Raspberry ketone compound, synthesis thereof and application of raspberry ketone compound in prevention and treatment of plant viruses, germs and diseases

Abstract

The invention relates to raspberry ketone compounds III-1III-13, V-1V-15 and VI-1VI-11, a preparation method of the raspberry ketone compounds III-1III-13, V-1V-15 and VI-1VI-11, and an application of the raspberry ketone compounds III-1III-13, V-1V- The invention provides a series of raspberry ketone compounds, develops an efficient synthesis method of the compounds, discovers the plant virus and plant pathogen resisting activity of the compounds, and lays a foundation for synthesis and biological activity research of the compounds. The raspberry ketone compounds III-1III-13, V-1V-15 and VI-1VI-11 disclosed by the invention have the activity of resisting plant viruses, can be used for inhibiting tobacco mosaic viruses, and meanwhile, the compounds show broad-spectrum activity of resisting plant pathogenic bacteria.

Description

Technical Field

[0001] This invention relates to a class of raspberry ketone compounds, their preparation, and their application in the prevention and control of plant viral and bacterial diseases, belonging to the field of agricultural protection technology. Background Technology

[0002] Plant viral and pathogenic diseases are increasingly becoming "invisible killers" in the global food security system. These diseases can directly lead to significant yield reductions and quality deterioration in major crops. Among them, viral diseases are particularly troublesome, often figuratively referred to as "plant cancer" in agricultural production due to their systemic infection characteristics and devastating damage. According to estimates from the Food and Agriculture Organization of the United Nations and related international agricultural research institutions, these diseases cause direct economic losses of tens of billions of US dollars annually worldwide, severely restricting the sustainable development capacity of modern agriculture. Most existing registered pesticides are primarily preventative, with significant shortcomings in curative activity. Many agents are chemically unstable, have short field retention periods, and struggle to maintain stable biological activity in complex and changing natural environments; moreover, for virus particles that have already invaded plant tissues and begun to replicate, existing agents often fail to effectively reach the site of action, exhibiting extremely low curative efficacy. Faced with the complex situation of synergistic infection and compound damage by viruses and pathogens, the agricultural science and technology community urgently needs to break through the traditional plant protection concept and develop green and efficient agents with both protective and curative effects, good environmental compatibility, and novel modes of action, based on new mechanisms of action, in order to cope with the increasingly severe challenges of plant diseases and ensure global food supply security and agricultural product quality safety.

[0003] Natural products, due to their novel structures, diverse skeletons, and abundant pharmacodynamic functional groups, can precisely recognize and bind to biomolecular targets, thus playing a vital role in pesticide and pharmaceutical development and serving as an important source for discovering new active molecules. Phenolic compounds, as one of the most widely distributed and diverse categories of plant secondary metabolites, have long attracted widespread attention due to their strong structural modifiability and diverse modes of action. Raspberry ketone (4-p-hydroxyphenyl-2-butanone, structural formula 1) is a naturally occurring phenolic derivative found in berries such as raspberries, strawberries, and cranberries. It is also a key precursor to many plant aroma components, possessing multiple biological functions including antioxidant, anti-inflammatory, and metabolism-promoting effects, demonstrating excellent development potential and application prospects. However, raspberry ketone itself suffers from high volatility, insufficient environmental stability, and excessive lipophilicity, severely limiting its persistence and targeted delivery efficiency in actual agricultural production. Based on the excellent biocompatibility and degradability of ester bonds, introducing functional fragments into the raspberry ketone core via esterification is a feasible strategy to improve its physicochemical properties and enhance its affinity for biological targets, thereby increasing its application value. Currently, systematic research on the application of raspberry ketone and its esterified derivatives in plant disease control, particularly in antiviral and antifungal activities, is still lacking, and related structural optimization and activity evaluation have not been systematically reported.

[0004]

[0005] Structural Formula 1 Summary of the Invention

[0006] To address the shortcomings of existing technologies, this invention provides a class of raspberry ketone compounds, their preparation method, and their application in the prevention and control of plant viral and fungal diseases. The raspberry ketone compounds of this patent exhibit excellent antiviral and antifungal activity against plant viruses and pathogens.

[0007] This invention uses raspberry ketone as the general formula and includes compounds in three categories: III, V, and VI. The specific structures are shown below as III-1–III-13, V-1–V15, and VI-1–VI-11 (structural formulas II, III, and IV).

[0008]

[0009] Structural Form 2

[0010]

[0011] Structural Form Three

[0012]

[0013] Structure Four

[0014] The preparation methods of the above-mentioned raspberry ketone compounds III-1–III-13, V-1–V15, and VI-1–VI-11 are as follows:

[0015] Prepared according to the methods shown in Equations 1 and 2.

[0016] In acetic acid and ethanol, 60 o Under C conditions, the ketone carbonyl group of compound I undergoes a condensation reaction with aminothiourea to form a hydrazone bond, yielding the key intermediate II. Subsequently, intermediate II is reacted in ethanol at 90°C. o Under C conditions, cyclization was achieved by reacting bromoketone compounds with different substituents for 5 hours, yielding the corresponding thiazole compounds III-1–III-13. In acetic acid and ethanol, 60… o Under C conditions, compound IV undergoes a condensation reaction with aminothiourea to form a hydrazone bond, yielding compounds V-1–V-15. Subsequently, the mixture is reacted in sodium acetate and methanol at room temperature for 5 hours to yield compounds VI-1–VI-11.

[0017]

[0018] Equation 1

[0019]

[0020] Equation 2

[0021] In Equation 1 above, R is the substituent shown in the structure of raspberry ketone derivative III-1–III-13; in Equation 2, R 1 R is the substituent shown in the structure of raspberry ketone derivatives V-1–V-15. 2 The substituents shown in the structure of raspberry ketone derivatives VI-1–VI-11 are used; raw materials I and IV were purchased directly from Bid Pharmaceutical Technology Co., Ltd.

[0022] The raspberry ketone compounds III-1–III-13, V-1–V15, and VI-1–VI-11 of this invention exhibit outstanding antiviral and antipathogenic activity against plant pathogens, and show significant inhibitory effects against tobacco mosaic virus (TMV), as well as apple ring rot fungus, wheat sheath blight fungus, tomato early blight fungus, rice blast fungus, pepper phytophthora, and rapeseed sclerotinia. Detailed Implementation

[0024] The following examples and test results are intended to further illustrate the present invention, but do not imply limitation of the invention.

[0025] Example 1: Synthesis of Compound II

[0026] Compound I (164 mg, 1 mmol) was dissolved in anhydrous ethanol (15 mL), followed by the addition of thiourea (109 mg, 1.2 mmol) and acetic acid (10 mL). The reaction mixture was stirred at 60 °C for 3 hours. After the reaction was completed as monitored by thin-layer chromatography (TLC), the solvent was evaporated, and acetic acid was neutralized by adding saturated NaHCO3 solution. After a period of time, a solid precipitate formed. The solid was collected by filtration under reduced pressure to obtain compound II.

[0027] Example 2: Synthesis of compounds III-1–III-13

[0028] Compound II (237 mg, 1 mmol) was dissolved in anhydrous ethanol (15 mL), followed by the addition of the corresponding bromoketone derivative (1.3 mmol). The reaction mixture was stirred at 90 °C for 5 hours. The reaction was confirmed to be complete by thin-layer chromatography (TLC), and the mixture was extracted three times with ethyl acetate (EA). The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, and filtered. The filtrate was concentrated to give compounds III-1–III-13.

