Flavonol derivatives and uses thereof

Abstract

The present application relates to the field of pesticides, in particular to a flavonol derivative and application thereof.The flavonol derivative of the present application is shown as (I), wherein R1 is selected from hydrogen, halogen, alkyl or alkoxy; R2 is selected from hydrogen, alkyl or alkoxy.The flavonol derivative of the present application has good bacteriostatic effect on rice sheath blight fungus, cucumber anthracnose fungus and strawberry botrytis cinerea, can be used for preventing and treating plant fungal diseases, and has low cost of raw material for synthesis and simple synthesis method.

Description

Technical Field

[0001] This invention relates to the field of pesticides, and more specifically to a flavonol derivative and its application. Background Technology

[0002] The control and suppression of plant pathogens is an important area of ​​pesticide research. Chemical control remains the primary method for preventing the spread and outbreaks of plant pathogenic fungi in agriculture, and the widespread use of fungicides has effectively controlled most plant pathogens. However, with the continuous expansion of fungicide use, plant pathogens have developed resistance to traditional fungicides. At the same time, the high toxicity of existing fungicides to non-target organisms and their serious environmental pollution have greatly limited their application in production. Therefore, the development of novel fungicides that are highly efficient, specific to target organisms, and environmentally friendly is of great importance and significance for ensuring increased and stable agricultural yields and food security.

[0003] Flavonol skeletons are widely found in natural products and bioactive molecules, with the highest concentrations in the flowers and leaves of dicotyledonous plants. These structures are extensively used in drug development. The physiological activities of flavonoids mainly include antitumor, antioxidant, anti-inflammatory, antiviral, antithrombotic, and vasodilatory effects.

[0004] On the other hand, in addition to their good medicinal activities, flavonol derivatives have also been discovered and developed for potential applications in pesticide creation. Flavonoids have broad-spectrum bactericidal effects, and their effectiveness against pathogenic fungi has also been preliminarily demonstrated.

[0005] In summary, flavonols possess broad-spectrum biological activity and play a crucial role in the discovery of novel pesticide lead compounds. Therefore, this invention modifies the hydroxyl groups of flavonols to create new compounds with highly efficient and broad-spectrum activity against plant pathogenic fungi. Summary of the Invention

[0006] In view of the shortcomings of the prior art, the first objective of the present invention is to provide a class of flavonol derivatives.

[0007] A second object of the present invention is to provide uses for the above-mentioned derivatives.

[0008] The technical solution adopted by this invention to solve its technical problem is:

[0009] In a first aspect, the present invention provides a flavonol derivative having the structure shown in general formula (I), or a pharmaceutically acceptable salt, solvate, optical isomer, or polymorph thereof:

[0010]

[0011] R1 is selected from hydrogen, halogen, alkyl or alkoxy.

[0012] R2 is selected from hydrogen, alkyl, alkoxy, benzyl, or 2-phenylethyl.

[0013] In a specific implementation scheme, R1 is selected from hydrogen, methyl, trifluoromethyl, halogen, or methoxy.

[0014] Preferably, R1 is selected from any one of hydrogen, 4-methyl, 3-methyl, 4-fluoro, 4-chloro, 4-bromo, 4-trifluoromethyl, 4-methoxy, and 4-tert-butyl.

[0015] More preferably, R1 is selected from hydrogen, 4-methyl, 3-methyl, 4-fluoro, 4-bromo, 4-trifluoromethyl, 4-methoxy, or 4-tert-butyl.

[0016] More preferably, R1 is selected from hydrogen, 4-fluoro, 4-methyl, 4-tert-butyl, 3-methyl, 4-bromo, and 4-trifluoromethyl.

[0017] In a specific implementation scheme, R2 is selected from ethyl, propyl, isopropyl, isobutyl, 3-methoxypropyl, 4-methoxyphenyl, 4-nitrophenyl, benzyl, or 2-phenylethyl.

[0018] Preferably, R2 is selected from ethyl, isopropyl, 3-methoxypropyl, benzyl, 2-phenylethyl, 4-methoxyphenyl or 4-nitrophenyl.

[0019] In specific embodiments, the present invention also protects the following flavonol derivatives, or pharmaceutically acceptable salts, solvates, optical isomers, or polymorphs thereof:

[0020]

[0021]

[0022]

[0023]

[0024] Thirdly, the present invention also protects the use of the flavonol derivatives described above, or their pharmaceutically acceptable salts, solvates, optical isomers or polymorphs, in the prevention and control of plant fungal diseases.

[0025] Fourthly, the present invention also protects the use of the flavonol derivatives described above, or their pharmaceutically acceptable salts, solvates, optical isomers or polymorphs, in the preparation of reagents for the prevention and control of plant fungal diseases.

[0026] In a specific implementation plan, the fungus is rice sheath blight fungus, cucumber anthracnose fungus, tomato early blight fungus, wheat scab fungus, apple spot fungus, or strawberry gray mold fungus.

[0027] In the specific implementation plan, the fungal diseases are rice sheath blight, cucumber anthracnose, tomato early blight, wheat scab, apple spot disease, or strawberry gray mold.

[0028] The derivatives provided by this invention exhibit significant inhibitory activity against plant pathogenic fungi and can be used to inhibit plant pathogenic fungi and control plant fungal diseases. The flavonol derivatives of this invention are suitable for inhibiting rice sheath blight, cucumber anthracnose, tomato early blight, wheat scab, apple spot, and strawberry gray mold, and are suitable for controlling rice sheath blight, cucumber anthracnose, tomato early blight, wheat scab, apple spot, and strawberry gray mold.

