Patent Grant
12063930
The invention relates to the technical field of chemical industry, in particular to a 4-(N-methyl) aminopiperidine myricetin derivatives containing sulfonamide, a preparation method of the 4-(N-methyl) aminopiperidine myricetin derivatives containing sulfonamide, and application of the 4-(N-methyl) aminopiperidine myricetin derivatives containing sulfonamide in inhibiting plant pathogens.
Myricetin (3′,4′,5′,3,5,7-hexahydroxyflavonol, also known as Cannabiscetin and Myricetol, is a polyhydroxyflavone compound separated from myricetin bark, chemical formula C15 H10 O8, relative molecular weight 318.24, yellow needle-like or granular crystal, melting point 324-326° C., soluble in methanol, ethanol and acetone, insoluble in chloroform and petroleum ether. It exists in Fagaceae, leguminosae, primulaceae, vitaceae, compositae and other plants. According to modern pharmacological activity research. Myricetin has a variety of pharmacological activities such as bacteriostasis, antiallergic, antiviral, hypoglycemic, anti-inflammatory, antioxidant, nerve protection and so on, showing rich resource advantages and great potential utilization value.
In 2007, Naz et al. (Journal of Food Science and Technology, 2007, 72, 341-345) studied the in vitro antibacterial activity of Myricetin against 4 genera of Staphylococcus, Corynebacterium, Streptococcus and Bacillus subtilis. The results showed that Myricetin had different degrees of antibacterial effect on the above 4 genera.
In 2009, Liu et al. (Journal of Zhejiang A&F University, 2009, 26, 95-99) conducted a systematic bacteriostasis action test on Myricetin by growth rate method. The experimental results showed that Myricetin had strong inhibitory activity on 6 plant pathogenic fungi including rice sheath blight fungus, Sclerotinia sclerotiorum, tomato Botrytis cinerea, wheat scab fungus, apple rot fungus, cotton Fusarium wilt, etc. The EC50 were: 0.32, 0.33, 1.09, 0.69, 0.34 and 2.09 g/L, and have higher inhibitory activity on rice sheath blight, rape Sclerotinia sclerotiorum and apple rot.
In 2012, Yu et al. (bioorganic chemistry and Pharmacochemistry Express, 2012, 22, 4049-4054) studied the inhibitory effect of Myricetin on SARS virus in vitro by performing fluorescence resonance energy transfer (FRET) double-stranded DNA derotation assay or using colorimetric basic hydrolysis assay. The study found that: Myricetin potentially inhibits SARS virus helicase protein and affects ATP enzyme activity, but has no helicase activity, and Myricetin has no cytotoxicity on normal breast epithelial MCF10A cells. Furthermore, Myricetin has a good inhibitory effect on SARS virus in vitro.
To sum up, Myricetin has certain biological activity in medicine and pesticide. Previous research work has less modification on Myricetin, mainly research on the biological activity of Myricetin itself, but there has been no report of introducing the active group of 4-(N-methyl) aminopiperidine containing sulfonamide into Myricetin to synthesize 4-(N-methyl) aminopiperidine myricetin derivatives containing sulfonamide and carrying out agricultural activity test.
The object of the present invention is to provide a 4-(N-methyl) aminopiperidine myricetin derivatives containing sulfonamide, which overcomes the above disadvantages and has a good control effect on plant pathogenic fungi, and can be used as an agricultural fungicide.
Another object of the present invention is to provide a preparation method of the sulfonamide-containing 4-(N-methyl) aminopiperidine myricetin derivatives.
Another object of the invention is to provide the application of the sulfonamide-containing 4-(N-methyl) aminopiperidine myricetin derivatives in inhibiting citrus canker germs and rice bacterial leaf blight germs.
The 4-(N-methyl) aminopiperidine myricetin derivatives containing sulfonamide of the invention has the following structural general formula:
Wherein, R is substituted phenyl or substituted aromatic heterocyclic group; n is the number of carbon in the carbon chain and is 2, 3, 4 and 5 respectively.