[0029] III-1: Yellow solid, yield 99%, mp 168–169 ºC. 1 H NMR (400 MHz, DMSO-d6) δ 10.93 (s, 1H, OH), 7.71 (d, J = 8.1 Hz, 2H, ArH), 7.23 (d, J = 8.2 Hz,2H, ArH), 7.19 (s, 1H, ArH), 7.07 (dd, J = 25.5, 1.96 (s, 3H, CH3). 13 C NMR (100 MHz, DMSO-d6)δ 170.4, 155.9, 138.0, 131.7, 130.7, 129.8, 129.7, 129.3, 126.1, 115.5,103.4, 100.0, 40.5, 31.4, 30.2, 23.4, 21.3, 17.5. HRMS (ESI) calcd forC 20 H 22 N3OS + (M+H)+ 352.1478, found 352.1483.

[0030] III-2: White solid, yield 75%, mp 172–173 ºC. 1 H NMR (400 MHz, DMSO-d6) δ 10.79 (s, 1H, OH), 7.87 (dd, J = 8.1, 5.8 Hz, 2H, ArH), 7.30 – 7.25 (m,1H, NH), 7.25 – 7.22 (m, 2H, ArH), 7.11 (d, J = 8.5 Hz, 1H, ArH), 7.04 (d, J= 8.4 Hz, 2H, ArH), 6.68 (t, J = 8.7 Hz, 2H, ArH), 2.78 – 2.66 (m, 2H, CH2),2.51 (d, J = 1.8 Hz, 2H, CH2), 2.00 – 1.84 (m, 3H, CH3). 13 C NMR (100 MHz,DMSO-d6) δ 170.5, 162.2 (d, J = 243.0 Hz), 156.1, 155.9, 131.8, 129.7, 128.2(d, J = 8.0 Hz), 116.1, 115.9, 115.5, 104.0, 31.4, 30.2, 23.4, 17.5. 19 F NMR(376 MHz, DMSO-d6) δ -114.3. HRMS (ESI) calcd for C 19 H 19 FN3OS + (M+H) + 356.1227,found 356.1233.

[0031] III-3: Yellow solid, yield 69%, mp 170–171 ºC. 1H NMR (400 MHz, DMSO-d6) δ 10.86 (s, 1H, OH), 8.30 – 8.24 (m, 2H, ArH), 8.10 (dd, J = 8.9, 1.3 Hz,2H, ArH), 7.64 (d, J = 1.3 Hz, 1H, NH), 7.13 – 7.05 (m, 1H, ArH), 7.04 (d, J= 8.4 Hz, 2H, ArH), 6.67 (dd, J = 8.4, 1.8 Hz, 2H, ArH), 2.79 – 2.69 (m, 2H,CH2), 2.50 – 2.47 (m, 2H, CH2), 1.94 (s, 3H, CH3). 2.49 (dd, J = 6.4, 4.6 Hz,2H, CH2), 1.95 – 1.91 (m, 3H, CH3). 13 C NMR (100 MHz, DMSO-d6) δ 171.0, 155.9,148.5, 146.6, 131.8, 129.7, 126.8, 124.6, 115.5, 108.9, 31.4, 17.4. HRMS(ESI) calcd for C 19 H 19 N4O3S + (M+H) + 383.1172, found 383.1177.

[0032] III-4: White solid, yield 75%, mp 176–177 ºC. 1 H NMR (400 MHz, DMSO-d6) δ 10.83 (s, 1H, OH), 8.06 (d, J = 8.2 Hz, 2H, ArH), 7.76 (d, J = 8.4 Hz,2H, ArH), 7.49 (d, J = 2.1 Hz, 1H, NH), 7.04 (d, J = 8.5 Hz, 2H, ArH), 6.69 –6.65 (m, 2H, ArH), 2.77 – 2.68 (m, 2H, CH2), 2.51 – 2.47 (m, 2H, CH2), 1.93(d, J = 10.6 Hz, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) δ 170.8, 155.9, 148.5,138.6, 131.8, 129.7, 128.9, 128.0 (q, J = 31.0 Hz), 126.6, 126.1, 123.5,115.5, 106.8, 31.4, 23.5, 17.4. 19 F NMR (376 MHz, DMSO-d6) δ -60.9. HRMS (ESI)calcd for C 20 H 19 F3N3OS + (M+H) + 406.1195, found 406.1191.

[0033] III-5: White solid, yield 46%, mp 172–173 ºC. 1 H NMR (400 MHz, DMSO-d6) δ 10.83 (s, 1H, NH), 9.41 (s, 1H, OH), 7.85 (d, J = 8.6 Hz, 2H, ArH),7.49 – 7.45 (m, 2H, ArH), 7.32 (s, 1H, ArH), 7.04 (d, J = 8.4 Hz, 2H, ArH),6.67 (d, J = 8.5 Hz, 2H, ArH), 2.78 – 2.68 (m, 2H, CH2), 2.50 (dd, J = 6.9,5.0 Hz, 2H, CH2), 1.93 (d, J = 8.9 Hz, 3H, CH3). 13 C NMR (100 MHz, DMSO-d6) δ156.0, 154.3, 133.1, 131.8, 130.0, 129.7, 129.1, 128.9, 127.8, 115.5, 105.0,31.4, 17.5. HRMS (ESI) calcd for C 19 H 19 ClN3OS + (M+H) + 372.0932, found 372.0938.

[0034] III-6: Yellow solid, yield 64%, mp 178–179 ºC.1 H NMR (400 MHz, DMSO-d6) δ 10.84 (s, 1H, OH), 8.10 (d, J = 8.6 Hz, 2H, ArH), 7.95 (d, J = 8.6 Hz,2H, ArH), 7.55 (d, J = 2.1 Hz, 1H, ArH), 7.04 (d, J = 8.5 Hz, 2H, ArH), 6.67(d, J = 8.5 Hz, 2H, ArH), 3.23 (s, 3H, CH3), 2.72 (d, J = 8.2 Hz, 2H, CH2),2.50 – 2.46 (m, 2H, CH2), 1.93 (d, J = 10.8 Hz, 3H, CH3). 13 C NMR (100 MHz,DMSO-d6) δ 170.8, 155.9, 153.4, 139.6, 131.8, 129.7, 128.0, 127.6, 126.6,115.5, 107.6, 44.1, 31.4, 17.4. HRMS (ESI) calcd for C 20 H 22 N3O3S2 + (M+H) + 416.1097, found 416.1091.

[0035] III-7: Yellow solid, yield 52%, mp 208–209 ºC. 1 H NMR (400 MHz, DMSO-d6) δ 9.20 (s, 1H, OH), 9.02 (s, 1H, NH), 7.75 (d, J = 6.8 Hz, 2H, ArH), 7.18– 6.95 (m, 5H, ArH, NH), 6.67 (d, J = 8.0 Hz, 2H, ArH), 3.79 (s, 3H, CH3),2.73 (d, J = 7.3 Hz, 2H, CH2), 2.51 (s, 2H, CH2), 1.96 (s, 3H, CH3). 13C NMR(100 MHz, DMSO-d6) δ 170.3, 159.9, 156.1, 131.7, 129.7, 127.7, 115.6, 114.7,114.3, 102.4, 55.8, 31.3, 17.7. HRMS (ESI) calcd for C 20 H 22 N3O2S + (M+H) + 368.1427, found 368.1434.

