Coumarin derivatives containing a dithioacetal unit, and methods of making and using the same

Abstract

The present application relates to a coumarin derivative containing a dithioacetal unit, a preparation method and use thereof. The coumarin derivative has excellent antiviral activity against cucumber mosaic virus and the like, and can be used for preparing a medicine or agent for preventing and treating plant viral diseases such as cucumber mosaic virus, and has simple structure and preparation process.

Description

Technical Field

[0001] This invention relates to the fields of chemical industry and pesticides, and more specifically to a coumarin derivative containing a dithioacetal unit, a method for preparing the coumarin derivative containing the dithioacetal unit, and its use in the preparation of drugs for the prevention and control of plant viral diseases. Background Technology

[0002] Plant viral diseases are a major category of diseases in agricultural production, often referred to as "plant cancer." The most common plant viral diseases include Cucumber Mosaic Virus (CMV), Tobacco Mosaic Virus (TMV), Potato Virus X (PVX), Tomato Yellow Leaf Curl Virus (TYLCV), Rice Stripe Virus (RSV), Southern Rice Black-Streaked Dwarf Virus (SRBSDV), Rice Black-Streaked Dwarf Disease (RBSDV), Rice Tooth Leaf Dwarf Virus (RRSV), and Maize Rough Dwarf Virus (MRDV). Among these, Cucumber Mosaic Virus (CMV) belongs to the genus Cucumovirus in the family Bromoviridae. It has a wide host range, infecting over 1200 plant species, including important economic crops such as cucumbers, watermelons, tomatoes, and peppers. Diseases caused by this virus lead to symptoms such as yellowing and wrinkling of leaves, mosaic patterns, and stunted growth, severely impacting crop yield and quality. Because viruses are absolute parasites in plants and lack a complete immune metabolic system, coupled with the lack of highly effective antiviral agents for plants, the prevention and control of plant viral diseases is quite difficult, causing huge economic losses to agricultural production. Considering environmental pollution and pesticide residues, there is an urgent need to develop an effective and green control agent.

[0003] Coumarins are widely distributed in nature and belong to the benzopyranone class. They consist of a benzene ring linked to a pyranone core, have a relatively small molecular weight, are relatively simple to synthesize, and possess a wide range of pharmacological characteristics. They are considered a promising class of bioactive heterocyclic compounds with antibacterial, insecticidal, and antiviral activities.

[0004] 2017. Prenylated isocoumarins from the fermentation products of the endophyticfungus aspergillus versicolor and their anti-tobacco mosaic virus activities[J]. Chem. Nat. Compd. 2017, 53 Two novel pentylated isocomonasins were isolated from the fermentation products of the endophytic fungus *Aspergillus verticololor* (436-439). Their structures were elucidated by spectroscopic methods, including a wide range of 1D and 2D NMR techniques. Their activity against tobacco mosaic virus (TMV) was evaluated. The results showed that the compounds possessed moderate anti-TMV activity.

[0005] In 2020, Chen Yahan et al. (Chen, Y.; Guo, D.; Lu, M.; Yue, J.; Liu, Y.; Shang, C.; An, D.; Zhao, M. Inhibitory effect of osthole from cnidium monnieri ontobacco mosaic virus (tmv) infection in nicotiana glutinosa[J]. Molecules 2020, 25 Osthol, a coumarin compound, was extracted from Cnidium monnieri. The antiviral activity of osthol against Tobacco Mosaic Virus (TMV) was determined using the half-leaf necrotic spot method. The results showed that osthol exhibited stronger antiviral activity against TMV infection than eugenol and ningnanmycin, with inactivation, protection, and therapeutic effects of 72.57%, 70.26%, and 61.97%, respectively. Observation of TMV particles revealed that osthol directly affects virus particles. Correspondingly, compared to the control, the level of capsid protein detected by Western blot was significantly reduced when the concentration of osthol in the tested plants increased. These results indicate that osthol possesses anti-TMV activity and can be used as a biological reagent for controlling plant viruses using the half-leaf method.

[0006] 2021 Wang Qingmin et al. (Wang Qingmin, Song Hongjian, Guo Zhonglin, Liu Yuxiu, Zhang Jingjing, Li Yongqiang. Application of coumarin derivatives in the control of plant viruses, fungicide and insecticide [P]). CN 113016806 Patent A.2021 discloses a patent for coumarin derivatives, most of which exhibit inhibitory effects against tobacco mosaic virus (TMV). Among these compounds, excellent anti-TMV activity was observed in in vivo inactivation, treatment, and protection modes, comparable to the efficacy of the commercial drug ribavirin.

[0007] In 2021, Fan Zhijin et al. (Fan Zhijin, Lü You, Wang Lifan, Li Kun, Hao Zesheng, Zhang Nailou, Wang Weibao, Liu Xiaoyu, Shang Wei, Tang Liangfu. A class of coumarin derivatives containing 3,4-dichloroisothiazol and their preparation methods and uses [P]. CN 112480103 (A.2021.) By introducing a 3,4-dichloroisothiazolium heterocycle into the lead structure of coumarin, a class of 4-position 3,4-dichloroisothiazolium heterocycle 7- or 5-position hydroxycoumarin derivatives were designed and synthesized, and their bioactivity was systematically screened and evaluated. Coumarin derivatives containing 3,4-dichloroisothiazolium, combined with any one or two of the aforementioned antiviral agents, form antiviral compositions for the prevention and control of viral diseases in agricultural, forestry, and horticultural plants, including rice dwarf virus, rice stripe leaf blight, yellow dwarf virus, pepper mosaic virus, tomato fern leaf virus, maize dwarf mosaic virus, tobacco vein necrosis virus, Cymbidium fern leaf virus, cauliflower mosaic virus, Cymbidium fern ringspot virus, and citrus virus diseases.

