A piperidine-containing myricetin derivative, its preparation method and application

Abstract

This invention provides a piperidine amide-containing myricetin derivative, its preparation method, and its application, belonging to the field of pesticide synthesis technology. Based on myricetin, this invention introduces piperidine and amide groups with excellent activity into the structure of myricetin, synthesizing a series of piperidine amide-containing myricetin derivatives. Through tests on the inhibitory activity of the synthesized piperidine amide-containing myricetin derivatives against plant pathogenic fungi, it was found that the piperidine amide-containing myricetin derivatives synthesized in this invention can effectively inhibit plant pathogenic fungi.

Description

Technical Field

[0001] This invention relates to the field of pesticide synthesis technology, and in particular to a piperidine amide-containing myricetin derivative, its preparation method, and its application. Background Technology

[0002] In recent years, plant pathogenic fungi have caused significant damage to crop production, leading to a decline in the quality and quantity of agricultural products and resulting in substantial economic losses. Chemically synthesized pesticides are primarily used for the prevention and treatment of these fungal diseases. However, long-term use of these chemically synthesized pesticides not only leads to pesticide resistance in harmful organisms but also causes environmental damage. Green pesticides derived from natural products possess advantages such as novel structures, high efficiency, low toxicity, easy decomposition in the environment, minimal or no residue in crops, and unique biological activity. Therefore, selecting lead structures from natural products and optimizing and developing these lead structures is of great significance for the creation of green pesticides.

[0003] Myricetin is a common plant-derived flavonol compound, widely found in berries, vegetables, and fruits. It is currently widely used in medicine, food, and health products, exhibiting various biological activities such as antibacterial, antiviral, antioxidant, and antitumor effects. Jiang et al. introduced a piperidine-containing sulfonamide structure into myricetin through active splicing and tested the inhibitory activity of the target compounds against Xoo, Xac, and Rs using a turbidimetric method. The results showed that some compounds had excellent inhibitory effects on *Xac* (citrus canker) and *Xoo* (rice bacterial blight), far superior to the control agents thiabendazole and tebuconazole. Tang et al. used myricetin as a lead compound, introducing ferulic acid and amide structures into its structure to obtain a series of myricetin derivatives, and tested their inhibitory activity against tobacco mosaic virus (TMV) using the hemifoliation method. The results showed that this series of compounds had good inhibitory effects on tobacco mosaic virus. Jiang et al. introduced piperidine and dithiocarbamate structures into myricetin and evaluated its inhibitory activity against Xoo, Xac, and Rs by turbidimetric assay. The results showed that some compounds inhibited the EC50 of Xac. 50The concentration was as low as 0.11 μg / mL, significantly superior to the control agents tebuconazole (48.9 μg / mL) and thiabendazole copper (60.0 μg / mL). Peng et al. introduced the active small molecule oxadiazole group into the structure of myricetin, synthesizing a series of myricetin derivatives containing 1,3,4-oxadiazole sulfide, and tested their anti-tissue mosaic virus (TMV) activity. The test results showed that the target compounds had good inhibitory activity against TMV at 500 μg / mL. Peng et al. introduced 1,3,4-oxadiazole sulfide containing sulfonate esters into myricetin and tested its antibacterial and anti-TMV virus activity. The results showed that the target compounds all had certain antibacterial and antiviral activities. SEM experiments showed that these compounds could cause deformation or even rupture of pathogen cell membranes, leading to pathogen death.

[0004] Piperidine is a heterocyclic ring containing "N" that is widely found in natural alkaloids. It not only has broad-spectrum biological activities such as antibacterial, antiviral, anticancer, and antioxidant effects, but also has the advantages of good selectivity, high activity, and low toxicity.

[0005] Amide groups, as important pharmacophores of commercially available succinate dehydrogenase inhibitors, remain a research hotspot for potential novel pesticides. Many studies have shown that amide compounds possess broad-spectrum biological activities, such as antibacterial, antiviral, insecticidal, and herbicidal effects, and are widely used in agricultural production.

[0006] In summary, myricetin compounds containing piperidine amide groups all exhibit good biological activity, but there are no reports on the antifungal activity of myricetin derivatives containing piperidine amide. Summary of the Invention

[0007] Therefore, the present invention aims to provide a piperidine amide-containing myricetin derivative, its preparation method and application. The piperidine amide-containing myricetin derivative provided by the present invention can effectively inhibit plant pathogenic fungi.

[0008] To achieve the above objectives, the present invention provides the following technical solution: a myricetin derivative containing piperidine amide, the structural formula of which is shown below:

[0009]

[0010] In the formula, n is 3 or 4; R is independently selected from one of alkyl, substituted amino, substituted or unsubstituted phenyl, or aromatic heterocyclic group.

[0011] Preferably, the alkyl group is ethyl or cyclopentylethyl; the substituted amino group is an amino group containing one or more methyl groups; the substituted phenyl group has one or more methyl, methoxy, nitro or halogen atoms at the ortho, meta and para positions on the benzene ring, or has one or more methyl, methoxy, nitro or halogen atoms at the ortho and meta positions on the benzene ring; the aromatic heterocyclic group is furanyl or pyridyl.

[0012] This invention also provides a method for preparing the piperidine amide-containing myricetin derivative described in the above technical solution, comprising the following steps:

[0013] (1) Using myricetin and CH3I as raw materials, the reaction was carried out in a solvent under alkaline conditions at room temperature for 48 h. After filtration, extraction and concentration, the product was refluxed in an alcohol solution under acidic conditions at 90 °C for 2 h to prepare intermediate a.

[0014] (2) Using intermediate a and dibromoalkane as raw materials, intermediate b was prepared by ice bath in a solvent under alkaline conditions for 10-12 hours.

[0015] (3) Using intermediate b and 4-(N-boc-amino)piperidine as raw materials and potassium carbonate as catalyst, intermediate c was prepared by reacting in acetonitrile solvent at 80°C for 8 hours.

[0016] (4) Using intermediate c as raw material and ethanol as solvent, 5% HCl solution was added dropwise under the condition of heating to 80℃ and reacted for 2h to remove boc protection. Then, the system was adjusted to alkaline with NaHCO3 aqueous solution to prepare intermediate d.

[0017] (5) Using intermediate d and substituted acyl chloride as raw materials and potassium carbonate as catalyst, myricetin derivatives containing piperidine amide were prepared in solvent at room temperature.

[0018] The chemical structural formulas of compounds a, b, c, and d are as follows:

[0019]

[0020] The dibromoalkane is Br-(CH2). n -Br, where n is 3 or 4.

[0021] Preferably, the molar ratio of myricetin and CH3I in step (1) is 10.8:(129-161).

[0022] Preferably, the molar ratio of intermediate a to dibromoalkane in step (2) is 12.9:(39.2-64.7).

[0023] Preferably, the molar ratio of intermediate b, 4-(N-boc-amino)piperidine and potassium carbonate in step (3) is 1.94:(3.53-4.42):(5.89-14.72).

[0024] Preferably, the molar ratio of intermediate d, acyl chloride and potassium carbonate in step (5) is (0.92-0.95):(0.8-0.9):(1.8-1.9).

[0025] The present invention also provides the application of the piperidine amide-containing myricetin derivatives described in the above technical solution in inhibiting plant pathogenic fungi; the plant pathogenic fungi are one or more of the following: rice sheath blight fungus, wheat scab fungus, rapeseed sclerotinia sclerotium, grape bud blight fungus, kiwifruit stem spot fungus, blueberry gray mold fungus, pepper phytophthora, and pepper anthracnose fungus.

[0026] Beneficial technical effects: This invention provides a piperidine amide-containing myricetin derivative, its preparation method, and its application. This invention introduces piperidine and amide groups with excellent activity into the structure of myricetin, synthesizing a series of piperidine amide-containing myricetin derivatives. Through the activity test of the synthesized piperidine amide-containing myricetin derivatives against plant pathogenic fungi, it was found that the piperidine amide-containing myricetin derivatives synthesized in this invention can effectively inhibit plant pathogenic fungi. Detailed Implementation

[0027] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the embodiments are provided to better illustrate the present invention, but the content of the present invention is not limited to the embodiments described. Therefore, non-essential improvements and adjustments made to the implementation schemes by those skilled in the art based on the above-described invention still fall within the protection scope of the present invention.

[0028] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit this disclosure. Singular expressions include plural expressions unless they have a distinct meaning in the context. As used herein, it should be understood that terms such as “comprising,” “having,” “including,” are intended to indicate the presence of features, numbers, operations, components, parts, elements, materials, or combinations thereof. The terminology of the invention is disclosed in the specification and is not intended to exclude the possibility that one or more other features, numbers, operations, components, parts, elements, materials, or combinations thereof may be present or added. As used herein, “ / ” may be interpreted as “and” or “or,” depending on the context.

[0029] This invention synthesizes a myricetin derivative containing piperidine amide, using myricetin as the starting material. Its structural formula is shown below:

[0030]

[0031] In the formula, n is 3 or 4; R is independently selected from one of alkyl, substituted amino, substituted or unsubstituted phenyl, or aromatic heterocyclic group.

[0032] In some embodiments, the alkyl group is ethyl or cyclopentylethyl; the substituted amino group is an amino group containing one or more methyl groups; the substituted phenyl group is a benzene ring containing one or more methyl, methoxy, nitro or halogen atoms at the ortho, meta and para positions, or a benzene ring containing one or more methyl, methoxy, nitro or halogen atoms at the ortho and meta positions; the aromatic heterocyclic group is furanyl or pyridyl.

[0033] This invention also provides a method for preparing the piperidine amide-containing myricetin derivative described in the above technical solution, comprising the following steps: (1)

[0035]

[0036] Using myricetin and CH3I as raw materials, the reaction was carried out in an alkaline solvent at room temperature for 48 h. After filtration, extraction and concentration, the product was refluxed in an acidic alcohol solution at 90 °C for 2 h to prepare intermediate a.

[0037] In some embodiments, the solvent is N,N-dimethylformamide; the extraction is performed using dichloromethane, and the organic phase is collected; the concentration is performed using vacuum distillation; and the reflux in an acidic alcohol solution for 2 hours further includes filtration and washing.

[0038] In this invention, the specific operation of the reaction in step (1) is as follows: Myricetin, anhydrous potassium carbonate and N,N-dimethylformamide (DMF) are added to a 250 mL three-necked flask. After stirring for 10 min, iodomethane is added to the system and the reaction is carried out at room temperature for 48 h. The solid is removed by filtration, the filtrate is collected and dispersed in water, extracted with dichloromethane, the organic phase is collected, and the solvent is removed by vacuum distillation to obtain a wine-red concentrated solution. Ethanol is added to the concentrated solution, and the reaction is heated to 90 °C for 30 min. 37% concentrated hydrochloric acid is added. After a large amount of solid precipitates, the mixture is refluxed for 2 h. The reaction solution is cooled, filtered, and the filter cake is washed several times with ethanol to obtain a pale yellow solid as intermediate a.

[0039] In this invention, the molar ratio of myricetin to CH3I is 10.8:(129-161); the molar ratio of myricetin to anhydrous potassium carbonate is 10.8:107.7. (2)

[0041]

[0042] Intermediate b was prepared by reacting intermediate a and dibromoalkane in an ice bath in a solvent under alkaline conditions for 10-12 hours.

[0043] In some embodiments, the solvent is DMF; after the reaction is completed, the reaction solution is dispersed with ice water to precipitate solids; after the solids are precipitated, the reaction solution is further subjected to filtration and washing steps; the washing is performed with water and petroleum ether respectively.

[0044] In this invention, the specific operation of the reaction in step (2) is as follows: intermediate a, anhydrous potassium carbonate and DMF are added to a 250 mL round bottom flask, stirred for 1 h under ice bath conditions, then dibromoalkane is added, and the reaction is continued for 10-12 h. After the reaction is completed, it is dispersed with ice water, a large amount of solid is precipitated, filtered, and the filter cake is washed with water and petroleum ether respectively to obtain a white solid as intermediate b.

[0045] In this invention, the molar ratio of intermediate a to dibromoalkane is 12.9:(39.2-64.7); the molar ratio of dibromoalkane to anhydrous potassium carbonate is 12.9:38.8. (3)

[0047]

[0048] Intermediate c was prepared by reacting intermediate b and 4-(N-boc-amino)piperidine in acetonitrile solvent at 80°C for 8 hours using potassium carbonate as catalyst.

[0049] In some embodiments, the reaction is further followed by filtration, washing, and rotary evaporation under reduced pressure; the washing is performed using dichloromethane.

[0050] In this invention, the specific operation of the reaction in step (3) is as follows: 4-(N-boc)aminopiperidine and anhydrous K2CO3 are added to 50 mL of acetonitrile solution, stirred at room temperature for 30 min, intermediate b is added to the system, the temperature is raised to 80 °C and reacted for 8 h. After the reaction is completed, the mixture is filtered, the filter cake is washed with dichloromethane, the filtrate is collected and evaporated under reduced pressure to obtain a wine-red oily crude product as intermediate c.

[0051] In this invention, the molar ratio of intermediate b, 4-(N-boc-amino)piperidine, and potassium carbonate is 1.94:(3.53-4.42):(5.89-14.72). (4)

[0053]

[0054] Using intermediate c as raw material and ethanol as solvent, after heating to 80℃, 5% HCl aqueous solution was added dropwise to remove boc protection, and then the system was adjusted to alkaline with NaHCO3 aqueous solution to prepare intermediate d.

[0055] In some embodiments, the concentration of the NaHCO3 aqueous solution is 5%; the alkaline pH value is 8-9; after adjusting to alkalinity, the process further includes extraction and vacuum rotary evaporation; the extraction is performed using dichloromethane.

[0056] In this invention, the specific operation of the reaction in step (4) is as follows: intermediate c is dissolved in 50 mL of ethanol in a 100 mL single-necked flask, 5% hydrochloric acid is added dropwise, and the reaction is carried out at 80 °C for 2 h. After the reaction is completed, a large amount of solvent is removed by rotary evaporation under reduced pressure, and then 30 mL of ethyl acetate is added and stirred continuously until a large amount of yellow solid precipitates. The mixture is filtered, the filter cake is dried, and after drying, the filter cake is dissolved with distilled water. Impurities are extracted with a small amount of ethyl acetate, the organic phase is discarded, the aqueous phase is collected, and the pH value is adjusted to 8-9 with 5% NaHCO3 solution. The aqueous phase is extracted with dichloromethane, the organic phase is collected, and the solvent is removed by rotary evaporation under reduced pressure to obtain a white solid as intermediate d. (5)

[0058]

[0059] Using intermediate d and substituted acyl chloride as raw materials and potassium carbonate as a catalyst, myricetin derivatives containing piperidine amide were prepared at room temperature in a solvent.

[0060] In some embodiments, the solvent is dichloromethane; the reaction time at room temperature is 30 min; after the reaction is completed, the reaction system is dispersed in water, and then extracted, dried, evaporated under reduced pressure, recrystallized or column chromatography is performed.

[0061] In this invention, the specific operation of the reaction in step (5) is as follows: intermediate d, anhydrous K2CO3 and dichloromethane are added to a 50mL round-bottom flask, stirred for 30min under ice bath conditions, the substituted acyl chloride is added dropwise, the reaction is carried out at room temperature for 30min, and after the reaction is completed, the system is dispersed in water, extracted three times with dichloromethane, the organic phase is collected, dried with anhydrous Na2SO4, and the crude product is obtained by rotary evaporation under reduced pressure. The target compound is then obtained by recrystallization with methanol or column chromatography. The volume ratio of dichloromethane to methanol is 25:1.

[0062] In this invention, the molar ratio of intermediate d, acyl chloride and potassium carbonate is (0.92-0.95):(0.8-0.9):(1.8-1.9).

[0063] To better understand the present invention, the following embodiments further illustrate the content of the present invention, but the content of the present invention is not limited to the following embodiments.

[0064] Example 1

[0065] The synthesis of N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)benzamide (compound number Z1) includes the following steps:

[0066] (1) Synthesis of 3-hydroxy-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one: 5,7-dihydroxy-3-(((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-2-(3,4,5-trihydroxyphenyl)-4H-chromen-4-one (5.0 g, 10.8 mmol) and anhydrous potassium carbonate (15.3 g, 107.7 mmol) were added to a 250 mL three-necked flask. 80 mL of DMF was stirred for about 10 min, and then iodomethane (8 mL, 129 mmol) was added to the system. The reaction was carried out at room temperature for about 48 h. The solid was removed by filtration, the filtrate was collected and dispersed in water, extracted with dichloromethane, and the organic phase was collected. The solvent was removed by vacuum distillation to obtain a wine-red concentrated solution. 100 mL of ethanol was added to the concentrated solution, and the reaction was heated to 90 °C for 30 min. 10 mL of concentrated hydrochloric acid was added, and after a large amount of solid precipitated, the mixture was refluxed for another 2 h. The reaction solution was cooled, filtered, and the filter cake was washed several times with ethanol to obtain a pale yellow solid with a yield of 80.7%.

[0067] (2) Synthesis of 3-(3-bromopropoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one: 5.0 g (12.9 mmol), anhydrous potassium carbonate (5.4 g, 38.8 mmol), and 100 mL of DMF were added to a 250 mL round-bottom flask. After stirring for 1 h in an ice bath, 3.9 mL (39.2 mmol) of 1,3-dibromopropane was added, and the reaction was continued for 10 h. After the reaction was completed, the mixture was dispersed in 500 mL of ice water, and a large amount of solid precipitated. The solid was filtered, and the filter cake was washed several times with water and petroleum ether to obtain a white solid with a yield of 91.5%.

[0068] (3) Synthesis of tert-butyl-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)carbamate: 4-(N-boc)aminopiperidine (0.72 g, 3.53 mmol) and anhydrous K₂CO₃ (0.82 g, 5.89 mmol) were added to 50 mL of acetonitrile solution. After stirring at room temperature for 30 min, 3-(3-bromopropoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (1.5 g, 2.94 mmol) was added to the system, and the mixture was heated to 80 °C and reacted for 8 h. After the reaction was complete, the mixture was filtered, the filter cake was washed three times with dichloromethane, the filtrate was collected and rotary evaporated under reduced pressure to obtain a wine-red oily crude product, which did not require further processing and was directly used for the next reaction.

[0069] (4) Preparation of 3-(3-(4-aminopiperidin-1-yl)propoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one: The crude product from step (3) was dissolved in 50 mL of ethanol in a 100 mL single-necked flask, and 8 mL of 5% hydrochloric acid aqueous solution was added dropwise. The mixture was refluxed at 80 °C for 2 h. After the reaction was completed, a large amount of solvent was removed by rotary evaporation under reduced pressure, and then 30 mL of ethyl acetate was added and stirred continuously until a large amount of yellow solid precipitated. The mixture was filtered and the filter cake was dried. After drying, the filter cake was dissolved in 200 mL of distilled water, and the impurities were extracted with a small amount of ethyl acetate. The organic phase was discarded, and the aqueous phase was collected. The pH was adjusted to 8-9 with 5% NaHCO3 solution, and the aqueous phase was extracted with dichloromethane. The organic phase was collected, and the solvent was removed by rotary evaporation under reduced pressure to obtain a white solid with a yield of 90.3%.

[0070] (5) Synthesis of N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)benzamide: 3-(3-(4-aminopiperidin-1-yl)propoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (0.5 g, 0.946 mmol), anhydrous K2CO3 (0.26 g, 1.89 mmol), 20 mL of dichloromethane was added to a 50 mL round-bottom flask and stirred for 30 min in an ice bath. Then, 0.13 g (0.9 mmol) of benzoyl chloride was added dropwise and the mixture was reacted at room temperature for 30 min. After the reaction was completed, the system was dispersed in 100 mL of water and extracted three times with dichloromethane. The organic phase was collected, dried over anhydrous Na2SO4, and evaporated under reduced pressure to obtain the crude product. The target compound was then obtained by recrystallization with methanol or column chromatography (dichloromethane:methanol = 25:1, V / V), with a yield of 55%.

[0071] Example 2

[0072] The synthesis of N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)-4-methylbenzamide (compound number Z2) was performed according to the same procedure as in Example 1, except that the benzoyl chloride in step (5) was replaced with an equimolar amount of 4-methylbenzoyl chloride. Yield: 59%.

[0073] Example 3

[0074] The synthesis of N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)-2-fluorobenzoamide (compound number Z3) was performed according to the same procedure as in Example 1, except that the benzoyl chloride in step (5) was replaced with an equimolar amount of 2-fluorobenzoyl chloride. Yield: 56%.

[0075] Example 4

[0076] Synthesis of 4-chloro-N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)benzamide (compound number Z4), the steps were the same as in Example 1, except that benzoyl chloride in step (5) was replaced with an equimolar amount of 4-chlorobenzoyl chloride. Yield: 52%.

[0077] Example 5

[0078] The synthesis of N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)-4-fluorobenzoamide (compound number Z5) was performed according to the same procedure as in Example 1, except that benzoyl chloride in step (5) was replaced with an equimolar amount of 4-fluorobenzoyl chloride. Yield: 62%.

[0079] Example 6

[0080] The synthesis of 4-bromo-N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)benzamide (compound number Z6) was performed according to the same procedure as in Example 1, except that benzoyl chloride in step (5) was replaced with an equimolar amount of 4-bromobenzoyl chloride. Yield: 62%.

[0081] Example 7

[0082] The synthesis of N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)-4-methoxybenzamide (compound number Z7) was carried out in the same manner as in Example 1, except that benzoyl chloride in step (5) was replaced with an equimolar amount of 4-methoxybenzoyl chloride.

[0083] Yield: 52%

[0084] Example 8

[0085] The synthesis of N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)-4-nitrobenzoamide (compound number Z8) was performed according to the same procedure as in Example 1, except that benzoyl chloride in step (5) was replaced with an equimolar amount of 4-nitrobenzoyl chloride. Yield: 55%.

[0086] Example 9

[0087] Synthesis of N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)furan-2-carboxamide (compound number Z9), following the same procedure as in Example 1, except that benzoyl chloride in step (5) was replaced with an equimolar amount of 2-furancarboxyl chloride. Yield: 55%.

[0088] Example 10

[0089] The synthesis of N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)isonicotinamide (compound number Z10) was performed according to the same procedure as in Example 1, except that benzoyl chloride in step (5) was replaced with an equimolar amount of isonicotinyl chloride hydrochloride. Yield: 61%.

[0090] Example 11

[0091] The synthesis of 3-cyclopentyl-N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)propionamide (compound number Z11) was performed according to the same procedure as in Example 1, except that benzoyl chloride in step (5) was replaced with an equimolar amount of 3-cyclopentylpropionyl chloride. Yield: 51%.

[0092] Example 12

[0093] The synthesis of N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)propionamide (compound number Z12) was performed according to the same procedure as in Example 1, except that benzoyl chloride in step (5) was replaced with an equimolar amount of propionyl chloride. Yield: 48%.

[0094] Example 13

[0095] The synthesis of 3-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)-1,1-dimethylurea (compound number Z13) was performed according to the same procedure as in Example 1, except that benzoyl chloride in step (5) was replaced with an equimolar amount of dimethylcarbamoyl chloride. Yield: 40%.

[0096] Example 14

[0097] Synthesis of 2,4-dichloro-N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)benzamide (compound number Z14), the steps were the same as in Example 1, except that benzoyl chloride in step (5) was replaced with an equimolar amount of 2,4-dichlorobenzoyl chloride. Yield: 54%.

[0098] Example 15

[0099] The synthesis of N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)-3,5-dimethylbenzamide (compound number Z15) was performed according to the same procedure as in Example 1, except that benzoyl chloride in step (5) was replaced with an equimolar amount of 3,5-dimethylbenzoyl chloride. Yield: 51%.