[0036] III-8: Yellow solid, yield 82%, mp 166–167 ºC. 1 H NMR (400 MHz, DMSO-d6) δ 10.42 (s, 1H, OH), 9.12 (s, 1H, NH), 7.02 (d, J = 8.4 Hz, 2H, ArH),6.65 (d, J = 8.4 Hz, 2H, ArH), 6.29 (s, 1H, ArH), 2.73 – 2.66 (m, 2H, CH2),2.45 (t, J = 7.7 Hz, 2H, CH2), 1.88 (s, 3H, CH3), 1.22 (s, 9H, CH3). 13 C NMR(100 MHz, DMSO-d6) δ 170.1, 155.8, 152.2, 151.5, 131.9, 129.7, 115.5, 99.8,34.7, 31.6, 30.1, 17.1. HRMS (ESI) calcd for C 17 H 24 N3OS + (M+H) + 318.1635, found318.1639.

[0037] III-9: Yellow solid, yield 20%, mp 169–170 ºC. 1H NMR (400 MHz, DMSO-d6) δ 10.64 (s, 1H, OH), 9.14 (s, 1H, NH), 7.84 (d, J = 8.0 Hz, 1H, ArH),7.73 (dd, J = 20.0, 7.5 Hz, 2H, ArH), 7.57 (d, J = 7.6 Hz, 1H, ArH), 7.11 (s,1H, ArH), 7.04 (d, J = 8.2 Hz, 2H, ArH), 6.67 (d, J = 8.2 Hz, 2H, ArH), 2.72(t, J = 7.7 Hz, 2H, CH2), 2.47 (d, J = 7.3 Hz, 2H, CH2), 1.91 (s, 3H, CH3). 13 CNMR (100 MHz, DMSO-d6) δ 170.8, 155.9, 152.8, 149.0, 147.0, 132.8, 131.9,131.1, 129.7, 129.4, 124.3, 115.5, 107.7, 31.5, 17.4. HRMS (ESI) calcd forC 19 H 19 N4O3S + (M+H) + 383.1172, found 383.1179.

[0038] III-10: Brown solid, yield 29%, mp 130–131 ºC. 1 H NMR (400 MHz, DMSO-d6) δ 10.73 (s, 1H, OH), 9.14 (s, 1H, NH), 8.03 (t, J = 7.8 Hz, 1H, ArH),7.30 (ddd, J = 26.3, 12.8, 7.1 Hz, 3H, ArH), 7.17 (d, J = 1.9 Hz, 1H, ArH),7.05 (d, J = 8.3 Hz, 2H, ArH), 6.67 (d, J = 8.3 Hz, 2H, ArH), 2.73 (t, J =7.7 Hz, 2H, CH2), 2.48 (d, J = 7.4 Hz, 2H, CH2), 1.94 (s, 3H, CH3). 13C NMR(100 MHz, DMSO-d6) δ 170.0, 160.0 (d, J = 247.0 Hz), 155.9, 152.4, 144.6,131.9, 129.7, 129.4 (d, J = 8.0 Hz), 125.1, 123.0 (d, J = 11.0 Hz), 116.5 (d,J = 22.0 Hz), 115.5, 108.6 (d, J = 15.0 Hz), 31.5, 17.3. 19 F NMR (376 MHz,DMSO-d6) δ -114.2. HRMS (ESI) calcd for C 19 H 19 FN3OS + (M+H) + 356.1227, found356.1221.

[0039] III-11: White solid, yield 52%, mp 225–226 ºC. 1 H NMR (400 MHz, DMSO-d6) δ 10.94 (s, 1H, OH), 7.96 (dd, J = 20.6, 8.1 Hz, 2H, ArH), 7.78 – 7.69(m, 4H, ArH), 7.48 (t, J = 7.5 Hz, 2H, ArH), 7.41 – 7.29 (m, 2H, ArH), 7.05(d, J = 8.0 Hz, 2H, ArH), 6.68 (d, J = 8.2 Hz, 2H, ArH), 6.49 (s, 1H, NH),2.78 – 2.68 (m, 2H, CH2), 2.52 (d, J = 10.1 Hz, 2H, CH2), 1.95 (d, J = 10.4Hz, 3H, CH3). 13 C NMR (100 MHz, DMSO-d6) δ 155.9, 131.8, 131.6, 129.7, 129.6,129.5, 128.1, 127.7, 127.3, 127.1, 115.5, 45.1, 31.5, 30.3, 28.8, 17.4. HRMS(ESI) calcd for C 25 H 24 N3OS +(M+H) + 414.1635, found 414.1639.

[0040] III-12: White solid, yield 54%, mp 205–206 ºC. 1 H NMR (400 MHz, DMSO-d6) δ 10.63 (d, J = 781.8 Hz, 1H, NH), 9.65 (s, 1H, OH), 7.81 (d, J = 7.1 Hz,1H, ArH), 7.40 (dd, J = 16.9, 9.4 Hz, 2H, ArH), 7.19 – 7.03 (m, 4H, ArH),6.69 (d, J = 8.2 Hz, 2H, ArH), 3.93 (s, 3H, CH3), 2.79 – 2.72 (m, 2H, CH2),2.56 (dd, J = 18.5, 11.3 Hz, 2H, CH2), 2.01 (d, J = 17.7 Hz, 3H, CH3). 13 C NMR(100 MHz, DMSO-d6) δ 168.8, 156.8, 155.9, 131.6, 130.7, 130.2, 121.2, 115.6,112.4, 107.4, 56.2, 31.3, 17.9. HRMS (ESI) calcd for C 20 H 22 N3O2S + (M+H) + 368.1427, found 368.1424.

[0041] III-13: White solid, yield 60%,mp 186–187 ºC. 1H NMR (400 MHz, DMSO-d6) δ 10.79 (s, 1H, NH), 9.77 (s, 1H, OH), 7.83 (d, J = 5.8 Hz, 2H, ArH), 7.42 (t, J = 6.8 Hz, 2H, ArH), 7.35 – 7.23 (m, 2H, ArH), 7.12 – 7.02 (m, 2H,ArH), 6.68 (t, J = 8.6 Hz, 2H, ArH), 2.78 – 2.70 (m, 2H, CH2), 2.51 (d, 2H,CH2), 1.95 (s, 3H, CH3). 13 C NMR (100 MHz, DMSO-d6) δ 170.4, 155.9, 133.5,131.7, 131.2, 129.2, 128.8, 128.6, 128.3, 126.2, 115.5, 104.4, 31.4, 30.2,23.4, 17.6. HRMS (ESI) calcd for C 19 H 20 N3OS + (M+H) + 338.1322, found 338.1328.

