Preparation method of novel plant virus resisting agent and derivative thereof and application of novel plant virus resisting agent and derivative thereof in foliar fertilizer

Abstract

The invention discloses a preparation method of a novel plant virus resisting agent and a derivative thereof, and application of the novel plant virus resisting agent and the derivative in foliar fertilizer. The general formula of the derivative is shown in the specification, wherein R is halogen, methyl, methoxyl or disubstituted or trisubstituted of any combination of the above substituent groups. The derivative disclosed by the invention has a relatively good inhibition effect on tobacco mosaic virus diseases, cucumber mosaic virus diseases and potato Y virus diseases. The compound II-15 has a relatively good inhibition effect on three virus diseases.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of chemical technology, in particular to a novel anti-plant virus agent and its derivative, and the use of the agent and its derivative in inhibiting tobacco mosaic virus disease, cucumber mosaic virus disease and potato virus Y disease. BACKGROUND

[0002] Plant virus disease is a very serious plant disease, and the outbreak is very widespread, the disaster is serious, and the prevention and control is very difficult. Tobacco mosaic virus (TMV), cucumber mosaic virus (CMV) and potato virus Y (PVY) are typical plant virus diseases affecting crop health. After the virus infects the host, it not only competes with the host for the necessary nutrients for growth, but also destroys the nutrient transport of the plant, changes the metabolic balance of the host plant, inhibits the photosynthesis of the plant, makes the plant difficult to grow, and produces symptoms such as deformation and yellowing. Even serious, it can cause the death of the host plant. Pesticide researchers have done a lot of work to effectively control plant virus diseases, but still cannot achieve the expected effect. So far, there is no inhibitory agent that can completely inhibit plant viruses. Therefore, the development of a new type of high-efficiency, low-toxicity, environment-friendly anti-disease and antibacterial agent has become one of the biggest challenges in agriculture.

[0003] Among the heterocyclic compounds, oxygen-containing heterocyclic compounds occupy an important position. Due to their unique biological activity, they have been favored by many chemists. Due to the good biological activity and environmental compatibility of coumarin heterocyclic compounds, they have become a research hotspot at home and abroad. In recent years, it has been found that compounds containing coumarin heterocyclic compounds have good anti-plant virus activity.

[0004] In summary, coumarin derivatives show certain antiviral activity, providing a reference for the development of new and efficient antiviral agents. On the basis of the previous work, a series of coumarin compounds containing sulfonamide structure are designed and synthesized, and their antiviral activity is studied, hoping to screen out high-activity antiviral drugs. SUMMARY

[0005] The present application aims to provide a preparation method of a coumarin compound with antiviral activity and containing sulfonamide structure.

[0006] Another object of the present application is the use of the coumarin compound in inhibiting tobacco mosaic virus disease, cucumber mosaic virus disease and potato virus Y disease.

[0007] The technical scheme of the present application is a novel anti-plant virus agent and its derivative, wherein the derivative has the following general formula (I):

[0008]

[0009] wherein: R is halogen, methyl, methoxy or di- or tri-substituted with any combination of the above substituents. Preferably, R is 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3-bromophenyl, 4-bromophenyl, 4-methoxyphenyl, 4-bromo-2-fluorophenyl, 2-fluorophenyl, 2,4-dichloro-phenyl, naphthyl, n-propyl, 4-cyanophenyl, 4-benzylbromophenyl, 4-chloro-3-nitrophenyl, 2-fluoro-3-chlorophenyl, phenyl, 4-fluorophenyl, 4-fluoro-2-bromophenyl, 2,4-dinitrophenyl, 3-methoxyphenyl.

[0010] Coumarin derivatives containing a sulfonamide structure, specific compounds are as follows:

[0011] Compound II-1 : N-(4-bromo-2-oxo-2H-chromen-6-yl)-2-chlorobenzenesulfonamide;

[0012] Compound II-2: N-(4-bromo-2-oxo-2H-chromen-6-yl)-3-chlorobenzenesulfonamide;

[0013] Compound II-3: N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-chlorobenzenesulfonamide;

[0014] Compound II-4: N-(4-bromo-2-oxo-2H-chromen-6-yl)-3-bromobenzenesulfonamide;

[0015] Compound II-5: N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-bromobenzenesulfonamide;

[0016] Compound II-6: N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-methoxybenzenesulfonamide;

[0017] Compound II-7: N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-bromo-2-fluorobenzenesulfonamide;

[0018] Compound II-8: N-(4-bromo-2-oxo-2H-chromen-6-yl)-2-fluorobenzenesulfonamide;

[0019] Compound II-9: N-(4-bromo-2-oxo-2H-chromen-6-yl)-2,4-dichlorobenzenesulfonamide;

[0020] Compound II-10: N-(4-bromo-2-oxo-2H-chromen-6-yl)naphthylsulfonamide;

[0021] Compound II-11 : N-(4-bromo-2-oxo-2H-chromen-6-yl)propylsulfonamide;

[0022] Compound II-12: N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-cyanophenylsulfonamide;

[0023] Compound II-13: N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-bromobenzylphenylsulfonamide;

[0024] Compound II-14: N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-chloro-2-nitrophenylsulfonamide;

[0025] Compound II-15: N-(4-bromo-2-oxo-2H-chromen-6-yl)-2-fluoro-3-chlorophenylsulfonamide;

[0026] Compound II-16: N-(4-bromo-2-oxo-2H-chromen-6-yl)phenylsulfonamide;

[0027] Compound II-17: N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-fluorophenylsulfonamide;

[0028] Compound II-18: N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-fluoro-2-bromophenylsulfonamide;

[0029] Compound II-19: N-(4-bromo-2-oxo-2H-chromen-6-yl)-2,4-dinitrophenylsulfonamide;

[0030] Compound II-20: N-(4-bromo-2-oxo-2H-chromen-6-yl)-3-methoxyphenylsulfonamide;

[0031] A novel anti-plant virus agent and a preparation method of derivatives thereof, comprising the following steps:

[0032] (1) 4-hydroxy coumarin: tetrabutylammonium bromide: phosphorus pentoxide 1:1.5:4, heating to reflux for 4-6 h, after the reaction is completed, the temperature is reduced to room temperature, and the system is washed with 10% sodium bicarbonate solution, and the system is extracted with an appropriate amount of toluene, and the organic layer is collected and evaporated under reduced pressure to obtain 4-bromocoumarin;

[0033]

[0034] (2) Add 4-bromocoumarin: nitric acid: sulfuric acid = 1:1~1.2:1.5, stir in an ice bath for 4-6 hours. After the reaction is complete, pour the reaction system into ice water with a magnetic stirrer and stir thoroughly. After the temperature drops to room temperature, filter and collect the solid to obtain 4-bromo-6-nitrocoumarin.

