CN116813588A - Flavonol derivative and application thereof - Google Patents
Flavonol derivative and application thereof Download PDFInfo
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- CN116813588A CN116813588A CN202310789005.6A CN202310789005A CN116813588A CN 116813588 A CN116813588 A CN 116813588A CN 202310789005 A CN202310789005 A CN 202310789005A CN 116813588 A CN116813588 A CN 116813588A
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- 150000002216 flavonol derivatives Chemical class 0.000 title claims abstract description 24
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 14
- 239000001257 hydrogen Substances 0.000 claims abstract description 14
- 241000123650 Botrytis cinerea Species 0.000 claims abstract description 7
- 208000031888 Mycoses Diseases 0.000 claims abstract description 7
- 241000813090 Rhizoctonia solani Species 0.000 claims abstract description 7
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 5
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 5
- 150000002367 halogens Chemical class 0.000 claims abstract description 5
- -1 3-methoxypropyl Chemical group 0.000 claims description 87
- 230000003287 optical effect Effects 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 239000012453 solvate Substances 0.000 claims description 12
- 240000008067 Cucumis sativus Species 0.000 claims description 9
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 claims description 9
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- 241000209140 Triticum Species 0.000 claims description 7
- 235000021307 Triticum Nutrition 0.000 claims description 7
- IQHSSYROJYPFDV-UHFFFAOYSA-N 2-bromo-1,3-dichloro-5-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC(Cl)=C(Br)C(Cl)=C1 IQHSSYROJYPFDV-UHFFFAOYSA-N 0.000 claims description 6
- 241000196324 Embryophyta Species 0.000 claims description 6
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 240000007594 Oryza sativa Species 0.000 claims description 5
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- 206010039509 Scab Diseases 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
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- 235000007688 Lycopersicon esculentum Nutrition 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 4
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- 241000233866 Fungi Species 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
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- 241000223218 Fusarium Species 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
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- 241001290235 Ceratobasidium cereale Species 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract 1
- 238000010189 synthetic method Methods 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 54
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- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 24
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
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- OTXINXDGSUFPNU-UHFFFAOYSA-N 4-tert-butylbenzaldehyde Chemical group CC(C)(C)C1=CC=C(C=O)C=C1 OTXINXDGSUFPNU-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
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- 229940079593 drug Drugs 0.000 description 5
- CEVMYGZHEJSOHZ-UHFFFAOYSA-N 1-bromo-3-methoxypropane Chemical compound COCCCBr CEVMYGZHEJSOHZ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 239000003899 bactericide agent Substances 0.000 description 4
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- HVQAJTFOCKOKIN-UHFFFAOYSA-N flavonol Chemical group O1C2=CC=CC=C2C(=O)C(O)=C1C1=CC=CC=C1 HVQAJTFOCKOKIN-UHFFFAOYSA-N 0.000 description 4
- OVWYEQOVUDKZNU-UHFFFAOYSA-N m-tolualdehyde Chemical compound CC1=CC=CC(C=O)=C1 OVWYEQOVUDKZNU-UHFFFAOYSA-N 0.000 description 4
- BEOBZEOPTQQELP-UHFFFAOYSA-N 4-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=C(C=O)C=C1 BEOBZEOPTQQELP-UHFFFAOYSA-N 0.000 description 3
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 3
- VOLRSQPSJGXRNJ-UHFFFAOYSA-N 4-nitrobenzyl bromide Chemical compound [O-][N+](=O)C1=CC=C(CBr)C=C1 VOLRSQPSJGXRNJ-UHFFFAOYSA-N 0.000 description 3
- TWFZGCMQGLPBSX-UHFFFAOYSA-N Carbendazim Natural products C1=CC=C2NC(NC(=O)OC)=NC2=C1 TWFZGCMQGLPBSX-UHFFFAOYSA-N 0.000 description 3
- 241000227653 Lycopersicon Species 0.000 description 3
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- JNPZQRQPIHJYNM-UHFFFAOYSA-N carbendazim Chemical compound C1=C[CH]C2=NC(NC(=O)OC)=NC2=C1 JNPZQRQPIHJYNM-UHFFFAOYSA-N 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
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- GJVDYPVZKAYDQI-UHFFFAOYSA-N 2-phenyl-3-propan-2-yloxychromen-4-one Chemical compound C(C)(C)OC1=C(OC2=CC=CC=C2C1=O)C1=CC=CC=C1 GJVDYPVZKAYDQI-UHFFFAOYSA-N 0.000 description 2
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 2
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- 239000005740 Boscalid Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
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- 230000009286 beneficial effect Effects 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
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- WYEMLYFITZORAB-UHFFFAOYSA-N boscalid Chemical compound C1=CC(Cl)=CC=C1C1=CC=CC=C1NC(=O)C1=CC=CN=C1Cl WYEMLYFITZORAB-UHFFFAOYSA-N 0.000 description 2
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
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- ZWVHTXAYIKBMEE-UHFFFAOYSA-N 2-hydroxyacetophenone Chemical compound OCC(=O)C1=CC=CC=C1 ZWVHTXAYIKBMEE-UHFFFAOYSA-N 0.000 description 1
- SOUGWDPPRBKJEX-UHFFFAOYSA-N 3,5-dichloro-N-(1-chloro-3-methyl-2-oxopentan-3-yl)-4-methylbenzamide Chemical compound ClCC(=O)C(C)(CC)NC(=O)C1=CC(Cl)=C(C)C(Cl)=C1 SOUGWDPPRBKJEX-UHFFFAOYSA-N 0.000 description 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
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Abstract
The invention relates to the field of pesticides, in particular to a flavonol derivative and application thereof. The flavonol derivative of the invention is shown as (I), wherein R 1 Selected from hydrogen, halogen, alkyl or alkoxy; r is R 2 Selected from hydrogen, alkyl or alkoxy. The flavonol derivative has good antibacterial effect on Rhizoctonia solani, rhizoctonia cerealis and Botrytis cinerea, can be used for preventing and controlling plant fungal diseases, and has the advantages of low cost of synthetic raw materials and simple synthetic method.
