Flavonol derivative containing benzimidazole active fragment and application thereof

Abstract

The invention discloses a flavonol derivative containing a benzimidazole active fragment and application of the flavonol derivative. The flavonol derivative has the advantages of being low in raw material cost, simple and convenient in synthetic route and the like. The obtained flavonol derivative has an excellent bacteriostatic effect on botrytis cinerea and can be used for preventing and treating botrytis cinerea diseases.

Description

Technical Field

[0001] The present invention relates to the field of pesticides, in particular to flavonol derivatives containing benzimidazole active fragments, and also to the application of the derivatives in preventing and controlling plant fungal diseases, and has the use of pesticide fungicides. Background Art

[0002] The prevention and control of plant pathogens is a key area of ​​pesticide research. Chemical control remains the primary method for preventing outbreaks of plant pathogenic fungi in agriculture, and the widespread use of fungicides has effectively controlled most plant pathogens. However, with the continued expansion of fungicide use, plant pathogens have developed resistance to traditional fungicides. Furthermore, existing fungicides suffer from high toxicity to non-target organisms and severe environmental pollution, significantly limiting their application in production. Therefore, the development of new fungicides that are highly effective, highly specific to target organisms, and environmentally friendly is crucial for ensuring increased and stable agricultural production and food security.

[0003] Flavonol skeletons are widely found in natural products and bioactive molecules, particularly in the flowers and leaves of dicotyledons. These structures are widely used in drug discovery. Flavonoids have been shown to have anti-tumor, antioxidant, anti-inflammatory, antiviral, anti-thrombotic, and vasodilatory properties.

[0004] On the other hand, in addition to their excellent medical activity, flavonol derivatives have also been discovered and developed for their potential application in the field of pesticide creation. Flavonoids have a broad spectrum of bactericidal effects, and their killing effect on pathogenic fungi has also been initially developed.

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

[0006] The purpose of the present invention is to provide a series of flavonol derivatives containing benzimidazole active fragments.

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

[0008] The technical solution adopted by the present invention to solve the technical problem is:

[0009] The first aspect of the present invention provides a flavonol derivative containing a benzimidazole active fragment having a structure represented by general formula (I):

[0010]

[0011] Among them, A is selected from or

[0012] R 1 Selected from alkyl, aryl, and heteroaryl.

[0013] R 2 Selected from aryl and heteroaryl.

[0014] In a specific embodiment, R 1 Selected from substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C 10 aryl, substituted or unsubstituted C5-C6-1,1-dione having one to three heteroatoms selected from N, O or S 10 Heteroaryl, wherein the alkyl, aryl, or heteroaryl is substituted by one, two, or three of the following substituents: C1-C4 alkyl, halogen, nitro, methoxy, or aryl, and the C1-C4 alkyl, methoxy, or aryl is substituted by one, two, or three halogen or methoxy groups;

[0015] In a specific embodiment, R 2 substituted or unsubstituted C6-C8 aryl, substituted or unsubstituted C5-C8 aryl having one to three heteroatoms selected from N, O or S 10 Heteroaryl, wherein the aryl or heteroaryl is substituted by one, two or three of the following substituents: C1-C4 alkyl, halogen, nitro, methoxy.

[0016] In a specific embodiment, the R 1 Selected from C1-C4 alkyl, substituted or position-substituted C6-C8 aryl, substituted or unsubstituted C5-C6 heteroaryl having a heteroatom selected from N, O or S, wherein the alkyl, aryl, heteroaryl is substituted by one, two or three of the following substituents: C1-C4 alkyl, halogen, nitro, methoxy, aryl, and the C1-C4 alkyl, methoxy, aryl is substituted by one, two or three halogens or methoxy groups.

[0017] In a specific embodiment, the R 2 Selected from substituted or unsubstituted C6-C7 aryl, substituted or unsubstituted C5-C6 heteroaryl having one heteroatom selected from N, O or S, wherein the aryl, heteroaryl is substituted by one, two or three of the following substituents: C1-C4 alkyl, halogen, nitro, methoxy.

[0018] In a specific embodiment, the halogen refers to fluorine, chlorine, or bromine.

[0019] In a specific embodiment, R 1Selected from ethyl, cyclopropyl, n-propyl, n-butyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methylphenyl, 4-methoxyphenyl, 4-tert-butylphenyl, 4-isopropylphenyl, 4-nitrophenyl, 4-trifluoromethoxyphenyl, 2-naphthyl, 3,5-dichlorophenyl, 2,4,6-trichlorophenyl, 2-methoxyphenyl, 2-fluorophenyl, 2-chlorophenyl, 2-thiophene, 5-chloro-2-thiophene, and 3-pyridine.

[0020] In a specific embodiment, R 2 Selected from phenyl, 2-chlorophenyl, 2-fluorophenyl, 2-methoxyphenyl, 4-methoxyphenyl, 2-methylphenyl, 2-thiophene.

[0021] In a more specific embodiment, the compound of the present invention is preferably the following specific compound:

[0022] Table 1 Names and structures of compounds I1-I30

[0023]

[0024]

[0025]

[0026]

[0027]

[0028] The second aspect of the present invention provides a flavonol derivative containing a benzimidazole active fragment shown in the general formula (I) wherein A is The preparation method is as follows: in the presence of potassium carbonate (K2CO3) and acetonitrile (CH3CN), benzimidazole flavonoid (II) reacts with sulfonyl chloride at room temperature to generate a flavonol derivative (I) containing a benzimidazole active fragment:

[0029]

[0030] Among the above structural formulas:

[0031] R 1 The corresponding groups have the same definitions as above.

[0032] The second aspect of the present invention provides a flavonol derivative containing a benzimidazole active fragment represented by general formula (I) wherein A is The preparation method comprises reacting benzimidazole flavonoid (II) with acyl chloride in the presence of potassium carbonate (K2CO3) and acetonitrile (CH3CN) at room temperature to generate a flavonol derivative (I) containing a benzimidazole active fragment:

[0033]

[0034] Among the above structural formulas:

[0035] R 2 The corresponding groups have the same definitions as above.

[0036] The third aspect of the present invention is the use of the aforementioned flavonol derivatives containing benzimidazole active fragments. Such derivatives have significant inhibitory activity against plant pathogenic fungi and can be used to inhibit plant pathogenic fungi and prevent and control plant fungal diseases.

[0037] The series of flavonol derivatives containing benzimidazole active fragments of the present invention are suitable for inhibiting tomato gray mold fungi and are suitable for preventing and controlling tomato gray mold.

[0038] Beneficial effects:

[0039] Compared with the prior art, the present invention has obvious beneficial effects. From the above technical scheme, it can be seen that: the present invention introduces benzimidazole, sulfone group and carbonyl fragments, which are excellent active groups, into the structure of flavonol, and designs and synthesizes flavonol derivatives (I) containing benzimidazole active fragments for the first time. The structure of this type of compound is novel; this type of compound is applied to research on anti-plant pathogenic fungi, and it is found that this type of compound has outstanding inhibitory activity against plant pathogenic fungi, reflecting the significant progress of the present technical scheme; among them, some compounds have an inhibitory activity against tomato gray mold that exceeds that of the control agents carbendazim and boscalid, and have outstanding application value. DETAILED DESCRIPTION

[0040] The essential features of the present invention can be seen from the following examples, which should not be construed as limiting the present invention. Reagents or instruments used without manufacturer's indication are considered to be commercially available conventional products.

