Curcumin analogues of benzopyran structure and preparation method and application thereof

Abstract

The application belongs to the technical field of pesticide chemistry, and particularly relates to a curcumin analogue with a benzopyran structure, a preparation method and application thereof. The application provides a curcumin analogue with a benzopyran structure, which has a structure shown in formula 1 or formula 2. The curcumin analogue provided by the application has a benzopyran structure, the benzopyran is a heterocyclic compound formed by fusing a benzene ring and a pyran ring, has an antibacterial effect, and, in combination with curcumin compounds, plays a synergistic antibacterial role and improves the broad-spectrum bacteriostatic performance of the compound.

Description

Technical Field

[0001] This invention belongs to the field of pesticide chemistry technology, specifically relating to a curcumin analog with a benzopyran structure, its preparation method, and its application. Background Technology

[0002] Curcuminoids are widely distributed in plants such as turmeric, turmeric, and calamus, and are a class of natural phenolic antioxidants. The core component, curcumin, has a basic structure consisting of two 4-hydroxy-3-methoxybenzene rings linked by a β-diketone group (i.e., a bisα,β-unsaturated ketone, -CH=CH-CO-CH2-CO-CH=CH-). Curcuminoids possess good biological activity and have been widely used in medicine, pesticides, and food. Their biological activities include anticancer, anti-inflammatory, antioxidant, neuroprotective, metabolic regulation, antibacterial, and antiviral effects.

[0003] However, in existing technologies, curcumin compounds have a relatively narrow bactericidal spectrum and are ineffective or have poor efficacy against some fungi or bacteria, which seriously affects their large-scale application in agriculture. Summary of the Invention

[0004] The purpose of this invention is to provide a curcumin analog with a benzopyran structure, its preparation method, and its applications. The curcumin analog provided by this invention exhibits broad-spectrum antibacterial activity; and compared to curcumin, it shows superior antibacterial effects against certain fungi.

[0005] This invention provides a curcumin analog with a benzopyran structure, having the structure shown in Formula 1 or Formula 2:

[0006]

[0007] The present invention also provides a method for preparing curcumin analogs having the structure shown in Formula 1 as described in the above technical solution, comprising the following steps:

[0008] 2,4-Dihydroxybenzaldehyde, 3-methyl-2-butenal, calcium chloride, triethylamine and alcohol were mixed and subjected to a cyclization reaction to obtain intermediate 2; the structure of intermediate 2 is shown in Formula 3.

[0009] Intermediate 2, acetone, and base are mixed and subjected to a first aldol condensation reaction to obtain intermediate 3; the structure of intermediate 3 is shown in Formula 4.

[0010] 3-Methoxy-4-hydroxybenzaldehyde, dichloromethane, 3,4-dihydro-2H-pyran, and pyridine p-toluenesulfonate were mixed and subjected to a hydroxyl protection reaction to obtain intermediate 4; the structure of intermediate 4 is shown in Formula 5.

[0011] Intermediate 3, intermediate 4, organic solvent and base are mixed and subjected to a second aldol condensation reaction to obtain intermediate 5; the structure of intermediate 5 is shown in Formula 6.

[0012] The intermediate 5, alcohol and acid were mixed and deprotected to obtain a curcumin analog having the structure shown in Formula 1.

[0013]

[0014] Preferably, in the cyclization reaction, the molar ratio of 2,4-dihydroxybenzaldehyde, 3-methyl-2-butenal, calcium chloride, and triethylamine is 1:1.5–3:1–3:2–5; the reaction temperature of the cyclization reaction is 50–100°C, and the reaction time is 2–5 h; in the first aldol condensation reaction, the molar ratio of intermediate 2, acetone, and base is 1:30–60:2–6; the reaction time of the first aldol condensation reaction is 24–48 h; and the hydroxyl protection reaction… The molar ratio of 3-methoxy-4-hydroxybenzaldehyde, 3,4-dihydro-2H-pyran, and pyridine p-toluenesulfonate is 1:3–6:0.1–1.0; the reaction temperature of the hydroxyl protection reaction is 30–60 °C, and the reaction time is 6–8 h; the molar ratio of intermediate 3 and intermediate 4 in the second aldol condensation reaction is 1:1–3; the reaction time of the second aldol condensation reaction is 6–10 h; and the reaction time of the deprotection reaction is 0.5–3 h.

[0015] Preferably, the base in the first aldol condensation reaction and the second aldol condensation reaction is sodium hydroxide; the sodium hydroxide is used in the form of a sodium hydroxide solution; the mass fraction of the sodium hydroxide solution is 20% to 40%; and the acid is hydrochloric acid.

[0016] The present invention also provides a method for preparing curcumin analogs having the structure shown in Formula 2 as described in the above technical solution, comprising the following steps:

[0017] 2,4-Dihydroxybenzaldehyde, 3-methyl-2-butenal, calcium chloride, triethylamine and alcohol were mixed and subjected to a cyclization reaction to obtain intermediate 2; the structure of intermediate 2 is shown in Formula 3.

[0018] The intermediate 2, iodomethane, ketone, and base were mixed and subjected to a methylation reaction to obtain intermediate 3; the structure of intermediate 3 is shown in Formula 4.

[0019] Intermediate 3, N-methyl-4-piperidinone, and anhydrous dichloromethane were mixed and subjected to a first aldol condensation reaction to obtain intermediate 4; the structure of intermediate 4 is shown in Formula 5.

[0020] 3-Methoxy-4-hydroxybenzaldehyde, anhydrous dichloromethane, 3,4-dihydro-2H-pyran, and pyridine p-toluenesulfonate were mixed and subjected to a hydroxyl protection reaction to obtain intermediate 5; the structure of intermediate 5 is shown in Formula 6.

[0021] Intermediate 4, intermediate 5, organic solvent and base are mixed and subjected to a second aldol condensation reaction to obtain intermediate 6; the structure of intermediate 6 is shown in Formula 7.

[0022] The intermediate 6, alcohol and acid were mixed and deprotected to obtain a curcumin analog having the structure shown in Formula 2.

[0023]

[0024] Preferably, in the cyclization reaction, the molar ratio of 2,4-dihydroxybenzaldehyde, 3-methyl-2-butenal, calcium chloride, and triethylamine is 1:1.5–3:1–3:2–5; the reaction temperature of the cyclization reaction is 50–100°C, and the reaction time is 2–5 h; in the methylation reaction, the molar ratio of intermediate 2, iodomethane, and base is 1:1–3:1–3; the methylation reaction temperature is 40–80°C, and the reaction time is 6–12 h; in the first aldol condensation reaction, the molar ratio of intermediate 3 and N-methyl-4-piperidinone is 1:2–6; the first aldol condensation reaction... The aldehyde condensation reaction is carried out at a temperature of 40–80 °C for 3–6 h; the molar ratio of 3-methoxy-4-hydroxybenzaldehyde, 3,4-dihydro-2H-pyran, and pyridine p-toluenesulfonate in the hydroxyl protection reaction is 1:3–6:0.1–1.0; the hydroxyl protection reaction is carried out at a temperature of 30–60 °C for 6–8 h; the molar ratio of intermediate 4 and intermediate 5 in the second aldol condensation reaction is 1:1–3; the reaction time of the second aldol condensation reaction is 6–12 h; and the deprotection reaction is carried out for 0.5–3 h.

