Preparation method of novel ferulic acid derivative containing sulfanilamide structure and application of ferulic acid derivative in agriculture

Abstract

The invention discloses a novel ferulic acid derivative containing a sulfanilamide structure, which is characterized in that the structural formula of the derivative is as follows: # imgabs0 #, and R is phenyl, substituted phenyl or heterocyclic ring. A biological activity determination result shows that the ferulic acid compound containing the sulfonamide structure has medium to excellent inhibitory activity on Xanthomonas oryzae pv. Oryzae, Xanthomonas citri pv. Citri and Xanthomonas syringae pv. Kiwifruit, and the compound B28 has the best activity; the inhibitory activities of the compound on rice bacterial leaf streak pathogen, citrus canker pathogen and kiwi fruit bacterial canker pathogen are respectively 82.7%, 80.7% and 79.9%, which are far higher than those of control medicaments thiediazole copper and zinc thiazole.

Description

Technical Field

[0001] The invention relates to the technical field of chemistry, in particular to a ferulic acid derivative plant growth regulator containing a sulfonamide structure, a preparation method of the compound and use of the composition thereof on bacterial leaf streak pathogen of rice, citrus canker pathogen and kiwi fruit bacterial canker pathogen. Background Art

[0002] Plant bacterial diseases seriously endanger food security, with the characteristics of strong suddenness, rapid epidemic speed and difficulty in control. Once the disease occurs, it will have a serious impact on the yield of crops, with a reduction of 10% to 30% in mild cases and more than 50% in severe cases. At present, the prevention and control measures for plant bacterial diseases are still mainly chemical control. For example, the control agents for rice bacterial blight include: chlorothiazide, thiophanate-methyl, chlorfenapyr and thiophanate-methyl, etc. However, due to the long-term single use of this type of traditional fungicide, the efficacy has decreased and obvious drug resistance has occurred. Therefore, in view of the severe problems such as the small number of existing drugs in the market, low efficacy, high resistance risk, and prominent drug resistance, it is of great practical significance to find small molecule compounds with special action mechanisms and novel structures in the creation of green fungicides.

[0003] The physiological functions of ferulic acid include regulating plant growth, inhibiting competing plants, absorbing minerals and water from roots, and protecting grains from aphids, insects, and fungi. Ferulic acid has a simple structure and a wide range of sources. In terms of the development and utilization of new drugs, it is a natural product structure that people focus on, and it is also one of the research hotspots for the creation of plant antibacterial agents in recent years. By introducing active substructures such as amides, ethers, and acylhydrazones into its structure, ferulic acid derivatives with good antibacterial activity can be found.

[0004] Sulfonamide structure is a common structural skeleton in the field of organic chemistry, and it can be found in many synthetic drugs. In recent years, more and more drugs and lead compounds have been discovered, and researchers have also conducted in-depth research in different fields of medicinal chemistry. These lead compounds have also shown a wide range of biological activities. Many compounds containing sulfonamide structures have good antifungal, herbicidal, anti-tumor, antiviral, anti-diabetic and other biological activities, and have been a hot area of ​​drug research in the pesticide and pharmaceutical industries in recent years.

[0005] In summary, derivatives containing the structure of the natural product ferulic acid have multiple biological activities and play an important role in the creation of new pesticides. In recent years, structural modification of the natural product ferulic acid has become one of the hot areas for the creation of new pesticides. By introducing active substructures such as amides, ethers, and acylhydrazones into its structure, derivatives with good antibacterial activity can be found, and the application of sulfonamide derivatives in pesticides is becoming more and more extensive. Based on the above research background, this paper will take ferulic acid and sulfonamide structures as the guide to design and synthesize ferulic acid derivatives containing sulfonamide structures with good biological activity. And take plant bacterial diseases as the research object, test its biological activity, and study its activity as a plant growth regulator, hoping to screen out highly active antibacterial plant growth regulators. Summary of the invention

[0006] The present invention aims to provide a method for preparing a biological plant growth regulator of a ferulic acid derivative containing a sulfonamide structure and having bactericidal activity and a composition thereof.

[0007] Another object of the present invention is to provide a novel compound having an inhibitory effect on rice bacterial leaf streak pathogen, citrus canker pathogen and kiwi fruit bacterial canker pathogen.

[0008] The technical solution of the present invention is: a novel ferulic acid derivative containing a sulfonamide structure, wherein the derivative has the following general formula (I):

[0009]

[0010] Wherein: R is phenyl, 2-fluorobenzene, 3-fluorobenzene, 4-fluorobenzene, 2-chlorobenzene, 3-chlorobenzene, 4-chlorobenzene, 2-bromobenzene, 3-bromobenzene, 4-bromobenzene, 2-trifluoromethylbenzene, 3-trifluoromethylbenzene, 4-trifluoromethylbenzene, 3-methoxybenzene, 4-methoxybenzene, 2-cyanobenzene, 3-cyanobenzene, 4-cyanobenzene, 2-nitrobenzene, 3-nitrobenzene, 4-nitrobenzene, 4-biphenyl, naphthalene, 2,5-difluorobenzene, 2,4-dichlorobenzene, 2-fluoro-3-chlorobenzene, 3-chloro-4-fluorobenzene, 2-fluoro-4-bromobenzene or a disubstituted substituted group of any combination thereof.

[0011] Preferably, R is phenyl, 2-fluorobenzene, 3-fluorobenzene, 4-fluorobenzene, 2-chlorobenzene, 3-chlorobenzene, 4-chlorobenzene, 2-bromobenzene, 3-bromobenzene, 4-bromobenzene, 2-trifluoromethylbenzene, 3-trifluoromethylbenzene, 4-trifluoromethylbenzene, 3-methoxybenzene, 4-methoxybenzene, 2-cyanobenzene, 3-cyanobenzene, 4-cyanobenzene, 2-nitrobenzene, 3-nitrobenzene, 4-nitrobenzene, 4-biphenyl, naphthalene, 2,5-difluorobenzene, 2,4-dichlorobenzene, 2-fluoro-3-chlorobenzene, 3-chloro-4-fluorobenzene, 2-fluoro-4-bromobenzene or a disubstituted substituted group or any combination of the above substituents.