The sulfonamide-containing 4-(N-methyl) aminopiperidine myricetin derivatives, wherein: The substituted phenyl group is a C1-6 alkyl group, a C1-6 alkoxy group, a nitro group, a halogen atom and a hydrogen atom in the ortho, meta and para position on the benzene ring.
The above-mentioned 4-(N-methyl) aminopiperidine myricetin derivatives containing sulfonamide, wherein: Substituted aromatic heterocyclic groups are thienophenyl, furyl, pyrrolyl, pyridyl and the like, and substituents on the substituted aromatic heterocyclic groups are ortho, meta and para position alkyl groups containing C1-6, C1-6 alkoxy groups, nitro groups, halogen atoms and hydrogen atoms.
The preparation method of the sulfonamide-containing 4-(N-methyl) aminopiperidine myricetin derivatives of the invention has the following synthetic route:
The application of the sulfonamide-containing 4-(N-methyl) aminopiperidine myricetin derivatives of the invention in inhibiting citrus canker germs and rice bacterial leaf blight germs.
Compared with the prior art, the invention has obvious beneficial effects, and can be seen from the above technical scheme: In the synthesis of intermediate a of the invention, crystalline potassium carbonate is cheaper than anhydrous potassium carbonate, and the yield is improved. In the invention, piperidine, an alkaloid structural unit, is mainly used as a bridge, and natural products myricetin and sulfonyl chloride are actively spliced, so that the obtained compound has higher bacteriostatic activity.
The preparation method of 5,7-dimethoxy-3-(3-(N-methyl (1-(4-methylbenzenesulfonyl) piperidyl)) amino) propoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one (target compound I1) is as follows:
4.64 g of Myricetin (10 mmol), 22.09 g K2CO3 (160 mmol) and 120 mL DMF are sequentially added into a 250 mL round bottom flask. After stirring at normal temperature for 0.5 to 1 h, 7.50 mL of methyl iodide (120 mmol) is slowly added dropwise, stirring at room temperature for 48 h, and monitoring the reaction by TLC (methanol:ethyl acetate=1:4, V/V). After the reaction is stopped, the precipitate is filtered and the filter residue is washed with dichloromethane, then the combined filtrates are, diluted with 100 mL of water, extracted three times with dichloromethane, the organic layers are combined, concentrated under reduced pressure, then the concentrate is dissolved in 30 mL of absolute ethyl alcohol to heat to reflux, after the solution is clarified, 10 mL of concentrated hydrochloric acid is added under reflux, then yellow solid is precipitated, the reaction is continued for 2 hours, cooled, filtered, and the crude product 3-hydroxy-3′,4′,5′,5,7-pentamethoxy myricetin (intermediate a) is obtained with a 54.4% yield.
1.17 g (3 mmol) of 3-hydroxy-3′,4′,5′,5,7-pentamethoxy myricetin (intermediate a), 1.66 g of K2CO3 (12 mmol) and 30 mL DMF are sequentially added into a 100 mL single-necked round bottom flask. After stirring at normal temperature for 0.5-1 h, 2.42 g of 1,3-dibromopropane (12 mmol) are added. The reaction is continued for 12 hours at this temperature, and the reaction (ethyl acetate) is monitored by TLC. After the reaction is stopped, the reaction solution is dispersed with 50 mL of water and extracted with ethyl acetate (3×25 ml). The obtained ethyl acetate layer is washed with 1 mol/L HCl, saturated NaHCO3 and saturated NaCl aqueous solution twice respectively. After that, the ethyl acetate layers are combined, dried over anhydrous Na2SO4 and the solvent is removed under reduced pressure, and the residue is purified by reduced pressure column chromatography (petroleum ether:ethyl acetate=2:1, V/V) to obtain a white solid (intermediate b) with a yield of 78.9%.
