CN115490649B - Malonic ester compound containing isothiazole benzene sulfonamide group with agricultural activity, preparation method and application - Google Patents
Malonic ester compound containing isothiazole benzene sulfonamide group with agricultural activity, preparation method and application Download PDFInfo
- Publication number
- CN115490649B CN115490649B CN202211030531.6A CN202211030531A CN115490649B CN 115490649 B CN115490649 B CN 115490649B CN 202211030531 A CN202211030531 A CN 202211030531A CN 115490649 B CN115490649 B CN 115490649B
- Authority
- CN
- China
- Prior art keywords
- isothiazole
- compound containing
- malonate
- benzene sulfonamide
- activity
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/02—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
- C07D275/03—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P3/00—Fungicides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Environmental Sciences (AREA)
- Wood Science & Technology (AREA)
- Plant Pathology (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Pest Control & Pesticides (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Dentistry (AREA)
- Health & Medical Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
The invention discloses an agricultural active malonate compound containing an isothiazole benzene sulfonamide group, which is characterized in that: the general formula is shown in the following formula (I):wherein R is 1 Is C1-C3 alkyl; r is R 2 Phenyl, substituted phenyl, furyl, cyclohexyl or pentyl. The compound has the activity of resisting tobacco mosaic virus, cucumber mosaic virus, fusarium graminearum, pepper fusarium wilt, pseudomonas tolla, citrus canker and kiwi fruit canker.
Description
Technical Field
The invention relates to the technical field of chemistry, in particular to an isothiazole benzene sulfonamide group-containing malonate compound with agricultural activity, a preparation method of the compound and application of the compound in inhibiting tobacco mosaic virus, cucumber mosaic virus, fusarium graminearum, pepper fusarium wilt, pseudomonas tolla, citrus canker and kiwi fruit canker.
Background
Among plant-invasive diseases, three types of fungal diseases, bacterial diseases and viral diseases are common. Fungal diseases are one of the main reasons for crop losses, 80% of crop diseases are caused by pathogenic fungi, the harmfulness of the fungal diseases is extremely high, common alternaria alternata and pepper fusarium wilt are: zinc thiazole, oxymetazol, carbendazim and the like, but the antibacterial agents bring great pressure to environmental protection. Plant virus disease is a global disease, and the number of plant virus species found worldwide is more than 950, and is the second most serious type of worldwide plant disease next to fungi in agricultural production. Viruses such as tobacco mosaic virus (Tobacco mosaic virus, TMV) and cucumber mosaic virus (Cucumber mosaic virus, CMV) are typical plant virus diseases affecting crop health, and can invade host cells to cause plant leaves to fade green until the whole plant is necrotic, so that huge economic losses are caused to crops, at present, ningnanmycin, ribavirin and the like are common anti-plant virus agents, but the problems of high cost, low efficiency and the like exist, in order to search for green and efficient anti-plant virus agents, agrichemicasts have studied a lot of ways from plant sources, chemical synthesis and the like, and effective antiviral agents are screened, however, a high-efficiency antiviral agent is not developed. Thus, the search for new, efficient, environmentally friendly anti-plant viral agents remains a significant challenge for pesticide researchers.
Heterocyclic compounds widely exist in the nature, and due to the structural diversity, the heterocyclic compounds have heterocyclic structures in a plurality of natural products with biological activity and some compounds with pharmaceutical activity, the heterocyclic compounds become hot spots for creating medicines, and isothiazole heterocyclic compounds have abundant biological activity and are widely applied to the fields of industry, agriculture, medicine and the like. In particular, isothiazole compounds play an important role in the control of fungal and viral diseases in agriculture. In recent years, compounds containing isothiazole heterocycle have been found to have better anti-plant virus activity and antifungal activity.
In 1996, ikeda et al (Ikeda, K.; ueyama, S.; endo, K; kate, C.Isothiazole derivatives, a process for production thereof and uses thereof: U.S. patent 5,484,934[ P.1996 ]) reported that the sulfonyl-containing isothiazole derivatives have good control effects on rice blast, cucumber downy mildew, tomato late blight, grape brown rot, white rot, dry rot, etc.
In 2001, pilk; ongton et al (Piclkongton, B.L.; aemstrong, S.; banrnes, N.J.; azine derivates as petcide:Wo,001055141[ P ].2001 ] reported that N-isothiazole derivatives have a certain activity against aphids and an inhibition rate against aphids of 80% -100% at a concentration of 500. Mu.g/mL.
In 2002, michelott et al (Michelotti, E.L.; young, D.H. hepatoline N-Acetonybenzamides and their use as fungicide: EP 1229037[ P ] 2002) reported that the bactericidal activity of an isothiazole derivative having an amide structure was 91.6% at a concentration of 100. Mu.g/mL and 100% at a concentration of 300. Mu.g/mL.
