CN115232070B - Quinolinone alkaloid derivative containing acylhydrazone group on 1-position nitrogen atom, and preparation method and application thereof - Google Patents

Quinolinone alkaloid derivative containing acylhydrazone group on 1-position nitrogen atom, and preparation method and application thereof Download PDF

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CN115232070B
CN115232070B CN202210783046.XA CN202210783046A CN115232070B CN 115232070 B CN115232070 B CN 115232070B CN 202210783046 A CN202210783046 A CN 202210783046A CN 115232070 B CN115232070 B CN 115232070B
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杨岩
孟亚楠
崔培培
吕永康
张建栋
庞晋纬
吴心阳
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Taiyuan University of Technology
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Abstract

The invention aims to provide a quinolinone alkaloid derivative containing an acylhydrazone group on a 1-position nitrogen atom, a preparation method thereof and application thereof in the aspect of controlling plant viruses, and belongs to the technical field of pesticides. Firstly, reacting 1H-quinolin-4-one with alpha-bromoethyl acetate in a solvent in the presence of a base at room temperature to form (oxo-4H-quinolin-1-yl) -ethyl acetate; secondly, reacting (oxo-4H-quinolin-1-yl) -ethyl acetate with water and hydrazine in a solvent to form (4-oxo-4H-quinolin-1-yl) -acethydrazide; thirdly, reacting (4-oxo-4H-quinolin-1-yl) -acethydrazide with aldehyde in a solvent to form a quinolinone alkaloid derivative having an acylhydrazone group on the 1-position nitrogen atom. The compound of the invention shows the activity of resisting the tobacco mosaic virus, and the activity of resisting the tobacco mosaic virus of part of the compounds is higher than that of ribavirin.

Description

Quinolinone alkaloid derivative containing acylhydrazone group on 1-position nitrogen atom, and preparation method and application thereof
Technical Field
The invention belongs to the technical field of pesticides, and particularly relates to a quinolinone alkaloid derivative containing an acylhydrazone group on a 1-position nitrogen atom, and a preparation method and application thereof.
Background
The plant virus has more than 900, can greatly reduce the yield of grains and cause huge economic loss. Tobacco mosaic virus is an RNA virus capable of infecting 260 plants of 38 families such as tomatoes, potatoes, peppers, etc., causing serious economic losses (Huang, y.q. et al j. Agric. Food chem. 2018, 66, 8253-8261). At present, common tobacco mosaic virus inhibitors are ningnanmycin and ribavirin. However, both plant virus inhibitors are not environmentally friendly and the antiviral activity is to be improved. At present, the literature reports that various natural product derivatives have anti-tobacco mosaic virus activity (Yang, s.et al molecular, 2021, 26, 383.zou, j.b. et al j.agric.food chem., 2020, 68, 15015-15026). However, quinolinone alkaloid derivatives have been rarely studied as tobacco mosaic virus inhibitors.
Disclosure of Invention
The invention aims to provide a quinolinone alkaloid derivative containing an acylhydrazone group on a 1-position nitrogen atom, a preparation method thereof and application thereof in the aspect of preventing and treating plant viruses. The quinolinone alkaloid derivative containing the acylhydrazone structure on the 1-position nitrogen atom shows good activity of resisting and treating the tobacco mosaic virus.
The invention adopts the following technical scheme:
a quinolinone alkaloid derivative containing acylhydrazone group on 1-position nitrogen atom has a structural general formula shown in formula (I):
Figure 407099DEST_PATH_IMAGE001
wherein, the compound of formula (I),r includes any one of a 2-10 carbon hydrocarbon group, a 3-6 carbon cycloalkyl group, a benzyl group, a phenethyl group, a naphthyl group, a substituted phenyl group, a 1-10 carbon nitrogen-containing heterocycle, a 1-10 carbon oxygen-containing heterocycle, and a 1-10 carbon sulfur-containing heterocycle.
Further, the substituent of the substituted phenyl group includes any one or both of hydrogen, hydroxyl, halogen atom, cyano, nitro, ester group, fluorine, trifluoromethyl, trifluoromethoxy, 1-5 carbon hydrocarbon group and 1-6 carbon alkoxy group, and contains 2 to 3 of the above substituents.
Further, a quinolinone alkaloid derivative containing an acylhydrazone group on the 1-position nitrogen atom includes (4-oxo-4H-quinolin-1-yl) -acetylbenzylidene hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-methyl-benzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-tert-butylbenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-phenylbenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (3-phenoxybenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-methylthiobenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-methylsulfonylbenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-pyrazol-1-benzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-fluoro-4-benzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-chlorobenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-bromobenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-nitrobenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-trifluoromethyl benzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (4-dimethylaminobenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (2-nitrobenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (pyridin-3-ylmethylene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (furan-2-ylmethylene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (thiophen-2-ylidene) acetyl (4-oxo-4-quinolin-1-yl) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (indol-2-ylmethylene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (benzofuran-3-ylmethylene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (9-ethyl-9H-carbazol-3-ylmethylene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (3, 4-dimethoxybenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (5-bromo-2-methoxybenzylidene) hydrazine, (4-oxo-4H-quinolin-1-yl) -acetyl (3, 5-dibromo-4-hydroxybenzylidene) hydrazine.
A preparation method of quinolinone alkaloid derivative containing acylhydrazone group on 1-position nitrogen atom comprises the following steps:
firstly, reacting 1H-quinolin-4-one with alpha-bromoethyl acetate in a solvent in the presence of a base at room temperature to form (oxo-4H-quinolin-1-yl) -ethyl acetate;
secondly, reacting (oxo-4H-quinolin-1-yl) -ethyl acetate with water and hydrazine in a solvent to form (4-oxo-4H-quinolin-1-yl) -acethydrazide;
thirdly, reacting (4-oxo-4H-quinolin-1-yl) -acethydrazide with aldehyde in a solvent to form a quinolinone alkaloid derivative having an acylhydrazone group on the 1-position nitrogen atom.
Further, the solvent in the first step comprises N, N-dimethylformamide.
Further, the base in the first step includes any one of cesium carbonate, sodium carbonate and potassium carbonate.
Further, the solvent in the second step comprises methanol.
Further, the reaction temperature in the second step is 65 ℃.
Further, the solvent in the third step includes any one of methanol, ethanol and acetonitrile.
Further, the temperature of the reaction in the third step is 20-130 ℃.
