.23 (t,J= 7.6 Hz, 3H), 1.16(dd,J= 13.9, 3.4 Hz, 1H), 0.95 (s, 3H), 0.91 (s, 3H), 0.91 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.67, 153.98, 141.67, 134.29, 128.66,119.85, 83.92, 49.41, 48.25, 45.00, 36.43, 28.50, 28.04, 27.13, 19.82, 18.99,15.67, 13.65.HRMS (ESI)m / zC 20 H 27 NO3Na + (M+Na) + Theoretical value 352.18831, measured value 352.18823. I-32(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl-2-oxo-2-((4-propylphenyl)amino)oxoacetate, yellow solid, yield 81%, melting point 165.5~166.0℃.

[0067] 1H NMR (400 MHz, CDCl3) δ 8.83 (s, 1H), 7.55 (d,J= 8.6 Hz, 2H), 7.17 (d,J= 8.6 Hz, 2H), 5.06 (ddd,J= 9.9, 3.4, 2.1 Hz, 1H), 2.59 – 2.55 (m, 2H),2.46 – 2.39 (m, 1H), 2.17 – 2.11 (m, 1H), 1.79 (d,J= 3.3 Hz, 1H), 1.75 (t,J=4.5 Hz, 1H), 1.66 – 1.61 (m, 2H), 1.43 – 1.37 (m, 1H), 1.36 – 1.30 (m, 1H),1.16 (dd,J= 13.9, 3.5 Hz, 1H), 0.95 (s, 3H), 0.93 (s, 3H), 0.91 (s, 3H), 0.91(s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.67, 153.98, 140.11, 134.31, 129.25,119.76, 83.91, 49.40, 48.24, 45.00, 37.62, 36.42, 28.04, 27.12, 24.62, 19.82,18.98, 13.87, 13.64.HRMS (ESI)m / zC 21 H 29 NO3Na + (M+Na) + Theoretical value 366.20396, measured value 366.20401. I-33(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl 2-((4-(tert-butyl)phenyl)amino)-2-oxoacetic acid ester, pale pink solid, yield 78%, melting point 63.2~63.7℃.

[0068] 1H NMR (400 MHz, CDCl3) δ 8.85 (s, 1H), 7.57 (d,J= 8.9 Hz, 2H), 7.38 (d,J= 8.8 Hz, 2H), 5.07 (ddd,J= 10.0, 3.5, 2.1 Hz, 1H), 2.48 – 2.39 (m, 1H), 2.18 – 2.10 (m, 1H), 1.84 – 1.76 (m, 1H), 1.75 (t,J= 4.5 Hz, 1H), 1.41 (d,J=8.8 Hz, 1H), 1.37 – 1.34 (m, 1H), 1.31 (s, 9H), 1.16 (dd,J= 13.9, 3.4 Hz,1H), 0.95 (s, 3H), 0.91 (s, 3H), 0.91 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.69, 154.00, 148.60, 134.04, 126.18,119.54, 83.95, 49.42, 48.26, 45.01, 36.44, 34.65, 31.46, 28.05, 27.14, 19.83,19.01, 13.66.HRMS (ESI)m / zC 22 H 31 NO3Na + (M+Na) + Theoretical value 380.21961, measured value 380.21970. I-34(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl-2-((4-methoxyphenyl)amino)-2-oxoacetic acid ester, white solid, yield 82%, melting point 131.4~131.9℃.

[0069] 1H NMR (400 MHz, CDCl3) δ 8.77 (s, 1H), 7.57 (d,J= 9.0 Hz, 2H), 6.90 (d,J= 9.2 Hz, 2H), 5.08 – 5.04 (m, 1H), 3.81 (s, 3H), 2.46 – 2.40 (m, 1H),2.16 – 2.11 (m, 1H), 1.84 – 1.77 (m, 1H), 1.74 (d,J= 4.5 Hz, 1H), 1.41 (d,J=11.6 Hz, 1H), 1.36 (d,J= 2.2 Hz, 1H), 1.18 – 1.13 (m, 1H), 0.95 (s, 3H), 0.91 (s, 3H), 0.91 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.73, 157.21, 153.88, 129.85, 121.36,114.47, 83.90, 55.62, 49.41, 48.25, 45.01, 36.43, 28.05, 27.14, 19.82, 18.99,13.65.HRMS (ESI)m / zC 19 H 25 NO4Na + (M+Na) + Theoretical value 354.16758, measured value 354.16754. I-35(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl-2-((4-ethoxyphenyl)amino)-2-oxoacetic acid ester, white solid, yield 77%, melting point 113.4~113.9℃.

[0070] 1H NMR (400 MHz, CDCl3) δ 8.77 (s, 1H), 7.56 (d,J= 9.2 Hz, 2H), 6.89 (d,J= 9.2 Hz, 2H), 5.08 – 5.04 (m, 1H), 4.03 (q,J= 7.0 Hz, 2H), 2.43 (td,J=9.4, 4.3 Hz, 1H), 2.16 – 2.09 (m, 1H), 1.79 (q,J= 4.4 Hz, 1H), 1.75 (d,J= 4.5Hz, 1H), 1.41 (t,J= 7.0 Hz, 3H), 1.36 (s, 1H), 1.34 (d,J= 4.8 Hz, 1H), 1.21 –1.13 (m, 1H), 0.94 (s, 3H), 0.91 (s, 3H), 0.90 (s, 3H).

[0071] 13 C NMR (101 MHz, CDCl3) δ 161.74, 156.59, 153.85, 129.71, 121.33,115.03, 83.86, 63.83, 49.41, 48.25, 45.01, 36.43, 28.04, 27.13, 19.82, 18.99,14.95, 13.65.

[0072] HRMS theoretical value C 20 H 27 NO4Na + (M+Na) + 368.18323, the measured value is 368.18298.

[0073] I-36(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl-2-((4-fluorophenyl)amino)-2-oxoacetic acid ester, white solid, yield 71%, melting point 142.9~143.4℃.

[0074] 1H NMR (400 MHz, CDCl3) δ 8.86 (s, 1H), 7.65 – 7.61 (m, 2H), 7.09 –7.04 (m, 2H), 5.07 (ddd,J= 10.0, 3.5, 2.1 Hz, 1H), 2.46 – 2.39 (m, 1H), 2.14– 2.08 (m, 1H), 1.86 – 1.77 (m, 1H), 1.76 (d,J= 4.5 Hz, 1H), 1.41 (d,J= 11.6Hz, 1H), 1.33 (d,J= 12.2 Hz, 1H), 1.15 (dd,J= 13.9, 3.5 Hz, 1H), 0.95 (s,3H), 0.91 (s, 3H), 0.90 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.51, 158.82, 154.12, 132.74, 121.54,116.21, 84.12, 49.42, 48.26, 44.99, 36.42, 28.04, 27.11, 19.81, 18.98, 13.64.HRMS (ESI)m / zC 18 H 22 FNO3Na + (M+Na) +理论值 342.14759, measured value 342.14780. I-37(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl-2-((4-chlorophenyl)amino)-2-oxoacetic acid ester, white solid, yield 82%, melting point 153.6~154.1℃.

[0075] 1H NMR (400 MHz, CDCl3) δ 8.86 (s, 1H), 7.61 (d,J= 8.9 Hz, 2H), 7.34 (d,J= 8.9 Hz, 2H), 5.07 (ddd,J= 10.0, 3.5, 2.1 Hz, 1H), 2.47 – 2.41 (m, 1H),2.12 (dd,J= 8.7, 4.4 Hz, 1H), 1.80 (d,J= 3.2 Hz, 1H), 1.76 (d,J= 4.6 Hz, 1H),1.41 (d,J= 13.3 Hz, 1H), 1.34 (d,J= 4.8 Hz, 1H), 1.15 (dd,J= 13.9, 3.5 Hz,1H), 0.95 (s, 3H), 0.91 (s, 3H), 0.91 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.38, 154.12, 135.20, 130.65, 129.45,121.05, 84.23, 49.44, 48.28, 45.00, 36.44, 28.05, 27.13, 19.82, 19.00, 13.65.HRMS (ESI)m / zC 18 H 22 ClNO3Na + (M+Na) +理论值 358.11804, determined value 358.11807.I-38(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl-2-((4-bromophenyl)amino)-2-oxoacetic acid ester, white solid, yield 86%, melting point 152.3~152.8℃.