[0008] In 2021, Wang Qingmin et al. (Guo, ZL; Zhou, P.; Song, HJ; Liu, Y.; Zhang, JJ; Li, YQ; Wang, QM Design, synthesis, and bioactivities of phthalideand coumarin derivatives based on the biosynthesis and structuresimplification of gossypol[J]. J. Agric. Food Chem. 2021, 69 (15123-15135.) A series of phthalide and coumarin derivatives with simpler structures were designed and synthesized. Bioassay results showed that these two series of target compounds had good activity against tobacco mosaic virus, superior to the commercial antiviral agent ningnanmycin at the same dose. Therefore, these compounds are promising candidates for the development of new antiviral agents against plants.

[0009] In summary, coumarins are widely found in various plants in nature and possess broad-spectrum biological activities. In pesticide chemistry research, coumarin structures are often used as carriers for various pharmacophores. However, the application of coumarins in the fight against plant viruses is currently relatively limited, and their application and research in the fight against cucumber mosaic virus are even less significant. Therefore, filling the gap in the application of coumarins in the fight against cucumber mosaic virus is of great importance.

[0010] Dithioacetal active units typically possess strong biological activity, effectively inhibiting the replication and spread of plant viruses. They also exhibit inhibitory effects against a variety of plant viruses, providing broad-based protection. They are suitable for various crops and virus types. Furthermore, dithioacetal compounds can reduce the risk of viruses developing resistance and have low toxicity to non-target organisms (such as beneficial insects, animals, and humans), aligning with the development trend of green pesticides.

[0011] In 2017, our team's Zhang Jian et al. (Zhang, J.; Zhao, L.; Zhu, C.; Wu, ZX; Zhang, GP; Gan, XH; Liu, DY; Pan, JK; Hu, DY; Song, BA) proposed a facile synthesis of novel vanillin derivatives incorporating a bis(2-hydroxyethyl)dithioacetal moiety as antiviral agents[J]. J. Agric. Food Chem 2017, 65 (4582–4588.) Using vanillin as a raw material, a series of vanillin derivatives containing dithioacetal were reported. Bioactivity assays showed that most compounds exhibited the best therapeutic and protective activity against PVY and CMV, exceeding that of the control drug. Among them, the optimal compound showed the best therapeutic and protective activity against PVY and CMV, with an effective concentration (EC50) of [missing value]. 50 The concentrations were 217.6 mg / L, 205.7 mg / L, 206.3 mg / L, and 186.2 mg / L, respectively, all of which were superior to those of ningnanmycin (440.5 mg / L, 425.3 mg / L and 426.1 mg / L, 405.3 mg / L) and ribavirin (848.0 mg / L, 808.1 mg / L and 858.2 mg / L, 766.5 mg / L), respectively.

[0012] In 2018, our team's Chen Jin et al. (Chen, J.; Shi, J.; Yu, L.; Liu, DY; Gan, XH; Song, BA; Hu, DY) designed, synthesized, and defended novel dithioacetal derivatives bearing a strobilurinmoiety[J]. J. Agric. Food Chem 2018, 66 (5335–5345.) reported dithioacetal compounds containing methoxyacrylates, most of which showed good activity against PVY, CMV, and TMV, exceeding that of the control drugs. The best-performing compound showed good inhibitory activity against PVY, CMV, and TMV. The protective activities were 148.4, 113.2, and 214.6 mg / L, respectively, and the therapeutic activity was EC50. 50 The concentrations were 125.3, 108.9, and 181.7 mg / L, respectively, which were significantly higher than those of ningnanmycin (425.3, 513.3, 242.7 mg / L and 440.5, 549.1, 373.8 mg / L, respectively), ribavirin (652.7, 665.4, 653.4 mg / L and 677.4, 690.3, 686.5 mg / L, respectively), and chitosan oligosaccharide (547.3, 570.6, 507.9 mg / L and 553.4, 582.8, 513.8 mg / L, respectively).

[0013] In summary, dithioacetals have been widely used by our team in the creation of agricultural antiviral agents in recent years, exhibiting excellent biological activity and undergoing numerous derivatizations. However, their application in coumarin structures has not yet been observed. Therefore, it is meaningful to introduce the dithioacetal active unit into the coumarin structure, design and synthesize coumarin derivatives containing dithioacetals, and study their antiviral activity. Summary of the Invention

[0014] One of the objectives of this invention is to provide the coumarin derivative containing a dithioacetal unit and its preparation method.

[0015] A second objective of this invention is to provide a composition of the coumarin derivative containing the above-mentioned dithioacetal unit.

[0016] Another object of the present invention is to provide the use of the above-mentioned coumarin derivatives containing dithioacetal units, or the compositions thereof.

[0017] Another object of the present invention is to provide a method for controlling agricultural viral diseases using the above-mentioned coumarin derivatives containing dithioacetal units, or the composition thereof, specifically by applying the coumarin derivatives containing dithioacetal units, or the composition thereof, to harmful substances or their living environment. More specifically, it is a method for contacting pests with the coumarin derivatives containing dithioacetal units or the composition thereof.