[0035]

[0036] (3) Add 4-bromo-6-nitrocoumarin: iron = 1:1 to 1.2:1.5, stir in an ice bath for 4-6 hours. After the reaction is complete, pour the reaction system into ice water with a magnetic stirrer and stir thoroughly. After the temperature drops to room temperature, filter and collect the solid to obtain 4-bromo-6-aminocoumarin.

[0037]

[0038] (4) 4-Bromo-6-aminocoumarin:substituted sulfonyl chloride:potassium carbonate = 1:1~1.2:1.5 was added and stirred at room temperature for 1 h. After the reaction was completed, the reaction system was extracted with ethyl acetate, the organic layer was collected, and the target compound was obtained by column chromatography.

[0039]

[0040] The application of the derivatives in the preparation of drugs for the prevention and control of plant viral diseases. The plant viral diseases mentioned are tobacco mosaic virus, cucumber mosaic virus, and potato virus Y, and their application in drugs and agents.

[0041] Compounds of N-(4-bromo-2-oxo-2H-benzopyran-6-yl) substituted sulfonamides have the following formula (2):

[0042]

[0043] The application of a coumarin containing a sulfonamide structure in the preparation of drugs for the prevention and treatment of tobacco mosaic virus disease, cucumber mosaic virus disease and potato virus Y disease.

[0044] The derivative is an N-(4-bromo-2-oxo-2H-benzopyran-6-yl)-substituted benzenesulfonamide.

[0045] A foliar fertilizer composition comprising the aforementioned derivative.

[0046] The derivative is N-(4-bromo-2-oxo-2H-benzopyran-6-yl)-4-chlorobenzenesulfonamide.

[0047] The application of the combined foliar fertilizer in the preparation of drugs for the prevention and control of plant viral diseases.

[0048] The plant viral disease is cucumber mosaic virus disease.

[0049] A plant growth regulator comprising the derivative.

[0050] The present application has the advantages that the raw materials are easy to obtain, the process is simple, and the reaction conditions are mild. The compound II-15 has the best inhibitory activity against TMV, CMV and PVY at 500 μg / mL, and the treatment activity and protection activity against the three viruses are 58.2%, 61.8%, 48.2%, 54.8%, 62.8% and 59.2% respectively, which are superior to the activity of ribavirin (49.2%, 55.4%; 43.4%, 46.2%; 57.2%, 50.2%) against the three viruses. DETAILED DESCRIPTION

[0051] Example 1: Synthesis of N-(4-bromo-2-oxo-2H-chromen-6-yl)-2-chlorobenzenesulfonamide (compound No. II-1), comprising the following steps:

[0052] (1) 4-hydroxy coumarin: tetrabutylammonium bromide: phosphorus pentoxide = 1:1.5:4, heating reflux for 4-6 h, after the reaction is completed, the temperature is reduced to room temperature, and then the system is washed with 10% sodium bicarbonate solution, extracted with an appropriate amount of toluene, collected organic layer, and evaporated under reduced pressure to obtain intermediate 4-bromocoumarin.

[0053] (2) 4-bromocoumarin: nitric acid: sulfuric acid = 1:1-1.2:1.5, ice bath stirring for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, stirred thoroughly, and after the temperature is reduced to room temperature, the solid is collected by filtration to obtain intermediate 4-bromo-6-nitrocoumarin.

[0054] (3) 4-bromo-6-nitrocoumarin: iron = 1:1-1.2:1.5, ice bath stirring for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, stirred thoroughly, and after the temperature is reduced to room temperature, the solid is collected by filtration to obtain 4-bromo-6-aminocoumarin.

[0055] (4) 4-bromo-6-aminocoumarin: 2-chlorobenzenesulfonyl chloride: potassium carbonate = 1:1-1.2:1.5, stirring at room temperature for 1 h, after the reaction is completed, the reaction system is extracted with ethyl acetate, the organic layer is collected, and column chromatography is used for separation and purification to obtain N-(4-bromo-2-oxo-2H-chromen-6-yl)-2-chlorobenzenesulfonamide, with a yield of 82.4%.

[0056] Example 2: Synthesis of N-(4-bromo-2-oxo-2H-chromen-6-yl)-3-chlorobenzenesulfonamide (Compound No. II-2) comprising the following steps:

[0057] (1) 4-hydroxy coumarin: tetrabutyl ammonium bromide: phosphorus pentoxide = 1:1.5:4, heating to reflux for 4-6h, after the reaction is completed, the temperature is reduced to room temperature, the system is washed with 10% sodium bicarbonate solution, the system is extracted with an appropriate amount of toluene, the organic layer is collected, and evaporated under reduced pressure to obtain the intermediate 4-bromocoumarin.

[0058] (2) 4-bromocoumarin: nitric acid: sulfuric acid = 1:1-1.2:1.5, ice bath stirring for 4-6h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, fully stirred, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain the intermediate 4-bromo-6-nitrocoumarin.

[0059] (3) 4-bromo-6-nitrocoumarin: iron = 1:1-1.2:1.5, ice bath stirring for 4-6h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, fully stirred, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain 4-bromo-6-aminocoumarin;

[0060] (4) 4-bromo-6-aminocoumarin: 3-chlorobenzenesulfonyl chloride: potassium carbonate = 1:1-1.2:1.5, stirring at room temperature for 1h, after the reaction is completed, the reaction system is extracted with ethyl acetate, the organic layer is collected, and separated and purified by column chromatography to obtain N-(4-bromo-2-oxo-2H-chromen-6-yl)-3-chlorobenzenesulfonamide, with a yield of 67.3%.

[0061] Example 3: Synthesis of N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-chlorobenzenesulfonamide (Compound No. II-3) comprising the following steps:

[0062] (1) 4-hydroxy coumarin: tetrabutyl ammonium bromide: phosphorus pentoxide = 1:1.5:4, heating to reflux for 4-6h, after the reaction is completed, the temperature is reduced to room temperature, the system is washed with 10% sodium bicarbonate solution, the system is extracted with an appropriate amount of toluene, the organic layer is collected, and evaporated under reduced pressure to obtain the intermediate 4-bromocoumarin.

[0063] (2) 4-bromocoumarin: nitric acid: sulfuric acid = 1:1-1.2:1.5, ice bath stirring for 4-6h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, fully stirred, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain the intermediate 4-bromo-6-nitrocoumarin.

[0064] (3) 4-bromo-6-nitrocoumarin: iron = 1 : 1 ~ 1.2: 1.5, ice bath stirring 4-6h, until the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, stirring, until the temperature drops to room temperature, after filtration to collect the solid, 4-bromo-6-amino coumarin is obtained;

[0065] (4) 4-bromo-6-amino coumarin: benzylamine: potassium carbonate = 1:1 ~ 1.2: 1.5, stirring at room temperature for 1h, until the reaction is completed, the reaction system is extracted with ethyl acetate, the organic layer is collected, and column chromatography is used for separation and purification, to obtain N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-chlorobenzenesulfonamide, the yield is 72.0%.

[0066] Example 4: Synthesis of N-(4-bromo-2-oxo-2H-chromen-6-yl)-3-bromobenzenesulfonamide (compound No. II-4), including the following steps:

[0067] (1) 4-hydroxycoumarin: tetrabutylammonium bromide: phosphorus pentoxide = 1:1.5:4, heating reflux 4-6h, until the reaction is completed, the temperature drops to room temperature, 10% sodium bicarbonate solution washes the system, the system is extracted with an appropriate amount of toluene, the organic layer is collected, and evaporated under reduced pressure to obtain the intermediate 4-bromocoumarin.

[0068] (2) 4-bromocoumarin: nitric acid: sulfuric acid = 1:1 ~ 1.2: 1.5, ice bath stirring 4-6h, until the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, stirring, until the temperature drops to room temperature, after filtration to collect the solid, the intermediate 4-bromo-6-nitrocoumarin is obtained.

[0069] (3) 4-bromo-6-amino coumarin: iron = 1 : 1 ~ 1.2: 1.5, ice bath stirring 4-6h, until the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, stirring, until the temperature drops to room temperature, after filtration to collect the solid, 4-bromo-6-amino coumarin is obtained;

[0070] (4) 4-bromo-6-amino coumarin: 3-bromobenzenesulfonyl chloride: potassium carbonate = 1:1 ~ 1.2: 1.5, stirring at room temperature for 1h, until the reaction is completed, the reaction system is extracted with ethyl acetate, the organic layer is collected, and column chromatography is used for separation and purification, to obtain N-(4-bromo-2-oxo-2H-chromen-6-yl)-3-bromobenzenesulfonamide, the yield is 76.8%.

[0071] Example 5: Synthesis of N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-bromobenzenesulfonamide (compound No. II-5), including the following steps:

[0072] (1) 4-hydroxycoumarin: tetrabutylammonium bromide: phosphorus pentoxide = 1:1.5:4, heating to reflux for 4-6 h, after the reaction is completed, the temperature is reduced to room temperature, the system is washed with 10% sodium bicarbonate solution, the system is extracted with an appropriate amount of toluene, the organic layer is collected, and evaporated under reduced pressure to obtain the intermediate 4-bromocoumarin.

[0073] (2) 4-bromocoumarin: nitric acid: sulfuric acid = 1:1-1.2:1.5, ice bath stirring for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, fully stirred, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain the intermediate 4-bromo-6-nitrocoumarin.

[0074] (3) 4-bromo-6-nitrocoumarin: iron = 1:1-1.2:1.5, ice bath stirring for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, fully stirred, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain 4-bromo-6-aminocoumarin;

[0075] (4) 4-bromo-6-aminocoumarin: 4-bromobenzenesulfonyl chloride: potassium carbonate = 1:1-1.2:1.5, stirring at room temperature for 1 h, after the reaction is completed, the reaction system is extracted with ethyl acetate, the organic layer is collected, and separated and purified by column chromatography to obtain N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-bromobenzenesulfonamide, with a yield of 64.2%.

[0076] Example 6: Synthesis of N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-methoxybenzenesulfonamide (compound No. II-6), comprising the following steps:

[0077] (1) 4-hydroxycoumarin: tetrabutylammonium bromide: phosphorus pentoxide = 1:1.5:4, heating to reflux for 4-6 h, after the reaction is completed, the temperature is reduced to room temperature, the system is washed with 10% sodium bicarbonate solution, the system is extracted with an appropriate amount of toluene, the organic layer is collected, and evaporated under reduced pressure to obtain the intermediate 4-bromocoumarin.

[0078] (2) 4-bromocoumarin: nitric acid: sulfuric acid = 1:1-1.2:1.5, ice bath stirring for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, fully stirred, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain the intermediate 4-bromo-6-nitrocoumarin.

[0079] (3) 4-bromo-6-nitrocoumarin: iron = 1:1-1.2:1.5, ice bath stirring for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, fully stirred, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain 4-bromo-6-aminocoumarin;

[0080] (4) 4-bromo-6-amino coumarin: 4-bromo-2-fluorobenzenesulfonyl chloride: potassium carbonate = 1 : 1 ~ 1.2: 1.5, stirring at room temperature for 1 h, after the reaction is completed, the reaction system is extracted with ethyl acetate, the organic layer is collected, and column chromatography is used for separation and purification to obtain N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-bromo-2-fluorobenzenesulfonamide with a yield of 80.1%.

[0081] Example 7: Synthesis of N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-bromo-2- fluorobenzenesulfonamide (compound No. II-7), including the following steps:

[0082] (1) 4-hydroxy coumarin: tetrabutylammonium bromide: phosphorus pentoxide = 1 : 1.5: 4, heating to reflux for 4-6 h, after the reaction is completed, the temperature is reduced to room temperature, the system is washed with 10% sodium bicarbonate solution, the system is extracted with an appropriate amount of toluene, the organic layer is collected, and evaporation under reduced pressure is performed to obtain intermediate 4-bromocoumarin.

[0083] (2) 4-bromocoumarin: nitric acid: sulfuric acid = 1 : 1 ~ 1.2: 1.5, stirring in an ice bath for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, stirring is performed, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain intermediate 4-bromo-6-nitrocoumarin.

[0084] (3) 4-bromo-6-nitrocoumarin: iron = 1 : 1 ~ 1.2: 1.5, stirring in an ice bath for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, stirring is performed, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain 4-bromo-6-amino coumarin;

[0085] (4) 4-bromo-6-amino coumarin: 4-bromo-2-fluorobenzenesulfonyl chloride: potassium carbonate = 1 : 1 ~ 1.2: 1.5, stirring at room temperature for 1 h, after the reaction is completed, the reaction system is extracted with ethyl acetate, the organic layer is collected, and column chromatography is used for separation and purification to obtain N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-bromo-2-fluorobenzenesulfonamide with a yield of 80.1%.

[0086] Example 8: Synthesis of N-(4-bromo-2-oxo-2H-chromen-6-yl)-2-fluorobenzenesulfonamide (compound No. II-8), including the following steps:

[0087] (1) 4-hydroxycoumarin: tetrabutylammonium bromide: phosphorus pentoxide = 1 : 1.5 : 4, heating to reflux for 4-6 h, after the reaction is completed, the temperature is reduced to room temperature, the system is washed with 10% sodium bicarbonate solution, the system is extracted with an appropriate amount of toluene, the organic layer is collected, and evaporated under reduced pressure to obtain the intermediate 4-bromocoumarin.

[0088] (2) 4-bromocoumarin: nitric acid: sulfuric acid = 1 : 1-1.2 : 1.5, ice bath stirring for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, stirred thoroughly, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain the intermediate 4-bromo-6-nitrocoumarin.

[0089] (3) 4-bromo-6-nitrocoumarin: iron = 1 : 1-1.2 : 1.5, ice bath stirring for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, stirred thoroughly, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain 4-bromo-6-aminocoumarin;

[0090] (4) 4-bromo-6-aminocoumarin: -2 fluorobenzenesulfonyl chloride: potassium carbonate = 1 : 1-1.2 : 1.5, stirring at room temperature for 1 h, after the reaction is completed, the reaction system is extracted with ethyl acetate, the organic layer is collected, and separated and purified by column chromatography to obtain N-(4-bromo-2-oxo-2H-chromen-6-yl)-2-fluorobenzenesulfonamide with a yield of 72.0%.

[0091] Example 9: Synthesis of N-(4-bromo-2-oxo-2H-chromen-6-yl)-2,4-dichlorobenzenesulfonamide (compound No. II-9), comprising the following steps:

[0092] (1) 4-hydroxycoumarin: tetrabutylammonium bromide: phosphorus pentoxide = 1 : 1.5 : 4, heating to reflux for 4-6 h, after the reaction is completed, the temperature is reduced to room temperature, the system is washed with 10% sodium bicarbonate solution, the system is extracted with an appropriate amount of toluene, the organic layer is collected, and evaporated under reduced pressure to obtain the intermediate 4-bromocoumarin.

[0093] (2) 4-bromocoumarin: nitric acid: sulfuric acid = 1 : 1-1.2 : 1.5, ice bath stirring for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, stirred thoroughly, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain the intermediate 4-bromo-6-nitrocoumarin.

[0094] (3) 4-bromo-6-nitrocoumarin: iron = 1 : 1-1.2 : 1.5, ice bath stirring for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, stirred thoroughly, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain 4-bromo-6-aminocoumarin;

[0095] (4) 4-bromo-6-amino coumarin: 2,4-dichlorobenzenesulfonyl chloride: potassium carbonate = 1 : 1 ~ 1.2: 1.5, stirring at room temperature for 1 h, after the reaction is completed, the reaction system is extracted with ethyl acetate, the organic layer is collected, and column chromatography is used for separation and purification to obtain N-(4-bromo-2-oxo-2H-chromen-6-yl)-2,4-dichlorobenzenesulfonamide with a yield of 73.3%.

[0096] Example 10: Synthesis of N-(4-bromo-2-oxo-2H-chromen-6-yl)naphthylsulfonamide (compound No. II-10), comprising the following steps:

[0097] (1) 4-hydroxy coumarin: tetrabutylammonium bromide: phosphorus pentoxide = 1 : 1.5: 4, heating to reflux for 4-6 h, after the reaction is completed, the temperature is reduced to room temperature, the system is washed with 10% sodium bicarbonate solution, the system is extracted with an appropriate amount of toluene, the organic layer is collected, and evaporated under reduced pressure to obtain the intermediate 4-bromocoumarin.

[0098] (2) 4-bromocoumarin: nitric acid: sulfuric acid = 1 : 1 ~ 1.2: 1.5, stirring in an ice bath for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, stirred thoroughly, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain the intermediate 4-bromo-6-nitrocoumarin.

[0099] (3) 4-bromo-6-nitrocoumarin: iron = 1 : 1 ~ 1.2: 1.5, stirring in an ice bath for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, stirred thoroughly, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain 4-bromo-6-amino coumarin;

[0100] (4) 4-bromo-6-amino coumarin: naphthylsulfonyl chloride: potassium carbonate = 1 : 1 ~ 1.2: 1.5, stirring at room temperature for 1 h, after the reaction is completed, the reaction system is extracted with ethyl acetate, the organic layer is collected, and column chromatography is used for separation and purification to obtain N-(4-bromo-2-oxo-2H-chromen-6-yl)naphthylsulfonamide with a yield of 63.9%.

[0101] Example 11: Synthesis of N-(4-bromo-2-oxo-2H-chromen-6-yl)propylsulfonamide (compound No. II-11), comprising the following steps:

[0102] (1) 4-hydroxycoumarin: tetrabutylammonium bromide: phosphorus pentoxide = 1:1.5:4, heating to reflux for 4-6 h, after the reaction is completed, the temperature is reduced to room temperature, the system is washed with 10% sodium bicarbonate solution, the system is extracted with an appropriate amount of toluene, the organic layer is collected, and evaporated under reduced pressure to obtain the intermediate 4-bromocoumarin.

[0103] (2) 4-bromocoumarin: nitric acid: sulfuric acid = 1:1-1.2:1.5, ice bath stirring for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, fully stirred, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain the intermediate 4-bromo-6-nitrocoumarin.

[0104] (3) 4-bromo-6-nitrocoumarin: iron = 1:1-1.2:1.5, ice bath stirring for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, fully stirred, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain 4-bromo-6-aminocoumarin;

[0105] (4) 4-bromo-6-aminocoumarin: propylsulfonyl chloride: potassium carbonate = 1:1-1.2:1.5, stirring at room temperature for 1 h, after the reaction is completed, the reaction system is extracted with ethyl acetate, the organic layer is collected, and separated and purified by column chromatography to obtain N-(4-bromo-2-oxo-2H-chromen-6-yl) propylsulfonamide, with a yield of 65.9%.

[0106] Example 12: Synthesis of N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-cyanobenzenesulfonamide (compound No. II-12), comprising the following steps:

[0107] (1) 4-hydroxycoumarin: tetrabutylammonium bromide: phosphorus pentoxide = 1:1.5:4, heating to reflux for 4-6 h, after the reaction is completed, the temperature is reduced to room temperature, the system is washed with 10% sodium bicarbonate solution, the system is extracted with an appropriate amount of toluene, the organic layer is collected, and evaporated under reduced pressure to obtain the intermediate 4-bromocoumarin.

[0108] (2) 4-bromocoumarin: nitric acid: sulfuric acid = 1:1-1.2:1.5, ice bath stirring for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, fully stirred, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain the intermediate 4-bromo-6-nitrocoumarin.

[0109] (3) 4-bromo-6-nitrocoumarin: iron = 1:1-1.2:1.5, ice bath stirring for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, fully stirred, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain 4-bromo-6-aminocoumarin;

[0110] (4) 4-bromo-6-amino coumarin: 4-cyanobenzenesulfonyl chloride: potassium carbonate = 1:1~1.2:1.5, stirring at room temperature for 1 h, after the reaction is completed, the reaction system is extracted with ethyl acetate, the organic layer is collected, and column chromatography is used for separation and purification to obtain N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-cyanobenzenesulfonamide with a yield of 86.2%.

[0111] Example 13: Synthesis of N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-bromobenzylbenzenesulfonamide (compound No. II-13), including the following steps:

[0112] (1) 4-hydroxycoumarin: tetrabutylammonium bromide: phosphorus pentoxide = 1:1.5:4, heating to reflux for 4-6 h, after the reaction is completed, the temperature is reduced to room temperature, the system is washed with 10% sodium bicarbonate solution, the system is extracted with an appropriate amount of toluene, the organic layer is collected, and evaporation under reduced pressure is performed to obtain the intermediate 4-bromocoumarin.

[0113] (2) 4-bromocoumarin: nitric acid: sulfuric acid = 1:1~1.2:1.5, stirring in an ice bath for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, and after sufficient stirring, the temperature is reduced to room temperature, the solid is collected by filtration to obtain the intermediate 4-bromo-6-nitrocoumarin.

[0114] (3) 4-bromo-6-nitrocoumarin: iron = 1:1~1.2:1.5, stirring in an ice bath for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, and after sufficient stirring, the temperature is reduced to room temperature, the solid is collected by filtration to obtain 4-bromo-6-amino coumarin;

[0115] (4) 4-bromo-6-amino coumarin: 4-bromobenzylbenzenesulfonyl chloride: potassium carbonate = 1:1~1.2:1.5, stirring at room temperature for 1 h, after the reaction is completed, the reaction system is extracted with ethyl acetate, the organic layer is collected, and column chromatography is used for separation and purification to obtain N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-bromobenzylbenzenesulfonamide with a yield of 68.5%.

[0116] Example 14: Synthesis of N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-chloro-2-nitrobenzenesulfonamide (compound No. II-14), including the following steps:

[0117] (1) 4-hydroxycoumarin: tetrabutylammonium bromide: phosphorus pentoxide = 1:1.5:4 by weight, heated to reflux for 4-6 h, after the reaction is completed, the temperature is reduced to room temperature, the system is washed with 10% sodium bicarbonate solution, the system is extracted with an appropriate amount of toluene, the organic layer is collected, and evaporated under reduced pressure to obtain the intermediate 4-bromocoumarin.

[0118] (2) 4-bromocoumarin: nitric acid: sulfuric acid = 1:1-1.2:1.5 by weight, ice bath stirring for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, fully stirred, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain the intermediate 4-bromo-6-nitrocoumarin.

[0119] (3) 4-bromo-6-nitrocoumarin: iron = 1:1-1.2:1.5 by weight, ice bath stirring for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, fully stirred, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain 4-bromo-6-aminocoumarin.

[0120] (4) 4-bromo-6-aminocoumarin: 4-chloro-2-nitrobenzenesulfonyl chloride: potassium carbonate = 1:1-1.2:1.5 by weight, stirring at room temperature for 1 h, after the reaction is completed, the reaction system is extracted with ethyl acetate, the organic layer is collected, and separated and purified by column chromatography to obtain N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-chloro-2-nitrobenzenesulfonamide, with a yield of 76.8%.

[0121] Example 15: Synthesis of N-(4-bromo-2-oxo-2H-chromen-6-yl)-2-fluoro-3-chlorobenzenesulfonamide (compound No. II-15), comprising the following steps:

[0122] (1) 4-hydroxycoumarin: tetrabutylammonium bromide: phosphorus pentoxide = 1:1.5:4 by weight, heated to reflux for 4-6 h, after the reaction is completed, the temperature is reduced to room temperature, the system is washed with 10% sodium bicarbonate solution, the system is extracted with an appropriate amount of toluene, the organic layer is collected, and evaporated under reduced pressure to obtain the intermediate 4-bromocoumarin.

[0123] (2) 4-bromocoumarin: nitric acid: sulfuric acid = 1:1-1.2:1.5 by weight, ice bath stirring for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, fully stirred, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain the intermediate 4-bromo-6-nitrocoumarin.

[0124] (3) 4-bromo-6-nitrocoumarin: iron = 1 : 1 ~ 1.2: 1.5, stirring in ice bath for 4-6h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, stirred thoroughly, after the temperature drops to room temperature, the solid is collected by filtration, to obtain 4-bromo-6-amino coumarin;

[0125] (4) 4-bromo-6-amino coumarin: 2-fluoro-3-chlorobenzenesulfonyl chloride: potassium carbonate = 1:1 ~ 1.2:1.5, stirring at room temperature for 1h, after the reaction is completed, the reaction system is extracted with ethyl acetate, the organic layer is collected, and separated and purified by column chromatography to obtain N-(4-bromo-2-oxo-2H-chromen-6-yl)-2-fluoro-3-chlorobenzenesulfonamide with a yield of 63.4%.

[0126] Example 16: Synthesis of N-(4-bromo-2-oxo-2H-chromen-6-yl) benzenesulfonamide (compound No. II-16), comprising the following steps:

[0127] (1) 4-hydroxycoumarin: tetrabutylammonium bromide: phosphorus pentoxide = 1:1.5:4, heating to reflux for 4-6h, after the reaction is completed, the temperature drops to room temperature, the system is washed with 10% sodium bicarbonate solution, the system is extracted with appropriate amount of toluene, the organic layer is collected, and evaporated under reduced pressure to obtain intermediate 4-bromocoumarin.

[0128] (2) 4-bromocoumarin: nitric acid: sulfuric acid = 1:1 ~ 1.2:1.5, stirring in ice bath for 4-6h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, stirred thoroughly, after the temperature drops to room temperature, the solid is collected by filtration, to obtain intermediate 4-bromo-6-nitrocoumarin.

[0129] (3) 4-bromo-6-nitrocoumarin: iron = 1 : 1 ~ 1.2: 1.5, stirring in ice bath for 4-6h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, stirred thoroughly, after the temperature drops to room temperature, the solid is collected by filtration, to obtain 4-bromo-6-amino coumarin;

[0130] (4) 4-bromo-6-amino coumarin: benzene sulfonyl chloride: potassium carbonate = 1:1 ~ 1.2:1.5, stirring at room temperature for 1h, after the reaction is completed, the reaction system is extracted with ethyl acetate, the organic layer is collected, and separated and purified by column chromatography to obtain N-(4-bromo-2-oxo-2H-chromen-6-yl) benzenesulfonamide with a yield of 73.8%.

[0131] Example 17: Synthesis of N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-fluorobenzenesulfonamide (compound No. II-17), comprising the following steps:

[0132] (1) 4-hydroxycoumarin: tetrabutylammonium bromide: phosphorus pentoxide = 1:1.5:4, heating to reflux for 4-6 h, after the reaction is completed, the temperature is reduced to room temperature, the system is washed with 10% sodium bicarbonate solution, the system is extracted with an appropriate amount of toluene, the organic layer is collected, and evaporated under reduced pressure to obtain the intermediate 4-bromocoumarin.

[0133] (2) 4-bromocoumarin: nitric acid: sulfuric acid = 1:1-1.2:1.5, ice bath stirring for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, fully stirred, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain the intermediate 4-bromo-6-nitrocoumarin.

[0134] (3) 4-bromo-6-nitrocoumarin: iron = 1:1-1.2:1.5, ice bath stirring for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, fully stirred, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain 4-bromo-6-aminocoumarin;

[0135] (4) 4-bromo-6-aminocoumarin: 4-fluorobenzenesulfonyl chloride: potassium carbonate = 1:1-1.2:1.5, stirring at room temperature for 1 h, after the reaction is completed, the reaction system is extracted with ethyl acetate, the organic layer is collected, and separated and purified by column chromatography to obtain N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-fluorobenzenesulfonamide, with a yield of 68.4%.

[0136] Example 18: Synthesis of N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-fluoro-2- bromobenzenesulfonamide (compound No. II-18), comprising the following steps:

[0137] (1) 4-hydroxycoumarin: tetrabutylammonium bromide: phosphorus pentoxide = 1:1.5:4, heating to reflux for 4-6 h, after the reaction is completed, the temperature is reduced to room temperature, the system is washed with 10% sodium bicarbonate solution, the system is extracted with an appropriate amount of toluene, the organic layer is collected, and evaporated under reduced pressure to obtain the intermediate 4-bromocoumarin.

[0138] (2) 4-bromocoumarin: nitric acid: sulfuric acid = 1:1-1.2:1.5, ice bath stirring for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, fully stirred, after the temperature is reduced to room temperature, the solid is collected by filtration to obtain the intermediate 4-bromo-6-nitrocoumarin.

[0139] (3) 4-bromo-6-nitrocoumarin: iron = 1 : 1 ~ 1.2: 1.5, stirring in ice bath for 4-6h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, stirred thoroughly, after the temperature drops to room temperature, the solid is collected by filtration, to obtain 4-bromo-6-amino coumarin;

[0140] (4) 4-bromo-6-amino coumarin: -4-fluoro-2-bromobenzenesulfonyl chloride: potassium carbonate = 1:1 ~ 1.2:1.5, stirring at room temperature for 1h, after the reaction is completed, the reaction system is extracted with ethyl acetate, the organic layer is collected, and separated and purified by column chromatography to obtain N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-fluoro-2-bromobenzenesulfonamide with a yield of 73.6%.

[0141] Example 19: Synthesis of N-(4-bromo-2-oxo-2H-chromen-6-yl)-2,4-dinitrobenzenesulfonamide (compound No. II-20), comprising the following steps:

[0142] (1) 4-hydroxycoumarin: tetrabutylammonium bromide: phosphorus pentoxide = 1:1.5:4, heating to reflux for 4-6h, after the reaction is completed, the temperature drops to room temperature, the system is washed with 10% sodium bicarbonate solution, the system is extracted with appropriate amount of toluene, the organic layer is collected, and evaporated under reduced pressure to obtain intermediate 4-bromocoumarin.

[0143] (2) 4-bromocoumarin: nitric acid: sulfuric acid = 1:1 ~ 1.2:1.5, stirring in ice bath for 4-6h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, stirred thoroughly, after the temperature drops to room temperature, the solid is collected by filtration, to obtain intermediate 4-bromo-6-nitrocoumarin.

[0144] (3) 4-bromo-6-nitrocoumarin: iron = 1 : 1 ~ 1.2: 1.5, stirring in ice bath for 4-6h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, stirred thoroughly, after the temperature drops to room temperature, the solid is collected by filtration, to obtain 4-bromo-6-amino coumarin;

[0145] (4) 4-bromo-6-amino coumarin: -2,4-dinitrobenzenesulfonyl chloride: potassium carbonate = 1:1 ~ 1.2:1.5, stirring at room temperature for 1h, after the reaction is completed, the reaction system is extracted with ethyl acetate, the organic layer is collected, and separated and purified by column chromatography to obtain N-(4-bromo-2-oxo-2H-chromen-6-yl)-2,4-dinitrobenzenesulfonamide with a yield of 66.7%.

[0146] Example 20: Synthesis of N-(4-bromo-2-oxo-2H-benzopyran-6-yl)-3-methoxybenzenesulfonamide (compound number II-21), comprising the following steps:

[0147] (1) 4-hydroxycoumarin: tetrabutylammonium bromide: phosphorus pentoxide 1:1.5:4 were fed and heated under reflux for 4-6 hours. After the reaction was completed and the temperature was lowered to room temperature, the system was washed with 10% sodium bicarbonate solution and extracted with an appropriate amount of toluene. The organic layer was collected and evaporated under reduced pressure to obtain the intermediate 4-bromocoumarin.

[0148] (2) Add 4-bromocoumarin: nitric acid: sulfuric acid = 1:1~1.2:1.5, stir in an ice bath for 4-6 hours. After the reaction is complete, pour the reaction system into ice water with a magnetic stirrer and stir thoroughly. After the temperature drops to room temperature, filter and collect the solid to obtain the intermediate 4-bromo-6-nitrocoumarin.

[0149] (3) Add 4-bromo-6-nitrocoumarin: iron = 1:1 to 1.2:1.5, stir in an ice bath for 4-6 hours. After the reaction is complete, pour the reaction system into ice water with a magnetic stirrer and stir thoroughly. After the temperature drops to room temperature, filter and collect the solid to obtain 4-bromo-6-aminocoumarin.

[0150] (4) 4-Bromo-6-aminocoumarin: 3-methoxybenzenesulfonyl chloride: potassium carbonate = 1:1~1.2:1.5 were added and stirred at room temperature for 1 h. After the reaction was completed, the reaction system was extracted with ethyl acetate, the organic layer was collected, and the organic layer was separated and purified by column chromatography to obtain N-(4-bromo-2-oxo-2H-benzopyran-6-yl)-3-methoxybenzenesulfonamide, with a yield of 77.5%.

[0151] The proton nuclear magnetic resonance spectra of the sulfonamide-containing coumarin derivatives synthesized in Examples II-1 to II-20 above ( 1 H NMR, carbon spectrum 13 The C10 NMR and high-resolution mass spectrometry (HRMS) data are shown in Table 1.

[0152] Table 1. Spectral data of compounds II-1 to II-20

[0153]

[0154]

[0155]

[0156]

[0157]

[0158] Example 21: Therapeutic and protective activities of the target compounds against tobacco mosaic virus, cucumber mosaic virus, potato virus Y

[0159] (1) Test method

[0160] A. Virus purification

[0161] The Gooding method (Gooding; et al. 1967) was used to obtain crude tobacco mosaic virus (cucumber mosaic virus, potato virus Y) extract. The upper leaves of Nicotiana glutinosa L. plants, which had been inoculated for more than 3 weeks, were homogenized in phosphate buffer, filtered through double gauze, centrifuged at 1000 rpm, treated twice with polyethylene glycol, and then centrifuged again. The precipitate was suspended in phosphate buffer to obtain the crude tobacco mosaic virus (cucumber mosaic virus, potato virus Y) extract. The entire process was performed at 4°C. The absorbance value at 260 nm was measured using a UV spectrophotometer, and the virus concentration was calculated according to the formula.

[0162] Virus concentration (mg / mL) = (A260 x dilution factor) / / E0.1% 1 cm 260 nm

[0163] Where E represents the extinction coefficient, which is the light absorption (optical density) value of a suspension with a concentration of 0.1% (1 mg / mL) at a wavelength of 260 nm and a light path of 1 cm. The E0.1% 1 cm 260 nm of tobacco mosaic virus (cucumber mosaic virus, potato virus Y) is 3.1.

[0164] B. Therapeutic activity of the agents against (cucumber mosaic virus, potato virus Y) infection: Nicotiana glutinosa plants with uniform growth were selected, and the virus juice was applied to the whole leaves using a brush. After inoculation, the leaves were rinsed with water. After the leaves dried, the agents were applied to the right half of the leaves, and the corresponding amount of solvent was applied to the left half as a control. Then, the plants were cultured in a light incubator with controlled temperature (23 ± 1°C) and light intensity (10000 Lux), and the number of necrotic spots was observed and recorded after 3-4 days. Three plants were used for each agent treatment, and each plant had 3-4 leaves. Each agent was tested three times according to the above method, and the inhibition rate was calculated according to the following formula.

[0165] C. In vivo protective effect of the agents against tobacco mosaic virus (cucumber mosaic virus, potato virus Y) infection

[0166] In vivo protection of the agent against tobacco mosaic virus (cucumber mosaic virus, potato Y virus) infection: select the heart leaf tobacco with the same growth potential, first use a brush to apply the agent on the right half of the leaf, and apply the corresponding amount of solvent on the left half of the leaf as a control. After the leaf dries, dip the brush in the virus solution and inoculate the whole leaf. After inoculation, rinse with water. Then keep the culture moist in a light incubator, control the temperature at 23±1°C, and the light at 10000Lux. Observe and record the number of dead spots after 3-4 days. Each agent treatment has 3 plants, and each plant has 3-4 leaves. Repeat each agent 3 times according to the above method, and calculate the inhibition rate according to the following formula.

[0167] Y = (C-A) / C x 100%

[0168] Where: Y is the inhibition rate of the compound on tobacco mosaic virus (cucumber mosaic virus, potato Y virus); C is the number of dead spots in the control group (left half of the leaf), and A is the number of dead spots in the control group (right half of the leaf).

[0169] (2) Biological test results

[0170] Table 3 Therapeutic and protective activity of target compounds on tobacco mosaic virus, cucumber mosaic virus, and potato Y virus

[0171]

[0172] The anti-TMV, CMV, PVY activity of the target compounds was tested by semi-leaf spot method at a concentration of 500 μg / mL, with ribavirin as the control drug. As can be seen from the biological activity determination results in Table 3, the coumarin compounds containing sulfonamide structures all showed certain anti-viral activity. Compounds I2, I9, I11, I14, I15 had good curative effects on TMV at 500 mg / L, being 54.6%, 57.3%, 49.6%, 58.2%, and 54.7%, respectively. Compounds I7, I9, I15 had good protective effects on TMV, being 57.2%, 62.5%, and 61.8%, respectively, which were better than the ribavirin group (49.2% and 55.4%, respectively). Compounds I9, I11, I15, and I18 had good curative activities on CMV at 500 mg / L, being 49.6%, 60.3%, 48.2%, and 53.6%, respectively. Compounds I9, I12, I15, and I20 had good protective activities on CMV at 500 mg / L, being 52.6%, 49.2%, 54.8%, and 47.8%, respectively, which were better than ribavirin (43.4% and 46.2%, respectively). Compounds I2, I5, I9, and I15 had good curative activities on PVY at 500 mg / L, being 59.3%, 58.4%, 58.1%, and 62.8%, respectively. Compounds I7, I11, and I15 had good protective activities on CMV at 500 mg / L, being 55.3%, 51.1%, and 59.2%, respectively, which were better than ribavirin (57.2% and 50.2%, respectively).

[0173] Example 22: Determination of plant growth regulating activity of the target compounds

[0174] (1) Test method

[0175] The plant growth regulating activity of the target compounds was determined by wheat coleoptile cutting test and radish cotyledon expansion method (Song Yangyang. Synthesis and biological activity of novel plant growth regulators containing ferrocenyl group [D]. Northwest University, 2011.). The required solution was prepared: citric acid 1.019 g, potassium phosphate dibasic trihydrate 2.350 g, and sugar 20 g were weighed and mixed to make up to 1 L to obtain a citric acid-phosphoric acid buffer solution with pH-5. Indole acetic acid (IAA) was used as the standard control in the wheat coleoptile test, and kinetin (KT) was used as the standard control in the radish cotyledon expansion method. An appropriate amount of the target compound and the control sample were weighed, dissolved with a few drops of DMF, and then a few drops of emulsifier (Tween-80) were added. The sample solution was prepared at a concentration of 100 μg / mL with the buffer solution, and then sequentially diluted to 50, 10, and 1 μg / mL. Agar 2.4 g was weighed, 400 mL of water was heated to dissolve, and then poured into a porcelain dish to cool to obtain the germination bed.

[0176] Wheat coleoptile cutting test: Take about 50 g of wheat seeds, soak for 4 h, rinse several times with water, drain the water, and evenly place them in the germination bed, cover with a film, and place in a 25 ± 1°C artificial climate box for dark culture. When the wheat coleoptile is 2.5-3 cm long, select those with consistent growth and cut the sensitive section with a blade, take one section per bud, shade, and place in distilled water for 1 h. Take 8 mL of sample solution each and add two filter paper sheets to a 9 cm diameter culture medium. Then place 10 cut coleoptile sections in each treatment, and then place in a 25 ± 1°C artificial climate box for dark culture. After 48 h, measure the total length of the 10 sections, compare with the blank buffer solution control, and at the same time compare with the standard solution of the same concentration, calculate the inhibition or promotion effect, and take it as the growth hormone function evaluation index. The calculation method is:

[0177] Effect = (treatment-blank) / blank * 100%

[0178] If the calculated result is positive, it indicates that there is a promotion effect: if it is negative, it indicates that there is an inhibition effect. Then perform efficacy evaluation. The evaluation criteria are:

[0179]

[0180] (2) Biological test results

[0181] Table 4 Plant growth regulator activity of some target compounds

[0182]

[0183] The plant growth activity test results of this series of target compounds are shown in Table 4. The preliminary biological activity test results show that the target compounds have certain plant growth activity, and the growth regulation activity is better at a concentration of 10 μg / mL.