[0076] 1H NMR (400 MHz, CDCl3) δ 8.88 (s, 1H), 7.56 (d,J= 9.0 Hz, 2H), 7.49 (d,J= 8.9 Hz, 2H), 5.06 (ddd,J= 10.0, 3.5, 2.2 Hz, 1H), 2.46 – 2.40 (m, 1H), 2.15 – 2.08 (m, 1H), 1.80 (d,J= 3.2 Hz, 1H), 1.75 (s, 1H), 1.40 (d,J= 9.4 Hz,1H), 1.34 – 1.29 (m, 1H), 1.15 (dd,J= 13.9, 3.4 Hz, 1H), 0.94 (s, 3H), 0.91(s, 3H), 0.90 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.36, 154.14, 135.70, 132.38, 121.36, 118.31, 84.23, 49.43, 48.27, 44.98, 36.42, 28.04, 27.11, 19.81, 18.98, 13.64. HRMS (ESI) m / z theoretical value C 18 H 22 BrNO3Na + (M+Na) + Theoretical values ​​402.06753 and 404.06603, measured values ​​402.06775 and 404.06558. I-39(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl-2-oxo-2-((4-(trifluoromethyl)phenyl)amino)oxoacetate, white solid, yield 72%, melting point 129.5~130.0℃.

[0077] 1H NMR (400 MHz, CDCl3) δ 9.03 (s, 1H), 7.78 (d,J= 8.4 Hz, 2H), 7.64 (d,J= 8.6 Hz, 2H), 5.07 (ddd,J= 9.9, 3.4, 2.1 Hz, 1H), 2.47 – 2.41 (m, 1H),2.15 – 2.09 (m, 1H), 1.80 (d,J= 3.3 Hz, 1H), 1.77 (s, 1H), 1.15 (dd,J= 13.9,3.5 Hz, 1H), 0.95 (s, 3H), 0.91 (s, 3H), 0.91 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.21, 154.39, 139.59, 126.67, 126.63, 84.42, 49.45, 48.28, 44.99, 36.43, 28.04, 27.11, 19.80, 18.98, 13.64.HRMS (ESI)m / zC 19 H 22 F3NO3Na + (M+Na) + Theoretical value 392.14440, measured value 392.14432.I-40(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl-2-oxo-2-((perfluorophenyl)amino)oxoacetic acid ester, white solid, yield 84%, melting point 172.4~172.9℃.

[0078] 1 H NMR (400 MHz, CDCl3) δ 8.48 (s, 1H), 5.08 (d,J= 4.5 Hz, 1H), 2.44(d,J= 4.2 Hz, 1H), 2.08 (s, 1H), 1.81 (d,J= 4.2 Hz, 1H), 1.76 (s, 1H), 1.39(s, 1H), 1.33 (s, 1H), 1.18 (s, 1H), 0.94 (s, 3H), 0.91 (s, 3H), 0.91 (s,3H). 13C NMR (101 MHz, CDCl3) δ 159.98, 154.60, 144.15, 141.64, 139.33,136.80, 84.78, 49.43, 48.29, 44.97, 36.38, 28.01, 27.07, 19.80, 18.94, 13.63.HRMS (ESI)m / zC 18 H 18 F5NO3Na + (M+Na) + Theoretical value 414.10991, measured value 414.10974. I-41(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl-2-((4-cyanophenyl)amino)-2-oxoacetic acid ester, white solid, yield 77%, melting point 131.2~131.7℃.

[0079] 1 H NMR (400 MHz, CDCl3) δ 9.03 (s, 1H), 7.78 (d,J= 8.9 Hz, 2H), 7.68 (d,J= 8.9 Hz, 2H), 5.08 (ddd,J= 9.9, 3.4, 2.1 Hz, 1H), 2.49 – 2.41 (m, 1H), 2.10 (dd,J= 8.6, 4.5 Hz, 1H), 1.81 (d,J= 3.2 Hz, 1H), 1.76 (d,J= 4.4 Hz, 1H), 1.42 (d,J= 11.0 Hz, 1H), 1.34 (d,J= 2.1 Hz, 1H), 1.15 (dd,J= 14.0, 3.5 Hz,1H), 0.95 (s, 3H), 0.92 (s, 3H), 0.91 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.00, 154.37, 140.43, 133.62, 119.90,118.59, 108.77, 84.64, 49.48, 48.31, 44.98, 36.43, 28.05, 27.11, 19.81,18.99, 13.65.HRMS (ESI) m / z C 19 H 22 N2O3 + (M+Na) +Theoretical value 349.15351, measured value 349.15189.I-42(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl-2-((4-nitrophenyl)amino)-2-oxoacetic acid ester, white solid, yield 77%, melting point 138.5~139.0℃.

[0080] 1 H NMR (400 MHz, CDCl3) δ 9.13 (s, 1H), 8.28 (d,J= 9.2 Hz, 2H), 7.84 (d,J= 9.2 Hz, 2H), 5.09 (ddd,J= 9.9, 3.5, 2.1 Hz, 1H), 2.48 – 2.43 (m, 1H),2.15 – 2.09 (m, 1H), 1.82 (d,J= 3.3 Hz, 1H), 1.78 (d,J= 4.4 Hz, 1H), 1.42 (d,J= 11.1 Hz, 1H), 1.33 (d,J= 9.5 Hz, 1H), 1.16 (dd,J= 14.0, 3.5 Hz, 1H), 0.96(s, 3H), 0.92 (s, 3H), 0.91 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.01, 154.28, 144.59, 142.14, 125.37,119.58, 90.79, 48.82, 48.41, 41.58, 40.09, 29.96, 26.57, 25.90, 20.37, 19.48.HRMS (ESI)m / zC 18 H 22 N2O5Na + (M+Na) + Theoretical value 369.14209, measured value 369.14212. I-43(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl-2-((2-chloro-4-nitrophenyl)amino)-2-oxoacetic acid ester, white solid, yield 51%, melting point 100.3~100.8℃.

[0081] 1H NMR (400 MHz, CDCl3) δ 9.75 (s, 1H), 8.74 (d,J= 9.2 Hz, 1H), 8.35 (d,J= 2.6 Hz, 1H), 8.23 ​​(dd,J= 9.2, 2.6 Hz, 1H), 5.11 (ddd,J= 10.0, 3.5, 2.2Hz, 1H), 2.51 – 2.44 (m, 1H), 2.09 (dd,J= 8.6, 4.6 Hz, 1H), 1.83 (d,J= 3.3Hz, 1H), 1.78 (t,J= 4.5 Hz, 1H), 1.45 (d,J= 11.6 Hz, 1H), 1.34 (d,J= 4.8 Hz,1H), 1.17 (dd,J= 13.9, 3.4 Hz, 1H), 0.96 (s, 3H), 0.93 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 160.40, 154.71, 144.39, 139.38, 125.37,124.19, 123.81, 120.54, 85.29, 49.79, 48.63, 45.29, 36.82, 28.38, 27.49,20.12, 19.29, 13.98.HRMS (ESI)m / zC 18 H 21 ClN2O5Na + (M+Na) + Theoretical value 403.10312, measured value 403.10327. I-44(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl-2-([1,1'-biphenyl]-4-amino)-2-oxoacetic acid ester, white solid, yield 83%, melting point 107.5~108.0℃.

[0082] 1H NMR (400 MHz, CDCl3) δ 8.93 (s, 1H), 7.73 (d,J= 8.6 Hz, 2H), 7.62(s, 2H), 7.59 (d,J= 7.0 Hz, 2H), 7.46 – 7.42 (m, 2H), 7.34 (t,J= 7.3 Hz, 1H), 5.09 (ddd,J= 10.0, 3.5, 2.1 Hz, 1H), 2.47 – 2.42 (m, 1H), 2.15 (dd,J= 8.6,4.6 Hz, 1H), 1.84 – 1.80 (m, 1H), 1.76 (s, 1H), 1.41 (d,J= 11.0 Hz, 1H), 1.37– 1.32 (m, 1H), 1.18 (dd,J= 13.9, 3.5 Hz, 1H), 0.96 (s, 3H), 0.92 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 161.56, 154.12, 140.35, 138.41, 135.77,128.98, 127.96, 127.51, 127.04, 120.15, 120.07, 84.11, 49.45, 48.28, 45.02,36.45, 28.06, 27.15, 19.84, 19.01, 13.67.HRMS (ESI)m / zC 24 H 27 NO3Na + (M+Na) + Theoretical value 400.18831, measured value 400.18829. I-45(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl-2-(benzylamino)-2-oxoacetic acid ester, white solid, yield 81%, melting point 102.2~102.7℃.