[0041] Example 1: Synthesis of 2-phenyl-3-((1-tosyl-1H-benzo[d]imidazol-2-yl)methoxy)-4H-chroman-4-one (I1)

[0042] 3-((1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (II) (1.0 mmol), p-toluenesulfonyl chloride (1.2 mmol), and potassium carbonate (3.0 mmol) were added to an 18 mL test tube. Acetonitrile (5.0 mL) was added and the mixture was stirred at room temperature for 10 hours to stop the reaction. 20 mL of water was added, and the mixture was extracted with ethyl acetate (3×10 mL). The mixture was washed with saturated brine (20 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to remove the solvent. The mixture was separated and purified using a silica gel column to obtain the compound 2-phenyl-3-((1-toluenesulfonyl-1H-benzo[d]imidazol-2-yl)methoxy)-4H-chroman-4-one (I1).

[0043]

[0044] Example 2 Synthesis of Compound 3-((1-((2-chlorophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I2)

[0045] The other steps are the same as in Example 1, except that p-toluenesulfonyl chloride is replaced by 2-chlorobenzenesulfonyl chloride.

[0046] Example 3 Synthesis of Compound 3-((1-((2-fluorophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I3)

[0047] The other steps are the same as in Example 1, except that p-toluenesulfonyl chloride is replaced by 2-fluorobenzenesulfonyl chloride.

[0048] Example 4 Synthesis of Compound 3-((1-((2-methoxyphenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I4)

[0049] The other steps are the same as in Example 1, except that p-toluenesulfonyl chloride is replaced by 2-methoxybenzenesulfonyl chloride.

[0050] Example 5 Synthesis of Compound 3-((1-((4-nitrophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I5)

[0051] The other steps are the same as in Example 1, except that p-toluenesulfonyl chloride is replaced by 4-nitrobenzenesulfonyl chloride.

[0052] Example 6 Synthesis of Compound 3-((1-((4-tert-butylphenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I6)

[0053] The other steps are the same as in Example 1, except that p-toluenesulfonyl chloride is replaced by 4-tert-butylbenzenesulfonyl chloride.

[0054] Example 7 Synthesis of Compound 3-((1-((4-fluorophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I7)

[0055] The other steps are the same as in Example 1, except that p-toluenesulfonyl chloride is replaced by 4-fluorobenzenesulfonyl chloride.

[0056] Example 8 Synthesis of Compound 3-((1-((4-trifluoromethylphenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I8)

[0057] The rest is the same as Example 1, except that p-toluenesulfonyl chloride is replaced by 4-trifluoromethylbenzenesulfonyl chloride.

[0058] Example 9 Synthesis of Compound 3-((1-((4-chlorophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I9)

[0059] The other steps are the same as in Example 1, except that p-toluenesulfonyl chloride is replaced by 4-chlorobenzenesulfonyl chloride.

[0060] Example 10 Synthesis of Compound 3-((1-((4-bromophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I10)

[0061] The other steps are the same as in Example 1, except that p-toluenesulfonyl chloride is replaced by 4-bromobenzenesulfonyl chloride.

[0062] Example 11 Synthesis of Compound 3-((1-((4-isopropylphenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I11)

[0063] The other steps are the same as in Example 1, except that p-toluenesulfonyl chloride is replaced by 4-isopropylbenzenesulfonyl chloride.

[0064] Example 12 Synthesis of Compound 3-((1-((4-methoxyphenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I12)

[0065] The other steps are the same as in Example 1, except that p-toluenesulfonyl chloride is replaced by 4-methoxybenzenesulfonyl chloride.

[0066] Example 13 Synthesis of Compound 3-((1-(ethylsulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I13)

[0067] The other steps are the same as in Example 1, except that p-toluenesulfonyl chloride is replaced by ethylsulfonyl chloride.

[0068] Example 14 Synthesis of Compound 3-((1-(cyclopropylsulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I14)

[0069] The other steps are the same as in Example 1, except that p-toluenesulfonyl chloride is replaced by cyclopropylsulfonyl chloride.

[0070] Example 15 Synthesis of Compound 2-phenyl-3-((1-(propylsulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-4H-chroman-4-one (I15)

[0071] The other steps are the same as in Example 1, except that p-toluenesulfonyl chloride is replaced by propylsulfonyl chloride.

[0072] Example 16 Synthesis of Compound 3-((1-(butylsulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I16)

[0073] The other steps are the same as in Example 1, except that p-toluenesulfonyl chloride is replaced by butylsulfonyl chloride.

[0074] Example 17 Synthesis of Compound 3-((1-(naphthalen-2-ylsulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I17)

[0075] The rest is the same as Example 1, except that p-toluenesulfonyl chloride is replaced by naphthyl-2-sulfonyl chloride.

[0076] Example 18 Synthesis of Compound 2-phenyl-3-((1-(thiophen-2-ylsulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-4H-chroman-4-one (I18)

[0077] The other steps are the same as in Example 1, except that p-toluenesulfonyl chloride is replaced by thiophene-2-sulfonyl chloride.

[0078] Example 19 Synthesis of Compound 2-phenyl-3-((1-(pyridin-3-ylsulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-4H-chroman-4-one (I19)

[0079] The rest is the same as Example 1, except that p-toluenesulfonyl chloride is replaced by pyridine-3-sulfonyl chloride.

[0080] Example 20 Synthesis of Compound 3-((1-((3,5-dichlorophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I20)

[0081] The other steps are the same as in Example 1, except that p-toluenesulfonyl chloride is replaced by 3,5-dichlorobenzenesulfonyl chloride.

[0082] Example 21 Synthesis of Compound 3-((1-((2,4,6-trichlorophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I21)

[0083] The other steps are the same as in Example 1, except that p-toluenesulfonyl chloride is replaced by 2,4,6-trichlorobenzenesulfonyl chloride.

[0084] Example 22 Synthesis of Compound 3-((1-((4-trifluoromethoxyphenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I22)

[0085] The other steps are the same as in Example 1, except that p-toluenesulfonyl chloride is replaced by 4-trifluoromethoxybenzenesulfonyl chloride.

[0086] Example 23 Synthesis of Compound 3-((1-((5-chlorothiophen-2-yl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I23)

[0087] The other steps are the same as in Example 1, except that p-toluenesulfonyl chloride is replaced by 5-chlorothiophene-2-sulfonyl chloride.