[0184] Example 23: Preparation of leaf fertilizer of II-3 composition

[0185] The components and contents of the leaf fertilizer in this example are as follows: per 100 mL of leaf fertilizer contains:

[0186] Standard compound II-3: 10 mg

[0187] Threonine chelated potassium: 10 mg

[0188] Superphosphate: 0.5 mg

[0189] Boric acid: 0.33 mg

[0190] Ferric sulfate: 0.1 mg

[0191] Ammonium molybdate: 0.1 mg

[0192] Magnesium sulfate: 0.1 mg

[0193] Water: Balance

[0194] Potassium threonine chelate was dissolved in water, and then superphosphate, boric acid, ferric sulfate, ammonium molybdate, and magnesium sulfate were added. The mixture was stirred until homogeneous to obtain foliar fertilizer composition II-3. A comparative sample was prepared using the same method but without compound II-3.

[0195] Example 24: Activity of the II-3 composition foliar fertilizer

[0196] (1) Fertilization method

[0197] Cucumber seeds were sown in a seedling substrate. Five days after emergence, the foliar fertilizer composition II-3 (diluted 50 times) mentioned in Example 23 of this invention was sprayed once, followed by spraying once every 15 days. After 3 months of cultivation, the seedlings were transplanted into the field. Seven days after transplanting, the foliar fertilizer composition II-3 (diluted 50 times) mentioned in Example 23 of this invention was sprayed once, followed by spraying once a month for a total of 5 sprays (one spray after 7 days + one spray per month (4 times)). After that, routine field management was carried out.

[0198] (2) Determination of potassium content in leaves

[0199] Twenty-four hours after the last foliar fertilizer application, the potassium content in cucumber leaves and rhizomes was determined using flame photometry and calculated using the following formula:

[0200] Potassium content in leaves = (mass of potassium / dry weight of leaves) × 100%;

[0201] Potassium content in rhizomes = (mass of potassium / dry weight of rhizomes) × 100%.

[0202] Table 5. Determination of potassium content in leaves

[0203]

[0204]

[0205] (3) Incidence of cucumber mosaic virus disease

[0206] The incidence of cucumber mosaic virus disease was investigated 10 days after the last application of foliar fertilizer.

[0207] The incidence rate of cucumber mosaic virus disease = (number of infected plants / total number of plants) × 100%, with 30 plants investigated in each group.

[0208] Table 6. Incidence rate of cucumber mosaic virus disease

[0209]

[0210] As can be seen from Table 5 and Table 6, spraying the II-3 composition foliar fertilizer mentioned in the embodiment 23 of the present application can significantly increase the potassium content in the leaves and rhizomes of the plants, and further enhance the resistance of the cucumber to the cucumber mosaic virus.

[0211] The embodiment of the present application is used to illustrate the technical solution of the present application. The effect of the present application is that the synthesis route is simple, the yield is high, and a new type of efficient antiviral agent for preventing and treating plant viral diseases is obtained. In addition, the II-3 composition foliar fertilizer mentioned in the present application can significantly increase the potassium content in the leaves and rhizomes of the plants, and further enhance the resistance of the cucumber to the cucumber mosaic virus.

Claims

1. A novel anti-phytoviral agent and its derivatives, characterized by: The derivative is as follows: R is 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3-bromophenyl, 4-bromophenyl, 4-methoxyphenyl, 4-bromo-2-fluorophenyl, 2-fluorophenyl, 2,4-dichloro-phenyl, naphthyl, n-propyl, 4-cyanophenyl, 4-benzylbromophenyl, 4-chloro-3-nitrophenyl, 2-fluoro-3-chlorophenyl, phenyl, 4-fluorophenyl, 4-fluoro-2-bromophenyl, 2,4-dinitrophenyl or 3-methoxyphenyl.

2. The coumarin derivative containing a sulfonamide structure according to claim 1, characterized by: The method comprises the following steps:

3. The method for preparing a coumarin containing a sulfonamide structure as described in claim 1, characterized in that: The synthesis steps and process conditions are as follows: 4-hydroxycoumarin:tetrabutylammonium bromide:phosphorus pentoxide are added in a molar ratio of 1:1-2:4, heated to reflux for 4-6 h, after the reaction is completed, the temperature is lowered to room temperature, the system is washed with sodium bicarbonate solution, the system is extracted with toluene, the organic layer is collected, and evaporated under reduced pressure to obtain substituted 4-bromocoumarin; 4-bromocoumarin:nitric acid:sulfuric acid are added in a ratio of 1:1-1.2:1.5, ice-bath stirring is performed for 4-6 h, after the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer, stirring is performed, after the temperature is lowered to room temperature, the solid is collected by filtration to obtain 4-bromo-6-nitrocoumarin; 4-bromo-6-nitrocoumarin is subjected to iron catalysis to obtain 4-bromo-6-aminocoumarin; 4-bromo-6-nitrocoumarin:substituted sulfonyl chloride:potassium carbonate are added in a ratio of 1:1-1.2:1.5, stirring is performed at room temperature, after the reaction is completed, the reaction system is extracted with ethyl acetate, the organic layer is collected, and column chromatography is used for separation and purification to obtain the target compound.

4. A process for the preparation of a coumarin containing sulfonamide structure according to claim 3, characterized by:

5. Use of a coumarin derivative containing a sulfonamide structure according to claim 1 or 2 in the preparation of a medicine for preventing and treating tobacco mosaic virus disease, cucumber mosaic virus disease and potato Y virus disease. The derivative is N-(4-bromo-2-oxo-2H-chromen-6-yl) substituted phenyl sulfonamide.

6. The compound of claim 1, wherein: The composition comprises the derivative according to claim 1.

7. A foliar composition characterized in that: The derivative is N-(4-bromo-2-oxo-2H-chromen-6-yl)-4-chlorophenyl sulfonamide.

8. The composition of claim 7, wherein:

9. Use of the combined foliar fertilizer according to claim 7 or 8 in the preparation of a medicine for preventing and treating plant virus diseases. The plant virus disease is cucumber mosaic virus disease.

10. The foliage fertilizer composition of claim 9, wherein: The derivative is N-(4-bromo-2-oxo-2H-chromen-6-yl) substituted phenyl sulfonamide.

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