[0025] Preferably, the base in the methylation reaction is potassium carbonate; the base in the second aldol condensation reaction is sodium hydroxide; and the acid is hydrochloric acid.

[0026] The present invention also provides salts, hydrates, or solvent compounds of curcumin analogs with the benzopyran structure described in the above technical solutions.

[0027] The present invention provides a pesticide formulation comprising one or more of the curcumin analogues with the benzopyran structure described in the above technical solution, and salts, hydrates, or solvent compounds of the curcumin analogues with the benzopyran structure described in the above technical solution.

[0028] The present invention also provides the application of curcumin analogs with the benzopyran structure described in the above technical solutions, salts, hydrates or solvent compounds of curcumin analogs with the benzopyran structure, or the pesticide formulations described therein in the prevention and control of fungal and bacterial diseases.

[0029] Beneficial effects:

[0030] This invention provides a curcumin analog with a benzopyran structure, having the structure shown in Formula 1 or Formula 2. The curcumin analog provided by this invention has a benzopyran structure. Benzopyran is a heterocyclic compound formed by the fusion of a benzene ring and a pyran ring, possessing antibacterial effects. When combined with curcumin-like compounds, it exerts a synergistic antibacterial effect, enhancing the broad-spectrum antibacterial performance of the compound. Attached Figure Description

[0031] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings used in the embodiments will be briefly described below.

[0032] Figure 1 For compound WY10 1 H-NMR spectrum;

[0033] Figure 2 For compound WY10 13 C-NMR spectrum;

[0034] Figure 3 MS chromatogram of compound WY10;

[0035] Figure 4 For compound WY24 1 H-NMR spectrum;

[0036] Figure 5 For compound WY24 13 C-NMR spectrum;

[0037] Figure 6 MS spectrum of compound WY24;

[0038] Figure 7 Figure 1 shows the results of experiments on the inhibition of fungal hyphal growth by compounds WY10 and curcumin.

[0039] Figure 8 Figure 1 shows the results of experiments on the inhibition of fungal hyphal growth by compounds WY24 and curcumin;

[0040] Figure 9 The figure shows the results of experiments on the antibacterial effects of compounds WY10, WY24, and curcumin on bacterial growth. Detailed Implementation

[0041] This invention provides a curcumin analog with a benzopyran structure, having the structure shown in Formula 1 or Formula 2:

[0042]

[0043] The compounds with the structures shown in Formula 1 or Formula 2 provided by this invention exhibit superior inhibitory effects against some fungi compared to curcumin. For example, Formula 1 shows a higher inhibition rate against rice blast fungus than curcumin; Formula 2 shows higher inhibition rates against Fusarium graminearum, target spot fungus of tobacco, gray spot fungus of corn, and Fusarium oxysporum than curcumin.

[0044] The present invention also provides a method for preparing curcumin analogs having the structure shown in Formula 1 as described in the above technical solution, comprising the following steps:

[0045] 2,4-Dihydroxybenzaldehyde, 3-methyl-2-butenal, calcium chloride, triethylamine and alcohol were mixed and subjected to a cyclization reaction to obtain intermediate 2; the structure of intermediate 2 is shown in Formula 3.

[0046] Intermediate 2, acetone, and base are mixed and subjected to a first aldol condensation reaction to obtain intermediate 3; the structure of intermediate 3 is shown in Formula 4.

[0047] 3-Methoxy-4-hydroxybenzaldehyde, dichloromethane, 3,4-dihydro-2H-pyran, and pyridine p-toluenesulfonate were mixed and subjected to a hydroxyl protection reaction to obtain intermediate 4; the structure of intermediate 4 is shown in Formula 5.

[0048] Intermediate 3, intermediate 4, organic solvent and base are mixed and subjected to a second aldol condensation reaction to obtain intermediate 5; the structure of intermediate 5 is shown in Formula 6.

[0049] The intermediate 5, alcohol and acid were mixed and deprotected to obtain a curcumin analog having the structure shown in Formula 1.

[0050]

[0051] In this invention, 2,4-dihydroxybenzaldehyde, 3-methyl-2-butenal, calcium chloride, triethylamine, and an alcohol are mixed and subjected to a cyclization reaction to obtain intermediate 2; the structure of intermediate 2 is shown in Formula 3:

[0052]

[0053] In this invention, the molar ratio of 2,4-dihydroxybenzaldehyde, 3-methyl-2-butenal, calcium chloride, and triethylamine in the cyclization reaction is preferably 1:1.5–3:1–3:2–5, specifically 1:2:1:3; the reaction temperature of the cyclization reaction is preferably 50–100°C, specifically 60°C, 80°C, and 90°C; the reaction time is preferably 2–5 h, specifically 3 h and 4 h; the alcohol is preferably anhydrous ethanol; this invention does not have special requirements for the amount of alcohol used, as long as the reaction proceeds smoothly.

[0054] After the cyclization reaction is completed, the present invention preferably performs post-treatment on the obtained reaction solution. The post-treatment preferably includes: removing the alcohol by vacuum distillation to obtain a crude product; purifying the crude product by column chromatography to obtain intermediate 2; the eluent used for column chromatography purification is preferably a mixed solution of petroleum ether (PE) and ethyl acetate (EA); the volume ratio of petroleum ether to ethyl acetate is preferably 30:1.

[0055] After obtaining intermediate 2, the present invention mixes intermediate 2, acetone, and alkali to carry out a first aldol condensation reaction to obtain intermediate 3; the structure of intermediate 3 is shown in Formula 4:

[0056]

[0057] In this invention, the molar ratio of intermediate 2, acetone, and base in the first aldol condensation reaction is preferably 1:40-50:2-6, specifically 1:46:4; the base is preferably sodium hydroxide; the sodium hydroxide is preferably used in the form of a sodium hydroxide solution; the mass fraction of the sodium hydroxide solution is 20%-40%; the first aldol condensation reaction is preferably carried out at room temperature, and the reaction time is preferably 24-48 hours.

[0058] After the first aldol condensation reaction is completed, the present invention preferably performs post-treatment on the obtained reaction solution. The post-treatment preferably includes: removing acetone from the reaction solution by vacuum distillation to obtain a crude product; extracting the crude product sequentially, and drying, filtering and concentrating the obtained extracted organic phase by vacuum distillation sequentially to obtain intermediate 3; the extractant used for extraction is preferably a mixed solution of ethyl acetate and water; after extraction, the obtained product is located in the organic layer.

[0059] In this invention, 3-methoxy-4-hydroxybenzaldehyde, dichloromethane, 3,4-dihydro-2H-pyran, and pyridine p-toluenesulfonate are mixed and subjected to a hydroxyl protection reaction to obtain intermediate 4; the structure of intermediate 4 is shown in Formula 5:

[0060]

[0061] In this invention, the molar ratio of 3-methoxy-4-hydroxybenzaldehyde, 3,4-dihydro-2H-pyran, and pyridine p-toluenesulfonate in the hydroxyl protection reaction is preferably 1:3–6:0.1–1.0, specifically 1:5:0.1; the reaction temperature of the hydroxyl protection reaction is preferably 30–60°C, specifically 40°C and 50°C; the reaction time is preferably 6–8 h, specifically 7 h or 7.5 h; dichloromethane is used as a solvent, and this invention does not have special requirements for the amount of dichloromethane used, as long as it is sufficient to ensure the smooth progress of the reaction.