0.38 g (1.78 mmol) of 4-(N-methyl) amino-N-Boc piperidine, 0.5 g (3.57 mmol) of K2CO3 and 40 mL of acetonitrile are added to a 100 mL single-necked round bottom flask. After stirring at normal temperature for 0.5-1 h, 1 g (1.96 mmol) of 3-(3-bromopropoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one (intermediate B) is added, followed by heating to 80° C., and stirring at this temperature for 4-6 h. the reaction is monitored by TLC, when the reaction is finished, cooled to room temperature, filtered to remove potassium carbonate and solid impurities, and the solvent is removed under reduced pressure to obtain a crude product (intermediate c) in the form of a burgundy oil for later use, yield: 91.7%.
In Step 3, tert-butyl 4-((3-(5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-benzopyran-3-yl) oxy) propyl) (methyl) amino tert-butyl) piperidine-1-carboxylic acid (intermediate c) is dissolved in a 100 mL single-necked round bottom flask with about 30 mL methanol, then 10 ml of 6 mol/L methanol hydrochloride solution is added and stirred at room temperature for about 2 hours. The reaction is monitored by TLC, when the reaction is finished, a small amount of methanol is added to dissolve after the solvent is removed under reduced pressure, then 20 mL of ethyl acetate is added, and the mixture is continuously stirred until a yellow solid is precipitated, filtered, washed with ethyl acetate and dichloromethane respectively, and naturally dried to obtain a yellow solid (intermediate d), yield: 93.2%.
0.5 g (0.86 mmol) of 5,7-dimethoxy-3-(3-(methyl (piperidin-4-yl) amino) propoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one hydrochloride (intermediate d), 0.36 g (2.59 mmol) of K2CO3 and 20 ml of anhydrous ethanol are added into a 50 mL single-necked round bottom flask, and stirring at room temperature is carried out until there is a large amount of white solid, then 0.16 g (0.86 mmol) of p-toluenesulfonyl chloride is added, and stirring is continued for about 2 hours. The reaction is monitored by TLC and when it finished, the mixture is poured into 100 mL of water, extracted with dichloromethane (3×20 mL), the organic layers are combined, washed with saturated brine (3×20 mL), dried over anhydrous sodium sulfate, filtrated and the solvent is removed under reduced pressure to obtain a crude product, which is purified by column chromatography (ethyl acetate:methanol=5:1˜1:10, V/V) to obtain the target compound I1, yield: 48.2%.
The preparation method of 5,7-dimethoxy-3-(3-(N-methyl (1-(naphthalene-2-ylsulfonyl) piperidyl)) amino) propoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one (target compound I2) is as follows:
As in step (1) of Embodiment 1.
As in step (2) of Embodiment 1.
As in step (3) of Embodiment 1.
As in step (4) of Embodiment 1.
As in step (5) of Embodiment 1, the difference is that naphthalene-2-sulfonyl chloride is used as the raw material, yield: 66.9%.
The preparation method of 5,7-dimethoxy-3-(3-(N-methyl (1-(4-fluorophenyl sulfonyl) piperidyl)) amino) propoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one (target compound I3) is as follows:
As in step (1) of Embodiment 1.
As in step (2) of Embodiment 1.
As in step (3) of Embodiment 1.
As in step (4) of Embodiment 1.
As in step (5) of Embodiment 1, the difference is that 4-fluorobenzenesulfonyl chloride is used as the raw material, yield: 45.3%.
The preparation method of 5,7-dimethoxy-3-(3-(N-methyl (1-(thiophene-2-ylsulfonyl) piperidyl)) amino) propoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one (target compound I4) is as follows:
As in step (1) of Embodiment 1.
As in step (2) of Embodiment 1.
As in step (3) of Embodiment 1.
As in step (4) of Embodiment 1.
As in step (5) of Embodiment 1, the difference is that thiophenesulfonyl chloride is used as the raw material, yield: 63.3%.
The preparation method of 5,7-dimethoxy-3-(3-(N-methyl(1-(4-methoxybenzenesulfonyl) piperidyl)) amino) propoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one (target compound I5) is as follows:
As in step (1) of Embodiment 1.
