CN107602496B - Chiral complementary alkyl heterocyclic compound and application thereof as bactericide - Google Patents

Abstract

The invention relates to chiral complementary alkyl heterocyclic compounds and application thereof as bactericides, wherein the chemical structural general formula of the compounds is shown as the following formula (I):

in the general formula (I), the 8-position steric configuration is R or S;

Description

Chiral complement alkyl heterocyclic compounds and their use as fungicides

technical field

The present invention relates to a novel chiral complement alkyl heterocyclic compound and its use as a fungicide; in particular, it refers to the application of the compound in the prevention and control of agricultural fungal diseases, which belongs to the technical field of pesticides.

Background technique

Plant pathogens are low-level organisms among harmful organisms, and they are also organisms with strong reproductive ability. At present, the loss caused by plant diseases is increasing year by year, and the global annual loss caused by diseases is more than 11%, such as rice blast in grain crops, rice sheath blight, wheat scab, potato late blight, botrytis cinerea on fruits and vegetables Wait. On the other hand, the problems of residual pesticide residues, negative impact on the environment, and drug resistance of harmful organisms are becoming more and more serious (Thornton, J. Pure Appl. Chem. 2001, 73, 1231-1236.). The No. 1 Central Document in 2016 emphasized strengthening the reform of the agricultural supply side and improving the effective supply of agricultural products such as grain; the current requirements for reducing the application of pesticides and chemical fertilizers and increasing efficiency point out new directions for green plant protection and new requirements for the creation of new pesticides. The increasingly prominent problem of resistance requires the majority of pesticide chemists to develop some fungicides with new mechanisms of action or new chemical structures. Because natural products have many advantages such as novel chemical structures, diverse modes of action, and good environmental compatibility, they not only occupy an important position in the development of medicines, but are also one of the important ways to create new pesticides (Wu Wenjun. From natural products to new pesticide creation- Principle. Methods., 2006, Beijing: Chemical Industry Press. Newman, D.J.et al.J.Med.Chem.2008, 51, 2589-2599. ACS Symposium Series 2015, 1204, 55-62. Pest management science 2017, 73, 700-715.).

Drimane meroterpenoids are an important class of natural products, widely distributed in nature, with a wide range of biological activities, such as antitumor, anti-HIV, antifeedant activity, neurotoxicity, antimalarial activity, antibacterial activity et al (Studies in Natural Products Chemistry 2015, 45, Chapter 6, 147-215.). In recent years, important progress has also been made in the chemical and chemical biology research on Drimane-like heterosesquiterpenes natural products and their analogs, such as: such compounds exhibit significant inositol-5-phosphatase activation ( MacKenzie, L.F., WO2014110036A1, 2014; Org.Lett.2005, 7, 1073-1076.); Phil.S.Baran of Sripps Institute developed a diversified synthesis of Drimane-like natural products based on sclare boronate . Such compounds are less studied in pesticide chemistry; but the potential antibacterial activity aroused our interest (J.Org.Chem.1973, 38, 2383-2386.), and we also found that these compounds have better Antibacterial activity (Chinese invention patent, application number 201610762193.3; application publication number CN106397254A; Eur.J.Med.Chem.2017, 136, 114-121.), on the other hand long synthetic route, intermediate isomerization and chemical The stoichiometric transition metal catalysis further limits the research of such compounds in chemical biology. Based on function-oriented diversity synthesis, we introduce diverse heterocycles into the Drimane skeleton, which not only enriches the structural library, but also improves the physicochemical properties of the compounds, which in turn helps to improve the druggability of such compounds and promote their chemical biology. research and exploration.

The invention completes the construction of chiral chiral alkyl heterocyclic compounds with diverse structures and finds that such compounds have good antifungal activity, which is of great significance for developing green and environment-friendly new fungicides.