[0042] Example 3: Synthesis of compounds V-1–V-15

[0043] Compound IV (1 mmol) was dissolved in anhydrous ethanol (15 mL), and thiourea (1.2 mmol) and acetic acid (10 mL) were added. The mixture was stirred at 60 °C for 3 hours. After the reaction was completed by thin-layer chromatography (TLC), the solvent was removed under reduced pressure, and then acetic acid was neutralized with saturated sodium bicarbonate (NaHCO3) solution, resulting in the precipitation of a solid precipitate. The solid was collected by filtration under reduced pressure to obtain target compounds V-1 to V-15.

[0044] V-1: Yellow solid, yield 98%, mp 228–229 ºC. 1H NMR (400 MHz, DMSO-d6)δ 9.97 (s, 1H, NH), 8.39 (dd, J = 22.9, 8.8 Hz, 4H, ArH), 8.05 (s, 1H, NH),7.48 (s, 1H, NH), 7.38 (dd, J = 27.1, 8.3 Hz, 2H, ArH), 7.25 (t, J = 10.5 Hz,2H, ArH), 2.90 (t, J = 7.7 Hz, 2H, CH2), 2.57 (t, J = 7.8 Hz, 2H, CH2), 1.95(s, 3H, CH3). 13 C NMR (100 MHz, DMSO-d6) δ 179.0, 163.7, 153.9, 151.0, 149.0,140.1, 135.0, 131.7, 129.9, 124.5, 121.9, 31.3, 23.5, 17.3. HRMS (ESI) calcdfor C 17 H 19 N4O5S2 + (M+H) + 423.0791, found 423.0797.

[0045] V-2:White solid, yield 83%, mp 208–209 ºC. 1 H NMR (400 MHz, DMSO-d6) δ9.98 (s, 1H, NH), 8.26 – 8.15 (m, 2H, NH), 8.05 (d, J = 14.6 Hz, 1H, ArH),7.45 (dd, J = 18.9, 10.3 Hz, 3H, ArH), 7.40 – 7.26 (m, 2H, ArH), 7.20 (t, J =10.4 Hz, 2H, ArH), 2.89 (t, J = 7.7 Hz, 2H, CH2), 2.56 (t, J = 7.7 Hz, 2H,CH2), 1.94 (d, J = 4.7 Hz, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) δ 179.0, 166.0(d, J = 251.0 Hz), 164.2, 153.9, 149.1, 139.8, 133.2 (d, J = 10.0 Hz), 129.8(d, J = 7.0 Hz), 126.1, 122.1, 116.6 (d, J = 22.0 Hz), 32.2, 31.3, 30.5,23.5, 17.2. 19 F NMR (376 MHz, DMSO-d6) δ -104.8. HRMS (ESI) calcd forC 18 H 19 FN3O2S + (M+H) + 360.1177, found 360.1184.

[0046] V-3:White solid, yield 92%, mp 175–176 ºC. 1 H NMR (400 MHz, DMSO-d6) δ9.97 (s, 1H, NH), 8.05 (s, 1H, NH), 7.49 (s, 1H, NH), 7.38 (dd, J = 25.6, 8.3Hz, 2H, ArH), 7.19 (t, J = 10.2 Hz, 2H, ArH), 6.99 (s, 2H, ArH), 2.89 (t, J =7.7 Hz, 2H, CH2), 2.75 – 2.53 (m, 2H, CH2), 2.37 (s, 6H, CH3), 2.28 (s, 3H,CH3), 1.94 (d, J = 4.3 Hz, 3H, CH3). 13 C NMR (100 MHz, DMSO-d6) δ 179.0, 168.3,153.9, 148.8, 140.0, 135.3, 130.3, 130.0, 128.9, 122.0, 21.2, 19.9, 17.3.HRMS (ESI) calcd for C 21 H 26 N3O2S + (M+H) + 384.1740, found 384.1734.

[0047] V-4:White solid, yield 63%,mp 151–152 ºC. 1 H NMR (400 MHz, DMSO-d6) δ9.97 (s, 1H, NH), 8.05 (s, 1H, NH), 7.47 (s, 1H, NH), 7.42 – 7.30 (m, 4H,ArH), 7.18 (t, J = 10.4 Hz, 2H, ArH), 3.87 (s, 6H, CH3), 3.78 (s, 3H, CH3),2.89 (t, J = 7.6 Hz, 2H, CH2), 2.56 (t, J = 7.7 Hz, 2H, CH2), 1.93 (d, J = 4.6Hz, 3H, CH3). 13 C NMR (100 MHz, DMSO-d6) δ 179.0, 164.8, 153.9, 153.4, 149.2,142.8, 139.7, 129.8, 124.5, 122.1, 107.6, 60.7, 56.6, 31.3, 17.2. HRMS (ESI)calcd for C 21 H 26 N3O5S + (M+H) + 432.1588, found 432.1581.

[0048] V-5:White solid, yield 99%, mp 141–142 ºC. 1 H NMR (400 MHz, DMSO-d6) δ9.97 (s, 1H, NH), 8.06 (d, J = 7.0 Hz, 2H, NH), 7.55 (dd, J = 23.7, 16.4 Hz,2H, ArH), 7.43 – 7.30 (m, 4H, ArH), 7.19 (t, J = 10.2 Hz, 2H, ArH), 2.89 (t,J = 7.6 Hz, 2H, CH2), 2.58 (s, 3H, CH3), 2.52 (d, J = 15.1 Hz, 2H, CH2), 1.94(s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) δ 179.0, 166.0, 153.9, 149.1, 140.4,139.7, 133.4, 132.3, 131.2, 129.8, 129.0, 126.7, 122.2 , 31.3, 21.7, 17.3.HRMS (ESI) calcd for C 19 H 22 N3O2S + (M+H) + 356.1427, found 356.1435.

[0049] V-6:White solid, yield 79%, mp 164–165 ºC. 1 H NMR (400 MHz, DMSO-d6) δ9.98 (s, 1H, NH), 8.17 – 7.98 (m, 2H, NH), 7.83 – 7.72 (m, 1H, ArH), 7.61 –7.29 (m, 5H, ArH), 7.21 (t, J = 10.2 Hz, 2H, ArH), 2.89 (t, J = 7.7 Hz, 2H,CH2), 2.57 (t, J = 7.7 Hz, 2H, CH2), 1.94 (d, J = 4.7 Hz, 3H, CH3). 13 C NMR(100 MHz, DMSO-d6) δ 179.0, 162.6, 161.8 (d, J = 257.0 Hz), 153.9, 153.8,149.0, 148.8, 139.9, 136.5 (d, J = 9.0 Hz), 132.7, 129.9, 129.8, 129.5, 125.3(d, J = 3.0 Hz), 122.1, 118.0, 117.9, 117.6, 115.5, 32.2, 31.3, 30.5, 23.5,17.3. 19 F NMR (376 MHz, DMSO-d6) δ -109.6. HRMS (ESI) calcd for C 18 H 19 FN3O2S + (M+H) + 360.1177, found 360.1183.