[0012] A novel ferulic acid derivative containing a sulfonamide structure, the specific compound is as follows:

[0013] Compound B1: (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-(phenylsulfonyl)piperazin-1-yl)prop-2-en-1-one;

[0014] Compound B2: (E)-1-(4-((2-fluorophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one;

[0015] Compound B3: (E)-1-(4-((3-fluorophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one;

[0016] Compound B4: (E)-1-(4-((4-fluorophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one;

[0017] Compound B5: (E)-1-(4-((2-chlorophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one;

[0018] Compound B6: (E)-1-(4-((3-chlorophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one;

[0019] Compound B7: (E)-1-(4-((4-chlorophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one;

[0020] Compound B8: ((E)-1-(4-((2-bromophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one;

[0021] Compound B9: (E)-1-(4-((3-bromophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one;

[0022] Compound B10: (E)-1-(4-((4-bromophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one;

[0023] Compound B11: (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-((2-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)prop-2-en-1-one;

[0024] Compound B12: (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-((3-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)prop-2-en-1-one;

[0025] Compound B13: (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-(4-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)prop-2-en-1-one;

[0026] Compound B14: (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-(3-methoxyphenylsulfonyl)piperazin-1-yl)prop-2-en-1-one;

[0027] Compound B15: (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-(4-methoxyphenylsulfonyl)piperazin-1-yl)prop-2-en-1-one;

[0028] Compound B16: (E)-2-(4-(3-(4-hydroxy-3-methoxyphenyl)acryloyl)piperazin-1-yl)sulfonyl)benzonitrile;

[0029] Compound B17: (E)-3-((4-(3-(4-hydroxy-3-methoxyphenyl)acryloyl)piperazin-1-yl)sulfonyl)benzonitrile;

[0030] Compound B18: (E)-4-(4-(3-(4-hydroxy-3-methoxyphenyl)acryloyl)piperazin-1-yl)sulfonyl)benzonitrile;

[0031] Compound B19: (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-(2-nitrophenyl)sulfonyl)piperazin-1-yl)prop-2-en-1-one;

[0032] Compound B20: (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-(3-nitrophenyl)sulfonyl)piperazin-1-yl)prop-2-en-1-one;

[0033] Compound B21: (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-(4-nitrophenyl)sulfonyl)piperazin-1-yl)prop-2-en-1-one.

[0034] Compound B22: (E)-1-(4-([1,1'-biphenyl]-4-ylsulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one.

[0035] Compound B23: (E)-3-(4-Hydroxy-3-methoxyphenyl)-1-(4-(naphthalen-2-ylsulfonyl)piperazin-1-yl)prop-2-en-1-one.

[0036] Compound B24: (E)-1-(4-(2,6-difluorophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one.

[0037] Compound B25: (E)-1-(4-(2,4-dichlorophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one.

[0038] Compound B26: (E)-1-(4-((3-chloro-2-fluorophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one.

[0039] Compound B27: (E)-1-(4-((3-chloro-4-fluorophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one.

[0040] Compound B28: (E)-1-(4-((4-bromo-2-fluorophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one.

[0041] A method for preparing a purine derivative comprises the following steps:

[0042] (1) Anhydrous piperazine: various sulfonyl chlorides: triethylamine = 1:1-1.2:2, DCM 15 mL, react at room temperature for 5 h, and after the reaction is completed, pour the reaction system into saturated brine, extract with dichloromethane, collect the organic layer, and separate and purify by column chromatography to obtain the target compounds A1-A28;

[0043]

[0044] (2) Add intermediate A1-A28: ferulic acid: EDCI: HOBt: = 1:1.2:1.2:1.2, add 5 mL of dry DMF, react at 0°C for 4 h, and after the reaction is completed, pour the mixture into water and extract with ethyl acetate three times to separate the organic phase. The organic layer is then washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated. The crude product is purified by silica gel column chromatography using petroleum ether / ethyl acetate (1:1, v / v) as the eluent to obtain the target compound B1-B28;

[0045]

[0046] The derivative is used in preparing medicines and medicaments for preventing and controlling rice bacterial leaf streak pathogen, kiwi fruit bacterial canker pathogen and citrus canker pathogen.

[0047] A compound pesticide composition, characterized in that: the composition comprises the purine derivative according to claim 1 and Zhongshengmycin. The mass ratio of the derivative to Zhongshengmycin is 1:2-2:1. The derivative is B28.

[0048] The composition is used in the preparation of a drug for preventing and treating plant bacterial diseases, wherein the plant bacterial diseases are rice bacterial leaf streak pathogen, citrus canker pathogen and kiwi fruit bacterial canker pathogen.

[0049] A novel plant growth regulator is compound B28, a compound of the following formula (II):

[0050]

[0051] Beneficial effects of the present invention: From the results of biological activity assay, it can be seen that the ferulic acid compounds containing a sulfonamide structure have moderate to excellent inhibitory activity against rice bacterial leaf streak pathogen, citrus canker pathogen and kiwi bacterial canker pathogen, among which compound B28 has the best activity, with inhibitory activities against rice bacterial leaf streak pathogen, citrus canker pathogen and kiwi bacterial canker pathogen being 82.7%, 80.7% and 79.9%, respectively, which are much higher than the control agents thiophanate-copper and thiazole zinc.

[0052] From the results of biological activity determination, it can be seen that the activity of the composite composition against rice bacterial leaf streak, citrus canker and kiwifruit canker is improved compared with the compounds before compounding. The inhibitory activity of composition 3 (B28: Zhongshengmycin wettable powder = 2:1) against rice bacterial leaf streak, citrus canker and kiwifruit bacterial canker reached 93.6%, 88.5% and 86.2% respectively. Therefore, the composite composition of B28 and Zhongshengmycin has a synergistic effect on rice bacterial leaf streak, citrus canker and kiwifruit bacterial canker.

[0053] In the wheat germination experiment, some compounds in this series showed a certain effect in promoting wheat seed germination, especially compounds B1 and B7, which showed better wheat seed germination activity than the control drug DA-6 at 20μg / mL. Overall, among the five concentrations, 20μg / mL had the highest germination rate.

[0054] The cucumber cotyledon expansion test of some target compounds showed that this series of compounds had certain cytokinin activity, among which compound B2 had an activity higher than that of the control drug thiolone at a concentration of 10 μg / mL. DETAILED DESCRIPTION

[0055] The synthesis method of the target compound B1-B28 is as follows. First, using triethylamine (TEA) as a catalyst, anhydrous piperazine reacts with various sulfonyl chlorides in dichloromethane to obtain the key intermediate A. Then, at room temperature, using 1-hydroxybenzotriazole (HOBt) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) as coupling agents, it is directly condensed with ferulic acid in DMF solvent to obtain the target compound with a yield of 58% to 75%. 1 H NMR, 13 The structures of the synthesized compounds were characterized by C NMR and HRMS.

[0056]

[0057] Preparation of target compound:

[0058] Intermediate A1-A28 (1.0 mmol) and ferulic acid (1.2 mmol) were subjected to acid amine coupling at room temperature with EDCI (1.2 mmol) and HOBt (1.2 mmol) in dry DMF (5 mL), and the reaction process was monitored by thin layer chromatography (TLC). After the reaction was completed, the mixture was poured into water and extracted three times with ethyl acetate to separate the organic phase. The organic layer was then washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated. The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate (1:1, v / v) as eluent to obtain the target compound B1-B28.