Further, the aldehyde in the third step includes any one of benzaldehyde, 4-methylbenzaldehyde, 4-t-butylbenzaldehyde, 4-phenylbenzaldehyde, 3-methoxybenzaldehyde, 4-methylthiobenzaldehyde, 4-methylsulfonylbenzaldehyde, pyrazole-1-carbaldehyde, 4-fluorobenzaldehyde, 4-chlorobenzaldehyde, 4-bromobenzaldehyde, 4-nitrobenzaldehyde, 4-trifluoromethylbenzaldehyde, 4-dimethylaminobenzaldehyde, 2-nitrobenzaldehyde, pyridine-3-carbaldehyde, furan-2-carbaldehyde, thiophene-2-carbaldehyde, thiazole-4-carbaldehyde, indole-2-carbaldehyde, benzofuran-3-carbaldehyde, 9-ethyl-9H-carbazol-3-carbaldehyde, 3, 4-dimethoxybenzaldehyde, 5-bromo-2-methoxybenzaldehyde and 3, 5-dibromo-4-hydroxybenzaldehyde.
A quinolinone alkaloid derivative containing an acylhydrazone group on a 1-position nitrogen atom is applied to prevention and treatment of tobacco mosaic virus.
The beneficial effects of the invention are as follows:
the compound of the invention shows the activity of resisting the tobacco mosaic virus, and the activity of resisting the tobacco mosaic virus of part of the compounds is higher than that of ribavirin.
Drawings
FIG. 1 is a flow chart of the preparation method of the invention.
Detailed Description
The following examples and green test results are intended to further illustrate the invention and are not meant to limit the invention.
As shown in fig. 1:
in the first step, preparation of compound b:
DMF (100 mL), compound a (4.35 g,30 mmol), K were added sequentially in a 250 mL single-necked flask 2 CO 3 (6.22 g,45 mmol) and ethyl bromoacetate (8.02 g,48 mmol). The reaction was stirred at room temperature for 12 hours and TLC monitored the reaction was complete. Water (100 mL) was added to the reaction mixture, followed by CH 2 Cl 2 The extraction was performed three times and the organic phases were combined. The organic phase was washed three times with saturated brine (200 mL), dried over anhydrous sodium sulfate, spin-distilled to remove the solvent, and subjected to column chromatography (eluent: CH) 2 Cl 2 /CH 3 Oh=20:1) to give b (5.364 g, 77.4%) as a white solid. Melting point 157 o C。 1 H NMR (400Hz，CDCl 3 ) 8.45 (d，J = 8.0 Hz，1H)，7.66 - 7.62 (m，1H)，7.47 (d，J = 7.6 Hz，1H)，7.40 - 7.37 (m，1H)，7.19 (d，J = 8.4 Hz，1H)，6.29 (d，J = 7.6 Hz，1H)，4.77 (s，2H)，4.24 (q，J = 7.2 Hz，2H)，1.25 (t，J = 7.2 Hz，3H). 13 C NMR (100Hz，CDCl 3 ) 178.4，167.2，143.7，140.2，132.5，127.3，127.1，124.0，114.6，110.8，62.4，54.0，14.1. ESI-HRMS(m/z):Calcd. for C 13 H 14 NO 3 [M+H] + 232.0974；found 232.0965。
In the second step, preparation of compound c:
methanol (300 mL), compound b (2.31 g,10 mmol) and hydrazine hydrate (5 g,80%,100 mmol) were added sequentially to a 500 mL single-port flask, and the reaction was refluxed for 8 hours, followed by TLC to monitor the completion of the reaction. The reaction solution was cooled to room temperature, and most of the methanol was removed by rotary evaporation until a large amount of white solid was precipitated. Filtration under reduced pressure afforded c (1.775 g, 81.8%) as a white solid, melting point 240 o C。 1 H NMR (400Hz，DMSO-d 6 ) 9.53 (s，1H)，8.17 (d，J = 7.2 Hz，1H)，7.92 (d，J = 7.6 Hz，1H)，7.72 - 7.68 (m，1H)，7.44 (d，J = 8.8 Hz，1H)，7.39 - 7.35 (m，1H)，6.07 (d，J = 7.6 Hz，1H)，4.86 (s，2H)，4.36 (s，2H). 13 C NMR (100Hz，DMSO-d 6 ) 176.5，166.0，145.7，140.3，132.0，126.5，125.7，123.3，116.0，108.7，52.8. ESI-HRMS(m/z):Calcd. for C 11 H 12 N 3 O 2 [M+H] + 218.0930；found 218.0924。
Third step, quinolinone alkaloid derivative (I) containing acylhydrazone group on 1-position nitrogen atom 1 - I 25 ) Is prepared from the following steps:
example 1
(4-oxo-4H-quinolin-1-yl) -acetylbenzylidene hydrazine (I) 1 ) Is a benzaldehyde.
Methanol (50 mL), compound c (0.217 g,1 mmol), benzaldehyde d were added sequentially to a 100mL round bottom flask 1 (0.106 g,1 mmol) and the reaction was refluxed for 12 hours and monitored by TLC. The reaction solution was cooled to room temperature, and most of the methanol was removed by rotary evaporation until a large amount of white solid was precipitated. Filtering under reduced pressure to obtain yellow solid I 1 (0.2308 g, 75.7%). Melting point 260 ℃. 1 H NMR (400Hz，DMSO-d 6 ) 11.93 and 11.84 (s，1H)，8.19 (dd，J = 8.0，2.0 Hz，1H)，8.10 (s，1H)，8.01 - 7.97 (m，1H)，7.81 - 7.78 (m，2H)，7.73 - 7.65 (m，2H)，7.50 - 7.44 (m，3H)，7.39 - 7.35 (m，1H)，6.12 - 6.09 (m，1H)，5.55 (s，2H). 13 C NMR (100Hz，DMSO-d 6 ) 176.5，168.3 and 163.9，147.7 and 144.3，145.7 and 145.5，140.7，133.9，131.9，130.1，128.8，127.1，126.4，125.7 and 125.5，123.2 and 123.1，116.5 and 116.1，108.8，53.2 and 52.8. ESI-HRMS(m/z):Calcd.for C 18 H 16 N 3 O 2 [M+H] + 306.1237; found 306.1239。
Example 2
(4-oxo-4H-quinolin-1-yl) -acetyl (4-methyl-benzylidene) hydrazine (I) 2 ) The aldehyde is 4-methylbenzaldehyde.