[0029] Beneficial effects:

[0030] Compared with the prior art, the present invention has significant beneficial effects. As can be seen from the above technical solution, the present invention applies flavonol derivatives to the research on resistance to plant pathogenic fungi, and finds that such compounds have outstanding inhibitory activity against plant pathogenic fungi, demonstrating the significant progress of the present technical solution; among them, some compounds have inhibitory activity against rice sheath blight, cucumber anthracnose fungus and strawberry gray mold fungus exceeding that of the control agents carbendazim and cymoxanil, and have obvious application value. Detailed Implementation

[0031] The essential features of the present invention can be seen from the following embodiments, but they should not be regarded as any limitation on the present invention.

[0032] If the manufacturer of the reagents or instruments used is not specified, they are considered to be conventional products that can be purchased on the market.

[0033]

[0034] Example 1 Synthesis of 3-propoxy-2-(4-methylphenyl)-4H-1-benzopyran-4-one (I1)

[0035] 2-Hydroxyacetophenone (1.2 mmol) and p-methylbenzaldehyde (1.26 mmol) were added to 20 mL of water at room temperature, and pyrrolidine (12.04 mmol) was added to the suspension and reacted for 12 hours. After the reaction, the mixture was poured into cold water and acidified to pH 4 with aqueous hydrochloric acid (30%, v / v). The precipitate was then filtered and washed with water and ethanol. The crude product was purified by silica gel column chromatography, eluting with diethyl ether and ethyl acetate (30:1, v / v) to give intermediate 3. 3 (2 mmol) and potassium carbonate (4 mmol) were stirred at 50 °C for 15 min, and then 1-bromopropane (123 mg, 1 mmol) was added dropwise to the reaction mixture, which was gradually heated to 60 °C. Samples were extracted at different time intervals and analyzed by TLC until the reaction was complete. The mixture was then cooled to room temperature, poured into water, and extracted to ethyl acetate. The organic layer was washed with water and dried on anhydrous Na₂SO₄. The organic phase was concentrated under vacuum to give a colorless liquid as the product. The residue was purified by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (30:1, v / v) to give the target compound.

[0036] Example 2 Synthesis of 2-(4-bromophenyl)-3-propoxy-4H-1-benzopyran-4-one (I2)

[0037] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with p-bromobenzaldehyde.

[0038] Example 3 Synthesis of 2-(4-tert-butyl)phenyl-3-propoxy-4H-1-benzopyran-4-one (I3)

[0039] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with p-tert-butylbenzaldehyde.

[0040] Example 4 Synthesis of 2-(3-methylphenyl)-3-propoxy-4H-1-benzopyran-4-one (I4)

[0041] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with p-3-methylbenzaldehyde.

[0042] Example 5 Synthesis of 3-(1-methylethoxy)-2-phenyl-4H-1-benzopyran-4-one (I5)

[0043] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with p-benzaldehyde and 1-bromopropane is replaced with bromoisopropyl.

[0044] Example 6 Synthesis of 3-(2-methylpropoxy)-2-phenyl-4H-1-benzopyran-4-one (I6)

[0045] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with p-benzaldehyde and 1-bromopropane is replaced with bromoisobutyl.

[0046] Example 7 Synthesis of 2-(4-tert-butyl)phenyl-3-(2-methylpropoxy)-4H-1-benzopyran-4-one (I7)

[0047] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with p-tert-butylbenzaldehyde and 1-bromopropane is replaced with bromoisobutyl.

[0048] Example 8 Synthesis of 3-(3-methoxypropoxy)-2-phenyl-4H-1-benzopyran-4-one (I8)

[0049] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with benzaldehyde and 1-bromopropane is replaced with 3-bromopropyl methyl ether.

[0050] Example 9 Synthesis of 3-(3-methoxypropoxy)-2-(4-fluorophenyl)-4H-1-benzopyran-4-one (I9)

[0051] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with 4-fluorobenzaldehyde and 1-bromopropane is replaced with 3-bromopropyl methyl ether.

[0052] Example 10 Synthesis of 3-(3-methoxypropoxy)-2-(4-methylphenyl)-4H-1-benzopyran-4-one (I10)

[0053] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with p-methylbenzaldehyde and 1-bromopropane is replaced with 3-bromopropyl methyl ether.

[0054] Example 11 Synthesis of 3-(3-methoxypropoxy)-2-(3-methylphenyl)-4H-1-benzopyran-4-one (I11)

[0055] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with 3-methylbenzaldehyde and 1-bromopropane is replaced with 3-bromopropyl methyl ether.

[0056] Example 12 Synthesis of 2-(3-methylphenyl)-3-phenylmethoxy-4H-1-benzopyran-4-one (I12)

[0057] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with 3-methylbenzaldehyde and 1-bromopropane is replaced with benzyl bromide.

[0058] Example 13 Synthesis of 2-(4-bromophenyl)-3-phenylmethoxy-4H-1-benzopyran-4-one (I13)

[0059] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with p-bromobenzaldehyde and 1-bromopropane is replaced with benzyl bromide.

[0060] Example 14 Synthesis of 2-(4-fluorophenyl)-3-phenylmethoxy-4H-1-benzopyran-4-one (I14)

[0061] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with p-fluorobenzaldehyde and 1-bromopropane is replaced with benzyl bromide.

[0062] Example 15 Synthesis of 2-[4-trifluoromethylphenyl]-3-phenylmethoxy-4H-1-benzopyran-4-one (I15)

[0063] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with p-trifluoromethylbenzaldehyde and 1-bromopropane is replaced with benzyl bromide.

[0064] Example 16 Synthesis of 2-(4-fluorophenyl)-3-(2-phenylethoxy)-4H-1-benzopyran-4-one (I16)

[0065] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with p-fluorobenzaldehyde and 1-bromopropane is replaced with beta-bromophenylethane.

[0066] Example 17 Synthesis of 2-(4-bromophenyl)-3-(2-phenylethoxy)-4H-1-benzopyran-4-one (I17)

[0067] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with p-bromobenzaldehyde, and 1-bromopropane is replaced with beta-bromophenylethane.