[0088] Compounds I2-I23 were synthesized sequentially according to the method of Example 1. The structures of the synthesized flavonol derivatives (I2-I23) containing a benzimidazole active fragment were confirmed by nuclear magnetic resonance spectroscopy (NMR) and high-resolution mass spectrometry (HRMS). The physicochemical parameters and spectral data of the target compounds are shown below:

[0089] 2-Phenyl-3-((1-tosyl-1H-benzo[d]imidazol-2-yl)methoxy)-4H-chroman-4-one (I1): yellow solid, yield 77%, melting point 190.5-191.2°C; 1H NMR(500MHz, CDCl3)δ8.36(dd,J=8.0,1.7Hz,1H),7.93(dd,J=8.3,6.6Hz,3H),7.90–7.87(m,2H),7.79–7.72(m,1H),7.64(d,J=7.9Hz,1H),7.59(d,J= 8.4Hz,1H),7.49(t,J=7.5Hz,1H),7.42–7.38(m,1H),7.37–7.33(m,1H),7. 29(d,J=8.2Hz,2H),7.23(dd,J=11.1,7.3Hz,3H),5.74(s,2H),2.41(s,3H); 13 C NMR (125MHz, CDCl3) δ174.6,157.0,155.3,149.0,145.9,141.7,139.4,135.0,133.5,132.5,130.2,130.1,130. 0,128.4,127.9,127.1,125.8,125.4,124.7,124.5,124.2,120.6,118.0,113.4,67.1,21.6; HRMS(ESI)m / z[M+H] + Calcd.For C 30 H 23 N2O5S:533.1328,Found:533.1325.

[0090] 3-((1-((2-chlorophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I2): yellow solid, yield 68.1%, melting point 163.8-165.1°C; 1 H NMR (500MHz, CDCl3) δ8.35–8.17(m,2H),7.84(dd,J=7.8,1.9Hz,2H),7.71–7.64(m,1H),7.58(d ,J=7.1Hz,1H),7.54–7.37(m,5H),7.34(dd,J=7.8,1.4Hz,1H),7.25–7.16(m,5H),5.70(s,2H); 13C NMR (125MHz, CDCl3) δ174.6,156.9,155.4,150.3,141.4,139.3,135.5,135.4,133.5,132.9,132.4,132.3,131.8,13 0.1,120.0,128.4,128.0,127.2,125.8,125.2,124.7,124.5,124.2,120.8,118.0,113.1,67.3; HRMS(ESI)m / z[M+H] + Calcd.For C 29 H 20 ClN2O5S:543.0781,Found:543.0778.

[0091] 3-((1-((2-Fluorophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I3): yellow solid, yield 52.6%, melting point 166.8-167.5°C; 1 H NMR(500MHz, CDCl3)δ8.38(dd,J=8.0,1.7Hz,1H),8.24–8.16(m,1H),7.89(dd,J=6.6,3.1Hz,2H),7.81–7.75(m,1H),7.71(dd,J=6.2,3.3Hz ,1H),7.68–7.62(m,2H),7.60(d,J=8.4Hz,1H),7.51(t,J=7.4Hz,1H), 7.41–7.34(m,3H),7.29–7.24(m,3H),7.17–7.09(m,1H),5.76(s,2H); 13 C NMR(125MHz, CDCl3)δ174.6,159.2(d,J=258.6Hz),157.1,155.4,149.5,141.5 ,139.2,137.0(d,J=8.8Hz),133.5,132.3,130.4,130.1(d,J=5.6Hz),130.0,12 8.4,127.9,126.0(d,J=15.0Hz),125.9,125.3,124.7(d,J=2.5Hz),124.6,124 .5,124.2,120.6,118.0,117.6(d,J=20.7Hz),113.4,66.9; HRMS(ESI)m / z[M+H] + Calcd.For C 29 H 20FN2O5S:527.1077,Found:527.1069.

[0092] 3-((1-((2-methoxyphenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I4): yellow solid, yield 80.2%, melting point 193.9-195.0°C; 1 H NMR (500MHz, CDCl3) δ8.31(dd,J=7.9,1.8Hz,1H),8.14(dd,J=7.8,1.8Hz,1H),7.95(dd,J=7.8,1.8Hz,2H),7.78–7.64(m,1H),7.59(d,J=6.8 Hz,1H),7.56–7.45(m,3H),7.43(t,J=7.6Hz,1H),7.25–7.16(m,5H),7.06(t,J=7.8Hz,1H),6.82(d,J=8.4Hz,1H),5.71(s,2H),3.68(s,3H); 13 C NMR (125MHz, CDCl3) δ174.7,157.2,157.1,155.4,150.9,141.6,139.4,136.6,133.5,132.4,130.8,130.2,130.1,128. 5,128.0,125.8,125.1,124.8,124.7,124.2,124.1,120.3,120.2,118.0,113.1,112.4,67.2,55.9; HRMS(ESI)m / z[M+H] + Calcd.For C 30 H 23 N2O6S:539.1277,Found:539.1277.

[0093] 3-((1-((4-Nitrophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I5): yellow solid, yield 66.8%, melting point 167.7-168.5°C; 1 H NMR (500MHz, CDCl3) δ8.39–8.30(m,2H),8.29–8.21(m,3H),7.98(d,J=8.1Hz,1H),7.91–7.86(m, 2H),7.82–7.70(m,2H),7.59(d,J=8.4Hz,1H),7.52–7.39(m,3H),7.36–7.24(m,3H),5.74(s,2H); 13C NMR (125MHz, CDCl3) δ174.5,156.5,155.3,150.9,149.1,143.1,141.7,139.6,133.7,132.5,130.5,130.2,12 8.9,128.5,128.2,126.2,125.8,125.3,124.9,124.4,124.1,121.2,118.1,113.2,67.6; HRMS(ESI)m / z[M+H] + Calcd.For C 29 H 20 N3O7S:554.1022,Found:554.1024.

[0094] 3-((1-((4-tert-Butylphenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I6): white solid, yield 81.5%, melting point 161.2-163.0°C; 1 H NMR (500MHz, CDCl3) δ8.41–8.35(m,1H),7.99(d,J=8.8Hz,2H),7.95(d,J=8.2Hz,1H),7.89(d,J=6.4Hz,2H),7.81–7.72(m,1H),7. 62(dd,J=19.3,8.2Hz,2H),7.56–7.46(m,3H),7.44–7.39(m,1H),7.38–7.32(m,1H),7.26–7.18(m,3H),5.74(s,2H),1.32(s,9H); 13 C NMR(125MHz,CDCl3)δ13C NMR(126MHz,Chloroform-d)δ174.7,158.8,157.1,155.4,148.9,141.7,139.4,134.9,133.5,132.6,130.1,130.1,128 .5,127.9,127.0,126.6,125.9,125.4,124.7,124.5,124.2,120.6,118.0,113.5,67.1,35.3,30.8; HRMS(ESI)m / z[M+H] + Calcd.For C 33 H 29 N2O5S:565.1797,Found:565.1784.

[0095] 3-((1-((4-Fluorophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I7): yellow solid, yield 58.3%, melting point 154.7-155.2°C; 1 H NMR (500MHz, CDCl3) δ8.31–8.18(m,1H),8.06(dd,J=8.8,4.7Hz,2H),7.84(dd,J=14.1,7.7Hz,3H),7.74–7.65(m,1H),7.61(d,J=7.9Hz ,1H),7.52(d,J=8.4Hz,1H),7.41(t,J=7.5Hz,1H),7.33(dt,J=25.6,7.5Hz,2H),7.23–7.16(m,3H),7.09(t,J=8.5Hz,2H),5.66(s,2H); 13 C NMR (125MHz, CDCl3) δ174.6,166.1(d,J=258.5Hz),156.8,155.3,149.0,141.7,139.5,133.8(d,J=2.9Hz),133.6,132.5,130.4,130.3(d ,J=4.3Hz),130.2,130.1,128.5,128.0,125.8,125.7,124.8,124.2,120.8,118.0,116.8(d,J=22.9Hz),113.3,67.3; HRMS(ESI)m / z[M+H] + Calcd.For C 29 H 20 FN2O5S:527.1077,Found:527.1066.