0.229g of pale yellow solid was obtained in 71.8% yield. Melting point 232 ℃. 1 H NMR (400Hz，DMSO-d 6 ) 11.88 and 11.79 (s，1H)，8.23 and 8.06 (s，1H)，8.19 (d，J = 8.0 Hz，1H)，8.01 - 7.97 (m，1H)，7.73 - 7.59 (m，3H)，7.50 - 7.35 (m，2H)，7.29 - 7.24 (m，2H)，6.12 - 6.09 (m，1H)，5.53 and 5.06 (s，2H)，2.35 and 2.33 (s，3H). 13 C NMR (100Hz，DMSO-d 6 ) 176.7，168.2 and 163.3，147.8 and 144.5，145.8 and 145.6，140.7，140.0，132.2 and 132.0，131.2，129.5，127.2 and 127.1，126.4，125.6，123.4 and 123.2，116.6，108.9，53.3 and 52.9，21.1. ESI-HRMS(m/z):Calcd. for C 19 H 18 N 3 O 2 [M+H] + 320.1399；found 320.1396。
Example 3
(4-oxo-4H-quinolin-1-yl) -acetyl (4-t-butylbenzylidene) hydrazine (I) 3 ) The aldehyde is 4-tert-butylbenzaldehyde.
0.2266g of pale yellow solid was found to be 62.8% yield. Melting point of more than 300 o C。 1 H NMR (400Hz, DMSO-d 6 ) 11.87 and 11.80 (s, 1H), 8.24 and 8.07 (s, 1H), 8.20 (d, J = 8.0 Hz, 1H), 8.01 and 7.98 (d, J = 7.6 Hz, 1H), 7.73 - 7.70 (m, 2H), 7.67 - 7.63 (m, 1H), 7.50 -7.48 (m, 2H), 7.46 -7.35 (m, 2H), 6.12 - 6.09 (m, 1H), 5.52 and 5.06 (s, 2H), 1.30 and 1.28 (s, 9H). 13 C NMR (100Hz, DMSO-d 6 ) 176.6, 168.1 and 163.2, 153.1 and 153.0, 147.7 and 144.4, 145.8 and 145.6, 140.7 and 140.5, 132.1 and 132.0, 131.2, 127.0 and 126.9, 126.4 and 125.6, 123.4 and 123.2, 116.4 and 116.1, 108.8, 53.3 and 52.8, 34.6, 31.0. ESI-HRMS(m/z):Calcd. for C 22 H 24 N 3 O 2 [M+H] + 362.1869; found 362.1864。
Example 4
(4-oxo-4H-quinolin-1-yl) -acetyl (4-phenylbenzylidene) hydrazine (I 4 ) The aldehyde is 4-phenylbenzaldehyde.
0.3509g of white solid was obtained in 92.1% yield. Melting point 260 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 11.97 and 11.89 (s, 0.75H), 8.32 and 8.14 (s, 0.24H), 8.20 (d, J = 7.6 Hz, 1H), 8.02 (d, J = 8.0 Hz,1H), 7.90 - 7.88 and 7.82 - 7.66 (m, 7H), 7.51 -7.46 (m, 3H), 7.42 - 7.35 (m, 2H), 6.13 -6.10 (m, 1H), 5.57 and 5.09 (s, 1H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 168.3 and 163.4, 147.3 and 144.0, 145.8 and 145.6, 144.0, 141.6, 140.7 and 140.5, 139.3, 133.0, 132.0, 129.1, 128.0, 127.8 and 127.7, 127.0, 126.7 and 126.4, 125.7 and 125.6, 123.4 and 123.2, 116.6 and 116.2, 108.9, 53.3 and 52.9. ESI-HRMS(m/z):Calcd. for C 24 H 20 N 3 O 2 [M+H] + 382.1556; found 382.1554。
Example 5
(4-oxo-4H-quinolin-1-yl) -acetyl (3-phenoxybenzal) hydrazine (I) 5 ) The aldehyde is 3-methoxybenzaldehyde.
0.2344g of yellow solid was found to be 70.0% yield. Melting Point 202 o C。 1 H NMR (400Hz, DMSO-d 6 ) 12.01 and 11.90 (s, 1H), 8.26 and 8.07 (s, 1H), 8.21 (d, J = 8.0 Hz, 1H), 8.02 (d, J =7.6 Hz, 1H), 7.72 - 7.66 (m, 1H), 7.47 - 7.35 (m, 5H), 7.05 - 7.01 (m, 1H), 6.14 - 6.10 (m, 1H), 5.57 and 5.09 (s, 2H), 3.82 and 3.79 (s, 3H). 13 C NMR (100Hz, DMSO-d 6 ) 177.1, 168.8 and 163.9, 160.0, 148.1 and 144.7, 146.3 and 146.1, 141.4 and 140.9, 135.8, 132.6 and 132.4, 130.4, 126.9, 126.2 and 126.0, 123.9 and 123.7, 120.5 and 120.3, 117.0 and 116.9, 116.6, 112.1 and 112.0, 109.3, 55.7 and 55.6, 53.8 and 53.3. ESI-HRMS(m/z):Calcd. for C 19 H 18 N 3 O 3 [M+H] + 336.1348; found 336.1343。
Example 6
(4-oxo-4H-quinolin-1-yl) -acetyl (4-methylthiobenzylidene) hydrazine (I 6 ) Is 4-methylthiobenzaldehyde.
0.1436g of yellow solid was found to be 42.8% yield. Melting point 265 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 11.90 and 11.83 (s, 1H), 8.22 and 8.05 (s, 1H), 8.20 (d, J = 8.0 Hz, 1H), 8.00 (d, J = 7.6 Hz, 1H), 7.73 - 7.63 (m, 3H),7.50 -7.44 (m, 1H), 7.40 -7.30 (m, 3H), 6.12 -6.09 (m, 1H), 5.33 and 5.07 (s, 2H), 2.51 and 2.50 (s, 3H). 13 C NMR (100Hz, DMSO-d 6 ) 177.1, 168.6 and 163.7, 147.8 and 144.5, 146.2 and 146.1, 141.8 and 141.5, 141.2 and 140.9, 132.6 and 132.4, 130.8, 128.1 and 128.0, 126.9, 126.2 and 126.1, 123.8 and 123.7, 117.0 and 116.6, 109.3, 53.8 and 53.3, 14.7 and 14.6. ESI-HRMS(m/z):Calcd. for C 19 H 18 N 3 O 2 S [M+H] + 352.1120; found 352.1117。
Example 7
(4-oxo-4H-quinolin-1-yl) -acetyl (4-methanesulfonyl benzylidene) hydrazine (I 7 ) Is 4-methanesulfonyl benzaldehyde.
