CN108299416A - A kind of inhibitor of acetolactate synthetase and its application in herbicide - Google Patents
A kind of inhibitor of acetolactate synthetase and its application in herbicide Download PDFInfo
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- CN108299416A CN108299416A CN201810333985.8A CN201810333985A CN108299416A CN 108299416 A CN108299416 A CN 108299416A CN 201810333985 A CN201810333985 A CN 201810333985A CN 108299416 A CN108299416 A CN 108299416A
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- formula
- acetolactate
- herbicide
- inhibitor
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
Abstract
The invention discloses a kind of inhibitor of acetolactate synthetase, structural formula is formula（Ⅰ）, it measures and finds through in vitro activity of acetolactate synthase, formula（Ⅰ）With tribenuron-methyl to the IC of acetolactate synthestase50Value is respectively 0.58 and 0.70 μ g/L, formula（Ⅰ）With acetolactate synthestase inhibitory activity, the herbicide of type can be inhibited to be used for the control of weeds of agriculture field as acetolactate synthestase.
Description
Technical field
The present invention relates to agriculture germ plasm resource and its prevention and control more particularly to a kind of inhibitor of acetolactate synthetase and its
Application in herbicide.
Background technology
Acetolactate synthestase（Acetolactate Synthase, ALS）It is catalysis branched-chain amino acid-valine, bright
The key enzyme of first stage in propylhomoserin, isoleucine biosynthetic process, it can be urged in the synthesis of valine and leucine
The pyruvic acid for changing 2 molecules generates α-acetolactic acid and CO2, the pyruvic acid and 1 of 1 molecule is catalyzed in the synthesis of isoleucine
The α of a molecule-batanone acid generates 2- aldehyde-base -2- hydroxybutyric acids and CO2.ALS inhibitor class herbicides are by inhibiting plant
The activity of interior ALS enzymes blocks the biosynthesis of branched-chain amino acid, and then influences the synthesis of protein and inhibit cell division, from
And lead to plant tissue chlorosis, yellow, so that the growth and development of plant is suppressed and gradually death, is finally reached chemical weed control
Purpose.Mainly there is sulfonylurea (sulfony- using more extensive ALS inhibitor class herbicide in the world at present
Lureas, SU), imidazolone type (imidazolinones, IMI), sulfonamide carbonyltriazolinone (sulfonylamino
Carbonyl triazolino-nes, SCT), triazolo pyrimidine class (triazolopyrimidines, TP), pyrimidine phosphorothioate benzene first
Esters of gallic acid (pyrimidinylthiobenzoates, PTB) etc..
With the extensive use of the herbicide of inhibitor of acetolactate synthetase class, ALS inhibitor class herbicides are generated
The weeds type of resistance increases sharply, so far, the whole world have 44 it is national 159 kinds total（97 kinds dicotyledonous and 62 kinds
Unifacial leaf）Weeds produce resistance to ALS inhibitor class herbicides, wherein middle Kuomintang-Communist reports 14.The second of new construction type
The exploitation of acyl lactic acid synthetase inhibitors is an important process in herbicide field.
Invention content
The purpose of the present invention is to provide a kind of compound, structural formula is formula（Ⅰ）
。
Further, formula（Ⅰ）The salt of the compound of expression or its solvated compounds.
Another object of the present invention is to provide a kind of Formulas（Ⅰ）Synthetic route be
Wherein, compound 5 is Formula of the present invention（Ⅰ）.
Further, the synthetic method of each step is as follows in said synthesis route：
(1) 2- trifloro methyl phenols, N-iodosuccinimide and DMF are dissolved in suitable solvent, heating reaction 2 hours, warp
It is filtered, washed, dries, crystallizes, generate compound 2；
(2) compound 2 is mixed with phosphorus oxychloride in DMF, heating reaction enough time, is added to system under microwave condition
Water, through extraction, drying, concentration, pillar layer separation obtains compound 3；
(3) compound 3 is dissolved in toluene, isoxazole -4- amine is added in system, add catalyst and triethylamine, heating reaction 4
Hour, through washing, liquid separation, drying, concentration, last pillar layer separation obtains compound 4；
(4) compound 4 and corresponding the boric acid catalytic coupling in DMF, it is post-treated to obtain compound 5.
Further, the reaction dissolvent in the step (1) is that dichloromethane, acetonitrile and tetrahydrofuran etc. are suitable molten
Agent, preferably dichloromethane.
Further, the reaction temperature in the step (1) is 60 DEG C -100 DEG C, preferably 80 DEG C.
Further, the heating temperature in the step (2) is 80 DEG C -150 DEG C, preferably 130 DEG C.
Further, the reaction time in the step (2) is -2 hours 0.5 hour, preferably 1 hour.
Further, the heating temperature in the step (3) is 40 DEG C -80 DEG C, preferably 50 DEG C.
Formula of the present invention is confirmed in test example（Ⅰ）It, can be with inhibitor of acetolactate synthetase effect
As herbicide, Formula of the present invention（Ⅰ）Also there is insecticidal action.
Another object of the present invention is to provide a kind of Formulas（Ⅰ）As application of the herbicide in agricultural.
Another object of the present invention is to provide a kind of Formulas（Ⅰ）As application of the insecticide in agricultural.
Specific implementation mode
Embodiment 1：Formula（Ⅰ）Synthesis
The synthesis of 1.1 4- iodo -2- trifloro methyl phenols
2- trifloro methyl phenols (10 mmol) are dissolved in 20 ml dichloromethane, 2 ml DMF are added thereto, are stirred 10 minutes,
Then N-iodosuccinimide (12 mmol) is added thereto, system temperature rises to 80 DEG C or so, reacts 2 hours, system drop
To room temperature, filtering removes insoluble matter, and surplus solution is washed twice with 2% diluted hydrochloric acid aqueous solution, organic phase anhydrous sodium sulfate
Dry, after filtering, natural solvent flashing crystallization obtains 2.5g off-white color 4- iodo -2- trifloro methyl phenol crystal, yield 87%
。1H-NMR (400 MHz, CDCl3) δ: 5.09(s, 1H), 6.48(d, 1H), 7.81(m, 2H). 13C-NMR(75
MHz, CDCl3) δ: 84.79, 119.05, 124.47, 132.07, 141.65, 158.07. LC-MS(ESI, pos,
ion) m/z: 289 [M+H]。
The synthesis of 1.2 1- chlorine-4-iodine generation -2- trifluoromethylbenzenes
4- iodo -2- the trifloro methyl phenols (10 mmol) that 1.1 obtain are dissolved in 20 ml DMF, phosphorus oxychloride is then added
(10.5 mmol), system is placed under microwave environment, is heated to 130 DEG C, is reacted 1 hour.After the completion of reaction, system is down to room
30 ml water are added in temperature thereto, stir 10 minutes, add the extraction of 30 ml dichloromethane, and organic phase is dry with anhydrous sodium sulfate
Dry, solvent is evaporated off in filtering, filtrate decompression, and residue uses petroleum ether as eluant, eluent, and it is light to obtain 2.1 g for flash column chromatography separation
The solid powder of yellow 1- chlorine-4-iodine generation -2- trifluoromethylbenzenes, yield 69%.1H-NMR (400 MHz, CDCl3) δ: 7.09
(d,1H), 7.92(m, 2H). 13C-NMR(75 MHz, CDCl3) δ: 84.79, 123.12, 130.38, 130.47,
131.79, 133.18, 140.45. LC-MS(ESI, pos, ion) m/z: 306 [M+H]。
The synthesis of 1.3 N- (4- chloro -3- trifluoromethyls)-isoxazole -4- amine
1- chlorine-4-iodines generation -2- trifluoromethylbenzenes (10 mmol) that reaction 1.2 obtains are dissolved in 20 ml toluene, in system according to
Secondary addition isoxazole -4- amine (12mmol), acid chloride (0.5 mmol), 2,2 '-two (diphenylphosphoryl group) -1,1 '-dinaphthalene (12
Mmol), after ten minutes, 10 ml cesium carbonates (10 mmol) aqueous solution is added in 3 ml triethylamines, stirring, is heated to 50 DEG C of reactions 4
Hour, after reaction, 20 ml water being added into system, stirs 20 minutes, liquid separation, organic phase is dried with anhydrous sodium sulfate,
Concentration, flash column chromatography separation, obtains 2.2 g yellow N- (4- chloro -3- trifluoromethyls)-isoxazole -4- amine powder, produces
Rate 84%.1H-NMR (400 MHz, CDCl3) δ:6.15(s, 1H), 7.66(m, 2H), 8.20(m, 3H).13C-NMR
(75 MHz, CDCl3) δ: 117.22, 121.1, 123.12, 123.90, 125.97, 128.00, 129.59,
142.06, 148.44, 150.77. LC-MS(ESI, pos, ion) m/z: 263 [M+H]。
The synthesis of 1.4 N- [4- (4- fluoro thiophene -2- bases) -3- trifluoromethyls]-isoxazole -4- amine
N- (4- chloro -3- trifluoromethyls)-isoxazole -4- amine (10 mmol) that 1.3 obtain is dissolved in 30 ml N, N- bis-
In methylformamide, system rouses 20 min of argon gas, then the air in emptying system is added tetra-triphenylphosphine palladium, is warming up to 60
DEG C, continue to stir half an hour, 4- fluoro thiophene -2- boric acid (12 mmol) is added thereto, adds 10 ml sodium carbonate (1 g)
Aqueous solution is warming up to 90 DEG C, stirs 5 hours, and whole process holding is passed through argon gas, then cools down, removes solvent under reduced pressure, solid is fast
It is white to obtain 3.0 g N- [4- (4- fluoro thiophene -2- bases) -3- trifluoromethyls]-isoxazole -4- amines by chromatographic column for speed
Color solid, yield 91%.1H-NMR (400 MHz, CDCl3) δ: 5.89(s, 1H), 7.16(dd, 1H), 7.41(m,
3H), 7.66(d, 1H), 7.75(d, 1H), 8.24(s, 1H). 13C-NMR(75 MHz, CDCl3) δ: 113.89,
114.43, 119.15, 123.9, 124.05, 124.19, 125.89, 125.98, 130.14, 136.11,
141.34, 148.44, 150.77, 162.12.LC-MS(ESI, pos, ion) m/z: 329 [M+H]。
Test example 1：Acetolactate synthestase（ALS）Vitality test
Activity of acetolactate synthase measures correlation technique and refers to FAN Z J, QIAN C F, LI Z M, et al.