[0083] 1H NMR (400 MHz, CDCl3) δ 7.37 (s, 1H), 7.35 (d,J= 5.6 Hz, 2H), 7.31 (d,J= 3.9 Hz, 2H), 5.01 (ddd,J= 10.0, 3.5, 2.1 Hz, 1H), 4.52 (dd,J= 6.1, 2.4Hz, 2H), 2.42 – 2.37 (m, 1H), 2.09 (s, 1H), 1.78 (s, 1H), 1.72 (s, 1H), 1.37(d,J= 13.3 Hz, 1H), 1.31 (d,J= 12.1 Hz, 1H), 1.11 (d,J= 10.4 Hz, 1H), 0.92(s, 3H), 0.89 (s, 3H), 0.88 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 161.28, 156.53, 137.79, 133.98, 129.64,128.08, 89.51, 48.67, 48.40, 43.82, 43.69, 41.58, 39.92, 29.89, 26.61, 25.91,21.24, 20.34, 19.48.HRMS (ESI)m / zC 19 H 25 NO3Na + (M+Na) + Theoretical value 338.17321, measured value 338.17120. I-46(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl 2-((1H-pyrrolo-1-yl)amino)-2-oxoacetic acid ester, white solid, yield 83%, melting point 142.0-147.0℃.

[0084] 1H NMR (400 MHz, CDCl3) δ 9.38 (s, 1H), 6.69 (t,J= 2.3 Hz, 2H), 6.22(t,J= 2.3 Hz, 2H), 5.08 (ddd,J= 9.9, 3.5, 2.1 Hz, 1H), 2.44 (d,J= 4.2 Hz,1H), 2.06 (qd,J= 8.3, 4.7 Hz, 1H), 1.85 – 1.78 (m, 1H), 1.76 (s, 1H), 1.44 –1.37 (m, 1H), 1.35 – 1.28 (m, 1H), 1.16 (dd,J= 14.0, 3.5 Hz, 1H), 0.94 (s,3H), 0.91 (s, 3H), 0.91 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 159.85, 155.36, 121.19, 108.52, 84.43, 49.41, 48.30, 44.97, 36.41, 28.03, 27.11, 19.81, 18.97, 13.65. HRMS (ESI) m / z theoretical value C 16 H 23 N₂O₃(M+H) + 291.17032, the measured value is 291.17030. Example 4: Structural characterization of several compounds with Formula II structure. In this example, the compounds with Formula II structure are named in this invention using consecutive Arabic numerals.

[0085] II-11,3,3-Trimethylbicyclo[2.2.1]hept-2-ylN-[(4-methylphenyl)carbamoyl]carbamate, white solid, yield 63%, melting point 188.5-189.0℃.

[0086] 1H NMR (400 MHz, CDCl3) δ 9.79 (s, 1H), 7.88 (s, 1H), 7.41 (d,J= 8.6Hz, 2H), 7.12 (d,J= 8.1 Hz, 2H), 4.36 (d,J= 2.0 Hz, 1H), 2.32 (s, 3H), 1.77(s, 1H), 1.74 (s, 1H), 1.73 (d,J= 6.8 Hz, 1H), 1.72 – 1.66 (m, 1H), 1.62 (s,1H), 1.50 (d,J= 5.6 Hz, 1H), 1.23 (dd,J= 10.5, 1.7 Hz, 1H), 1.14 (s, 3H), 1.10 (s, 4H), 0.86 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 155.27, 151.56, 134.92, 133.68, 129.52, 120.09, 88.56, 48.55, 48.38, 41.42, 39.88, 29.84, 26.51, 25.86, 20.96, 20.20, 19.49. HRMS (ESI) m / z theoretical value C 19 H 27 N2O 3+ (M+H) + 331.20162, determined value 331.20151.II-21,3,3-trimethylbicyclo[2.2.1]hept-2-ylN-[(4-ethylphenyl)carbamoyl]carbamate, white solid, yield 57%, melting point 157.2-157.7℃.

[0087] 1H NMR (400 MHz, CDCl3) δ 9.79 (s, 1H), 7.81 (s, 1H), 7.43 (d,J= 8.6Hz, 2H), 7.14 (d,J= 8.7 Hz, 2H), 4.36 (d,J= 2.0 Hz, 1H), 2.62 (d,J= 7.6 Hz,2H), 1.77 (s, 1H), 1.76 (s, 1H), 1.74 (s, 1H), 1.70 (d,J= 8.7 Hz, 1H), 1.61(d,J= 10.4 Hz, 1H), 1.51 – 1.46 (m, 1H), 1.25 (d,J= 1.7 Hz, 1H), 1.22 (s,3H), 1.14 (s, 3H), 1.10 (s, 3H), 0.86 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 155.10, 151.17, 140.28, 135.01, 128.39, 120.31, 88.71, 48.54, 48.37, 41.42, 39.87, 29.84, 28.42, 26.55, 25.87, 20.19, 19.50, 15.81. HRMS (ESI) m / z theoretical value C 20 H 29 N2O3 + (M+H) + 345.21727, measured value 345.21674.II-31,3,3-trimethylbicyclo[2.2.1]hept-2-yl(4-biphenyl)urethane, white solid, yield 54%, melting point 174.7-175.2℃.

[0088] 1H NMR (400 MHz, CDCl3) δ 9.95 (s, 1H), 7.71 (s, 1H), 7.60 (s, 2H), 7.57 (s, 3H), 7.43 (s, 2H), 7.33 (t,J= 7.4 Hz, 2H), 4.38 (d,J= 2.0 Hz, 1H),1.78 (s, 1H), 1.75 (d,J= 2.4 Hz, 1H), 1.73 (s, 1H), 1.70 (s, 1H), 1.61 (d,J=8.2 Hz, 1H), 1.54 – 1.48 (m, 2H), 1.25 (d,J= 8.8 Hz, 1H), 1.16 (s, 3H), 1.11 (s, 3H), 0.88 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 155.09, 151.06, 140.71, 137.14, 136.75, 128.91, 127.73, 127.22, 127.00, 120.45, 88.91, 48.55, 48.37, 41.42, 39.89, 29.85, 26.57, 25.88, 20.21, 19.52. HRMS (ESI) m / z theoretical value C 24 H 28 N2O3Na + (M+Na) + 415.19921, the measured value is 415.19864.II-41,3,3-trimethylbicyclo[2.2.1]hept-2-yl(4-benzylphenyl)urethane, white solid, yield 50%, melting point 178.4-178.9℃.

[0089] 1H NMR (400 MHz, CDCl3) δ 9.78 (s, 1H), 7.43 (d,J= 8.6 Hz, 2H), 7.33(s, 1H), 7.29 (d,J= 7.0 Hz, 2H), 7.22 – 7.16 (m, 3H), 7.14 (d,J= 8.6 Hz, 2H), 4.35 (d,J= 2.0 Hz, 1H), 3.95 (s, 2H), 1.76 (d,J= 4.0 Hz, 1H), 1.71 (d,J= 2.6Hz, 1H), 1.67 (d,J= 4.2 Hz, 1H), 1.58 (s, 1H), 1.51 – 1.45 (m, 1H), 1.23 (d,J= 8.8 Hz, 1H), 1.14 (s, 3H), 1.09 (s, 3H), 0.85 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 154.85, 150.55, 141.27, 137.18, 135.39, 129.61, 129.01, 128.60, 126.22, 120.49, 88.96, 48.50, 48.34, 41.46, 39.83, 29.82, 26.56, 25.85, 20.17, 19.49. HRMS (ESI) m / z theoretical value 2(C 25 H 30 N2O3)Na + (M+Na) + 835.43845, the measured value is 835.44501.II-51,3,3-trimethylbicyclo[2.2.1]hept-2-ylN-[(4-fluorophenyl)carbamoyl]carbamate, white solid, yield 57%, melting point 175.4-175.9℃.