[0059] 2. Spectral data of target compounds

[0060]

[0061] (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-(phenylsulfonyl)piperazin-1-yl)prop-2-en-1-one(B1): white solid, mp 161–163℃, yield: 58.0%. 1H NMR(400MHz,DMSO-d6,ppm)δ:9.44(s,1H),7.76–7.71(m,3H),7.67–7.63(m,2H),7.36(d,J=15.3Hz,1H),7.28(s,1H),7.05(d,J=8.2Hz,1H),6.97(d,J=15.3Hz,1H),6.75(d,J=8.1Hz,1H),3.84–3.77(m,5H),3.66(t,J=16.0Hz,2H),2.91(t,J=5.0Hz,4H); 13 C NMR(100MHz,DMSO-d6,ppm)δ:165.0,148.6,147.8,142.8,134.6,133.4,129.5,127.6,126.5,122.6,115.4,114.0,111.2,55.8,46.1,44.2.HRMS(ESI)m / z:[M+Na] + calcd for C 20 H 22 N2O5SNa:425.1142,found:425.1137.

[0062]

[0063] (E)-1-(4-((2-fluorophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)pro p-2-en-1-one(B2):white solid,mp 159–161℃,yield:68.5%. 1 HNMR(400MHz,DMSO-d6,ppm)δ:9.44(s,1H),7.82–7.74(m,2H),7.52–7.42(m,2H),7.38(d,J=15.2Hz,1H),7.29(s,1H),7.07(d,J=8.2Hz,1H),7.00(d,J=15.3Hz,1H),6.76(d,J=8.1Hz,1H),3.81(s,3H),3.66(t,J=16.0Hz,4H),3.09(t,J=5.0Hz,4H); 13 C NMR(100MHz,DMSO-d6,ppm)δ:165.0,158.3(d, 1 J C-F =252.0Hz),148.6,147.8,142.8,136.3(d, 3J C-F =8.0Hz),131.0,126.5,125.3(d, 4 J C-F =4.0Hz),123.5(d, 2 J C-F =15.0Hz),122.7,117.8(d, 2 J C-F =22.0Hz),115.4,114.1,111.2,55.8,46.0,44.5.HRMS(ESI)m / z:[M+Na] + calcd forC 20 H 21 FN2O5SNa:443.1047,found:443.1045.

[0064]

[0065] (E)-1-(4-((3-fluorophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)pro p-2-en-1-one(B3):white solid,mp 152–153℃,yield:62.4%. 1 HNMR(400 MHz,DMSO-d6,ppm)δ:9.44(s,1H),7.61–7.57(m,4H),7.36(d,J=15.2 Hz,1H),7.28(s,1H),7.06(dd,J=8.2,2.0 Hz,1H),6.98(d,J=15.3 Hz,1H),6.75(d,J=8.1 Hz,1H),3.84–3.81(m,5H),3.67(t,J=16.0 Hz,2H),2.97(t,J=5.0 Hz,4H); 13 C NMR(100MHz,DMSO-d6,ppm)δ:164.9,161.9(d, 1 J C-F =248.0 Hz),148.6,147.8,142.8,136.8(d, 3 J C-F =7.0 Hz),131.9(d, 3 J C-F =8.0 Hz),126.5,123.8(d, 4 J C-F =3.0 Hz),122.6,120.6(d,2 J C-F =21.0 Hz),115.4,114.6(d, 2 J C-F =24.0 Hz),114.0,111.1,55.8,46.0,44.3.HRMS(ESI)m / z:[M+Na] + calcd for C 20 H 21 FN2O5SNa:443.1047,found:443.1041.

[0066]

[0067] (E)-1-(4-((4-fluorophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)pro p-2-en-1-one(B4):white solid,mp 170–172℃,yield:64.6%. 1 HNMR(400 MHz,DMSO-d6,ppm)δ:9.44(s,1H),7.84–7.80(m,2H),7.51–7.46(m,2H),7.37(d,J=15.2 Hz,1H),7.28(s,1H),7.06(dd,J=8.2,2.0 Hz,1H),6.98(d,J=15.3 Hz,1H),6.76(d,J=8.1 Hz,1H),3.84–3.81(m,5H),3.64(t,J=16.0 Hz,2H),2.92(t,J=5.0 Hz,4H); 13 C NMR(100 MHz,DMSO-d6,ppm)δ:164.9,164.8(d, 1 J C-F =251.0Hz),148.6,147.8,142.8,131.0(d, 4 J C-F =2.0 Hz),130.7(d, 3 J C-F =9.0 Hz),126.5,122.6,116.7(d, 2 J C-F =22.0Hz),115.4,114.0,111.2,55.8,46.3,44.2.HRMS(ESI)m / z:[M+Na] + calcd forC 20 H21 FN2O5SNa:443.1047,found:443.1041.

[0068]

[0069] (E)-1-(4-((2-chlorophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)pr op-2-en-1-one(B5):white solid,mp 161–162℃,yield:61.3%. 1 HNMR(400 MHz,DMSO-d6,ppm)δ:9.44(s,1H),7.99(dd,J=7.9,1.5 Hz,1H),7.73–7.66(m,2H),7.57(t,J=8.3 Hz,1H),7.40(d,J=15.2 Hz,1H),7.30(s,1H),7.08(dd,J=8.2,2.0Hz,1H),7.01(d,J=15.3 Hz,1H),6.77(d,J=8.1 Hz,1H),3.81(s,3H),3.68(t,J=16.0 Hz,4H),3.22(t,J=5.0 Hz,4H); 13 C NMR(100 MHz,DMSO-d6,ppm)δ:165.0,148.6,147.8,142.8,135.0,134.8,132.5,131.7,131.0,128.0,126.6,122.8,115.4,114.1,111.2,55.8,45.5,44.7.HRMS(ESI)m / z:[M+Na] + calcd for C 20 H 21 ClN2O5SNa:459.0752,found:459.0751.

[0070]

[0071] (E)-1-(4-((3-chlorophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)pr op-2-en-1-one(B6):white solid,mp 184–185℃,yield:63.8%. 1HNMR(400 MHz,DMSO-d6,ppm)δ:9.43(s,1H),7.82–7.68(m,4H),7.37(d,J=15.3 Hz,1H),7.28(s,1H),7.06(dd,J=8.2,1.9 Hz,1H),6.98(d,J=15.2 Hz,1H),6.76(d,J=8.1 Hz,1H),3.89–3.73(m,5H),3.65(t,J=14.3 Hz,2H),2.97(t,J=5.0 Hz,4H); 13 C NMR(100MHz,DMSO-d6,ppm)δ:164.9,148.6,147.8,142.7,136.7,134.3,133.4,131.6,127.0,126.5,126.3,122.6,115.4,114.0,111.1,55.8,46.0,44.2.HRMS(ESI)m / z:[M+Na] + calcdfor C 20 H 21 ClN2O5SNa:459.0752,found:459.0743.