SUMMARY OF THE INVENTION

The technical problem to be solved by the present invention is to provide a preparation method of a chiral complement alkyl heterocyclic compound and its application in preventing and controlling plant fungal diseases. The chiral tonic alkyl heterocyclic compound of the present invention exhibits a good inhibitory effect on fungal diseases, and its physical and chemical properties are significantly improved compared with the natural tonic hetero sesquiterpenes, and the medicinal properties are also good. Further improve.

The chiral complement alkyl heterocyclic compound provided by the present invention has the structure shown in the following general formula (I),

The stereoconfiguration of the 8-position in the general formula (I) is R or S,

代表：In general formula (I)

represent:

(1) Isoxazolines and isoxazoles, refers to 5-substituted isoxazolines and isoxazoles compounds of 3-fortified alkyl, specifically including the compounds shown below:

R is the following substituent:

(2) Pyrazolines, refer to pyrazoline compounds substituted by 3-fortified alkyl 5-, specifically including the compounds shown below:

Wherein the substituent represented by R is shown in (1);

R ₂ is the following substituent:

(3) Pyrimidines refer to pyrimidines 6-substituted with 4-fortified alkyl, specifically including the following compounds:

Wherein the substituent represented by R is shown in (1);

R ₂ is the following substituent (n=0, 1, 2):

(4) Benzimidazopyrimidines, specifically including the compounds shown below:

The substituent represented by R is shown in (1).

(5) Diazepines, specifically including the compounds shown below:

The substituent represented by R is shown in (1), and the substituent represented by R ₂ is shown in (3).

The present invention also includes the pesticide chemically acceptable salts of the chiral tomyl heterocyclic compounds represented by the general formula (I).

The compounds involved in the present invention can be chemically completed according to the following synthetic routes.

Synthesis method one:

The synthetic route takes the cheap and easily available natural product sclareol as the starting material, firstly oxidatively degrades it under the oxidation condition of potassium permanganate to obtain the carboxylate carboxylate, and then treats and cyclizes it under the acidic condition, Preparation of sclareolide. The ring-opening of sclareolide under the nucleophilic attack of methyllithium to form methyl ketone intermediate A, and Aldol condensation and dehydration of aldehydes under alkaline conditions to obtain α,β-unsaturated ketone compounds B. Hydroxylamine hydrochloride is used as a michael donor to condense with α,β-unsaturated ketone compound B to form isoxazoline compound C under alkaline conditions.

Synthesis method two:

The synthetic route is similar to the synthetic method 1. The reaction medium is changed, the reaction temperature is increased, and the α, β-unsaturated ketone compound B and hydroxylamine hydrochloride obtained in the synthetic method 1 are still used as raw materials, and the isoxazole compound D is condensed. .

Synthesis method three:

This synthetic route still uses the α, β-unsaturated ketone compound B obtained in the synthetic method 1 as the raw material, changes the Michael donor from hydroxylamine hydrochloride to phenylhydrazine compounds, and condenses into pyrazoline compounds under alkaline conditions D.

Synthesis method four:

This synthetic route still uses the α, β-unsaturated ketone compound B obtained in the synthetic method 1 as the raw material, changes the Michael donor from hydroxylamine hydrochloride to guanidine hydrochloride compound, and condenses into the pyrimidine compound F under alkaline conditions, and in Under the condition of Chan-Lam coupling reaction, the arylation of pyrimidine amine is completed by using boronic acid compound to obtain pyrimidine compound F1.

Synthesis method five:

The synthetic route uses the pyrimidine compound F obtained in the synthetic method 4 as the raw material, and utilizes the nucleophilic substitution reaction of halogenated hydrocarbon or the Ullman coupling reaction to realize the arylation or alkylation of the pyrimidine amine to obtain the pyrimidine compound F2.

Synthesis method six:

This synthetic route uses the α, β-unsaturated ketone compound B obtained in the synthetic method 1 as the raw material, changes the Michael donor from hydroxylamine hydrochloride to 2-aminobenzimidazole compound, and condenses to benzimidazole under alkaline conditions Pyrimidine compounds G.