[0050] V-7:White solid, yield 77%, mp 211–212 ºC. 1 H NMR (400 MHz, DMSO-d6) δ9.97 (s, 1H, NH), 8.13 (d, J = 8.5 Hz, 2H, ArH), 8.06 (s, 1H, NH), 7.68 (d, J= 8.5 Hz, 2H, ArH), 7.48 (s, 1H, NH), 7.36 (dd, J = 27.3, 8.3 Hz, 2H, ArH),7.20 (t, J = 10.5 Hz, 2H, ArH), 2.89 (t, J = 7.7 Hz, 2H, CH2), 2.72 – 2.53(m, 2H, CH2), 1.94 (d, J = 4.6 Hz, 3H, CH3). 13 C NMR (100 MHz, DMSO-d6) δ179.0, 164.4, 153.9, 149.0, 139.9, 139.4, 132.1, 130.3, 128.4, 122.0, 31.3,17.3. HRMS (ESI) calcd for C 18 H 19 ClN3O2S + (M+H) + 376.0811, found 376.0806.

[0051] V-8:White solid, yield 90%, mp 159–160 ºC. 1 H NMR (400 MHz, DMSO-d6) δ9.98 (s, 1H, NH), 8.06 (s, 1H, NH), 7.98 – 7.85 (m, 2H, ArH), 7.56 (d, J =7.6 Hz, 1H, NH), 7.49 (t, J = 7.3 Hz, 2H, ArH), 7.32 (d, J = 8.1 Hz, 2H,ArH), 7.17 (d, J = 8.1 Hz, 2H, ArH), 2.89 (t, J = 7.7 Hz, 2H, CH2), 2.56 (t,J = 7.7 Hz, 2H, CH2), 2.42 (s, 3H, CH3), 1.94 (s, 3H, CH3). 13C NMR (100 MHz,DMSO-d6) δ 179.0, 165.3, 153.9, 149.2, 139.7, 138.9, 135.1, 130.6, 129.8,129.4, 127.4, 122.1, 31.3, 21.3, 17.3. HRMS (ESI) calcd for C 19 H 22 N3O2S + (M+H) + 356.1427, found 356.1432.

[0052] V-9:White solid, yield 99%, mp 207–208 ºC. 1 H NMR (400 MHz, DMSO-d6) δ9.97 (s, 1H, NH), 8.05 (s, 1H, NH), 7.74 (s, 2H, ArH), 7.48 (s, 1H, NH), 7.35(dd, J = 26.9, 8.2 Hz, 3H, ArH), 7.17 (t, J = 10.3 Hz, 2H, ArH), 2.88 (t, J =7.7 Hz, 2H, CH2), 2.56 (t, J = 7.7 Hz, 2H, CH2), 2.37 (s, 6H, CH3), 1.94 (s,3H, CH3). 13 C NMR (100 MHz, DMSO-d6) δ 179.0, 154.0, 139.7, 138.8, 135.8),129.8, 129.5, 127.9, 122.1, 31.3, 21.2, 17.3. HRMS (ESI) calcd for C 20 H 24 N3O2S + (M+H) + 370.1584, found 370.1581.

[0053] V-10:Yellow solid, yield 94%, mp 175–176 ºC. 1H NMR (400 MHz, DMSO-d6)δ 9.95 (s, 1H, NH), 8.45 (d, J = 8.3 Hz, 2H, ArH), 8.13 (d, J = 8.3 Hz, 2H,ArH), 8.05 (s, 1H, NH), 7.42 (s, 1H, NH), 7.33 – 7.21 (m, 2H, ArH), 6.98 (t,J = 10.5 Hz, 2H, ArH), 2.83 (t, J = 7.7 Hz, 2H, CH2), 2.48 (d, J = 8.2 Hz,2H, CH2), 1.89 (d, J = 5.8 Hz, 3H, CH3). 13 C NMR (100 MHz, DMSO-d6) δ 179.0,153.7, 151.5, 147.3, 141.9, 140.0, 130.5, 125.5, 122.3, 31.1, 17.3. HRMS(ESI) calcd for C 18 H 19 N4O4S + (M+H) + 387.1122, found 387.1128.

[0054] V-11:White solid, yield 90%, mp 138–139 ºC. 1 H NMR (400 MHz, DMSO-d6)δ 9.96 (s, 1H, NH), 8.05 (s, 1H, NH), 7.47 (s, 1H, NH), 7.30 (dd, J = 27.7,8.2 Hz, 2H, ArH), 7.00 (t, J = 10.0 Hz, 2H, ArH), 2.85 (t, J = 7.8 Hz, 2H,ArH), 2.70 – 2.51 (m, 2H, CH2), 1.91 (d, J = 6.7 Hz, 3H, CH3), 1.29 (s, 9H,CH3). 13 C NMR (100 MHz, DMSO-d6) δ 179.0, 176.9, 153.9, 149.3, 139.4, 130.1,121.9, 115.6, 31.3, 28.8, 27.3, 17.2. HRMS (ESI) calcd for C 16H 24 N3O2S + (M+H) + 322.1584, found 322.1589.

[0055] V-12:Yellow solid, yield 85%, mp 127–128 ºC. 1 H NMR (400 MHz, DMSO-d6)δ 9.94 (s, 1H, NH), 8.04 (s, 1H, NH), 7.43 (s, 1H, NH), 7.13 (d, J = 8.3 Hz,2H, ArH), 6.84 (d, J = 8.4 Hz, 2H, ArH), 5.31 (dd, J = 54.6, 13.9 Hz, 2H,ArH), 4.51 (d, J = 5.1 Hz, 2H, CH2), 2.76 (t, J = 7.7 Hz, 2H, CH2), 2.52 –2.46 (m, 2H, CH2), 1.90 (d, J = 10.0 Hz, 3H, CH3). 13 C NMR (100 MHz, DMSO-d6) δ178.9, 156.8, 154.2, 134.4, 133.9, 129.7, 117.7, 114.9, 68.6), 31.2, 17.2.HRMS (ESI) calcd for C 14 H 20 N3OS + (M+H) + 278.1322, found 278.1326.

[0056] V-13:White solid, yield 86%, mp 144–145 ºC. 1H NMR (400 MHz, DMSO-d6)δ 9.95 (s, 1H, NH), 8.03 (s, 1H, NH), 7.43 (s, 1H, NH), 7.31 (d, J = 7.7 Hz,2H, ArH), 7.18 (d, J = 7.6 Hz, 2H, ArH), 7.12 (t, J = 5.9 Hz, 2H, ArH), 6.90(t, J = 9.3 Hz, 2H, ArH), 5.00 (s, 2H, CH2), 2.76 (t, J = 7.8 Hz, 2H, CH2),2.50 – 2.44 (m, 2H, CH2), 2.30 (s, 3H, CH3), 1.91 (s, 3H, CH3). 13 C NMR (100MHz, DMSO-d6) δ 178.9, 157.0, 154.2, 137.5, 134.7, 134.0, 129.7, 129.5,128.2, 115.1, 69.5, 31.2, 21.2, 17.2. HRMS (ESI) calcd for C 19 H 24 N3OS + (M+H) + 342.1635, found 342.1641.

[0057] V-14:White solid, yield 89%,mp 120–121 ºC. 1 H NMR (400 MHz, DMSO-d6) δ9.94 (s, 1H, NH), 8.04 (s, 1H, NH), 7.64 (s, 1H, NH), 7.52 (d, J = 7.9 Hz,1H, ArH), 7.44 (d, J = 7.5 Hz, 2H, ArH), 7.35 (t, J = 7.8 Hz, 1H, ArH), 7.15(d, J = 8.2 Hz, 2H, ArH), 6.91 (d, J = 8.3 Hz, 2H, ArH), 5.07 (s, 2H, CH2),2.77 (t, J = 7.7 Hz, 2H, CH2), 2.48 (d, J = 7.6 Hz, 2H, CH2), 1.91 (s, 3H,CH3). 13HRMS (ESI) calcd forC 18 H 21 BrN3OS + (M+H) + 406.0583, found 406.0578.