In conclusion, the isothiazole derivative shows a certain bactericidal and insecticidal activity. In order to create novel efficient antiviral agents and bactericides, the invention designs and synthesizes a series of malonate compounds containing N-5-methylisothiazole benzene sulfonamide groups on the basis of early work, and is expected to screen high-activity antiviral drugs and antibacterial drugs.
Disclosure of Invention
The invention aims to provide a malonate compound containing an isothiazole benzene sulfonamide group and a preparation method thereof.
The invention also aims at preventing and controlling the activities of tobacco mosaic virus, cucumber mosaic virus, fusarium graminearum, pepper fusarium wilt, pseudomonas tolla, citrus canker and kiwi fruit canker.
The technical scheme of the invention is as follows: an agricultural active malonate compound containing isothiazole benzene sulfonamide group, which has the following formula (I):
wherein R is 1 Is C1-C3 alkyl; r is R 2 Phenyl, substituted phenyl, furyl, cyclohexyl or pentyl.
The C1-C3 alkyl is methyl, ethyl or isopropyl.
The substituent of the substituted phenyl is halogen, methyl or methoxy.
The preparation method of the malonic ester compound containing the isothiazole benzene sulfonamide group with agricultural activity is characterized by comprising the following steps of: the synthesis method of the malonate compound containing the isothiazole benzene sulfonamide group by using 4-amino-N- (5-methylisothiazole-3-yl) benzene sulfonamide, substituted aldehyde and malonate as raw materials and toluene as a solvent through a microwave method comprises the following synthesis routes:
the synthesis steps and the process conditions are as follows: adding 4-amino-N- (5-methylisothiazole-3-yl) benzenesulfonamide, substituted aldehyde and malonate as raw materials into a single-mouth bottle, adding toluene, reacting in a microwave reactor for 2-4 hours, recovering solvent under reduced pressure, and separating by column chromatography to obtain the target product.
The column chromatographic separation conditions are petroleum ether: ethyl acetate=6:1V/V.
The malonic ester compound containing the isothiazole benzene sulfonamide group with agricultural activity is applied to the preparation of medicines and medicaments for preventing and treating crop diseases.
The crop diseases comprise tobacco mosaic virus, cucumber mosaic virus, fusarium graminearum, pepper fusarium wilt, pseudomonas tolla, citrus canker and kiwi fruit canker.
Wherein part of the compounds (I) 1 -I 7 ) The structural characteristics of (2) are as follows:
I 1 ：R 1 ＝Et R 2 ＝Ph；
I 2 ：R 1 ＝i-Pr R 2 ＝4-Br-Ph；
I 3 ：R 1 ＝Me R 2 ＝4-Me-Ph；
I 4 ：R 1 ＝Et R 2 ＝4-OMe-Ph；
I 5 ：R 1 ＝Et R 2 ＝Furyl；
I 6 ：R 1 ＝Me R 2 ＝Ch；
I 7 ：R 1 ＝Et R 2 ＝Pen。
the invention has the beneficial effects that: the malonate compound containing the isothiazole benzene sulfonamide group with the activity of resisting tobacco mosaic virus, cucumber mosaic virus, dactylotheca sp, pepper fusarium wilt, pseudomonas tolla, citrus canker and kiwi canker is synthesized. And in the present invention, compound I 5 The activity of the composition for preventing and treating tobacco mosaic virus or cucumber mosaic virus is superior to that of a commercial control reagent Ningnanmycin in treatment, protection and passivation. In the compounds of the invention I 3 And I 5 The inhibition rate to the fusarium graminearum and the pepper fusarium wilt is obviously better than that of the commercial control medicament hymexazol. In the present inventionOf the compounds I of (2) 5 The inhibition activity of the bacterial strain on the pseudomonas tolla, the citrus canker and the kiwi fruit canker is equivalent to that of the commercial control medicament thiabendazole. Compound I in the present invention 5 The plant inhibitor has better inhibition activity on various plant diseases.
Detailed Description
Example 1: diethyl 2- ((((4- (N- (5-methylisothiazol-3-yl) sulfamoyl) phenyl) amino) (phenyl) methyl) malonate;
in a 100mL single-necked flask, 4-amino-N- (5-methylisothiazol-3-yl) benzenesulfonamide (0.001 mol), benzaldehyde (0.001 mol) and diethyl malonate (0.0015 mol) were added, p-xylene (40 mL) was added as a solvent, the temperature was raised and the flow was reversed, TLC was used to monitor the progress of the reaction, the reaction was terminated after 4 hours, and the solvent was recovered under reduced pressure and subjected to column chromatography (petroleum ether: ethyl acetate=8:1V/V) to obtain the objective product.