[0068] Example 18 Synthesis of 2-(3-methylphenyl)-3-(2-phenylethoxy)-4H-1-benzopyran-4-one (I18)

[0069] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with 3-methylbenzaldehyde and 1-bromopropane is replaced with beta-bromophenylethane.

[0070] Example 19 Synthesis of 2-[4-trifluoromethylphenyl]-3-(2-phenylethoxy)-4H-1-benzopyran-4-one (I19)

[0071] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with p-trifluoromethylbenzaldehyde and 1-bromopropane is replaced with beta-bromophenylethane.

[0072] Example 20 Synthesis of 2-(4-tert-butyl)phenyl-3-(2-phenylethoxy)-4H-1-benzopyran-4-one (I20)

[0073] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with p-tert-butylbenzaldehyde and 1-bromopropane is replaced with beta-bromophenylethane.

[0074] Example 21 Synthesis of 2-(4-fluorophenyl)-3-[(4-methylphenyl)methoxy]-4H-1-benzopyran-4-one (I21)

[0075] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with p-fluorobenzaldehyde and 1-bromopropane is replaced with 4-methylbenzyl bromide.

[0076] Example 22 Synthesis of 2-(4-methylphenyl)-3-[(4-methoxyphenyl)methoxy]-4H-1-benzopyran-4-one (I22)

[0077] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with p-methylbenzaldehyde and 1-bromopropane is replaced with 4-methoxybenzyl bromide.

[0078] Example 23 Synthesis of 2-(4-fluorophenyl)-3-[(4-methoxyphenyl)methoxy]-4H-1-benzopyran-4-one (I23)

[0079] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with p-fluorobenzaldehyde and 1-bromopropane is replaced with 4-methoxybenzyl bromide.

[0080] Example 24 Synthesis of 2-[(4-trifluoromethyl)phenyl]-3-[(4-methoxyphenyl)methoxy]-4H-1-benzopyran-4-one (I24)

[0081] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with p-trifluoromethylbenzaldehyde and 1-bromopropane is replaced with 4-methoxybenzyl bromide.

[0082] Example 25 Synthesis of 2-(4-methylphenyl)-3-[(4-nitrophenyl)methoxy]-4H-1-benzopyran-4-one (I25)

[0083] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with p-methylbenzaldehyde and 1-bromopropane is replaced with 4-nitrobenzyl bromide.

[0084] Example 26 Synthesis of 2-(4-fluorophenyl)-3-[(4-nitrophenyl)methoxy]-4H-1-benzopyran-4-one (I26)

[0085] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with p-fluorobenzaldehyde and 1-bromopropane is replaced with 4-nitrobenzyl bromide.

[0086] Example 27 Synthesis of 2-(4-fluorophenyl)-3-[(4-nitrophenyl)methoxy]-4H-1-benzopyran-4-one (I27)

[0087] The rest is the same as in Example 1, except that p-methylbenzaldehyde is replaced with 3-methylbenzaldehyde and 1-bromopropane is replaced with 4-nitrobenzyl bromide.

[0088] Compounds I2-I27 were synthesized sequentially according to the method in Example 1. The structures of the synthesized flavonol-containing derivatives (I1-I27) were confirmed by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HRMS). The physicochemical parameters and spectral data of the compounds are shown below:

[0089] 3-Propoxy-2-(4-methylphenyl)-4H-1-benzopyran-4-one (I1): Yellow liquid, yield 42%, melting point 102-103℃; 1 H NMR (500MHz, CDCl3) δ8.24(d,J=8.0Hz,1H),8.01(d,J=8.2Hz,2H),7.63(t,J=8.4,1H),7.50(d,J=8.5Hz,1H),7.36( t,J=7.0Hz,1H),7.29(d,J=8.0Hz,2H),3.99(t,J=6.8Hz,2H),2.41(s,3H),1.73–1.62(m,2H),0.93(t,J=7.4Hz,3H); 13 C NMR (300MHz, CDCl3) δ175.21,158.69,155.68,140.81,137.62,133.47,130.72,130.55,130.36 ,129.88,126.01,125.58,124.78,124.66,118.18,72.64,23.11,20.02,10.17; HRMS(m / z)[M+H] + calcd for C 19 H 18 O3(M+H) + :294.1256,found:294.1251.

[0090] 2-(4-Bromophenyl)-3-propoxy-4H-1-benzopyran-4-one (I2): Yellow liquid, yield 48%, melting point 109-110℃; 1 H NMR (500MHz, CDCl)3 )δ8.26(d,J=8.0,Hz,1H),8.05–7.97(m,2H),7.69–7.57(m,1H),7.66(d,J=2.0Hz,1H),7.64(d,J=2.0Hz,1 H),7.53–7.42(m,1H),7.41–7.35(m,1H),4.02(t,J=6.8Hz,2H),1.73–1.68(m,2H),0.93(t,J=7.4Hz,3H); 13 C NMR (300MHz, CDCl3) δ175.78,158.69,155.68,140.94,137.62,133.47,130.72,130.55,130.36 ,129.88,126.01,125.58,124.72(d,J=35.3Hz),118.36,74.86,23.51,10.17; HRMS(m / z)calcd forC 18 H 15 BrO3(M+H) + :358.0205,found:358.0209.

[0091] 2-(4-tert-butyl)phenyl-3-propoxy-4H-1-benzopyran-4-one (I3): yellow liquid, yield 32%, melting point 106-107℃; 1 H NMR(500MHz, CDCl3)δ8.26(d,J=8.0Hz,1H),8.12–8.05(m,2H),7.69–7.62(m,1H),7.56–7.49(m,3H ),7.38–7.21(m,1H),4.03(t,J=6.8Hz,2H),1.77–1.65(m,2H),1.38(s,9H),0.95(t,J=7.4Hz,3H); 13 C NMR (300MHz, CDCl3) δ175.14,155.25,154.66,140.67,138.30,133.67,131.68,130.08,129.72,129.08,12 8.48,126.46,125.96,125.18,124.89,124.23,118.03,72.99,36.61,30.19,28.66,19.42; HRMS(m / z)calcd for C 22 H 24 O3(M+H) + :336.1725,found:336.1719.