As in step (2) of Embodiment 1.
As in step (3) of Embodiment 1.
As in step (4) of Embodiment 1.
As in step (5) of Embodiment 1, the difference is that 4-methoxybenzenesulfonyl chloride is used as the raw material, yield: 62.4%.
The preparation method of 5,7-dimethoxy-3-(3-(N-methyl (1-(4-nitrobenzenesulfonyl) piperidyl)) amino) propoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one (target compound I6) is as follows:
As in step (1) of Embodiment 1.
As in step (2) of Embodiment 1.
As in step (3) of Embodiment 1.
As in step (4) of Embodiment 1.
As in step (5) of Embodiment 1, the difference is that 4-nitrobenzenesulfonyl chloride is used as the raw material, yield: 95.8%.
The preparation method of 5,7-dimethoxy-3-(3-(N-methyl (1-(benzenesulfonyl) piperidinyl)) amino) propoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one (target compound I7) is as follows:
As in step (1) of Embodiment 1.
As in step (2) of Embodiment 1.
As in step (3) of Embodiment 1.
As in step (4) of Embodiment 1.
As in step (5) of Embodiment 1, the difference is that benzenesulfonyl chloride is used as the raw material, yield: 55.3%.
The preparation method of 5,7-dimethoxy-3-(3-(N-methyl (1-(pyridine-2-ylsulfonyl) piperidyl)) amino) propoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one (target compound I8) is as follows:
As in step (1) of Embodiment 1.
As in step (2) of Embodiment 1.
As in step (3) of Embodiment 1.
As in step (4) of Embodiment 1.
As in step (5) of Embodiment 1, the difference is that pyridine-2-sulfonyl chloride is used as the raw material, yield: 47.6%.
The preparation method of 5,7-dimethoxy-3-(3-(N-methyl (1-(quinoline-7-ylsulfonyl) piperidyl)) amino) propoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one (target compound I9) is as follows:
As in step (1) of Embodiment 1.
As in step (2) of Embodiment 1.
As in step (3) of Embodiment 1.
As in step (4) of Embodiment 1.
As in step (5) of Embodiment 1, the difference is that quinoline-7-sulfonyl chloride is used as the raw material, yield: 44.7%.
The preparation method of 5,7-dimethoxy-3-(3-(N-methyl (1-(2-nitrobenzenesulfonyl) piperidyl)) amino) propoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one (target compound I10) is as follows:
As in step (1) of Embodiment 1.
As in step (2) of Embodiment 1.
As in step (3) of Embodiment 1.
As in step (4) of Embodiment 1.
As in step (5) of Embodiment 1, the difference is that 2-nitrobenzenesulfonyl chloride is used as the raw material, yield: 45.5%.
The preparation method of 5,7-dimethoxy-3-(4-(N-methyl (1-(4-methylbenzenesulfonyl) piperidyl)) amino) butoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one (target compound I11) is as follows:
As in step (1) of Embodiment 1.
As in step (2) of Embodiment 1. The difference is that 1,4-dibromobutane is used as a raw material.
As in step (3) of Embodiment 1.
As in step (4) of Embodiment 1.
As in step (5) of Embodiment 1, yield: 33.1%.
The preparation method of 5,7-dimethoxy-3-(4-(N-methyl (1-(naphthalene-2-ylsulfonyl) piperidyl)) amino) butoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one (target compound I12) is as follows:
As in step (1) of Embodiment 1.
As in step (2) of Embodiment 11.
As in step (3) of Embodiment 1.
As in step (4) of Embodiment 1.
As in step (5) of Embodiment 2, yield: 33.6%.
The preparation method of 5,7-dimethoxy-3-(4-(N-methyl (1-(3-fluorophenyl sulfonyl) piperidyl)) amino) butoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one (target compound I13) is as follows:
As in step (1) of Embodiment 1.
As in step (2) of Embodiment 11.
As in step (3) of Embodiment 1.