[0062] After the hydroxyl protection reaction is completed, the present invention preferably performs post-treatment on the obtained reaction solution. The post-treatment preferably includes: removing dichloromethane from the reaction solution by vacuum distillation to obtain a crude product; extracting the crude product; and sequentially drying, filtering, concentrating by vacuum distillation, and purifying by column chromatography to obtain intermediate 4. The extractant used in the extraction is a mixed solution of ethyl acetate and water. After extraction, the obtained product is located in the organic layer. The eluent used in the column chromatography purification is preferably a mixed solution of petroleum ether and ethyl acetate. The volume ratio of petroleum ether to ethyl acetate is preferably 10:1.

[0063] After obtaining intermediate 3, the present invention mixes intermediate 3, intermediate 4, organic solvent and base to carry out a second aldol condensation reaction to obtain intermediate 5; the structure of intermediate 5 is shown in Formula 6:

[0064]

[0065] In this invention, the molar ratio of intermediate 3 to intermediate 4 in the second aldol condensation reaction is preferably 1:1 to 3, specifically 1:2; the second aldol condensation reaction is preferably carried out at room temperature, and the reaction time is preferably 6 to 10 hours, specifically 8 hours or 9 hours; the alkali is preferably sodium hydroxide; the sodium hydroxide is preferably used in the form of a sodium hydroxide solution; the mass fraction of the sodium hydroxide solution is 20% to 40%; the organic solvent is preferably one or more of toluene, tetrahydrofuran, dioxane, N,N-dimethylformamide, dimethyl sulfoxide, and ethanol, and the ethanol is preferably anhydrous ethanol. The amount of solvent used is sufficient to dissolve the raw materials in the system and achieve a suitable viscosity to allow the reaction to proceed smoothly.

[0066] After the second aldol condensation reaction, the present invention preferably performs post-treatment on the obtained reaction solution. The post-treatment preferably includes: removing the organic solvent from the reaction solution by vacuum distillation to obtain a crude product; extracting the crude product; and sequentially drying, filtering, concentrating by vacuum distillation, and purifying the obtained organic phase by column chromatography to obtain intermediate 5. The extractant used in the extraction is a mixed solution of ethyl acetate and water. After extraction, the obtained product is located in the organic layer. The eluent used in the column chromatography purification is preferably a mixed solution of petroleum ether and ethyl acetate. The volume ratio of petroleum ether to ethyl acetate is preferably 8:1.

[0067] After obtaining intermediate 5, the present invention mixes intermediate 5, alcohol, and acid to carry out a deprotection reaction to obtain a curcumin analog having the structure shown in Formula 1. In the present invention, the deprotection reaction is preferably carried out at room temperature, and the deprotection reaction time is preferably 0.5 to 3 hours, specifically 1 hour or 2 hours; the acid is preferably hydrochloric acid, and the molar concentration of the acid is preferably 2 to 4 M, specifically 3 M; the molar ratio of the acid to intermediate 5 is preferably 0.5 to 1.5:1, specifically 1:1; the alcohol is preferably methanol; the present invention preferably mixes intermediate 5 and alcohol, and then slowly adds the acid dropwise.

[0068] After the deprotection reaction is completed, the present invention preferably performs post-treatment on the obtained reaction solution. The post-treatment preferably includes: removing the alcohol from the reaction solution by vacuum distillation to obtain a crude product; extracting the crude product; and sequentially drying, filtering, concentrating by vacuum distillation, and purifying the obtained organic phase by column chromatography to obtain a curcumin analog having the structure shown in Formula 1. The extractant used in the extraction is a mixed solution of ethyl acetate and water. After extraction, the obtained product is located in the organic layer. The eluent used in the column chromatography purification is a mixed solution of petroleum ether and ethyl acetate. The volume ratio of petroleum ether to ethyl acetate is 5:1.

[0069] The present invention also provides a method for preparing curcumin analogs having the structure shown in Formula 2 as described in the above technical solution, comprising the following steps:

[0070] 2,4-Dihydroxybenzaldehyde, 3-methyl-2-butenal, calcium chloride, triethylamine and alcohol were mixed and subjected to a cyclization reaction to obtain intermediate 2; the structure of intermediate 2 is shown in Formula 3.

[0071] The intermediate 2, iodomethane, ketone, and base were mixed and subjected to a methylation reaction to obtain intermediate 3; the structure of intermediate 3 is shown in Formula 4.

[0072] Intermediate 3, N-methyl-4-piperidinone, and anhydrous dichloromethane were mixed and subjected to a first aldol condensation reaction to obtain intermediate 4; the structure of intermediate 4 is shown in Formula 5.

[0073] 3-Methoxy-4-hydroxybenzaldehyde, anhydrous dichloromethane, 3,4-dihydro-2H-pyran, and pyridine p-toluenesulfonate were mixed and subjected to a hydroxyl protection reaction to obtain intermediate 5; the structure of intermediate 5 is shown in Formula 6.

[0074] Intermediate 4, intermediate 5, organic solvent and base are mixed and subjected to a second aldol condensation reaction to obtain intermediate 6; the structure of intermediate 6 is shown in Formula 7.

[0075] The intermediate 6, alcohol and acid were mixed and deprotected to obtain a curcumin analog having the structure shown in Formula 2.

[0076]

[0077] In this invention, 2,4-dihydroxybenzaldehyde, 3-methyl-2-butenal, calcium chloride, triethylamine, and an alcohol are mixed and subjected to a cyclization reaction to obtain intermediate 2; the structure of intermediate 2 is shown in Formula 3:

[0078]

[0079] In this invention, the molar ratio of 2,4-dihydroxybenzaldehyde, 3-methyl-2-butenal, calcium chloride, and triethylamine in the cyclization reaction is preferably 1:1.5–3:1–3:2–5, specifically 1:2:1:3; the reaction temperature of the cyclization reaction is preferably 50–100°C, specifically 80°C or 90°C; the reaction time is preferably 2–5 h, specifically 2.5 h or 3 h; and the alcohol is preferably anhydrous ethanol.

[0080] After the cyclization reaction is completed, the present invention preferably performs post-treatment on the obtained reaction solution. The post-treatment preferably includes: removing the alcohol by vacuum distillation to obtain a crude product; purifying the crude product by column chromatography to obtain intermediate 2; the eluent used in the column chromatography purification is a mixed solution of petroleum ether and ethyl acetate; the volume ratio of petroleum ether to ethyl acetate is 30:1.