[0092] 2-(3-Methylphenyl)-3-propoxy-4H-1-benzopyran-4-one (I4): Yellow liquid, yield 46%, melting point 102-103℃; 1 H NMR(500MHz, CDCl3)δ8.30(d,J=8.0Hz,1H),7.66–7.58(m,1H),7.49(d,J=7.6,Hz,1H),7.45(dd,J=8.5,1.0Hz,1H), 7.40–7.35(m,2H),7.35–7.27(m,2H),3.87(t,J=6.5Hz,2H),2.37(s,3H),1.49–1.42(m,2H),0.66(t,J=7.4Hz,3H); 13 C NMR (300MHz, CDCl3) δ175.21,158.69,155.68,140.81,137.62,133.47,130.72,130.36,129 .88,126.01,125.58,124.78,124.66,118.18,74.86,23.11,20.02,10.17; HRMS(m / z)calcd for C 19 H 18 O3(M+H) + :294.1256,found:294.1259.

[0093] 3-(1-Methylethoxy)-2-phenyl-4H-1-benzopyran-4-one (I5): Yellow liquid, yield 32%, melting point 106-107℃; 1 H NMR(500MHz, CDCl3)δ8.26(dd,J=8.0,1.7Hz,1H),8.20–8.10(m,2H),7.72–7.63(m,1H),7.54(d,J=8.4 Hz,1H),7.50(dd,J=5.3,2.0Hz,3H),7.40(t,J=7.5Hz,1H),4.74–4.60(m,1H),1.18(d,J=6.2Hz,6H).; 13 C NMR (300MHz, CDCl3) δ175.14,155.25,154.66,140.67,138.30,133.67,131.68,130.08, 129.72,129.08,126.46,125.96,124.89,124.23,118.03,72.99,36.61; HRMS(m / z)calcd for C 18 H 16 O3(M+H)+ :280.1099,found:280.1112.

[0094] 3-(2-methylpropoxy)-2-phenyl-4H-1-benzopyran-4-one (I6): yellow liquid, yield 46%, melting point 115-116℃; 1 H NMR (500MHz, CDCl3) δ8.27(d,J=8.0Hz,1H),8.14–8.06(m,2H),7.67(t,J=8.6Hz,1H),7.58–7. 47(m,4H),7.40–7.34(m,1H),3.81(d,J=6.6Hz,2H),2.03–1.96(m,1H),0.94(d,J=6.7Hz,6H); 13 C NMR (300MHz, CDCl3) δ175.14,155.25,154.66,140.67,138.30,133.67,131.68,130.08,129 .72,129.08,126.46,125.96,124.89,124.23,118.03,72.99,36.61,20.52; HRMS(m / z)calcd for C 19 H 18 O3(M+H) + :294.1256,found:294.1261.

[0095] 2-(4-tert-butyl)phenyl-3-(2-methylpropoxy)-4H-1-benzopyran-4-one (I7): yellow liquid, yield 52%, melting point 121-122℃; 1 H NMR(500MHz, CDCl3)δ8.24(d,J=8.0Hz,1H),8.09–8.02(m,2H),7.68–7.61(m,1H),7.55–7.48(m,3H),7. 37(t,J=7.9Hz,1H),3.81(d,J=6.6Hz,2H),2.11–2.01(m,1H),1.40–1.37(m,9H),0.96(d,J=6.7Hz,6H); 13C NMR (300MHz, CDCl3) δ175.14,155.25,154.66,140.67,138.30,133.67,131.68,130.08,129.72,129.08 ,128.48,126.46,125.96,124.89,124.23,118.03,72.99,36.61,30.19,28.72,19.54; HRMS(m / z)calcd forC 23 H 26 O3(M+H) + :350.1882,found:350.1885.

[0096] 3-(3-methoxypropoxy)-2-phenyl-4H-1-benzopyran-4-one (I8): white solid, yield 48%, melting point 131-132℃; 1 H NMR(500MHz, CDCl3)δ8.26(d,J=8.0,Hz,1H),8.13–8.04(m,2H),7.68(m,1H),7.57–7.44(m,4H),7 .40–7.31(m,1H),4.15(t,J=6.3Hz,2H),3.46(t,J=6.4Hz,2H),3.27(s,3H),1.98(t,J=6.4Hz,2H); 13 C NMR (300MHz, CDCl3) δ175.25,156.30,155.35,141.24,140.37,133.42,129.26,128.71 ,128.28,125.87,124.69,124.29,118.07,69.75,69.54,58.70,30.45; HRMS(m / z)calcd for C 19 H 18 O4(M+H) + :310.1205,found:310.1201.

[0097] 3-(3-methoxypropoxy)-2-(4-fluorophenyl)-4H-1-benzopyran-4-one (I9): yellow solid, yield 22%, melting point 101-102℃; 1H NMR(500MHz, CDCl3)δ8.25(d,J=7.9,Hz,1H),8.03–7.96(m,2H),7.63(d,J=1.7Hz,1H),7.55–7.48(m,1H),7.3 5(t,J=1.3Hz,1H),7.35–7.28(m,2H),4.10(s,2H),3.45(s,2H),3.28(s,3H),2.43(s,3H),2.07–1.93(m,2H); 13 C NMR (300MHz, CDCl3) δ175.14,155.25,154.66,140.67,138.30,133.67,131.68,130.08,129.72,129 .08,126.46,125.96,124.89,124.23,118.03,69.78,69.56,58.73,30.43,21.39.; HRMS(m / z)calcd forC 20 H 20 O4(M+H) + :324.1362,found:324.1368.