[0090] 1H NMR (400 MHz, CDCl3) δ 9.84 (s, 1H), 7.53 (s, 1H), 7.47 (d,J= 4.8Hz, 2H), 7.03 (d,J= 8.9 Hz, 2H), 4.36 (d,J= 2.0 Hz, 1H), 1.77 (d,J= 4.4 Hz,1H), 1.71 (t,J= 2.3 Hz, 1H), 1.69 (d,J= 6.4 Hz, 1H), 1.61 (d,J= 10.4 Hz, 1H), 1.51 (d,J= 7.0 Hz, 1H), 1.48 (s, 1H), 1.24 (d,J= 8.8 Hz, 1H), 1.14 (s, 3H),1.10 (s, 3H), 0.85 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 155.05, 151.10, 133.40, 121.88, 119.70, 115.85, 88.97, 48.53, 48.35, 41.39, 39.87, 29.82, 26.54, 25.84, 20.18, 19.49. HRMS (ESI) m / z theoretical value C 18 H 23 FN2O3Na + (M+Na) + 357.15849, the measured value is 357.15850.II-61,3,3-trimethylbicyclo[2.2.1]hept-2-yl(4-bromophenyl)urethane, brown solid, yield 60%, melting point 194.5-195.0℃.

[0091] 1 H NMR (400 MHz, CDCl3) δ 9.93 (s, 1H), 7.83 (s, 1H), 7.46 (s, 2H), 7.43 (s, 2H), 4.36 (s, 1H), 1.77 (d,J= 4.3 Hz, 1H), 1.73 (s, 1H), 1.71 (s,1H), 1.61 (d,J= 11.2 Hz, 1H), 1.52 (s, 1H), 1.43 (s, 1H), 1.24 (d,J= 10.4 Hz,1H), 1.14 (s, 3H), 1.10 (s, 3H), 0.86 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 154.95, 150.66, 136.55, 132.08, 121.68, 116.89, 89.15, 48.52, 48.34, 41.39, 39.86, 29.82, 26.55, 25.84, 20.18, 19.49. HRMS (ESI) m / z theoretical value C 18 H 23 BrN2O3Na + (M+Na) + 417.07842, the measured value is 417.07837.II-71,3,3-trimethylbicyclo[2.2.1]hept-2-yl(4-iodophenyl)urethane, brown solid, yield 57%, melting point 196.5-197.0℃.

[0092] 1 H NMR (400 MHz, CDCl3) δ 9.93 (s, 1H), 7.89 (s, 1H), 7.61 (d,J= 8.9Hz, 2H), 7.33 (d,J= 8.9 Hz, 2H), 4.36 (d,J= 2.0 Hz, 1H), 1.77 (d,J= 4.0 Hz,1H), 1.73 (d,J= 2.6 Hz, 1H), 1.71 (s, 1H), 1.62 (d,J= 1.8 Hz, 1H), 1.59 (s,1H), 1.53 – 1.48 (m, 1H), 1.24 (d,J= 8.7 Hz, 1H), 1.14 (s, 3H), 1.10 (s, 3H), 0.86 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 154.95, 150.66, 136.55, 132.08, 121.68, 116.89, 89.15, 48.52, 48.34, 41.39, 39.86, 29.82, 26.55, 25.84, 20.17, 19.48. HRMS (ESI) m / z theoretical value C 18 H 23 IN2O3Na + (M+Na) +465.06456, measured value 465.06440.II-81,3,3-trimethylbicyclo[2.2.1]hept-2-ylN-[(4-trifluoromethylphenyl)carbamoyl]carbamate, white solid, yield 51%, melting point 168.4-168.9℃.

[0093] 1 H NMR (400 MHz, CDCl3) δ 10.16 (s, 1H), 8.24 (s, 1H), 7.67 (d,J= 8.8Hz, 2H), 7.56 (d,J= 8.8 Hz, 2H), 4.37 (d,J= 2.0 Hz, 1H), 1.79 (s, 1H), 1.78(s, 1H), 1.74 (s, 1H), 1.72 (s, 1H), 1.61 (d,J= 8.7 Hz, 1H), 1.54 – 1.49 (m,1H), 1.25 (d,J= 8.8 Hz, 1H), 1.15 (s, 3H), 1.11 (s, 3H), 0.87 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 155.05, 150.99, 140.59, 126.38, 126.34, 119.70, 89.25, 48.55, 48.34, 41.39, 39.90, 29.82, 26.54, 25.82, 20.18, 19.48. HRMS (ESI) m / z theoretical value C 19 H 23 F3N2O3Na + (M+Na) + 407.15530, measured value 407.15470.II-91,3,3-trimethylbicyclo[2.2.1]hept-2-ylN-[(4-cyanophenyl)carbamoyl]carbamate, white solid, yield 45%, melting point 175.4-175.9℃.

[0094] 1H NMR (400 MHz, CDCl3) δ 10.22 (s, 1H), 7.67 (d,J= 8.9 Hz, 2H), 7.61 (d,J= 8.9 Hz, 2H), 4.37 (d,J= 2.0 Hz, 1H), 1.78 (d,J= 4.0 Hz, 1H), 1.74 (d,J=6.1 Hz, 1H), 1.71 (s, 1H), 1.67 (d,J= 8.8 Hz, 1H), 1.61 (d,J= 10.5 Hz, 1H), 1.50 (d,J= 5.5 Hz, 1H), 1.25 (d,J= 8.8 Hz, 1H), 1.15 (s, 3H), 1.10 (s, 3H), 0.85 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 155.06, 151.04, 141.59, 133.36, 119.93, 118.98, 107.24, 89.38, 48.55, 48.31, 41.36, 39.89, 29.80, 26.52, 25.81, 20.17, 19.46. HRMS (ESI) m / z theoretical value C 19 H 23 N3O3Na + (M+Na) + 364.16316, measured value 364.16268.II-10(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-ylN-[(4-methylphenyl)carbamoyl]carbamate, white solid, yield 64%, melting point 186.4-187.2℃.

[0095] 1H NMR (400 MHz, CDCl3) δ 9.80 (s, 1H), 7.94 (s, 1H), 7.40 (d,J= 8.4Hz, 2H), 7.11 (d,J= 8.4 Hz, 2H), 4.93 (ddd,J= 9.9, 3.5, 2.1 Hz, 1H), 2.40 (d,J= 3.9 Hz, 1H), 2.32 (s, 3H), 1.95 (d,J= 4.2 Hz, 1H), 1.79 (d,J= 3.4 Hz, 1H), 1.73 (t,J= 4.5 Hz, 1H), 1.36 (d,J= 4.0 Hz, 1H), 1.28 (d,J= 2.8 Hz, 1H), 1.12(dd,J= 13.8, 3.4 Hz, 1H), 0.93 (s, 3H), 0.91 (s, 3H), 0.89 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 155.03, 151.12, 134.87, 133.79, 129.60, 120.13, 82.71, 49.11, 48.09, 44.95, 36.65, 28.06, 27.03, 20.97, 19.84, 18.95, 13.59. HRMS (ESI) m / z theoretical value C 19 H 26 N2O3H + (M+H) + 331.20162, determined value 331.20112.II-11(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-ylN-[(4-ethylphenyl)carbamoyl]carbamate, white solid, yield 65%, melting point 156.7-157.2℃.

[0096] 1H NMR (400 MHz, CDCl3) δ 9.76 (s, 1H), 7.41 (d,J= 8.6 Hz, 2H), 7.23(s, 1H), 7.15 (d,J= 8.6 Hz, 2H), 4.95 – 4.90 (m, 1H), 2.61 (q,J= 7.5 Hz, 2H), 2.40 (d,J= 4.0 Hz, 1H), 1.87 (d,J= 3.8 Hz, 1H), 1.78 (d,J= 3.3 Hz, 1H), 1.74 (d,J= 4.4 Hz, 1H), 1.36 (d,J= 13.1 Hz, 1H), 1.27 (s, 1H), 1.22 (d,J= 7.6 Hz,3H), 1.11 (dd,J= 13.9, 3.5 Hz, 1H), 0.93 (s, 3H), 0.90 (s, 3H), 0.89 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 154.52, 150.36, 140.05, 134.64, 128.15, 120.02, 82.56, 48.78, 47.80, 44.61, 36.33, 28.11, 27.75, 26.75, 19.52, 18.63, 15.49, 13.30. HRMS (ESI) m / z theoretical value C 20 H 29 N2O3H + (M+H) + 345.21727, measured value 345.21650.II-12(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-ylN-[(biphenyl-4-yl)carbamoyl]carbamate, brown solid, yield 61%, melting point 188.4-191.4℃.