[0072]

[0073] (E)-1-(4-((4-chlorophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)pr op-2-en-1-one(B7):white solid,mp 171–173℃,yield:64.7%. 1 HNMR(400 MHz,DMSO-d6,ppm)δ:9.44(s,1H),7.75–7.72(m,4H),7.37(d,J=15.2 Hz,1H),7.28(s,1H),7.06(dd,J=8.3,2.0 Hz,1H),6.97(d,J=15.3 Hz,1H),6.76(d,J=8.1 Hz,1H),3.82–3.72(m,5H),3.65(t,J=14.3 Hz,2H),2.94(t,J=4.9 Hz,4H); 13C NMR(100MHz,DMSO-d6,ppm)δ:164.9,148.6,147.8,142.8,138.3,133.6,129.7,129.5,126.5,122.6,115.4,114.0,111.2,55.8,46.4,44.1.HRMS(ESI)m / z:[M+Na] + calcd forC 20 H 21 ClN2O5SNa:459.0752,found:459.0749.

[0074]

[0075] (E)-1-(4-((2-bromophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)pr op-2-en-1-one(B8):white solid,mp 162–163℃,yield:58.9%. 1 HNMR(400 MHz,DMSO-d6,ppm)δ:9.44(s,1H),8.01(dd,J=7.5,2.0 Hz,1H),7.90(dd,J=7.5,1.7Hz,1H),7.62–7.58(m,2H),7.41(d,J=15.2 Hz,1H),7.30(s,1H),7.08(dd,J=8.2,2.0 Hz,1H),7.02(d,J=15.3 Hz,1H),6.77(d,J=8.1 Hz,1H),3.84–3.76(m,5H),3.65(t,J=16.0 Hz,2H),3.24(t,J=5.0 Hz,4H); 13 C NMR(100 MHz,DMSO-d6,ppm)δ:165.0,148.6,147.8,142.8,136.8,136.0,134.6,131.8,128.4,126.6,122.6,119.5,115.4,114.1,111.2,55.8,46.0,44.6.HRMS(ESI)m / z:[M+Na] + calcd for C 20 H 21 BrN2O5SNa:503.0247,found:503.0237.

[0076]

[0077] (E)-1-(4-((3-bromophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)pr op-2-en-1-one(B9):white solid,mp 152–153℃,yield:59.7%. 1 HNMR(400 MHz,DMSO-d6,ppm)δ:9.44(s,1H),7.95(d,J=7.3 Hz,1H),7.87(s,1H),7.76(d,J=7.9 Hz,1H),7.61(t,J=8.0 Hz,1H),7.37(d,J=15.2 Hz,1H),7.28(s,1H),7.06(dd,J=8.2,2.0 Hz,1H),6.98(d,J=15.3 Hz,1H),6.76(d,J=8.1 Hz,1H),3.84–3.79(m,5H),3.67(t,J=16.0 Hz,2H),2.97(t,J=5.0 Hz,4H); 13 C NMR(100 MHz,DMSO-d6,ppm)δ:165.0,148.6,147.8,142.8,136.8,136.3,131.8,129.7,126.6,126.5,122.6,122.6,115.4,114.0,111.1,55.8,45.9,44.0.HRMS(ESI)m / z:[M+Na] + calcd for C 20 H 21 BrN2O5SNa:503.0247,found:503.0233.

[0078]

[0079] (E)-1-(4-((4-bromophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)pr op-2-en-1-one(B10):white solid,mp 193–194℃,yield:64.6%. 1HNMR(400 MHz,DMSO-d6,ppm)δ:9.44(s,1H),7.87–7.84(m,2H),7.69–7.65(m,2H),7.37(d,J=15.3 Hz,1H),7.28(s,1H),7.06(dd,J=8.2,2.0 Hz,1H),6.97(d,J=15.3 Hz,1H),6.76(d,J=8.1 Hz,1H),3.84–3.81(m,5H),3.64(t,J=16.0 Hz,2H),2.93(t,J=5.0 Hz,4H); 13 C NMR(100 MHz,DMSO-d6,ppm)δ:164.9,148.6,147.8,142.8,134.0,132.6,129.6,127.5,126.5,122.7,115.4,114.0,111.1,55.8,46.5,44.5.HRMS(ESI)m / z:[M+Na] + calcd forC 20 H 21 BrN2O5SNa:503.0247,found:503.0240.

[0080]

[0081] (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-((2-(trifluoromethyl)phenyl)sulfonyl)piperaz in-1-yl)prop-2-en-1-one(B11):white solid,mp 155–156℃,yield:59.6%. 1 H NMR(400 MHz,DMSO-d6,ppm)δ:9.45(s,1H),8.08–8.03(m,2H),7.92–7.89(m,2H),7.41(d,J=15.3 Hz,1H),7.30(s,1H),7.08(dd,J=8.2,2.0 Hz,1H),7.02(d,J=15.3Hz,1H),6.77(d,J=8.1 Hz,1H),3.87–3.73(m,5H),3.65(t,J=16.0 Hz,2H),3.23(t,J=4.9 Hz,4H); 13C NMR(100 MHz,DMSO-d6,ppm)δ:165.0,148.6,147.8,142.8,136.5,133.7,133.6 131.3,128.7(q, 3 J C-F =6.0 Hz),126.6,126.2,122.7,122.6(q, 1 J C-F =272.0 Hz),115.4,114.1,111.2,55.8,45.7,44.8.HRMS(ESI)m / z:[M+Na] + calcd for C 21 H 21 F3N2O5SNa:493.1015,found:493.1013.

[0082]

[0083] (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-((3-(trifluoromethyl)phenyl)sulfonyl)piperaz in-1-yl)prop-2-en-1-one(B12):white solid,mp 166–167℃,yield:66.3%. 1 H NMR(400 MHz,DMSO-d6,ppm)δ:9.44(s,1H),8.13(d,J=7.9 Hz,1H),8.08(d,J=7.9Hz,1H),7.98(s,1H),7.91(t,J=8.0 Hz,1H),7.37(d,J=15.2 Hz,1H),7.28(s,1H),7.06(dd,J=8.2,1.9 Hz,1H),6.98(d,J=15.3 Hz,1H),6.76(d,J=8.1 Hz,1H),3.84–3.77(m,5H),3.68(t,J=16.0 Hz,2H),3.00(t,J=4.0 Hz,4H); 13 C NMR(100MHz,DMSO-d6,ppm)δ:164.9,148.6,147.8,142.8,136.2,131.7,131.3,130.3(q, 3 J C-F =4.0 Hz),130.2(q, 2 J C-F =32.0 Hz),126.5,123.9(q,3 J C-F =5.0 Hz),123.4(q, 1 J C-F =270.0 Hz),122.7,115.4,114.0,111.1,55.8,46.3,44.3.HRMS(ESI)m / z:[M+Na] + calcd for C 21 H 21 F3N2O5SNa:493.1015,found:493.1014.