Example 2: diisopropyl 2- ((4-bromophenyl) ((4- (N- (5-methylisothiazol-3-yl) sulfamoyl) phenyl) amino) methyl) malonate;
in a 100mL single-necked flask, 4-amino-N- (5-methylisothiazol-3-yl) benzenesulfonamide (0.001 mol), 4-bromobenzaldehyde (0.001 mol) and diisopropyl malonate (0.0015 mol) were added, p-xylene (40 mL) was added as a solvent, the reaction was heated and refluxed, TLC was used to monitor the progress of the reaction, the reaction was completed for 5 hours, and the solvent was recovered under reduced pressure and subjected to column chromatography (petroleum ether: ethyl acetate: 8:1V/V) to obtain the objective product.
Example 3: dimethyl 2- ((((4- (N- (5-methylisothiazol-3-yl) sulfamoyl) phenyl) amino) (p-tolyl) methyl) malonate;
in a 100mL single-necked flask, 4-amino-N- (5-methylisothiazol-3-yl) benzenesulfonamide (0.001 mol), 4-methylbenzaldehyde (0.001 mol) and dimethyl malonate (0.0015 mol) were added, p-xylene (40 mL) was added as a solvent, the temperature was raised and the flow was reversed, TLC was used to monitor the progress of the reaction, the reaction was completed for 4 hours, the solvent was recovered under reduced pressure, and the target product was obtained by column chromatography separation (petroleum ether: ethyl acetate=8:1V/V).
Example 4: diethyl 2- ((4-methoxyphenyl) ((4- (N- (5-methylisothiazol-3-yl) sulfamoyl) phenyl) amino) methyl) malonate;
in a 100mL single-necked flask, 4-amino-N- (5-methylisothiazol-3-yl) benzenesulfonamide (0.001 mol), 4-methoxybenzaldehyde (0.001 mol) and ethyl malonate (0.0015 mol) were added, p-xylene (40 mL) was added as a solvent, the temperature was raised and the flow was reversed, TLC was used to monitor the progress of the reaction, the reaction was completed for 5 hours, and the solvent was recovered under reduced pressure, followed by column chromatography (petroleum ether: ethyl acetate=8:1V/V) to obtain the objective product.
Example 5: diethyl 2- (furan-2-yl ((4- (N- (5-methylisothiazol-3-yl) sulfamoyl) phenyl) amino) methyl) malonate;
in a 100mL single-necked flask, 4-amino-N- (5-methylisothiazol-3-yl) benzenesulfonamide (0.001 mol), 2-furaldehyde (0.001 mol) and ethyl malonate (0.0015 mol) were added, p-xylene (40 mL) was added as a solvent, the temperature was raised and the flow was reversed, TLC was used to monitor the progress of the reaction, the reaction was completed for 5 hours, the solvent was recovered under reduced pressure, and the target product was obtained by column chromatography (petroleum ether: ethyl acetate=8:1V/V).
Example 6: dimethyl 2- (cyclohexyl ((4- (N- (5-methylisothiazol-3-yl) sulfamoyl) phenyl) amino) methyl) malonate;
in a 100mL single-necked flask, 4-amino-N- (5-methylisothiazol-3-yl) benzenesulfonamide (0.001 mol), cyclohexylformaldehyde (0.001 mol) and dimethyl malonate (0.0015 mol) were added, p-xylene (40 mL) was added as a solvent, the temperature was raised and the flow was reversed, TLC was used to monitor the progress of the reaction, the reaction was completed for 4 hours, the solvent was recovered under reduced pressure, and the solvent was separated by column chromatography (petroleum ether: ethyl acetate=8:1V/V) to obtain the objective product.
Example 7: diethyl 2- (1- ((4- (N- (5-methylisothiazol-3-yl) sulfamoyl) phenyl) amino) hexyl) malonate;
in a 100mL single-necked flask, 4-amino-N- (5-methylisothiazol-3-yl) benzenesulfonamide (0.001 mol), hexanal (0.001 mol) and diethyl malonate (0.0015 mol) were added, p-xylene (40 mL) was added as a solvent, the temperature was raised and the flow was reversed, TLC was used to monitor the progress of the reaction, the reaction was completed for 5 hours, toluene was recovered under reduced pressure, and the objective product was obtained by column chromatography (petroleum ether: ethyl acetate=8:1V/V).
