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CN101817799A - Cyanoacrylate compound and application thereof in pesticide and medicine - Google Patents

Cyanoacrylate compound and application thereof in pesticide and medicine Download PDF

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Publication number
CN101817799A
CN101817799A CN200910204728A CN200910204728A CN101817799A CN 101817799 A CN101817799 A CN 101817799A CN 200910204728 A CN200910204728 A CN 200910204728A CN 200910204728 A CN200910204728 A CN 200910204728A CN 101817799 A CN101817799 A CN 101817799A
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cyanoacrylate
activity
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methylamine
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CN101817799B (en
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汪清民
刘玉秀
刘少华
蔡保理
李永红
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Nankai University
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Nankai University
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Abstract

本发明涉及氰基丙烯酸酯类化合物及在农药和医药上的应用。本发明的氰基丙烯酸酯类化合物(A)表现出很好的除草活性，用于阔叶杂草及禾本科杂草的除草，还具有杀菌活性、植物生长调节活性和抗肿瘤活性，可作为除草剂、杀菌剂、植物生长调节剂和抗肿瘤试剂。其中，R1：苯基、噁唑、异噁唑、噁二唑、喹啉，或上述杂环上被氟、氯、溴、C1-C6烷基、取代苯基、C1-C6烷氧基或C1-C6烷胺基取代；R2：C1-C3烷基、甲硫基，X：CH2或NH。

Figure 200910204728.5_AB_0
The invention relates to cyanoacrylate compound and its application in pesticide and medicine. The cyanoacrylate compound (A) of the present invention exhibits good herbicidal activity, is used for the weeding of broad-leaved weeds and grass weeds, and also has bactericidal activity, plant growth regulating activity and antitumor activity, and can be used as Herbicides, fungicides, plant growth regulators and antineoplastic agents. Among them, R 1 : phenyl, oxazole, isoxazole, oxadiazole, quinoline, or the above heterocycles are replaced by fluorine, chlorine, bromine, C 1 -C 6 alkyl, substituted phenyl, C 1 -C 6 alkoxy or C 1 -C 6 alkylamino; R 2 : C 1 -C 3 alkyl, methylthio, X: CH 2 or NH.
Figure 200910204728.5_AB_0

Description

Cyanoacrylate compound reaches in agricultural chemicals and application pharmaceutically
Technical field
The present invention relates to cyanoacrylate compound reaches in agricultural chemicals and application pharmaceutically.
Background technology
Cyanoacrylate compound is class photosynthesis photosystem II (PSII) electron transfer inhibitor as weedicide, patent CN 1246474A discloses cyanoacrylate compound and the biological activity that contains sulfenyl pyridyl-methanamine base, after finding that phenyl ring becomes pyridine ring in the alpha-cyanoacrylate ester molecule, its weeding activity improves greatly.Patent CN 1483320A discloses a kind of heterocycle methylamino cyanoacrylate compound and weeding activity of containing, and biological activity determination is the result show: this compounds has very high weeding activity to broadleaf weeds and gramineous weeds.Patent CN1594294A discloses the cyanoacrylate compound and the biological activity of fluorinated pyridine methylamino, finds that this compounds has very high Hill reactive behavior and weeding activity.Patent CN1603307A discloses cyanacrylate derivant and preparation method and biological activity, and the compound of report has antitumor and anti-phytoviral activity.Patent CN1760176A discloses the synthetic and weeding activity of Z-2-cyano group-3-(N-(S)-Alpha-Methyl p-fluorin benzyl amine group)-2-pentenoic acid ethoxy ethyl ester, and indoor and field efficacy shows: this compound can be prevented and kill off broadleaf weeds behind the corn field seedling.Patent CN101020677 discloses the alpha-cyanoacrylate ester cpds that heterocycle methylamino-s such as pyridine, thiazole, pyrimidine, pyridazine, furans, tetrahydrofuran (THF) replace, find that this compounds not only has weeding activity to broadleaf weeds and gramineous weeds, also has fungicidal activity and plant growth regulating activity and anti-phytoviral activity.Patent CN101318976 discloses cyanoacrylate derivative and preparation method and the biological activity that contains the α-An Jilinsuan ester, and part of compounds shows the activity of higher Antiphytoviral.
Summary of the invention
The purpose of this invention is to provide cyanoacrylate compound (A) reaches in agricultural chemicals and application pharmaceutically.The invention provides many new chemical structures and new compound.Biological activity determination is the result show: part of compounds A has very high weeding activity, and part also has sterilization, plant growth regulating and anti-tumor activity.