0.2884g of yellow solid was found to be 75.3% yield. The melting point is greater than 300 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 12.18 and 12.09 (s, 1H), 8.35 and 8.17(s, 1H), 8.20 (d, J = 8.0 Hz, 1H), 8.07 - 7.96 (m, 5H), 7.73 -7.65 (m, 1H), 7.51 -7.46 (m, 1H), 7.40 - 7.35 (m, 1H), 6.11 (d, J = 7.6 Hz, 1H), 5.59 and 5.12 (s, 2H). 3.27 and 3.25 (s, 3H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 168.7 and 163.8, 145.9 and 142.6, 145.8 and 145.6, 141.6 and 141.4, 140.7 and 140.5, 138.7, 132.2 and 132.0, 127.8, 127.5, 126.4, 125.8 and 125.6, 123.5 and 123.3, 116.6 and 116.2, 108.9, 53.3 and 52.9, 43.4. ESI-HRMS(m/z):Calcd. for C 19 H 18 N 3 O 4 S [M+H] + 384.1018; found 384.1015。
Example 8
(4-oxo-4H-quinoline)-1-yl) -acetyl (4-pyrazol-1-yl-benzylidene) hydrazine (I 8 ) The aldehyde is pyrazole-1-formaldehyde.
White solid 0.26g, yield 70.1%. Melting point 284 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 11.98 and 11.89 (s, 1H), 8.60 and 8.58 (s, 1H), 8.30 and 7.80 (s, 1H), 8.19 (d, J = 8.0 Hz, 1H), 8.12 (s, 1H), 8.01 (d, J = 7.6 Hz, 1H), 7.97 - 7.91 and 7.85 -7.82 (m, 4H), 7.74 - 7.66 (m, 1H), 7.51 - 7.46 (m, 1H), 7.41 -7.35 (m, 1H), 6.59 (s, 1H), 6.11 (d, J = 7.2 Hz, 1H), 5.58 and 5.09 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 168.3 and 163.4, 146.9 and 146.3, 145.8 and 145.6, 141.5, 140.8 and 140.7, 140.6 and 140.5, 132.2 and 132.0, 131.7 and 131.6, 128.5 and 128.4, 128.0 and 127.9, 126.4, 125.8 and 125.6, 123.4 and 123.2, 118.5 and 118.4, 116.6 and 116.2, 108.9, 108.3, 53.3 and 52.9. ESI-HRMS(m/z):Calcd. for C 21 H 18 N 5 O 2 [M+H] + 372.1461; found 372.1457。
Example 9
(4-oxo-4H-quinolin-1-yl) -acetyl (4-fluorobenzylidene) hydrazine (I 9 ) The aldehyde is 4-fluorobenzaldehyde.
0.2515g of yellow solid was found to be 77.9% yield. Melting point 280 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 11.93 and 11.85 (s, 1H), 8.27 and 8.03 (s, 1H), 8.20 - 8.17 (m, 1H), 8.00 -7.97 (m, 1H), 7.88 - 7.65 (m, 3H), 7.49 - 7.27 (m, 4H), 6.11 - 6.08 (m, 1H), 5.54 and 5.06 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.6 and 164.3, 168.3 and 163.3, 146.6 and 143.2, 145.7 and 145.5, 140.7 and 139.6, 132.1 and 132.0, 129.3, 129.2, 126.4, 125.7 and 125.5, 123.3 and 123.1, 116.5, 116.1 and 116.0, 115.7, 108.8, 53.3 and 52.8. ESI-HRMS(m/z):Calcd. for C 18 H 15 FN 3 O 2 [M+H] + 324.1148; found 324.1145。
Example 10
(4-oxo-4H-quinolin-1-yl) -acetyl (4-chlorobenzyl) hydrazine (I 10 ) The aldehyde is 4-chlorobenzaldehyde.
Yellow solid 0.179g, yield 52.8%. Melting point 260 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 12.03 and 11.92 (s, 1H), 8.27 and 8.08 (s, 1H), 8.19 (d, J = 8.4 Hz, 1H), 8.01 - 7.97 (m, 1H), 7.83 and 7.74 (m, 2H), 7.69 - 7.64 (m, 1H), 7.55 - 7.44 (m, 3H), 7.40 - 7.34 (m, 1H), 6.12 -6.09 (m, 1H), 5.55 and 5.08 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7 and 176.6, 168.4 and 163.5, 146.5 and 143.1, 145.8 and 145.6, 140.7 and 140.5, 134.8 and 134.6, 132.9, 132.1 and 132.0, 129.0 and 128.9, 128.8 and 128.7, 126.5 and 126.4, 125.7 and 125.6, 123.4 and 123.2, 116.6 and 116.2, 108.9, 53.3 and 52.8. ESI-HRMS(m/z):Calcd. for C 18 H 15 ClN 3 O 2 [M+H] + 340.0853; found 340.0849。
Example 11
(4-oxo-4H-quinolin-1-yl) -acetyl (4-bromobenzylidene) hydrazine (I) 11 ) The aldehyde is 4-bromobenzaldehyde.
0.2845g of yellow solid was found to be 74.1% yield. Melting point 282 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 12.00 and 11.91 (s, 1H), 8.25 and 8.06 (s, 1H), 8.21-8.17 (m, 1H), 8.00-7.97 (m, 1H), 7.77 -7.45 (m, 2H), 7.68 - 7.65 (m, 3H), 7.49 - 7.44 (m, 1H), 7.40 - 7.35 (m, 1H), 6.12 - 6.07 (m, 1H), 5.55 and 5.07 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.5, 168.4 and 163.4, 146.3 and 143.1, 145.7 and 145.5, 140.6, 133.2, 131.8 and 131.7, 128.9, 126.4, 125.5, 123.3, 123.1, 116.5, 108.8, 53.2 and 52.8. ESI-HRMS(m/z):Calcd. for C 18 H 15 BrN 3 O 2 [M+H] + 384.0348; found 384.0345。
Example 12
(4-oxo-4H-quinolin-1-yl) -acetyl (4-nitrobenzyl) hydrazine (I) 12 ) The aldehyde is 4-nitrobenzaldehyde.