[0096] 3-((1-((4-Trifluoromethylphenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I8): yellow solid, yield 79.8%, melting point 157.5-158.3°C; 1 H NMR (500MHz, CDCl3) δ8.32(d,J=8.0Hz,1H),8.27(d,J=8.2Hz,2H),7.96(d,J=8.2Hz,1H),7.91(d ,J=7.7Hz,2H),7.74(m,4H),7.61(d,J=8.4Hz,1H),7.53–7.38(m,3H),7.31(m,3H),5.76(s,2H); 13C NMR (125MHz, CDCl3) δ174.6,156.8,155.3,149.0,141.7,141.2,139.5,135.9(q,J=32.5Hz),133.6,132.5,130.4,130.2,128.5,128.1 ,127.9,126.6(q,J=3.75Hz),125.9,125.8,125.1,124.9,124.1,122.7(q,J=272.5Hz),121.0,118.0,113.3,67.4; HRMS(ESI)m / z[M+H] + Calcd.For C 30 H 20 F3N2O5S:577.1045,Found:577.1031.

[0097] 3-((1-((4-Chlorophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I9): white solid, yield 64.7%, melting point 188.3-188.9°C; 1 H NMR(500MHz, CDCl3)δ8.26(dd,J=7.9,1.8Hz,1H),8.03–7.95(m,2H),7.91–7.77(m,3H),7.73–7.66(m ,1H),7.62(d,J=7.5Hz,1H),7.53(d,J=7.9Hz,1H),7.45–7.29(m,5H),7.24–7.16(m,3H),5.66(s,2H); 13 CNMR (125MHz, CDCl3) δ174.7,157.0,155.5,149.2,141.8,141.6,139.7,136.4,133.8,132.6,130.5,130.3,1 29.9,128.8,128.6,128.2,126.0,125.9,125.1,125,0,124.3,121.0,118.2,113.5,67.4.HRMS(ESI)m / z[M+H] + Calcd.For C 29 H 20 ClN2O5S:543.0781,Found:543.0771.

[0098] 3-((1-((4-Bromophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I10): yellow solid, yield 55.4%, melting point 198.5-199.7°C; 1 H NMR(500MHz, CDCl3)δ8.26(dd,J=7.8,1.8Hz,1H),7.95–7.79(m,5H),7.72–7.67(m,1H),7.62(d,J=7. 9Hz,1H),7.54(t,J=8.6Hz,3H),7.47–7.39(m,1H),7.39–7.29(m,2H),7.24–7.16(m,3H),5.66(s,2H); 13 C NMR (125MHz, CDCl3) δ174.6,156.8,155.3,149.0,141.7,139.5,136.7,133.6,132.7,132.4,130.3,130.1,13 0.1,128.7,128.5,128.0,125.8,125.7,124.9,124.8,124.2,120.9,118.0,113.3,67.3; HRMS(ESI)m / z[M+H] + Calcd.For C 29 H 20 BrN2O5S:587.0276,Found:587.0262.

[0099] 3-((1-((4-Isopropylphenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I11): yellow solid, yield 70.1%, melting point 145.5-146.7°C; 1 H NMR (500MHz, CDCl3) δ8.31–8.28(m,1H),7.91(d,J=8.1Hz,2H),7.87(d,J=8.2Hz,1H),7.81(d,J=6.9Hz,2H),7.74–7.65(m,1H),7.54(dd,J= 19.6,8.1Hz,2H),7.42(t,J=7.6Hz,1H),7.36–7.25(m,4H),7.20–7.07(m,3H),5.66(s,2H),2.89(hept,J=6.9Hz,1H),1.17(d,J=6.9Hz,6H); 13C NMR (125MHz, CDCl3) δ174.6,157.1,156.5,155.4,148.9,141.7,139.4,135.3,133.5,132.6,130.2,130.1,128.4,1 27.9,127.7,127.3,125.9,125.4,124.7,124.5,124.2,120.6,118.0,113.5,67.1,34.2,23.4; HRMS(ESI)m / z[M+H] + Calcd.For C 32 H 27 N2O5S:551.1641,Found:551.1633.

[0100] 3-((1-((4-Methoxyphenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I12): yellow solid, yield 67.7%, melting point 175.5-176.1°C; 1 H NMR (500MHz, CDCl3) δ8.28(dd,J=8.1,1.8Hz,1H),7.93(d,J=9.2Hz,2H),7.83(dd,J=15.8,7.9Hz,3H),7.72–7.65(m,1H),7.57(d,J=7.9 Hz,1H),7.51(d,J=8.3Hz,1H),7.41(t,J=7.6Hz,1H),7.36–7.24(m,2H),7.19–7.11(m,3H),6.89–6.83(m,2H),5.67(s,2H),3.77(s,3H); 13 C NMR (125MHz, CDCl3) δ174.6,164.3,156.9,155.4,149.0,141.7,139.5,133.5,132.5,130.2,130.1,129.5,129. 2,128.4,127.9,125.8,125.4,124.7,124.5,124.2,120.6,118.0,114.6,113.4,67.2,55.7; HRMS(ESI)m / z[M+H] + Calcd.For C 30 H 23 N2O6S:539.1277,Found:539.1266.

[0101] 3-((1-(Ethylsulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I13): yellow solid, yield 50.8%, melting point 183.1-185.0°C; 1 H NMR (500MHz, CDCl3) δ8.12(dd,J=8.0,1.8Hz,1H),8.00(dd,J=6.6,3.0Hz,2H),7.88(d,J=8.0Hz,1H),7.67(t,J= 7.5Hz,2H),7.52(d,J=8.5Hz,1H),7.44–7.29(m,6H),5.44(s,2H),3.73(q,J=7.3Hz,2H),1.41(t,J=7.6Hz,3H); 13 C NMR (125MHz, CDCl3) δ174.7,156.7,155.3,149.2,141.4,140.0,133.7,133.6,130.8,130.4,128.6, 128.5,125.8,125.6,124.8,124.6,124.1,120.7,118.0,113.5,67.9,50.2,7.8; HRMS(ESI)m / z[M+H] + Calcd.For C 25 H 21 N2O5S:461.1171,Found:461.1160.

[0102] 3-((1-(Cyclopropylsulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I14): yellow solid, yield 45.2%, melting point 166.0-166.5°C; 1 H NMR(500MHz, CDCl3)δ8.18(dd,J=8.0,1.8Hz,1H),8.05–7.95(m,2H),7.82(dd,J=7.3,2.1Hz,1H),7.67(td,J=7.5,2.1Hz, 2H),7.53(dd,J=8.3,2.4Hz,1H),7.43–7.30(m,6H),5.53(s,2H),3.34–3.13(m,1H),1.53–1.43(m,2H),1.16–1.02(m,2H); 13C NMR (125MHz, CDCl3) δ174.7,156.6,155.3,149.1,141.6,140.0,133.6,133.4,130.6,130.4,128.6, 128.4,125.9,125.5,124.8,124.5,124.1,120.7,118.0,113.5,67.8,32.7,6.5; HRMS(ESI)m / z[M+H] + Calcd.For C 26 H 21 N2O5S:473.1171,Found:473.1157.