Description
Technical Field
The invention relates to the field of pesticides, in particular to a flavonol derivative and application thereof.
Background
The prevention and control inhibition of plant pathogens is an important field of pesticide science research, chemical prevention and control is still a main method for preventing epidemic outbreaks of plant pathogenic fungi in agriculture, and the wide use of bactericides enables a plurality of plant pathogens to be effectively controlled. However, as the use scale of bactericides continues to expand, plant pathogens have developed resistance to traditional bactericides. Meanwhile, the problems of high toxicity to non-target organisms and serious environmental pollution in the existing medicaments also cause great limitation in production application. Therefore, the development of the novel bactericide which has high efficiency, good target biospecificity and environmental friendliness has important effect and significance for guaranteeing the yield and stable yield of agriculture and grain safety.
Flavonol backbones are widely found in natural products and active molecules, with most flowers and leaves in dicotyledonous plants. The structure is widely applied to the creation work of medicines. The physiological activities of the flavonoid compounds mainly comprise anti-tumor, antioxidant, anti-inflammatory, antiviral, antithrombotic, vasodilating and the like.
On the other hand, the flavonol derivative has good medical activity and potential application value in the field of pesticide creation, and is also found and developed. The flavonoid compound has broad-spectrum sterilization effect, and meanwhile, the sterilization effect on pathogenic fungi is primarily developed.
In conclusion, the flavonol compounds have broad-spectrum biological activity and play an important role in the discovery process of novel pesticide lead compounds. In view of this, the present invention modifies the hydroxyl group of flavonols to create novel compounds that inhibit plant pathogenic fungi with a highly potent broad spectrum of activity.
Disclosure of Invention
In view of the shortcomings of the prior art, a first object of the present invention is to provide a flavonoid alcohol derivative.
A second object of the present invention is to provide the use of the above derivatives.
The technical scheme adopted for solving the technical problems is as follows:
in a first aspect, the present invention provides a flavonol derivative having a structure represented by general formula (I), or a pharmaceutically acceptable salt, solvate, optical isomer or polymorph thereof:
R 1 selected from hydrogen, halogen and alkanesA group or an alkoxy group.
R 2 Selected from hydrogen, alkyl, alkoxy, benzyl or 2-phenylethyl.
In particular embodiments, R 1 Selected from hydrogen, methyl, trifluoromethyl, halogen or methoxy.
Preferably, R 1 Any one selected from hydrogen, 4-methyl, 3-methyl, 4-fluoro, 4-chloro, 4-bromo, 4-trifluoromethyl, 4-methoxy and 4-tert-butyl.
More preferably, R 1 Selected from hydrogen, 4-methyl, 3-methyl, 4-fluoro, 4-bromo, 4-trifluoromethyl, 4-methoxy or 4-tert-butyl.
More preferably, the R 1 Selected from the group consisting of hydrogen, 4-fluoro, 4-methyl, 4-t-butyl, 3-methyl, 4-bromo, 4-trifluoromethyl.
In particular embodiments, R 2 Selected from ethyl, propyl, isopropyl, isobutyl, 3-methoxypropyl, 4-methoxyphenyl, 4-nitrophenyl, benzyl or 2-phenylethyl.
Preferably, said R 2 Selected from ethyl, isopropyl, 3-methoxypropyl, benzyl, 2-phenylethyl, 4-methoxyphenyl or 4-nitrophenyl.
In specific embodiments, the present invention also protects the following flavonol derivatives, or pharmaceutically acceptable salts, solvates, optical isomers or polymorphs thereof:
in a third aspect, the present invention also provides the use of a flavonol derivative as hereinbefore described, or a pharmaceutically acceptable salt, solvate, optical isomer or polymorph thereof, in the control of fungal plant diseases.