0.3148g of pale yellow solid was obtained in 90.0% yield. Melting point 292 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 12.26 and 12.15 (s, 1H), 8.32 - 8.28 (m, 2H), 8.20 - 8.17 (m, 2H), 8.08 - 7.97 (m, 3H), 7.71 - 7.65 (m, 1H), 7.50 - 7.47 (m, 1H), 7.41 - 7.35 (m, 1H), 6.12 - 6.10 (m, 1H), 5.60 and 5.12 (s, 0.42H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 168.8 and 164.8, 148.0 and 147.9, 145.8 and 145.6, 145.4 and 142.0, 140.7, 140.2, 132.8 and 132.0, 128.2 and 128.1, 126.4, 125.8 and 125.6, 124.0, 123.4 and 123.3, 116.6 and 116.2, 108.9, 53.3 and 52.9. ESI-HRMS(m/z):Calcd. for C 18 H 15 N 4 O 4 [M+H] + 351.1093; found 351.1087。
Example 13
(4-oxo-4H-quinolin-1-yl) -acetyl (4-trifluoromethylbenzylidene) hydrazine (I) 13 ) Is 4-trifluoromethyl benzaldehyde.
0.2582g of yellow solid was found to be 69.2% yield. Melting point 270 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 12.14 and 12.05 (s, 1H), 8.35 and 8.16 (s, 1H), 8.21- 8.18 (m, 1H), 8.03- 7.92 (m, 3H), 7.84 -7.80 (m, 2H), 7.69 -7.65 (m, 1H), 7.50 - 7.46 (m, 1H), 7.39 -7.35 (m, 1H), 6.13 - 6.10 (m, 1H), 5.58 and 5.11 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 168.7 and 163.7, 145.8 and 145.6, 142.7, 140.7 and 140.5, 137.9, 132.2 and 132.0, 127.8 and 127.7, 126.4, 125.7, 125.6, 125.5, 123.4 and 123.2, 116.6 and 116.2, 108.9, 53.3 and 52.8. ESI-HRMS(m/z):Calcd. for C 19 H 15 F 3 N 3 O 2 [M+H] + 374.1116; found 374.1110。
Example 14
(4-oxo-4H-quinolin-1-yl) -acetyl (4-dimethylaminobenzylidene) hydrazine (I) 14 ) The aldehyde is 4-dimethylaminobenzaldehyde.
Orange solid 0.255g, 73.3% yield. Melting point 160 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 11.65 and 11.57 (s, 1H), 8.19 (d, J = 8.0 Hz, 1H), 8.11 and 7.95(s, 1H), 8.01- 7.96 (m, 1H), 7.69 - 7.57 (m, 3H), 7.52 - 7.34 (m, 2H), 6.77 -6.72 (m, 2H), 6.11 - 6.08 (m, 1H), 5.48 and 5.02 (s, 2H), 2.97 and 2.96 (s, 6H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 167.6 and 162.6, 151.7 and 151.5, 148.5 and 145.3, 145.9 and 145.7, 140.7 and 140.5, 132.2 and 132.0, 128.6, 128.4, 126.5 and 126.4, 125.7 and 125.6, 123.4 and 123.2, 121.2 and 121.1, 116.5 and 116.2, 111.8, 108.8 and 108.7, 53.4 and 52.8, 39.8. ESI-HRMS(m/z):Calcd. for C 20 H 21 N 4 O 2 [M+H] + 349.1665; found 349.1660。
Example 15
(4-oxo-4H-quinolin-1-yl) -acetyl (2-nitrobenzyl) hydrazine (I) 15 ) The aldehyde is 2-nitrobenzaldehyde.
0.278g of pale yellow solid was obtained in 79.4% yield. Melting point 250 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 12.29 and 12.14 (s, 1H), 8.49 (s, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.20 (d, J = 7.6 Hz, 1H), 8.10 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 7.6 Hz, 1H), 7.85 - 7.82 (m, 1H), 7.72 - 7.67 (m, 2H), 7.52 - 7.47 (m, 1H), 7.40 - 7.35 (m, 1H), 6.13 - 6.10 (m, 1H), 5.57 and 5.12 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 168.6 and 163.8, 148.2 and 148.1, 145.7 and 145.5, 143.4 and 140.0, 140.7 and 140.5, 133.9 and 133.6, 133.2 and 132.0, 130.9 and 130.8, 128.6 and 128.5, 128.2 and 128.1, 126.4, 125.7 and 125.6, 124.8 and 124.6, 123.4 and 123.3, 116.5 and 116.2, 108.9, 53.2 and 52.8.ESI-HRMS(m/z):Calcd. for C 18 H 15 N 4 O 4 [M+H] + 351.1093; found 351.1090。
Example 16
(4-oxo-4H-quinolin-1-yl) -acetyl (pyridin-3-ylmethylene) hydrazine (I) 16 ) Is pyridine-3-formaldehyde.
0.2381g of yellow solid was found to be 77.8% yield. Melting point 260 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 12.09 and 12.01 (s, 1H), 8.97 and 8.86 (s, 1H), 8.63 - 8.60 (m, 1H), 8.33 - 8.18 (m, 2H), 8.13 (s, 1H), 7.99 (d, J = 7.60 Hz, 1H), 7.69 - 7.65 (m, 1H), 7.51 - 7.35 (m, 3H), 6.10 (d, J = 7.60 Hz, 1H), 5.58 and 5.09 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 168.6 and 163.6, 150.9 and 150.7, 148.9 and 148.7, 145.8 and 145.6, 145.2 and 141.7, 140.7 and 140.5, 133.8 and 133.6, 132.2 and 132.0, 129.9, 126.4, 125.8 and 125.6, 124.1 and 124.0, 123.5 and 123.3, 116.6 and 116.2, 108.9, 53.3 and 52.9. ESI-HRMS(m/z):Calcd. for C 17 H 15 N 4 O 2 [M+H] + 307.1195; found 307.1190。
Example 17
(4-oxo-4H-quinolin-1-yl) -acetyl (furan-2-ylmethylene) hydrazine (I 17 ) The aldehyde is furan-2-formaldehyde.