Synthesis method seven:

This synthetic route still uses the α, β-unsaturated ketone compound B obtained in the synthetic method 1 as the raw material, changes the Michael donor from hydroxylamine hydrochloride to o-phenylenediamine compound, and condenses to diazepine under alkaline conditions Class compound H. Then, according to the method of amine alkylation or arylation in method four or five, the structure optimization of the diazepine compound is realized.

The chiral complement alkyl heterocyclic compound provided by the invention has the characteristics of cheap and easy-to-obtain raw materials, few synthesis steps and diversified structures.

The compounds involved in the present invention include the chemically acceptable salts of the chiral tomyl heterocyclic compounds represented by the general formula (I).

The fungi selected in the bacteriostatic activity of the chiral compatiment alkyl heterocyclic compounds provided by the present invention include Rhizoctonia solani, Rhizoctonia cerealis, Sclerotinia solani scleotiorum), Fusarium graminearum, Gaeumanomyce graminis, Botrytis cinerea, Phytophthora infestans, Phytophthora capsici, early tomato Alternaria solani, Fusarium fujikuroi, Fusarium sulphureum, Colletotrichum lagenarium, Phyricularia cerealis.

Detailed ways

The present invention can be further illustrated and understood through the following examples and experimental results of biological activity assay, but it is not intended to limit the present invention.

Example 1: (1R, 2R, 4aS, 8aS)-2,5,5,8a-tetramethyl-1-((5-phenyl-4,5-dihydroisoxazol-3-yl)methane Synthesis of Base) Decalin-2-ol (Complementary Alkylisoxazoline C1)

The first step: the synthesis of ((+)-sclareolide) of sclareolide;

The natural product sclareol (-)-sclareol (10.0 g, 32.4 mmol, 1.0 equiv) was dissolved in 200 mL of anhydrous acetone, the system was placed in an ice bath, and 60 mL of acetic anhydride was added to it; Potassium manganate powder (30.7 g, 194.5 mol, 6 equiv). The system was gradually returned to room temperature, magnetic stirring, and thin-layer chromatography (TLC) was followed to detect the progress of the reaction. After the raw materials were consumed, an aqueous solution of sodium carbonate (20.0 g/150 mL) was slowly added to quench the reaction, and the stirring was continued for 0.5 hours. mixture.

To this mixture was added 2N aqueous sodium hydroxide solution (50 mL), the reaction was refluxed for 2 hours, returned to room temperature, and the reaction system was acidified to pH=3 with 2N hydrochloric acid. Precipitation was precipitated, the filter cake was washed with cold water, and the filter cake was dried under vacuum to obtain a light yellow solid, which was separated by silica gel column chromatography (200-300 m, PE/EtOAc=8:1) to obtain a white solid sclareolide 4.95 g, 61% yield.

The second step: the synthesis of intermediate methyl complement ketone A;

Weigh sclareolide (+)-sclareolide (20.0 g, 79.8 mmol, 1.0 equiv) into a 500 mL eggplant-shaped bottle, dissolve it with anhydrous ether (250 mL), and slowly add methyl group to it at -78°C Lithium ether solution (1.5M inEt ₂ O, 100 mL, 150 mmol) was used to stir the reaction, followed by TLC to monitor the reaction until the sclareolide disappeared completely. 10% aqueous sulfuric acid solution was slowly added to the system to quench the reaction, and the reaction was naturally returned to room temperature. After separation, the inorganic phase was extracted with ether (150 mL×2), and the organic phases were combined, washed with saturated sodium bicarbonate solution (2×150 mL), water (150 mL) and saturated sodium chloride solution (100 mL) in turn, and the mixture was washed with water without After drying over magnesium sulfate, the solvent was evaporated under reduced pressure to obtain methyl ketone A (yield>90%), which was directly used in the next reaction.