[0103] 2-Phenyl-3-((1-(propylsulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-4H-chroman-4-one (I15): yellow solid, yield 42.6%, melting point 170.1-170.9°C; 1 H NMR(500MHz, CDCl3)δ8.13(dd,J=8.0,1.7Hz,1H),8.03–7.96(m,2H),7.88(d,J=8.0Hz,1H),7.66(t,J=7.8Hz,2H),7. 52(d,J=8.5Hz,1H),7.43–7.32(m,6H),5.46(s,2H),3.65(t,J=5.0Hz,2H),2.00–1.82(m,2H),1.01(t,J=7.4Hz,3H); 13 C NMR (125MHz, CDCl3) δ174.7,156.7,155.3,149.2,141.4,140.0,133.7,133.6,130.7,130.4,128.6,128 .4,125.8,125.6,124.8,124.6,124.1,120.7,118.0,113.4,68.0,57.1,16.8,12.7; HRMS(ESI)m / z[M+H] + Calcd.For C 26 H 23 N2O5S:475.1328,Found:475.1313.

[0104] 3-((1-(Butylsulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I16): yellow solid, yield 47.8%, melting point 155.6-156.7°C; 1H NMR (500MHz, CDCl3) δ8.13(dd,J=8.0,1.8Hz,1H),7.98(dd,J=7.2,2.6Hz,2H),7.87(d,J=8.0Hz,1H),7.67(t,J=7.3Hz,2H),7.52(d, J=8.4Hz,1H),7.44–7.31(m,6H),5.46(s,2H),3.67(t,J=5.0Hz,2H),1.90–1.76(m,2H),1.40(h,J=7.3Hz,2H),0.88(t,J=7.4Hz,3H); 13 C NMR (125MHz, CDCl3) δ174.6,156.7,155.3,149.2,141.4,140.0,133.7,133.6,130.7,130.4,128.6,128.4, 125.8,125.6,124.8,124.6,124.1,120.7,118.0,113.4,68.0,55.2,24.7,21.3,13.3; HRMS(ESI)m / z[M+H] + Calcd.For C 27 H 25 N2O5S:489.1484,Found:489.1466.

[0105] 3-((1-(naphthalen-2-ylsulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I17): yellow solid, yield 67.0%, melting point 164.4-165.8°C; 1 H NMR (500MHz, CDCl3) δ8.67(d,J=1.7Hz,1H),8.28(dd,J=8.0,1.7Hz,1H),7.94(t,J=8.9Hz,2H),7.87–7.77(m,5H),7.74–7.66(m,1H),7.6 6–7.55(m,3H),7.52(d,J=8.4Hz,1H),7.42(t,J=7.5Hz,1H),7.34(t,J=7.2Hz,1H),7.28(d,J=7.5Hz,1H),7.16–7.08(m,3H),5.74(s,2H); 13C NMR (125MHz, CDCl3) δ174.6,156.9,155.4,149.1,141.7,139.5,135.5,134.7,133.6,132.7,131.8,130.2,130.1(2C),129.9,129 .8,129.6,129.3,128.4,128.0,127.9,125.9,125.5,124.7,124.6,124.2,121.3,120.7,118.0,113.5,67.2; HRMS(ESI)m / z[M+H] + Calcd.For C 33 H 23 N2O5S:559.1328,Found:559.1311.

[0106] 2-Phenyl-3-((1-(thiophen-2-ylsulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-4H-chroman-4-one (I18): yellow solid, yield 63.9%, melting point 151.2-151.9°C; 1 H NMR (500MHz, CDCl3) δ8.28(dd,J=7.9,1.8Hz,1H),7.91–7.79(m,4H),7.71–7.66(m,1H),7.59(dd,J=9.1,6.5Hz,2H),7.52(d,J= 8.4Hz,1H),7.41(t,J=7.6Hz,1H),7.36(t,J=7.6Hz,1H),7.30(t,J=7.6Hz,1H),7.19(m,3H),7.00(t,J=4.5Hz,1H),5.66(s,2H); 13 C NMR (125MHz, CDCl3) δ174.6,157.0,155.4,148.9,141.8,139.4,137.8,134.6,134.4,133.5,132.3,130.2(2 C),128.5,128.0,127.9,125.9,125.6,124.8,124.7,124.2,120.8,118.0,113.6,67.1; HRMS(ESI)m / z[M+H] + Calcd.For C 27 H 19 N2O5S2:515.0735,Found:515.0730.

[0107] 2-Phenyl-3-((1-(pyridin-3-ylsulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-4H-chroman-4-one (I19): yellow solid, yield 38.5%, melting point 194.5-195.3°C; 1 H NMR (500MHz, CDCl3) δ9.28(d,J=2.4Hz,1H),8.75(d,J=4.8Hz,1H),8.38(d,J=8.2Hz,1H),8.20(d,J=8.0Hz,1H),7.91(d,J=8.2Hz,1H),7.8 1(d,J=7.6Hz,2H),7.67(t,J=7.9Hz,1H),7.62(d,J=8.0Hz,1H),7.51(d,J=8.4Hz,1H),7.43–7.30(m,4H),7.26–7.18(m,3H),5.65(s,2H); 13 C NMR (125MHz, CDCl3) δ174.5,156.8,155.3,154.9,149.0,148.0,141.6,139.6,135.2,134.7,133.6,132.4,130.4 ,130.2,128.5,128.1,126.0,125.8,125.1,124.8,124.1,123.9,121.0,118.0,113.3,67.5; HRMS(ESI)m / z[M+H] + Calcd.For C 28 H 20 N3O5S:510.1124,Found:510.1114.

[0108] 3-((1-((3,5-Dichlorophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I20): yellow solid, yield 55.9%, melting point 160.7-161.6°C; 1 H NMR(500MHz, CDCl3)δ8.22(dd,J=8.0,1.8Hz,1H),7.94(d,J=1.8Hz,2H),7.87–7.76(m,3H),7.71–7.60(m,2H),7. 50(d,J=8.5Hz,1H),7.45(t,J=1.8Hz,1H),7.42–7.31(m,3H),7.28–7.22(m,1H),7.21–7.16(m,2H),5.65(s,2H); 13C NMR (125MHz, CDCl3) δ174.5,156.7,155.3,149.0,141.6,140.4,139.5,136.3,134.5,133.6,132.5,130.4,13 0.2,128.5,128.1,126.1,125.9,125.8,125.1,124.8,124.2,121.1,118.0,113.2,67.4; HRMS(ESI)m / z[M+H] + Calcd.ForC 29 H 19 Cl2N2O5S:577.0392,Found:577.0393.