The earthy yellow solid is 0.281g and the yield is 95.3 percent. Melting point 270 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 11.90 and 11.82 (s, 1H), 8.20 (d, J = 8.0 Hz, 1H), 8.16 and 7.99 (s, 1H), 8.00 (d, J = 8.4 Hz, 1H), 7.87 and 7.83 (s, 1H), 7.71 - 7.64 (m, 1H), 7.49 - 7.34 (m, 2H), 6.98 - 6.95 (d, J = 3.6 Hz, 1H), 6.66 - 6.65 and 6.63 - 6.62 (m, 1H), 6.13 - 6.10 (m, 1H), 5.45 and 5.07(s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 168.0 and 163.3, 148.9, 145.8 and 145.7, 145.4 and 145.2, 140.7 and 140.5, 138.2 and 134.6, 132.1 and 132.0, 129.4, 125.8 and 125.6, 123.4 and 123.2, 116.5 and 116.2, 114.3 and 114.1, 112.3, 108.9, 53.3 and 52.8. ESI-HRMS(m/z):Calcd. for C 16 H 14 N 3 O 3 [M+H] + 296.1035; found 296.1030。
Example 18
(4-oxo-4H-quinolin-1-yl) -acetyl (thiophen-2-ylmethylene) hydrazine (I) 18 ) The aldehyde is thiophene-2-formaldehyde.
0.2781g of white solid was found to be 89.4% yield. Melting point 290 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 11.87 and 11.81 (s, 1H), 8.47 and 8.27 (s, 1H), 8.18 (d, J = 8.0 Hz, 1H), 8.00 - 7.98 (d, J = 7.6 Hz, 1H), 7.73 - 7.65 (m, 2H), 7.51 - 7.49 (m, 1H), 7.47 - 7.34 (m, 2H), 7.16 - 7.13 (m, 1H), 6.11 - 6.08 (m, 1H), 5.42 and 5.05 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.6, 167.8 and 163.1, 145.7 and 145.6, 142.9 and 139.6, 140.6 and 140.4, 138.6 and 138.5, 132.1 and 132.0, 131.4 and 130.9, 129.2 and 128.9, 127.9, 126.4, 125.7 and 125.5, 123.3 and 123.2, 116.4 and 116.1, 108.8, 53.2 and 52.6. ESI-HRMS(m/z):Calcd. for C 16 H 14 N 3 O 2 S[M+H] + 312.0807; found 312.0802。
Example 19
(4-oxo-4H-quinolin-1-yl) -acetyl (thiazol-4-ylmethylene) hydrazine (I) 19 ) The aldehyde is thiazole-4-formaldehyde.
0.1695g of white solid was found to be 54.3% yield. Melting point 226 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 11.95 and 11.89 (s, 1H), 9.21 -9.18 (m, 1H), 8.41 and 8.26 - 8.16 (m, 3H), 8.01 - 7.97 (m, 1H), 7.73 - 7.65 (m, 1H), 7.49 - 7.35 (m, 2H), 6.11 - 6.08 (m, 1H), 5.49 and 5.08 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.6, 168.2 and 163.4, 155.2 and 155.1, 151.2 and 151.1, 145.7 and 145.6, 140.6 and 140.4, 139.1, 132.1 and 132.0, 126.4, 125.7 and 125.6, 123.3 and 123.2, 120.2 and 119.9, 116.4 and 115.6, 108.8, 53.3 and 52.7. ESI-HRMS(m/z):Calcd. for C 15 H 13 N 4 O 2 S[M+H] + 313.0759; found 313.0753。
Example 20
(4-oxo-4H-quinolin-1-yl) -acetyl (indol-2-ylmethylene) hydrazine (I) 20 ) The aldehyde is indole-2-carbaldehyde.
Yellow solid 0.1505g, 43.8% yield. The melting point is greater than 300 ℃. 1 H NMR (400 Hz, DMSO-d 6 ) 11.89 (s, 1H), 11.56 - 11.48 (s, 1H), 8.30 and 8.11 (s, 1H), 8.22 - 8.19 (m, 1H), 8.05 and 8.00 (d, J = 7.6 Hz, 1H), 7.74 - 7.69 (m, 1H), 7.59 - 7.37 (m, 4H), 7.21 - 7.13 (m, 1H), 7.05 - 7.00 (m, 1H), 6.87 (s, 1H), 6.12 (d, J = 8.0 Hz, 1H), 5.61 and 5.09 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.6, 168.2 and 163.6, 145.8 and 145.6, 140.5, 137.9 and 137.5, 136.6, 133.2 and 132.7, 132.1, 127.8 and 127.5, 126.5, 125.7, 123.5 and 123.4, 123.3 and 123.2, 121.0 and 120.8, 119.6, 116.2, 112.0 and 111.5, 108.9, 107.4 and 106.4, 53.4 and 52.6. ESI-HRMS(m/z):Calcd. for C 20 H 17 N 4 O 2 [M+H] + 345.1352; found 345.1347。
Example 21
(4-oxo-4H-quinolin-1-yl) -acetyl (benzofuran-3-ylmethylene) hydrazine (I 21 ) The aldehyde is benzofuran-3-carbaldehyde.
White solid 0.3296g, yield 95.5%. Melting point 260 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 11.97 and 11.89 (s, 1H), 8.55 (m, 1H), 8.47 and 8.31 (s, 1H), 8.32 (d, J = 8.0 Hz, 1H), 8.22 - 8.18 (m, 1H), 8.06 - 7.99 (m, 1H), 7.72 and 7.63 (m, 2H), 7.54 - 7.35 (m, 4H), 6.12 (d, J = 8.0 Hz, 1H), 5.63 and 5.10 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 168.0 and 162.9, 155.2 and 154.3, 149.5 and 149.3, 145.8 and 145.7, 141.0 and 140.8, 138.1, 132.2 and 132.0, 126.5 and 126.4, 125.7, 125.6, 124.0, 123.8 and 123.7, 123.4 and 123.2, 117.5 and 117.4, 116.7 and 116.2, 111.5, 108.9, 53.3 and 52.9. ESI-HRMS(m/z):Calcd. for C 20 H 16 N 3 O 3 [M+H] + 346.1192; found 346.1187。
Example 22
(4-oxo-4H-quinolin-1-yl) -acetyl (9-ethyl-9H-carbazol-3-ylmethylene) hydrazine (I) 22 ) The aldehyde is 9-ethyl-9H-carbazole-3-carbaldehyde.