In a fourth aspect, the present invention also provides the use of a flavonol derivative as hereinbefore described, or a pharmaceutically acceptable salt, solvate, optical isomer or polymorph thereof, in the manufacture of a medicament for controlling plant fungal diseases.
In specific embodiments, the fungus is Rhizoctonia solani, rhizoctonia cerealis, rhizoctonia solani, alternaria alternata, alternaria malis, or Botrytis cinerea.
In specific embodiments, the fungal disease is rice sheath blight, cucumber anthracnose, tomato early blight, wheat scab, apple alternaria leaf spot, or strawberry gray mold.
The derivative provided by the invention has remarkable inhibition activity on plant pathogenic fungi, and can be applied to inhibiting plant pathogenic fungi and preventing and controlling plant fungal diseases. The flavonol derivative is suitable for inhibiting sheath blight of rice, anthracnose of cucumber, early blight of tomato, gibberella wheat, alternaria mali and gray mold of strawberry, and is suitable for preventing and controlling sheath blight of rice, anthracnose of cucumber, early blight of tomato, scab of wheat, alternaria mali and gray mold of strawberry.
The beneficial effects are that:
compared with the prior art, the invention has obvious beneficial effects, and the technical scheme can be adopted as follows: the invention applies flavonol derivatives to research on plant pathogenic fungi resistance, discovers that the compounds have outstanding inhibition activity on plant pathogenic fungi resistance, and represents obvious progress of the technical scheme; wherein, the inhibition activity of part of the compounds to rice sheath blight, cucumber anthracnose and strawberry gray mold bacteria exceeds that of the control agents carbendazim and zoxamide, and the application value is obvious.
Detailed Description
The essential features of the invention can be seen from the following examples, which should not be regarded as limiting the invention in any way.
The reagents or instrumentation used are not manufacturer specific and are considered to be commercially available conventional products.
Example 13 Synthesis of propoxy-2- (4-methylphenyl) -4H-1-benzopyran-4-one (I1)
2-hydroxyacetophenone (1.2 mmol) and p-methylbenzaldehyde (1.26 mmol) were added to 20ml of water at room temperature, and pyrrolidine (12.04 mmol) was added to the suspension to react for 12 hours. After the reaction was completed, the mixture was poured into cold water and acidified to ph=4 with aqueous hydrochloric acid (30%, v/v). Next, the precipitate was filtered, washed with water and ethanol. The crude product was purified by column chromatography on silica gel eluting with diethyl ether and ethyl acetate (30:1, v/v) to give the target compound mixture which was poured into cold water and acidified to ph=4 with aqueous hydrochloric acid (30%, v/v). Next, the precipitate was filtered, washed with water and ethanol. The crude product was purified by column chromatography on silica gel 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℃for 15 min, then 1-bromopropane (123 mg, 1 mmol) was added dropwise to the reaction, and the mixture was gradually heated to 60 ℃. Samples were withdrawn at various time intervals and analyzed by TLC until the reaction was complete. Then cooled to room temperature, poured into water, and extracted into ethyl acetate. The organic layer was washed with water and dried over anhydrous Na2SO 4. The organic phase was concentrated in vacuo to give a colorless liquid as product. The residue was purified by silica gel column chromatography eluting with petroleum ether and ethyl acetate (30:1, v/v) to give the title compound.
Example 22 Synthesis of- (4-bromophenyl) -3-propoxy-4H-1-benzopyran-4-one (I2)
The other points are the same as in example 1 except that p-methylbenzaldehyde is changed to p-bromobenzaldehyde.
Example 32 Synthesis of- (4-tert-butyl) phenyl-3-propoxy-4H-1-benzopyran-4-one (I3)
The other points are the same as in example 1 except that p-methylbenzaldehyde is replaced with p-tert-butylbenzaldehyde.
Example 42 Synthesis of- (3-methylphenyl) -3-propoxy-4H-1-benzopyran-4-one (I4)
The other points are the same as in example 1 except that p-methylbenzaldehyde is changed to p-3-methylbenzaldehyde.
Example 53 Synthesis of- (1-methylethoxy) -2-phenyl-4H-1-benzopyran-4-one (I5)
The procedure is as in example 1, except that p-tolualdehyde is replaced with p-benzaldehyde and 1-bromopropane is replaced with bromoisopropyl.
Example 63 Synthesis of- (2-methylpropyloxy) -2-phenyl-4H-1-benzopyran-4-one (I6)
The procedure is as in example 1, except that p-tolualdehyde is replaced with p-benzaldehyde and 1-bromopropane is replaced with bromoisobutyl.
Example 72 Synthesis of- (4-tert-butyl) phenyl-3- (2-methylpropyloxy) -4H-1-benzopyran-4-one (I7)
The procedure is as in example 1, except that p-methylbenzaldehyde is replaced with p-tert-butylbenzaldehyde and 1-bromopropane is replaced with bromoisobutyl.