The present invention is the compound of following general formula (A):
Figure G2009102047285D00021
Wherein, among the general formula A, R 1: phenyl, oxazole, isoxazole, oxadiazole, quinoline, or on the above-mentioned heterocycle by fluorine, chlorine, bromine, C 1-C 6Alkyl, substituted-phenyl, C 1-C 6Alkoxyl group or C 1-C 6Alkylamino radical replaces; R 2: C 1-C 3Alkyl, methylthio group, X:CH 2Or NH.
The synthetic route of The compounds of this invention (A) is as follows:
The preparation of 2-substituted-phenyl-4-oxazole methylamine:
Figure G2009102047285D00022
The preparation of 5-replacement-2-oxazole methylamine:
Figure G2009102047285D00023
2-, the preparation of 3-or 6-quinoline methylamine:
Figure G2009102047285D00024
The preparation of 3-substituted-phenyl-5-oxadiazole methylamine:
Figure G2009102047285D00031
The preparation of 3-substituted-phenyl-5-isoxazole methylamine:
Figure G2009102047285D00032
The preparation of 3-alkyl-5-isoxazole methylamine:
Figure G2009102047285D00033
The preparation of 3-bromo-5-isoxazole methylamine:
Figure G2009102047285D00034
The preparation of substituted phenylhydrazines:
Figure G2009102047285D00041
Cyanoacrylate target compound A's is synthetic:
Figure G2009102047285D00042
Synthetic route of the present invention is described below: 2-cyano group-3-methoxyl group-2-olefin(e) acid ethoxy ethyl ester or 2-cyano group-3,3-diformazan sulfenyl vinylformic acid ethoxy ethyl ester and various heterocyclic methyl amine, mol ratio is respectively 1: 1, mix stirring down with dehydrated alcohol, reacted several hours, precipitation, column chromatography for separation get target compound A.
Cyanoacrylate compound (A) shows good weeding activity, is used for the weeding of broadleaf weeds and gramineous weeds, and cauline leaf is handled active in soil treatment; Activity to the broad-leaved rape is higher than Gramineae barnyard grass grass; It is active and promote the cucumber cotyledons activity of taking root that part of compounds also has the ring rot of apple of killing bacterium; Part of compounds can effectively suppress BEL-7402 human liver cancer cell and HL-60 human leukemia.The application of cyanoacrylate compound (A) on agricultural chemicals is as weedicide, sterilant and plant-growth regulator, is as anti-tumor agent comprising salmosin pharmaceutically using.
Substantial characteristics of the present invention can be embodied from following embodiment, but it should not to be considered as be that the present invention is imposed any restrictions.
Embodiment
Embodiment 1:2-replaces the preparation (with the example that synthesizes of 2-benzene base oxazole-4-methylamine) of phenyl oxazole-4-methylamine:
In the 50mL there-necked flask, add benzamide 1.50g, 1,3-Dichloro acetone 3.15g is heated to 130 ℃ of reaction 1h.Add entry, use CH 2Cl 2Extraction.Filtering and concentrating, recrystallization obtain white crystal 2-phenyl-4-Lv Jia Ji oxazole 1.68g, fusing point 53-55 ℃, yield 70.1%.
In the 100mL single port bottle, add 2-phenyl-4-Lv Jia Ji oxazole 0.96g, dry DMF 10mL stirs adding potassium phthalimide 0.93g down, room temperature reaction 5 hours.Add entry, filter, the solid recrystallization obtains white crystal N-(2-benzene base oxazole-4-methyl) phthalic imidine, fusing point 133-135 ℃, yield 86.3%. 1H?NMR(400MHz，CDCl 3)：4.87(s，2H，CH 2)，7.41(s，3H)，7.67(s，1H)，7.72(m，2H)，7.87(m，2H)，7.99(s，2H)。
In the 50mL single port bottle, add N-(2-Ben Ji oxazole-4-methyl) phthalic imidine 1.22g, dehydrated alcohol 20mL, hydrazine hydrate 0.24g, reflux 4 hours.React the filtering reacting liquid that finishes, filtrate concentrating obtains yellow oil 2-phenyl-4-oxazole methylamine 0.51g, further purifies. 1H?NMR(400MHz，CDCl 3)：1.75(br?s，2H，NH 2)，3.83(s，2H，CH 2)，7.42-7.43(m，3H)，7.53(s，1H)，7.99-8.01(s，2H)。
Synthetic (with the example that synthesizes of 5-Yi Bing Ji oxazole-2-methylamine) of embodiment 2:5-Wan Ji oxazole-2-methylamine:
In the 250mL four-hole bottle, add the diethyl ether solution that contains diazomethane, cooling drips the diethyl ether solution 10mL that contains isobutyryl chloride 2.13g down, reacts 24 hours.Remove excessive diazomethane, behind the anhydrous magnesium sulfate drying, filtering and concentrating obtains yellow oily liquid 2.20g, yield 99.2%.Further do not purify.