[0109] 3-((1-((2,4,6-Trichlorophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I21): yellow solid, yield 50.2%, melting point 129.4-130.6°C; 1 H NMR(500MHz, CDCl3)δ8.28(dd,J=8.0,1.7Hz,1H),7.86(dd,J=7.7,2.0Hz,2H),7.73–7.67(m,1H),7.65–7.60(m,1H),7.53(d,J= 8.4Hz,1H),7.48(dd,J=7.2,2.0Hz,1H),7.42(t,J=7.5Hz,1H),7.35(s,2H),7.31–7.27(m,2H),7.25–7.18(m,3H),5.69(s,2H); 13 C NMR (125MHz, CDCl3) δ174.4,156.6,155.3,150.4,141.2,140.2,139.4,136.9,133.5,132.8,132.1,131.5, 130.1(2C),128.4,128.1,125.8,125.6,124.7(2C),124.2,121.0,118.0,112.6,67.5; HRMS(ESI)m / z[M+H] + Calcd.For C 29 H 18 Cl3N2O5S:611.0002,Found:611.0015.

[0110] 3-((1-((4-Trifluoromethoxyphenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I22): yellow solid, yield 71.6%, melting point 127.6-128.5°C; 1 H NMR (500MHz, CDCl3) δ8.25(d,J=7.9Hz,1H),8.11(dd,J=8.7,2.4Hz,2H),7.85(dd,J=12.7,8.2Hz,3H),7.70(t, J=7.9Hz,1H),7.62(d,J=7.8Hz,1H),7.53(d,J=8.4Hz,1H),7.44–7.30(m,3H),7.26–7.17(m,5H),5.67(s,2H); 13 C NMR (125MHz, CDCl3) δ174.6,156.8,155.4,153.4,149.0,141.8,139.6,135.9,133.6,132.5,130.3,130.2,129.7,128.5 ,128.1,125.9,125.8,124.9,124.8,124.2,120.9,120.8,120.0(q,J=258.8Hz),118.0,113.3,67.3; HRMS(ESI)m / z[M+H] + Calcd.For C 30 H 20 F3N2O6S:593.0994,Found:593.1006.

[0111] 3-((1-((5-chlorothiophen-2-yl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I23): yellow solid, yield 67.7%, melting point 159.3-160.1°C; 1 H NMR(500MHz, CDCl3)δ8.28(dd,J=8.0,1.7Hz,1H),7.83(dd,J=7.7,4.1Hz,3H),7.73–7.61(m,3H) ,7.53(d,J=8.4Hz,1H),7.45–7.31(m,3H),7.25–7.17(m,3H),6.82(d,J=4.2Hz,1H),5.64(s,2H); 13CNMR (125MHz, CDCl3) δ174.6,156.9,155.4,148.9,141.8,140.4,139.4,135.3,134.1,133.6,132.2,130.3,1 30.2,128.5,128.0,127.3,125.9,125.8,125.0,124.8,124.2,120.9,118.0,113.5,67.2; HRMS(ESI)m / z[M+H] + Calcd.For C 27 H 18 ClN2O5S2:549.0346,Found:549.0341.

[0112] Example 24: Synthesis of 3-((1-benzoyl-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I24)

[0113] 3-((1H-Benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (II) (1.0 mmol), benzoyl chloride (1.2 mmol), and potassium carbonate (3.0 mmol) were added to an 18 mL test tube. Acetonitrile (5.0 mL) was added and the mixture was stirred at room temperature for 10 hours to stop the reaction. 20 mL of water was added, and the mixture was extracted with ethyl acetate (3×10 mL). The mixture was washed with saturated brine (20 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to remove the solvent. The mixture was then separated and purified using a silica gel column to obtain compound 3-((1-benzoyl-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I24).

[0114]

[0115] Example 25 Synthesis of Compound 3-((1-(2-chlorobenzoyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I25)

[0116] The rest is the same as Example 24, except that benzoyl chloride is replaced by 2-chlorobenzoyl chloride.

[0117] Example 26 Synthesis of Compound 3-((1-(2-fluorobenzoyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I26)

[0118] The rest is the same as Example 24, except that benzoyl chloride is replaced by 2-fluorobenzoyl chloride.

[0119] Example 27 Synthesis of Compound 3-((1-(2-methoxybenzoyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I27)

[0120] The rest is the same as Example 24, except that benzoyl chloride is replaced by 2-methoxybenzoyl chloride.

[0121] Example 28 Synthesis of Compound 3-((1-(4-methoxybenzoyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I28)

[0122] The other steps are the same as in Example 1, except that benzoyl chloride is replaced by 4-methoxybenzoyl chloride.

[0123] Example 29 Synthesis of Compound 3-((1-(2-methylbenzoyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I29)

[0124] The rest is the same as Example 24, except that benzoyl chloride is replaced by 2-methylbenzoyl chloride.

[0125] Example 30 Synthesis of Compound 2-phenyl-3-((1-(thiophene-2-carbonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-4H-chroman-4-one (I30)

[0126] The rest is the same as Example 24, except that benzoyl chloride is replaced by thiophene-2-carbonyl chloride.

[0127] Compounds I24-I30 were synthesized sequentially according to the method of Example 24. The structures of the synthesized series of flavonol derivatives (I24-I30) containing benzimidazole active fragments were confirmed by nuclear magnetic resonance spectroscopy (NMR) and high-resolution mass spectrometry (HRMS). The physicochemical parameters and spectral data of the target compounds are shown below:

[0128] 3-((1-Benzoyl-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I24): yellow solid, yield 72.2%, melting point 157.3-158.5°C; 1H NMR(500MHz, CDCl3)δ8.20(dd,J=8.0,1.7Hz,1H),7.91(dd,J=7.6,2.1Hz,2H),7.75–7.61(m,5H),7.47(dd,J=8 .3,6.9Hz,3H),7.37(t,J=7.5Hz,1H),7.26–7.21(m,3H),7.14–7.04(m,1H),6.67(d,J=8.3Hz,1H),5.55(s,2H); 13 C NMR (125MHz, CDCl3) δ174.5,167.9,156.3,155.2,151.2,142.2,139.6,133.8,133.7,133.4,133.0,130.4,130.3 ,130.0,128.8,128.5,128.1,125.9,124.6,124.3,124.1,123.9,120.5,117.9,113.6,67.4; HRMS(ESI)m / z[M+H] + Calcd.For C 30 H 21 N2O4:473.1501,Found:473.1500.

[0129] 3-((1-(2-Chlorobenzoyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I25): yellow solid, yield 56.1%, melting point 155.5-156.9°C; 1 H NMR(500MHz, CDCl3)δ8.24(d,J=7.9Hz,1H),7.99–7.80(m,2H),7.74–7.61(m,2H),7.58(t,J=7.7Hz,1H),7.54–7.47( m,3H),7.42(dt,J=19.6,7.4Hz,2H),7.29(d,J=7.6Hz,4H),7.09(t,J=7.8Hz,1H),6.49(d,J=8.3Hz,1H),5.45(s,2H); 13C NMR (125MHz, CDCl3) δ174.5,165.1,156.6,155.3,151.0,142.4,139.5,133.8,133.5,132.9,132.7,131.7,130.5,130.4 ,130.3,129.6,128.5,128.1,127.5,125.9,125.1,124.7,124.6,124.1,120.6,118.0,113.3,68.1; HRMS(ESI)m / z[M+H] + Calcd.For C 30 H 20 ClN2O4:507.1112,Found:507.1109.