Example 83 Synthesis of- (3-methoxypropoxy) -2-phenyl-4H-1-benzopyran-4-one (I8)
The procedure is as in example 1, except that p-methylbenzaldehyde is changed to benzaldehyde and 1-bromopropane is changed to 3-bromopropyl methyl ether.
Example 93 Synthesis of- (3-methoxypropoxy) -2- (4-fluorophenyl) -4H-1-benzopyran-4-one (I9)
The procedure is as in example 1, except that p-methylbenzaldehyde is changed to 4-fluorobenzaldehyde and 1-bromopropane is changed to 3-bromopropyl methyl ether.
EXAMPLE 10 Synthesis of 3- (3-methoxypropoxy) -2- (4-methylphenyl) -4H-1-benzopyran-4-one (I10)
The procedure is as in example 1, except that p-methylbenzaldehyde is changed to p-methylbenzaldehyde and 1-bromopropane is changed to 3-bromopropyl methyl ether.
EXAMPLE 11 Synthesis of 3- (3-methoxypropoxy) -2- (3-methylphenyl) -4H-1-benzopyran-4-one (I11)
The procedure is as in example 1, except that p-methylbenzaldehyde is changed to 3-methylbenzaldehyde and 1-bromopropane is changed to 3-bromopropyl methyl ether.
EXAMPLE 12 Synthesis of 2- (3-methylphenyl) -3-phenylmethoxy-4H-1-benzopyran-4-one (I12)
The procedure is as in example 1, except that p-methylbenzaldehyde is changed to 3-methylbenzaldehyde and 1-bromopropane is changed to benzyl bromide.
EXAMPLE 13 Synthesis of 2- (4-bromophenyl) -3-phenylmethoxy-4H-1-benzopyran-4-one (I13)
The procedure is as in example 1, except that p-methylbenzaldehyde is changed to p-bromobenzaldehyde and 1-bromopropane is changed to benzyl bromide.
EXAMPLE 14 Synthesis of 2- (4-fluorophenyl) -3-phenylmethoxy-4H-1-benzopyran-4-one (I14)
The procedure is as in example 1, except that p-methylbenzaldehyde is changed to p-fluorobenzaldehyde and 1-bromopropane is changed to benzyl bromide.
EXAMPLE 15 Synthesis of 2- [ 4-trifluoromethylphenyl ] -3-phenylmethoxy-4H-1-benzopyran-4-one (I15)
The procedure is as in example 1, except that p-methylbenzaldehyde is changed to p-trifluoromethylbenzaldehyde and 1-bromopropane is changed to benzyl bromide.
EXAMPLE 16 Synthesis of 2- (4-fluorophenyl) -3- (2-phenylethoxy) -4H-1-benzopyran-4-one (I16)
The procedure is as in example 1, except that p-methylbenzaldehyde is changed to p-fluorobenzaldehyde and 1-bromopropane is changed to beta-bromophenylethane.
EXAMPLE 17 Synthesis of 2- (4-bromophenyl) -3- (2-phenylethoxy) -4H-1-benzopyran-4-one (I17)
The procedure is as in example 1, except that p-methylbenzaldehyde is changed to p-bromobenzaldehyde and 1-bromopropane is changed to beta-bromophenylethane
EXAMPLE 18 Synthesis of 2- (3-methylphenyl) -3- (2-phenylethoxy) -4H-1-benzopyran-4-one (I18)
The procedure is as in example 1, except that p-methylbenzaldehyde is changed to 3-methylbenzaldehyde and 1-bromopropane is changed to beta-bromophenylethane
EXAMPLE 19 Synthesis of 2- [ 4-trifluoromethylphenyl ] -3- (2-phenylethoxy) -4H-1-benzopyran-4-one (I19)
The procedure is as in example 1, except that p-methylbenzaldehyde is changed to p-trifluoromethylbenzaldehyde and 1-bromopropane is changed to beta-bromophenylethane
EXAMPLE 20 Synthesis of 2- (4-tert-butyl) phenyl-3- (2-phenylethoxy) -4H-1-benzopyran-4-one (I20)
The procedure is as in example 1, except that p-methylbenzaldehyde is replaced by p-tert-butylbenzaldehyde and 1-bromopropane is replaced by beta-bromophenylethane
EXAMPLE 21 Synthesis of 2- (4-fluorophenyl) -3- [ (4-methylphenyl) methoxy ] -4H-1-benzopyran-4-one (I21)
The procedure is as in example 1, except that p-methylbenzaldehyde is changed to p-fluorobenzaldehyde and 1-bromopropane is changed to 4-methyl bromobenzyl.
EXAMPLE 22 Synthesis of 2- (4-methylphenyl) -3- [ (4-methoxyphenyl) methoxy ] -4H-1-benzopyran-4-one (I22)
The procedure is as in example 1, except that p-methylbenzaldehyde is changed to p-methylbenzaldehyde and 1-bromopropane is changed to 4-methoxybromobenzyl.