0.3214g of white solid was found to be 78.8% yield. The melting point is greater than 300 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 11.84 and 11.78 (s, 1H), 8.55 and 8.46 (s, 1H), 8.25 - 8.19 (m, 3H), 8.06 - 7.95 (m, 2H), 7.74 - 7.64 (m, 3H), 7.54 - 7.48 (m, 2H), 7.41 - 7.36 (m, 1H), 7.27 - 7.23 (m, 1H), 6.13 - 6.10 (m, 1H), 5.61 and 5.08 (s, 2H), 4.49 (q, J = 6.80 Hz, 2H), 1.34 (t, J = 6.80 Hz, 3H). 13 C NMR (100Hz, DMSO-d 6 ) 176.6, 167.9, 145.8 and 145.6, 145.5, 140.7, 140.6, 140.0, 132.1 and 132.0, 126.4, 126.2, 125.7 and 125.6, 124.9, 124.5, 123.2, 122.3, 122.1, 120.6, 120.3, 119.3, 116.5 and 116.0, 109.5, 109.4, 108.8, 52.9, 37.1, 13.7. ESI-HRMS(m/z):Calcd. for C 26 H 23 N 4 O 2 [M+H] + 423.1821; found 423.1814。
Example 23
(4-oxo-4H-quinolin-1-yl) -acetyl (3, 4-dimethoxybenzylidene) hydrazine (I) 23 ) The aldehyde is 3, 4-dimethoxy benzaldehyde.
0.2902g of yellow solid with a yield of 79.5% and a melting point of 170 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 11.79 and 11.74 (s, 1H), 8.20 - 8.17 (m, 1H), 8.02 -7.97 (m, 2H), 7.70 - 7.66 (m, 1H), 7.49 - 7.35 (m, 3H), 7.29 - 7.24 (m, 1H), 7.04 - 7.01 (m, 1H), 6.11 - 6.08 (m, 1H), 5.54 and 5.05 (s, 2H), 3.82 - 3.78 (m, 6H). 13 C NMR (100Hz, DMSO-d 6 ) 176.5, 168.0 and 162.8, 150.7, 149.0, 145.7 and 145.6, 144.4, 140.7, 132.1 and 131.9, 126.6 and 126.5, 126.4, 125.5, 123.3 and 123.1, 121.9 and 121.6, 116.5, 111.5, 108.8, 108.7, 55.6, 55.5, 52.9. ESI-HRMS(m/z):Calcd. for C 20 H 20 N 3 O 4 [M+H] + 366.1454; found 366.1446。
Example 24
(4-oxo-4H-quinolin-1-yl) -acetyl (5-bromo-2-methoxybenzylidene) hydrazine (I 24 ) The aldehyde is 5-bromo-2-methoxybenzaldehyde.
Yellow solid 0.3296g, yield 79.6%. Melting point 290 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 12.04 and 11.87 (s, 1H), 8.34 (s, 1H), 8.19 (d, J = 7.6 Hz, 1H), 8.10 (s, 1H), 7.98 (d, J = 8.0 Hz, 1H), 7.69 - 7.65 (m, 1H), 7.58 (d, J = 9.2 Hz, 1H), 7.46 (d. J = 8.8 Hz, 1H), 7.38 - 7.34 (m, 1H), 7.10 (d, J = 8.8 Hz, 1H), 6.09 (d, J = 7.6 Hz, 1H), 5.58 and 5.06 (s, 2H), 3.87 (s, 3H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 168.4, 156.9, 145.8 and 145.6, 140.7 and 140.5, 138.4, 133.9 and 133.8, 132.2 and 131.9, 127.7 and 127.5, 126.5 and 126.4, 125.8 and 125.5, 124.1 and 124.0, 123.4 and 123.2, 116.7 and 116.2, 114.5 and 114.3, 112.7 and 112.5, 108.9 and 108.8, 56.2, 53.4 and 53.0. ESI-HRMS(m/z):Calcd. for C 19 H 17 BrN 3 O 3 [M+H] + 414.0453; found 414.0452。
Example 25
(4-oxo-4H-quinolin-1-yl) -acetyl (3, 5-dibromo-4-hydroxybenzylidene) hydrazine (I 25 ) The aldehyde is 3, 5-dibromo-4-hydroxybenzaldehyde.
0.433g of pale yellow solid is obtained with a yield of 90.4%. Melting point 295 ℃. 1 H NMR (400Hz, DMSO-d 6 ) 12.00 and 11.86 (s, 1H), 8.18 (d, J = 8.0 Hz, 1H), 8.01 -7.80 (m, 4H), 7.71 - 7.65 (m, 1H), 7.48 -7.44 (m, 1H), 7.38 - 7.34 (m, 1H), 6.11 - 6.08 (m, 1H), 5.57 and 5.06 (s, 2H). 13 C NMR (100Hz, DMSO-d 6 ) 176.7, 168.4, 152.2, 145.6, 141.6, 140.7 and 140.5, 132.0, 130.8, 128.5, 126.4, 125.5, 123.2, 116.8, 112.2 and 112.1, 108.8, 53.0. ESI-HRMS(m/z):Calcd. for C 18 H 14 Br 2 N 3 O 3 [M+H] + 477.9402; found 477.9401。
Example 26
The tobacco mosaic virus resistance activity was measured as follows:
1. virus purification and concentration determination:
the virus purification and concentration measurement are carried out by compiling tobacco mosaic virus SOP standard according to a measuring room generated by elements of university of south China. After 2 times of polyethylene glycol centrifugation treatment, the concentration of the virus crude extract is measured, and the virus crude extract is refrigerated at 4 ℃ for standby.
2. Compound solution preparation:
after weighing, adding DMF to dissolve the raw materials to obtain 1×10 5 Mu g/mL mother liquor, and then diluting the mother liquor to the required concentration by using an aqueous solution containing 1 permillage Tween 80; the Ningnan mycin preparation is directly diluted by water.
3. In vivo passivation:
selecting 3-5 She Qishan Xie smoke with uniform growth vigor, mixing the medicament with an equal volume of virus juice, inactivating for 30 min, performing friction inoculation, wherein the virus concentration is 20 mu g/mL, washing with running water after inoculation, repeating for 3 times, and setting 1 millTween 80 aqueous solution for comparison. The number of lesions was counted after 3 d and the result was calculated.
4. In vivo therapeutic action:
3-5 She Qishan Xiyan with uniform growth vigor is selected, virus is inoculated to whole leaves of a writing brush, the virus concentration is 10 mu g/mL, and the whole leaves are washed by flowing water after inoculation. After leaf surface is dried, spraying and applying the whole plant, repeating for 3 times every treatment, and setting 1%Tween 80 water solution as a control. And 3, after d, recording the number of the lesions, and calculating the control effect.