For example I above 1 -I 7 The yield, physical form and elemental analysis of the synthesized malonate compound containing the N-thiazole benzenesulfonamide group are shown in the table 1, and the nuclear magnetic resonance hydrogen spectrum is shown in the specification 1 HNMR) data are shown in Table 2, nuclear magnetic resonance carbon spectrum @, shown in Table 2 13 C NMR) data are shown in table 3, infrared spectrum (IR) data are shown in table 4, and Mass Spectrum (MS) data are shown in table 5:
TABLE 1 physicochemical Properties and elemental analysis of target Compounds
TABLE 2 target compounds 1 H NMR data
TABLE 3 target compounds 13 C NMR data
TABLE 4 Infrared data for target compounds
TABLE 5 Mass Spectrometry of target Compounds
| Compounds of formula (I) | MS(ESI):m/z |
| I 1 | 518([M+H] + ),540([M+Na] + ),556([M+K] + ). |
| I 2 | 624([M+H] + ),644([M+Na] + ),660([M+K] + ) |
| I 3 | 504([M+H] + ),526([M+Na] + ),542([M+K] + ) |
| I 4 | 548([M+H] + ),570([M+Na] + ),586([M+K] + ) |
| I 5 | 508([M+H] + ),530([M+Na] + ),546([M+K] + ) |
| I 6 | 496([M+H] + ),518([M+Na] + ),534([M+K] + ) |
| I 7 | 512([M+H] + ),534([M+Na] + ),550([M+K] + ) |
Example 8: therapeutic, inactivating and protective activities of target compounds against tobacco mosaic virus
(1) Test method
A. Virus purification
Adopting a good method (good; et al 1967), selecting upper leaves of a plant infected by a TMV system host heart leaf smoke (Nicotiana glutinosa L.) after inoculation for more than 3 weeks, homogenizing in a phosphoric acid buffer solution, filtering with double-layer gauze, centrifuging at 1000rpm, treating with polyethylene glycol for 2 times, centrifuging, and suspending the precipitate with the phosphoric acid buffer solution to obtain a TMV crude extract. The whole experiment was carried out at 4 ℃. The absorbance value of the wavelength of 260nm is measured by an ultraviolet spectrophotometer, and the virus concentration is calculated according to a formula.
Virus concentration (mg/mL) = (A260×dilution)/E0.1% 1cm260nm
Wherein E represents the extinction coefficient, i.e. the value of the light absorption (optical density) at an optical path length of lcm for a suspension having a concentration of 0.1% (1 mg/mL) at a wavelength of 260 nm. E0.1% of TMV 1cm260nm is 3.1.
B. Active therapeutic effects of agents on TMV infection: selecting a leaf tobacco with consistent growth vigor, dipping a writing brush in virus juice, inoculating the virus to the whole leaf, and flushing with clear water after inoculation. After the leaves were dried, the right half She Tushi of the dose and the left half She Tushi of the corresponding dose of solvent were used as controls. Subsequently, the culture was kept under humidity in an illumination incubator at a temperature of 23.+ -. 1 ℃ for 10000Lux under illumination for 3-4d, and the number of generated spots was observed and recorded. 3 plants are arranged for each medicament treatment, and 3 to 4 leaves are arranged for each plant. The inhibition was calculated as follows by repeating the above method 3 times per agent.
C. In vivo protection of TMV infection by agents
In vivo protection of TMV infection by agents: selecting leaf tobacco with consistent growth vigor, firstly using a writing brush to prepare She Tushi medicament on the right half and a solvent with a dosage corresponding to She Tushi on the left half as a control, dipping the leaf by the pen after the leaf is dried, inoculating the virus on the whole leaf, and flushing with clear water after inoculation. Subsequently, the culture was kept under humidity in an illumination incubator at a temperature of 23.+ -. 1 ℃ for 10000Lux under illumination for 3-4d, and the number of generated spots was observed and recorded. 3 plants are arranged for each medicament treatment, and 3 to 4 leaves are arranged for each plant. The inhibition was calculated as follows by repeating the above method 3 times per agent.
D. In vivo inactivation of TMV infection by agents
The in-vivo deactivation of the medicament on TMV infection comprises selecting leaf tobacco with consistent growth vigor, scattering carborundum on whole leaves, mixing and deactivating the compound with an equal volume of virus juice for 30 minutes, manually rubbing and inoculating the compound with a gang pen to right half leaf of the age-appropriate leaf tobacco scattered with carborundum, mixing and inoculating a solvent with a corresponding dose with the virus juice to left half leaf of the age-appropriate leaf tobacco scattered with carborundum, observing and recording the number of generated dead spots after 3-4 d. 3 plants are arranged for each medicament treatment, and 3 to 4 leaves are arranged for each plant. The inhibition was calculated as follows by repeating the above method 3 times per agent.
Y＝(C-A)/C×100％
Wherein: y is the inhibition rate of the compound on tobacco mosaic virus; c is the number of the dead spots in the control group (left half leaf), and A is the number of the dead spots in the control group (right half leaf).
(2) Biological test results
TABLE 6 treatment, protection and inactivation Activity of target Compounds against tobacco mosaic Virus
The anti-TMV activity of the target compound is tested by adopting a half-leaf spot-drying method with the concentration of 500 mug/mL and Ningnanmycin as a control medicament, and the biological activity measurement result of the table 6 shows that the malonate compound containing the isothiazole benzene sulfonamide group has medium to excellent inhibitory activity on TMV, wherein the compound I 5 The method is superior to the control medicament Ningnanmycin in treatment, protection and passivation.