[0097] 1H NMR (400 MHz, CDCl3) δ 9.92 (s, 1H), 7.58 (s, 2H), 7.57 (s, 3H), 7.43 (t,J= 7.6 Hz, 2H), 7.35 – 7.30 (m, 2H), 4.95 (ddd,J= 9.9, 3.5, 2.1 Hz,1H), 2.42 (d,J= 3.7 Hz, 1H), 1.89 (t,J= 4.1 Hz, 1H), 1.79 (d,J= 3.4 Hz, 1H), 1.74 (t,J= 4.6 Hz, 1H), 1.38 (d,J= 12.8 Hz, 1H), 1.27 (d,J= 4.3 Hz, 1H), 1.13(d,J= 10.4 Hz, 1H), 0.94 (s, 3H), 0.91 (s, 3H), 0.90 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 154.73, 150.31, 140.69, 137.23, 136.67, 128.92, 127.81, 127.23, 127.01, 120.47, 83.15, 49.11, 48.15, 44.91, 36.66, 28.09, 27.09, 19.84, 18.95, 13.63. HRMS (ESI) m / z theoretical value C 24 H 28 N2O3Na + (M+Na) + 415.19921, determined value 415.19866.II-13(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-ylN-[(4-benzylphenyl)carbamoyl]carbamate, white solid, yield 57%, melting point 191.2-192.2℃.

[0098] 1H NMR (400 MHz, CDCl3) δ 9.94 (s, 1H), 7.61 (s, 1H), 7.59 (s, 3H), 7.57 (s, 2H), 7.54 (s, 1H), 7.44 (d,J= 7.3 Hz, 2H), 7.32 (d,J= 7.3 Hz, 1H), 4.96 – 4.93 (m, 1H), 4.01 (d,J= 9.9 Hz, 2H), 1.88 (d,J= 3.5 Hz, 1H), 1.75 (d,J= 4.3 Hz, 1H), 1.62 (d,J= 4.5 Hz, 1H), 1.28 (d,J= 2.4 Hz, 1H), 1.13 (d,J=10.4 Hz, 1H), 0.94 (s, 3H), 0.90 (s, 3H), 0.86 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 154.81, 150.51, 140.70, 137.21, 136.70, 128.92, 127.80, 127.23, 127.00, 120.45, 83.08, 49.64, 49.12, 48.14, 45.24, 39.18, 28.43, 26.05, 20.34, 18.82, 13.47. HRMS (ESI) m / z theoretical value 2(C 25 H 30 N2O3)Na + (M+Na) + 835.44051, the measured value is 835.43839.II-14(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-ylN-[(4-fluorophenyl)carbamoyl]carbamate, white solid, yield 58%, melting point 174.7-175.2℃.

[0099] 1H NMR (400 MHz, CDCl3) δ 9.87 (s, 1H), 8.01 (s, 1H), 7.48 (dd,J= 9.0,4.8 Hz, 2H), 7.03 – 6.98 (m, 2H), 4.92 (ddd,J= 10.0, 3.5, 2.1 Hz, 1H), 2.40(d,J= 3.9 Hz, 1H), 1.93 (t,J= 4.0 Hz, 1H), 1.79 (d,J= 3.4 Hz, 1H), 1.74 (d,J=4.5 Hz, 1H), 1.36 (d,J= 10.9 Hz, 1H), 1.26 (d,J= 2.4 Hz, 1H), 1.12 (dd,J=13.9, 3.4 Hz, 1H), 0.93 (s, 3H), 0.90 (s, 3H), 0.89 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 160.63, 158.22, 155.18, 151.71, 133.46, 121.70, 115.57, 82.74, 49.13, 48.08, 44.95, 36.65, 28.03, 26.99, 19.81, 18.94, 13.57. HRMS (ESI) m / z theoretical value C 18 H 23 FN2O3Na + (M+Na) + 357.15849, determined value 357.15851.II-15(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-ylN-[(4-bromophenyl)carbamoyl]carbamate, brown solid, yield 60%, melting point 194.1-194.6℃.

[0100] 1 H NMR (400 MHz, CDCl3) δ 10.10 (s, 1H), 7.65 (d,J= 8.6 Hz, 2H), 7.58 (d,J= 9.0 Hz, 2H), 7.34 (s, 1H), 4.37 (d,J= 2.0 Hz, 1H), 1.77 (s, 1H), 1.70(s, 1H), 1.68 (s, 1H), 1.60 (s, 1H), 1.56 (s, 3H), 1.50 (s, 1H), 1.23 (s,1H), 1.15 (s, 3H), 1.10 (s, 3H).13 C NMR (101 MHz, CDCl3) δ 155.07, 151.30, 136.61, 132.04, 121.56, 116.80, 82.94, 49.14, 48.10, 44.93, 36.65, 28.05, 27.00, 19.83, 18.95, 13.59. HRMS (ESI) m / z theoretical value C 18 H 23 BrN2O3Na + (M+Na) + 417.07842, the measured value is 417.07813.II-16(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-ylN-[(4-iodophenyl)carbamoyl]carbamate, brown solid, yield 55%, melting point 196.4-196.9℃.

[0101] 1 H NMR (400 MHz, CDCl3) δ 9.89 (s, 1H), 7.61 (d,J= 8.9 Hz, 2H), 7.30 (d,J= 8.9 Hz, 2H), 4.95 – 4.90 (m, 1H), 2.39 (d,J= 7.7 Hz, 1H), 1.86 (d,J=3.7 Hz, 1H), 1.78 (s, 1H), 1.74 (d,J= 4.4 Hz, 1H), 1.35 (s, 1H), 1.25 (d,J=3.1 Hz, 1H), 1.10 (dd,J= 13.8, 3.2 Hz, 1H), 0.93 (s, 3H), 0.90 (s, 3H), 0.88 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 154.81, 150.53, 138.06, 137.27, 121.93, 87.44, 83.19, 49.12, 48.14, 44.90, 36.64, 28.06, 27.05, 19.83, 18.94, 13.61. HRMS (ESI) m / z theoretical value C18H23IN2O3Na+ (M+Na)+ 465.06456, The measured value is 465.06427.II-17(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-ylN-[(4-trifluoromethylphenyl)carbamoyl]carbamate, a yellow solid with a yield of 47% and a melting point of 187.3-187.8℃.

[0102] 1 H NMR (400 MHz, CDCl3) δ 10.09 (s, 1H), 7.64 (d,J= 8.4 Hz, 2H), 7.57(d,J= 8.9 Hz, 2H), 7.15 (s, 1H), 4.97 – 4.92 (m, 1H), 2.41 (d,J= 3.7 Hz, 1H), 1.85 (d,J= 3.8 Hz, 1H), 1.79 (d,J= 3.3 Hz, 1H), 1.75 (d,J= 4.4 Hz, 1H), 1.36 (s, 1H), 1.26 (s, 1H), 1.11 (dd,J= 13.8, 3.4 Hz, 1H), 0.93 (s, 3H), 0.90 (s,3H), 0.89 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 153.43, 142.42, 133.50, 119.87, 119.10, 118.29, 106.21, 81.89, 49.00, 48.08, 44.92, 36.84, 28.18, 27.24, 19.85, 18.96, 13.68. HRMS (ESI) m / z theoretical value C 19 H 23 F3N2O3Na + (M+Na) + 407.15530, measured value 407.15469.II-18(1S,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-ylN-[(4-cyanophenyl)carbamoyl]carbamate, white solid, yield 44%, melting point 164.7-165.2℃.