[0081] After obtaining intermediate 2, the present invention mixes intermediate 2, iodomethane, ketone and base for methylation reaction to obtain intermediate 3; the structure of intermediate 3 is shown in Formula 4:

[0082]

[0083] In this invention, the molar ratio of intermediate 2, iodomethane, and base in the methylation reaction is preferably 1:1 to 3:1 to 3, specifically 1:3:3; the reaction temperature of the methylation reaction is preferably 40 to 80°C, specifically 50°C, 60°C, or 70°C; the reaction time is preferably 6 to 12 hours, specifically 8 hours, 10 hours, or 11 hours; the ketone is preferably acetone; the base is preferably potassium carbonate; and the potassium carbonate is preferably added in the form of solid potassium carbonate.

[0084] After the methylation reaction is completed, the present invention preferably performs post-treatment on the obtained reaction solution. The post-treatment preferably includes: removing the ketone from the reaction solution by vacuum distillation to obtain a crude product; extracting the crude product; and sequentially drying, filtering, concentrating by vacuum distillation, and purifying the obtained organic phase by column chromatography to obtain intermediate 3. The extractant used in the extraction is a mixed solution of ethyl acetate and water. After extraction, the obtained product is located in the organic layer. The eluent used in the column chromatography purification is a mixed solution of petroleum ether and ethyl acetate. The volume ratio of petroleum ether to ethyl acetate is 30:1.

[0085] After obtaining intermediate 3, the present invention mixes intermediate 3, N-methyl-4-piperidinone, and dichloromethane to carry out a first aldol condensation reaction to obtain intermediate 4; the structure of intermediate 4 is shown in Formula 5:

[0086]

[0087] In this invention, the molar ratio of intermediate 3 and N-methyl-4-piperidinone in the first aldol condensation reaction is preferably 1:2 to 6, specifically 1:3, 1:4 or 1:5; the reaction temperature of the first aldol condensation reaction is preferably 40 to 80°C, specifically 45°C, 50°C or 60°C, and the reaction time is preferably 3 to 6 hours, specifically 3.5 hours, 4 hours or 5 hours; the dichloromethane is preferably anhydrous dichloromethane.

[0088] After the first aldol condensation reaction, the present invention preferably performs post-treatment on the obtained reaction solution. The post-treatment preferably includes: extracting the reaction solution, and sequentially drying, filtering, concentrating by vacuum distillation, and purifying by column chromatography to obtain intermediate 4; the extractant used in the extraction is a mixed solution of dichloromethane and water; after extraction, the obtained product is located in the organic layer; the eluent used in the column chromatography purification is a mixed solution of dichloromethane and methanol; the volume ratio of dichloromethane to methanol is 100:1.

[0089] In this invention, 3-methoxy-4-hydroxybenzaldehyde, anhydrous dichloromethane, 3,4-dihydro-2H-pyran, and pyridine p-toluenesulfonate are mixed and subjected to a hydroxyl protection reaction to obtain intermediate 5; the structure of intermediate 5 is shown in Formula 6:

[0090]

[0091] In this invention, the molar ratio of 3-methoxy-4-hydroxybenzaldehyde, 3,4-dihydro-2H-pyran, and pyridine p-toluenesulfonate in the hydroxyl protection reaction is preferably 1:3-6:0.1-1.0, specifically 1:5:0.1; the reaction temperature of the hydroxyl protection reaction is preferably 30-60°C, specifically 35°C, 40°C, or 50°C, and the reaction time is preferably 6-8 hours, specifically 6.5 hours, 7 hours, or 7.5 hours.

[0092] After the hydroxyl protection reaction is completed, the present invention preferably performs post-treatment on the obtained reaction solution. The post-treatment preferably includes: removing dichloromethane from the reaction solution by vacuum distillation to obtain a crude product; extracting the crude product; and sequentially drying, filtering, concentrating by vacuum distillation, and purifying by column chromatography to obtain intermediate 4. The extractant used in the extraction is a mixed solution of ethyl acetate and water. After extraction, the obtained product is located in the organic layer. The eluent used in the column chromatography purification is a mixed solution of petroleum ether and ethyl acetate. The volume ratio of petroleum ether to ethyl acetate is 10:1.

[0093] After obtaining intermediates 4 and 5, the present invention mixes intermediates 4 and 5, an organic solvent, and a base to carry out a second aldol condensation reaction to obtain intermediate 6; the structure of intermediate 6 is shown in Formula 7:

[0094]

[0095] In this invention, the molar ratio of intermediate 4 to intermediate 5 in the second aldol condensation reaction is preferably 1:1 to 3, specifically 1:1.5, 1:2, or 1:2.5; the reaction time of the second aldol condensation reaction is preferably 6 to 12 hours, specifically 7 hours, 8 hours, or 9 hours; the alkali is preferably sodium hydroxide; the sodium hydroxide is preferably used in the form of a sodium hydroxide solution; the mass fraction of the sodium hydroxide solution is preferably 20% to 40%; the organic solvent is preferably one or more of toluene, tetrahydrofuran, dioxane, N,N-dimethylformamide, dimethyl sulfoxide, or ethanol; the ethanol is preferably anhydrous ethanol; the amount of solvent used is sufficient to dissolve the raw materials in the system and achieve a suitable viscosity to allow the reaction to proceed smoothly.

[0096] After the second aldol condensation reaction, the present invention preferably performs post-treatment on the obtained reaction solution. The post-treatment preferably includes: removing the organic solvent from the reaction solution by vacuum distillation to obtain a crude product; extracting the crude product; and sequentially drying, filtering, concentrating by vacuum distillation, and purifying by column chromatography to obtain intermediate 6. The extractant used in the extraction is a mixed solution of dichloromethane and water. After extraction, the obtained product is located in the organic layer. The eluent used in the column chromatography purification is a mixed solution of dichloromethane and methanol. The volume ratio of dichloromethane to methanol is 50:1.

[0097] After obtaining intermediate 6, the present invention mixes intermediate 6, alcohol, and acid to carry out a deprotection reaction to obtain a curcumin analog having the structure shown in Formula 2. In the present invention, the deprotection reaction is preferably carried out at room temperature, and the reaction time is preferably 0.5 to 3 hours, specifically 1 hour or 2 hours; the acid is preferably hydrochloric acid, and the molar concentration of the acid is preferably 2 to 4 M, specifically 3 M; the molar ratio of the acid to intermediate 5 is preferably 0.5 to 1.5:1, specifically 1:1; the alcohol is preferably methanol; the present invention preferably mixes intermediate 5 and alcohol, and then slowly adds the acid dropwise.

[0098] After the deprotection reaction is completed, the present invention preferably performs post-treatment on the obtained reaction solution. The post-treatment preferably includes: removing the alcohol from the reaction solution by vacuum distillation to obtain a crude product; extracting the crude product; and sequentially drying, filtering, concentrating by vacuum distillation, and purifying by column chromatography to obtain a curcumin analog having the structure shown in Formula 2. The extraction solvent used is a mixed solution of dichloromethane and water. After extraction, the obtained product is located in the organic layer. The eluent used for column chromatography purification is a mixed solution of dichloromethane and methanol. The volume ratio of dichloromethane to methanol is 30:1.

[0099] The present invention also provides salts, hydrates or solvent compounds of curcumin analogs with the benzopyran structure described in the above technical solutions.

[0100] The present invention provides a pesticide formulation comprising one or more of the curcumin analogues with the benzopyran structure described in the above technical solution, and salts, hydrates, or solvent compounds of the curcumin analogues with the benzopyran structure described in the above technical solution.