[0018] Another object of the present invention is to provide a mechanism of action for preventing and controlling plant viral diseases using the above-mentioned compounds or compositions.

[0019] The objective of this invention and the solution to its main technical problem are achieved by the following technical solution:

[0020] The coumarin derivatives containing dithioacetal units of the present invention are compounds having the structure shown in formula (I):

[0021]

[0022] In the formula:

[0023] R 1 Selected from hydrogen and unsubstituted alkoxy groups;

[0024] R 2 Selected from hydrogen;

[0025] R 3 Selected from any substituted or unsubstituted aryl group;

[0026] R 4 Selected from unsubstituted alkyl, substituted or unsubstituted aryl, or C2–C6 alkylene (such as ethylene).

[0027] Furthermore, R is preferred. 1 Specifically selected from hydrogen and methyl; R 2 Specifically selected from: hydrogen; R 3 Specifically selected from: substituted phenyl; R 4 The radical is selected from ethyl, propyl, butyl, cyclohexyl, isopropyl, isobutyl, chlorophenyl, 2,4-dichlorophenyl, fluorophenyl, tolyl, methoxyphenyl, and ethylene.

[0028] The preferred specific compounds are as follows:

[0029] Compound D1: (E)-2-(2-(((8-(bis(ethylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-2-(methoxyimino)acetic acid methyl ester;

[0030] Compound D2: (E)-2-(2-(((8-(bis(propylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester;

[0031] Compound D3: (E)-2-(2-(((8-(bis(butyrothio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-2-(methoxyimino)acetic acid methyl ester;

[0032] Compound D4: (E)-2-(2-(((8-(bis(cyclohexylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester;

[0033] Compound D5: Methyl(E)-2-(2-(((8-(1,3-dithio-2-yl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester;

[0034] Compound D6: (E)-2-(2-(((8-(bis(isopropylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester;

[0035] Compound D7: Methyl(E)-2-(2-(((8-(bis(tert-butylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester;

[0036] Compound D8: (E)-2-(2-(((8-(bis(ethylthio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-2-(methoxyimino)acetic acid methyl ester;

[0037] Compound D9: (E)-2-(2-(((8-(bis(propylthio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester;

[0038] Compound D10: (E)-2-(2-(((8-(bis(butyrothio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-2-(methoxyimino)acetic acid methyl ester;

[0039] Compound D11: (E)-2-(2-(((8-(bis(cyclohexylthio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester;

[0040] Compound D12: Methyl(E)-2-(2-(((8-(1,3-dithio-2-yl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester;

[0041] Compound D13: Methyl(E)-2-(2-(((8-(bis(isopropylthio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester;

[0042] Compound D14: Methyl(E)-2-(2-(((8-(bis(tert-butylthio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester;

[0043] Compound D15: (E)-2-(2-(((8-(bis(ethylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-3-methoxyacrylate;

[0044] Compound D16: (E)-2-(2-(((8-(bis(propylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-3-methoxyacrylate;

[0045] Compound D17: (E)-2-(2-(((8-(bis(butyrothio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-3-methoxyacrylate;

[0046] Compound D18: (E)-2-(2-(((8-(bis(cyclohexylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-3-methoxyacrylate;

[0047] Compound D19: Methyl(E)-2-(2-(((8-(1,3-dithio-2-yl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-3-methoxyacrylate;

[0048] Compound D20: (E)-2-(2-(((8-(bis(isopropylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-3-methoxyacrylate;

[0049] Compound D21: (E)-2-(2-(((8-(bis(tert-butylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-3-methoxyacrylate;

[0050] Compound D22: (E)-2-(2-(((8-(bis(ethylthio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-3-methoxyacrylate;

[0051] Compound D23: (E)-2-(2-(((8-(bis(propylthio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-3-methoxyacrylate;

[0052] Compound D24: (E)-2-(2-(((8-(bis(butyrothio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-3-methoxyacrylate;

[0053] Compound D25: (E)-2-(2-(((8-(bis(cyclohexylthio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-3-methoxyacrylate;

[0054] Compound D26: Methyl(E)-2-(2-(((8-(1,3-dithio-2-yl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-3-methoxyacrylate;

[0055] Compound D27: (E)-2-(2-(((8-(bis(isopropylthio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-3-methoxyacrylate;

[0056] Compound D28: (E)-2-(2-(((8-(bis(tert-butylthio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-3-methoxyacrylate;

[0057] Compound D29: Methyl(E)-2-(2-(((8-(bis((4-chlorophenyl)thio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester;

[0058] Compound D30: (E)-2-(2-(((8-(bis(((2,4-dichlorophenyl)thio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester;

[0059] Compound D31: (E)-2-(2-(((8-(bis((4-fluorophenyl)thio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester;

[0060] Compound D32: (E)-2-(2-(((8-(bis(p-tolyl)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-2-(methoxyimino)acetic acid methyl ester;

[0061] Compound D33: (E)-2-(2-(((8-(bis(benzylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-2-(methoxyimino)acetic acid methyl ester;

[0062] Compound D34: Methyl(E)-2-(2-(((8-(bis((4-methoxyphenyl)thio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester.