As in step (4) of Embodiment 1
As in step (5) of Embodiment 3, yield: 36.0%.
The preparation method of 5,7-dimethoxy-3-(4-(N-methyl (1-(thiophene-2-ylsulfonyl) piperidyl)) amino) butoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one (target compound I14) is as follows:
As in step (1) of Embodiment 1.
As in step (2) of Embodiment 11.
As in step (3) of Embodiment 1.
As in step (4) of Embodiment 1.
As in step (5) of Embodiment 4, yield: 58.6%.
The preparation method of 5,7-dimethoxy-3-(4-(N-methyl(1-(4-methoxybenzenesulfonyl) piperidyl)) amino) butoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one (target compound I15) is as follows:
As in step (1) of Embodiment 1.
As in step (2) of Embodiment 11.
As in step (3) of Embodiment 1.
As in step (4) of Embodiment 1.
As in step (5) of Embodiment 5, yield: 61.2%.
The preparation method of 5,7-dimethoxy-3-(4-(N-methyl (1-(4-nitrobenzenesulfonyl) piperidyl)) amino) butoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one (target compound I16) is as follows:
As in step (1) of Embodiment 1.
As in step (2) of Embodiment 11.
As in step (3) of Embodiment 1.
As in step (4) of Embodiment 1.
As in step (5) of Embodiment 6, yield: 49.5%.
The preparation method of 5,7-dimethoxy-3-(4-(N-methyl (1-(benzenesulfonyl) piperidinyl)) amino) butoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one (target compound I17) is as follows:
As in step (1) of Embodiment 1.
As in step (2) of Embodiment 11.
As in step (3) of Embodiment 1.
As in step (4) of Embodiment 1.
As in step (5) of Embodiment 7, yield: 49.5%.
The preparation method of 5,7-dimethoxy-3-(4-(N-methyl (1-(pyridine-2-ylsulfonyl) piperidyl)) amino) butoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one (target compound I18) is as follows:
As in step (1) of Embodiment 1.
As in step (2) of Embodiment 11.
As in step (3) of Embodiment 1.
As in step (4) of Embodiment 1.
As in step (5) of Embodiment 8, yield: 72.2%.
The preparation method of 5,7-dimethoxy-3-(4-(N-methyl (1-(quinoline-7-ylsulfonyl) piperidyl)) amino) butoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one (target compound I19) is as follows:
As in step (1) of Embodiment 1.
As in step (2) of Embodiment 11.
As in step (3) of Embodiment 1.
As in step (4) of Embodiment 1.
As in step (5) of Embodiment 9, yield: 98.2%.
T The preparation method of 5,7-dimethoxy-3-(4-(N-methyl (1-(2-nitrobenzenesulfonyl) piperidyl)) amino) butoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one (target compound I20) is as follows:
As in step (1) of Embodiment 1.
As in step (2) of Embodiment 11.
As in step (3) of Embodiment 1.
As in step (4) of Embodiment 1.
As in step (5) of Embodiment 10, yield: 60.8%.
The physicochemical properties and mass spectrum data of the synthesized sulfonamide-containing 4-(N-methyl) aminopiperidine myricetin derivative are shown in Table 1, and the nuclear magnetic resonance hydrogen spectrum (1H NMR) and carbon spectrum (13C NMR) data are shown in Table 2.