The third step: the synthesis of α,β-unsaturated ketone compound B1;

Weigh methyl ketone A (267 mg, 1.0 mmol, 1.0 equiv.) in a 50 mL round-bottomed flask, dissolve with 10 mL of methanol, and slowly add sodium methoxide (65 mg, 1.2 mmol, 1.2 equiv) under ice bath conditions, After magnetic stirring for 20 min, benzaldehyde (106 mg, 1.0 mmol, 1.0 equiv.) was added thereto, heated to reflux, and the progress of the reaction was monitored by TLC. After the reaction was completed, the solvent was evaporated under reduced pressure, 15 mL each of saturated ammonium chloride and ethyl acetate were added to the system, the inorganic phase was extracted with ethyl acetate (2×15 mL), the organic phases were combined, and saturated sodium chloride (10 mL) was added to the system. ) was washed, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. After separation by column chromatography (PE/EtOAc=8:1, v/v), the unsaturated ketone B1 was obtained as a white solid.

The fourth step: the synthesis of complement alkyl isoxazoline C1;

Weigh α,β-unsaturated ketone compound B1 (355mg, 1.0mmol, 1.0equiv.) in a 50mL round-bottom flask, add 10mL of ethanol to dissolve, and add potassium tert-butoxide (449mg, 4.0mmol, 4.0mL) to the system at one time equiv.) and hydroxylamine hydrochloride (139 mg, 2.0 mmol, 2.0 equiv.), heated to reflux, and the progress of the reaction was monitored by TLC. After the reaction was completed, the solvent was evaporated under reduced pressure, 15 mL each of saturated ammonium chloride and ethyl acetate were added to the system, the inorganic phase was extracted with ethyl acetate (2×15 mL), the organic phases were combined, and saturated sodium chloride (10 mL) was added to the system. ), and dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure. After separation by column chromatography (PE/EtOAc = 5:1, v/v), a white solid was obtained as a white solid complement alkylisoxazoline C1 (171 mg, yield 46.3%). Mp 122.9～124.5 (°C); ¹ H NMR (400MHz, CDCl ₃ ) δ 0.80 (s, 3H, CH ₃ ), 0.83 (s, 3H, CH ₃ ), 0.88 (s, 3H, CH ₃ ), 1.15 (dd, J ₁ =14.20 Hz, J ₂ = 4.24 Hz, 1H, H in naphthane ring), 1.19 (td, J ₁ =9.02 Hz, J ₂ =4.08 Hz, 1H, H in naphthane ring), 1.21 (s, 3H, CH ₃ ), 1.29 (td, J1 ₌ 12.08Hz, J2= _3.24Hz , 1H, H in naphthane ring), 1.40～1.46 (m, 3H, H in naphthane ring), 1.57 (dt, J1 ₌ 12.72Hz, J2= _3.60Hz , 1H, H in naphthane ring), 1.58～1.64 (m, 3H, H in naphthane ring), 1.66 (br, 1H, OH), 1.74 (dd, J ₁ =J ₂ =4.80Hz, 1H, H in naphthane ring) , 1.91 (dt, J ₁ =12.40 Hz, J ₂ =3.32 Hz, 1H, H in naphthane ring), 2.47 (m, 2H, CH ₂ -CO), 3.02 (dd, J ₁ =16.92 Hz, J ₂ = 8.60 Hz, 1H, Ph-CH-CH ₂ ), 3.41 (dd, J ₁ =16.92 Hz, J ₂ =10.64 Hz, 1H, Ph-CH-CH ₂ ), 5.52 (dd, J ₁ =10.64 Hz, J ₂ = 8.60 Hz, 1H, Ph-CH-CH2), 7.29-7.36 (m, 5H, aromatic H). ¹³ CNMR (100 MHz, CDCl ₃ ) δ 15.14 (CH ₃ ), 18.42 (CH ₂ ), 20.41 ( _CH2 ), 21.48( _CH3 ), 23.63( _CH3 ), 23.73( _CH2 ), 33.26(C), 33.40( _CH3 ), 38.90(C), 39.65( _CH2 ), 41.71( _CH2 ), 44.32( _CH2 ), 46.08( _CH2 ), 55.93(CH), 57.87(CH), 73.67(C), 81. 51(CH), 125.92(2×CH), 127.96(CH), 128.61(2×CH), 141.21(C), 161.30(C). ESI-MS calcd for C ₂₄ H ₃₅ NNaO ₂ [M+Na ⁺ ]: 392.26, found: 392.30; C ₂₄ H ₃₄ NO[MH ₂ O+H ⁺ ]: 352.26, found: 352.31. The structure of complement alkylisoxazoline C1 was further verified by single crystal (CCDC: 1555836).