[0084]

[0085] (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-((4-(trifluoromethyl)phenyl)sulfonyl)piperaz in-1-yl)prop-2-en-1-one(B13):white solid,mp 184–186℃,yield:70.5%. 1 H NMR(400 MHz,DMSO-d6,ppm)δ:9.44(s,1H),8.03–7.95(m,4H),7.37(d,J=15.2Hz,1H),7.28(s,1H),7.06(dd,J=8.3,2.0 Hz,1H),6.97(d,J=15.3 Hz,1H),6.76(d,J=8.1 Hz,1H),3.85–3.81(m,5H),3.67(t,J=20.0 Hz,2H),2.99(t,J=4.0 Hz,4H); 13 C NMR(100 MHz,DMSO-d6,ppm)δ:164.9,148.6,147.8,142.8,138.9,133.0(q, 2 J C-F =32.0 Hz),128.6,126.7(q, 3 J C-F =4.0 Hz),126.5,123.4(q, 1 J C-F =271.0 Hz),122.6,115.4,114.0,111.2,55.8,46.0,44.3.HRMS(ESI)m / z:[M+Na] + calcd for C 21 H 21F3N2O5SNa:493.1015,found:493.1012.

[0086]

[0087] (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-((3-methoxyphenyl)sulfonyl)piperazin-1-yl)p rop-2-en-1-one(B14):white solid,mp 156–158℃,yield:64.9%. 1 HNMR(400 MHz,DMSO-d6,ppm)δ:9.44(s,1H),7.57(t,J=8.1 Hz,1H),7.36(d,J=15.2 Hz,1H),7.32–7.28(m,3H),7.19(dd,J=2.6,1.7 Hz,1H),7.05(dd,J=8.2,2.0 Hz,1H),6.98(d,J=15.3 Hz,1H),6.75(d,J=8.1 Hz,1H),3.84(s,3H),3.81–3.72(m,5H),3.64(t,J=12.0 Hz,2H),2.93(t,J=5.1 Hz,4H); 13 C NMR(100 MHz,DMSO-d6,ppm)δ:164.9,159.6,148.6,147.8,142.8,135.8,130.7,126.5,122.6,119.6,119.2,115.4,114.0,112.4,111.2,55.8,55.7,46.1,44.2.HRMS(ESI)m / z:[M+Na] + calcd for C 21 H 24 N2O6SNa:455.1247,found:455.1239.

[0088]

[0089] (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)p rop-2-en-1-one(B15):white solid,mp 151–152℃,yield:69.5%. 1HNMR(400 MHz,DMSO-d6,ppm)δ:9.44(s,1H),7.69–7.65(m,2H),7.37(d,J=15.2 Hz,1H),7.28(s,1H),7.17–7.13(m,2H),7.06(dd,J=8.2,2.0 Hz,1H),6.98(d,J=15.2 Hz,1H),6.76(d,J=8.1 Hz,1H),3.84(s,3H),3.82–3.72(m,5H),3.65(t,J=8.0 Hz,2H),2.86(t,J=5.0 Hz,4H); 13 C NMR(100 MHz,DMSO-d6,ppm)δ:164.9,162.9,148.6,147.8,142.8,129.9,126.5,125.9,122.7,115.4,114.7,114.0,111.1,55.8,55.7,46.4,44.2.HRMS(ESI)m / z:[M+Na] + calcd for C 21 H 24 N2O6SNa:455.1247,found:455.1247.

[0090]

[0091] (E)-2-((4-(3-(4-hydroxy-3-methoxyphenyl)acryloyl)piperazin-1-yl)sulfonyl)benzonitril e(B16):white solid,mp 160–162℃,yield:65.1%. 1 H NMR(400MHz,DMSO-d6,ppm)δ:9.44(s,1H),8.16(d,J=7.6 Hz,1H),8.02(d,J=7.9 Hz,1H),7.97–7.88(m,2H),7.39(d,J=15.2 Hz,1H),7.29(s,1H),7.07(dd,J=8.2,2.0 Hz,1H),7.01(d,J=15.2 Hz,1H),6.76(d,J=8.1 Hz,1H),3.85–3.81(m,5H),3.67(t,J=16.0Hz,2H),3.15(t,J=5.0 Hz,4H); 13C NMR(100 MHz,DMSO-d6,ppm)δ:165.0,148.6,147.8,142.8,137.7,136.4,134.1,133.9,130.3,126.5,122.7,116.5,115.4,114.0,111.2,109.8,55.8,46.1,44.3.HRMS(ESI)m / z:[M+Na] + calcd for C 21 H 21 N3O5SNa:450.1094,found:450.1086.

[0092]

[0093] (E)-3-((4-(3-(4-hydroxy-3-methoxyphenyl)acryloyl)piperazin-1-yl)sulfonyl)benzonitril e(B17):white solid,mp 160–161℃,yield:67.2%. 1 H NMR(400MHz,DMSO-d6,ppm)δ:9.44(s,1H),8.22–8.18(m,2H),8.06(d,J=8.2 Hz,1H),7.85(t,J=7.9 Hz,1H),7.37(d,J=15.2 Hz,1H),7.29(s,1H),7.06(d,J=8.2 Hz,1H),6.98(d,J=15.3Hz,1H),6.76(d,J=8.1 Hz,1H),3.85–3.81(m,5H),3.66(t,J=12.0 Hz,2H),3.00(t,J=5.1 Hz,4H); 13 C NMR(100 MHz,DMSO-d6,ppm)δ:164.9,148.6,147.8,142.8,137.0,136.2,132.0,131.2,130.9,126.5,122.7,117.5,115.4,114.0,113.0,111.1,55.8,46.3,44.2.HRMS(ESI)m / z:[M+Na] + calcd for C 21 H 21 N3O5SNa:450.1094,found:450.1090.

[0094]

[0095] (E)-4-((4-(3-(4-hydroxy-3-methoxyphenyl)acryloyl)piperazin-1-yl)sulfonyl)benzonitril e(B18):white solid,mp 179–181℃,yield:69.4%. 1 H NMR(400MHz,DMSO-d6,ppm)δ:9.44(s,1H),8.13–8.11(m,2H),7.94–7.91(m,2H),7.37(d,J=15.2Hz,1H),7.28(s,1H),7.06(dd,J=8.1,2.0 Hz,1H),6.97(d,J=15.2 Hz,1H),6.76(d,J=8.1 Hz,1H),3.84–3.72(m,5H),3.66(t,J=16.0 Hz,2H),2.98(t,J=5.0 Hz,4H); 13 C NMR(100 MHz,DMSO-d6,ppm)δ:164.9,148.6,147.8,142.8,139.0,133.6,128.3,126.5,122.6,117.6,115.8,115.4,114.0,111.2,55.8,46.1,44.2.HRMS(ESI)m / z:[M+Na] + calcd forC 21 H 21 N3O5SNa:450.1094,found:450.1084.