In the 100mL four-hole bottle, add the 15mL chloromethyl cyanide, cooling adds the boron trifluoride ether solution of 6mL down, drips the chloromethyl cyanide solution 10mL that contains top described yellow oily liquid 1.9g then, drips Bi Fanying 1h.Be poured in the beaker that fills ice and ether separatory extraction, organic phase anhydrous magnesium sulfate drying.Filtering and concentrating obtains yellow oily liquid 2-chloromethyl-5-Yi Bing Ji oxazole 1.8g, and yield 67.6% is not further purified. 1H?NMR(400MHz，CDCl 3)：1.25(d， 3J HH＝7.2Hz，6H，CH 3)，2.92-2.99(m，1H，CH)，4.55(s，2H，CH 2)，6.68(s，1H)。
In the 100mL single port bottle, add 2-chloromethyl-5-Yi Bing Ji oxazole 0.96g, dry DMF 10mL stirs adding potassium phthalimide 1.11g down, room temperature reaction 5h.Add entry in reaction flask, filter, the solid recrystallization gets white crystal N-(5-different third basic oxazole-2-methyl) phthalic imidine 1.48g, fusing point 140-142 ℃, yield 91.1%. 1H?NMR(400MHz，CDCl 3)：1.21(d， 3J HH＝6.8Hz，6H，CH 3)，2.88-2.95(m，1H，CH)，4.94(s，2H，CH 2)，6.60(s，1H)，7.74-7.76(m，2H)，7.86-7.89(m，2H)。
In the 50mL single port bottle, add N-(5-Yi Bing Ji oxazole-2-methyl) phthalic imidine 1.08g, dehydrated alcohol 20mL, hydrazine hydrate 0.24g, reflux 4h, the reaction filtering reacting liquid that finishes, filtrate concentrate yellow oil 5-Yi Bing Ji oxazole-2-imines 0.32g, yield 72.7% is not further purified. 1H?NMR(400MHz，CDCl 3)：1.19(d， 3J HH＝6.8Hz，6H，CH 3)，1.70(br?s，2H，NH 2)，2.85-2.92(m，1H，CH)，3.85(s，2H，CH 2)，6.56(s，1H)。
Embodiment 3:2-, the preparation of 3-or 6-quinoline methylamine: (with the example that synthesizes of 2-quinoline methylamine):
In the 250mL single port bottle, add 2-toluquinoline 3g, tetracol phenixin 100mL, NBS 3.7g, AIBN 0.05g, heating reflux reaction 4h, cooled and filtered.The dry after-filtration of filtrate concentrates, and column chromatography gets yellow oily 2-bromomethyl quinoline, yield 41.6%.
In the 100mL single port bottle, add 2-bromomethyl quinoline 1.46g, dry DMF 10mL, stir adding potassium phthalimide 1.22g down, room temperature reaction 5h.Add the 45mL frozen water in reaction flask, filter, the filter cake recrystallization gets white solid N-(quinoline-2-methyl) phthalic imidine 1.72g, fusing point 171-173 ℃, yield 90.0%. 1HNMR(400MHz，CDCl 3)：5.20(s，2H，CH 2)，7.36-7.49(m，2H)，7.65-7.75-7.78(m，4H)，7.90-7.92(m，2H)，7.97-8.10(m，2H)。
In the 50mL single port bottle, add N-(quinoline-2-methyl) phthalic imidine 1.72g, dehydrated alcohol 20mL, hydrazine hydrate 0.35g, reflux reaction in 4 hours finishes, filtering reacting liquid, filtrate concentrate 2-quinoline methylamine 0.82g, light yellow oil, yield 87.2%. 1H?NMR(400MHz，CDCl 3)：3.02(br?s，2H，NH 2)，4.23(s，2H，CH 2)，7.37-7.51(m，2H)，7.69-7.79(m，2H)，8.04-8.10(m，2H)。
The preparation of embodiment 4:3-substituted benzene oxadiazole-5-methylamine (with the example that is prepared as of 3-Dui trifluoromethyl Ben oxadiazole-5-methylamine):
In 25mL single port bottle, add 0.69g oxammonium hydrochloride, 1mL water, 0.4g NaOH stirs a moment.In reaction flask, drip again and contain the ethanolic soln 7mL of 1.46g to trifluoromethyl benzyl cyanide, heating reflux reaction 18 hours.Reaction adds entry after finishing, and uses CH 2Cl 2Extraction.The dry after-filtration of extraction liquid concentrates and obtains white solid 4-trifluoromethyl-N '-hydroxybenzene carbonamidine 1.22g, fusing point 128-129 ℃, yield 70.2%. 1H?NMR(400MHz，CDCl 3)：4.92(br?s，3H)，7.67(d， 3J HH＝8.4Hz，2H)，7.75(d， 3J HH＝8.4Hz，2H)。