Embodiment 2: (1R, 2R, 4aS, 8aS)-1-((2-amino-6-phenylpyrimidin-4-yl)methyl)-2,5,5,8a-tetramethyldecahydronaphthalene Synthesis of -2-alcohol (complement alkyl pyrimidine F1)

Weigh α,β-unsaturated ketone compound B1 (355mg, 1.0mmol, 1.0equiv.) in a 50mL round-bottom flask, add 10mL of ethanol to dissolve, and add potassium tert-butoxide (449mg, 4.0mmol, 4.0mL) to the system at one time equiv.) and guanidine hydrochloride (191 mg, 2.0 mmol, 2.0 equiv.), heated to reflux, and the progress of the reaction was monitored by TLC. After the reaction was completed, the solvent was evaporated under reduced pressure, 15 mL each of saturated ammonium chloride and ethyl acetate were added to the system, the inorganic phase was extracted with ethyl acetate (2×15 mL), the organic phases were combined, and saturated sodium chloride (10 mL) was added to the system. ), and dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure. After separation by column chromatography (PE/EtOAc=5:1, v/v), a white solid was obtained as a complement of alkylpyrimidine F1 (yield 30.2%). Mp205.5～206.3 (°C); ¹ H NMR (400 MHz, CDCl _{3 )} )δ0.81(s, 3H, CH ₃ ), 0.86(s, 3H, CH ₃ ), 0.90(s, 3H, CH ₃ ), 0.95(dd, J ₁ =12.20Hz, J ₂ =2.28Hz, 1H , H in naphthane ring), 1.09 (td, J1 ₌ 13.12Hz, J2= _3.88Hz , 1H, H in naphthane ring), 1.25 (s, 3H, _CH3 ), 1.29 (m, 1H, H in naphthane ring) ring), 1.32～1.42 (m, 3H, H in naphthane ring), 1.52 (td, J ₁ =12.76Hz, J ₂ =3.88Hz, 1H, H innaphthane ring), 1.61 (dt, J ₁ =13.32Hz, J ₂ =3.52Hz, 1H, H in naphthane ring), 1.66-1.76 (m, 3H, H in naphthane ring), 2.01 (dt, J ₁ =12.60Hz, J ₂ =3.28Hz, 1H, H innaphthane ring) , 2.66(dd, J1 ₌ 15.20Hz, J2=3.16Hz, 1H, pyrimidyl- _CH2 ), 2.82(dd, J1 ₌ 15.20Hz, J2=4.96Hz, 1H, pyrimidyl- _CH2 ), 5.13(s , br, 2H, NH2), 6.93 (s, 1H, H inpyrimidyl ring), 7.46～7.49 (m, 3H, aromatic H), 7.96～7.99 (m, 2H, aromatic H). ¹³ CNMR (100MHz, CDCl3) δ 15.64( _CH3 ), 18.40( _CH2 ), 20.51( _CH2 ), 21.43( _CH3 ), 24.68( _CH3 ), 33.29(C), 33.35( _CH3 ), 33.50( _CH2 ), 39.55 (CH ₂ ), 39.61(C), 41.81(CH ₂ ), 44.17(CH ₂ ), 56.17(CH), 60.47(CH), 72.40(C), 106.90(CH), 127.17(2×CH), 128.74 (2×CH), 130.57 (CH), 137.35(C), 162.47(C), 165.99(C), 173.72(C). ESI-MS _calcd for _{C25H34N3 [ MH2O} +H ⁺ ]: 376.28, found _376.32 ; _{C25H36N 3} O[M+H ⁺ ]: 394.29, found 394.38. The structure of pyrimidine compound F1 was further verified by single crystal (CCDC: 1555837).