In order to further study the anti-TMV activity of malonate compounds containing N-5-methylisothiazole benzenesulfonamide group, I in the compounds is measured 5 Is used for treating EC 50 Values, results are shown in Table 7.
TABLE 7 part of the therapeutic Activity of target Compounds against TMV EC 50 Value of
As can be seen from the results, I in the compounds 5 EC on TMV therapeutic Activity 50 215.9 and 181.2 mug/mL respectively, which is superior to the control medicament Ningnanmycin 221.1 mug/mL
Example 9: therapeutic, inactivating and protective activities of target compounds against cucumber mosaic virus
(1) Test method
A. Virus purification
Adopting a method of Chen (Chen, J.; et al 2017), selecting and inoculating for more than 3 weeks, infecting upper leaves of a host Nicotiana tabacum.L plant by a CMV system, homogenizing in a phosphate buffer, filtering by double-layer gauze, centrifuging at 8000g, treating by polyethylene glycol for 2 times, centrifuging again, and suspending the precipitate by the phosphate buffer to obtain the CMV refined extract. The whole experiment was performed at 4℃and the absorbance at 260nm was measured with an ultraviolet spectrophotometer, and the virus concentration was calculated according to the formula.
Virus concentration (mg/mL) = (A260×dilution)/E0.1% 1cm260nm
Wherein E represents the extinction coefficient, i.e.the value of the light absorption (optical density) at an optical path length of l cm, of a suspension having a concentration of 0.1% (1 mg/mL) at a wavelength of 260 nm. E0.1% of CMV 1cm260nm is 5.0.
B. Active therapeutic effects of agents on CMV infection: selecting purslane in 5-6 leaf period with growing vigor, topping, spreading silicon carbide uniformly on whole leaves, dipping virus juice (6×10-3 mg/mL) on whole leaves with a gang pen, inoculating virus, naturally airing, and washing with clear water. After the leaves are dried, the left half She Qing is lightly coated with a writing brush Shi Yaoji, the right half She Tushi is used as a control, the number of dead spots is recorded after 6-7 days, and the inhibition rate is calculated according to the following formula.
C. In vivo protection of CMV infection by agents
In vivo protection of CMV infection by agents: selecting purslane in 5-6 leaf period with consistent growth vigor, lightly coating Shi Yaoji on the left half She Qing by using a writing brush, using solvent with corresponding concentration on the right half She Tushi as a control, scattering silicon carbide evenly on the whole leaves after 24 hours, dipping virus juice (6X 10-3 mg/mL) of the whole leaf inoculated virus by using a gang pen, flushing by using clear water, recording the number of dead spots after 6-7 days, and calculating the inhibition rate according to the following formula.
D. In vivo inactivation of CMV infection by agents
The in-vivo deactivation of CMV infection by the agent comprises topping purslane in 5-6 leaf period with consistent growth vigour, sprinkling carborundum on whole leaves, and adding phosphoric acid buffer solution to the CMV; diluting the virus to 6X 10-3mg/mL, mixing the compound with an equal volume of virus juice, inactivating for 30 minutes, manually rubbing and inoculating the compound to the left half leaf of Portulaca oleracea with silicon carbide, mixing a solvent with the virus juice at a corresponding dosage, inoculating the compound to the right half leaf of Portulaca oleracea with silicon carbide, recording the number of dead spots after 6-7 days, and calculating the inhibition rate according to the following formula.
X％＝(CK－T)/CK×100
X is the relative inhibition rate (%),
CK average number of dead spots of half leaves without applied agent
T average number of dead spots of half leaf coated with Shi Yaoji
Wherein CK and T are the average of three replicates of each group
(2) Biological test results
TABLE 8 treatment, protection and inactivation Activity of target Compounds against cucumber mosaic Virus
The anti-CMV activity of the target compound is tested by adopting a half-leaf spot-drying method with the concentration of 500mg/L and Ningnanmycin as a control medicament, and the biological activity measurement result of the table 8 shows that the malonate compound containing the isothiazole benzene sulfonamide group has medium to excellent inhibitory activity on CMV, wherein I 2 And I 5 The method is superior to the control medicament Ningnanmycin in treatment, protection and passivation.
In order to further study the anti-CMV activity of malonate compounds containing isothiazole benzenesulfonamide groups, we determined I in the compounds 2 And I 5 Is used for treating EC 50 Values, results are shown in Table 7.
TABLE 9 therapeutic Activity of partial target Compounds against CMVEC of (2) 50 Value of
As can be seen from the results, I 2 And I 5 EC for CMV protective Activity 50 180.9 and 199.8. Mu.g/mL, respectively, are superior to the control agent, ningnanmycin 226.7. Mu.g/mL.