[0098] 3-(3-Methoxypropoxy)-2-(4-Methylphenyl)-4H-1-benzopyran-4-one (I10): white solid, yield 37%, melting point 115-116 °C; ¹H NMR (500 MHz, CDCl₃) δ 8.25 (d, J = 7.9, Hz, 1H), 8.03–7.96 (m, 2H), 7.63 (d, J = 1.7 Hz, 1H), 7.55–7.48 (m, 1H), 7.35 (t, J = 1.3 Hz, 1H), 7.35–7.28 (m, 2H), 4.10 (s, 2H), 3.45 (s, 2H), 3.28 (s, 3H), 2.43 (s, 3H), 2.07–1.93 (m, 2H); ¹³C NMR (300MHz, CDCl3) δ175.14,155.25,154.66,140.67,138.30,133.67,131.68,130.08,129.72,129 .08,126.46,125.96,124.89,124.23,118.03,69.78,69.56,58.73,30.43,21.39.; HRMS(m / z)calcd for C20H20O4(M+H)+:324.1362,found:324.1368.

[0099] 3-(3-methoxypropoxy)-2-(3-methylphenyl)-4H-1-benzopyran-4-one (I11): yellow solid, yield 34%, melting point 110-112℃; 1 H NMR(500MHz, CDCl3)δ8.26(dd,J=5.9,1.3Hz,1H),8.03–7.98(m,2H),7.73–7.63(m,1H),7.55–7.50(m,1H),7.43–7.36( m,1H),7.32(d,J=6.0Hz,2H),4.14(t,J=4.8Hz,2H),3.50(t,J=4.8Hz,2H),3.29(s,3H),2.33(s,3H),2.06–1.95(m,2H); 13 C NMR (300MHz, CDCl3) δ175.14,155.25,154.66,140.67,138.30,133.67,131.68,130.08,129.72,12 9.08,126.46,125.96,124.89,124.23,118.03,69.78,69.56,58.73,30.43,21.74; HRMS(m / z)calcd for C 20 H 20 O4(M+H) + :324.1362,found:324.1358.

[0100] 2-(3-Methylphenyl)-3-phenylmethoxy-4H-1-benzopyran-4-one (I12): yellow solid, yield 44%, melting point 131-132℃; 1 H NMR (500MHz, CDCl3) δ8.36–8.31(m,1H),7.66(t,J=9.5Hz,1H),7.43(d,J=8.0Hz,2H),7.41–7.37(m,1H),7.33(d,J =7.7Hz,1H),7.29–7.22(m,2H),7.21–7.17(m,1H),7.16–7.10(m,2H),7.03–6.97(m,2H),5.06(s,2H),2.17(s,3H); 13C NMR (300MHz, CDCl3) δ175.28,156.77,155.43,140.04,138.05,136.83,133.51,131.52,130.97,129. 51,128.95,128.33,128.17,126.06,125.89,124.78,124.33,118.16,74.31,21.54; HRMS(m / z)calcd for C 23 H 18 O3(M+H) + :324.1256,found:324.1251.

[0101] 2-(4-bromophenyl)-3-phenylmethoxy-4H-1-benzopyran-4-one (I13): yellow solid, yield 46%, melting point 141-142℃; 1 H NMR (500MHz, CDCl3) δ8.30–8.24(m,1H),7.84–7.77(m,2H),7.69–7.64(m,1H),7.53–7.48(m,1H) ,7.47–7.43(m,2H),7.42–7.36(m,1H),7.29–7.21(m,3H),7.20–7.16(m,2H),4.98–4.93(m,2H); 13 C NMR (126MHz, CDCl3) δ175.14,155.25,154.66,140.67,138.30,133.67,131.68,130.08,129. 72,129.08,128.48,126.46,125.96,125.18,124.89,124.23,118.03,71.82; HRMS(m / z)calcd for C 22 H 15 BrO3(M+H) + :406.0205,found:406.0211.

[0102] 2-(4-fluorophenyl)-3-phenylmethoxy-4H-1-benzopyran-4-one (I14): yellow solid, yield 40%, melting point 152-153℃; 1H NMR(500MHz, CDCl3)δ8.28(d,J=8.0Hz,1H),8.07–7.97(m,2H),7.66(t,J=8.7Hz,1H),7.55–7.46(m ,1H),7.40–7.31(m,1H),7.30(d,J=6.7Hz,2H),7.26–7.19(m,3H),7.16–7.06(m,2H),5.13(s,2H); 13 C NMR (300MHz, CDCl3) δ175.08,165.15,162.64,155.21,139.56,136.45,133.57,131.19,131.10,128.96,128 .27(d,J=6.4Hz),127.15,127.12,125.83,124.84,124.15,118.02,115.57,115.35,74.15; HRMS(m / z)calcd forC 22 H 15 FO3(M+H) + :346.1005,found:346.1004.

[0103] 2-[4-trifluoromethylphenyl]-3-phenylmethoxy-4H-1-benzopyran-4-one (I15): yellow solid, yield 22%, melting point 155-156℃; 1 H NMR(500MHz, CDCl3)δ8.34(d,J=8.0Hz,1H),8.10(d,J=8.1Hz,2H),7.78–7.67(m,3H),7.56(d, J=8.5Hz,1H),7.47(t,J=7.6Hz,1H),7.38(d,J=6.3Hz,1H),7.26(d,J=4.7Hz,4H),5.20(s,2H); 13 C NMR (300MHz, CDCl3) δ175.24,155.38,154.84,140.30,136.19,134.49,133.92,132.21,131.95,129.29,129 .11,128.44,128.36,126.00,125.21(d,J=3.8Hz),125.11,124.23,118.17,118.12,74.46; HRMS(m / z)calcd forC 23 H 15 F3O3(M+H) + :396.0973,found:396.0968.