[0101] In this invention, the pesticide formulation preferably further includes one or two of a carrier or excipients. This invention does not impose any particular limitations on the excipients and their types, or on the preparation method of the pesticide formulation; any preparation method of pesticide formulations containing antibacterial compounds well-known to those skilled in the art can be used.

[0102] As one embodiment of the present invention, the pesticide formulation may be an injection, tablet, capsule, aerosol, suppository, film, pellet, ointment, controlled-release agent, sustained-release agent, or nano-formulation.

[0103] The present invention also provides the application of curcumin analogs with the benzopyran structure described in the above technical solutions, salts, hydrates or solvent compounds of curcumin analogs with the benzopyran structure, or the pesticide formulations described therein in the prevention and control of fungal and bacterial diseases.

[0104] In this invention, the fungal disease is preferably a disease caused by one or more of the following: rice blast fungus, rice sheath blight fungus, sunflower sclerotinia sclerotinia, tobacco red spot fungus, corn gray spot fungus, Fusarium oxysporum, Fusarium graminearum, and tobacco target spot fungus.

[0105] In this invention, the bacterial disease is preferably caused by one or more of the following: rice bacterial blight pathogen, tobacco wildfire pathogen, Chinese cabbage soft rot pathogen, and tobacco bacterial wilt pathogen.

[0106] To further illustrate the present invention, the following detailed description, in conjunction with the accompanying drawings and embodiments, describes the benzopyran-structured curcumin analogues, their preparation methods, and applications provided by the present invention, but these descriptions should not be construed as limiting the scope of protection of the present invention.

[0107] Example 1

[0108] Preparation of curcumin analogs having the structure shown in Formula 1:

[0109] Step (a): Anhydrous ethanol (15 mL) was added to a reaction flask containing 2,4-dihydroxybenzaldehyde (1.0 g, 7.24 mmol) and 3-methyl-2-butenal (1399 μL, 14.48 mmol), followed by calcium chloride (803 mg, 7.24 mmol) and triethylamine (2871 μL, 21.72 mmol). The reaction was carried out at 80 °C for 2 h, and monitored by TLC (PE to EA volume ratio of 30:1). After the reaction was completed, the anhydrous ethanol was removed under reduced pressure after the reaction solution was cooled to room temperature. The residue was separated and purified by column chromatography (PE to EA volume ratio of 30:1) to obtain a yellow oily product, namely intermediate 2 (823 mg, yield: 55.66%).

[0110] Step (b): Add acetone (20 ml) to the reaction flask containing intermediate 2 (1.2 g, 5.88 mmol), then add an appropriate amount of 40% NaOH solution. React at room temperature for 48 h, and monitor the reaction by TLC (the volume ratio of PE to EA as the developing solvent is 6:1). After the reaction is complete, remove the solvent acetone by vacuum distillation. Extract the residue three times in a mixture of ethyl acetate and water. Combine the organic layers, dry with anhydrous magnesium sulfate, filter, and concentrate by vacuum distillation. Wash the concentrate three times with ethyl acetate to obtain a yellow solid product, namely intermediate 3 (1.03 g, yield: 71.5%).

[0111] Step (c): Anhydrous dichloromethane (20 mL) was added to a reaction flask containing 3-methoxy-4-hydroxybenzaldehyde (2.0 g, 13.15 mmol), along with DHP (6.0 mL, 65.73 mmol) and PPTS (330.33 mg, 1.31 mmol). The reaction was carried out at 40 °C for 8 h, and the reaction was monitored by TLC (the volume ratio of PE to EA was 10:1). After the reaction was completed, the solvent dichloromethane was removed by vacuum distillation. The residue was extracted three times in a mixed solution of ethyl acetate and water. The organic layers were combined, dried with anhydrous magnesium sulfate, filtered, and concentrated by vacuum distillation. The concentrate was purified by column chromatography (the volume ratio of PE to EA was 10:1) to obtain a colorless oily product, namely intermediate 5 (2.5 g, yield: 80.50%).

[0112] Step (d): Add 15 mL of anhydrous ethanol to a reaction flask containing intermediate 3 (500 mg, 2.05 mmol) and intermediate 5 (967.16 mg, 4.09 mmol), add an appropriate amount of 40% NaOH solution, and react at room temperature for 8 h. Monitor the reaction by TLC (evolving solvent PE to EA volume ratio 8:1). After the reaction, remove the solvent anhydrous ethanol by vacuum distillation. Extract the residue three times in a mixture of ethyl acetate and water. Combine the organic layers, dry with anhydrous magnesium sulfate, filter, and concentrate by vacuum distillation. Separate and purify the concentrate by column chromatography (mobile phase PE to EA volume ratio 8:1) to obtain a yellow-green oily product, namely intermediate 6 (658 mg, yield: 71.99%).

[0113] Step (e): Add methanol (10 mL) to a reaction flask containing intermediate 6 (300 mg, 0.67 mmol), and slowly add 4-5 drops of 3M HCl solution. React at room temperature for 0.5 h, and monitor the reaction by TLC (e.g., PE to EA volume ratio 5:1). After the reaction, remove the solvent methanol by vacuum distillation. Extract the residue three times in a mixture of ethyl acetate and water. Combine the organic layers, dry with anhydrous magnesium sulfate, filter, and concentrate by vacuum distillation. Separate and purify the concentrate by column chromatography (mobile phase PE to EA volume ratio 5:1) to obtain the crude product. Wash the crude product three times with methanol to obtain a yellow solid product, which is a curcumin analog with the structure of Formula 1, denoted as compound WY10 (45 mg, yield: 17.7%).

[0114] The 1H NMR and mass spectrometry data of compound WY10 are as follows:

[0115] 1 H NMR (400MHz, DMSO-d6) δ9.75-9.55(m,2H),7.97(d,J=15.7Hz,1H),7.65(d,J=15.8Hz,1H),7.56(d,J=8.6Hz,1H),7.35(s,1H),7.23-7.12(m,2 H),7.06(d,J=15.9Hz,1H),6.83(d,J=8.1Hz,1H),6.75(d,J=10.0Hz,1H),6.40(d,J=8.5Hz,1H),5.76-5.70(m,1H),3.85(s,3H),1.38(s,6H).

[0116] 13 C NMR(101MHz,DMSO-d6)δ188.14,155.73,152.80,149.40,147.99,142.72,137.46,129.03,128.25,12 6.39,123.73,123.25,122.55,116.67,116.19,115.71,111.41,110.18,109.14,76.13,55.69,27.55.

[0117] ESI-MS m / z: 379.4 [M+H] + HPLC purity: 95.76%.

[0118] Figure 1 For compound WY10 1 H-NMR spectrum.

[0119] Figure 2 For compound WY1013 C-NMR spectrum.