[0058] V-15: White solid, yield 60%, mp 118–119 ºC. 1 H NMR (400 MHz, DMSO-d6)δ 9.96 (s, 1H, NH), 8.03 (d, J = 13.9 Hz, 1H, ArH), 7.52 (d, J = 36.9 Hz, 1H, ArH), 7.29 (dd, J = 26.7, 8.4 Hz, 2H, ArH), 7.00 (t, J = 5.6 Hz, 2H, ArH), 2.84 (s, 2H, CH2), 2.55 (d, J = 7.3 Hz, 2H, CH2), 2.51 (d, J = 8.5 Hz, 2H,CH2), 1.92 (d, J = 5.8 Hz, 3H, CH3), 1.62 (s, 2H, CH2), 1.40 – 1.25 (m, 6H,CH2), 0.88 (t, J = 6.7 Hz, 3H, CH3). 13 HRMS (ESI) calcd for C 18 H 28 N3O2S + (M+H) + 350.1897, found 350.1891.

[0059] Example 4: Synthesis of compounds VI-1–VI-11

[0060] The corresponding compound V (1 mmol) and anhydrous sodium acetate (1 mmol) were dissolved in anhydrous methanol, and then ethyl bromoacetate (1.2 mmol) was added dropwise to the stirred solution. The reaction system was stirred at room temperature for 5 hours. After the reaction was completed, the mixture was poured into ice water, and a solid precipitated. The solid was collected by vacuum filtration to give the target compounds VI-1–VI-11.

[0061] VI-1: White solid, yield 15%, mp 241–242 ºC. 1 H NMR (400 MHz, DMSO-d6)δ 7.74 (s, 2H, ArH), 7.41 – 7.29 (m, 3H, ArH), 7.15 (d, J = 8.1 Hz, 2H, ArH), 3.74 (s, 2H, CH2), 2.89 (t, J = 7.5 Hz, 2H, CH2), 2.60 (t, J = 7.6 Hz, 2H,CH2), 2.37 (s, 6H, CH3), 1.97 (s, 3H, CH3). 13 C NMR (100 MHz, DMSO-d6) δ 165.4,164.6, 149.2, 139.8, 138.8, 135.8, 129.9, 129.6, 129.4, 127.9, 122.1, 33.5,31.4, 21.2, 18.0. HRMS (ESI) calcd for C 22 H 24 N3O3S + (M+H) + 410.1533, found 410.1537.

[0062] VI-2: White solid, yield 89%, mp 219–220 ºC. 1H NMR (400 MHz, DMSO-d6)δ 11.72 (s, 1H, NH), 7.97 – 7.89 (m, 2H, ArH), 7.56 (d, J = 7.5 Hz, 1H, ArH),7.49 (t, J = 7.6 Hz, 1H, ArH), 7.35 (d, J = 8.2 Hz, 2H, ArH), 7.17 (d, J =8.2 Hz, 2H, ArH), 3.80 (s, 2H, CH2), 2.89 (t, J = 7.6 Hz, 2H, CH2), 2.61 (t, J= 7.7 Hz, 2H, CH2), 2.42 (s, 3H, CH3), 1.97 (s, 3H, CH3). 13 C NMR (100 MHz,DMSO-d6) δ 174.5, 165.4, 149.2, 139.7, 138.9, 135.1, 130.6, 129.9, 129.4,127.4, 122.1, 33.1, 31.4, 21.3, 18.0. HRMS (ESI) calcd for C 21 H 22 N3O3S + (M+H) + 396.1376, found 396.1371.

[0063] VI-3:White solid, yield 43%, mp 148–149 ºC. 1 H NMR (400 MHz, DMSO-d6)δ 11.71 (s, 1H, NH), 8.45 (d, J = 8.7 Hz, 2H, ArH), 8.14 (d, J = 8.7 Hz, 2H,ArH), 7.28 (d, J = 8.3 Hz, 2H, ArH), 6.98 (d, J = 8.3 Hz, 2H, ArH), 3.78 (s,2H, CH2), 2.83 (t, J = 7.6 Hz, 2H, CH2), 2.55 (t, J = 7.6 Hz, 2H, CH2), 1.93(s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) δ 151.5, 147.4, 141.9, 140.1, 130.5,125.5, 122.3, 33.5, 33.1, 31.2, 18.0. HRMS (ESI) calcd for C 20 H 19 N4O5S + (M+H) + 427.1071, found 427.1077.

[0064] VI-4:White solid, yield 64%, mp 181–182 ºC. 1 H NMR (400 MHz, DMSO-d6)δ 11.73 (s, 1H, NH), 8.23 – 8.16 (m, 2H, ArH), 7.47 – 7.40 (m, 2H, ArH), 7.35(d, J = 8.5 Hz, 2H, ArH), 7.19 (d, J = 8.5 Hz, 2H, ArH), 3.80 (s, 2H, CH2),2.89 (t, J = 7.7 Hz, 2H, CH2), 2.61 (t, J = 7.7 Hz, 2H, CH2), 1.97 (s, 3H,CH3). 13 C NMR (100 MHz, DMSO-d6) δ 174.4, 166.0 (d, J = 251.0 Hz), 165.6,164.2, 149.1, 139.8, 133.2 (d, J = 10.0 Hz), 129.9, 126.1, 122.1, 116.6 (d, J= 22.0 Hz), 33.1, 31.3, 18.0.

[0065] 19 F NMR (376 MHz, DMSO-d6) δ -104.8. HRMS (ESI) calcd for C 20 H 19 FN3O3S + (M+H) + 400.1126, found 400.1132.

[0066] VI-5:White solid, yield 86%, mp 165–166 ºC. 1H NMR (400 MHz, DMSO-d6)δ 11.71 (s, 1H, NH), 7.64 (s, 1H, ArH), 7.52 (d, J = 7.9 Hz, 1H, ArH), 7.44(d, J = 7.7 Hz, 1H, ArH), 7.35 (t, J = 7.8 Hz, 1H, ArH), 7.17 (d, J = 8.6 Hz,2H, ArH), 6.91 (d, J = 8.6 Hz, 2H, ArH), 5.08 (s, 2H, CH2), 3.79 (s, 2H, CH2),2.78 (t, J = 7.7 Hz, 2H, CH2), 2.54 (d, J = 8.3 Hz, 2H, CH2), 1.94 (s, 3H,CH3). 13 C NMR (100 MHz, DMSO-d6) δ 165.8, 156.8, 140.6, 134.3, 131.1, 130.6,129.7, 127.0, 122.2, 115.1, 68.6, 33.1, 31.2, 17.9. HRMS (ESI) calcd forC 20 H 21 BrN3O2S + (M+H) + 446.0532, found 446.0535.