[0063] The present invention discloses a method for preparing a coumarin derivative containing a dithioacetal unit, the synthetic route of which is as follows:

[0064]

[0065] Further details are as follows:

[0066]

[0067] The preferred synthesis route is as follows:

[0068]

[0069] The present invention also provides a composition comprising the aforementioned coumarin derivative containing a dithioacetal unit, and agriculturally usable adjuvants or fungicides, antiviral agents or herbicides; preferably, the formulation of the composition is selected from emulsifiable concentrates (EC), powders (DP), wettable powders (WP), granules (GR), aqueous solutions (AS), suspensions (SC), ultra-low volume sprays (ULV), soluble powders (SP), microcapsules (MC), fumigants (FU), emulsions (EW), and water-dispersible granules (WG).

[0070] This invention provides the use of a coumarin derivative containing a dithioacetal unit, or a composition thereof, in the preparation of a drug for preventing and controlling agricultural viral diseases.

[0071] Preferably, the agricultural viral disease is cucumber mosaic virus disease.

[0072] The term "alkyl" as used here refers to both branched and straight-chain saturated hydrocarbon groups having a specific number of carbon atoms. For example, "C 1-10 Alkyl (or alkylene) refers to C1, C2, C3, C4, C5, C6, C7, C8, C9, and C10 alkyl groups. Additionally, for example, "C 1-6 "Alkyl" means an alkyl group having 1 to 6 carbon atoms. Alkyl groups can be unsubstituted or substituted, such that one or more of their hydrogen atoms are replaced by other chemical groups. Examples of alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), propyl (such as n-propyl and isopropyl), butyl (such as n-butyl, isobutyl, tert-butyl), pentyl (such as n-pentyl, isopentyl, neopentyl) and the like.

[0073] The term "cycloalkyl" refers to cycloalkyl groups, including mono-, di-, or polycyclic systems. 3-7 The purpose of cycloalkyl groups is to include C3, C4, C5, C6, and C7 cycloalkyl groups. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, norbornyl, and their analogues. As used herein, “carbocyclic” or “carbocyclic remnant” refers to any stable 3, 4, 5, 6, or 7-membered monocyclic or bicyclic, or 7, 8, 9, 10, 11, 12, or 13-membered bicyclic or tricyclic, which may be saturated, partially unsaturated, unsaturated, or aromatic. Examples of these carbocyclic rings include, but are not limited to, cyclopropyl, cyclobutyl, cyclobutenyl, cyclopentyl, pentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, adamantyl, cyclooctyl, cyclooctenyl, cyclooctadiene, [3.3.0]bicyclooctane, [4.3.0]bicyclononane, [4.4.0]bicyclodecane, [2.2.2]bicyclooctane, fluorenyl, phenyl, naphthyl, indanyl, adamantyl, anthracene, and tetrahydronaphthyl (naphthyl). As mentioned above, bridged rings are also included in the definition of carbocyclic rings (such as [2.2.2]bicyclooctane). Unless otherwise specified, preferred carbocyclic rings are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl. When the term "carbocyclic ring" is used, it is intended to include "aryl". A bridged ring occurs when one or more carbon atoms are connected to two non-adjacent carbon atoms. Preferred bridges are one or two carbon atoms. It is noted that a bridge always transforms a monocyclic ring into a bicyclic ring. When the rings are bridged, the substituents of the rings are also present on the bridges.

[0074] The term "aryl" refers to a monocyclic or bicyclic aromatic hydrocarbon group, such as phenyl and naphthyl, having 6 to 12 carbon atoms in the ring moiety, each of which can be substituted.

[0075] The term "halogen" or "halogen atom" refers to fluorine, chlorine, bromine, and iodine.

[0076] Compared with existing technologies, this invention has significant advantages as follows: This invention uses coumarin, a natural product, as a lead raw material to synthesize a series of compounds that retain coumarin while also containing a dithioacetal structure. The synthetic route of this invention achieves high reaction yields, and the derivatives of this invention exhibit good therapeutic, protective, and passivating effects against CMV. Furthermore, their structures and preparation processes are simple. Attached Figure Description

[0077] Figure 1 The results of the anti-CMV therapeutic activities of compound D3 and ningnanmycin at a concentration of 500 μg / mL are shown in the figure. The left figure is the D3 treatment group and the right figure is the ningnanmycin treatment group.

[0078] Figure 2 The results of the protective activities of compound D3 and ningnanmycin against CMV at a concentration of 500 μg / mL are shown in the figure. The left figure is the D3 protection group and the right figure is the ningnanmycin protection group.

[0079] Figure 3 The results of the anti-CMV passivation activity of compound D3 and ningnanmycin at a concentration of 500 μg / mL are shown in the figure. The left figure is the D3 passivation group and the right figure is the ningnanmycin passivation group. Specific Implementation

[0081] The present invention will be further illustrated below through examples. It should be understood that the methods described in the examples are merely illustrative and not intended to limit the invention. Simple modifications to the preparation methods of the present invention within the framework of the present invention's concept are all within the scope of protection claimed by the present invention. All raw materials and solvents used in the examples are commercially available reagents of the corresponding purity.