Example 10: inhibition activity of target compound on fusarium graminearum
(1) Test method
The bacteriostatic activity of the compounds was determined using the ex vivo growth rate method (Ye, y.h.; et al, 2014). Potato dextrose agar medium (PDA medium: potato 200g, agar 20g, glucose 20g, distilled water 1000 mL) is heated to a molten state (40-60 ℃), 10mL of the liquid medicine (10 times of the final concentration of the liquid medicine) is poured into 90mL of PDA medium, fully and uniformly shaken, uniformly poured into a culture dish with the diameter of 9cm, horizontally placed, and cooled and solidified. The 4mm diameter bacterial dish is picked up by a puncher at the edge of the fresh pathogenic bacteria colony which has been cultivated for 4d, the bacterial dish is placed in the center of a reagent-containing PDA flat plate in an inverted mode, then the bacterial dish is placed in a 27 ℃ constant temperature and humidity incubator for inverted cultivation, observation is started when a blank control colony grows to be close to two thirds of the flat plate, the colony diameter is measured by a crisscross method, and the average value is obtained (Song Suqin, et al, 2004). The blank was not dosed, but contained the same concentration of solvent and 0.5% Tween 20, and each treatment was repeated three times. The inhibition of hyphal growth by the agent was calculated by the following formula:
I(％)＝(C-T)/(C-0.4)×100％
where I is inhibition, C is blank diameter (cm), and T is treatment diameter (cm).
(2) Biological test results
Table 10 inhibition Activity of target Compounds against Rhizoctonia cerealis, pepper blight bacteria
As can be seen from the results in Table 10, most of the compounds showed high inhibitory activity against Rhizoctonia cerealis and Rhizoctonia cerealis at a concentration of 50. Mu.g/mL. Wherein I in the compound 3 And I 5 The inhibition rate to the fusarium graminearum and the pepper fusarium graminearum is higher than 90%, which is obviously better than commercial control medicament hymexazol.
Example 11: inhibitory Activity of target Compounds against Pseudomonas tolla, umbelliferae, actinidia canker
(1) Test method
The bactericidal activity of the compounds was determined by nephelometry (Fan, z.j.; et al, 1996). The test compound was prepared at a concentration of 100. Mu.g/mL. NB medium (3.0 g beef extract, 5.0g peptone, 1.0g yeast powder, 10.0g glucose, 1000mL distilled water, pH 7.0-7.2) was prepared, a small piece of medium containing Pseudomonas tolla, ulmaria citrifolia, and Actinidia canker was inoculated and circulated, and placed into two NB medium, plugged, and shake-cultured at constant temperature of 28deg.C and 180rpm until the growth log phase (OD=0.6-0.8) was reached for use. mu.L of the bacterial liquid, 4mL of water-Tween (1% Tween 20) and 1mL of the prepared compound solution were taken, and the test tube was incubated at 28.+ -. 1 ℃ and continuously shaken at 180rpm for 1-3 days. Bacterial growth was monitored by measuring optical density at 595nm (OD 595), but with the same concentration of solvent and 0.1% Tween 20 as a blank, copper thiabendazole as a control agent, and each treatment was repeated three times. The inhibition of bacteria by the agent was calculated by the following formula:
I＝(Ctur-Ttur)/Ctur×100％
where I is the inhibition rate, ctur represents the corrected turbidity value of bacterial growth in the non-drug treated tube (blank), ttur represents the corrected turbidity value of bacterial growth in the compound treated tube.
(2) Biological test results
Table 11 inhibition Activity of target Compounds against Pseudomonas tolla, umbelliferae, actinidia canker
As can be seen from the biological activity test results in Table 11, a part of the compounds show better inhibition activity on Pseudomonas tolla, uyghuris citri and Uyghur, wherein the compound I 5 The inhibition activity of the composition on pseudomonas tolla, canker orange and kiwi fruit canker is equivalent to that of a commercial control medicament thiabendazole.
The embodiment of the invention is assisted with the technical scheme of the invention. The invention has the advantages of simple synthetic route and higher yield, and obtains a novel and high-efficiency novel drug with inhibiting effect on tobacco mosaic disease, cucumber mosaic disease, soft rot of edible fungi, pepper wilt, edible fungus maculopathy, citrus canker and kiwi canker.
Claims (7)
1. An agriculturally active malonate compound containing an isothiazole benzene sulfonamide group, characterized in that: the general formula is shown in the following formula (I):
wherein R is 1 Is C1-C3 alkyl; r is R 2 Phenyl, substituted phenyl, furyl, cyclohexyl or pentyl; the substituent of the substituted phenyl is halogen, methyl or methoxy.
2. The agriculturally active malonate compound containing an isothiazole benzenesulfonamide group according to claim 1, characterized in that: the C1-C3 alkyl is methyl, ethyl or isopropyl.