[0104] 2-(4-fluorophenyl)-3-(2-phenylethoxy)-4H-1-benzopyran-4-one (I16): yellow solid, yield 42%, melting point 141-143℃; 1 H NMR (500MHz, CDCl3) δ8.24(d,J=8.0Hz,1H),7.97–7.88(m,2H),7.64(t,J=8.6Hz,1H),7.48(d,J=8.4Hz,1H), 7.37(t,J=8.1Hz,1H),7.30–7.16(m,5H),6.99(t,J=8.7Hz,2H),4.29(t,J=6.7Hz,2H),3.04(t,J=6.7Hz,2H); 13 C NMR (300MHz, CDCl3) δ175.07,165.04,162.54,155.12,154.69,140.22,138.33,133.54,130.76,129.07,128.42 ,126.85(d,J=3.3Hz),126.39,125.81,124.78,124.09,117.95,115.60,115.39,72.81,36.58; HRMS(m / z)calcd for C 23 H 17 FO3(M+H) + :360.1162,found:360.1170.

[0105] 2-(4-bromophenyl)-3-(2-phenylethoxy)-4H-1-benzopyran-4-one (I17): yellow solid, yield 54%, melting point 156-157℃; 1 H NMR(500MHz, CDCl3)δ8.25(dd,J=8.0,1.7Hz,1H),7.83–7.76(m,2H),7.67–7.61(m,1H),7.50(dd,J=8.5,1.0Hz,1H),7.46–7.42(m,2H),7.41– 7.37(m,1H),7.27–7.24(m,2H),7.23–7.20(m,1H),7.19(d,J=1.8Hz,1H),7.18(d,J=1.4Hz,1H),4.31(t,J=6.8Hz,2H),3.04(t,J=6.8Hz,2H); 13C NMR (300MHz, CDCl3) δ175.14,155.25,154.66,140.67,138.30,133.67,131.68,130.08,129.72, 129.08,128.48,126.46,125.96,125.18,124.89,124.23,118.03,72.99,36.61; HRMS(m / z)calcd for C 23 H 17 BrO3(M+H) + :420.0361,found:420.0364.

[0106] 2-(3-Methylphenyl)-3-(2-phenylethoxy)-4H-1-benzopyran-4-one (I18): yellow solid, yield 46%, melting point 121-122℃; 1 H NMR(500MHz, CDCl3)δ8.18(dd,J=8.0,1.7Hz,1H),7.76–7.74(m,1H),7.71–7.68(m,1H),7.58–7.55(m,1H),7.44(dd,J=8.5,1.0Hz,1H),7. 31–7.28(m,1H),7.19(dd,J=5.4,1.0Hz,2H),7.18–7.14(m,2H),7.13–7.08(m,3H),4.23–4.18(m,2H),2.97(t,J=7.1Hz,2H),2.31(s,3H); 13 C NMR (300MHz, CDCl3) δ175.28,156.13,155.38,140.63,138.27,138.14,133.47,131.51,130.93,129.07(d,J=3.3Hz ),128.42(d,J=2.7Hz),126.36,126.02,125.92,124.73,124.30,118.10,73.02,36.70,21.64; HRMS(m / z)calcdfor C 24 H 20 O3(M+H) + :356.1412,found:356.1408.

[0107] 2-[4-trifluoromethylphenyl]-3-(2-phenylethoxy)-4H-1-benzopyran-4-one (I19): yellow solid, yield 26%, melting point 134-135℃; 1H NMR(500MHz, CDCl3)δ8.28(dd,J=4.8,1.0Hz,1H),8.01(d,J=4.9Hz,2H),7.70–7.62(m,1H),7.55(t,J=5.4Hz, 3H),7.43(m,1H),7.27–7.21(m,3H),7.18(dd,J=4.7,1.0Hz,2H),4.35(t,J=4.0Hz,2H),3.05(t,J=4.0Hz,2H); 13 C NMR (300MHz, CDCl3) δ175.25,155.30,154.05,141.14,138.30,134.12,132.05,131.79,129.07,128.90,12 8.50,126.53,126.00,125.29(d,J=3.9Hz),125.06,124.19,122.77,118.12,73.17,36.57; HRMS(m / z)calcd for C 24 H 17 F3O3(M+H) + :410.1130,found:410.1135.

[0108] 2-(4-tert-butyl)phenyl-3-(2-phenylethoxy)-4H-1-benzopyran-4-one (I20): yellow solid, yield 39%, melting point 131-133℃; 1 H NMR(500MHz, CDCl3)δ8.26(dd,J=8.0,1.3Hz,1H),7.94–7.88(m,2H),7.65–7.58(m,1H),7.51(d,J=8.4Hz ,1H),7.42–7.34(m,3H),7.30–7.17(m,5H),4.33–4.26(m,2H),3.09(t,J=6.9Hz,2H),1.38–1.34(m,9H); 13 C NMR (300MHz, CDCl3) δ175.27,156.07,155.34,154.13,140.41,138.52,133.44,129.23,128.44(d,J=3 .9Hz),128.01,126.35,125.90,124.70,124.28,118.07,72.94,36.71,35.01,31.27; HRMS(m / z)calcd for C 27 H 26 O3(M+H) +:398.1882,found:398.1876.

[0109] 2-(4-Fluorophenyl)-3-[(4-methylphenyl)methoxy]-4H-1-benzopyran-4-one (I21): yellow solid, yield 40%, melting point 152-153℃; 1 H NMR(500MHz, CDCl3)δ8.32(dd,J=7.9,1.7Hz,1H),8.06–7.98(m,2H),7.76–7.66(m,1H),7.53(d,J= 8.4Hz,1H),7.49–7.40(m,1H),7.23–7.10(m,4H),7.07(d,J=7.8Hz,2H),5.12(s,2H),2.33(s,3H); 13 C NMR (300MHz, CDCl3) δ175.15,165.14,162.63,155.50,155.22,139.56,138.04,133.52,133.41,131.19,131.10, 129.07,128.92,127.22,127.18,125.86,124.80,124.17,117.99,115.49,115.27,74.04,21.23; HRMS(m / z)calcd for C 23 H 17 FO3(M+H) + :360.1162,found:360.1165.