In the 100mL there-necked flask, add 4-trifluoromethyl-N '-hydroxybenzene carbonamidine 1.0g (4.9mmol), chloroform 20mL, drip the 10mL chloroformic solution that contains chloroacetyl chloride 0.55g, drip the 10mL chloroformic solution that contains triethylamine 0.65g again, drip complete stirring at room 5h.Reaction solution washing after drying.Filtering and concentrating, column chromatography for separation obtain white solid 0.75g, and fusing point 126-128 ℃, yield 54.7%. 1H?NMR(400MHz，CDCl 3)：4.32(s，2H，CH 2)，5.31(br?s，2H，NH 2)，7.69(d， 3J HH＝8.4Hz，2H，Ph)，7.82(d， 3J HH＝8.4Hz，2H，Ph)。White solid 0.61g 5 hours postcooling of reflux in dimethylbenzene are concentrated, and column chromatography for separation gets faint yellow oily thing 5-chloromethyl-3-to three fluorine first oxadiazole 0.55g, yield 95.1%.
In the 100mL single port bottle, add 5-chloromethyl-3-Dui San Fu Jia oxadiazole 0.47g, dry DMF 10mL stirs adding potassium phthalimide 0.33g down, room temperature reaction 5 hours.Add entry in reaction flask, filter, the filter cake recrystallization obtains faint yellow solid N-(3-is to three fluorine first oxadiazole-5-methyl) phthalic imidine 0.64g, fusing point 146-147 ℃, yield 95.2%.
In the 50mL single port bottle, add N-(3-Dui San Fu Jia oxadiazole-5-methyl) phthalic imidine 0.64g, dehydrated alcohol 20mL, hydrazine hydrate 0.17g, reflux reaction in 4 hours finishes, and filters, and filtrate concentrating obtains yellow oily liquid 3-Dui trifluoromethyl Ben oxadiazole-5-methylamine 0.35g,, further do not purify. 1H?NMR(400MHz，CDCl 3)：4.32(br?s，2H，CH 2)，5.31(s，2H，NH 2)，7.69(d， 3J HH＝8.4Hz，2H，Ph)，7.82(d， 3J HH＝8.4Hz，2H，Ph)。
The preparation of embodiment 5:3-replacement-5-isoxazole methylamine: (with 3-(4-chloro-phenyl-) isoxazole-5-methylamine is an example)
In the 100mL there-necked flask, add oxammonium hydrochloride 3.82g, 4-chloro-benzaldehyde 7.03g and water 15mL, add yellow soda ash 2.86g in the aqueous solution of 15mL.Reheat backflow 2h reacts the after-filtration that finishes and gets the 4-chloro-benzaldehyde oxime.With dichloromethane extraction filtrate can be again a small amount of 4-chloro-benzaldehyde oxime.Altogether 4-chloro-benzaldehyde oxime 7.28g, thick yield 93.6%, fusing point: 108-110 ℃.
In the 100mL single port bottle, add 4-chloro-benzaldehyde oxime 1.56g, propargyl bromide 1.42g, methylene dichloride 30mL.Cooling drips concentration down and is about 8% aqueous sodium hypochlorite solution 30mL, dropwises reaction 8h.The dichloromethane extraction reaction solution, dry after-filtration concentrates, and column chromatography for separation gets white crystal 5-brooethyl-3-(4-chloro-phenyl-) isoxazole 2.25g, yield 95.1%. 1H?NMR(CDCl 3)：δ4.51(s，2H)，6.61(s，1H)，7.44(d，J＝8.4Hz，2H)，7.73(d，J?8.4Hz，2H).
In the 50mL there-necked flask, (4-chloro-phenyl-) isoxazole 2.17g, dry DMF10mL stir adding potassium phthalimide 1.48g down, room temperature reaction 8h to add 5-brooethyl-3-.Reaction finishes, and adds entry, filters, and gets white solid N-[3-(4-chloro-phenyl-) isoxazole-5-methyl] phthalic imidine 2.61g, thick yield 96.7%, fusing point 173-175 ℃. 1H?NMR(CDCl 3)：δ5.03(s，2H)，6.54(s，1H)，7.39(d，J＝8.4Hz，2H)，7.68(d，J＝8.4Hz，2H)，7.74-7.78(m，2H)，7.88-7.91(m，2H).