3. The method for preparing an agriculturally active malonate compound containing an isothiazole benzenesulfonamide group according to claim 1, characterized by comprising the steps of: the synthesis method of the malonate compound containing the isothiazole benzene sulfonamide group by using 4-amino-N- (5-methylisothiazole-3-yl) benzene sulfonamide, substituted aldehyde and malonate as raw materials and toluene as a solvent through a microwave method comprises the following synthesis routes:
4. the method for preparing an agriculturally active malonate compound containing an isothiazole benzenesulfonamide group according to claim 3, characterized by comprising the steps of: the synthesis steps and the process conditions are as follows: adding 4-amino-N- (5-methylisothiazole-3-yl) benzenesulfonamide, substituted aldehyde and malonate as raw materials into a single-mouth bottle, adding toluene, reacting in a microwave reactor for 2-4 hours, recovering solvent under reduced pressure, and separating by column chromatography to obtain the target product.
5. The method for preparing an agriculturally active malonate compound containing an isothiazole benzenesulfonamide group according to claim 4, characterized by comprising the steps of: the column chromatographic separation conditions are petroleum ether: ethyl acetate=6:1V/V.
6. Use of a malonate compound having an isothiazole benzenesulfonamide group having agricultural activity according to any one of claims 1 to 3 for the preparation of a medicament for the control of crop diseases.
7. The use according to claim 6, characterized in that: the crop diseases comprise tobacco mosaic virus, cucumber mosaic virus, fusarium graminearum, pepper fusarium wilt, pseudomonas tolla, citrus canker and kiwi fruit canker.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211030531.6A CN115490649B (en) | 2022-08-26 | 2022-08-26 | Malonic ester compound containing isothiazole benzene sulfonamide group with agricultural activity, preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211030531.6A CN115490649B (en) | 2022-08-26 | 2022-08-26 | Malonic ester compound containing isothiazole benzene sulfonamide group with agricultural activity, preparation method and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115490649A CN115490649A (en) | 2022-12-20 |
| CN115490649B true CN115490649B (en) | 2023-08-08 |
Family
ID=84467176
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211030531.6A Active CN115490649B (en) | 2022-08-26 | 2022-08-26 | Malonic ester compound containing isothiazole benzene sulfonamide group with agricultural activity, preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115490649B (en) |
Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101817803A (en) * | 2010-04-29 | 2010-09-01 | 贵州大学 | Beta-amino acid esters having optical activity and containing benzothiazole groups and synthetic method and application thereof |
| CN108033916A (en) * | 2017-12-18 | 2018-05-15 | 贵州理工学院 | A kind of preparation of amino acid esters compound and its purposes of prevention tobacco diseases |
| CN108101854A (en) * | 2017-12-18 | 2018-06-01 | 贵州理工学院 | A kind of preparation of amino acid esters compound and its purposes of resisting tobacco mosaic virus containing pyrimidine structure |
| CN112079852A (en) * | 2020-08-21 | 2020-12-15 | 洛阳师范学院 | Zn (II) complex based on ASBSA and 4, 4' bipyridyl ligand and preparation method and application thereof |
| CN115232088A (en) * | 2022-08-26 | 2022-10-25 | 贵州理工学院 | Thiazole sulfonamide derivative, preparation method and application thereof |
| CN115232085A (en) * | 2022-08-26 | 2022-10-25 | 贵州理工学院 | Malonate type compound, preparation method and application thereof |
| CN115322147A (en) * | 2022-08-26 | 2022-11-11 | 贵州理工学院 | Benzene sulfonamide derivative, preparation method and application |
| CN115490647A (en) * | 2022-08-26 | 2022-12-20 | 贵州大学 | Malonate compound containing chiral isoxazole benzene sulfonamide group, preparation method and application |
| CN115521267A (en) * | 2022-08-26 | 2022-12-27 | 贵州大学 | Benzenesulfonamide compound containing N-5-chloroisoxazole malonate structure, preparation method and application |
| CN115521248A (en) * | 2022-08-26 | 2022-12-27 | 贵州理工学院 | Chiral alpha-amino malonate compounds containing N-pyridyl benzene sulfonamide, and preparation method and application thereof |
| CN115677606A (en) * | 2022-08-26 | 2023-02-03 | 贵州理工学院 | Chiral malonate type compound, preparation and application thereof |
-
2022
- 2022-08-26 CN CN202211030531.6A patent/CN115490649B/en active Active
Patent Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101817803A (en) * | 2010-04-29 | 2010-09-01 | 贵州大学 | Beta-amino acid esters having optical activity and containing benzothiazole groups and synthetic method and application thereof |
| CN108033916A (en) * | 2017-12-18 | 2018-05-15 | 贵州理工学院 | A kind of preparation of amino acid esters compound and its purposes of prevention tobacco diseases |