[0103] 11H NMR (400 MHz, CDCl3) δ 10.16 (s, 1H), 8.18 (s, 1H), 7.65 (d, J = 8.7 Hz, 2H), 7.56 (d, J = 8.8 Hz, 2H), 4.94 (ddd, J = 9.9, 3.4, 2.1 Hz, 1H), 2.41 (d, J = 3.7 Hz, 1H), 1.94 (s, 1H), 1.81 (d, J = 3.3 Hz, 1H), 1.75 (d, J = 4.6 Hz, 1H), 1.38 (d, J = 10.8 Hz, 1H), 1.28 (d, J = 4.8 Hz, 1H), 1.11 (d, J = 3.4 Hz, 1H), 0.94 (s, 3H), 0.91 (s, 3H), 0.90 (s, 3H). 13 13C NMR (101 MHz, CDCl3) δ 154.94, 150.91, 140.60, 126.41, 126.37, 119.66, 83.28, 49.15, 48.15, 44.92, 36.65, 28.06, 27.04, 19.82, 18.95, 13.61. HRMS (ESI) m / z calculated for C 19 1 23 H + N3O3Na + It should be noted that in the original text, there seems to be an error in line where it says "C " and then jumps to other content. The corrected translation assumes it should be "13C NMR" as it is a common carbon NMR spectroscopy notation in chemistry. If this is not the case, please provide more context or clarify the original text.364.16316, measured value 364.16210. Example 5: Activity of compounds with structures shown in Formula I and Formula II against cotton bollworm. In this example, the activity of compounds of Formula I and Formula II against cotton bollworm was determined by the immersion method. The specific operating steps are as follows. Referring to the "Guidelines for Indoor Bioassay Testing of Pesticides - Insecticides" NY / T1154.6—2006, the toxicity of compounds of Formula I and Formula II against 3rd instar larvae of cotton bollworm was determined. Second-instar larvae of cotton bollworms with consistent growth and uniform size were selected. They were gently picked up with a soft brush and placed in a beaker containing a solution of the appropriate concentration of pesticide. The larvae were immersed for 10 seconds. After immersion, the larvae were transferred to clean filter paper to absorb excess pesticide and then transferred to 24-well rearing boxes (12.5 cm × 8.4 cm × 2.6 cm), with one larva per well to avoid interference. All rearing boxes were then placed in an artificial insect culture chamber with the following conditions: temperature (26±1)℃, relative humidity (60±10)%, and photoperiod 16L:8D (16 h light / 8 h darkness). Fresh artificial feed was provided periodically to ensure normal feeding. Each treatment was replicated three times, with 15–20 larvae per replicate. Mortality was assessed at 24 h, 48 h, and 72 h post-treatment. A larva was considered dead upon gentle touch with a soft brush if no spontaneous activity was observed. The mortality rate and corrected mortality rate were calculated. The activities of compounds of formula I and II against cotton bollworm are shown in Table 1.

[0104] Table 1. Activity of compounds of formula I and II against cotton bollworm.

[0105] As shown in Table 1, the tested compounds exhibited varying degrees of insecticidal activity against cotton bollworm, with mortality rates ranging from 3.33% to 59.81%. Among them, compound II-8 showed the most outstanding insecticidal activity, with a mortality rate of 59.81%, comparable to the control agent lufenuron (60%). Compound II-11 also showed good activity, with a mortality rate of 52.97%, exceeding 50%. In addition, compounds I-1 (46.67%), II-17 (46.33%), and II-6 (42.40%) also showed moderate to high insecticidal effects.

[0106] Example 6: Activity of Compounds I and II against Cotton Aphids In this example, the activity of compounds I and II against cotton aphids was determined using the leaf-dip and insect-dip method. The specific operating steps are as follows.

[0107] Referring to the "Guidelines for Indoor Bioassay Testing of Pesticides - Insecticides" NY / T1154.6—2006, the toxicity of Formula I and Formula II compounds to cotton aphids was determined. Leaves infested with cotton aphids were immersed in the pesticide solution for 5 seconds, then air-dried and placed in petri dishes with moistened filter paper. The dishes were sealed with plastic wrap and punctured, then transferred to an artificial insect incubator (temperature 26±1℃, relative humidity 60±10%, photoperiod 16L:8D). 24 hours after treatment, the test insects were gently touched with a No. 0 brush; inaction was considered death. Each treatment was repeated in triplicate, with 30-50 aphids per replicate. Mortality rates were also calculated and corrected. The activities of each Formula I compound against cotton aphids are shown in Table 2.

[0108] Table 2. Activity of Compound I against Cotton Aphids

[0109] Table 2 shows that the tested compounds exhibited varying degrees of insecticidal activity against cotton aphids, with mortality rates ranging from 16.06% to 73.33%. Compound I-25 showed the most significant activity, achieving a mortality rate of 73.33%. Furthermore, compounds I-18 (65.70%), I-26 (65.63%), I-7 (62.77%), I-24 (61.74%), I-35 (61.22%), I-17 (60.89%), and I-22 (60.16%) all showed mortality rates exceeding 60%, indicating good insecticidal potential. The mortality rates of most compounds were concentrated between 40% and 60%, indicating moderate activity.

[0110] Example 7: Antibacterial Activity of Compound I (1) In this example, the inhibitory activity of Compound I against common plant pathogens was determined using the growth rate method. The specific operation steps are as follows: The in vitro bioactivity of the target compound against Rhizoctonia solani, Cynotrophomonas chrysogenum, Fusarium graminearum, and Fusarium oxysporum was tested using the mycelial growth inhibition rate method. 1 mL of each agent's stock solution was added to 100 mL of PDA medium, and an appropriate amount of the target compound's stock solution was added to prepare a drug-containing medium with a mass concentration of 50 mg / L. Carbendazim triadimefon treated in the same manner was used as a positive control, and 1 mL of DMSO was added to the blank control. Pour the prepared drug-treated culture medium into petri dishes. In a clean bench, use a 5mm diameter punch to create holes in the medium and cut out mycelial cakes. Using an inoculation needle, inoculate the mycelial cakes, hyphae side down, into the center of the cooled, solidified drug-treated culture medium. Cover the dishes, seal them with sealing film, and incubate them in a 28±1 ℃ mold incubator. Each treatment has three replicates. When the colony diameter in the blank control group reaches three-quarters of the petri dish diameter, measure the colony diameter using the cross-cross method and calculate the hyphal growth inhibition rate. The inhibitory activities of each compound I against common plant pathogens are shown in Table 3.

[0111] Table 3. Results of antibacterial activity tests (inhibition rate %) of compound I.

[0112] As shown in Table 3, at a concentration of 50 μg / mL, most of the tested compounds exhibited varying degrees of inhibitory activity against the four plant pathogenic fungi. Among them, the compounds showed significant inhibitory effects against *Fusarium graminearum* I-25 and *Fusarium oxysporum*, with some compounds such as I-23 and I-25 showing inhibition rates close to or exceeding those of the commercial fungicide triadimefon, demonstrating good broad-spectrum antifungal potential. However, their inhibitory activity against *Meliocytoplasma aurea* and *Rhizoctonia solani* was generally weak, exhibiting a clear selective antifungal characteristic overall.

[0113] Inhibitory activity against Fusarium graminearum: The tested compounds showed significant differences in activity against this bacterium, with inhibition rates ranging from 11.69% to 70.71%. Among them, compounds I-25 (70.71%), I-23 (69.53%), and I-34 (59.82%) showed the most prominent inhibitory activity, although slightly lower than the positive control triadimefon (77.63%), they were close to its level. In addition, the inhibition rates of I-37 (59.56%), I-18 (51.87%), I-21 (51.82%), I-28 (50.93%), I-31 (50.67%), I-36 (50.96%), and I-46 (50.29%) all exceeded 50%, showing good antibacterial potential.

[0114] Inhibitory activity against Fusarium oxysporum: The compounds exhibited inhibition rates ranging from 2.09% to 69.80% against this bacterium. I-23 showed the best activity, with an inhibition rate of 69.80%, exceeding that of the positive control triadimefon (64.56%). I-24 (60.20%), I-26 (58.90%), I-25 (58.66%), and I-21 (54.41%) all showed inhibition rates exceeding 50%, demonstrating excellent antibacterial effects. Notably, I-45 and I-37 showed extremely low inhibition rates against this bacterium, at 4.52% and 2.09%, respectively, exhibiting significant selectivity.

[0115] Inhibitory activity against *Cyclocarya aurea*: Overall, the compounds showed relatively weak inhibitory activity against this fungus, with most inhibition rates between 10% and 50%, significantly lower than the positive control triadimefon (90.16%). Among them, compounds with relatively good activity included I-1 (57.32%), I-4 (53.40%), and I-5 (50.13%), with inhibition rates slightly exceeding 50%.

[0116] Inhibitory activity against Rhizoctonia solani: Compound I-1 showed the highest inhibition rate against Rhizoctonia solani, at 44.98%; I-16 (42.13%) and I-25 (40.00%) also showed some inhibitory effects.

[0117] (2) Effects of compound I-25 on ROS, ergosterol, and relative conductivity of Fusarium oxysporum: After treatment with compound I-25, the ROS content of Fusarium oxysporum cells gradually increased within 24 hours, and the increase slowed down after 24 hours, maintaining a relative value. In Figure 4, A represents the effect of compound I-25 on reactive oxygen species in Fusarium oxysporum, B represents the ergosterol content, and C represents the effect on cell membrane permeability.

[0118] Figure 4A shows the dynamic changes in intracellular reactive oxygen species (ROS) content in *Fusarium oxysporum* cells after treatment with I-25, TDM, and DMSO control over 48 hours of culture. In the DMSO control group, ROS content remained at a low level throughout, without significant fluctuations. Both I-25 and TDM treatments induced ROS accumulation, but there were differences between the two treatments—the TDM group showed a rapid increase in ROS content from 0-6 hours followed by sustained growth; while the I-25 group also showed a rapid increase initially, the growth rate was slower than that of TDM. Both I-25 and TDM can induce oxidative stress in fungal cells, but TDM is more effective than I-25 in inducing ROS accumulation. Figure 4B shows the changes in intracellular ergosterol content in *Fusarium oxysporum* over 48 hours after treatment with I-25, TDM, and DMSO control: In the DMSO control group, the ergosterol content showed a slow upward trend, remaining at a high level after 48 hours; both I-25 and TDM treatments reduced the ergosterol content, but the effects differed. The I-25 group showed a rapid decrease in content from 0 to 6 hours, followed by relative stability, while the TDM group showed a more significant decrease. Therefore, both I-25 and TDM can inhibit the synthesis of this substance, but TDM has a stronger inhibitory effect than I-25. Figure 4C shows the trend of relative cell membrane permeability of *Fusarium oxysporum* over 24 hours after treatment with I-25, TDM, and DMSO control: the relative cell membrane permeability of the DMSO control group remained at a low level without significant fluctuations, indicating that fungal cell membrane permeability is stable under normal conditions; both I-25 and TDM treatments significantly increased cell membrane permeability, but the process and magnitude of the effect differed. The TDM group rapidly increased to 50% within 0-4 hours, then slowly increased to nearly 60% at 2 hours; the I-25 group showed a slightly slower rate of increase, with relative cell membrane permeability of approximately 50% at 24 hours. Both I-25 and TDM can disrupt the integrity of fungal cell membranes, but TDM has a more significant effect on increasing cell membrane permeability.

[0119] (3) Observation of PI staining of Fusarium oxysporum by compound I-25: The changes in cell membrane integrity of Fusarium oxysporum under different treatment conditions were detected by PI staining. Figure 5 shows the results of cytoplasmic staining using the PI staining method. The results showed that only weak and scattered red background signals were visible in the single fluorescence channel of the blank control group, and the hyphae were intact in the corresponding bright field image, indicating that the hyphae cell membrane structure was intact under normal growth conditions and could effectively block PI from entering the cell. The red fluorescence signal in the single fluorescence channel of the I-25 treatment group was significantly enhanced and highly consistent with the spatial distribution of hyphae in the bright field. The fluorescence-bright field superimposed image further confirmed that obvious red fluorescence appeared in the hyphae area, indicating that I-25 treatment had caused partial damage to the hyphae cell membrane, allowing PI to penetrate and stain. In contrast, the red fluorescence signal intensity of the TDM treatment group was higher and the distribution was more dense, almost completely covering the hyphae area in the single fluorescence channel. The superimposed image showed that its fluorescence signal was significantly stronger than that of the I-25 group, indicating that TDM caused more extensive and severe damage to the cell membrane structure.

[0120] (4) Effect of compound I-25 on hyphal morphology of Fusarium oxysporum: To further investigate the damage mechanism of I-25 and TDM on Fusarium oxysporum, scanning electron microscopy and transmission electron microscopy were used to observe the hyphal morphology and cell ultrastructure after different treatments. The results are shown in Figure 6 (Figure 6 shows the effect of compound I-25 on hyphal morphology and ultrastructure of Fusarium oxysporum. The left column of Figure 6 is SEM image, with scale bars of 20.0 μm, 20.0 μm and 50.0 μm from top to bottom. The right column of Figure 6 is TEM image, with a scale bar of 1 μm). In the DMSO control group, the hyphal surface was smooth, the morphology was full and the structure was continuous, and no obvious damage was observed. After treatment with I-25 (50 mg / L), the hyphae showed local shrinkage and aggregated damage (as shown by the arrows), but the overall continuity was still maintained, which was considered as mild local damage. In contrast, the TDM-treated group showed more severe hyphal damage: the hyphae exhibited extensive twisting and collapse, accompanied by significant structural rupture (as indicated by the arrows), with numerous fragmented hyphal remnants visible in the field of view, and the overall morphological integrity was essentially lost. The DMSO control group showed clear cell outlines, intact cell walls and membranes, and regular morphology and normal structure of organelles such as mitochondria (arrows indicate intact mitochondria). Cells treated with I-25 showed altered cell wall structure, blurred cell membrane boundaries (as indicated by the arrows), and certain morphological abnormalities in organelles. The TDM-treated group showed even more severe ultrastructural damage: unclear cell wall and membrane boundaries, localized breaks and gaps (as indicated by the arrows), numerous vacuolated areas in the cytoplasm, and complete degradation of organelles such as mitochondria, rendering their normal functional structures unrecognizable.

[0121] (5) Molecular docking: To clarify the specific target of compound I-25 in the ergosterol synthesis pathway, this invention systematically evaluated its binding affinity with 10 key enzyme proteins in this pathway using molecular docking technology. The three-dimensional structures of these 10 key proteins were constructed through homology modeling, and all models passed comprehensive evaluation. Molecular docking results showed that among all tested proteins, ERG13 (3-hydroxy-3-methylglutaryl-CoA synthase) had the strongest binding affinity to I-25, with the optimal conformation having a binding energy of -8.7 kcal / mol; the binding energies of other docking conformations were stable between -6.8 and -8.4 kcal / mol, significantly lower than the binding energies of other proteins (mainly between -5.0 and -7.3 kcal / mol) (Table 4). These results indicate that the interaction between I-25 and ERG13 is energy-advantaged, suggesting that it has high affinity and binding stability with this protein.

[0122] Table 4 shows the binding energies of the selected proteins and molecules.

[0123] Figure 7A shows the two-dimensional interaction diagram of the docking of compound I-25 with ERG13 molecules, and Figure 7B shows the three-dimensional binding conformation of compound I-25 (cyan) at the active site of the ERG13 protein. To further explore the structural basis of the high binding stability between I-25 and ERG13, this invention selects the conformation with the lowest docking energy for interaction visualization analysis (Figure 7A). Analysis results show that I-25 is tightly bound to the active site of ERG13 through a variety of non-covalent interactions: its pyrrole ring, as an aromatic pharmacophore, forms π-π T-type stacking and π-σ interactions with residues such as phenylalanine-307 (PHE-307) and phenylalanine-116 (PHE-116) in the active pocket; at the same time, the hydrophobic [2.2.1] bicycloheptane skeleton generates extensive van der Waals forces and alkyl interactions with residues such as alanine-129 (ALA-129), methionine-114 (MET-114), isoleucine-119 (ILE-119), tyrosine-450 (TYR-450), and glycine-123 (GLY-123), constructing a stable hydrophobic network.

[0124] From a three-dimensional structural perspective, I-25 (shown in cyan) is precisely embedded in the active site of ERG13 (B in Figure 7), with its pharmacophore and active cavity exhibiting highly complementary polar and hydrophobic distributions. This compound is completely embedded in a sub-pocket formed by hydrophobic residues such as tryptophan-381 (TRP-381), phenylalanine-307 (PHE-307), tyrosine-450 (TYR-450), isoleucine-119 (ILE-119), and asparagine-58 (ASN-58), a binding mode crucial for maintaining binding stability. Furthermore, the amide bond of I-25 forms key salt bridges with glutamate-131 (GLU-131) and aspartic acid-356 (ASP-356), an interaction that may hinder the entry of the substrate 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) into the catalytic site, thereby inhibiting enzyme activity.

[0125] The aforementioned molecular and structural evidence indicates that I-25 inhibits the growth of *Fusarium oxysporum* by specifically targeting ERG13. Its mechanism of action is as follows: I-25 binds stably to the substrate-binding pocket of ERG13 in a high-affinity conformation (binding energy -8.7 kcal / mol). Through steric hindrance and competitive binding, it effectively prevents HMG-CoA from approaching the catalytic site, thereby inhibiting a crucial early step in the ergosterol synthesis pathway. This inhibition leads to decreased ergosterol levels, increased reactive oxygen species accumulation, and damage to the cell membrane structure within the fungus, ultimately resulting in suppressed hyphal growth and inhibited spore germination. Since ERG13 is highly conserved in fungi and lacks homologous proteins in animals, this targeting mechanism also explains the highly selective antifungal activity and low cytotoxicity of I-25 to host cells. These findings provide important theoretical support for the further development and application of I-25 as a potential antifungal lead compound.