[0067] VI-6:White solid, yield 65%, mp 195–196 ºC. 1 H NMR (400 MHz, DMSO-d6)δ 11.72 (s, 1H, NH), 7.29 (d, J = 8.5 Hz, 2H, ArH), 6.98 (d, J = 8.5 Hz, 2H,ArH), 3.79 (s, 2H, CH2), 2.85 (t, J = 7.7 Hz, 2H, CH2), 2.58 (t, J = 7.7 Hz,2H, CH2), 1.96 (s, 3H, CH3), 1.29 (s, 9H, CH3). 13C NMR (100 MHz, DMSO-d6) δ176.9, 174.4, 165.6, 149.3, 139.4, 129.8, 121.9, 33.1, 31.4, 27.3, 18.0. HRMS(ESI) calcd for C 18 H 24 N3O3S + (M+H) + 362.1533, found 362.1539.

[0068] VI-7:White solid, yield 33%, mp 158–159 ºC. 1 H NMR (400 MHz, DMSO-d6)δ 11.74 (s, 1H, NH), 7.37 (d, J = 8.3 Hz, 2H, ArH), 7.18 (d, J = 8.4 Hz, 2H,ArH), 6.99 (s, 2H, ArH), 3.76 (s, 2H, CH2), 2.89 (s, 2H, CH2), 2.61 (d, J =8.0 Hz, 2H, CH2), 2.37 (s, 6H, CH3), 2.28 (s, 3H, CH3), 1.96 (d, J = 8.8 Hz,3H, CH3). 13 C NMR (100 MHz, DMSO-d6) δ 175.1, 168.3, 165.1, 148.8, 140.1,135.3, 130.2, 130.0, 129.83, 128.9, 122.0, 33.3, 31.4, 21.2, 19.9, 18.0. HRMS(ESI) calcd for C 23 H 26 N3O3S + (M+H) + 424.1689, found 424.1697.

[0069] VI-8:White solid, yield 49%, mp 209–210 ºC. 1H NMR (400 MHz, DMSO-d6)δ 11.73 (s, 1H, NH), 8.09 (td, J = 7.8, 1.5 Hz, 1H, ArH), 7.81 – 7.73 (m, 1H,ArH), 7.43 (dd, J = 16.3, 8.7 Hz, 2H, ArH), 7.35 (d, J = 8.4 Hz, 2H, ArH),7.19 (d, J = 8.4 Hz, 2H, ArH), 3.80 (s, 2H, CH2), 2.89 (t, J = 7.6 Hz, 2H,CH2), 2.61 (t, J = 7.7 Hz, 2H, CH2), 1.97 (s, 3H, CH3). 13 C NMR (100 MHz, DMSO-d6) δ 175.1, 166.7 (d, J = 329.0 Hz), 163.4, 148.8, 140.1, 135.3, 130.2,130.0, 129.8, 128.9, 122.0 (d, J = 9.0 Hz), 33.3, 31.4, 21.2, 19.9, 18.0. 19 FNMR (376 MHz, DMSO-d6) δ -109.6. HRMS (ESI) calcd for C 20 H 19 FN3O3S + (M+H) + 400.1126, found 400.1133.

[0070] VI-9:White solid, yield 44%, mp 185–186 ºC. 1 H NMR (400 MHz, DMSO-d6)δ 11.73 (s, 1H, NH), 8.13 (d, J = 8.6 Hz, 2H, ArH), 7.68 (d, J = 8.6 Hz, 2HArH), 7.35 (d, J = 8.5 Hz, 2H ArH), 7.19 (d, J = 8.4 Hz, 2H ArH), 3.79 (s,2H, CH2), 2.89 (t, J = 7.6 Hz, 2H, CH2), 2.61 (t, J = 7.7 Hz, 2H, CH2), 1.97(s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) δ 174.6, 165.5, 164.4, 149.1, 139.9,139.4, 132.1, 129.9, 129.6, 128.4, 122.0, 33.2, 31.4, 18.0. HRMS (ESI) calcdfor C 20 H 19 ClN3O3S + (M+H) + 416.0830, found 416.0834.

[0071] VI-10:White solid, yield 22%, mp 190–191 ºC. 1 H NMR (400 MHz, DMSO-d6)δ 11.71 (s, 1H, NH), 7.31 (d, J = 7.9 Hz, 2H, ArH), 7.17 (dd, J = 13.9, 8.2Hz, 4H, ArH), 6.89 (d, J = 8.6 Hz, 2H, ArH), 5.00 (s, 2H, CH2), 3.79 (s, 2H,CH2), 2.77 (t, J = 7.7 Hz, 2H, CH2), 2.53 (d, J = 8.3 Hz, 2H, CH2), 2.30 (s,3H, CH3), 1.94 (s, 3H, CH3). 13 C NMR (100 MHz, DMSO-d6) δ 174.4, 165.8, 157.0,137.4, 134.7, 134.0, 129.7, 129.4, 128.2, 115.1, 69.5, 33.1, 31.2, 21.3,17.9. HRMS (ESI) calcd for C 21 H 24 N3O2S + (M+H) + 382.1584, found 382.1589.

[0072] VI-11:White solid, yield 47%, mp 142–143 ºC. 1H NMR (400 MHz, DMSO-d6)δ 11.72 (s, 1H, NH), 7.28 (d, J = 8.4 Hz, 2H, ArH), 7.00 (d, J = 8.4 Hz, 2H,ArH), 3.79 (s, 2H, CH2), 2.85 (t, J = 7.7 Hz, 2H, CH2), 2.56 (dt, J = 11.7, 7.8 Hz, 4H, CH2), 1.96 (s, 3H, CH3), 1.61 (dd, J = 14.8, 7.3 Hz, 2H, CH2), 1.39 – 1.26 (m, 6H, CH2), 0.88 (t, J = 6.7 Hz, 3H, CH3). 13 C NMR (100 MHz, DMSO-d6) δ 149.1, 129.8, 122.0, 34.0, 33.1, 31.4, 28.6, 24.8, 22.5, 18.0,14.4. HRMS (ESI) calcd for C 20 H 28 N3O3S + (M+H) + 390.1846, found 390.1853.

[0073] Example 5: Determination of activity against tobacco mosaic virus, the determination procedure is as follows:

[0074] 1. Virus purification and concentration determination:

[0075] Virus purification and concentration determination were performed in accordance with the SOP (Standard Operating Procedure) for tobacco mosaic virus prepared by the Bioassay Laboratory of the Institute of Elementsology, Nankai University. The crude virus extract was centrifuged twice with polyethylene glycol, and the concentration was determined. It was then stored at 4 °C for later use.

[0076] 2. Preparation of compound solutions:

[0077] Weigh the original drug, dissolve it in DMF, and prepare a solution of 1 × 10⁻⁶. 5 The stock solution is prepared at µg / mL. Before use, it is diluted to the required concentration with an aqueous solution containing 1‰ Tween-80. The ribavirin preparation used as a control is diluted directly with deionized water.

[0078] 3. In vivo protection:

[0079] Select uniformly growing 3–5 leaf stage *Nicotiana sambac* plants for whole-plant spraying. Each treatment was replicated in triplicate, with a 1‰ Tween-80 aqueous solution used as a control. 24 hours after application, 500-mesh emery was sprinkled on the leaves as an abrasive. Then, using a brush dipped in a 10 µg / mL virus solution, the leaves were gently rubbed twice along the veins, with the palm of the hand supporting the underside of the leaf during inoculation. Immediately after inoculation, the leaves were rinsed with running water. The number of leaf lesions was recorded 3 days after inoculation, and the control effect was calculated.