| CN108101854A (en) * | 2017-12-18 | 2018-06-01 | 贵州理工学院 | A kind of preparation of amino acid esters compound and its purposes of resisting tobacco mosaic virus containing pyrimidine structure |
| CN112079852A (en) * | 2020-08-21 | 2020-12-15 | 洛阳师范学院 | Zn (II) complex based on ASBSA and 4, 4' bipyridyl ligand and preparation method and application thereof |
| CN115232088A (en) * | 2022-08-26 | 2022-10-25 | 贵州理工学院 | Thiazole sulfonamide derivative, preparation method and application thereof |
| CN115232085A (en) * | 2022-08-26 | 2022-10-25 | 贵州理工学院 | Malonate type compound, preparation method and application thereof |
| CN115322147A (en) * | 2022-08-26 | 2022-11-11 | 贵州理工学院 | Benzene sulfonamide derivative, preparation method and application |
| CN115490647A (en) * | 2022-08-26 | 2022-12-20 | 贵州大学 | Malonate compound containing chiral isoxazole benzene sulfonamide group, preparation method and application |
| CN115521267A (en) * | 2022-08-26 | 2022-12-27 | 贵州大学 | Benzenesulfonamide compound containing N-5-chloroisoxazole malonate structure, preparation method and application |
| CN115521248A (en) * | 2022-08-26 | 2022-12-27 | 贵州理工学院 | Chiral alpha-amino malonate compounds containing N-pyridyl benzene sulfonamide, and preparation method and application thereof |
| CN115677606A (en) * | 2022-08-26 | 2023-02-03 | 贵州理工学院 | Chiral malonate type compound, preparation and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| Asymmetric Mannich reaction: Synthesis of novel chiral 5-(substituted aryl)-1, 3, 4-thiadiazole derivatives with anti-plant-virus potency;Song Bai等;《Heterocyclic Communications》;第25卷(第01期);第47-51页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115490649A (en) | 2022-12-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN115521270B (en) | Malonate compound containing N-oxazolesulfonamide group, preparation method and application | |
| CN115232088B (en) | Thiazole sulfonamide derivative, preparation method and application thereof | |
| CN115322147B (en) | Benzenesulfonamide derivative, preparation method and application | |
| CN115677606B (en) | Chiral malonate compound, preparation and application thereof | |
| CN108033916B (en) | Preparation of amino acid ester compound and application of amino acid ester compound in preventing and treating tobacco diseases | |
| WO1987003591A1 (en) | Novel imidazole derivatives, bactericides containing them, and process for their preparation | |
| CN115232085B (en) | Malonate compound, preparation method and application thereof | |
| CN115521267B (en) | Benzenesulfonamide compound containing N-5-chloroisoxazole malonate structure, preparation method and application | |
| CN115490647B (en) | Malonate compound containing chiral isoxazole benzenesulfonamide group, preparation method and application | |
| CN115490649B (en) | Malonic ester compound containing isothiazole benzene sulfonamide group with agricultural activity, preparation method and application | |
| CN115521248B (en) | Chiral alpha-aminomalonate compound containing N-pyridyl benzenesulfonamide, preparation method and application | |
| CN111349038B (en) | Indolylhydrazone compounds, preparation method thereof and application thereof in preventing and treating plant diseases | |
| CN113287619B (en) | Application of Pityriacitrin alkaloid and derivative thereof in resisting plant viruses and germs | |
| CN115521271B (en) | Chiral malonate compound containing N-isothiazole benzene sulfonamide group, preparation method and application | |
| CN115521269B (en) | Chiral malonate compound containing benzenesulfonamide group, preparation method and application | |
| CN115583924B (en) | Chiral malonate compound containing N-thiazole benzenesulfonamide group, preparation method and application | |
| CN115462383A (en) | Application of Almazole D alkaloid and derivatives thereof in resisting plant viruses and pathogenic bacteria | |
| CN109651216B (en) | Naphthalene derivative containing dithioacetal, and preparation method, medicine and application thereof | |
| CN108570009B (en) | 3-halogen diarylamine pyrazole amide compound and application thereof in pesticide | |
| CN113016806B (en) | Application of coumarin derivatives in preventing and treating plant viruses, killing bacteria and killing insects | |
| CN113045474B (en) | Application of alkaloid arnodine and derivatives thereof in preventing and treating plant virus and bacterial diseases | |
| CN111349080B (en) | Indole acylhydrazone compound, preparation method thereof and application of indole acylhydrazone compound in prevention and treatment of plant diseases | |
| Malathi et al. | Efficacy of thiophanate methyl against red rot of sugarcane | |
| CN108101855B (en) | Preparation method and application of amino acid ester compound containing 4-piperidyl-6-methylpyrimidine heterocycle | |
| CN110156685B (en) | Aromatic cyclopentenopyridine, and synthesis method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |