Chalcone derivatives containing a piperidine sulfonamide structure, and preparation method and application thereof

Abstract

The application discloses a chalcone derivative containing a piperidine sulfonamide structure and a preparation method and application thereof, and belongs to the field of chemical technology. The chalcone derivative containing the piperidine sulfonamide structure provided by the application has good inhibitory activity on multiple test plant fungi, and can be used as a potential anti-plant fungicide. The solvent and the medicine used in the preparation method provided by the application are common organic reagents and chemical medicines, and raw materials are easy to obtain. Moreover, the method has relatively mild reaction conditions, simple post-treatment and high yield, and the yield can reach 40% to 92%.

Description

Technical Field

[0001] This invention belongs to the field of chemical technology, specifically relating to a chalcone derivative containing a piperidine sulfonamide structure, its preparation method, and its application. Background Technology

[0002] Plant pathogenic fungi pose a serious threat to crop yields and safety, hindering global agricultural development. Fungal infections in crops have become a significant agricultural problem worldwide, impacting not only agricultural production but also human health. Fungicides play a crucial role in plant disease control; however, the widespread use of traditional fungicides has exacerbated the problem of fungal resistance and pesticide residues. Therefore, researchers have been dedicated to developing highly efficient, low-toxicity, broad-spectrum, and environmentally friendly fungicides. Natural products, characterized by low toxicity, environmental friendliness, and good bioactivity, are often used as lead compounds in drug design and synthesis. Chalcones are the core skeletal unit of flavonoid natural products and are abundant in natural products. Chalcones and their derivatives possess a wide range of bioactivities, including antibacterial, insecticidal, herbicidal, antiviral, antitumor, anti-inflammatory, and antioxidant effects, and have been increasingly used in agricultural synthesis in recent years.

[0003] In 2017, Bhale et al. (Bioorganic Med. Chem. Lett. 2017, 27: 1502-1507.) designed and synthesized a series of chalcone derivatives containing indole groups. In vitro antitumor evaluation of the target compounds against human breast cancer (MCF-7) cell lines showed that they possessed high antitumor activity. Some of the target compounds exhibited excellent anti-MCF-7 activity, comparable to the control agent doxorubicin.

[0004] In 2018, Zhou et al. (Bioorganic Med. Chem. Lett., 2018, 28: 2091-2097) designed and synthesized a series of chalcone derivatives containing purine and benzylsulfonamide groups. Bioactivity tests showed that the synthesized compounds exhibited good antiviral activity against TMV. Some of these compounds showed better activity in resisting TMV inactivation than their control agent, ningnanmycin.

[0005] In 2019, Guo et al. (RSCAdv.2019,9:24942-24950.) designed and synthesized a series of chalcone derivatives containing thiophene sulfonate. Antibacterial bioactivity tests showed that some compounds exhibited good antibacterial activity, superior to the control agents tebuconazole and thiamethoxam.

[0006] In 2020, Chen et al. (J Heterocycl Chem. 2020, 57: 983-990.) designed and synthesized a series of chalcone derivatives containing triazole thioethers. The antibacterial bioactivity test results showed that most of the compounds had good antibacterial activity against Citrus canker, Tobacco blight and Rice bacterial blight, and some compounds had better antibacterial activity against Citrus canker than the control agent tebuconazole.

[0007] In summary, there are currently no reports on the introduction of piperidine sulfonyl structures into chalcone derivatives and the testing of their antifungal bioactivity. Summary of the Invention

[0008] The purpose of this invention is to provide a chalcone derivative containing a piperidine sulfonamide structure, its preparation method, and its application.

[0009] To achieve the above objectives, the present invention provides the following technical solution:

[0010] One of the technical solutions of this invention is to provide a chalcone derivative containing a piperidine sulfonamide structure, with the general structural formula shown in Formula I:

[0011]

[0012] In Formula I, R1 is phenyl, substituted phenyl, thiophene, or furanyl; R2 is alkyl or substituted phenyl.

[0013] Preferably, R1 is a phenyl, a methyl, fluorine, chlorine or bromine-substituted phenyl, a phenyl with simultaneous chlorine substitution at both the ortho and meta positions, a 2-thienyl or 2-furanyl;

[0014] R2 is a C1-C6 alkyl group, or a substituted phenyl group with one or more substituents located at the para, ortho, and meta positions on the benzene ring, wherein the substituents are selected from methyl, trifluoromethyl, nitro, methoxy, fluorine, chlorine, or bromine.

[0015] The second technical solution of the present invention provides a method for preparing the above-mentioned chalcone derivative containing a piperidine sulfonamide structure, comprising the following steps:

[0016] (1) with p-hydroxyacetophenone and Using raw materials, the reaction produces under alkaline conditions.

[0017] (2) Continue with Using dibromopropane as a raw material, an acid-binding agent is added, and the reaction produces...

[0018] (3) with 1-tert-butoxycarbonyl-4-methylaminopiperidine and Using it as a raw material, an acid-binding agent is added, and the reaction produces...

[0019] (4) Using hydrochloric acid as a raw material, a reaction is carried out to prepare...

[0020] (5) with Using [a specific ingredient] as a raw material, an acid-binding agent is added, and the reaction produces the chalcone derivative containing the piperidine sulfonamide structure.

[0021] Preferably, the reaction in step (1) is carried out in the solvent ethanol; To replace benzaldehyde, furan-2-carboxaldehyde, or thiophene-2-carboxaldehyde; alkaline conditions are provided by a 5 wt.% sodium hydroxide solution;

[0022] The reaction in step (2) is carried out in the solvent acetonitrile; the acid-binding agent is potassium carbonate;

[0023] The reaction in step (3) is carried out in the solvent dichloromethane; the acid-binding agent is triethylamine; It is 4-(N-methyl-4-substituted phenyl)sulfonyl chloride or 4-N-methylethylsulfonyl chloride;

[0024] The reaction in step (4) is carried out in the solvent ethanol;

[0025] The reaction in step (5) is carried out in the solvent acetonitrile; the acid-binding agent is potassium carbonate.

[0026] More preferably, the preparation method provided by the present invention includes the following steps:

[0027] (1) Using 20-30 mmol of p-hydroxyacetophenone, 20-40 mmol of substituted benzaldehyde, 20-30 mmol of furan-2-carboxaldehyde, or 20-30 mmol of thiophene-2-carboxaldehyde as raw materials, and 60-90 mL of ethanol as solvent, (E)-1-(4-hydroxyphenyl)-3-(substituted aromatic)-2-propen-1-one or (E)-1-(4-hydroxyphenyl)-3-(furan-2-yl)propen-2-en-1-one or (E)-1-(4-hydroxyphenyl)-3-(thiophene-2-yl)propen-2-en-1-one were prepared under alkaline conditions of (30-50 mL) 5% sodium hydroxide solution.