EXAMPLE 23 Synthesis of 2- (4-fluorophenyl) -3- [ (4-methoxyphenyl) methoxy ] -4H-1-benzopyran-4-one (I23)
The procedure is as in example 1, except that p-methylbenzaldehyde is changed to p-fluorobenzaldehyde and 1-bromopropane is changed to 4-methoxybromobenzyl.
EXAMPLE 24 Synthesis of 2- [ (4-trifluoromethyl) phenyl ] -3- [ (4-methoxyphenyl) methoxy ] -4H-1-benzopyran-4-one (I24)
The procedure is as in example 1, except that p-methylbenzaldehyde is changed to p-trifluoromethylbenzaldehyde and 1-bromopropane is changed to 4-methoxybromobenzyl.
EXAMPLE 25 Synthesis of 2- (4-methylphenyl) -3- [ (4-nitrophenyl) methoxy ] -4H-1-benzopyran-4-one (I25)
The procedure is as in example 1, except that p-methylbenzaldehyde is changed to p-methylbenzaldehyde and 1-bromopropane is changed to 4-nitrobenzyl bromide.
EXAMPLE 26 Synthesis of 2- (4-fluorophenyl) -3- [ (4-nitrophenyl) methoxy ] -4H-1-benzopyran-4-one (I26)
The procedure is as in example 1, except that p-methylbenzaldehyde is changed to p-fluorobenzaldehyde and 1-bromopropane is changed to 4-nitrobenzyl bromide.
EXAMPLE 27 Synthesis of 2- (4-fluorophenyl) -3- [ (4-nitrophenyl) methoxy ] -4H-1-benzopyran-4-one (I27)
The procedure is as in example 1, except that p-methylbenzaldehyde is changed to 3-methylbenzaldehyde and 1-bromopropane is changed to 4-nitrobenzyl bromide.
The compounds I2-I27 were synthesized sequentially by the method of example 1, and the structures of the synthesized flavonol-containing derivatives (I1-I27) were confirmed by nuclear magnetic resonance spectroscopy (NMR) and High Resolution Mass Spectrometry (HRMS), and the physicochemical parameters and spectral data of the compounds are shown below:
3-propoxy-2- (4-methylphenyl) -4H-1-benzopyran-4-one (I1): yellow liquid with 42 percent yield and 102-103 ℃ melting point; 1 H NMR(500MHz,CDCl 3 )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,CDCl 3 )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 O 3 (M+H) + :294.1256,found:294.1251.
2- (4-bromophenyl) -3-propoxy-4H-1-benzopyran-4-one (I2): yellow liquid with yield 48% and melting point 109-110deg.C; 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,1H),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,CDCl 3 )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 for C 18 H 15 BrO 3 (M+H) + :358.0205,found:358.0209.
2- (4-tert-butyl) phenyl-3-propoxy-4H-1-benzopyran-4-one (I3): yellow liquid with yield of 32% and melting point of 106-107 ℃; 1 H NMR(500MHz,CDCl 3 )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,CDCl 3 )δ175.14,155.25,154.66,140.67,138.30,133.67,131.68,130.08,129.72,129.08,128.48,126.46,125.96,125.18,124.89,124.23,118.03,72.99,36.61,30.19,28.66,19.42；HRMS(m/z)calcd for C 22 H 24 O 3 (M+H) + :336.1725,found:336.1719.
2- (3-methylphenyl) -3-propoxy-4H-1-benzopyran-4-one (I4): yellow liquid with 46% yield and 102-103 ℃ melting point; 1 H NMR(500MHz,CDCl 3 )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 O 3 (M+H) + :294.1256,found:294.1259.
3- (1-methylethoxy) -2-phenyl-4H-1-benzopyran-4-one (I5): yellow liquid with yield of 32% and melting point of 106-107 ℃; 1 H NMR(500MHz,CDCl 3 )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＝8.4Hz,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,CDCl 3 )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 O 3 (M+H) + :280.1099,found:280.1112.
3- (2-methylpropyloxy) -2-phenyl-4H-1-benzopyran-4-one (I6): yellow liquid with 46% yield and 115-116 ℃ melting point; 1 H NMR(500MHz,CDCl 3 )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,CDCl 3 )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 O 3 (M+H) + :294.1256,found:294.1261.
2- (4-tert-butyl) phenyl-3- (2-methylpropyloxy) -4H-1-benzopyran-4-one (I7): yellow liquid with yield of 52% and melting point of 121-122 ℃; 1 H NMR(500MHz,CDCl 3 )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)； 13 C NMR(300MHz,CDCl3)δ175.14,155.25,154.66,140.67,138.30,133.67,131.68,130.08,129.72,129.08,128.48,126.46,125.96,124.89,124.23,118.03,72.99,36.61,30.19,28.72,19.54；HRMS(m/z)calcd for C 23 H 26 O 3 (M+H) + :350.1882,found:350.1885.
3- (3-methoxypropoxy) -2-phenyl-4H-1-benzopyran-4-one (I8): white solid, yield 48%, melting point 131-132 ℃; 1 H NMR(500MHz,CDCl 3 )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,CDCl 3 )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 O 4 (M+H) + :310.1205,found:310.1201.
3- (3-methoxypropoxy) -2- (4-fluorophenyl) -4H-1-benzopyran-4-one (I9): yellow solid, yield 22%, melting point 101-102 ℃; 1 H NMR(500MHz,CDCl 3 )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),7.35(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,CDCl 3 )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 C 20 H 20 O 4 (M+H) + :324.1362,found:324.1368.
3- (3-methoxypropoxy) -2- (4-methylphenyl) -4H-1-benzopyran-4-one (I10): white solid, yield 37%, melting point 115-116 ℃;1H NMR (500 MHz, CDCl 3) delta 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 (300 MHz, CDCl 3). Delta. 175.14,155.25,154.66,140.67,138.30,133.67,131.68,130.08,129.72,129.08,126.46,125.96,124.89,124.23,118.03,69.78,69.56,58.73,30.43,21.39; HRMS (M/z) calcd for C20H20O4 (M+H) +:324.1362, found:324.1368.
3- (3-methoxypropoxy) -2- (3-methylphenyl) -4H-1-benzopyran-4-one (I11): yellow solid, 34% yield, 110-112 ℃ melting point; 1 H NMR(500MHz,CDCl 3 )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,CDCl 3 )δ175.14,155.25,154.66,140.67,138.30,133.67,131.68,130.08,129.72,129.08,126.46,125.96,124.89,124.23,118.03,69.78,69.56,58.73,30.43,21.74；HRMS(m/z)calcd for C 20 H 20 O 4 (M+H) + :324.1362,found:324.1358.
2- (3-methylphenyl) -3-phenylmethoxy-4H-1-benzopyran-4-one (I12): yellow solid, yield 44%, melting point 131-132 ℃; 1 H NMR(500MHz,CDCl 3 )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)； 13 C NMR(300MHz,CDCl 3 )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 O 3 (M+H) + :324.1256,found:324.1251.
2- (4-bromophenyl) -3-phenylmethoxy-4H-1-benzopyran-4-one (I13): yellow solid, yield 46%, melting point 141-142 ℃; 1 H NMR(500MHz,CDCl 3 )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,CDCl 3 )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 BrO 3 (M+H) + :406.0205,found:406.0211.
2- (4-fluorophenyl) -3-phenylmethoxy-4H-1-benzopyran-4-one (I14): yellow solid, yield 40%, melting point 152-153 ℃; 1 H NMR(500MHz,CDCl 3 )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,CDCl 3 )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 for C 22 H 15 FO 3 (M+H) + :346.1005,found:346.1004.
2- [ 4-trifluoromethylphenyl group]-3-phenylmethoxy-4H-1-benzopyran-4-one (I15): yellow solid, 22% yield, melting point 155-156 ℃; 1 H NMR(500MHz,CDCl 3 )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,CDCl 3 )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 for C 23 H 15 F 3 O 3 (M+H) + :396.0973,found:396.0968.
2- (4-fluorophenyl) -3- (2-phenylethoxy) -4H-1-benzopyran-4-one (I16): yellow solid, 42% yield), melting point 141-143 ℃; 1 H NMR(500MHz,CDCl 3 )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,CDCl 3 )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 FO 3 (M+H) + :360.1162,found:360.1170.
2- (4-bromophenyl) -3- (2-phenylethoxy) -4H-1-benzopyran-4-one (I17): yellow solid, yield 54%, melting point 156-157 ℃; 1 H NMR(500MHz,CDCl 3 )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)； 13 C NMR(300MHz,CDCl 3 )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 BrO 3 (M+H) + :420.0361,found:420.0364.
2- (3-methylphenyl) -3- (2-phenylethoxy) -4H-1-benzopyran-4-one (I18): yellow solid, yield 46%, melting point 121-122 ℃; 1 H NMR(500MHz,CDCl 3 )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,CDCl 3 )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)calcd for C 24 H 20 O 3 (M+H) + :356.1412,found:356.1408.
2- [ 4-trifluoromethylphenyl group]-3- (2-phenylethoxy) -4H-1-benzopyran-4-one (I19): yellow solid, yield 26%, melting point 134-135 ℃; 1 H NMR(500MHz,CDCl 3 )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,CDCl 3 )δ175.25,155.30,154.05,141.14,138.30,134.12,132.05,131.79,129.07,128.90,128.50,126.53,126.00,125.29(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 F 3 O 3 (M+H) + :410.1130,found:410.1135.
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,CDCl 3 )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,CDCl 3 )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 O 3 (M+H) + :398.1882,found:398.1876.
2- (4-fluorophenyl) -3- [ (4-methylphenyl) methoxy group]-4H-1-benzopyran-4-one (I21): yellow solid, yield 40%, melting point 152-153 ℃; 1 H NMR(500MHz,CDCl 3 )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,CDCl 3 )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 FO 3 (M+H) + :360.1162,found:360.1165.