Example 3: (1R, 2R, 4aS, 8aS)--2,5,5,8a-tetramethyl-1-((4-phenylbenzo[4,5]imidazo[1,2-a] Synthesis of pyrimidin-2-yl)methyl)decalin-2-ol (complementary alkyl benzimidazopyrimidine G1)

Weigh α,β-unsaturated ketone compound B1 (355mg, 1.0mmol, 1.0equiv.) in a 25mL round-bottom flask, add DMF (5mL) to dissolve, and add potassium tert-butoxide (449mg, 4.0mmol) to the system in turn , 4.0 equiv.) and 2-aminobenzimidazole (266 mg, 2.0 mmol, 2.0 equiv.), heated to reflux, and the progress of the reaction was monitored by TLC. After the reaction was complete, 20 mL of saturated ammonium chloride solution was added to the system, the inorganic phase was extracted with ethyl acetate (3×20 mL), the organic phases were combined, washed with water (3×10 mL), saturated sodium chloride (10 mL) in turn, and anhydrous sodium sulfate After drying, the solvent was evaporated under reduced pressure. Column chromatography (PE/EtOAc=4:1, v/v) yielded a yellow solid complementing the alkylbenzimidazopyrimidine G1 (yield 53.5%). Mp199.1～201.7(℃); ¹ H NMR(400MHz, CDCl ₃ )δ0.81(s, 3H, CH ₃ ), 0.88(s, 3H, CH ₃ ), 0.93(s, 3H, CH ₃ ), 1.09 (m, 2H, H in naphthane ring), 1.26 (s, 3H, CH ₃ ), 1.28 (m, 1H, H in naphthane ring), 1.31～1.35 (m, 3H, H in naphthane ring), 1.56～ 1.59 (m, 3H, H in naphthane ring), 1.72 (dm, J ₁ =13.68 Hz, 1H, H in naphthane ring), 1.92 (s, br, 1H, OH), 1.99 (dt, J ₁ =12.72 Hz , J2= _3.20Hz , 1H, H in naphthane ring), 2.41 (dd, J1 ₌ 4.64Hz, J2= _4.60Hz , 1H, Hin naphthane ring), 2.93 (dd, J1 _{= 16.32Hz} , J2 =4.60Hz, 1H, pyrimidyl- _CH2 ), 3.19 (dd, J1 ₌ 16.32Hz, J2=4.48Hz, 1H, pyrimidyl- _CH2 ), 6.64 (d, J1 ₌ 8.44Hz, 1H, aromatic H) , 6.70 (s, 1H, H in pyrimidyl ring), 6.99 (m, 1H, aromatic H), 7.42 (ddd, J ₁ =7.16Hz, J ₂ =7.16Hz, J ₃ =1.08Hz, 1H, aromatic H) , 7.57～7.71 (m, 5H, aromatic H), 7.91 (d, J=8.16Hz, 1H, aromatic H). ESI-MS calcd for C ₃₁ H ₃₈ N ₃ O [M+H ⁺ ]: 468.30, found _468.43 ; _C31H37N3NaO [ _M +Na ⁺ ]: 490.28, found 490.41.

Embodiment 4: Determination of the antibacterial activity of chiral complement alkyl heterocyclic compounds

The antibacterial activity in vitro was evaluated by the plate inhibition mycelial growth rate method, and the test strains were selected and activated on the PDA plate, including Rhizoctonia solani, Sclerotia sclerotiorum (Sclerotias cleotiorum), and Fusarium spp. graminearum), Gaeumanomycegraminis, Botrytis cinerea, Phytophthorainfestans, Phytophthora capsici, Alternariasolani, Phytophthora capsici (Alternariasolani) Fusarium fujikuroi), potato dry rot fungus (Fusarium sulphureum), cucumber anthracnose fungus (Colletotrichum lagenarium), rice blast fungus (Phyricularia cerealis). The compounds were configured into PDA drug-containing plates with a series of gradient concentrations, and the test strains were made into a 5mm diameter bacterial cake and placed in the center of the drug-containing petri dish. The colony diameter of each drug-containing plate was measured by the cross method, and the inhibition rate of the compound on the growth of mycelium was calculated. The inhibition rate of the disease was calculated according to the following formula:

Using statistical software SPSS 20.0 to calculate the concentration of the compound when the inhibition rate is 50%, namely the EC ₅₀ value. Repeat 3 times to get the average value. Taking carbendazim as a positive control, the EC ₅₀ value (μg/mL) of each compound against phytopathogenic fungi.

Table 1 The antibacterial activity of tonic alkyl heterocyclic compounds (50mg/L)

Note: R.S.: Rhizoctonia solani, Rhizoctonia solani; S.S.: Sclerotinia scleotiorum, Sclerotinia sclerotiorum; B.C.: Botrytis cinerea, Botrytis cinerea; F.G.: Fusarium graminearum, Fusarium head blight; P.C.: Phytophthora capsici, pepper blight Mildew; G.G.: Gaeumanomycesgraminis, Wheat-eaten fungus; A.S.: Alternaria solani, Tomato early blight; F.S.: Fusariumsulphureum, Potato dry-rot; C.L.: Colletotrichum lagenarium, Cucumber anthracnose; F.F.: Fusarium fujikuroi, Oryza sativa.

Table 2 The antibacterial activity of pyrimidines (50mg/L)

Table 3 The properties and antibacterial activities of the alkyl isoxazolines and pyrimidines (EC ₅₀ , mg/L)

Note: Ligand availability LE = -1.37 Log( _EC50 )/number of heavy atoms. a: Based on _EC50 value against Botrytis cinerea, b: Based on _EC50 value against Fusarium head.

From the data in Table 1, it can be seen that the chiral complement alkyl heterocyclic compounds showed good inhibitory activity against the 10 important plant pathogens tested. From the control spectrum, these compounds are effective against rice sheath blight It has obvious inhibitory effect on bacteria, rape sclerotiorum, tomato gray mold and wheat scab, and at 50mg/L, it especially shows excellent inhibitory effect on tomato gray mold; The isoxazolines and complement alkylpyrimidines deserve further optimization.

From the data in Table 2, it can be seen that the free amino group in the chiral complement alkyl pyrimidines is crucial to the antibacterial activity; the introduction of substituents (whether electron withdrawing or electron donating groups) into the benzene ring does not Conducive to the improvement of antibacterial activity. The target compounds obtained with simple starting materials showed the best activity against Botrytis cinerea and S. cerevisiae. The EC ₅₀ values were determined for the potential complement alkyl isoxazolines and pyrimidines, and their physicochemical properties and ligand availability were analyzed (Table 3). Tomato Botrytis cinerea showed a good inhibitory effect, and the EC ₅₀ values were as low as 3.22mg/L and 5.90mg/L, which were significantly higher than the positive control carbendazim. Good activity was also shown (EC ₅₀ =9.51 mg/L).

The chiral complement alkyl heterocyclic compounds involved in the present invention and their use as fungicides have been described through specific examples. Those skilled in the art can learn from the content of the present invention and appropriately change the raw materials, process conditions and other links to To achieve other corresponding purposes, the related changes do not depart from the content of the present invention, and all similar replacements and modifications are obvious to those skilled in the art and are deemed to be included in the scope of the present invention.

Claims (6)

1. The chiral complement of the alkyl heterocyclic compound shown in the following general formula (I) and its pesticide chemically acceptable salt,

in, The stereoconfiguration of the 8-position in the general formula (I) is R or S,

Represents a heterocyclic compound selected from isoxazoline, isoxazole, pyrazoline, pyrimidine, benzimidazopyrimidine or diazepine. 2. the compound shown in the general formula I of claim 1, is characterized in that, comprises following compound:

Substituent R represents: open-chain and cyclic aliphatic substituents of C1-C18; phenyl; methyl, hydroxy, methoxy, nitro, halogen, difluoromethyl and trifluoromethyl substituted on the benzene ring Phenyl; pyridyl; pyridyl substituted with methyl, ethyl, methoxy, amino, cyano, nitro, difluoromethyl and trifluoromethyl on the pyridine ring; thiazole; halogen on the thiazole ring, Methyl, amino, cyano, nitro, difluoromethyl and trifluoromethyl substituted thiazoles; pyrazine; pyrazine ring with halogen, methyl, amino, cyano, nitro, difluoromethyl and Trifluoromethyl substituted pyrazine; furan; furan ring substituted with halogen, methyl, amino, cyano, nitro, difluoromethyl and trifluoromethyl; Substituent R ₂ represents: open-chain and cyclic aliphatic substituents of C1-C18; phenyl; methyl, hydroxy, methoxy, nitro, halogen, difluoromethyl and trifluoromethyl are substituted on the benzene ring phenyl; benzyl; benzyl substituted with C1-C6 hydrocarbyl at the benzylic position; phenethyl; methyl, hydroxy, methoxy, halogen, nitro, difluoromethyl and trifluoromethyl on the benzene ring Substituted phenethyl; thiazole; furan; furan ring with halogen, methyl, amino, cyano, nitro, difluoromethyl and trifluoromethyl substituted furans; pyridyl; pyridine ring with methyl, Ethyl, methoxy, amino, cyano, nitro, difluoromethyl and trifluoromethyl substituted pyridines; Ar represents: phenyl; phenyl substituted with methyl, hydroxyl, methoxy, nitro, halogen, difluoromethyl and trifluoromethyl on the benzene ring; pyridyl; methyl, ethyl on the pyridine ring , methoxy, amino, cyano, nitro, difluoromethyl and trifluoromethyl substituted pyridines. 3. the application of the chiral complement alkyl heterocyclic compound shown in claim 1 or 2 on preventing and treating agricultural plant pathogenic fungi, it is characterized in that being selected from following pathogenic bacteria: rice sheath blight (Rhizoctonia solani), wheat grain Blight (Rhizoctonia cerealis), Sclerotinia sclerotiorum (Sclerotinia scleotiorum), Fusarium graminearum, Gaeumanomyce graminis, Botrytis cinerea, Phytophthora infestans), Phytophthora capsici, Alternaria solani, Fusarium fujikuroi, Fusarium sulphureum, Colletotrichumlagenarium, Rice blast Phyricularia cerealis). 4. application according to claim 3, is characterized in that, described agricultural plant pathogenic fungi are rape sclerotiorum (Sclerotinia scleotiorum), wheat scab (Fusarium graminearum) and tomato botrytis cinerea (Botrytis cinerea). 5. The use according to claim 3 or 4, the compound can be processed into emulsifiable concentrates, aqueous emulsions, microemulsions, wettable powders, water dispersible granules or suspensions. 6. the application of the described chiral complement alkyl heterocyclic compound of claim 1 in preventing and treating plant diseases, it is characterized in that it is used as one or more combinations in bacteriostatic agent and commercialized fungicide in preparation compound Use in bactericides; commercial bactericides are selected from azoxystrobin, pyraclostrobin, pyrimethanil, fluconazole, fenfluconazole, bixafen, flufenox, fluoride Pyridoxine, Fluopyram, Isothiazide, Fluoxastrobin, Tristrofen, Benzodiazepine, Fluthiazol, Prothioconazole, Trioxystrobin, Cycloconazole, Manganese Zinc, epoxiconazole, tebuconazole, boscalid, metalaxyl, picoxystrobin, difenoconazole, propiconazole, chlorothalonil, thiazide, methiazine, isothiazide Bacteriocin, Ningnamycin, Allylisothiazole, Flumorpholine, Dimethomorpholine; Copper Hydroxide, Copper Sulfate, Copper Oxychloride, Streptomycin, Kasugamycin, Ethanol, Dichloroisocyanurate Uric acid, trichloroisocyanuric acid, chlorobromoisocyanuric acid.