[0096]

[0097] (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-((2-nitrophenyl)sulfonyl)piperazin-1-yl)prop-2-en-1-one(B19):yellow solid,mp 173–175℃,yield:67.8%. 1HNMR(400 MHz,DMSO-d6,ppm)δ:9.45(s,1H),8.02–7.99(m,2H),7.94–7.84(m,2H),7.41(d,J=15.2 Hz,1H),7.31(s,1H),7.08(dd,J=8.2,2.0 Hz,1H),7.03(d,J=15.2 Hz,1H),6.77(d,J=8.1 Hz,1H),3.82–3.72(m,5H),3.66(t,J=16.0 Hz,2H),3.23(t,J=5.2 Hz,4H); 13 C NMR(100 MHz,DMSO-d6,ppm)δ:165.0,148.6,148.0,147.8,142.9,135.1,132.4,130.5,128.7,126.6,124.3,122.7,115.4,114.0,111.2,55.8,46.2,44.5.HRMS(ESI)m / z:[M+Na] + calcd for C 20 H 21 N3O7SNa:470.0992,found:470.0989.

[0098]

[0099] (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-((3-nitrophenyl)sulfonyl)piperazin-1-yl)prop-2-en-1-one(B20):yellow solid,mp 208–210℃,yield:69.6%. 1 HNMR(400 MHz,DMSO-d6,ppm)δ:9.43(s,1H),8.54(d,J=8.3 Hz,1H),8.37(s,1H),8.18(d,J=8.1 Hz,1H),7.94(t,J=8.0 Hz,1H),7.36(d,J=15.3 Hz,1H),7.27(s,1H),7.05(dd,J=8.2,2.0 Hz,1H),6.97(d,J=15.3 Hz,1H),6.75(d,J=8.1 Hz,1H),3.85–3.80(m,5H),3.67(t,J=16.0 Hz,2H),3.03(t,J=5.0 Hz,4H); 13C NMR(100 MHz,DMSO-d6,ppm)δ:164.8,148.6,148.2,147.8,142.8,136.4,133.5,131.6,128.0,126.5,122.7,122.2,115.4,113.9,111.1,55.8,46.3,44.2.HRMS(ESI)m / z:[M+Na] + calcd for C 20 H 21 N3O7SNa:470.0992,found:470.0987.

[0100]

[0101] (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-((4-nitrophenyl)sulfonyl)piperazin-1-yl)prop-2-en-1-one(B21):yellow solid,mp 199–200℃,yield:70.8%. 1 HNMR(400 MHz,DMSO-d6,ppm)δ:9.44(s,1H),8.44–8.41(m,2H),8.03–7.99(m,2H),7.36(d,J=15.2 Hz,1H),7.27(s,1H),7.05(dd,J=8.2,2.0 Hz,1H),6.97(d,J=15.2 Hz,1H),6.75(d,J=8.1 Hz,1H),3.85–3.80(m,5H),3.67(t,J=16.0 Hz,2H),3.00(t,J=4.9 Hz,4H); 13 C NMR(100 MHz,DMSO-d6,ppm)δ:164.9,150.2,148.6,147.8,142.9,140.4,129.1,126.5,124.8,122.7,115.4,113.9,111.2,55.8,46.3,44.2.HRMS(ESI)m / z:[M+Na] + calcd forC 20 H 21 N3O7SNa:470.0992,found:470.0986.

[0102]

[0103] (E)-1-(4-([1,1'-biphenyl]-4-ylsulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one(B22):white solid,mp 196–197℃,yield:74.6%. 1 HNMR(400MHz,DMSO-d6,ppm)δ:9.44(s,1H),7.94–7.92(m,2H),7.82–7.80(m,2H),7.76–7.72(m,2H),7.52–7.49(m,2H),7.44(d,J=7.0 Hz,1H),7.36(d,J=15.2 Hz,1H),7.28(s,1H),7.05(dd,J=8.2,1.9 Hz,1H),6.98(d,J=15.3 Hz,1H),6.75(d,J=8.2 Hz,1H),3.85–3.80(m,5H),3.68(t,J=16.0 Hz,2H),2.96(t,J=4.9 Hz,4H); 13 C NMR(100 MHz,DMSO-d6,ppm)δ:165.0,148.6,147.8,144.9,142.8,138.3,133.3,129.2,128.7,128.3,127.7,127.2,126.5,122.7,115.4,114.0,111.1,55.8,46.5,44.3.HRMS(ESI)m / z:[M+Na] + calcdfor C 26 H 26 N2O5SNa:501.1455,found:501.1449.

[0104]

[0105] (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-(naphthalen-2-ylsulfonyl)piperazin-1-yl)pro p-2-en-1-one(B23):white solid,mp 182–183℃,yield:73.6%. 1HNMR(400 MHz,DMSO-d6,ppm)δ:9.43(s,1H),8.45(s,1H),8.19(dd,J=18.3,8.3 Hz,2H),8.07(d,J=8.1 Hz,1H),7.77–7.66(m,3H),7.33(d,J=15.2 Hz,1H),7.25(s,1H),7.03(dd,J=8.2,2.0 Hz,1H),6.95(d,J=15.2 Hz,1H),6.74(d,J=8.1 Hz,1H),3.86–3.79(m,5H),3.68(t,J=16.0 Hz,2H),2.99(t,J=4.9 Hz,4H); 13 C NMR(100 MHz,DMSO-d6,ppm)δ:164.9,148.6,147.8,142.7,134.5,132.0,131.8,129.5,129.4,129.1,128.9,127.9,127.7,126.5,122.8,122.6,115.4,114.0,111.1,55.7,46.4,44.3.HRMS(ESI)m / z:[M+Na] + calcd for C 24 H 24 N2O5SNa:475.1298,found:475.1289.

[0106]

[0107] (E)-1-(4-((2,6-difluorophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one(B24):white solid,mp 160–161℃,yield:70.1%. 1 HNMR(400MHz,DMSO-d6,ppm)δ:9.44(s,1H),7.78(t,J=8.5 Hz,1H),7.41–7.29(m,4H),7.07(dd,J=8.2,2.0 Hz,1H),7.01(d,J=15.3 Hz,1H),6.77(d,J=8.1 Hz,1H),3.83–3.72(m,5H),3.68(t,J=16.0 Hz,2H),3.16(t,J=4.9 Hz,4H); 13C NMR(100MHz,DMSO-d6,ppm)δ:165.0,159.0(dd, 1 J C-F =255.0, 3 J C-F =4.0 Hz),148.6,147.8,142.8,136.4(t, 3 J C-F =11.0Hz),126.6,122.6,115.4,114.1,113.8(dd, 2 J C-F =24.0, 4 J C-F =3.0 Hz),113.4(t, 2 J C-F =17.0 Hz),111.2,55.8,45.8,44.3.HRMS(ESI)m / z:[M+Na] + calcd for C 20 H 20 F2N2O5SNa:461.0953,found:461.0945.

[0108]

[0109] (E)-1-(4-((2,4-dichlorophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one(B25):white solid,mp 167–169℃,yield:66.3%. 1 HNMR(400MHz,DMSO-d6,ppm)δ:9.45(s,1H),7.98–7.91(m,2H),7.66(dd,J=8.6,2.2 Hz,1H),7.40(d,J=15.2 Hz,1H),7.30(s,1H),7.08(dd,J=8.2,2.0 Hz,1H),7.01(d,J=15.2Hz,1H),6.77(d,J=8.1 Hz,1H),3.83–3.70(m,5H),3.65(t,J=8.0 Hz,2H),3.23(t,J=4.9 Hz,4H); 13C NMR(100 MHz,DMSO-d6,ppm)δ:165.0,148.6,147.8,142.8,138.7,134.0,133.0,132.3,131.9,128.1,126.5,122.6,115.4,114.1,111.2,55.8,45.9,44.7.HRMS(ESI)m / z:[M+Na] + calcd for C 20 H 20 Cl2N2O5SNa:493.0362,found:493.0360.