[0120] Figure 3 MS chromatogram of compound WY10; from Figures 1-3 As can be seen from this, compound WY10 has the structure shown in Formula 1:

[0121]

[0122] Example 2

[0123] Preparation of curcumin analogs having the structure shown in Formula 2:

[0124] Step (a): Anhydrous ethanol (15 mL) was added to a reaction flask containing 2,4-dihydroxybenzaldehyde (1.0 g, 7.24 mmol) and 3-methyl-2-butenal (1399 μL, 14.48 mmol), followed by calcium chloride (803 mg, 7.24 mmol) and triethylamine (2871 μL, 21.72 mmol). The reaction was carried out at 80 °C for 2 h, and monitored by TLC (PE to EA volume ratio of 30:1). After the reaction was completed, the anhydrous ethanol was removed under reduced pressure after the reaction solution was cooled to room temperature. The residue was purified by column chromatography (PE to EA volume ratio of 30:1) to obtain a yellow oily product, namely intermediate 2 (823 mg, yield: 55.66%).

[0125] Step (b): Acetone (15 mL) and potassium carbonate (1.02 g, 7.34 mmol) were added to a reaction flask containing intermediate 2 (500 mg, 2.45 mmol) and methyl iodide (456 μL, 7.34 mmol). The reaction was carried out at 60 °C for 12 h, and monitored by TLC (PE to EA volume ratio of 30:1). After the reaction was completed, the acetone was removed under reduced pressure after the reaction solution was cooled to room temperature. The residue was extracted three times in a mixture of ethyl acetate and water. The organic layers were combined, dried with anhydrous magnesium sulfate, filtered, and concentrated by vacuum distillation. The concentrate was purified by column chromatography (PE to EA volume ratio of 30:1) to obtain a yellow oily product, intermediate 3 (446 mg, yield: 83.47%).

[0126] Step (c): Anhydrous dichloromethane (15 mL) was added to a reaction flask containing intermediate 3 (1 g, 4.58 mmol) and N-methyl-4-piperidinone (2.59 mL, 22.91 mmol). The reaction was carried out at 40 °C for 4 h, and the reaction was monitored by TLC (the volume ratio of CH2Cl2 to MeOH was 100:1). After the reaction was completed, the mixture was extracted three times in a mixed solution of dichloromethane and water. The organic layers were combined, dried with anhydrous magnesium sulfate, filtered, and concentrated by vacuum distillation. The concentrate was purified by column chromatography (the volume ratio of mobile phase CH2Cl2 to MeOH was 100:1) to obtain a yellow oily product, namely intermediate 4 (877 mg, yield: 61.07%).

[0127] Step (d): Anhydrous dichloromethane (20 mL) was added to a reaction flask containing 3-methoxy-4-hydroxybenzaldehyde (2.0 g, 13.15 mmol), along with DHP (6.0 mL, 65.73 mmol) and PPTS (330.33 mg, 1.31 mmol). The reaction was carried out at 40 °C for 8 h, and the reaction was monitored by TLC (the volume ratio of PE to EA was 10:1). After the reaction was completed, the solvent dichloromethane was removed by vacuum distillation. The residue was extracted three times in a mixed solution of ethyl acetate and water. The organic layers were combined, dried with anhydrous magnesium sulfate, filtered, and concentrated by vacuum distillation. The concentrate was purified by column chromatography (the volume ratio of PE to EA was 10:1) to obtain a colorless oily product, namely intermediate 6 (2.5 g, yield: 80.50%).

[0128] Step (e): Anhydrous ethanol (15 mL) was added to a reaction flask containing intermediate 4 (500 mg, 1.60 mmol) and intermediate 6 (753.89 mg, 3.19 mmol), and an appropriate amount of 40% NaOH solution was added. The reaction was carried out at room temperature for 8 h, and the reaction was monitored by TLC (the volume ratio of CH2Cl2 to MeOH was 50:1). After the reaction was completed, the solvent anhydrous ethanol was removed by vacuum distillation. The residue was extracted three times in a mixed solution of ethyl acetate and water. The organic layers were combined, dried with anhydrous magnesium sulfate, filtered, and concentrated by vacuum distillation. The concentrate was purified by column chromatography (the volume ratio of CH2Cl2 to MeOH was 50:1) to obtain a yellow oily product, namely intermediate 7 (476 mg, yield: 56.12%).

[0129] Step (f): Add methanol (10 mL) to a reaction flask containing intermediate 7 (200 mg, 0.38 mmol), and slowly add 4-5 drops of 3M HCl solution. React at room temperature for 0.5 h. Monitor the reaction by TLC (the volume ratio of CH2Cl2 to MeOH as the developing solvent is 30:1). After the reaction is complete, remove the solvent methanol by vacuum distillation. Extract the residue three times in a mixed solution of ethyl acetate and water, combine the organic layers, dry with anhydrous magnesium sulfate, filter, and concentrate by vacuum distillation. Separate and purify the concentrate by column chromatography (the volume ratio of CH2Cl2 to MeOH as the mobile phase is 30:1) to obtain the crude product. Wash the crude product three times with methanol to obtain a yellow solid product, which is the curcumin analog with the structure shown in Formula 2, denoted as compound WY24 (48 mg, yield: 28.51%).

[0130] The 1H NMR and mass spectrometry data of compound WY24 are as follows:

[0131] 1 H NMR (400MHz, CDCl3) δ8.02(s,1H),7.81(s,1H),7.01(d,J=8.5Hz,1H),6.95(s,2H),6.90(s,1H),6.63(d,J=2.7Hz ,1H),6.60(s,1H),5.67(d,J=10.0Hz,1H),3.94-3.88(m,5H),3.79(s,2H),3.73(s,3H),2.50(s,3H),1.45(s,6H).

[0132] 13 C NMR (101MHz, CDCl3) δ186.51,156.38,155.45,147.11,146.68,137.14,132.37,131.69,131.06,130.75,130.7 3,127.86,124.44,121.04,116.82,115.14,114.83,113.61,112.31,63.01,57.37,57.10,56.08,45.68,28.23.

[0133] ESI-MS m / z: 448.4 [M+H] + HPLC purity: 97.02%.

[0134] Figure 4 For compound WY24 1 H-NMR spectrum.

[0135] Figure 5 For compound WY24 13C-NMR spectrum.

[0136] Figure 6 MS chromatogram of compound WY24; from Figures 4-6 As can be seen from this, compound WY24 has the structure shown in Formula 2:

[0137]

[0138] Test case

[0139] Antifungal activity assay

[0140] The experimental pathogenic fungi were Magnaphalthe oryzae (rice blast fungus), Rhizoctonia solani (rice sheath blight fungus), Sclerotinia sclerotiorum (sunflower sclerotiorum), Alteraria alternata (tobacco red spot fungus), Cercospora zeae maydis (corn gray spot fungus), Fusarium oxysporum (Fusarium oxysporum), Fusarium graminearum (grass Fusarium), and Rhizoctonia solani (tobacco target spot fungus).

[0141] The antibacterial activity of compounds WY10 and WY24 was tested using a fungal hyphal growth assay, as follows:

[0142] (1) Preparation of culture medium: The test compounds were dissolved in DMSO to prepare a stock solution with a concentration of 50 mmol / L. The stock solution was then added to PDA medium and diluted to prepare PDA medium plates containing the test samples, so that the final concentrations of the test compounds were 40 μmol / L, 60 μmol / L and 80 μmol / L. The PDA medium without any compound was designated as the blank group; the PDA medium containing only DMSO was designated as control group 1; the PDA medium containing 60 μmol / L curcumin was designated as control group 2; the PDA medium containing 40 μmol / L, 60 μmol / L and 80 μmol / L compound WY10 was designated as WY10-1, WY10-2 and WY10-3, respectively; the PDA medium containing 40 μmol / L, 60 μmol / L and 80 μmol / L compound WY24 was designated as WY24-1, WY24-2 and WY24-3, respectively.