50mL single port bottle, and the product N-[3-above adding (4-chloro-phenyl-) isoxazole-5-methyl] phthalic imidine 1.69g, dehydrated alcohol 20mL, hydrazine hydrate 0.60g, reflux 2h.Reaction finishes, and filtering reacting liquid gets light yellow solid 3-(4-chloro-phenyl-)-5-isoxazole methylamine 0.86g after filtrate concentrates, thick yield 82.7%. 1H?NMR(CDCl 3)：δ1.58(s，2H)，4.02(s，2H)，6.43(s，1H)，7.42(d，J＝8.4Hz，2H)，7.72(d，J＝8.4Hz，2H).
The preparation of embodiment 6:3-bromo-5-isoxazole methylamine:
Add methylene dichloride 100mL in the 250mL four-hole bottle, propargyl bromide 2.86g, sodium bicarbonate 2.5g and water 10mL stir the mixed solution that drips dibromo formoxime 4.1g and methylene dichloride 20mL down, drip complete stirring at room 2h, add entry 50mL separatory again.The dry after-filtration of organic layer concentrates, and column chromatography for separation gets colourless oil liquid 3-bromo-5-brooethyl isoxazole, productive rate 50.0%. 1H?NMR(CDCl 3)：δ4.44(s，2H)，6.41(s，1H).
In the 50mL there-necked flask, add 3-bromo-5-brooethyl isoxazole 6.86g, dry DMF10mL stirs adding potassium phthalimide 5.5g down, room temperature reaction 8h.Reaction finishes, and adds entry, filters, and gets white solid N-[3-bromine-isoxazole-5-methyl] O-phthalic base imines 8.5g, thick yield 98.8%, fusing point 156-157 ℃. 1H?NMR(CDCl 3)：δ4.99(s，2H)，6.36(s，1H)，7.73-7.79(m，2H)，7.79-7.92(m，2H).
50mL single port bottle, the product N-[3-bromine-isoxazoles-5-methyl above adding] O-phthalic base imines 6.0g, dehydrated alcohol 50mL, 80% hydrazine hydrate 1.45g, reflux 6h.Reaction finishes, and filtering reacting liquid gets light yellow liquid 3.3g after filtrate concentrates, thick yield 95.6%. 1H?NMR(CDCl 3)：δ1.57(s，2H)，3.94(s，2H)，6.21(s，1H).
Embodiment 7: the preparation of substituted phenylhydrazines (with the example that synthesizes of 2,4 dichloro benzene hydrazine):
Add 2,4 dichloro aniline 5.00g and 40mL concentrated hydrochloric acid in the 250mL four-hole bottle, cooling drips the 12mL aqueous solution of Sodium Nitrite 2.77g down, dropwises and reacts 90min again.Drip two hydrated stannous chloride 17.40g then, the 15mL hydrochloric acid soln, dropwise back stirring at room 1.5h, filter the hydrochloride crude product that obtains the 2,4 dichloro benzene hydrazine, recrystallization obtains the needle-like crystal 4.38g of the hydrochloride of 2,4 dichloro benzene hydrazine.It is soluble in water, and the adding dilute NaOH solution is 9-10 to the pH of solution, and filtration obtains 2,4 dichloro benzene hydrazine 4.2g, fusing point 93-94 ℃.
Synthesizing of embodiment 8:2-cyano group-3-(5-Yi Bing Ji oxazole-2-methylamino)-4-methyl-2-pentenoic acid ethoxy ethyl ester:
In 50ml single port bottle, add 1.5mmol 5-sec.-propyl-2-oxazole methylamine crude product, 1mmol 2-cyano group-3-methoxyl group-4-methyl-2-pentenoic acid ethoxy ethyl ester and 15mL ethanol, reflux 2 hours is to reacting completely.Concentrate the back column chromatography for separation and get product, yield 70.4%.
Synthesizing of embodiment 9:2-cyano group-3-(quinoline-3-methylamino)-3-methylthio group vinylformic acid ethoxy ethyl ester:
In the 50ml single port bottle, add 1.5mmol 3-quinoline methylamine, 1.5mmol 3,3 ,-diformazan sulfenyl-2-alpha-cyanoacrylate ethoxy ethyl ester, 20ml ethanol, reflux 1.5h.Concentrate the back column chromatography and promptly obtain product, productive rate 96.8%, fusing point 83-84 ℃.