[0110] 2-(4-Methylphenyl)-3-[(4-methoxyphenyl)methoxy]-4H-1-benzopyran-4-one (I22): yellow solid, yield 53%, melting point 163-164℃; 1 H NMR(500MHz, CDCl3)δ8.29(dd,J=4.8,1.0Hz,1H),7.97–7.91(m,2H),7.71–7.64(m,1H),7.55–7.51(m,1H ),7.44–7.38(m,1H),7.29–7.24(m,1H),6.80–6.75(m,2H),5.05(s,2H),3.78(s,2H),2.49–2.39(m,2H); 13C NMR (126MHz, CDCl3) δ175.31,159.61,156.78,155.38,141.12,139.65,133.40,130.70,129.11,128 .98,128.87,128.33,125.88,124.71,124.29,118.11,113.66,73.75,55.33,21.66; HRMS(m / z)calcd for C 24 H 20 O4(M+H) + :372.1363,found:372.1369.

[0111] 2-(4-Fluorophenyl)-3-[(4-methoxyphenyl)methoxy]-4H-1-benzopyran-4-one (I23): yellow solid, yield 43%, melting point 168-170℃; 1 H NMR (400MHz, CDCl3) δ8.29(dd,J=8.1,1.6Hz,1H),8.01(dd,J=8.6,5.5Hz,2H),7.71–7.62(m,1H),7.50(d,J=8.4Hz,1H ),7.40(t,J=7.5Hz,1H),7.21(d,J=8.3Hz,2H),7.13(t,J=8.7Hz,2H),6.76(d,J=8.3Hz,2H),5.09(s,2H),3.76(s,3H); 13 CNMR(300MHz, CDCl3)δ175.23,159.69,155.59,155.26,139.46,133.60,131.23(d,J=20.6Hz),130.78,129.84 (d,J=7.6Hz),128.64,127.26,125.86,124.87,118.09,115.53,115.36,113.64,73.85,55.29; HRMS(m / z)calcd for C 23 H 17 O4(M+H) + :376.3834,found:376.3845.

[0112] 2-[(4-trifluoromethyl)phenyl]-3-[(4-methoxyphenyl)methoxy]-4H-1-benzopyran-4-one (I24): yellow solid, yield 29%, melting point 183-185℃; 1H NMR(500MHz, CDCl3)δ8.22(dd,J=8.4,1.6Hz,1H),7.97(d,J=8.1Hz,2H),7.66–7.57(m,3H),7.44(d, J=8.0Hz,1H),7.35(t,J=8.3Hz,1H),7.09–7.03(m,2H),6.65–6.59(m,2H),5.02(s,2H),3.67(s,3H); 13 C NMR NMR (300MHz, CDCl3) δ175.23,164.92,162.91,159.69,155.60,155.26,139.46,133.60,131.26,131.19,130. 78,128.64,127.28,125.86,124.87,124.18,118.09,114.46,114.28,113.64,73.85,55.27; HRMS(m / z)calcd for C 24 H 17 FO4(M+H) + :376.3834,found:376.3845.

[0113] 2-(4-Methylphenyl)-3-[(4-nitrophenyl)methoxy]-4H-1-benzopyran-4-one (I25): yellow solid, yield 22%, melting point 104-106℃; 1 H NMR(500MHz, CDCl3)δ8.28(dd,J=8.0,1.7Hz,1H),7.95–7.90(m,2H),7.68–7.65(m,1H),7.55–7 .48(m,1H),7.43–7.35(m,1H),7.34–7.22(m,4H),6.80–6.73(m,2H),5.04(s,2H),2.43(s,3H); 13 C NMR (300MHz, CDCl3) δ175.34,159.59,156.82,155.38,141.14,139.63,133.43,130.72,129.12, 128.95,128.88,128.32,125.89,124.73,124.28,118.12,113.65,73.75,21.68; HRMS(m / z)calcd for C 23 H 17 NO5(M+H) + :387.1107,found:387.1102.

[0114] 2-(4-Fluorophenyl)-3-[(4-nitrophenyl)methoxy]-4H-1-benzopyran-4-one (I26): yellow solid, yield 37%, melting point 169-170℃; 1 H NMR(500MHz, CDCl3)δ8.31(dd,J=8.1,1.7Hz,1H),8.21–8.12(m,2H),8.09–7.98(m,2H),7.74–7 .68(m,1H),7.55(dd,J=13.6,8.5Hz,3H),7.50–7.42(m,1H),7.22(d,J=8.5Hz,2H),5.26(s,2H); 13 C NMR (101MHz, CDCl3) δ174.85,165.34,162.83,155.54,155.25,147.66,143.99,139.33,133.86,131.14,1 31.05,128.86,126.83,125.82,125.10,124.06,123.51,118.08,115.85,115.64,72.54; HRMS(m / z)calcd for C 22 H 14 FNO5(M+H) + :391.0856,found:391.0861.

[0115] 2-(3-Methylphenyl)-3-[(4-nitrophenyl)methoxy]-4H-1-benzopyran-4-one (I27): yellow solid, yield 42%, melting point 143-145℃; 1 H NMR (500MHz, CDCl3) δ8.31–8.26(m,1H),8.14–8.08(m,2H),7.79–7.73(m,2H),7.74–7.68(m,1H),7.55(d,J=8.4Hz,1 H),7.49(d,J=8.5Hz,2H),7.46–7.41(m,1H),7.37(t,J=7.6Hz,1H),7.32(d,J=7.7Hz,1H),5.22(s,2H),2.40(s,3H); 13C NMR (101MHz, CDCl3) δ175.14,155.25,154.66,140.67,138.30,133.67,131.68,130.08,129.72, 129.08,128.48,126.46,125.96,125.18,124.89,124.23,118.03,72.99,36.61; HRMS(m / z)calcd for C 23 H 17 NO5(M+H) + :387.1107,found:387.1104.