[0100] Example 16

[0101] The synthesis of N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)benzamide (compound number Z16) includes the following steps:

[0102] (1) Synthesis of 3-hydroxy-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one: Same as step 1 in Example 1.

[0103] (2) Synthesis of 3-(4-bromobutoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one: Same as step 2 in Example 1, except that 1,3-dibromopropane was replaced with an equal amount to obtain 1,4-dibromobutane.

[0104] (3) Synthesis of tert-butyl-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl-4H-chromene-3-yl)oxy)piperidin-4-yl)carbamate: Same as step 3 in Example 1, except that 3-(3-bromopropoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one is replaced with an equal amount of 3-(4-bromobutoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one.

[0105] (4) Preparation of 3-(4-(4-aminopiperidin-1-yl)-butoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one: Same as step 4 in Example 1, except that tert-butyl-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromene-3-yl)propoxy)piperidin-4-yl)carbamate is replaced with an equal amount of tert-butyl-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl-4H-chromene-3-yl)oxy)piperidin-4-yl)carbamate.

[0106] (5) Synthesis of N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)benzamide: 3-(4-(4-aminopiperidin-1-yl)-butoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (0.5 g, 0.92 mmol) and anhydrous K₂CO₃ (0.25 g, 1.84 mmol) were prepared. 0.12 g (0.88 mmol) was added to 20 mL of dichloromethane solution, stirred in an ice bath for 30 min, and then benzoyl chloride (0.12 g, 0.88 mmol) was added dropwise. The reaction was stopped after reacting at room temperature for 30 min. The reaction system was dispersed in 100 mL of water, extracted three times with dichloromethane, the organic phase was collected, dried with Na2SO4, and the crude product was obtained by rotary evaporation under reduced pressure. The target compound (dichloromethane:methanol = 25:1, V / V) was then obtained by recrystallization with methanol or column chromatography, with a yield of 58%.

[0107] Example 17

[0108] The synthesis of N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)-4-methylbenzamide (compound number Z17) was performed according to the same procedure as in Example 16, except that benzoyl chloride in step (5) was replaced with an equimolar amount of 4-methylbenzoyl chloride. Yield: 60%.

[0109] Example 18

[0110] The synthesis of N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)-2-fluorobenzoamide (compound number Z18) was performed according to the same procedure as in Example 16, except that benzoyl chloride in step (5) was replaced with an equimolar amount of 2-fluorobenzoyl chloride. Yield: 68%.

[0111] Example 19

[0112] Synthesis of 4-chloro-N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)benzamide (compound number Z19), the steps were the same as in Example 16, except that benzoyl chloride in step (5) was replaced with an equimolar amount of 4-chlorobenzoyl chloride. Yield: 62%.

[0113] Example 20

[0114] N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)-4-fluorobenzoamide (compound number Z20), the procedure was the same as in Example 16, except that benzoyl chloride in step (5) was replaced with an equimolar amount of 4-fluorobenzoyl chloride. Yield: 61%.

[0115] Example 21

[0116] The synthesis of 4-bromo-N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)benzamide (compound number Z21) was performed according to the same procedure as in Example 16, except that benzoyl chloride in step (5) was replaced with an equimolar amount of 4-bromobenzoyl chloride. Yield: 46%.

[0117] Example 22

[0118] The synthesis of N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)-4-methoxybenzamide (compound number Z22) was performed according to the same procedure as in Example 16, except that benzoyl chloride in step (5) was replaced with an equimolar amount of 4-methoxybenzoyl chloride. Yield: 42%.

[0119] Example 23

[0120] The synthesis of N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)-4-nitrobenzoamide (compound number Z23) was performed according to the same procedure as in Example 16, except that benzoyl chloride in step (5) was replaced with an equimolar amount of 4-nitrobenzoyl chloride. Yield: 67%.

[0121] Example 24

[0122] N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)furan-2-carboxamide (compound number Z24), the procedure was the same as in Example 16, except that benzoyl chloride in step (5) was replaced with an equimolar amount of 2-furancarboxyl chloride. Yield: 81%.

[0123] Example 25

[0124] N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)isonicotinamide (compound number Z25), the procedure was the same as in Example 16, except that benzoyl chloride in step (5) was replaced with an equimolar amount of isonicotinyl chloride hydrochloride. Yield: 48%.

[0125] Example 26

[0126] 3-Cyclopentyl-N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)propionamide (compound number Z26), the procedure is the same as in Example 16, except that benzoyl chloride in step (5) is replaced with an equimolar amount of 3-cyclopentylpropionyl chloride. Yield: 65%.

[0127] Example 27

[0128] N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)propionamide (compound number Z27), the procedure was the same as in Example 16, except that benzoyl chloride in step (5) was replaced with an equimolar amount of propionyl chloride. Yield: 59%.