[0130] 3-((1-(2-Fluorobenzoyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I26): yellow solid, yield 43.9%, melting point 156.0-157.5°C; 1 H NMR (500MHz, CDCl3) δ8.24(dd,J=8.0,2.2Hz,1H),7.87(dd,J=5.3,2.6Hz,2H),7.67(d,J=7.8Hz,3H),7.52(dd,J=19.5,7.7Hz, 2H),7.40(t,J=7.7Hz,1H),7.31(t,J=7.7Hz,1H),7.26–7.17(m,5H),7.11(t,J=7.9Hz,1H),6.67(d,J=8.3Hz,1H),5.49(s,2H); 13 C NMR(125MHz, CDCl3)δ174.5,163.4,159.9(d,J=256.3Hz),156.6,155.3,150.8,1 42.3,139.4,134.8(d,J=8.4Hz),133.5,133.0,130.7,130.6,130.3(d,J=8.8Hz) ,130.2,128.5,128.0,125.9,124.9(d,J=3.5Hz),124.7,124.4,124.2,122.4(d, J=13.4Hz),120.6,118.0,116.8(d,J=20.6Hz),113.1,67.8; HRMS(ESI)m / z[M+H] + Calcd.For C 30 H 20 FN2O4:491.1407,Found:491.1401.

[0131] 3-((1-(2-Methoxybenzoyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I27): yellow solid, yield 78.3%, melting point 148.1-149.0°C; 1 H NMR (500MHz, CDCl3) δ8.24(dd,J=8.0,1.7Hz,1H),7.89(dd,J=7.6,2.2Hz,2H),7.69–7.63(m,2H),7.60–7.53(m,1H),7.49(d,J=8.4Hz ,1H),7.43–7.35(m,2H),7.25–7.18(m,4H),7.12–7.01(m,2H),6.96(d,J=8.4Hz,1H),6.64(d,J=8.3Hz,1H),5.46(s,2H),3.56(s,3H); 13 C NMR (125MHz, CDCl3) δ174.5,166.0,157.1,156.6,155.3,150.9,142.3,139.4,133.9,133.4,133.1,130.3,130.2,130.0,1 28.5,127.9,125.8,124.6,124.5,124.2,124.0,123.5,121.1,120.3,117.9,113.4,111.6,67.9,55.6; HRMS(ESI)m / z[M+H] + Calcd.For C 31 H 23 N2O5:503.1607,Found:503.1609.

[0132] 3-((1-(4-Methoxybenzoyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I28): yellow solid, yield 80.2%, melting point 143.5-1145.1°C; 1 H NMR(500MHz, CDCl3)δ8.18(dd,J=8.0,1.6Hz,1H),7.98–7.82(m,2H),7.73–7.55(m,4H),7.46(dd,J=8.6,1.2Hz,1H),7. 39–7.32(m,1H),7.26–7.20(m,4H),7.14–7.07(m,1H),6.96–6.87(m,2H),6.85–6.78(m,1H),5.55(s,2H),3.89(s,3H); 13C NMR (125MHz, CDCl3) δ174.5,167.1,164.4,156.2,155.2,151.1,142.1,139.6,134.0,133.4,132.9,130.4,130.3,1 28.5,128.1,125.8,124.8,124.6,124.2,124.1,123.7,120.4,117.9,114.1,113.4,67.2,55.6; HRMS(ESI)m / z[M+H] + Calcd.For C 31 H 23 N2O5:503.1607,Found:503.1613.

[0133] 3-((1-(2-Methylbenzoyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one (I29): yellow solid, yield 69.8%, melting point 127.7-128.5°C; 1 H NMR(500MHz, CDCl3)δ8.24(dd,J=8.0,1.7Hz,1H),7.92(dd,J=8.0,1.7Hz,2H),7.75–7.62(m,2H),7.53–7.48(m,2H),7 .43–7.34(m,2H),7.31–7.22(m,6H),7.06(td,J=7.8,7.3,1.2Hz,1H),6.43(d,J=8.3Hz,1H),5.50(s,2H),2.32(s,3H); 13 C NMR (125MHz, CDCl3) δ174.5,168.1,156.4,155.3,151.3,142.4,139.7,137.4,133.6,133.4,133.2,132.1,131.5,130.5,1 30.3,128.7,128.5,128.1,126.3,125.9,124.7,124.7,124.2,124.1,120.5,118.0,113.5,68.1,19.4; HRMS(ESI)m / z[M+H] + Calcd.For C 31 H 23 N2O4:487.1658,Found:487.1637.

[0134] 2-Phenyl-3-((1-(thiophene-2-carbonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-4H-chroman-4-one (I30): yellow solid, yield 51.7%, melting point 177.6-178.9°C; 1 H NMR (500MHz, CDCl3) δ8.19(dd,J=8.0,1.7Hz,1H),7.96–7.87(m,2H),7.79(dd,J=5.0,1.2Hz,1H),7.69(dd,J=8.0,0.9Hz,1H),7.66–7.59(m,1H),7.50( dd,J=3.9,1.3Hz,1H),7.47(dd,J=8.4,1.1Hz,1H),7.41–7.32(m,1H),7.28 –7.23(m,4H),7.17(dd,J=15.4,1.2Hz,1H),7.14–7.08(m,2H),5.57(s,2H); 13 C NMR (125MHz, CDCl3) δ174.5,161.1,156.3,155.2,150.6,142.1,139.6,136.3,136.2,136.0,133.9,133.4,130.3 ,130.2,128.5,128.2,128.1,125.9,124.6,124.3,124.1,123.9,120.5,117.9,113.1,66.9; HRMS(ESI)m / z[M+H] + Calcd.For C 28 H 19 N2O4S:479.1066,Found:479.1047.

[0135] Application Examples

[0136] Example 31: Bactericidal activity of flavonol derivatives I1-I30 containing a benzimidazole active fragment of formula (I) of the present invention

[0137] The mycelial growth method was used to determine the bioactivity of flavonol derivatives I1-I30 containing a benzimidazole active fragment against six plant pathogens, including rice sheath blight (Rhizoctoriza solani), tomato gray mold (Botrytis cinerea), tomato early blight (Alternaria solani), wheat head blight (Gibberella zeae), apple rot (Valsa mali), and cucumber anthracnose (Colletotrichum orbiculare). The specific steps are as follows:

[0138] 1. Weigh 15 mg of the original drug and dissolve it in 0.6 mL of DMF to prepare a stock solution;

[0139] 2. Take 0.1 mL of the mother solution and add it to 50 mL of sterile potato dextrose agar medium (PDA medium) and shake well to obtain a 50 mg / L drug-containing medium;

[0140] 3. Pour equal amounts of the above-mentioned drug-containing culture medium into three sterile culture dishes with a diameter of 9 cm while it is still hot, cool and solidify, and inoculate a 0.5 cm diameter bacterial cake in the center of the culture medium;

[0141] 4. Set up a blank control without the test agent, and repeat each treatment 3 times;

[0142] 5. Place the above culture dish in a constant temperature incubator at 25±1℃ and culture in the dark. After the colony diameter is about 7.0 to 7.5 cm, measure the colony diameter and calculate the inhibition rate of each agent.