[0143] (2) Mycelial growth test of pathogenic fungi: Using a punch, 5mm diameter fungal discs were made at the edge of fresh colonies. Activated pathogenic fungi were inoculated onto different groups of culture media and incubated at 28℃ until the control colonies (without the test drug) nearly filled the plates. The colony diameter was measured using the cross-hatching method (subtracting the 5mm disc diameter). The mycelial growth of the pathogenic fungi was observed and recorded. The results are as follows: Figure 7 and Figure 8 As shown.

[0144] Figure 7 The figure shows the results of the test on the inhibition of fungal hyphal growth by compounds WY10 and curcumin.

[0145] Figure 8 The figure shows the results of the test on the inhibition of fungal hyphal growth by compounds WY24 and curcumin.

[0146] from Figure 7 and Figure 8 As can be seen, the solvent DMSO has no inhibitory effect on fungal hyphae, while compounds WY10, WY24 and curcumin all inhibit hyphal growth.

[0147] The formula for calculating the mycelial growth inhibition rate is as follows: Inhibition rate (%) = (C1 - C2) / (C1 - 0.5) × 100

[0148] In the formula: C1 is the diameter of colony 1 in the control group; C2 is the diameter of colony 1 in the drug treatment; 0.5 is the diameter of the bacterial dish.

[0149] Repeat the above operation three times, take the average value to calculate the colony diameter, and the calculation results are shown in Table 1 and Table 2 below.

[0150] Table 1. Inhibition rate (%) of different concentrations of compounds WY10 and curcumin on mycelial growth of pathogenic fungi.

[0151] Rice blast fungus 0.96 25.70 30.33 13.51 Rice sheath blight fungus 22.10 24.64 45.11 29.30 Sunflower sclerotinia stem rot 0.02 7.41 60.26 7.52 Tobacco star bacterium 2.49 32.77 44.79 34.61 gray spot fungus of corn 1.21 19.20 27.32 17.82 Fusarium oxysporum 5.02 7.33 21.12 17.56

[0152] As shown in Table 1, when the concentration of compound WY10 reached 40 μmol / L, it exhibited significant mycelial growth inhibitory activity against *Rhizoctonia solani*, with an inhibition rate of 22.1%. At a concentration of 60 μmol / L, it showed significant mycelial growth inhibitory activity against *Bacillus oryzae*, *Aureobasidium aizoon*, and *Gnaphalium affine*, with inhibition rates of 25.7%, 32.77%, and 19.2%, respectively. At a concentration of 80 μmol / L, it showed significant mycelial growth inhibitory activity against the pathogenic fungi *Sclerotinia sclerotiorum* and *Fusarium oxysporum*, with inhibition rates of 60.26% and 21.12%, respectively. Furthermore, at the same antifungal concentration, compound WY10 showed significantly better inhibitory effects against *Bacillus oryzae* than curcumin; at 60 μmol / L, curcumin's inhibition rate was 13.51%, while WY10-2 reached 25.7%.

[0153] Table 2. Inhibition rates (%) of different concentrations of compounds WY24 and curcumin on mycelial growth of pathogenic fungi.

[0154] Fusarium graminearum 51.98 42.28 42.07 21.47 Tobacco target spot pathogen 49.69 68.25 86.73 34.07 Sunflower sclerotinia stem rot 8.08 8.76 23.09 7.52 gray spot fungus of corn 41.62 47.50 47.91 17.82 Fusarium oxysporum 17.28 32.82 33.49 17.42 Tobacco star bacterium 46.14 39.91 50.41 34.61

[0155] As shown in Table 2, compound WY24 exhibited significant inhibitory activity against the mycelial growth of most tested pathogenic fungi at a concentration of 40 μmol / L. These pathogens included *Fusarium graminearum*, *Tobacco Target Spot*, *Maize Gray Spot*, *Fusarium oxysporum*, and *Tobacco Red Spot*, with inhibition rates of 51.98%, 49.69%, 41.62%, 17.28%, and 46.14%, respectively. At a concentration of 80 μmol / L, it showed significant inhibitory activity against the pathogenic fungus *Sclerotinia sunflower*. The mycelial growth inhibitory activity was 23.09%; moreover, compound WY24 showed better inhibitory effects than curcumin against all the above-mentioned bacteria, with significantly higher inhibition rates against Fusarium graminearum, Tobacco Target Spot Bacterium, Corn Gray Spot Bacterium, and Fusarium oxysporum. Curcumin's inhibition rates against these bacteria were 21.47%, 34.07%, 17.82%, and 17.42%, respectively, while WY24 reached 42.28%, 68.25%, 47.50%, and 32.82%.

[0156] The above-mentioned fungal mycelial growth test results showed that compounds WY10 and WY24, at a concentration of 80 μmol / L, were able to inhibit the tested pathogenic fungi. Compound WY10 showed significant inhibitory activity against most pathogenic fungi at a concentration of 60 μmol / L; compound WY24 showed significant inhibitory activity against most pathogenic fungi at a concentration of 40 μmol / L. Therefore, these two compounds possess broad-spectrum antifungal activity. Furthermore, compared to curcumin, compounds WY10 and WY24 exhibited superior inhibitory effects against some fungi. WY10 showed a 12.19% higher inhibition rate against *Fusarium graminearum* than curcumin; WY24 showed higher inhibition rates against *Fusarium graminearum*, *Tobacco Target Spot*, *Maize Gray Spot*, and *Fusarium oxysporum* than curcumin by 20.81%, 34.18%, 29.68%, and 15.4%, respectively.

[0157] Antibacterial activity assay

[0158] The experimental pathogens were Xanthomonas oryzaepv. Oryza (bacterial blight of rice), Pseudomonas syringaepv. Tabaci (wildfire of tobacco), Erwinia carotovora subsp. carotovora (soft rot of Chinese cabbage), and Ralstonia solanacearum (bacterial wilt of tobacco).

[0159] The antibacterial activity of compounds WY10 and WY24 was tested using a bacterial growth rate assay, as follows:

[0160] (1) Preparation of liquid culture medium: The test compound was dissolved in DMSO to prepare a stock solution with a concentration of 50 mmol / L, which was then added to LB culture medium to prepare culture solutions with final concentrations of 40 μmol / L, 60 μmol / L, and 80 μmol / L of the test compound. LB culture medium containing no compound was designated CK; LB culture medium containing only DMSO was designated DMSO; LB culture medium containing 60 μmol / L curcumin was designated C60; LB culture medium containing 40 μmol / L, 60 μmol / L, and 80 μmol / L compound WY10 was designated 10⁻¹, 10⁻², and 10⁻³, respectively; and LB culture medium containing 40 μmol / L, 60 μmol / L, and 80 μmol / L compound WY24 was designated 24⁻¹, 24⁻², and 24⁻³, respectively.