5. Living body protecting action:
3-5 She Qishan Xiyan with uniform growth vigor is selected, the whole plant is sprayed and applied, each treatment is repeated for 3 times, and 1 permillage of Tween 80 aqueous solution is used for comparison. 24 After h, the leaf surface is spread with silicon carbide (500 meshes), the whole leaf surface is dipped with a virus liquid by a writing brush, the whole leaf surface is lightly rubbed for 2 times along the branch pulse direction, the lower part of the leaf surface is supported by a palm, the virus concentration is 10 mu g/mL, and the leaf surface is washed by running water after inoculation. And 3, after d, recording the number of the lesions, and calculating the control effect.
Inhibition ratio (%) = [ (control number of dried spots-number of treated dried spots)/control number of dried spots ] ×100%.
Tables 1 to 8 show quinolinone alkaloid derivatives I 1 -I 25 Is of the structure of (a)
TABLE 1
Figure 571364DEST_PATH_IMAGE002
TABLE 2
Figure 16252DEST_PATH_IMAGE003
TABLE 3 Table 3
Figure 494637DEST_PATH_IMAGE004
TABLE 4 Table 4
Figure 606950DEST_PATH_IMAGE005
TABLE 5
Figure 410958DEST_PATH_IMAGE006
TABLE 6
Figure 608721DEST_PATH_IMAGE007
TABLE 7
Figure 392263DEST_PATH_IMAGE008
TABLE 8
Figure 359082DEST_PATH_IMAGE009
Tables 9-12 are quinolinone alkaloid derivatives I 1 -I 25 Is effective in resisting tobacco mosaic virus
TABLE 9
Figure 599570DEST_PATH_IMAGE010
Table 10
Figure 753471DEST_PATH_IMAGE011
TABLE 11
Figure 839239DEST_PATH_IMAGE012
Table 12
Figure 660564DEST_PATH_IMAGE013

Claims (8)

1. A quinolinone alkaloid derivative containing an acylhydrazone group on the nitrogen atom at position 1, characterized in that: the structural general formula is as followsThe formula (I) is as follows:
Figure QLYQS_1
wherein R is selected from naphthyl or substituted phenyl;
the substituent in the substituted phenyl is selected from any one or 2-3 substituents in hydrogen, hydroxyl, halogen atom, cyano, nitro, trifluoromethyl, trifluoromethoxy, 1-5 carbon alkyl and 1-6 carbon alkoxy.
2. A quinolinone alkaloid derivative containing an acylhydrazone group on the nitrogen atom at position 1, characterized by a structure selected from the group consisting of:
Figure QLYQS_2
wherein R is phenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-biphenyl, 3-methoxyphenyl, 4-methylthiophenyl, 4-methylsulfonylphenyl, 4- (pyrazol-1-yl) phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-nitrophenyl, 4-trifluoromethylphenyl, 4-dimethylaminophenyl, 2-nitrophenyl, pyridin-3-yl, furan-2-yl, thiophen-2-yl, thiazol-4-yl, indol-2-yl, benzofuran-3-yl, 9-ethyl-9H-carbazol-3-yl, 3, 4-dimethoxyphenyl, 5-bromo-2-methoxyphenyl, (4-oxo-3, 5-dibromo-4-hydroxyphenyl).
3. A process for the preparation of quinolinone alkaloid derivatives containing an acylhydrazone group on the nitrogen atom in position 1 as defined in claim 1 or 2, characterized in that: the method comprises the following steps:
firstly, reacting 1H-quinolin-4-one with alpha-bromoethyl acetate in a solvent in the presence of a base at room temperature to form (oxo-4H-quinolin-1-yl) -ethyl acetate;
secondly, reacting (oxo-4H-quinolin-1-yl) -ethyl acetate with water and hydrazine in a solvent to form (4-oxo-4H-quinolin-1-yl) -acethydrazide;
thirdly, reacting (4-oxo-4H-quinolin-1-yl) -acethydrazide with aldehyde in a solvent to form a quinolinone alkaloid derivative having an acylhydrazone group on the 1-position nitrogen atom.
4. A process for the preparation of quinolinone alkaloid derivatives containing an acylhydrazone group on the nitrogen atom in position 1 according to claim 3, characterized in that: the solvent in the first step is selected from N, N-dimethylformamide; the base is selected from any one of cesium carbonate, sodium carbonate and potassium carbonate.
5. A process for the preparation of quinolinone alkaloid derivatives containing an acylhydrazone group on the nitrogen atom in position 1 according to claim 3, characterized in that: in the second step the solvent is selected from methanol; the reaction temperature was 65 ℃.
6. A process for the preparation of quinolinone alkaloid derivatives containing an acylhydrazone group on the nitrogen atom in position 1 according to claim 3, characterized in that: the solvent in the third step is selected from any one of methanol, ethanol and acetonitrile; the temperature of the reaction is 20-130 ℃.
7. A process for the preparation of quinolinone alkaloid derivatives containing an acylhydrazone group on the nitrogen atom in position 1 according to claim 3, characterized in that: in the third step, the aldehyde is selected from any one of benzaldehyde, 4-methylbenzaldehyde, 4-tert-butylbenzaldehyde, 4-phenylbenzaldehyde, 3-methoxybenzaldehyde, 4-methylthiobenzaldehyde, 4-methylsulfonylbenzaldehyde, pyrazol-1-ylbenzaldehyde, 4-fluorobenzaldehyde, 4-chlorobenzaldehyde, 4-bromobenzaldehyde, 4-nitrobenzaldehyde, 4-trifluoromethylbenzaldehyde, 4-dimethylaminobenzaldehyde, 2-nitrobenzaldehyde, pyridine-3-formaldehyde, furan-2-formaldehyde, thiophene-2-formaldehyde, thiazole-4-formaldehyde, indole-2-formaldehyde, benzofuran-3-formaldehyde, 9-ethyl-9H-carbazole-3-formaldehyde, 3, 4-dimethoxybenzaldehyde, 5-bromo-2-methoxybenzaldehyde and 3, 5-dibromo-4-hydroxybenzaldehyde.
8. Use of a quinolinone alkaloid derivative containing an acylhydrazone group on the 1-position nitrogen atom as defined in claim 1 or 2 for controlling tobacco mosaic virus.
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