[0143] 6. The formula for calculating the fungal inhibition rate of the compound is as follows: Inhibition rate = (blank control colony diameter - test agent colony diameter) ÷ (blank control colony diameter - 5 mm) × 100%.

[0144] The results of the inhibitory activity test of compounds I1-I30 against rice sheath blight, tomato gray mold, tomato early blight, wheat scab, apple rot and cucumber anthracnose are shown in Table 2:

[0145] Table 2 Inhibition results of compounds I1-I30 on 6 pathogens

[0146]

[0147]

[0148] b The commercial pesticides carbendazim and boscalid were used as control pesticides.

[0149] The data in Table 2 show that target compound I exhibits a certain degree of antibacterial activity against all six pathogens, particularly against Botrytis cinerea. Six compounds, I3, I7, I8, I9, I18, and I23, exhibited inhibition rates exceeding 90% against Botrytis cinerea.

[0150] By analyzing the inhibition rate data obtained from the initial screening, the compounds with inhibition rates greater than 70% were further subjected to EC 50 Toxicity determination: The specific determination method is as follows:

[0151] Weigh the test compound to prepare a stock solution, gradually dilute and prepare a gradient concentration solution, make a drug-containing plate, use carbendazim and boscalid as control drugs, and follow the activity screening method to calculate the inhibition rate at each concentration. Use DPS statistical software to calculate the effective inhibition rate at the medium concentration (EC 50 ).

[0152] EC of some compounds 50 The results of toxicity assay are shown in Table 3:

[0153] Table 3 EC of some compounds 50 Toxicity assaya

[0154]

[0155] a Repeat three times and take the average value.

[0156] As can be seen from Table 3, the EC values ​​of compounds I21, I23, 50 Less than 1μg / mL, equivalent to the control drug boscalid.

[0157] The above description is merely a preferred embodiment of the present invention and does not constitute any form of limitation to the present invention. Any simple modification, equivalent change, and modification made to the above embodiment based on the technical essence of the present invention without departing from the content of the technical solution of the present invention shall fall within the scope of the technical solution of the present invention.

Claims

1. A flavonol derivative containing a benzimidazole active fragment or a pharmaceutically acceptable salt thereof represented by the following general formula (I): in, A is selected from or R 1 Selected from substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C 10 aryl, substituted or unsubstituted C5-C6-1,1-dione having one to three heteroatoms selected from N, O or S 10 Heteroaryl, wherein the alkyl, aryl, or heteroaryl is substituted by one, two, or three of the following substituents: C1-C4 alkyl, halogen, nitro, methoxy, or aryl, and the C1-C4 alkyl, methoxy, or aryl is substituted by one, two, or three halogen or methoxy groups; R 2 substituted or unsubstituted C6-C8 aryl, substituted or unsubstituted C5-C8 aryl having one to three heteroatoms selected from N, O or S 10 Heteroaryl, wherein the aryl or heteroaryl is substituted by one, two or three of the following substituents: C1-C4 alkyl, halogen, nitro, methoxy.

2. The flavonol derivative containing a benzimidazole active fragment or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that: The R 1 Selected from C1-C4 alkyl, substituted or position-substituted C6-C8 aryl, substituted or unsubstituted C5-C6 heteroaryl having a heteroatom selected from N, O or S, wherein the alkyl, aryl, heteroaryl is substituted by one, two or three of the following substituents: C1-C4 alkyl, halogen, nitro, methoxy, aryl, and the C1-C4 alkyl, methoxy, aryl is substituted by one, two or three halogens or methoxy groups.

3. The flavonol derivative containing a benzimidazole active fragment or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that: The R 2 Selected from substituted or unsubstituted C6-C7 aryl, substituted or unsubstituted C5-C6 heteroaryl having one heteroatom selected from N, O or S, wherein the aryl, heteroaryl is substituted by one, two or three of the following substituents: C1-C4 alkyl, halogen, nitro, methoxy.

4. The flavonol derivative containing a benzimidazole active fragment or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that: The halogen refers to fluorine, chlorine and bromine.

5. The flavonol derivative containing a benzimidazole active fragment or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that: R 1 Selected from ethyl, cyclopropyl, n-propyl, n-butyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methylphenyl, 4-methoxyphenyl, 4-tert-butylphenyl, 4-isopropylphenyl, 4-nitrophenyl, 4-trifluoromethoxyphenyl, 2-naphthyl, 3,5-dichlorophenyl, 2,4,6-trichlorophenyl, 2-methoxyphenyl, 2-fluorophenyl, 2-chlorophenyl, 2-thiophene, 5-chloro-2-thiophene, and 3-pyridine.

6. The flavonol derivative containing a benzimidazole active fragment or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that: R 2 Selected from phenyl, 2-chlorophenyl, 2-fluorophenyl, 2-methoxyphenyl, 4-methoxyphenyl, 2-methylphenyl, 2-thiophene.

7. Flavonol derivatives containing benzimidazole active fragments as shown below or pharmaceutically acceptable salts thereof: 2-phenyl-3-((1-tosyl-1H-benzo[d]imidazol-2-yl)methoxy)-4H-chroman-4-one; 3-((1-((2-chlorophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 3-((1-((2-fluorophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 3-((1-((2-methoxyphenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 3-((1-((4-nitrophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 3-((1-((4-Fluorophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 3-((1-((4-chlorophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 3-((1-((4-bromophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 3-((1-((4-methoxyphenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 3-((1-((4-tert-Butylphenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 3-((1-((4-isopropylphenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 3-((1-((4-trifluoromethylphenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 3-((1-((4-trifluoromethoxyphenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 3-((1-((3,5-dichlorophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 3-((1-((2,4,6-trichlorophenyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 3-((1-(ethylsulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 3-((1-(cyclopropylsulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 2-phenyl-3-((1-(propylsulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-4H-chroman-4-one; 3-((1-(Butylsulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 3-((1-(naphthalen-2-ylsulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 2-phenyl-3-((1-(thiophen-2-ylsulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-4H-chroman-4-one; 2-phenyl-3-((1-(pyridin-3-ylsulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-4H-chroman-4-one; 3-((1-((5-chlorothien-2-yl)sulfonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 3-((1-Benzoyl-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 3-((1-(2-chlorobenzoyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 3-((1-(2-Fluorobenzoyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 3-((1-(2-methoxybenzoyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 3-((1-(4-methoxybenzoyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 3-((1-(2-methylbenzoyl)-1H-benzo[d]imidazol-2-yl)methoxy)-2-phenyl-4H-chroman-4-one; 2-phenyl-3-((1-(thiophene-2-carbonyl)-1H-benzo[d]imidazol-2-yl)methoxy)-4H-chroman-4-one.

8. A pharmaceutical composition, characterized in that The pharmaceutical composition contains the flavonol derivative containing a benzimidazole active fragment according to any one of claims 1 to 7 or a pharmaceutically acceptable salt thereof.

9. Use of the flavonol derivative containing a benzimidazole active fragment or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 7, and the pharmaceutical composition according to claim 8 in preventing and controlling plant fungal diseases.

10. The use according to claim 9, characterized in that The fungal disease is tomato gray mold.

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