[0028]

[0029] (2) Using (E)-1-(4-hydroxyphenyl)-3-(substituted aromatic)prop-2-en-1-one (10-20 mmol) or (E)-1-(4-hydroxyphenyl)-3-(furan-2-yl)prop-2-en-1-one (10-20 mmol) or (E)-1-(4-hydroxyphenyl)-3-(thiophen-2-yl)prop-2-en-1-one (10-20 mmol) as raw materials, in K2CO3 (30-40 mmol) as binder The following preparations were made using acetonitrile (30–60 mL) as an acid and 1,3-dibromopropane (30–40 mmol) to prepare (E)-1-(4-(3-bromopropoxy)phenyl)-3-(substituted aromatic)prop-2-en-1-one or (E)-1-(4-(3-bromopropoxy)phenyl)-3-(furan-2-yl)prop-2-en-1-one or (E)-1-(4-(3-bromopropoxy)phenyl)-3-(thiophen-2-yl)prop-2-en-1-one;

[0030]

[0031] (3) Using 1-tert-butoxycarbonyl-4-methylaminopiperidine (4-10 mmol) and substituted sulfonyl chloride (5-10 mmol) as raw materials, triethylamine (5-10 mmol) as an acid-binding agent, and dichloromethane (10-30 mL) as a solvent, 4-((N-methyl-4-substituted phenyl)sulfonamide)piperidine-1-carboxylic acid tert-butyl ester or 4-(N-methylethylsulfonamide)piperidine-1-carboxylic acid tert-butyl ester was prepared.

[0032]

[0033] (4) 4-((N-methyl-4-substituted phenyl)sulfonamido)piperidine-1-carboxylic acid tert-butyl ester (1-3 mmol) or 4-(N-methylethylsulfonamido)piperidine-1-carboxylic acid tert-butyl ester (1-3 mmol) reacted with hydrochloric acid (20-35 mmol) in ethanol (10-20 mL) to prepare N-methyl-N-(piperidine-4-yl)-4-substituted benzenesulfonamide or N-methyl-N-(piperidine-4-yl)ethylsulfonamide;

[0034]

[0035] (5) (E)-1-(4-(3-bromopropoxy)phenyl)-3-(substituted aromatic)prop-2-en-1-one (1-3 mmol) or (E)-1-(4-(3-bromopropoxy)phenyl)-3-(furan-2-yl)prop-2-en-1-one (1-3 mmol) or (E)-1-(4-(3-bromopropoxy)phenyl)-3-(thiophen-2-yl)prop-2-en-1-one (1-3 mmol) undergo a substitution reaction with N-methyl-N-(piperidin-4-yl)-4-substituted benzenesulfonamide (1-2 mmol) or N-methyl-N-(piperidin-4-yl)ethylsulfonamide (1-2 mmol) under the conditions of K2CO3 (5-15 mmol) as an acid-binding agent and acetonitrile (30-50 mL) as a solvent to generate chalcone derivatives containing the piperidinesulfonamide structure.

[0036]

[0037] The third technical solution of the present invention provides the application of the above-mentioned chalcone derivative containing piperidine sulfonamide structure in the preparation of fungicides against plant fungi.

[0038] Preferably, the plant fungi include *Sclerotinia sclerotiorum*, *Phomopsis sp.*, *Phytophthora capsica Leonian*, *Fusarium oxysporum*, *Botrytis cinerea*, *Colletotrichum capsica*, *Colletotrichum gloeosporioides*, *Fusarium dimerum*, *Rhizoctonia solani*, *Fusarium graminearum*, and *Neoscytalidium dimidiatum*.

[0039] The beneficial technical effects of the present invention are as follows:

[0040] The chalcone derivatives containing piperidine sulfonamide structures provided by this invention have good inhibitory activity against multiple tested plant fungi and can be used as potential anti-plant fungicides.

[0041] The solvents and reagents used in the preparation method provided by this invention are all common organic reagents and chemicals, and the raw materials are readily available. Furthermore, this method has relatively mild reaction conditions, simple post-processing, and high yield, ranging from 42% to 91%. Detailed Implementation

[0042] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention. It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the present invention.

[0043] Furthermore, regarding the numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, are also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0044] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar to or equivalent to those described herein may be used in the implementation or testing of this invention.

[0045] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0046] Example 1

[0047] The synthesis of (E)-N-methyl-N-(1-(3-(4-(3-(p-tolyl)acryloyl)phenoxy)propyl)piperidin-4-yl)-4-(trifluoromethyl)benzenesulfonamide (compound number X1) includes the following steps:

[0048] (1) Synthesis of (E)-1-(4-hydroxyphenyl)-3-(p-tolyl)prop-2-en-1-one: 3.0 g of 4-hydroxyacetophenone, 3.2 g of p-tolualdehyde, and 70.0 mL of ethanol were added to a round-bottom flask. 35 mL of 5 wt.% sodium hydroxide solution was slowly added dropwise under ice bath conditions, and the mixture was stirred electromagnetically for 48 h. After the reaction was complete, the mixture was poured into a 1000 mL beaker containing ice water. The pH was adjusted to 4 with 5 wt.% dilute hydrochloric acid solution, and a large amount of pale yellow solid precipitated. The solid was filtered under reduced pressure and recrystallized from a petroleum ether / ethyl acetate system (10:1) to obtain the pale yellow solid in 80% yield.

[0049] (2) Synthesis of (E)-1-(4-(3-bromopropoxy)phenyl)-3-(p-tolyl)prop-2-en-1-one: (E)-1-(4-hydroxyphenyl)-3-(p-tolyl)prop-2-en-1-one (3.0 g), K2CO3 (5.2 g), and 75.0 mL of acetonitrile were added to a 250 mL round-bottom flask. The temperature was controlled at approximately 85 °C, and the mixture was stirred magnetically for 60 min. Then, 4.0 mL of 1,3-dibromopropane was slowly added dropwise, and the reaction was allowed to proceed for 6 h. The reaction was monitored by TCL. After the reaction was complete, the system was transferred to a beaker containing 50.0 mL of ice water. A white solid precipitated out. The solid was filtered under reduced pressure, and the filter cake was washed with petroleum ether to obtain a white solid with a yield of 86%.

[0050] (3) Synthesis of 4-((N-methyl-4-(trifluoromethyl)phenyl)sulfonamide)piperidine-1-carboxylic acid tert-butyl ester: 1.2 g of 4-(methylamino)piperidine-1-carboxylic acid tert-butyl ester was placed in a 100 mL round-bottom flask, and 20.0 mL of dichloromethane was added. Triethylamine solution (0.7 mL) was slowly added dropwise with stirring. 1.2 g of 4-(trifluoromethyl)benzenesulfonyl chloride was added dropwise using a constant-pressure separatory funnel under ice bath conditions. After the addition was complete, the reaction was continued under ice bath conditions with stirring for 1 h. The solvent was removed by vacuum distillation, and the solid was washed three times with water and air-dried at room temperature to obtain a white solid with a yield of 98%.