1H NMR, 13C NMR (TMS is internal standard)
1H NMR (400 MHz, DMSO) δ 7.60 (d, J = 8.2 Hz, 2H, Ph-H),
13C NMR (101 MHz, DMSO) δ 172.66, 164.19, 160.75,
1H NMR (400 MHz, DMSO) δ 8.43 (s, 1H, Naphthyl-H),
13C NMR (101 MHz, DMSO) δ 172.66, 164.20, 160.76, 158.62,
1H NMR (400 MHz, DMSO) δ 7.80 (dd, J = 8.7, 5.2 Hz, 2H,
13C NMR (101 MHz, DMSO) δ 172.67, 166.28, 163.78, 160.72,
19F NMR (472 MHz, Chloroform) δ −108.20
1H NMR (400 MHz, DMSO) δ 8.04 (dd, J = 5.0, 1.2 Hz, 1H,
13C NMR (101 MHz, DMSO) δ 172.72, 164.24, 160.72, 158.64,
1H NMR (400 MHz, DMSO) δ 7.68-7.61 (m, 2H, Ph-H), 7.34
13C NMR (101 MHz, DMSO) δ 172.66, 164.18, 163.09, 160.73,
1H NMR (400 MHz, DMSO) δ 8.48-8.42 (m, 2H, Ph-H),
13C NMR (101 MHz, DMSO) δ 172.66, 164.18, 160.72, 158.61,
1H NMR (400 Mhz, DMSO) δ 7.71 (dd, J = 7.9, 6.7 Hz, 3H,
13C NMR (101 MHz, DMSO) δ 172.66, 160.70, 158.60, 153.09,
1H NMR (400 MHz, DMSO) δ 8.93-8.86 (m, 2H, Pyridiyl-H),
13C NMR (101 MHz, DMSO) δ 172.66, 164.18, 160.71, 158.62,
1H NMR (400 MHz, DMSO) δ 9.07 (dd, J = 4.2, 1.8 Hz, 1H,
13C NMR (101 MHz, DMSO) δ 172.66, 164.17, 160.70, 158.60,
1H NMR (400 MHz, DMSO) δ 7.98 (t, J = 7.7 Hz, 2H, Ph-H),
13C NMR (101 MHz, DMSO) δ 172.67, 164.20, 160.74, 158.63,
1H NMR (400 MHz, DMSO) δ 7.60 (d, J = 7.1 Hz, 2H, Ph-H),
13C NMR (101 MHz, DMSO) δ 172.66, 164.18, 160.72, 158.61,
1H NMR (400 MHz, DMSO) δ 8.42 (s, 1H, Naphthyl-H) 8.19 (d, J = 7.8 Hz, 1H,
13C NMR (101 MHz, DMSO) δ 172.64, 164.15, 160.70, 158.58, 153.08,
1H NMR (400 MHz, DMSO) δ 7.83-7.77 (m, 2H, Ph-H), 7.48 (t,
13C NMR (101 MHz, DMSO) δ 172.67, 166.27, 164.27, 164.19, 163.77, 160.72,
19F NMR (376 MHz, DMSO) δ −106.09.
1H NMR (400 MHz, DMSO) δ 8.04 (dd, J = 5.0, 1.1 Hz, 1H, Thienyl-H),
13C NMR (101 MHz, DMSO) δ 172.67, 164.20, 160.72, 158.62, 153.12, 152.03,
1H NMR (400 MHz, DMSO) δ 7.65 (d, J = 8.8 Hz, 2H, Ph-H), 7.37 (s, 2H, Ph-H),
13C NMR (101 MHz, DMSO) δ 172.66, 164.18, 163.08, 160.72, 158.61, 153.11,
1H NMR (400 MHz, DMSO) δ 8.44 (d, J = 8.8 Hz, 2H, Ph-H), 8.00 (d, J =
1H NMR (400 MHz, DMSO) δ 7.75-7.68 (m, 3H, Ph-H), 7.67-7.61 (m,
13C NMR (101 MHz, DMSO) δ 172.66, 164.18, 160.71, 158.61, 153.10, 151.98,
1H NMR (400 MHz, DMSO) δ 8.91-8.87 (m, 2H, Pyridyl-H), 8.16 (d, J = 8.0 Hz,
13C NMR (101 NHz, DMSO) δ 172.67, 164.18, 160.71, 158.61, 154.10, 153.10,
1H NMR (400 MHz, DMSO) δ 9.07 (dd, J = 4.2, 1.7 Hz, 1H, Quinolyl-H), 8.53
13C NMR (101 MHz, DMSO) δ 172.66, 164.17, 160.70, 158.60, 153.09, 151.96, 151.77,
1H NMR (400 MHz, DMSO) δ 7.99 (d, J = 7.7, 6.2, 1.5 Hz, 2H, Ph-H), 7.88
13C NMR (101 MHz, DMSO) δ 172.68, 164.19, 160.73, 158.62, 153.12, 152.00, 148.33,
(1) Test Method
Using turbidimetric method, the inhibitory activity of the target compound on citrus canker pathogen (Xanthomonas oryzae pv. oryzae), tobacco bacterial wilt pathogen (Ralstonia solanacearum) and rice bacterial wilt pathogen (Xanthomonas axonopodis pv. citri) is tested. The specific operation steps are as follows:
(2) Results of Bioactivity Test Against Plant Pathogens
atested three times on average.