Synthesizing of embodiment 10:2-cyano group-3-(3-trifluoromethyl Ben oxadiazole-5-methylamino)-4-methyl-2-pentenoic acid ethoxy ethyl ester:
In 50ml single port bottle, add 1.5mmol 3-trifluoromethyl Ben oxadiazole-5-methylamine crude product, 1.5mmol 2-cyano group-3-methoxyl group-4-methyl-2-pentenoic acid ethoxy ethyl ester and 15mL ethanol, reflux 2 hours is to reacting completely.Concentrate the back column chromatography for separation and get the oily product, yield 47.1%.
Embodiment 11:2-cyano group-3-(synthesizing of 3-(2,6-dichlorophenyl) isoxazole-5-methylamino)-4-methyl-2-pentenoic acid ethoxy ethyl ester:
In 50ml single port bottle, add 1.5mmol 3-(2,6-dichlorophenyl) isoxazole-5-methylamine crude product, 1.5mmol 2-cyano group-3-methoxyl group-4-methyl-2-pentenoic acid ethoxy ethyl ester and 15mL ethanol, reflux 2 hours is to reacting completely.Concentrate the back column chromatography for separation and get the oily product, yield 70.6%.
Synthesizing of embodiment 12:2-cyano group-3-(2,6-dichlorobenzene diazanyl)-2-pentenoic acid ethoxy ethyl ester:
In 50ml single port bottle, add 1mmol 2, the 6-dichloro phenyl hydrazine, 1mmol 2-cyano group-3-methoxyl group-2-pentenoic acid ethoxy ethyl ester and 5mL ethanol, cooling down, reaction 30min filters, filter cake is with cold ethanol rinse.The filter cake column chromatography for separation gets product, yield 30%, fusing point 98-99 ℃.
With synthetic other target compounds (A) of similar approach.Concrete outcome sees Table 1.
The materialization data of table 1 target compound A
Figure G2009102047285D00091
Figure G2009102047285D00101
Figure G2009102047285D00121
Figure G2009102047285D00131
Embodiment 13: the primary dcreening operation of weeding activity is measured:
Adopt pot-culture method to measure the live body weeding activity of target compound: put into a certain amount of soil in the plastics cuvette of diameter 8cm, add a certain amount of water, after planting cover certain thickness soil, cultivate in greenhouse, it is preceding with plastic covered to come up.Every day in addition quantitative clear water to keep normal growth.Cauline leaf (one heart stage of seedling one leaf) is handled.Test examination material: rape (Brassica napus), Amaranthus retroflexus (Amaranthus retroflexus), barnyard grass grass (Echinochloacrusgalli (L.) Beauv.) and lady's-grass (Digitaria sanguinalis (L.) Scop.).Handle 10 to 15 days " Invest, Then Investigate " results, measure the overground part fresh weight, suppress percentage ratio with fresh weight and represent drug effect.The results are shown in Table 2.
The weeding activity inhibiting rate (%) of table 2 target compound A (dosage 100 gram/mus)
Figure G2009102047285D00132
Figure G2009102047285D00141
Figure G2009102047285D00151
The result shows: part of compounds A shows good weeding activity; Cauline leaf is handled active in soil treatment; Activity to the broad-leaved rape is higher than Gramineae barnyard grass grass.
Embodiment 14: the outstanding compound of activity is reduced dosage carry out multiple sieve mensuration:
Measuring method the results are shown in Table 3 with embodiment 12.
The weeding activity of table 3 part of compounds A sieves result (inhibiting rate %) again
Figure G2009102047285D00152
Figure G2009102047285D00161
The result shows: majority of compounds has higher weeding activity under the dosage of 50 gram/mus.Reduce to the dosage of 25 gram/mus, still have part of compounds to keep fine weeding activity.
Embodiment 15: to the test of the plant growth regulating activity and the fungicidal activity of compd A:
Adopt the isolated cucumber cotyledon rooting method to measure the plant growth regulating activity of compound.Cucumber variety is No. 4, Tianjin section, behind the seed-soaking, be sowed at and fill in the 0.7% agar enamel tray with cover, after darkroom (26 ℃) cultivate 3d, selected cotyledon of the same size is stand-by. and the filter paper method in the phytohormone activity substance-measuring is all adopted in the sample preparation, sample determination concentration is 10mg/L, and sample all adopts the dimethyl formamide dissolving. specific practice is: get the 3mg sample, be dissolved in the 3mL dimethyl formamide, dilute 10 times, get 0.3mL again and evenly drip on the filter paper of 6cm diameter, treat that solvent is air-dry after, in the incubator of 6cm diameter, put into 1 of the filter paper that contains sample, distilled water 3mL, 10 of cotyledons are the sample preparation of 10mg/L, with distilled water is contrast, each is handled 2 times and repeats, and cotyledon is (26 ℃) cultivation 5d in the darkroom, measures the number of taking root of per 10 slice, thin piece petiole bases.The results are shown in Table 4.