[0129] Example 28

[0130] 3-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)-1,1-dimethylurea (compound number Z28), the procedure is the same as in Example 16, except that benzoyl chloride in step (5) is replaced with an equimolar amount of dimethylcarbamoyl chloride. Yield: 67%.

[0131] Example 29

[0132] The synthesis of 2,4-dichloro-N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)benzamide (compound number Z29) was performed according to the same procedure as in Example 16, except that benzoyl chloride in step (5) was replaced with an equimolar amount of 2,4-dichlorobenzoyl chloride. Yield: 62%.

[0133] Example 30

[0134] N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)-3,5-dimethylbenzamide (compound number Z30), the procedure was the same as in Example 16, except that benzoyl chloride in step (5) was replaced with an equimolar amount of 3,5-dimethylbenzoyl chloride. Yield: 40%.

[0135] The physicochemical properties and mass spectrometry data of the piperidine amide-containing myricetin derivatives synthesized in Examples 1-30 are shown in Table 1, and the proton nuclear magnetic resonance spectra are also shown. 1 H NMR and carbon spectroscopy (H NMR) 13 The C NMR data are shown in Table 2.

[0136] Table 1 Physicochemical properties and mass spectrometry analysis data of the target compound

[0137]

[0138]

[0139] Table 2. Nuclear magnetic resonance spectral data of the target compound

[0140]

[0141]

[0142]

[0143]

[0144]

[0145]

[0146]

[0147]

[0148]

[0149]

[0150]

[0151]

[0152]

[0153]

[0154]

[0155]

[0156]

[0157] Experimental Example 1: Activity Test Against Plant Pathogenic Fungi

[0158] (1) Test method

[0159] The mycelial growth rate method was used to evaluate the in vitro activity of eight plant pathogenic fungi: *Rhizoctonia solani* (Rs), *Fusarium graminearum* (Fg), *Sclerotinia sclerotiorum* (Ss), *Botrytis cinerea* (Bd), *Actinidia kiwifruit* (Ps), *Botrytis cinerea* (Bc), *Phytophthora capsulatum* (Pc), and *Anthracnose fungi* (Cc). Azoxystrobin, a commercial fungicide, was used as a positive control. The specific steps are as follows:

[0160] Dissolve 10 mg of the test drug in 1 mL of DMSO. Add 150 μL of the solution to 1450 μL of melted PDA medium to prepare a drug-containing medium with a concentration of 100 μg / mL. After shaking well, pour the drug-containing medium evenly into three sterilized petri dishes and allow it to solidify naturally at room temperature. Inoculate a 5.00 mm diameter mycelial cake in the center of each petri dish and seal the dishes with sealing film. Add 150 μL of DMSO as a negative control and a commercial azoxystrobin as a positive control. Incubate the petri dishes at 28℃ for 2–5 days. Measure the colony diameter using the cross-cross method and calculate the inhibition rate of the test drug against the tested fungi using SPSS. Each treatment was repeated three times. The inhibition rate was calculated as follows:

[0161] Inhibition rate I (%) = (C tur -T tur ) / (C tur -0.4)×100

[0162] C tur The control colony diameter is the same as the colony diameter treated with DMSO.

[0163] T tur : Colony diameter after chemical treatment;

[0164] 0.4: Diameter of the mushroom cake;

[0165] I: Inhibition rate.

[0166] PDA medium: 200g potato, 20g glucose, 18g agar, 1000mL distilled water;

[0167] Cut the peeled potatoes into chunks, boil them in 500mL of distilled water for 20 minutes, filter with gauze, collect the filtrate, add 20g of glucose and 18g of agar to it, boil again, and after the agar dissolves, add distilled water to make up to 1000mL.

[0168] (2) The results of the bioactivity test against plant pathogenic fungi are shown in Table 3.

[0169] Table 3. In vitro antifungal activity of Z1-Z30 at 100 μg / mL

[0170]

[0171]

[0172] As shown in Table 3, all target compounds exhibited inhibitory activity against the eight fungi at a concentration of 100 μg / mL. Among them, Z11 and Z26 showed better inhibitory activity against the eight fungi. The inhibition rates of Z11 and Z26 against Rs, Ss, Bd, and Ps were 90.6% and 91%, 100% and 97.5%, 90.5% and 91.2%, and 97% and 97.9%, respectively, significantly better than azoxystrobin (85.7%, 61.8%, 79.0%, and 79.7%). The inhibitory activities of Z11 and Z26 against Fg, Pc, and Cc were 64.7% and 69.7%, 62.6% and 63.6%, and 64.2% and 69.2%, respectively, comparable to azoxystrobin (66.7%, 60.3%, and 63.1%).

[0173] The above experimental activity data indicate that the derivatives containing piperidine amide have a certain inhibitory effect on plant pathogenic fungi. Some of the target compounds show excellent activity against plant pathogens and can be used as potential anti-plant pathogen drugs with good application prospects.