[0082] Example 1: Synthesis of (E)-2-(2-(((8-(bis(ethylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-2-(methoxyimino)acetic acid methyl ester (compound number D1), the synthesis method is as follows:

[0083] (1) Synthesis of 7-hydroxy-2-oxo-2H-benzopyran-8-carboxaldehyde:

[0084] The starting materials 7-hydroxy-2H-benzopyran-2-one (12 mmol) and hexamethylenetetramine (50 mmol) were added to acetic acid (30 mL), heated to 75 °C, refluxed for 6 h, and then 20% hydrochloric acid (30 mL) was added. The temperature was maintained at 75 °C, and the reaction was continued for 1 h. The reaction was then stopped, cooled to room temperature, poured into crushed ice, extracted with ethyl acetate, washed with saturated brine, dried with anhydrous sodium sulfate, and purified by column chromatography to obtain 1.60 g of 7-hydroxy-2-oxo-2H-benzopyran-8-carboxaldehyde, a yellow solid, with a yield of 72%.

[0085] (2) Synthesis of (E)-2-(2-(bromomethyl)phenyl)-2-(methoxyimino)acetic acid methyl ester:

[0086] Methoxyacrylate (24.13 mmol, 5 g), N-bromosuccinimide (26.54 mmol, 4.72 g), and azobisisobutyronitrile (2.41 mmol, 396 mg) were placed in a 100 mL three-necked flask. 50 mL of carbon tetrachloride was added as solvent, and the mixture was stirred and heated to reflux. The reaction was monitored by TLC. Once the starting material disappeared, the reaction was stopped, cooled to room temperature, and the undissolved solids were removed by filtration. The filtrate was collected, dissolved, and purified by column chromatography to obtain a pale yellow liquid, (E)-2-(2-(bromomethyl)phenyl)-2-(methoxyimino)acetic acid methyl ester 5.92 g, with a yield of 86%.

[0087] (3) Synthesis of methyl 2-((E)-2-(2-((((8-formyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetate:

[0088] Potassium carbonate (10 mmol) was added to a solution of 7-hydroxy-2-oxo-2H-benzopyran-8-carboxaldehyde (5 mmol) in N,N-dimethylformamide (30 mL), heated to 80 °C for 1 h, cooled to room temperature, and then intermediate (E)-2-(2-(bromomethyl)phenyl)-2-(methoxyimino)acetic acid methyl ester (Example 1 (2)) (5 ​​mmol) and potassium iodide (5 mmol) were added. The mixture was heated to 80 °C and the reaction was monitored by TLC. The reaction was stopped when the starting material was completely eliminated. The mixture was cooled to room temperature, poured into ice water, and the pH was adjusted to acidic with dilute hydrochloric acid. The filter cake was collected by filtration and purified by column chromatography to obtain intermediate (E)-2-(2-((((8-formyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester, 1.23 g of yellow solid, with a yield of 62%.

[0089] (4) Synthesis of methyl (E)-2-(2-(((8-(bis(ethylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-2-(methoxyimino)acetate:

[0090] (E)-2-(2-((((8-formyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester (Example 1 (3)) (1 mmol) and thiol (2.2 mmol) were dissolved in dichloromethane (15 mL) at room temperature, and then NaHSO4·SiO2 (5 mmol) catalyst was added. The reaction was detected by TLC. After the starting material was completely converted, the solid silica was removed by filtration, and the filtrate was concentrated under vacuum to obtain the crude product. The crude product was purified by column chromatography to obtain (E)-2-(2-(((8-(bis(ethylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester, white solid, 417 mg, yield: 83%.

[0091] Example 2: Methyl (E)-2-(2-(((8-(bis(propylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetate (compound number D2), synthesized as follows:

[0092] The method and conditions for synthesis are the same as in Example 1 (4), except that propanethiol is used as the raw material.

[0093] Example 3: (E)-2-(2-(((8-(bis(butyrothio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-2-(methoxyimino)acetic acid methyl ester (compound number D3), synthesized as follows:

[0094] The method and conditions for synthesis are the same as in Example 1 (4), except that butanethiol is used as the raw material.

[0095] Example 4: Methyl ((E)-2-(2-(((8-(bis(cyclohexylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetate (compound number D4), synthesized as follows:

[0096] The method and conditions for synthesis are the same as in Example 1 (4), except that cyclohexylthiol is used as the raw material.

[0097] Example 5: Methyl (E)-2-(2-(((8-(1,3-dithio-2-yl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester (compound number D5), synthesized as follows:

[0098] The method and conditions for synthesis are the same as in Example 1 (4), except that ethylenedithiol is used as the raw material.

[0099] Example 6: (E)-2-(2-(((8-(bis(isopropylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester (compound number D6), synthesized as follows:

[0100] The method and conditions for synthesis are the same as in Example 1 (4), except that isopropyl mercaptan is used as the raw material.

[0101] Example 7: Methyl (E)-2-(2-(((8-(bis(tert-butylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester (compound number D7), synthesized as follows:

[0102] The method and conditions for synthesis, as in Example 1 (4), differ in that tert-butylthiol is used as the raw material.

[0103] Example 8: (E)-2-(2-(((8-(bis(ethylthio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-2-(methoxyimino)acetic acid methyl ester (compound number D8), synthesized as follows:

[0104] (1) Synthesis of 7-hydroxy-4-methyl-2-oxo-2H-chromene-8-carboxaldehyde

[0105] As in Example 1(1), the method and conditions for synthesis differ in that 7-hydroxy-4-methyl-2H-chromone-2-one is used as the raw material.

[0106] (2) Synthesis of methyl (E)-2-(2-((((8-formyl-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetate)

[0107] The method and conditions for synthesis are the same as in Example 1 (3), except that 7-hydroxy-4-methyl-2-oxo-2H-chromene-8-carboxaldehyde (Example 8 (1)) is used as the raw material.