Adopt the Plating (Disc paper method) that exsomatizes to measure the fungicidal activity of target compound to gibberella saubinetii (P.zeae), tomato epidemic disease (A.solani) morning, peanut foxiness (C.rachidicola), apple wheel line (P.piricola) and withered (C.cucumerinum) the five kinds of thalline of cucumber; Adopt biomass growth rate assay method (mycelium growth rate test), reagent agent is diluted to certain multiple under aseptic condition, respectively drawing 1mL (500ug/mL) soup then injects in the culture dish, add the 9mL substratum more respectively, make 50 μ g/mL pastille flat boards after shaking up, do blank with the flat board that adds the 1mL aqua sterilisa. the punch tool with diameter 4mm cuts the bacterium dish along the mycelia outer rim, move on the pastille flat board, every processing triplicate. culture dish is placed on the interior .72h of cultivation of (24 ± 1) ℃ constant incubator " Invest, Then Investigate " and handles bacterium dish expansion diameter, average, relatively calculate relative bacteriostasis rate with blank. relative inhibition (%)=(control group bacterium dish expansion mean diameter-treatment group bacterium dish expansion mean diameter)/control group bacterium dish expansion mean diameter.The results are shown in Table 4.
The plant growth regulating activity (10mg/L) of table 4 part of compounds A and fungicidal activity (50mg/L) data.(inhibiting rate %)
Figure G2009102047285D00171
The result shows: part of compounds A is to apple wheel line performance fungicidal activity, and several compounds have good plant growth regulating activity.
Embodiment 16: to the anti-tumor activity body outer screening test of compd A (measuring unit: The National Center for Drug Screening):
(Methyl-Thiazol-Tetrozolium, MTT) reduction method is measured the restraining effect of part of compounds A to the growth of HL-60 human leukemia cell line to adopt tetrazolium.Select the adherent tumour cell of logarithmic phase for use, after trysinization, use RPMI 1640 substratum that contain 10% calf serum to be made into the cell suspension of 5000/ml, be seeded in 96 well culture plates, 200 μ l are inoculated in every hole, and 37 ℃, 5%CO2 cultivates 24h.The substratum that contains the different concns sample that experimental group renews, control group then changes the substratum that contains the equal-volume solvent, establishes 3～5 parallel holes for every group, and 37 ℃, 5%CO2 cultivates 72h.Abandoning supernatant, every hole add the serum free medium .37 ℃ of continuation of the freshly prepared 0.2mg/ml of the containing MTT of 200 μ l and cultivate 4h.Carefully abandoning supernatant, and add 200 μ l DMSO, behind miniature ultrasonic vibrator mixing, is 570nm with the tested wavelength on microplate reader, and reference wavelength is that 450nm measures optical density value, calculates inhibiting rate.
(sulforhodamine B, SRB) the protein staining method is measured the restraining effect of part of compounds A to the growth of BEL-7402 human hepatoma cell strain to adopt the sulphonyl rhodamine B.Select the adherent tumour cell of logarithmic phase for use, after trysinization, use RPMI 1640 substratum that contain 10% calf serum to be made into the cell suspension of 5000/ml, be seeded in 96 well culture plates, 200 μ l are inoculated in every hole, and 37 ℃, 5%CO2 cultivates 24h.50% Tricholroacetic Acid (TCA) the liquid 50ul (final concentration is 10%) that each aperture adds precooling is fixing.Outwell stationary liquid, aperture is washed 5 times with deionized water, dries dry air.Every hole added 100ul SRB liquid (0.4% solution that is made into 1% acetic acid), room temperature placement 10 minutes.Do not wash 5 times dry air with 1% acetate solution with protein bound SRB.Bonded SRB dissolves with 150ul10mmol/l non-buffering Tris alkali lye (ph10.5).Measure the OD value of each aperture, calculating inhibiting rate at 515nm wavelength place with the dull and stereotyped reader of automatization spectrophotometric.
The results are shown in Table 5.
Table 5: compd A is to growth of tumour cell inhibiting rate %
Figure G2009102047285D00191
The result shows that majority of compounds is 10 in concentration -4The time HL-60 human leukemia cell line and BEL-7402 human hepatoma cell strain all had obvious restraining effect, 10 -5The time A-47 still demonstrate restraining effect.