2- (4-methylphenyl) -3- [ (4-methoxyphenyl) methoxy group]-4H-1-benzopyran-4-one (I22): yellow solid, yield 53%, melting point 163-164 ℃; 1 H NMR(500MHz,CDCl 3 )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)； 13 C NMR(126MHz,CDCl 3 )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 O 4 (M+H) + :372.1363,found:372.1369.
2- (4-fluorophenyl) -3- [ (4-methoxyphenyl) methoxy group]-4H-1-benzopyran-4-one (I23): yellow solid, yield 43%, melting point 168-170 ℃; 1 H NMR(400MHz,CDCl 3 )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,CDCl 3 )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 O 4 (M+H) + :376.3834,found:376.3845.
2- [ (4-trifluoromethyl) phenyl ]]-3- [ (4-methoxyphenyl) methoxy group]-4H-1-benzopyran-4-one (I24): yellow solid, yield 29%, melting point 183-185 ℃; 1 H NMR(500MHz,CDCl 3 )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,CDCl 3 )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 FO 4 (M+H) + :376.3834,found:376.3845.
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,CDCl 3 )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,CDCl 3 )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 NO 5 (M+H) + :387.1107,found:387.1102.
2- (4-fluorophenyl) -3- [ (4-nitrophenyl) methoxy group]-4H-1-benzopyran-4-one (I26): yellow solid, yield 37%, melting point 169-170 ℃; 1 H NMR(500MHz,CDCl 3 )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,CDCl 3 )δ174.85,165.34,162.83,155.54,155.25,147.66,143.99,139.33,133.86,131.14,131.05,128.86,126.83,125.82,125.10,124.06,123.51,118.08,115.85,115.64,72.54；HRMS(m/z)calcd for C 22 H 14 FNO 5 (M+H) + :391.0856,found:391.0861.
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,CDCl 3 )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,1H),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)； 13 C NMR(101MHz,CDCl 3 )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 NO 5 (M+H) + :387.1107,found:387.1104.
example 28: the bactericidal activity of the flavonol derivatives I1-I27
The biological activity of the flavonol derivatives I1-I27 on 6 tested plant pathogenic bacteria of tomato early blight bacteria (Alternaria solani), wheat scab bacteria (Gibberella zeae), rice sheath blight bacteria (Rhizoctoriza solani), apple spot bacteria (Alternaria leafspot), strawberry gray mold bacteria (Botrytis cinerea) and Cucumber anthracnose bacteria (Cuumber anthracis) is determined by adopting a hypha growth method, and the specific operation steps are as follows:
1. weighing 15mg of raw medicine, dissolving in 0.6mLDMF, and preparing mother liquor;
2. adding 0.1mL of mother solution into 50mL of sterile potato dextrose agar medium (PDA medium) and shaking uniformly to obtain 50mg/L of drug-containing medium;
3. pouring the hot and equivalent culture medium into three sterile culture dishes with the diameter of 9 cm, cooling and solidifying, and inoculating a bacterial cake with the diameter of 0.5cm in the center of the culture medium;
4. a blank without test agent was set, and each treatment was repeated 3 times;
5. the above dishes were placed in a constant temperature incubator at 25.+ -. 1 ℃ for dark culture until the colony diameter was about 7.0 to 7.5 cm, and then the colony diameter was measured to calculate the inhibition ratio of each agent.
6. The formula for calculating the inhibition rate of the compound to fungi is as follows: antibacterial ratio = (diameter of control colony-diameter of test agent colony)/(diameter of control colony-5 mm) ×100%.
The test results of the inhibitory activities of the compounds I1-I27 on tomato early blight bacteria, wheat scab bacteria, rice sheath blight bacteria, apple alternaria alternate bacteria, strawberry gray mold bacteria and cucumber anthracnose bacteria are shown in Table 2:
TABLE 2 inhibition of 6 pathogens by Compounds I1-I27
/>
a Repeating for three times, and taking an average value; b taking a commercial medicament carbendazim as a control medicament; c the commercial drug boscalid is used as a control medicament.
The data in Table 2 show that the target compound I has a degree of antibacterial activity against six pathogens, especially against Rhizoctonia solani, botrytis cinerea and Rhizoctonia cerealis. The inhibition rate of 17 compounds to Rhizoctonia solani is more than 70%, namely I1, I3, I4, I5, I8, I9, I10, I11, I12, I13, I15, I18, I19, I22, I23, I24 and I26, and the inhibition rate of 4 compounds to Botrytis cinerea is more than 70%, namely I5, I8, I9 and I21; 3 compounds with the inhibition rate of more than 70 percent on cucumber anthracnose are I5, I8 and I9 respectively
Further EC of compounds with inhibition rate higher than 70% on corresponding germs respectively by analyzing inhibition rate data obtained by primary screening 50 The toxicity measurement method comprises the following steps:
weighing a compound to be tested to prepare mother solution, gradually diluting the mother solution to prepare a solution with gradient concentration, preparing a drug-containing flat plate, taking boscalid as a reference drug, respectively calculating the inhibition rate under each concentration according to an active preliminary screening method in the rest operation, and counting the softness by DPSThe component can obtain a linear regression equation and effectively inhibit the concentration (EC 50 ) And 95% confidence interval.