[0110]

[0111] (E)-1-(4-((3-chloro-2-fluorophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyp henyl)prop-2-en-1-one(B26):white solid,mp 157–158℃,yield:67.4%. 1 H NMR(400 MHz,DMSO-d6,ppm)δ:9.44(s,1H),7.95(t,J=6.6 Hz,1H),7.75(t,J=6.3Hz,1H),7.45(t,J=7.6 Hz,1H),7.39(d,J=15.2 Hz,1H),7.29(s,1H),7.07(dd,J=8.2,2.0 Hz,1H),7.00(d,J=15.3 Hz,1H),6.76(d,J=8.1 Hz,1H),3.87–3.75(m,5H),3.64(t,J=8.0 Hz,2H),3.14(t,J=4.9 Hz,4H); 13 C NMR(100 MHz,DMSO-d6,ppm)δ:164.9,153.8(d, 1 J C-F =254.0 Hz),148.6,147.8,142.7,136.1,129.7,126.6,126.0(d, 3 J C-F =5.0Hz),125.5(d, 2 J C-F =15.0 Hz),122.6,122.1(d, 2 J C-F=18.0 Hz),115.4,114.1,111.2,55.8,46.0,44.4.HRMS(ESI)m / z:[M+Na] + calcd for C 20 H 20 FClN2O5SNa:477.0658,found:477.0654.

[0112]

[0113] (E)-1-(4-((3-chloro-4-fluorophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyp henyl)prop-2-en-1-one(B27):white solid,mp 160–161℃,yield:69.7%. 1 H NMR(400MHz,DMSO-d6,ppm)δ:9.43(s,1H),7.95(dd,J=6.8,2.3Hz,1H),7.78(dd,J=8.7,4.5Hz,1H),7.68(t,J=8.8Hz,1H),7.37(d,J=15.2Hz,1H),7.28(s,1H),7.06(dd,J=8.2,2.0Hz,1H),6.99(d,J=15.3Hz,1H),6.76(d,J=8.1Hz,1H),3.84–3.72(m,5H),3.67(t,J=16.0Hz,2H),2.98(t,J=5.0Hz,4H); 13 C NMR(100MHz,DMSO-d6,ppm)δ:164.9,160.1(d, 1 J C-F =253.0Hz),148.6,147.8,142.8,132.3(d, 4 J C-F =4.0Hz),130.1,129.1(d, 3 J C-F =9.0Hz),126.5,122.7,121.3(d, 2 J C-F =19.0Hz),118.3(d, 2 J C-F =22.0Hz),115.4,114.0,111.1,55.8,46.3,44.3.HRMS(ESI)m / z:[M+Na] +calcd forC 20 H 20 FClN2O5SNa:477.0658,found:477.0656.

[0114]

[0115] (E)-1-(4-((4-bromo-2-fluorophenyl)sulfonyl)piperazin-1-yl)-3-(4-hydroxy-3-methoxyp henyl)prop-2-en-1-one(B28):white solid,mp 158–160℃,yield:68.8%. 1 H NMR(400MHz,DMSO-d6,ppm)δ:9.44(s,1H),7.89(dd,J=9.9,1.8Hz,1H),7.70–7.65(m,2H),7.39(d,J=15.2Hz,1H),7.29(s,1H),7.07(dd,J=8.3,2.0Hz,1H),7.00(d,J=15.3Hz,1H),6.76(d,J=8.1Hz,1H),3.84–3.79(m,5H),3.64(t,J=8.0Hz,2H),3.11(t,J=5.0Hz,4H); 13 C NMR(100MHz,DMSO-d6,ppm)δ:165.0,158.2(d, 1 J C-F =258.0Hz),148.6,147.8,142.7,132.2,128.5(d, 4 J C-F =3.0Hz),128.3(d, 3 J C-F =10.0Hz),126.6,123.2(d, 3 J C-F =14.0Hz),122.6,121.2(d, 2 J C-F =25.0Hz),115.4,114.1,111.2,55.8,45.9,44.4.HRMS(ESI)m / z:[M+Na] + calcd for C 20 H 20 FBrN2O5SNa:521.0152,found:521.0147.

[0116] 3. Antimicrobial activity data of target compounds

[0117] The classical turbidity method was used to determine the inhibitory effects of compounds B1-B28 on three plant pathogens (Psa, Xoc, Xac). Pure dimethyl sulfoxide was used as a negative control, and the fungicides zinc thiazole and thiophanate-methyl were used as positive controls. The inhibitory effects of the compounds on pathogens were detected at concentrations of 100 and 50 μg / mL. 40 μL of NB containing bacteria Psa, Xoc or Xac was mixed with 4 mL of NB and 1 mL of 0.1% Tween-20 solution containing the tested compound or BMT. The NB solvent was prepared as follows: 3.0 g beef extract, 5.0 g peptone, 1.0 g yeast powder, 10.0 g glucose, 1000 mL distilled water, pH 7.0-7.2. The above solutions were incubated at 28±1°C and shaken continuously at 180 rpm for 1 to 3 days. By measuring the optical density at 595 nm (OD 595 ) to monitor bacterial growth.

[0118] 4. I=(C tur -T tur ) / C tur ×100%

[0119] The corrected NB bacterial growth turbidity value is expressed as: C tur , blank control group; T tur , combined treatment group; I, ​​inhibitory effect of the combined treatment group on bacteria.

[0120] Table 1. In vitro antibacterial activity of compounds B1-B28 against Xanthomonas oryzae, Xanthomonas citri var. citri and Xanthomonas avium

[0121]

[0122]

[0123] From the results of biological activity assay in Table 1, it can be seen that the ferulic acid compounds containing sulfonamide structure have moderate to excellent inhibitory activity against rice bacterial leaf streak fungus, citrus canker and kiwi bacterial canker fungus, among which compound B28 has the best activity, with inhibitory activities against rice bacterial leaf streak fungus, citrus canker and kiwi bacterial canker fungus of 82.7%, 80.7% and 79.9%, respectively, which are much higher than the control agents thiophanate-copper and thiazole zinc.

[0124] 4. Preparation of target compound B28 composition

[0125] The wettable powder of the target compound B28 and Zhongshengmycin is used to prepare a composite composition. In each composition, the ratio of the target compound B28 and Zhongshengmycin is calculated according to the mass ratio. The following preparations of the target compound B28 and Zhongshengmycin are prepared as needed.