[0051] (4) Synthesis of N-methyl-N-(piperidin-4-yl)-4-(trifluoromethyl)benzenesulfonamide: 1.0 g of 4-((N-methyl-4-(trifluoromethyl)phenyl)sulfonamido)piperidin-1-carboxylic acid tert-butyl ester, 1.0 mL of hydrochloric acid, and 20.0 mL of ethanol were placed in a 100 mL round-bottom flask. The temperature was controlled at around 70 °C, and the reaction was continued for 5 h. The solvent was removed by vacuum distillation to obtain the crude product. The crude product was purified by column chromatography (petroleum ether:ethyl acetate = 3:1, v / v) to obtain a white solid with a yield of 71%.

[0052] (5) Synthesis of (E)-N-methyl-N-(1-(3-(4-(3-(p-tolyl)acryloyl)phenoxy)propyl)piperidin-4-yl)-4-(trifluoromethyl)benzenesulfonamide: N-methyl-N-(piperidin-4-yl)-4-(trifluoromethyl)benzenesulfonamide (0.8 g), K2CO3 (2.6 g), and CH3CN (30.0 mL) were added to a 100 mL round-bottom flask. After reflux at 80 °C for 60 min, (E)-1-(4-(3-bromopropyl) 1.1 g of (p-tolyl)prop-2-en-1-one was heated under reflux for 36 h. The reaction mixture was filtered, and the solid was washed with dichloromethane. The organic phases were combined and concentrated under reduced pressure to remove the organic solvent. The crude product was purified by column chromatography (petroleum ether:ethyl acetate = 2:1, v / v) to give (E)-N-methyl-N-(1-(3-(4-(3-(p-tolyl)acryloyl)phenoxy)propyl)piperidin-4-yl)-4-(trifluoromethyl)benzenesulfonamide as a white solid with a yield of 58%.

[0053] Example 2

[0054] The synthesis of (E)-N-methyl-4-nitro-N-(1-(3-(4-(3-(p-tolyl)acryloyl)phenoxy)propyl)piperidin-4-yl)benzenesulfonamide (compound number X2) includes the following steps:

[0055] (1) Synthesis of (E)-1-(4-hydroxyphenyl)-3-(p-tolyl)prop-2-en-1-one: as in step (1) of Example 1.

[0056] (2) Synthesis of (E)-1-(4-(3-bromopropoxy)phenyl)-3-(p-tolyl)prop-2-en-1-one: as in step (2) of Example 1.

[0057] (3) 4-((N-methyl-4-nitrophenyl)sulfonamide)piperidine-1-carboxylic acid tert-butyl ester: as in step (3) of Example 1, except that 4-nitrobenzenesulfonyl chloride is used as the raw material.

[0058] (4) Synthesis of N-methyl-4-nitro-N-(piperidin-4-yl)benzenesulfonamide: as in step (4) of Example 1, except that 4-((N-methyl-4-nitrophenyl)sulfonamide)piperidin-1-carboxylic acid tert-butyl ester is used as the raw material.

[0059] (5) Synthesis of (E)-N-methyl-4-nitro-N-(1-(3-(4-(3-(p-tolyl)acryloyl)phenoxy)propyl)piperidin-4-yl)benzenesulfonamide: as in step (5) of Example 1, except that N-methyl-4-nitro-N-(piperidin-4-yl)benzenesulfonamide is used as the raw material.

[0060] Example 3

[0061] The synthesis of (E)-4-chloro-N-methyl-N-(1-(3-(4-(3-(p-tolyl)acryloyl)phenoxy)propyl)piperidin-4-yl)benzenesulfonamide (compound number X3) includes the following steps:

[0062] (1) Synthesis of (E)-1-(4-hydroxyphenyl)-3-(p-tolyl)prop-2-en-1-one: as in step (1) of Example 1.

[0063] (2) Synthesis of (E)-1-(4-(3-bromopropoxy)phenyl)-3-(p-tolyl)prop-2-en-1-one: as in step (2) of Example 1.

[0064] (3) Synthesis of 4-((4-chloro-N-methylphenyl)sulfonamide)piperidine-1-carboxylic acid tert-butyl ester: as in step (3) of Example 1, except that 4-chlorobenzenesulfonyl chloride is used as the raw material.

[0065] (4) Synthesis of 4-chloro-N-methyl-N-(piperidin-4-yl)benzenesulfonamide: as in step (4) of Example 1, except that 4-((4-chloro-N-methylphenyl)sulfonamide)piperidin-1-carboxylic acid tert-butyl ester is used as the raw material.

[0066] (5) Synthesis of (E)-4-chloro-N-methyl-N-(1-(3-(4-(3-(p-tolyl)acryloyl)phenoxy)propyl)piperidin-4-yl)benzenesulfonamide: as in step (5) of Example 1, except that 4-chloro-N-methyl-N-(piperidin-4-yl)benzenesulfonamide is used as the raw material.

[0067] Example 4

[0068] The synthesis of (E)-4-methoxy-N-methyl-N-(1-(3-(4-(3-(p-tolyl)acryloyl)phenoxy)propyl)piperidin-4-yl)benzenesulfonamide (compound number X4) includes the following steps:

[0069] (1) Synthesis of (E)-1-(4-hydroxyphenyl)-3-(p-tolyl)prop-2-en-1-one: as in step (1) of Example 1.

[0070] (2) Synthesis of (E)-1-(4-(3-bromopropoxy)phenyl)-3-(p-tolyl)prop-2-en-1-one: as in step (2) of Example 1.

[0071] (3) Synthesis of 4-((4-methoxy-N-methylphenyl)sulfonamide)piperidine-1-carboxylic acid tert-butyl ester: as in step (3) of Example 1, except that 4-methoxybenzenesulfonyl chloride is used as the raw material.

[0072] (4) Synthesis of 4-methoxy-N-methyl-N-(piperidin-4-yl)benzenesulfonamide: as in step (4) of Example 1, except that 4-((4-methoxy-N-methylphenyl)sulfonamide)piperidin-1-carboxylic acid tert-butyl ester is used as the raw material.

[0073] (5) Synthesis of (E)-4-methoxy-N-methyl-N-(1-(3-(4-(3-(p-tolyl)acryloyl)phenoxy)propyl)piperidin-4-yl)benzenesulfonamide: as in step (5) of Example 1, except that 4-methoxy-N-methyl-N-(piperidin-4-yl)benzenesulfonamide is used as the raw material.

[0074] Example 5

[0075] The synthesis of (E)-N-(1-(3-(4-(3-(furan-2-yl)acryloyl)phenoxy)piperidin-4-yl)-N-methylethanesulfonamide (compound number X5) includes the following steps:

[0076] (1) Synthesis of (E)-3-(furan-2-yl)-1-(4-hydroxyphenyl)prop-2-en-1-one: as in step (1) of Example 1, except that furan-2-carboxaldehyde is used as the raw material.

[0077] (2) Synthesis of (E)-1-(4-(3-bromopropoxy)phenyl)-3-(furan-2-yl)prop-2-en-1-one: as in step (2) of Example 1, except that (E)-3-(furan-2-yl)-1-(4-hydroxyphenyl)prop-2-en-1-one is used as the raw material.

[0078] (3) Synthesis of 4-(N-methylethylsulfonamide)piperidine-1-carboxylic acid tert-butyl ester: as in step (3) of Example 1, except that ethanesulfonyl chloride is used as the raw material.

[0079] (4) Synthesis of N-methyl-N-(piperidin-4-yl)ethanesulfonamide: as in step (4) of Example 1, except that 4-(N-methylethylsulfonamide)piperidin-1-carboxylic acid tert-butyl ester is used as the raw material.

[0080] (5) Synthesis of (E)-N-(1-(3-(4-(3-(furan-2-yl)acryloyl)phenoxy)piperidin-4-yl)-N-methylethanesulfonamide: as in step (5) of Example 1, except that (E)-1-(4-(3-bromopropoxy)phenyl)-3-(furan-2-yl)prop-2-en-1-one and N-methyl-N-(piperidin-4-yl)ethanesulfonamide are used as raw materials.

[0081] Example 6

[0082] The synthesis of (E)-N-(1-(3-(4-(3-(furan-2-yl)acryloyl)phenoxy)propyl)piperidin-4-yl)-N-methyl-4-nitrobenzenesulfonamide (compound number X6) includes the following steps:

[0083] (1) Synthesis of (E)-3-(furan-2-yl)-1-(4-hydroxyphenyl)prop-2-en-1-one: as in step (1) of Example 1, except that furan-2-carboxaldehyde is used as the raw material.

[0084] (2) Synthesis of (E)-1-(4-(3-bromopropoxy)phenyl)-3-(furan-2-yl)prop-2-en-1-one: as in step (2) of Example 1, except that (E)-3-(furan-2-yl)-1-(4-hydroxyphenyl)prop-2-en-1-one is used as the raw material.

[0085] (3) 4-((N-methyl-4-nitrophenyl)sulfonamide)piperidine-1-carboxylic acid tert-butyl ester: as in step (3) of Example 1, except that 4-nitrobenzenesulfonyl chloride is used as the raw material.

[0086] (4) Synthesis of N-methyl-4-nitro-N-(piperidin-4-yl)benzenesulfonamide: as in step (4) of Example 1, except that 4-((N-methyl-4-nitrophenyl)sulfonamide)piperidin-1-carboxylic acid tert-butyl ester is used as the raw material.

[0087] (5) Synthesis of (E)-N-(1-(3-(4-(3-(furan-2-yl)acryloyl)phenoxy)propyl)piperidin-4-yl)-N-methyl-4-nitrobenzenesulfonamide: as in step (5) of Example 1, except that (E)-1-(4-(3-bromopropoxy)phenyl)-3-(furan-2-yl)prop-2-en-1-one and N-methyl-4-nitro-N-(piperidin-4-yl)benzenesulfonamide are used as raw materials.

[0088] Example 7

[0089] The synthesis of (E)-N-(1-(3-(4-(3-(furan-2-yl)acryloyl)phenoxy)propyl)piperidin-4-yl)-4-methoxy-N-methylbenzenesulfonamide (compound number X7) includes the following steps:

[0090] (1) Synthesis of (E)-3-(furan-2-yl)-1-(4-hydroxyphenyl)prop-2-en-1-one: as in step (1) of Example 1, except that furan-2-carboxaldehyde is used as the raw material.

[0091] (2) Synthesis of (E)-1-(4-(3-bromopropoxy)phenyl)-3-(furan-2-yl)prop-2-en-1-one: as in step (2) of Example 1, except that (E)-3-(furan-2-yl)-1-(4-hydroxyphenyl)prop-2-en-1-one is used as the raw material.

[0092] (3) Synthesis of 4-((4-methoxy-N-methylphenyl)sulfonamide)piperidine-1-carboxylic acid tert-butyl ester: as in step (3) of Example 1, except that 4-methoxybenzenesulfonyl chloride is used as the raw material.

[0093] (4) Synthesis of 4-methoxy-N-methyl-N-(piperidin-4-yl)benzenesulfonamide: as in step (4) of Example 1, except that 4-((4-methoxy-N-methylphenyl)sulfonamide)piperidin-1-carboxylic acid tert-butyl ester is used as the raw material.

[0094] (5) Synthesis of (E)-N-(1-(3-(4-(3-(furan-2-yl)acryloyl)phenoxy)propyl)piperidin-4-yl)-4-methoxy-N-methylbenzenesulfonamide: as in step (5) of Example 1, except that (E)-1-(4-(3-bromopropoxy)phenyl)-3-(furan-2-yl)prop-2-en-1-one and 4-methoxy-N-methyl-N-(piperidin-4-yl)benzenesulfonamide are used as raw materials.

[0095] Example 8

[0096] The synthesis of (E)-N-(1-(3-(4-(3-(4-fluorophenyl)acryloyl)phenoxy)propyl)piperidin-4-yl)-N-methylethanesulfonamide (compound number X8) includes the following steps:

[0097] (1) Synthesis of (E)-3-(4-fluorophenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one: as in step (1) of Example 1, except that p-4-fluorobenzaldehyde is used as the raw material.

[0098] (2) Synthesis of (E)-1-(4-(3-bromopropoxy)phenyl)-3-(4-fluorophenyl)prop-2-en-1-one: as in step (2) of Example 1, except that (E)-3-(4-fluorophenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one is used as the raw material.

[0099] (3) Synthesis of 4-(N-methylethylsulfonamide)piperidine-1-carboxylic acid tert-butyl ester: as in step (3) of Example 1, except that ethanesulfonyl chloride is used as the raw material.

[0100] (4) Synthesis of N-methyl-N-(piperidin-4-yl)ethanesulfonamide: as in step (4) of Example 1, except that 4-(N-methylethylsulfonamide)piperidin-1-carboxylic acid tert-butyl ester is used as the raw material.

[0101] (5) Synthesis of (E)-N-(1-(3-(4-(3-(4-fluorophenyl)acryloyl)phenoxy)propyl)piperidin-4-yl)-N-methylethanesulfonamide: as in step (5) of Example 1, except that (E)-1-(4-(3-bromopropoxy)phenyl)-3-(4-fluorophenyl)prop-2-en-1-one and N-methyl-N-(piperidin-4-yl)ethanesulfonamide are used as raw materials.

[0102] Example 9

[0103] The synthesis of (E)-N-(1-(3-(4-(3-(4-chlorophenyl)acryloyl)phenoxy)propyl)piperidin-4-yl)-N-methylethanesulfonamide (compound number X9) includes the following steps:

[0104] (1) Synthesis of (E)-3-(4-chlorophenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one: as in step (1) of Example 1, except that p-4-chlorobenzaldehyde is used as the raw material.

[0105] (2) Synthesis of (E)-1-(4-(3-bromopropoxy)phenyl)-3-(4-chlorophenyl)prop-2-en-1-one: as in step (2) of Example 1, except that (E)-3-(4-chlorophenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one is used as the raw material.

[0106] (3) Synthesis of 4-(N-methylethylsulfonamide)piperidine-1-carboxylic acid tert-butyl ester: as in step (3) of Example 1, except that ethanesulfonyl chloride is used as the raw material.

[0107] (4) Synthesis of N-methyl-N-(piperidin-4-yl)ethanesulfonamide: as in step (4) of Example 1, except that 4-(N-methylethylsulfonamide)piperidin-1-carboxylic acid tert-butyl ester is used as the raw material.

[0108] (5) Synthesis of (E)-N-(1-(3-(4-(3-(4-chlorophenyl)acryloyl)phenoxy)propyl)piperidin-4-yl)-N-methylethanesulfonamide: as in step (5) of Example 1, except that (E)-1-(4-(3-bromopropoxy)phenyl)-3-(4-chlorophenyl)prop-2-en-1-one and N-methyl-N-(piperidin-4-yl)ethanesulfonamide are used as raw materials.

[0109] Example 10

[0110] The synthesis of (E)-N-(1-(3-(4-(3-(4-bromophenyl)acryloyl)phenoxy)propyl)piperidin-4-yl)-N-methylethanesulfonamide (compound number X10) includes the following steps:

[0111] (1) Synthesis of (E)-3-(4-bromophenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one: as in step (1) of Example 1, except that p-4-bromobenzaldehyde is used as the raw material.

[0112] (2) Synthesis of (E)-1-(4-(3-bromopropoxy)phenyl)-3-(4-bromophenyl)prop-2-en-1-one: as in step (2) of Example 1, except that (E)-3-(4-bromophenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one is used as the starting material.

[0113] (3) Synthesis of 4-(N-methylethylsulfonamide)piperidine-1-carboxylic acid tert-butyl ester: as in step (3) of Example 1, except that ethanesulfonyl chloride is used as the raw material.

[0114] (4) Synthesis of N-methyl-N-(piperidin-4-yl)ethanesulfonamide: as in step (4) of Example 1, except that 4-(N-methylethylsulfonamide)piperidin-1-carboxylic acid tert-butyl ester is used as the raw material.

[0115] (5) Synthesis of (E)-N-(1-(3-(4-(3-(4-bromophenyl)acryloyl)phenoxy)propyl)piperidin-4-yl)-N-methylethanesulfonamide: as in step (5) of Example 1, except that (E)-1-(4-(3-bromopropoxy)phenyl)-3-(4-bromophenyl)prop-2-en-1-one and N-methyl-N-(piperidin-4-yl)ethanesulfonamide are used as raw materials.

[0116] Example 11

[0117] The synthesis of (E)-N-(1-(3-(4-(3-(2,4-dichlorophenyl)acryloyl)phenoxy)propyl)piperidin-4-yl)-4-methoxy-N-methylbenzenesulfonamide (compound number X11) includes the following steps:

[0118] (1) Synthesis of (E)-3-(2,4-dichlorophenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one: as in step (1) of Example 1, except that 2,4-dichlorobenzaldehyde is used as the raw material.

[0119] (2) Synthesis of (E)-1-(4-(3-bromopropoxy)phenyl)-3-(2,4-dichlorophenyl)prop-2-en-1-one: as in step (2) of Example 1, except that (E)-3-(2,4-dichlorophenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one is used as the starting material.

[0120] (3) Synthesis of 4-((4-methoxy-N-methylphenyl)sulfonamide)piperidine-1-carboxylic acid tert-butyl ester: as in step (3) of Example 1, except that 4-methoxybenzenesulfonyl chloride is used as the raw material.

[0121] (4) Synthesis of 4-methoxy-N-methyl-N-(piperidin-4-yl)benzenesulfonamide: as in step (4) of Example 1, except that 4-((4-methoxy-N-methylphenyl)sulfonamide)piperidin-1-carboxylic acid tert-butyl ester is used as the raw material.

[0122] (5) Synthesis of (E)-N-(1-(3-(4-(3-(2,4-dichlorophenyl)acryloyl)phenoxy)propyl)piperidin-4-yl)-4-methoxy-N-methylbenzenesulfonamide: as in step (5) of Example 1, except that (E)-1-(4-(3-bromopropoxy)phenyl)-3-(2,4-dichlorophenyl)prop-2-en-1-one and 4-methoxy-N-methyl-N-(piperidin-4-yl)benzenesulfonamide are used as raw materials.

[0123] Example 12

[0124] The synthesis of (E)-N-methyl-4-nitro-N-(1-(3-(4-(3-(thiophen-2-yl)acryloyl)phenoxy)piperidin-4-yl)benzenesulfonamide (compound number X12) includes the following steps:

[0125] (1) Synthesis of (E)-1-(4-hydroxyphenyl)-3-(thiophen-2-yl)prop-2-en-1-one: as in step (1) of Example 1, except that thiophen-2-carboxaldehyde is used as the raw material.

[0126] (2) Synthesis of (E)-1-(4-(3-bromopropoxy)phenyl)-3-(thiophen-2-yl)prop-2-en-1-one: as in step (2) of Example 1, except that (E)-1-(4-hydroxyphenyl)-3-(thiophen-2-yl)prop-2-en-1-one is used as the starting material.

[0127] (3) 4-((N-methyl-4-nitrophenyl)sulfonamide)piperidine-1-carboxylic acid tert-butyl ester: as in step (3) of Example 1, except that 4-nitrobenzenesulfonyl chloride is used as the raw material.

[0128] (4) Synthesis of N-methyl-4-nitro-N-(piperidin-4-yl)benzenesulfonamide: as in step (4) of Example 1, except that 4-((N-methyl-4-nitrophenyl)sulfonamide)piperidin-1-carboxylic acid tert-butyl ester is used as the raw material.

[0129] (5) Synthesis of (E)-N-methyl-4-nitro-N-(1-(3-(4-(3-(thiophen-2-yl)acryloyl)phenoxy)piperidin-4-yl)benzenesulfonamide: as in step (5) of Example 1, except that (E)-1-(4-(3-bromopropoxy)phenyl)-3-(thiophen-2-yl)prop-2-en-1-one and N-methyl-4-nitro-N-(piperidin-4-yl)benzenesulfonamide are used as raw materials.

[0130] Example 13

[0131] The synthesis of (E)-4-chloro-N-methyl-N-(1-(3-(4-(3-(thiophen-2-yl)acryloyl)phenoxy)propyl)piperidin-4-yl)benzenesulfonamide (compound number X13) includes the following steps:

[0132] (1) Synthesis of (E)-1-(4-hydroxyphenyl)-3-(thiophen-2-yl)prop-2-en-1-one: as in step (1) of Example 1, except that thiophen-2-carboxaldehyde is used as the raw material.

[0133] (2) Synthesis of (E)-1-(4-(3-bromopropoxy)phenyl)-3-(thiophen-2-yl)prop-2-en-1-one: as in step (2) of Example 1, except that (E)-1-(4-hydroxyphenyl)-3-(thiophen-2-yl)prop-2-en-1-one is used as the starting material.

[0134] (3) Synthesis of 4-((4-chloro-N-methylphenyl)sulfonamide)piperidine-1-carboxylic acid tert-butyl ester: as in step (3) of Example 1, except that 4-chlorobenzenesulfonyl chloride is used as the raw material.

[0135] (4) Synthesis of 4-chloro-N-methyl-N-(piperidin-4-yl)benzenesulfonamide: as in step (4) of Example 1, except that 4-((4-chloro-N-methylphenyl)sulfonamide)piperidin-1-carboxylic acid tert-butyl ester is used as the raw material.

[0136] (5) Synthesis of (E)-4-chloro-N-methyl-N-(1-(3-(4-(3-(thiophen-2-yl)acryloyl)phenoxy)propyl)piperidin-4-yl)benzenesulfonamide: as in step (5) of Example 1, except that (E)-1-(4-(3-bromopropoxy)phenyl)-3-(thiophen-2-yl)prop-2-en-1-one and 4-chloro-N-methyl-N-(piperidin-4-yl)benzenesulfonamide are used as raw materials.

[0137] Example 14

[0138] The synthesis of (E)-N-methyl-N-(1-(3-(4-(3-(thiophen-2-yl)acryloyl)phenoxy)piperidin-4-yl)ethanesulfonamide (compound number X14) includes the following steps:

[0139] (1) Synthesis of (E)-1-(4-hydroxyphenyl)-3-(thiophen-2-yl)prop-2-en-1-one: as in step (1) of Example 1, except that thiophen-2-carboxaldehyde is used as the raw material.

[0140] (2) Synthesis of (E)-1-(4-(3-bromopropoxy)phenyl)-3-(thiophen-2-yl)prop-2-en-1-one: as in step (2) of Example 1, except that (E)-1-(4-hydroxyphenyl)-3-(thiophen-2-yl)prop-2-en-1-one is used as the starting material.

[0141] (3) Synthesis of 4-(N-methylethylsulfonamide)piperidine-1-carboxylic acid tert-butyl ester: as in step (3) of Example 1, except that ethanesulfonyl chloride is used as the raw material.

[0142] (4) Synthesis of N-methyl-N-(piperidin-4-yl)ethanesulfonamide: as in step (4) of Example 1, except that 4-(N-methylethylsulfonamide)piperidin-1-carboxylic acid tert-butyl ester is used as the raw material.

[0143] (5) Synthesis of (E)-N-methyl-N-(1-(3-(4-(3-(thiophen-2-yl)acryloyl)phenoxy)piperidin-4-yl)ethanesulfonamide: as in step (5) of Example 1, except that (E)-1-(4-(3-bromopropoxy)phenyl)-3-(thiophen-2-yl)prop-2-en-1-one and N-methyl-N-(piperidin-4-yl)ethanesulfonamide are used as raw materials.

[0144] Example 15

[0145] The synthesis of (E)-4-methoxy-N-methyl-N-(1-(3-(4-(3-(thiophen-2-yl)acryloyl)phenoxy)propyl)piperidin-4-yl)benzenesulfonamide (compound number X15) includes the following steps:

[0146] (1) Synthesis of (E)-1-(4-hydroxyphenyl)-3-(thiophen-2-yl)prop-2-en-1-one: as in step (1) of Example 1, except that thiophen-2-carboxaldehyde is used as the raw material.

[0147] (2) Synthesis of (E)-1-(4-(3-bromopropoxy)phenyl)-3-(thiophen-2-yl)prop-2-en-1-one: as in step (2) of Example 1, except that (E)-1-(4-hydroxyphenyl)-3-(thiophen-2-yl)prop-2-en-1-one is used as the starting material.

[0148] (3) Synthesis of 4-((4-methoxy-N-methylphenyl)sulfonamide)piperidine-1-carboxylic acid tert-butyl ester: as in step (3) of Example 1, except that 4-methoxybenzenesulfonyl chloride is used as the raw material.

[0149] (4) Synthesis of 4-methoxy-N-methyl-N-(piperidin-4-yl)benzenesulfonamide: as in step (4) of Example 1, except that 4-((4-methoxy-N-methylphenyl)sulfonamide)piperidin-1-carboxylic acid tert-butyl ester is used as the raw material.

[0150] (5) Synthesis of (E)-4-methoxy-N-methyl-N-(1-(3-(4-(3-(thiophen-2-yl)acryloyl)phenoxy)propyl)piperidin-4-yl)benzenesulfonamide: as in step (5) of Example 1, except that (E)-1-(4-(3-bromopropoxy)phenyl)-3-(thiophen-2-yl)prop-2-en-1-one and 4-methoxy-N-methyl-N-(piperidin-4-yl)benzenesulfonamide are used as raw materials.

[0151] Example 16

[0152] The synthesis of (E)-N-methyl-N-(1-(3-(4-(3-(thiophen-2-yl)acryloyl)phenoxy)piperidin-4-yl)-4-(trifluoromethyl)benzenesulfonamide (compound number X16) includes the following steps:

[0153] (1) Synthesis of (E)-1-(4-hydroxyphenyl)-3-(thiophen-2-yl)prop-2-en-1-one: as in step (1) of Example 1, except that thiophen-2-carboxaldehyde is used as the raw material.

[0154] (2) Synthesis of (E)-1-(4-(3-bromopropoxy)phenyl)-3-(thiophen-2-yl)prop-2-en-1-one: as in step (2) of Example 1, except that (E)-1-(4-hydroxyphenyl)-3-(thiophen-2-yl)prop-2-en-1-one is used as the starting material.

[0155] (3) Synthesis of 4-((N-methyl-4-(trifluoromethyl)phenyl)sulfonamide)piperidine-1-carboxylic acid tert-butyl ester: as in step (3) of Example 1.

[0156] (4) Synthesis of N-methyl-N-(piperidin-4-yl)-4-(trifluoromethyl)benzenesulfonamide: as in step (4) of Example 1.

[0157] (5) Synthesis of (E)-N-methyl-N-(1-(3-(4-(3-(thiophen-2-yl)acryloyl)phenoxy)piperidin-4-yl)-4-(trifluoromethyl)benzenesulfonamide: as in step (5) of Example 1, except that (E)-1-(4-(3-bromopropoxy)phenyl)-3-(thiophen-2-yl)prop-2-en-1-one is used as the starting material.

[0158] Example 17

[0159] The synthesis of (E)-N-(1-(3-(4-(3-(2,4-dichlorophenyl)acryloyl)phenoxy)propyl)piperidin-4-yl)-N-methylethanesulfonamide (compound number X17) includes the following steps:

[0160] (1) Synthesis of (E)-3-(2,4-dichlorophenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one: as in step (1) of Example 1, except that 2,4-dichlorobenzaldehyde is used as the raw material.

[0161] (2) Synthesis of (E)-1-(4-(3-bromopropoxy)phenyl)-3-(2,4-dichlorophenyl)prop-2-en-1-one: as in step (2) of Example 1, except that (E)-3-(2,4-dichlorophenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one is used as the starting material.

[0162] (3) Synthesis of 4-(N-methylethylsulfonamide)piperidine-1-carboxylic acid tert-butyl ester: as in step (3) of Example 1, except that ethanesulfonyl chloride is used as the raw material.