EC of part of the Compounds 50 The toxicity measurements are shown in table 3:
TABLE 3 EC of partial Compounds 50 Toxicity determination a
/>
a Repeating for three times, and taking an average value; b the commercial medicament carbendazim is used as a control medicament.
As can be seen from Table 3, the compounds I1, I3, I4, I5, I8, I9, I10, I11, I12, I13, I15, I18, I19, I22, I23, I24, I26 have an EC on Rhizoctonia solani 50 2.21. Mu.g/mL, 1.35. Mu.g/mL, 2.32. Mu.g/mL, 8.83. Mu.g/mL, 5.24. Mu.g/mL, 1.21. Mu.g/mL, 6.37. Mu.g/mL, 5.54. Mu.g/mL, 0.21. Mu.g/mL, 9.34. Mu.g/mL, 2.77. Mu.g/mL, 1.36. Mu.g/mL, 0.26. Mu.g/mL, 0.18. Mu.g/mL, 0.06. Mu.g/mL, 0.35. Mu.g/mL, 1.37. Mu.g/mL, respectively; EC of compounds I I, I8, I9, I21 against Botrytis cinerea 50 6.47 μg/mL, 12.31 μg/mL, 9.32 μg/mL, 1.37 μg/mL, respectively; EC of compounds I5, I8 and I9 on cucumber anthracnose pathogen 50 2.14. Mu.g/mL, 11.07. Mu.g/mL, and 1.73. Mu.g/mL, respectively.
The foregoing description is only a preferred embodiment of the present invention, and is not intended to limit the invention in any way, and any simple modification, equivalent variation and variation of the above embodiments according to the technical matter of the present invention falls within the scope of the technical scheme of the present invention.
Claims (10)
1. A flavonol derivative having a structure represented by general formula (I), or a pharmaceutically acceptable salt, solvate, optical isomer or polymorph thereof:
R 1 selected from hydrogen, halogen, alkyl or alkoxy;
R 2 selected from hydrogen, alkyl or alkoxy.
2. The flavonol derivative according to claim 1, or a pharmaceutically acceptable salt, solvate, optical isomer or polymorph thereof, wherein R 1 Selected from hydrogen, methyl, trifluoromethyl, halogen or methoxy;
preferably, R 1 Any one selected from hydrogen, 4-methyl, 3-methyl, 4-fluoro, 4-chloro, 4-bromo, 4-trifluoromethyl, 4-methoxy and 4-tert-butyl;
more preferably, R 1 Any one selected from hydrogen, 4-methyl, 3-methyl, 4-fluoro, 4-bromo, 4-trifluoromethyl, 4-methoxy or 4-t-butyl.
3. The flavonol derivative according to claim 1, or a pharmaceutically acceptable salt, solvate, optical isomer or polymorph thereof, wherein R is 1 Selected from the group consisting of hydrogen, 4-fluoro, 4-methyl, 4-t-butyl, 3-methyl, 4-bromo, 4-trifluoromethyl.
4. The flavonol derivative according to claim 1, or a pharmaceutically acceptable salt, solvate, optical isomer or polymorph thereof, wherein R is 2 Selected from ethyl, propyl, isopropyl, isobutyl, 3-methoxypropyl, 4-methoxyphenyl, 4-nitrophenyl, benzyl or 2-phenylethyl.
5. The flavonol derivative according to claim 1, or a pharmaceutically acceptable salt, solvate, optical isomer or polymorph thereof, wherein R is 2 Selected from ethyl, isopropyl, 3-methoxypropyl, benzyl, 2-phenylethyl, 4-methoxyphenyl or 4-nitrophenyl.
6. A flavonol derivative, or a pharmaceutically acceptable salt, solvate, optical isomer or polymorph thereof, selected from any one of the following I1-I27:
7. use of a flavonol derivative according to any one of claims 1 to 6, or a pharmaceutically acceptable salt, solvate, optical isomer or polymorph thereof for controlling plant fungal diseases.
8. Use of a flavonol derivative according to any one of claims 1 to 6, or a pharmaceutically acceptable salt, solvate, optical isomer or polymorph thereof, for the preparation of a reagent for controlling plant fungal diseases.
9. The use according to any one of claims 7-8, wherein the fungus is rhizoctonia solani, colletotrichum cucumerinum, alternaria solani, gibberella wheat, alternaria mali or botrytis cinerea.
10. The use according to any one of claims 7-8, wherein the fungal disease is rice sheath blight, cucumber anthracnose, tomato early blight, wheat scab, apple alternaria leaf spot or strawberry gray mold.
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