Claims (16)

1. cyanoacrylate new compound is characterized in that it is that structure is the compound of (B):
2. cyanoacrylate new compound is characterized in that it is that structure is the compound of (C):
Figure F2009102047285C00012
3. cyanoacrylate new compound is characterized in that it is that structure is the compound of (D):
Figure F2009102047285C00013
4. cyanoacrylate new compound is characterized in that it is that structure is the compound of (E):
5. cyanoacrylate new compound is characterized in that it is that structure is the compound of (F):
Figure F2009102047285C00015
6. cyanoacrylate new compound is characterized in that it is that structure is the compound of (G):
7. cyanoacrylate new compound is characterized in that it is that structure is the compound of (H):
8. cyanoacrylate new compound is characterized in that it is that structure is the compound of (I):
Figure F2009102047285C00022
9. cyanoacrylate new compound is characterized in that it is that structure is the compound of (J):
Figure F2009102047285C00023
10. cyanoacrylate new compound is characterized in that it is that structure is the compound of (K):
Figure F2009102047285C00024
11. a cyanoacrylate new compound is characterized in that it is that structure is the compound of (L):
Figure F2009102047285C00025
12. a cyanoacrylate new compound is characterized in that it is that structure is the compound of (M):
Figure F2009102047285C00026
13. a cyanoacrylate new compound is characterized in that it is that structure is the compound of (N):
14. a cyanoacrylate new compound is characterized in that it is that structure is the compound of (O):
Figure F2009102047285C00032
15. a cyanoacrylate new compound is characterized in that it is that structure is the compound of (P):
Figure F2009102047285C00033
16. in agricultural chemicals and application pharmaceutically, it is characterized in that as weedicide, sterilant, plant-growth regulator and anti-tumor agent comprising salmosin as said these cyanoacrylate new compounds of claim 1-15.
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CN103304458A (en) * 2013-07-10 2013-09-18 南开大学 Bactericidal activity of cyanoacrylate compound containing 2-aryloxy propylamino structure
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CN103408478A (en) * 2013-07-10 2013-11-27 南开大学 Bactericidal activity of 2-aryloxy alanyl structure-containing cyano acrylamide compound
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CN111333579A (en) * 2020-04-17 2020-06-26 南通大学 Preparation and application of cyanoacrylate derivative containing 4-chloro-1-methyl-3-substituent pyrazole
CN111333578A (en) * 2020-04-17 2020-06-26 南通大学 Preparation and application of cyanoacrylates containing 1-methyl-3-(4-fluorophenyl)-4-chloropyrazole units
CN111499568A (en) * 2020-04-21 2020-08-07 南通大学 Preparation and application of cyanoacrylate derivative containing pyridine bi-4-mercaptoaryl unit

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Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103304460A (en) * 2013-07-10 2013-09-18 南开大学 Bactericidal activity of cyano acrylamide compound containing aryloxy propan-2-amino structure
CN103304458A (en) * 2013-07-10 2013-09-18 南开大学 Bactericidal activity of cyanoacrylate compound containing 2-aryloxy propylamino structure
CN103304459A (en) * 2013-07-10 2013-09-18 南开大学 Bactericidal activity of cyanoacrylate compound containing aryloxy propan-2-amino structure
CN103408478A (en) * 2013-07-10 2013-11-27 南开大学 Bactericidal activity of 2-aryloxy alanyl structure-containing cyano acrylamide compound
CN103304460B (en) * 2013-07-10 2015-04-01 南开大学 Bactericidal activity of cyano acrylamide compound containing aryloxy propan-2-amino structure
CN107522676A (en) * 2017-08-18 2017-12-29 南通大学 The preparation and application of the cyanacrylate derivant of Han oxazole biphenyl sulfenyl structures
CN107522676B (en) * 2017-08-18 2019-06-14 南通大学 Preparation and Application of Cyanoacrylate Derivatives Containing Oxazole Biphenyl Sulfide Structure
CN111333579A (en) * 2020-04-17 2020-06-26 南通大学 Preparation and application of cyanoacrylate derivative containing 4-chloro-1-methyl-3-substituent pyrazole
CN111333578A (en) * 2020-04-17 2020-06-26 南通大学 Preparation and application of cyanoacrylates containing 1-methyl-3-(4-fluorophenyl)-4-chloropyrazole units
CN111333578B (en) * 2020-04-17 2021-10-22 南通大学 Preparation and application of cyanoacrylates containing 1-methyl-3-(4-fluorophenyl)-4-chloropyrazole units
CN111499568A (en) * 2020-04-21 2020-08-07 南通大学 Preparation and application of cyanoacrylate derivative containing pyridine bi-4-mercaptoaryl unit
CN111499568B (en) * 2020-04-21 2021-08-17 南通大学 Preparation and Application of Cyanoacrylate Derivatives Containing Pyridine Bi-4-mercaptoaryl Units

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