[0080] 4. In vivo therapeutic effects:

[0081] Selected 3–5 leaf stage *Nicotiana sambac* plants with uniform growth were inoculated with a 10 µg / mL virus solution using a paintbrush. The leaves were rinsed with running water and allowed to air dry. Subsequently, a whole-plant spray was applied, with each treatment replicated three times. A 1‰ Tween-80 aqueous solution was used as a control. The number of lesions was assessed and recorded three days after inoculation to calculate the control effect.

[0082] 5. In vivo passivation effect:

[0083] Select uniformly growing 3–5 leaf stage *Nicotiana sambac*. Mix the pesticide with an equal volume of virus sap and inactivate for 30 min, then inoculate by friction. The virus concentration is 20 µg / mL. Rinse immediately with running water after inoculation. Repeat 3 times. Include a 1‰ Tween 80 aqueous solution as a control. Count the number of lesions after 3 days and calculate the results.

[0084] Inhibition rate (%) = [(Number of control necrotic spots - Number of treated necrotic spots) / Number of control necrotic spots] × 100%

[0085] First, the in vivo inactivation activity against tobacco mosaic virus (Tobacco Mosaic Virus) of all compounds was tested at a treatment dose of 500 µg / mL. Compounds with a relative inhibition rate greater than 50% were further tested for in vivo therapeutic and protective activity at a treatment dose of 500 µg / mL, and for in vivo inactivation, therapeutic, and protective activity against Tobacco Mosaic Virus at a treatment dose of 100 µg / mL. The positive control was the commercially available antiviral agent ribavirin.

[0086] Table 1. Results of anti-Tobacco Mosaic Virus (TMV) activity tests of raspberry compounds III-1–III-13, V-1–V-15, and VI-1–VI-11:

[0087]

[0088] As shown in Table 1 above, at a concentration of 500 µg / mL, raspberry ketone derivatives III-1–III-13, V-1–V-15, and VI-1–VI-11 all exhibited good antiviral activity against tobacco mosaic virus. Overall, the V series showed the best activity, with their inactivation activity superior to that of their positive control, ribavirin. Therefore, raspberry ketone compounds have the potential to be developed into antiviral agents.

[0089] Example 6: Antibacterial activity test, the determination procedure is as follows:

[0090] In vitro sterilization test, bacterial growth rate determination method (plate method): A quantitative amount of the drug was dissolved in an appropriate amount of acetone and diluted to the target concentration with an aqueous solution containing 200 µg / mL emulsifier. Then, 1 mL of different concentrations of drug solution and 9 mL of culture medium were added to each petri dish, and the mixture was thoroughly shaken to prepare a drug-containing plate with a final concentration of 50 µg / mL; a plate with 1 mL of sterile water was used as a blank control. Using a 4 mm diameter sterile punch, a bacterial disc was cut along the edge of the colony of the tested strain and inoculated into the center of the drug-containing plate. Each treatment was repeated three times. All petri dishes were placed in a constant temperature incubator at 24±1℃ and incubated in the dark. After 48 hours, the expansion diameter of the colonies in each treatment was measured and the average value was calculated. The relative inhibition rate was calculated by comparing with the blank control.

[0091]

[0092] Table 2. Results of the anti-plant pathogen activity tests of raspberry ketone compounds III-1–III-13, V-1–V-15, and VI-1–VI-11:

[0093]

[0094] As shown in Table 2, at a concentration of 50 μg / mL, all raspberry ketone compounds exhibited inhibitory activity against the six tested pathogens. In particular, these compounds showed significant activity against *Sclerotinia sclerotinia*, with compound III-8 exhibiting excellent antibacterial activity, showing inhibition rates exceeding 60% against four pathogens: rice blast, *Sclerotinia sclerotinia*, *Rhizoctonia solani*, and *Rhizoctonia solani*, and demonstrating excellent fungicidal activity against multiple pathogens. Compounds V-12-14 also showed excellent antibacterial activity against multiple pathogens. These results indicate that raspberry ketone compounds possess good development potential.

[0095] The present invention has been described above by way of example. It should be noted that any simple modifications, alterations or other equivalent substitutions that can be made by those skilled in the art without creative effort without departing from the core of the present invention fall within the protection scope of the present invention.

Claims

1. A class of raspberry ketone compounds, specifically one of the compounds shown in III-1–III-13, V-1–V-15 and VI-1–VI-11; .

2. Preparation method of III-1–III-13, V-1–V-15 and VI-1–VI-11 in claim 1: Synthesis of compounds III-1–III-13: Compound I (164 mg, 1 mmol) was dissolved in anhydrous ethanol (15 mL), followed by the addition of thiourea (109 mg, 1.2 mmol) and acetic acid (10 mL). The reaction mixture was stirred at 60 °C for 3 hours. After the reaction was completed by thin-layer chromatography (TLC), the solvent was evaporated, and acetic acid was neutralized by adding saturated NaHCO3 solution. After a period of time, a solid precipitate was precipitated. The solid was collected by vacuum filtration to obtain compound II. Compound II (237 mg, 1 mmol) was dissolved in anhydrous ethanol (15 mL), followed by the addition of the corresponding bromoketone derivative (1.3 mmol). The reaction mixture was stirred at 90 °C for 5 hours. The reaction was confirmed to be complete by thin-layer chromatography (TLC). The mixture was extracted three times with ethyl acetate (EA), and the organic layers were combined and washed with brine and anhydrous Na2SO4. The filtrate was dried and filtered, and concentrated to obtain compound III-1–III-13. Synthesis of compound V-1–V-13: The corresponding compound IV (1 mmol) was dissolved in anhydrous ethanol (15 mL), and thiourea (1.2 mmol) and acetic acid (10 mL) were added. The mixture was stirred at 60 °C for 3 hours. After the reaction was monitored by thin-layer chromatography (TLC), the solvent was removed under reduced pressure, and then acetic acid was neutralized with saturated sodium bicarbonate (NaHCO3) solution. A solid precipitate formed, which was collected by filtration under reduced pressure to obtain the target compound V-1–V-13. Synthesis of compound VI-1–VI-11: The corresponding compound V (1 mmol) and anhydrous sodium acetate (1 mmol) were dissolved in anhydrous methanol, and then ethyl bromoacetate (1.2 mmol) was added dropwise to the stirred solution. The reaction system was stirred at room temperature for 5 hours. After the reaction was complete, the mixture was poured into ice water, and a solid precipitated. The solid was collected by filtration under reduced pressure to obtain the target compound VI-1–VI-11. .

3. The application of the raspberry ketone compounds III-1–III-13, V-1–V-15, and VI-1–VI-11 as described in claim 1 in the prevention and control of plant viral diseases, characterized in that, The plant virus in question is tobacco mosaic virus.

4. The application of the raspberry ketone compounds III-1–III-13, V-1–V-15, and VI-1–VI-11 as described in claim 1 in the prevention and control of plant pathogenic diseases, characterized in that… The plant pathogens mentioned are apple ring rot fungus, wheat sheath blight fungus, tomato early blight fungus, rice blast fungus, pepper phytophthora, or rapeseed sclerotinia.

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