[0108] (3) Synthesis of (E)-2-(2-(((8-(bis(ethylthio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-2-(methoxyimino)acetic acid methyl ester (compound number D8)

[0109] As in Example 1 (4), the method and conditions for synthesis differ in that (E)-2-(2-((((8-formyl-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester is used as the raw material.

[0110] Example 9: (E)-2-(2-(((8-(bis(propylthio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester (compound number D9), synthesized as follows:

[0111] The method and conditions for synthesis, as in Example 8 (3), differ in that propanethiol is used as the raw material.

[0112] Example 10: (E)-2-(2-(((8-(bis(butyrothio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-2-(methoxyimino)acetic acid methyl ester (compound number D10), synthesized as follows:

[0113] The method and conditions for synthesis, as in Example 8 (3), differ in that butanethiol is used as the raw material.

[0114] Example 11: Methyl ((E)-2-(2-(((8-(bis(cyclohexylthio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetate (compound number D11), synthesized as follows:

[0115] The method and conditions for synthesis, as in Example 8 (3), differ in that cyclohexylthiol is used as the raw material.

[0116] Example 12: Methyl (E)-2-(2-(((8-(1,3-dithio-2-yl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester (compound number D12), synthesized as follows:

[0117] The method and conditions for synthesis, as in Example 8 (3), differ in that ethylenedithiol is used as the raw material.

[0118] Example 13: Methyl (E)-2-(2-(((8-(bis(isopropylthio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester (compound number D13), synthesized as follows:

[0119] The method and conditions for synthesis, as in Example 8 (3), differ in that isopropyl mercaptan is used as the raw material.

[0120] Example 14: Methyl (E)-2-(2-(((8-(bis(tert-butylthio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester (compound number D14), synthesized as follows:

[0121] The method and conditions for synthesis, as in Example 8 (3), differ in that tert-butyritin is used as the raw material.

[0122] Example 15: (E)-2-(2-(((8-(bis(ethylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-3-methoxyacrylate (compound number D15), synthesized as follows:

[0123] (1) Synthesis of (E)-2-(2-(chloromethyl)phenyl)-3-methoxyacrylate:

[0124] 3-Isochromone (5.0 g) and trimethyl orthoformate (35.8 g) were mixed and heated to 50 °C. Then, boron trifluoride ether (5 mL) was added, and the reaction was continued for 1 h. After cooling to room temperature, the filtrate was collected by filtration and solvent removal to obtain a brown solid. Then, thionyl chloride (33 g) was slowly added dropwise under ice bath. After the addition was completed, the system was heated to reflux. After 8 h, the reaction was stopped, cooled to room temperature, and then methanol (10 mL) was added dropwise under ice bath. After the addition was completed, the reaction was continued for 1 h and then stopped. After solvent removal, column chromatography was used to purify the solution to obtain 6.3 g of yellow solid (E)-2-(2-(chloromethyl)phenyl)-3-methoxyacrylate, with a yield of 65%.

[0125] (2) Synthesis of methyl methoxyacrylate (E)-2-(2-((((8-formyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-3-methoxyacrylate)

[0126] As in Example 1 (3), the method and conditions for synthesis differ in that (E)-2-(2-(chloromethyl)phenyl)-3-methoxyacrylate is used as the raw material.

[0127] Synthesis of (E)-2-(2-(((8-(bis(ethio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-3-methoxyacrylate

[0128] As in Example 1 (4), the method and conditions for synthesis differ in that (E)-2-(2-((((8-formyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-3-methoxyacrylate is used as the raw material.

[0129] Example 16: (E)-2-(2-(((8-(bis(propylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-3-methoxyacrylate (compound number D16), synthesized as follows:

[0130] The method and conditions for synthesis, as in Example 15 (3), differ in that propanethiol is used as the raw material.

[0131] Example 17: (E)-2-(2-(((8-(bis(butyrothio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-3-methoxyacrylate (compound number D17), synthesized as follows:

[0132] The method and conditions for synthesis, as in Example 15 (3), differ in that butanethiol is used as the raw material.

[0133] Example 18: (E)-2-(2-(((8-(bis(cyclohexylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-3-methoxyacrylate (compound number D18), synthesized as follows:

[0134] The method and conditions for synthesis, as in Example 15 (3), differ in that cyclohexylthiol is used as the raw material.

[0135] Example 19: Methyl (E)-2-(2-(((8-(1,3-dithio-2-yl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-3-methoxyacrylate (compound number D19), synthesized as follows:

[0136] The method and conditions for synthesis, as in Example 15 (3), differ in that ethylenedithiol is used as the raw material.

[0137] Example 20: (E)-2-(2-(((8-(bis(isopropylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-3-methoxyacrylate (compound number D20), synthesized as follows:

[0138] The method and conditions for synthesis, as in Example 15 (3), differ in that isopropyl mercaptan is used as the raw material.

[0139] Example 21: (E)-2-(2-(((8-(bis(tert-butylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-3-methoxyacrylate (compound number D21), synthesized as follows:

[0140] The method and conditions for synthesis, as in Example 15 (3), differ in that tert-butyritin is used as the raw material.

[0141] Example 22: (E)-2-(2-(((8-(bis(ethylthio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-3-methoxyacrylate (compound number D22), synthesized as follows:

[0142] (1) Synthesis of methyl (E)-2-(2-((((8-formyl-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetate)

[0143] The method and conditions for synthesis, as in Example 15 (2), differ in that 7-hydroxy-4-methyl-2-oxo-2H-chromene-8-carboxaldehyde is used as the raw material.

[0144] (2) Synthesis of (E)-2-(2-(((8-(bis(ethio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-3-methoxyacrylate

[0145] The method and conditions for synthesis as in Example 15 (3) differ in that (E)-2-(2-((((8-formyl-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester (Example 22 (1)) is used as the starting material.

[0146] Example 23: (E)-2-(2-(((8-(bis(propylthio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-3-methoxyacrylate (compound number D23), synthesized as follows:

[0147] The method and conditions for synthesis, as in Example 22(1), differ in that propanethiol is used as the raw material.

[0148] Example 24: (E)-2-(2-(((8-(bis(butyrothio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-3-methoxyacrylate (compound number D24), synthesized as follows:

[0149] The method and conditions for synthesis, as in Example 22(1), differ in that butanethiol is used as the raw material.

[0150] Example 25: (E)-2-(2-(((8-(bis(cyclohexylthio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-3-methoxyacrylate (compound number D25), synthesized as follows:

[0151] The method and conditions for synthesis, as in Example 22(1), differ in that cyclohexylthiol is used as the raw material.

[0152] Example 26: Methyl (E)-2-(2-(((8-(1,3-dithio-2-yl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-3-methoxyacrylate (compound number D26), synthesized as follows:

[0153] The method and conditions for synthesis, as in Example 22(1), differ in that ethylenedithiol is used as the raw material.

[0154] Example 27: (E)-2-(2-(((8-(bis(isopropylthio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-3-methoxyacrylate (compound number D27), synthesized as follows:

[0155] The method and conditions for synthesis, as in Example 22(1), differ in that isopropyl mercaptan is used as the raw material.

[0156] Example 28: (E)-2-(2-(((8-(bis(tert-butylthio)methyl)-4-methyl-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-3-methoxyacrylate (compound number D28), synthesized as follows:

[0157] The method and conditions for synthesis, as in Example 22(1), differ in that tert-butyritin is used as the raw material.

[0158] Example 29: Methyl (E)-2-(2-(((8-(bis((4-chlorophenyl)thio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester (compound number D29), synthesized as follows:

[0159] The method and conditions for synthesis in Example 1 (1) differ in that 4-chlorothiophenol is used as the raw material.

[0160] Example 30: (E)-2-(2-(((8-(bis((2,4-dichlorophenyl)thio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester (compound number D30), synthesized as follows:

[0161] The method and conditions for synthesis in Example 1 (1) differ in that 2,4-dichlorothiophenol is used as the raw material.

[0162] Example 31: Methyl ((E)-2-(2-(((8-(bis((4-fluorophenyl)thio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetate (compound number D31), synthesized as follows:

[0163] The method and conditions for synthesis in Example 1 (1) differ in that 4-fluorothiophenol is used as the raw material.

[0164] Example 32: (E)-2-(2-(((8-(bis(p-tolyl)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-2-(methoxyimino)acetic acid methyl ester (compound number D32), the synthesis method is as follows:

[0165] The method and conditions for synthesis in Example 1 (1) differ in that 4-methylthiophenol is used as the raw material.

[0166] Example 33: (E)-2-(2-(((8-(bis(benzylthio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methylmethyl)phenyl)-2-(methoxyimino)acetic acid methyl ester (compound number D33), synthesized as follows:

[0167] As in Example 1 (1), the method and conditions for synthesis differ in that benzyl thiol is used as the raw material.

[0168] Example 34: Methyl (E)-2-(2-(((8-(bis((4-methoxyphenyl)thio)methyl)-2-oxo-2H-benzopyran-7-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetic acid methyl ester (compound number D34), synthesized as follows:

[0169] As in Example 1 (1), the method and conditions for synthesis differ in that 4-methoxythiol is used as the raw material.

[0170] Table 1 Physicochemical properties of the target compounds in the examples

[0171]

[0172] The compound's proton nuclear magnetic resonance spectrum ( 1 H NMR) and carbon spectroscopy ( 13 The C NMR data are shown in Table 2.

[0173] Table 2. Spectral data of Examples 1-34 (Compounds D1-D34)

[0174]

[0175]

[0176]

[0177]

[0178]

[0179]

[0180] Example 1: Therapeutic, protective and inactivation tests of the target compound against cucumber mosaic virus.

[0181] (1) Extraction method

[0182] a. Virus purification:

[0183] The method reported by Zhou Xueping et al. (Zhou Xueping, Xu Zhixin, Xu Jing, Li Debao. Study on cucumber mosaic virus infecting loofah [J]) was adopted. Journal of South China Agricultural University 1995, 16 (2), 74-79.), Selected plants inoculated for more than 3 weeks, the upper leaves of the host plant, common tobacco K326, were infected with CMV systemically. The slurry was homogenized in phosphate buffer, filtered through double-layer gauze, centrifuged at 8000g, treated twice with polyethylene glycol, centrifuged again, and the precipitate was resuspended in phosphate buffer to obtain the purified CMV extract. The entire experiment was conducted at 4℃. The absorbance at 260nm wavelength was measured using a UV spectrophotometer, and the virus concentration was calculated according to the formula.