Specific activity determination of acetolactate synthase from maize(Zea mays
L.).In:Han W N, Zhen G Y. eds.The Proceedings of the 18th Asia-Pacific Weed
Science Society Conference, Beijing: Standards Press of China, 515-522, May
28-June 2,2001, concrete operation step is as follows：
1, preparation of reagents
Phosphate buffer：The K of 0.1mol/L pH7.02HPO4-KH2PO4；
Zyme extract：Sodium Pyruvate containing 1mmol/L, 0.5mmol/L MgCl2, 0.5mmol/L TPP's, 10 μm of ol/L FAD
The phosphate buffer of 0.1mol/L pH7.0；
Enzyme lysate：Sodium Pyruvate containing 20mmol/L, 0.5mmol/L MgCl20.1mol/L pH7.0 phosphate buffer；
Enzyme reaction solution：Sodium Pyruvate containing 20mmol/L, 0.5mmol/L MgCl2, 0.5mmol/L TPP's, 10 μm of ol/L FAD
The phosphate buffer of 0.1mol/L pH7.0；
5% alpha naphthol：It is dissolved in 2.5mol/L NaOH solutions；
0.5% creatine；3mol/L sulfuric acid；Saturated ammonium sulfate solution.
2, the extraction of acetolactate synthestase
3~4 wheel blade phase clearvers aerial part 1g are shredded and are put into precooling glass mortar, 4mL zyme extracts are added（Contain
1mmol/L Sodium Pyruvates, 0.5mmol/L MgCl2, 0.5mmol/L TPP, the 0.1mol/L pH7.0's of 10 μm of ol/L FAD
Phosphate buffer）And appropriate amount of quartz sand, quickly grinding homogenate, is placed in centrifuge tube and is settled to 8mL under condition of ice bath, in
25000g, 20min is centrifuged at 4 DEG C；Supernatant is taken to be slowly added to (NH4)2SO4Crystal is to 50% saturation degree, after precipitating 2h, in
25000g, 30min being centrifuged at 4 DEG C, abandoning supernatant, precipitation is dissolved in 6mL enzyme lysates（Sodium Pyruvate containing 20mmol/L,
0.5mmol/L MgCl20.1mol/L pH7.0 phosphate buffer）In it is to be measured.The above operation under the conditions of 0~4 DEG C into
Row.
3, in vitro activity of acetolactate synthase measures
0.9mL enzyme reaction solutions are added in 10mL tool plug test tubes（Sodium Pyruvate containing 20mmol/L, 0.5mmol/L MgCl2,
0.5mmol/L TPP, the phosphate buffer of the 0.1mol/L pH7.0 of 10 μm of ol/L FAD）, 1mL enzyme solutions and 0.1mL final concentrations
For the untested compound of 0,5,10,50,100,500 μ g a.i./L（Tribenuron-methyl or Formula of the present invention（Ⅰ））It is molten
Liquid, after shaking up in 35 DEG C of waters bath with thermostatic control dark reaction 1h, the 3mol/L H of 0.2mL are added2SO4Terminate reaction, 60 DEG C of water-bath decarboxylations
15min.0.5% creatines of 1mL and 5% alpha naphthols of 1mL is added（2.5mol/L NaOH solutions are prepared）, 60 DEG C of water-bath colour developings
15min is immediately placed in ice bath cooling 1min, in 525nm colorimetrics.Light absorption value is set to change to be catalyzed reaction in 1mg/L albumen 1h
0.001 is an enzyme activity unit U, using the enzyme activity unit number of 1mg/L soluble proteins as enzyme activity.Soluble protein content
It measures and uses Coomassie brilliant G-250 method.With enzyme activity inhibiting rate niqueMin (Y) and untested compound（Tribenuron-methyl or the present invention
The Formula（Ⅰ））Log concentration value (X) establishes regression equation (Y=a+bX), seeks IC50It is worth, at data DPS softwares
Reason.
4, in vitro activity of acetolactate synthase measurement result
| Untested compound | IC50（μg/L） |
| Tribenuron-methyl | 0.70 |
| Formula（Ⅰ） | 0.58 |
As seen from the above table, Formula of the present invention（Ⅰ）With acetolactate synthestase inhibitory activity, acetyl can be used as
Lactic acid synzyme inhibits the herbicide of type for the control of weeds of agriculture field.Formula of the present invention（Ⅰ）To not
It is still necessary to further study for the sensibility of kindred plant.
Test example 2：Insecticidal activity is tested
Formula of the present invention（Ⅰ）Insecticidal activity testing experiment has been carried out to diamondback moth and black peach aphid.It is specific as follows：
（1）The preparation of untested compound
By untested compound（Formula of the present invention（Ⅰ）Or positive control Tolfenpyrad）It is 1 with volume ratio:The third of 1
After ketone and methyl alcohol mixed liquor dissolving, with containing 0.1%（wt）Tween solution is diluted to required concentration.
（2）To the insecticidal activity of diamondback moth
Cabbage leaves are broken into the leaf dish of diameter 2cm with card punch, the pressure of airbrush spraying treatments is 10psi（It is roughly equal to
0.7kg/cm2）, per leaf dish positive and negative spraying, spouting liquid 0.5ml.Often processing is put into 10 2 age test worms after drying in the shade, and often handles 3
Secondary repetition.It is put into 25 DEG C after processing, is cultivated in relative humidity 60-70% observation ward, investigation survival borer population after 72 hours calculates dead
Die rate.
（3）To the insecticidal activity of black peach aphid
The culture dish of diameter 6cm is taken, ware bottom covers one layer of filter paper, and appropriate tap water moisturizing is added dropwise, from the wild cabbage of culture black peach aphid
Clip suitable size on plant（Diameter about 3cm）And with the cabbage leaves of 15-30 aphid, removing alatae worm and blade just
The aphid in face, blade back are placed in culture dish upwards.The pressure of airbrush spraying treatments is 10psi（It is roughly equal to 0.7kg/cm2）, often
Leaf dish positive and negative is sprayed, spouting liquid 0.5ml.Often processing is repeated 3 times.25 DEG C are put into after processing, relative humidity 60-70% observations
Indoor culture, investigation survival borer population, calculates the death rate after 48 hours.
（4）Test result
When untested compound and Tolfenpyrad liquor strength are 600mg/L, the insecticidal activity of diamondback moth and black peach aphid see the table below：
As seen from the above table, Formula of the present invention（Ⅰ）With insecticidal activity.Acetolactate synthestase plant, algae,
Escherichia coli, salmonella typhimurium, yeast, fungi, are not related to humans and animals, it can be concluded that compound of the present invention
Formula（Ⅰ）The insecticidal activity having is unrelated with acetolactate synthestase inhibitory activity, and it is still necessary to further for the mechanism of action of insecticidal activity
Research.
Claims (4)
1. a kind of compound, structural formula is formula（Ⅰ）
。
2. Formula as described in claim 1（Ⅰ）Synthetic route be
,
Wherein, compound 5 is Formula of the present invention（Ⅰ）.
3. Formula as described in claim 1（Ⅰ）With inhibitor of acetolactate synthetase effect.
4. Formula as described in claim 1（Ⅰ）It may be used as herbicide.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201810333985.8A CN108299416A (en) | 2018-04-14 | 2018-04-14 | A kind of inhibitor of acetolactate synthetase and its application in herbicide |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1522251A (en) * | 2001-05-09 | 2004-08-18 | ס������ũҩ��ʽ���� | Azole compounds, process for preparation of the same and use thereof |
| CN102123591A (en) * | 2008-03-20 | 2011-07-13 | 拜尔农作物科学股份公司 | Diaminopyrimidines as plant protection agents |
| JP2017075131A (en) * | 2015-10-16 | 2017-04-20 | 石原産業株式会社 | Pyridazinone compound or salt thereof, and herbicide comprising them |
-
2018
- 2018-04-14 CN CN201810333985.8A patent/CN108299416A/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1522251A (en) * | 2001-05-09 | 2004-08-18 | ס������ũҩ��ʽ���� | Azole compounds, process for preparation of the same and use thereof |
| CN102123591A (en) * | 2008-03-20 | 2011-07-13 | 拜尔农作物科学股份公司 | Diaminopyrimidines as plant protection agents |
| JP2017075131A (en) * | 2015-10-16 | 2017-04-20 | 石原産業株式会社 | Pyridazinone compound or salt thereof, and herbicide comprising them |
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Application publication date: 20180720 |