[0126] Example 8: Pot Control Efficacy of Compounds I and II against Pepper Root Rot This example used a pot method to determine the control efficacy of compound I-25 against pepper root rot. The specific operating steps are as follows: Compound I-25 and triadimefon were prepared to concentrations of 400 mg / L and 800 mg / L, respectively, ensuring that the final DMSO volume fraction was ≤1%. The activated *Fusarium oxysporum* was inoculated into PDA liquid medium and cultured at 28°C and 150 rpm for 7 days with shaking. The spore suspension was filtered through sterile gauze, counted using a hemocytometer, and the concentration was adjusted to 1×10⁻⁶. 6 Take 9 mL of the bacterial suspension and add 1 mL of DMSO to prepare a bacterial suspension stock solution containing 10% DMSO.

[0127] Substrate treatment was performed using the soil immersion inoculation method. The bacterial suspension was mixed with sterilized substrate at a ratio of 10 mL bacterial suspension / 100 g substrate. For the drug treatment groups, the corresponding drug stock solution was added simultaneously. After mixing, the substrates for each treatment were allowed to stand for 12 h. Four treatment groups were set up, with three biological replicates per group and 10 plants per replicate: negative control group (CK0, no pathogen or drug added, but an equal volume of sterile water containing 10% DMSO), positive control group (CK1, pathogen added, no drug added), drug control group (triadimefon group, pathogen added and 400 mg / L or 800 mg / L triadimefon), and treatment group (I-25 group, pathogen added and 400 mg / L or 800 mg / L compound I-25). The treated substrate was filled into nutrient pots (300 g per pot), and pepper seedlings (1 plant per pot) were transplanted. After transplanting, the seedlings were thoroughly watered with sterile water to promote seedling establishment and pathogen infection. After transplanting, the plants were placed in an artificial climate chamber with the following conditions: temperature 25±1℃, relative humidity 70±5%, light intensity 3000~5000 lx, 12 h light / 12 h dark, for 30 days. During this period, water was added by weighing to maintain the substrate humidity at 60%~70%.

[0128] Regularly observe the disease situation and irrigate with sterile water in a timely manner. Measure root length and fresh weight on the 7th day after treatment, conduct a disease index survey according to DB3708 / T 23-2023, and calculate the control efficacy according to formulas (1) and (2). The specific standards are as follows: Grade 0: Healthy roots with no discoloration symptoms and normal plant growth.

[0129] The first-level roots show slight discoloration, with the discolored roots accounting for less than 10% of the total root system, and the plant does not wilt.

[0130] The roots of level 3 plants turn brown, accounting for 11%-30% of the total root system, and the plants begin to wilt.

[0131] Level 5 discoloration affects 31% to 50% of the entire root system, and the plant shows obvious wilting.

[0132] Level 7 discoloration affects 51% to 80% of the entire root system, causing the plant to wilt.

[0133] Level 9 discoloration affects 81% of the entire root system, leading to complete plant death.

[0134] Disease index: (Equation 1); DI is the disease index of each group, Si is the disease grade, ni is the number of corresponding diseased plants, and N is the total number of samples.

[0135] Calculate the prevention and control effect: (Equation 2); CE represents the protective efficacy of each group, DI CK The disease index for the positive control group, DI TR The disease index for the experimental treatment group, DI NONEThe disease index serves as the negative control group.

[0136] Figure 1 shows the potted plant control efficacy of compound I-25 against pepper root rot. The disease symptom observation results in Figure 1 show that the negative control group plants exhibited obvious Fusarium oxysporum infection characteristics, with significant pepper root rot symptoms, specifically seedling wilting, growth stagnation, and even death (Figure 1A and Figure 1B). In stark contrast, pepper seedlings treated with compound I-25 or the control agent triadimefon showed significantly inhibited root rot symptoms and good plant growth (Figure 1C and Figure 1D). Further analysis indicates that the protective effect of compound I-25 on pepper exhibits a concentration-dependent characteristic (Figure 1E), achieving complete protection against pepper root rot under the high concentration treatment conditions set in the experiment. Statistical results of potted plant control effects show that the control effect of compound I-25 against pepper root rot significantly increases with increasing application concentration, demonstrating a clear dose-dependent effect. When the application concentration was 400 mg / L, the control efficacy of compound I-25 was 40.95%, which was significantly lower than that of the control agent triadimefon at the same concentration (51.90%). As the treatment concentration was increased to 800 mg / L, the control efficacy of compound I-25 was significantly enhanced, reaching 72.86%, which was not significantly different from that of the control agent triadimefon at the same concentration (71.43%) (P>0.05).

[0137] The above experimental results indicate that compound I-25 exhibits excellent control efficacy against pepper root rot caused by Fusarium oxysporum, and no significant phytotoxicity (such as leaf yellowing or growth inhibition) was observed within the tested concentration range. In conclusion, compound I-25 possesses the potential to be developed as a novel fungicide candidate compound, demonstrating high research value and application prospects.

[0138] As can be seen from the above examples, the terpene ester compounds provided by the present invention exhibit good insecticidal activity and good inhibitory effect on plant pathogens, and can be applied to the prevention and control of agricultural pests and diseases; at the same time, the preparation method is simple and easy to implement, suitable for industrial production and application, and is of great significance for the discovery of novel candidate molecules with high selectivity and environmental compatibility.

[0139] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. Other embodiments can be obtained based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A class of terpene ester compounds, characterized in that, It has the structure shown in Equation I or Equation II: R4 is selected from or n is 0 or 1, m is an integer from 0 to 5; R1 is selected from hydrogen or C1 to C6 alkyl, R2 is selected from hydrogen or C1 to C6 alkyl, R3 is selected from one or more of hydrogen, C1 to C6 saturated or unsaturated aliphatic hydrocarbon group, C1 to C6 alkoxy group, phenyl group, halogen, cyano group, hydroxyl group, nitro group, benzyl group, halogen-substituted C1 to C6 alkyl group and pyridyl group, and the number of R3 is 1 to 5.

2. The terpene ester compound according to claim 1, characterized in that, R1 and R2 are not both hydrogen, and R1 and R2 are not both C1~6 alkyl; R3 is selected from one, two, three, four or five of the following: hydrogen, methyl, ethyl, Cl, ethyl, tert-butyl, n-propyl, n-butyl, methoxy, phenyl, F, Br, I, trifluoromethyl, cyano, nitro, ethoxy and benzyl.

3. The terpene ester compound according to claim 1, characterized in that, It has any of the following structures: 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 。 4. A method for preparing the terpene ester compound according to any one of claims 1 to 3, characterized in that, The preparation method of the terpene ester compound of Formula I includes the following steps: reacting the compound of Formula III and oxaloyl chloride in an organic solvent to obtain the intermediate of Formula IV; reacting the intermediate of Formula IV and the compound of Formula V or Formula VII in an organic solvent to obtain the terpene ester compound of Formula I; the preparation method of the terpene ester compound of Formula II includes the following steps: reacting the compound of Formula III, bis(trichloromethyl) carbonate and sodium cyanate in an organic solvent to obtain the intermediate of Formula VI; reacting the intermediate of Formula VI and the compound of Formula V in an organic solvent to obtain the terpene ester compound of Formula II. 、 、 、 、 。 5. The application of the terpene ester compound according to any one of claims 1 to 3 or its pharmaceutically acceptable salt, or the terpene ester compound prepared by the preparation method according to claim 4, in the control of agricultural pests and diseases.

6. The use of the terpene ester compound according to any one of claims 1 to 3 or a pharmaceutically acceptable salt thereof, or the terpene ester compound prepared by the preparation method according to claim 4, in the preparation of insecticides.

7. The application according to claim 6, characterized in that, The insecticide is a drug that kills cotton bollworms and / or cotton aphids.

8. The use of the terpene ester compound according to any one of claims 1 to 3 or a pharmaceutically acceptable salt thereof, or the terpene ester compound prepared by the preparation method according to claim 4, in inhibiting plant pathogens, wherein the plant pathogens include one or more of Rhizoctonia solani, Cynosporium aureum, Fusarium graminearum, and Fusarium oxysporum.

9. The use of the terpene ester compound according to any one of claims 1 to 3 or a pharmaceutically acceptable salt thereof, or the terpene ester compound prepared by the preparation method according to claim 4, in the prevention and control of pepper root rot caused by Fusarium oxysporum.

10. A pharmaceutical composition, characterized in that, The active ingredient is a terpene ester compound prepared by any one of claims 1 to 3 or a pharmaceutically acceptable salt thereof, or a terpene ester compound prepared by the preparation method described in claim 4.

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