btook the inhibitory activity of commercial thiodiazole copper and bismerthiazol as the positive controls.
T Using turbidimetric method, the inhibitory activities of the target compounds against citrus canker, tobacco bacterial wilt and rice bacterial wilt are tested with commercial bactericides thiabendazole and fenvalerate as positive controls at the concentration of 100, 50 μg/mL (see Table 3). The test results showed that: All compounds have certain inhibition rates on the tested plant bacteria. Among them, when the concentration is 100 μg/mL, the inhibition rates of compounds I1-8, I14, I16-20 against citrus canker pathogen (Xac) are higher than that of thiodiazole copper (70.68%) and bismerthiazol (66.63%); the inhibition rates of compounds I10 and I11 to tobacco bacterial wilt (Rs) are higher than thiodiazole copper (40.20%) and bismerthiazol (65.69%). Compounds I1-2, I11-18 and I20 all had higher inhibition rates against Xanthomonas oryzae (Xoo) than thiodiazole copper (70.12%) and bismerthiazol (60.50%). When the concentration is 50 μg/mL, the inhibition rates of compounds I1-8 and I14-20 against citrus ulcer bacteria (Xac) is higher than that of thiodiazole copper (44.97%) and bismerthiazol (50.60%). The inhibition rate of compound I10 against tobacco bacterial wilt (Rs) is close to that of bismerthiazol (57.63%). The inhibition rates of I1-2, I10-15, I17-18 and I20 against Xoo are higher than that of thiodiazole copper (58.92%) and bismerthiazol (39.14%). The above experimental activity data showed that sulfonamide-containing 4-(N-methyl) amino piperidine myricetin derivatives has certain inhibitory effect on plant pathogens (citrus ulcer bacteria, tobacco Solanacearum, rice blight pathogen), and parts of the target compounds with good inhibitory activities on plant pathogens performance can be used as potential inhibition of plant pathogen drugs, which has a good application prospects.
In summary, it is only a preferred embodiment of the present invention and is not intended to limit the present invention in any form. Any simple modifications, equivalent changes and modifications made to the above embodiments according to the technical essence of the present invention without departing from the technical scheme of the present invention are still within the scope of the technical scheme of the present invention.
| Number | Date | Country | Kind |
|---|---|---|---|
| 201910528656.3 | Jun 2019 | CN | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/CN2019/124090 | 12/9/2019 | WO |
| Publishing Document | Publishing Date | Country | Kind |
|---|---|---|---|
| WO2020/253152 | 12/24/2020 | WO | A |
| Number | Date | Country |
|---|---|---|
| 104788416 | Jul 2015 | CN |
| 106518828 | Mar 2017 | CN |
| 109438433 | Aug 2019 | CN |
| 110183430 | Aug 2019 | CN |
| Entry |
|---|
| Jiang, Shichun, Design, Synthesis and Antibacterial Activities Against Xanthomonas Oryzae pv.Oryzae, Xanthomonas Axonpodis pv.Citri and Ralstonia Solanacearum of Novel Myricetin Derivatives Containing Sulfonamide Moiety, Pest Manag Sci. Sep. 5, 2019. |
| Number | Date | Country | |
|---|---|---|---|
| 20230131193 A1 | Apr 2023 | US |