[0174] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A piperidine amide-containing myricetin derivative having the following structural formula: The R and n in the structural formula correspond to the groups at the corresponding positions of the myricetin derivatives in the specific structures; The piperidine-containing myricetin derivatives are N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)benzamide, N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)-4-methylbenzamide, N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)-2-fluorobenzamide, and 4-chloro-N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)-2-fluorobenzamide. -dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)benzamide, N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)-4-fluorobenzamide, 4-bromo-N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)benzamide, N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)benzamide, N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen -3-yl)propoxy)piperidin-4-yl)-4-methoxybenzamide, N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)-4-nitrobenzamide, N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)furan-2-carboxamide, N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)isonicotinamide, 3-cyclopentyl -N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)propamide, N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)propamide, 3-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)-1,1-dimethylurea, 2,4-dichloro-N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)-1,1-dimethylurea, 2,4-dichloro-N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)-1,1-dimethylurea, 2,4-dichloro-N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)-1,1-dimethylurea,5-Trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)benzamide, N-(1-(3-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)propoxy)piperidin-4-yl)-3,5-dimethylbenzamide, N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)benzamide, N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)-4-methylbenzamide Formamide, N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromene-3-yl)butoxy)piperidin-4-yl)-2-fluorobenzamide, 4-chloro-N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromene-3-yl)butoxy)piperidin-4-yl)benzamide, N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromene-3-yl)butoxy)piperidin-4-yl)-4-fluorobenzamide, 4-bromo-N-(1-(4-(5,7-dimethoxy-4-oxy-2-) (3,4,5-Trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)benzamide, N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)-4-methoxybenzamide, N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)-4-nitrobenzamide, N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)-4-nitrobenzamide, N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl) N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromene-3-yl)butoxy)piperidin-4-yl)isonicotinamide, 3-cyclopentyl-N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromene-3-yl)butoxy)piperidin-4-yl)propionamide, N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromene-3-yl)butoxy)piperidin-4-yl)propionamide, 3-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromene-3-yl)butoxy)piperidin-4-yl)propionamide, 3-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromene-3-yl)butoxy)piperidin-4-yl)propionamide, 3-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromene-3-yl)butoxy)piperidin-4-yl)propionamide5-Trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)-1,1-dimethylurea, 2,4-dichloro-N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)benzamide, N-(1-(4-(5,7-dimethoxy-4-oxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)butoxy)piperidin-4-yl)-3,5-dimethylbenzamide, 2. The method for preparing the piperidine amide-containing myricetin derivative according to claim 1, characterized in that, Includes the following steps: (1) Using myricetin and CH3I as raw materials, the reaction was carried out in a solvent under alkaline conditions at room temperature for 48 h. After filtration, extraction and concentration, the product was refluxed in an alcohol solution under acidic conditions at 90 °C for 2 h to prepare intermediate a. (2) Using intermediate a and dibromoalkane as raw materials, intermediate b was prepared by ice bath in a solvent under alkaline conditions for 10-12 hours. (3) Using intermediate b and 4-(N-boc-amino)piperidine as raw materials and potassium carbonate as catalyst, intermediate c was prepared by reacting in acetonitrile solvent at 80°C for 8 hours. (4) Using intermediate c as raw material and ethanol as solvent, 5% HCl solution was added dropwise under the condition of heating to 80℃ and reacted for 2h to remove boc protection. Then, the system was adjusted to alkaline with NaHCO3 aqueous solution to prepare intermediate d. (5) Using intermediate d and substituted acyl chloride as raw materials and potassium carbonate as catalyst, myricetin derivatives containing piperidine amide were prepared in solvent at room temperature. The chemical structural formulas of intermediates a, b, c, and d are as follows: The dibromoalkane is Br-(CH2). n -Br, where n is 3 or 4; The structural formula of the myricetin is as follows: The substituted acyl chloride has the following structural formula:

3. The preparation method according to claim 2, characterized in that, The molar ratio of myricetin and CH3I in step (1) is 10.8:(129-161).

4. The preparation method according to claim 2, characterized in that, The molar ratio of intermediate a and dibromoalkane in step (2) is 12.9:(39.2-64.7).

5. The preparation method according to claim 2, characterized in that, The molar ratio of intermediate b, 4-(N-boc-amino)piperidine and potassium carbonate in step (3) is 1.94:(3.53-4.42):(5.89-14.72).

6. The preparation method according to claim 2, characterized in that, The molar ratio of intermediate d, substituted acyl chloride and potassium carbonate in step (5) is (0.92-0.95):(0.8-0.9):(1.8-1.9).

7. The application of the piperidine amide-containing myricetin derivative of claim 1 in inhibiting plant pathogenic fungi; wherein the plant pathogenic fungi are one or more of the following: rice sheath blight fungus, wheat scab fungus, rapeseed sclerotinia sclerotium, grape bud blight fungus, kiwifruit stem spot fungus, blueberry gray mold fungus, pepper phytophthora, and pepper anthracnose fungus.

Images