[0116] Example 28: Bactericidal activity of the flavonol derivatives I1-I27 of the present invention

[0117] The bioactivity of flavonol derivatives I1-I27 against six plant pathogens tested—Alternaria solani (tomato early blight), Gibberella zeae (wheat scab), Rhizoctoriza solani (rice sheath blight), Alternaria leafspot (apple spot), Botrytis cinerea (strawberry gray mold), and Cucumber anthrax—was determined using the mycelial growth method. The specific procedures are as follows:

[0118] 1. Weigh 15 mg of the original drug and dissolve it in 0.6 mL of LDM to prepare a stock solution;

[0119] 2. Take 0.1 mL of the stock solution and add it to 50 mL of sterile potato dextrose agar medium (PDA medium). Shake well to obtain a drug-containing medium of 50 mg / L.

[0120] 3. While the above-mentioned drug-containing culture medium is still hot, pour equal amounts into three sterile petri dishes with a diameter of 9 cm, let it cool and solidify, and inoculate a 0.5 cm diameter mycelium cake in the center of the culture medium;

[0121] 4. Include a blank control without the test reagent, and replicate each treatment three times;

[0122] 5. Place the above-mentioned petri dishes in a constant temperature incubator at 25±1℃ and incubate in the dark until the colony diameter is about 7.0 to 7.5 cm. Then, measure the colony diameter and calculate the inhibition rate of each drug.

[0123] 6. The formula for calculating the inhibition rate of the compound against fungi is as follows: Inhibition rate = (Coronavirus diameter of blank control - Coronavirus diameter of test agent) ÷ (Coronavirus diameter of blank control - 5mm) × 100%.

[0124] The inhibitory activity of compounds I1-I27 against *Early Blight* of tomato, *Fusarium graminearum* of wheat, *Rhizoctonia solani* of rice, *Sclerotium affine* of apple, *Botrytis cinerea* of strawberry, and *Anthracnose* of cucumber is shown in Table 2.

[0125] Table 2 shows the inhibitory effects of compounds I1-I27 on six pathogens.

[0126]

[0127]

[0128] a Repeat three times and take the average. b The commercial fungicide carbendazim was used as a control. c The commercial drug cyazofamid was used as a control agent.

[0129] Table 2 shows that target compound I exhibits antibacterial activity against all six pathogens, particularly against *Rhizoctonia solani*, *Botrytis cinerea*, and *Anthracnose*. A total of 17 compounds showed inhibition rates exceeding 70% against *Rhizoctonia solani*: I1, I3, I4, I5, I8, I9, I10, I11, I12, I13, I15, I18, I19, I22, I23, I24, and I26. Four compounds showed inhibition rates exceeding 70% against *Botrytis cinerea*: I5, I8, I9, and I21. Three compounds showed inhibition rates exceeding 70% against *Anthracnose*: I5, I8, and I9.

[0130] Analysis of the inhibition rate data obtained from the initial screening revealed that compounds with inhibition rates greater than 70% underwent further EC testing against the corresponding pathogens. 50 The specific methods for toxicity testing are as follows:

[0131] Weigh the test compound to prepare a stock solution, then gradually dilute it to prepare solutions of varying concentrations. Prepare drug-containing plates, using boscalid as a control. Perform the remaining operations according to the activity screening method, calculating the inhibition rate at each concentration. Using DPS statistical software, the linear regression equation and the median effective inhibitory concentration (EC50) can be obtained. 50 ) and 95% confidence interval.

[0132] EC of some compounds 50 The results of the toxicity test are shown in Table 3:

[0133] Table 3 shows the EC values ​​of some compounds. 50 Toxicity testing a

[0134]

[0135]

[0136] a Repeat three times and take the average. b The commercial fungicide carbendazim was used as the control.

[0137] As shown in Table 3, compounds I1, I3, I4, I5, I8, I9, I10, I11, I12, I13, I15, I18, I19, I22, I23, I24, and I26 exhibit EC50-95% seroconversion rate against rice sheath blight pathogens. 50 The concentrations of the active ingredients (CPI) against *Botrytis cinerea* were 2.21 μg / mL, 1.35 μg / mL, 2.32 μg / mL, 8.83 μg / mL, 5.24 μg / mL, 1.21 μg / mL, 6.37 μg / mL, 5.54 μg / mL, 0.21 μg / mL, 0.21 μg / mL, 9.34 μg / mL, 2.77 μg / mL, 1.36 μg / mL, 0.26 μg / mL, 0.18 μg / mL, 0.06 μg / mL, 0.35 μg / mL, and 1.37 μg / mL, respectively. The EC50 values ​​of compounds I, I5, I8, I9, and I21 against *Botrytis cinerea* were also observed. 50 The concentrations were 6.47 μg / mL, 12.31 μg / mL, 9.32 μg / mL, and 1.37 μg / mL, respectively; the EC5 values ​​of compounds I5, I8, and I9 against *Anthracnose causal agent* of cucumber anthracnose were also observed. 50 The concentrations were 2.14 μg / mL, 11.07 μg / mL, and 1.73 μg / mL, respectively.

[0138] 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 fall within the scope of the present invention.

Claims

1. A flavonol derivative or a pharmaceutically acceptable salt thereof, selected from any of the following compounds:

2. The application of the flavonol derivatives or their pharmaceutically acceptable salts as described in claim 1 in the prevention and control of plant fungal diseases; wherein the fungus is *Rhizoctonia solani*, *Anthracnose fungus*, or *Botrytis cinerea*.

3. The use of the flavonol derivatives of claim 1 or their pharmaceutically acceptable salts in the preparation of reagents for the prevention and control of plant fungal diseases; wherein the fungus is rice sheath blight fungus, cucumber anthracnose fungus or strawberry gray mold fungus.

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