[0163] (4) Synthesis of N-methyl-N-(piperidin-4-yl)ethanesulfonamide: as in step (4) of Example 1, except that 4-(N-methylethylsulfonamide)piperidin-1-carboxylic acid tert-butyl ester is used as the raw material.

[0164] (5) Synthesis of (E)-N-(1-(3-(4-(3-(2,4-dichlorophenyl)acryloyl)phenoxy)propyl)piperidin-4-yl)-N-methylethanesulfonamide: as in step (5) of Example 1, except that (E)-1-(4-(3-bromopropoxy)phenyl)-3-(2,4-dichlorophenyl)prop-2-en-1-one and N-methyl-N-(piperidin-4-yl)ethanesulfonamide are used as raw materials.

[0165] Example 18

[0166] The synthesis of (E)-N-methyl-N-(1-(3-(4-(3-(p-tolyl)acryloyl)phenoxy)propyl)piperidin-4-yl)ethanesulfonamide (compound number X18) includes the following steps:

[0167] (1) Synthesis of (E)-1-(4-hydroxyphenyl)-3-(p-tolyl)prop-2-en-1-one: as in step (1) of Example 1.

[0168] (2) Synthesis of (E)-1-(4-(3-bromopropoxy)phenyl)-3-(p-tolyl)prop-2-en-1-one: as in step (2) of Example 1.

[0169] (3) Synthesis of 4-(N-methylethylsulfonamide)piperidine-1-carboxylic acid tert-butyl ester: as in step (3) of Example 1, except that ethanesulfonyl chloride is used as the raw material.

[0170] (4) Synthesis of N-methyl-N-(piperidin-4-yl)ethanesulfonamide: as in step (4) of Example 1, except that 4-(N-methylethylsulfonamide)piperidin-1-carboxylic acid tert-butyl ester is used as the raw material.

[0171] (5) Synthesis of (E)-N-methyl-N-(1-(3-(4-(3-(p-tolyl)acryloyl)phenoxy)propyl)piperidin-4-yl)ethanesulfonamide: as in step (5) of Example 1, except that N-methyl-N-(piperidin-4-yl)ethanesulfonamide is used as the raw material.

[0172] Example 19

[0173] The synthesis of N-(1-(3-(4-cinnamylphenoxy)propyl)piperidin-4-yl)-N-methylethanesulfonamide (compound number X19) includes the following steps:

[0174] (1) Synthesis of (E)-1-(4-hydroxyphenyl)-3-phenyl-2-propen-1-one: as in step (1) of Example 1, except that benzoaldehyde is used as the raw material.

[0175] (2) Synthesis of (E)-1-(4-(3-bromopropoxy)phenyl)-3-phenyl-2-propen-1-one: as in step (2) of Example 1, except that (E)-1-(4-hydroxyphenyl)-3-phenyl-2-propen-1-one is used as the raw material.

[0176] (3) Synthesis of 4-(N-methylethylsulfonamide)piperidine-1-carboxylic acid tert-butyl ester: as in step (3) of Example 1, except that ethanesulfonyl chloride is used as the raw material.

[0177] (4) Synthesis of N-methyl-N-(piperidin-4-yl)ethanesulfonamide: as in step (4) of Example 1, except that 4-(N-methylethylsulfonamide)piperidin-1-carboxylic acid tert-butyl ester is used as the raw material.

[0178] (5) Synthesis of N-(1-(3-(4-cinnamylphenoxy)propyl)piperidin-4-yl)-N-methylethanesulfonamide: as in step (5) of Example 1, except that (E)-1-(4-(3-bromopropoxy)phenyl)-3-phenyl-2-propen-1-one and N-methyl-N-(piperidin-4-yl)ethanesulfonamide are used as raw materials.

[0179] Example 20

[0180] The synthesis of (E)-4-chloro-N-(1-(3-(4-(3-(furan-2-yl)acryloyl)phenoxy)propyl)piperidin-4-yl)-N-methylbenzenesulfonamide (compound number X20) includes the following steps:

[0181] (1) Synthesis of (E)-3-(furan-2-yl)-1-(4-hydroxyphenyl)prop-2-en-1-one: as in step (1) of Example 1, except that furan-2-carboxaldehyde is used as the raw material.

[0182] (2) Synthesis of (E)-1-(4-(3-bromopropoxy)phenyl)-3-(furan-2-yl)prop-2-en-1-one: as in step (2) of Example 1, except that (E)-3-(furan-2-yl)-1-(4-hydroxyphenyl)prop-2-en-1-one is used as the raw material.

[0183] (3) Synthesis of 4-((4-chloro-N-methylphenyl)sulfonamide)piperidine-1-carboxylic acid tert-butyl ester: as in step (3) of Example 1, except that 4-chlorobenzenesulfonyl chloride is used as the raw material.

[0184] (4) Synthesis of 4-chloro-N-methyl-N-(piperidin-4-yl)benzenesulfonamide: as in step (4) of Example 1, except that 4-((4-chloro-N-methylphenyl)sulfonamide)piperidin-1-carboxylic acid tert-butyl ester is used as the raw material.

[0185] (5) Synthesis of (E)-4-chloro-N-(1-(3-(4-(3-(furan-2-yl)acryloyl)phenoxy)propyl)piperidin-4-yl)-N-methylbenzenesulfonamide: as in step (5) of Example 1, except that (E)-1-(4-(3-bromopropoxy)phenyl)-3-(furan-2-yl)prop-2-en-1-one and 4-chloro-N-methyl-N-(piperidin-4-yl)benzenesulfonamide are used as raw materials.

[0186] The yields, physicochemical properties, and mass spectrometry data of compounds X1-X20 synthesized in Examples 1-20 are shown in Table 1. (1H NMR spectra are also provided.) 1 HNMR and carbon spectroscopy 13 The C NMR data are shown in Table 2.

[0187] Table 1 Physicochemical properties and mass spectrometry analysis data of the target compound

[0188]

[0189]

[0190] Table 2. 1H and 1C NMR spectra of the target compounds

[0191]

[0192]

[0193]

[0194]

[0195]

[0196] Test case

[0197] The test method for antifungal activity against plants is as follows:

[0198] Using the mycelial growth rate method (Zhang et al., Pestic Biochem Physiol, 2018, 147, 75-82.), the 20 synthesized compounds were subjected to in vitro antifungal experiments.

[0199] Preparation of potato dextrose agar (PDA) medium: Weigh 40.1g of potato dextrose agar, add 1000mL of distilled water, heat to boiling to dissolve, and while still hot, transfer 19.8mL of the medium into a 50mL Erlenmeyer flask, seal with a breathable sealing film, and autoclave at 121℃ for 20min for later use.