[0184] Virus concentration (mg / mL) = (A 260 (×dilution factor) / E.

[0185] Where E represents the extinction coefficient, which is the light absorption value of a 0.1% (1 mg / mL) suspension at a wavelength of 260 nm with an optical path length of 1 cm. The extinction coefficient of CMV is 5.0.

[0186] (2) In vivo test method for CMV infection by the agent

[0187] a. In vivo therapeutic effect of the drug on CMV infection:

[0188] Using the half-leaf necrotic spot method, with a pesticide concentration of 500 mg / L, select amaranth plants with 5-6 leaves of uniform growth for pruning. Sprinkle emery evenly over the entire leaf, and use a brush dipped in virus solution (6×10) -3 Inoculate the entire leaf with the virus (mg / mL), and after the amaranth leaves have air-dried naturally, rinse them with clean water. After the leaves have dried, gently apply the agent to the left half of the leaf with a brush, and apply the corresponding concentration of the solvent to the right half of the leaf as a control. Record the number of necrotic spots after 4-5 days, and calculate the inhibition rate according to the following formula.

[0189] b. The in vivo protective effect of the agent against CMV infection:

[0190] The half-leaf necrotic spot method was used, with a pesticide concentration of 500 mg / L. Amaranth plants with 5-6 leaves and uniform growth were pruned. The pesticide was lightly applied to the left half of the leaf with a brush, while the right half was treated with a corresponding concentration of the pesticide as a control. 24 hours later, carborundum was evenly sprinkled onto the entire leaf, and virus solution (6×10⁻⁶) was collected using a brush. -3 Inoculate the whole leaf with the virus (mg / mL), rinse with water, record the number of necrotic spots after 4-5 days, and calculate the inhibition rate according to the following formula.

[0191] c. The inactivating effect of the drug on CMV infection:

[0192] Using the half-leaf necrotic spot method, select amaranth plants with 5-6 leaves of uniform growth for pruning. The pesticide concentration is 500 mg / L. Mix the pesticide with virus solution (12 × 10⁻⁶). -3 Mix equal volumes of the virus solution (mg / mL) thoroughly. After half an hour, use a brush to collect 6×10 mg / mL of the virus solution. -3 (mg / mL) The left leaf was inoculated with the virus as a control. The right leaf was inoculated with the virus using a brush dipped in the mixture of drug and virus solution. After half an hour, the leaves were rinsed with water. The number of necrotic spots was recorded after 4-5 days, and the inhibition rate was calculated using the following formula.

[0193] Inhibition rate (%) = (Average number of necrotic spots on the untreated half-leaf - Average number of necrotic spots on the treated half-leaf) / Average number of necrotic spots on the untreated half-leaf

[0194] The average number of necrotic spots on the untreated half-leaf and the average number of necrotic spots on the treated half-leaf were both calculated using the average of three replicates for each group.

[0195] Table 3. Anti-CMV therapeutic, protective, and inactivating activities of the target compound at a concentration of 500 μg / mL

[0196]

[0197] The anti-CMV activity of coumarin derivatives containing dithioacetal was tested using the half-leaf necrotic spot method at a concentration of 500 mg / L, with ningnanmycin as a control agent. Table 3 shows the bioassay results, indicating that the therapeutic, protective, and inactivating activities of the coumarin derivatives containing dithioacetal were superior to those of the target compound obtained in Example 3, which showed therapeutic, protective, and inactivating activities of 58.7%, 61.4%, and 87.3%, respectively.

[0198] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Any simple modifications, equivalent changes, and alterations made to the above embodiments without departing from the technical essence of the present invention shall still fall within the scope of the present invention.

Claims

1. A coumarin derivative containing a dithioacetal unit, characterized in that, The coumarin derivatives containing dithioacetal units are compounds having the structure shown in formula (I): in R 1 Selected from hydrogen and methyl; X is selected from nitrogen or carbon; R 4 It is selected from ethyl, n-propyl, n-butyl, cyclohexyl, methylene with disulfide ring, isopropyl, tert-butyl, chlorophenyl, 2,4-dichlorophenyl, fluorophenyl, tolyl, and methoxyphenyl.

2. A coumarin derivative containing a dithioacetal unit according to claim 1, characterized in that: The following specific compounds were selected: 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 。 3. An agricultural composition, characterized in that... The composition contains a coumarin derivative containing a dithioacetal unit as described in any one of claims 1-2, and agriculturally applicable adjuvants or fungicides, antiviral agents or herbicides; the dosage form of the composition is selected from emulsifiable concentrates, powders, wettable powders, granules, aqueous solutions, suspensions, ultra-low volume sprays, soluble powders, microcapsules, fumigants, water emulsions, and water-dispersible granules.

4. The use of the coumarin derivative containing a dithioacetal unit as described in any one of claims 1-2, or the composition as described in claim 3, in the preparation of a drug for preventing and treating cucumber mosaic virus.

5. A method for preventing and controlling agricultural viral diseases, characterized in that: The coumarin derivative containing a dithioacetal unit as described in any one of claims 1-2, or the composition as described in claim 3, is applied to the harmful substance or its living environment; the agricultural viral disease is cucumber mosaic virus disease.

6. A method for protecting plants from agricultural viral diseases, comprising the step of contacting plant leaves with a coumarin derivative containing a dithioacetal unit as described in any one of claims 1-2, or the composition as described in claim 3; wherein the agricultural viral disease is cucumber mosaic virus.

Images