[0126] Composition 1: B28: Zhongshengmycin wettable powder = 1:1

[0127] Composition 2: B28: Zhongshengmycin wettable powder = 1:2

[0128] Composition 3: B28: Zhongshengmycin wettable powder = 2:1

[0129] Anti-rice bacterial leaf streak disease, citrus canker and kiwi fruit bacterial canker activity of the composition of target compound B28

[0130] The antimicrobial activity of the combination of target compound B28 and zhongshengmycin was tested against oxysporum streak pathogenicum of rice, citrus canker and kiwi fruit bacterial canker using the turbidity method (the antimicrobial activity test method mentioned previously).

[0131] Table 2 Inhibitory activity of drugs against bacterial leaf streak pathogen of rice, citrus canker pathogen and kiwi fruit bacterial canker pathogen

[0132]

[0133] The in vitro growth rate method was used to test the activity of the composition against rice bacterial leaf streak, citrus canker and kiwi fruit bacterial canker at a concentration of 100 μg / mL. From the biological activity test results in Table 2, it can be seen that the activity of the composite composition against rice bacterial leaf streak, citrus canker and kiwi fruit bacterial canker was improved compared with the compounds before compounding. The inhibitory activity of composition 3 (B28: Zhongshengmycin wettable powder = 2:1) against rice bacterial leaf streak, citrus canker and kiwi fruit bacterial canker reached 93.6%, 88.5% and 86.2%, respectively. Therefore, the composite composition of B28 and Zhongshengmycin has a synergistic effect on rice bacterial leaf streak, citrus canker and kiwi fruit bacterial canker.

[0134] 5. Plant growth regulating activity

[0135] (1) Wheat seed germination experiment

[0136] First, the target compound to be tested and the control drug DA-6 (aminoethyl ester) were each prepared into a 5% aqueous solution, and then they were diluted with distilled water to a concentration of 10μg / mL, 20μg / mL, 30μg / mL, 60μg / mL and 120μg / mL of plant growth regulator aqueous solution. Subsequently, wheat seeds with rounded appearance and full grains were carefully selected, and these seeds were cultivated with 5% target compound dilution solution, 5% DA-6 dilution solution and clean water for 8 hours. A total of 240 seeds were treated, and each treatment was repeated three times. After the treatment, the seeds were placed one by one in culture dishes of the same size, and double-layer filter paper was laid in the culture dishes, and the number of wheat seeds in each culture dish was ensured to be the same. The wheat seeds were germinated at a constant temperature of 25°C, and the wheat seeds were kept moist during this period. During the seed germination process, carefully observe the germination status of the wheat seeds. When the embryo length is about 0.5cm, take it as the standard. After one day, count the germination rate of all the wheat seeds in the culture dish. After completing the statistical work, calculate the germination promotion rate of each dilution compared with clean water. The specific test data is shown in the following table.

[0137] Table 3. Wheat germination test of some target compounds

[0138]

[0139]

[0140] In the wheat germination experiment, some compounds in this series showed a certain effect in promoting wheat seed germination, especially compounds B1 and B7, which showed better wheat seed germination activity than the control drug DA-6 at 20μg / mL. Overall, among the five concentrations, 20μg / mL had the highest germination rate.

[0141] (2) Cucumber cotyledon expansion experiment

[0142] First, the cucumber seeds required for the biological activity test were soaked, and then sown in an enamel dish with 0.7% agar and a lid, and placed in a dark environment at 26°C for 72 hours, and then carefully selected cucumber seedlings with relatively uniform cotyledon sizes for use. Sample preparation used the filter paper method in the determination of plant hormone active substances. The test concentrations of the samples were set at 10μg / mL and 1μg / mL, and the solvent was DMF. The specific operation process is as follows: first, the samples were prepared into 100μg / mL and 10μg / mL DMF mother solutions, and then 0.3mL of each of the three mother solutions of different concentrations was taken and evenly dripped on a filter paper with a diameter of 6cm. After the solvent was naturally dried, the filter paper containing the sample was placed in a culture dish of the same size as the filter paper, and 3mL of distilled water and 10 cotyledons were added to each culture dish, thus forming a 10μg / mL and 1μg / mL treatment group. The cucumber seeds treated with distilled water were used as the control group. All the culture dishes were placed at 6°C and 3000 Lux for cultivation. After 72 hours, the fresh weight of the cucumber cotyledons in each culture dish was measured. Each treatment was repeated twice to reduce the error. The relevant results were recorded. After the statistics were completed, the expansion promotion rate of the cotyledons of the cucumber seeds treated with the target compound dilution and thidiazuron was calculated compared with the cotyledons of the cucumber seeds treated with water. The detailed experimental results can be found in the table below.

[0143] Table 4. Cucumber cotyledon expansion test of some target compounds

[0144]

[0145]

[0146] The cucumber cotyledon expansion test of some target compounds showed that this series of compounds had certain cytokinin activity, among which compound B2 had an activity higher than that of the control drug thiolone at a concentration of 10 μg / mL.

Claims

1. A novel ferulic acid derivative containing a sulfonamide structure, characterized in that: The derivative structural formula is as follows: Wherein, R is phenyl, substituted phenyl, or heterocycle.

2. A novel ferulic acid derivative containing a sulfonamide structure according to claim 1, characterized in that: The R is phenyl, substituted phenyl, or heterocyclic ring; the substituted phenyl is halogen, trifluoromethyl, cyano, nitro, or mono- or di-substituted phenyl; and the heterocyclic ring is naphthalene.

3. The method for preparing a novel ferulic acid derivative containing a sulfonamide structure as claimed in claim 1, characterized in that: The reaction formula is as follows:

4. The method for preparing a novel ferulic acid derivative containing a sulfonamide structure according to claim 3, characterized in that: The method comprises the following steps: firstly, using triethylamine as a catalyst, anhydrous piperazine reacts with various sulfonyl chlorides in dichloromethane to obtain a key intermediate A; then, at room temperature, using 1-hydroxybenzotriazole and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride as coupling agents, directly condensing with ferulic acid in a DMF solvent to obtain a target compound.

5. Use of a novel ferulic acid derivative containing a sulfonamide structure as claimed in claim 1 or 2 in the preparation of drugs and medicaments for preventing and controlling bacterial leaf streak pathogen of rice, bacterial canker pathogen of kiwi fruit and bacterial canker pathogen of citrus.

6. A compound pesticide composition, characterized in that: The composition comprises the novel ferulic acid derivative containing sulfonamide structure as claimed in claim 1 and zhongshengmycin.

7. The composition according to claim 6, characterized in that: The mass ratio of the novel ferulic acid derivative containing a sulfonamide structure to zhongshengmycin is 1:2-2:

1.

8. Use of the composition according to claim 6 in the preparation of drugs for preventing and controlling rice bacterial leaf streak pathogen, citrus canker pathogen and kiwifruit canker pathogen.

9. The composition according to claim 6, characterized in that: The derivative is B28.

10. Application of the novel ferulic acid derivative containing sulfonamide structure as claimed in claim 1 or 2 in the preparation of plant growth regulators.

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