[0200] Antifungal activity test: Dissolve 3 mg of the compound in 300 μL of DMSO to prepare a solution. Wipe the laminar flow hood with 75% ethanol and ignite the alcohol lamp. In the laminar flow hood, add 200 μL of the prepared solution to 19.8 mL of DMSO medium and mix well. Divide the solution into three petri dishes and let cool. Use azoxystrobin as a positive control; the preparation method for azoxystrobin is the same as for the other positive control. Add 200 μL of DMSO medium to 19.8 mL of DMSO medium and mix well. Divide the solution into three petri dishes and let cool as a blank control. Using a 5 mm perforator sterilized at high temperature, punch the pre-activated inoculum into 5 mm diameter mycelial cakes. Use a sterilized inoculation needle to pick up the mycelial cakes and invert them onto the center of the cooled petri dishes. Seal the petri dishes, invert them, and incubate them in a 25°C incubator. Once the hyphae have grown to 3 / 4 of the height of the petri dish, measure the diameter of the hyphae using the cross-sectional method. Repeat the measurement three times for each sample, and calculate the inhibition rate using the following formula:

[0201] Inhibition rate (%) = (CK-C1) / (CK-5) × 100

[0202] CK: Mycelial diameter of blank control (colonies treated with DMSO)

[0203] C1: Mycelial diameter (mm) after chemical treatment

[0204] 5: Diameter of the inoculated mycelium cake (5mm)

[0205] The results of the bioactivity tests against plant fungi are shown in Tables 3 and 4.

[0206] Table 3. Inhibition rate of the target compound against plant fungi at a concentration of 100 μg / mL.

[0207]

[0208]

[0209] Note: a: Average of three parallel tests. b: The inhibitory activity of the fungicide azoxystrobin is a positive control.

[0210] Table 4. Inhibition rate of the target compound against plant fungi at a concentration of 100 μg / mL.

[0211]

[0212] Note: a: Average of three parallel tests. b: The inhibitory activity of the fungicide azoxystrobin is a positive control.

[0213] The mycelial growth rate method was used, with the fungicide azoxystrobin as a control, to test the inhibition rate of compounds X1–X20 at a concentration of 100 μg / mL against plant fungi. The results of the antifungal activity showed that the chalcone derivatives containing piperidine sulfonamide groups exhibited good antifungal activity against the tested fungal species. Compounds X4, X8, X9, X10, X14, X16, X17, X18, and X19 showed inhibition rates of 84.2%, 92.9%, 95.8%, 93.8%, 85.8%, 70.8%, 99.2%, 90.4%, and 84.6% against *Sclerotinia sclerotinia*, respectively, exceeding the 70.0% inhibition rate of azoxystrobin. Compounds X4, X6, X8, X9, X10, X14, X17, X18, and X19 exhibited inhibition rates of 71.9%, 62.9%, 81.4%, 91.0%, 88.6%, 61.4%, 91.4%, 89.5%, and 62.9% against *Actinidia kiwifruit*, respectively, exceeding the inhibition rate of azoxystrobin (60.5%). Compounds X4, X9, X10, X17, X18, and X20 showed inhibition rates of 78.7%, 84.3%, 87.7%, 86.0%, 76.6%, and 86.0% against *Actinidia chinensis*, respectively, exceeding the inhibition rate of azoxystrobin (74.0%). Compounds X3, X4, X7, X8, X9, X10, X11, X17, X18, X19, and X20 showed inhibition rates of 62.4%, 69.4%, 78.1%, 78.9%, 82.2%, 80.2%, 68.2%, 86.8%, 84.3%, 78.5%, and 67.4% against *Fusarium oxysporum*, *Fusarium graminearum*, and *Neoprothiolane diatomaceous*, respectively, exceeding the inhibition rates of azoxystrobin (58.8%). Furthermore, X9 showed inhibition rates of 43.6%, 40.5%, and 62.1% against *Fusarium oxysporum*, *Fusarium graminearum*, and *Neoprothiolane diatomaceous*, respectively, exceeding the inhibition rates of azoxystrobin (32.4%, 40.1%, and 57.9%). X10 showed inhibition rates of 41.3% and 64.2% against *Fusarium oxysporum* and *Neoprothiolane diatomaceous*, respectively, exceeding the inhibition rates of azoxystrobin (32.4% and 57.9%). X17 showed inhibition rates of 54.2% and 75.4% against *Anthracis capsici* and *Neoprothiolane davidii*, respectively, exceeding the inhibition rates of 51.3% and 57.9% for azoxystrobin. X18 showed inhibition rates of 42.7% and 78.8% against *Fusarium oxysporum* and *Neoprothiolane davidii*, respectively, exceeding the inhibition rates of 32.4% and 57.9% for azoxystrobin.

[0214] Compounds X4, X8, X9, X10, X17, X18 and X19 all showed good antifungal activity against a variety of tested fungal species, indicating that X4, X8, X9, X10, X17, X18 and X19 have broad-spectrum antifungal activity.

[0215] In summary, chalcone derivatives containing piperidine sulfonamide structures have inhibitory effects on plant fungi, and some of these compounds exhibit good antifungal activity, making them potential antifungal drugs with promising application prospects.

[0216] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A chalcone derivative containing a piperidine sulfonamide structure, characterized in that, The general structural formula is shown in Formula I: In Formula I, R1 is a phenyl, a phenyl with para-substituted methyl, fluorine, chlorine or bromine, a phenyl with simultaneous chlorine substitution at both the ortho and meta positions, a 2-thienyl or 2-furanyl. R2 is a C1-C6 alkyl group, or a substituted phenyl group with one or more substituents located at the para, ortho, and meta positions on the benzene ring, wherein the substituents are selected from methyl, trifluoromethyl, nitro, methoxy, fluorine, chlorine, or bromine.

2. A method for preparing the chalcone derivative containing the piperidine sulfonamide structure as described in claim 1, characterized in that, Includes the following steps: (1) with p-hydroxyacetophenone and Using raw materials, it reacts under alkaline conditions to produce ; (2) Continue with Using dibromopropane as a raw material, an acid-binding agent is added, and the reaction produces... ； (3) with 1-tert-butoxycarbonyl-4-methylaminopiperidine and Using it as a raw material, an acid-binding agent is added, and the reaction produces... ; (4) to and hydrochloric acid as raw materials, reaction to prepare ; (5) with and Using [a specific ingredient] as a raw material, an acid-binding agent is added, and the reaction produces the chalcone derivative containing the piperidine sulfonamide structure. .

3. The method for preparing a chalcone derivative containing a piperidine sulfonamide structure according to claim 2, characterized by, The acid-binding agent in step (2) is potassium carbonate; the acid-binding agent in step (3) is triethylamine; the acid-binding agent in step (5) is potassium carbonate.

4. The use of the chalcone derivative containing the piperidine sulfonamide structure as described in claim 1 in the preparation of a fungicide against plant fungi.

5. The application according to claim 4, characterized in that, The plant fungi are selected from Sclerotinia sclerotiorum rape, Actinidia kiwifruit, Phytophthora capsici, Fusarium capsici, Botrytis cinerea, Anthracnose, Colletotrichum capsici, Fusarium solani, Rhizoctonia solani, Rhizoctonia solani, Fusarium graminearum ... or Neodatura spp.

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