[0161] (2) Pathogenic bacterial growth rate test: Newly activated bacteria were picked and placed in 2 mL of LB culture medium and cultured at 30℃ and 220 rpm for 12 h with shaking. Then, 10 μL of bacterial suspension was taken and mixed with 2 mL of culture medium of different components in step (1). The mixed liquid was then divided into two parts. 1 mL of the liquid was taken to measure the OD600 before culture and recorded as OD1. Another 1 mL of the liquid was placed at 30℃ and cultured at 220 rpm for 16 h with shaking. The OD600 after culture was measured and recorded as OD2. The inhibitory effect of the test compound on the pathogenic bacteria was determined by calculating the OD growth rate of the pathogenic bacteria before and after culture in different treatment groups. The OD value of each bacteria was measured three times, and the average value was taken after calculating the growth rate.

[0162] Figure 9 The graph shows the results of experiments on the antibacterial effects of compounds WY10, WY24, and curcumin on bacterial growth; from Figure 9 It can be seen that the culture medium becomes turbid after incubation, indicating bacterial growth; the turbidity of the DMSO group and the CK group is similar, and DMSO does not inhibit bacterial growth; at the same time, the culture medium treated with compounds WY10, WY24, and curcumin is basically clear or has a lower degree of turbidity, inhibiting bacterial growth.

[0163] The formula for calculating the growth rate is as follows: Growth rate (%) = (OD2 - OD1) / OD1 × 100%

[0164] The calculated bacterial growth rates of compounds WY10 and WY24, and curcumin are shown in Table 3 below:

[0165] Table 3. Bacterial growth rate in culture media containing compounds WY10, WY24, and curcumin.

[0166] Rice white leaf blight 11.13 9.15 1.03 3.34 1.92 1.08 4.55 3.34 2.45 Tobacco Wildfire W11 21.49 11.56 6.51 8.05 5.67 4.01 10.49 7.64 5.77 Tobacco Wildfire D151 16.30 16.91 5.43 5.49 4.67 2.84 7.67 6.07 4.64 Tobacco wilt GY 14.89 13.49 4.88 5.73 4.61 3.15 6.70 4.47 2.00 soft and rotten Chinese cabbage 15.36 15.20 5.17 6.66 5.12 3.80 11.73 6.18 4.82 Tobacco keratosis 1-J 19.86 23.50 5.77 7.38 5.48 3.28 10.96 7.42 5.06

[0167] Compared with the control group, compounds WY10 and WY24 effectively inhibited the proliferation of rice bacterial blight, tobacco wildfire pathogen, Chinese cabbage soft rot pathogen, and tobacco wilt pathogen at a concentration of 40 μmol / L. Furthermore, the inhibitory activity against pathogenic bacteria significantly increased with the increase of the amount of compounds added to the culture medium. At the same concentration, compound WY10 showed better inhibitory effect on the tested pathogenic bacteria, similar to that of curcumin.

[0168] In summary, compounds WY10 and WY24 exhibit broad-spectrum antibacterial activity, inhibiting a variety of fungi and bacteria. Compared to curcumin, compounds WY10 and WY24 demonstrate superior inhibitory effects against certain fungi. WY10 showed a 12.19% higher inhibition rate against rice blast fungus than curcumin. WY24 showed 20.81%, 34.18%, 29.68%, and 15.4% higher inhibition rates against Fusarium graminearum, target spot fungus of tobacco, gray spot fungus of corn, and Fusarium oxysporum than curcumin, respectively.

[0169] 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. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A curcumin analog with a benzopyran structure, characterized in that, It has the structure shown in Equation 1: Formula 1.

2. The method for preparing the curcumin analog having the structure shown in Formula 1 of benzopyran as described in claim 1, characterized in that, Includes the following steps: 2,4-Dihydroxybenzaldehyde, 3-methyl-2-butenal, calcium chloride, triethylamine and alcohol were mixed and subjected to a cyclization reaction to obtain intermediate 2; the structure of intermediate 2 is shown in Formula 3. Intermediate 2, acetone, and base are mixed and subjected to a first aldol condensation reaction to obtain intermediate 3; the structure of intermediate 3 is shown in Formula 4. 3-Methoxy-4-hydroxybenzaldehyde, dichloromethane, 3,4-dihydro-2H-pyran, and pyridine p-toluenesulfonate were mixed and subjected to a hydroxyl protection reaction to obtain intermediate 4; the structure of intermediate 4 is shown in Formula 5. Intermediate 3, intermediate 4, organic solvent and base are mixed and subjected to a second aldol condensation reaction to obtain intermediate 5; the structure of intermediate 5 is shown in Formula 6. The intermediate 5, alcohol and acid were mixed and deprotected to obtain a curcumin analog having the structure shown in Formula 1. Formula 3; Equation 4; Formula 5; Formula 6.

3. The preparation method according to claim 2, characterized in that, In the cyclization reaction, the molar ratio of 2,4-dihydroxybenzaldehyde, 3-methyl-2-butenal, calcium chloride, and triethylamine is 1:1.5~3:1~3:2~5; the reaction temperature of the cyclization reaction is 50~100℃, and the reaction time is 2~5h; in the first aldol condensation reaction, the molar ratio of intermediate 2, acetone, and base is 1:30~60:2~6; the reaction time of the first aldol condensation reaction is 24~48h; in the hydroxyl protection reaction, 3... The molar ratio of methoxy-4-hydroxybenzaldehyde, 3,4-dihydro-2H-pyran, and pyridine p-toluenesulfonate is 1:3~6:0.1~1.0; the reaction temperature of the hydroxyl protection reaction is 30~60℃, and the reaction time is 6~8h; the molar ratio of intermediate 3 and intermediate 4 in the second aldol condensation reaction is 1:1~3; the reaction time of the second aldol condensation reaction is 6~10h; and the reaction time of the deprotection reaction is 0.5~3h.

4. The preparation method according to any one of claims 2 to 3, characterized in that, The base in the first aldol condensation reaction and the second aldol condensation reaction is sodium hydroxide; the sodium hydroxide is used in the form of a sodium hydroxide solution; the mass fraction of the sodium hydroxide solution is 20%~40%; and the acid is hydrochloric acid.

5. A salt of curcumin analogue with a benzopyran structure as described in claim 1.

6. A pesticide formulation, characterized in that, It includes the curcumin analogue with the benzopyran structure of claim 1 and the salt of the curcumin analogue with the benzopyran structure of claim 5.

7. The use of the curcumin analogue with the benzopyran structure of claim 1, the salt of the curcumin analogue with the benzopyran structure of claim 5, or the pesticide formulation of claim 6 in the control of fungal and bacterial diseases; The fungal diseases are caused by one or more of the following: rice blast fungus, rice sheath blight fungus, sunflower sclerotinia rot fungus, tobacco red spot fungus, corn gray spot fungus, Fusarium oxysporum, Fusarium graminearum, and tobacco target spot fungus; the bacterial diseases are caused by one or more of the following: rice bacterial blight fungus, tobacco wildfire fungus, Chinese cabbage soft rot fungus, and tobacco bacterial wilt fungus.

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