A fungistatic matrine hydrazine thiazole derivative, its preparation method and application

Abstract

The application discloses a kind of antifungal matrine hydrazine thiazole derivatives and preparation method and application, the antifungal matrine hydrazine thiazole derivative is as shown in figure 1, when preparing, first amino thiourea is dissolved and is refluxed with sophocarpine to obtain amino thiourea matrine intermediate;Amino thiourea matrine intermediate obtained is reacted with alpha-brominated R group ethanone, after reaction is ended, it is concentrated and dried, and column chromatography separation obtains antifungal matrine hydrazine thiazole derivative 5.The antifungal matrine hydrazine thiazole derivative obtained in the application not only has high bacteriostatic activity, but also simple preparation method, reaction condition is easy to control.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of pesticide synthesis, and relates to a preparation method and application of a fungistatic matrine hydrazine thiazole derivative. BACKGROUND

[0002] Matrine alkaloids are extracted from the traditional Chinese medicine Sophora flavescens, and have been the focus of attention in the past few decades. Matrine alkaloids belong to quinolinoridin analogs, which are composed of matrine, epima-trine, sophocarpine, sophoridine, oxymatrine, sophoramine, and sophoranol. Matrine alkaloids have many biological activities and therapeutic properties. For example, matrine exhibits a variety of effective actions, including anti-inflammatory, antiviral, antitumor, antiparasitic, antimicrobial, immunosuppressive, neuroprotective, and cardioprotective effects. On the other hand, matrine is also used to prepare surface imprinting materials for molecular selective recognition.

[0003] Matrine alkaloids are considered to be ideal lead compounds for further modification due to their good solubility, special chemical structure, and good safety. The development and screening of new active derivatives based on semi-synthetic strategies have attracted great interest of medical scientists, and have made challenging progress in the past few years. SUMMARY

[0004] The application aims to solve the problem of low bioavailability of matrine, and provides a fungistatic matrine hydrazine thiazole derivative which has fungistatic activity on plants.

[0005] The technical scheme is as follows:

[0006] The fungistatic matrine hydrazine thiazole derivative has the following structural formula:

[0007]

[0008] In the formula, R is any one of 3,4-dichlorophenyl, 4-hydroxyphenyl, phenyl, 4-chlorophenyl, 4-trifluoromethylphenyl, 4-methoxyphenyl, 4-methylphenyl, 4-iodophenyl, naphthyl, and 3-nitro-4-benzyloxyphenyl.

[0009] Another object of the application is a preparation method of the fungistatic matrine hydrazine thiazole derivative, which comprises the following steps:

[0010] In step S1, NaH is added to a reaction container one, a DMF solution is added, and amino-thiourea is added to the reaction container one to stir the solution, so as to obtain an amino-thiourea pre-reaction solution.

[0011] Step S2, adding sophoridine into the aminothiourea reaction solution of step S1 to perform a reflux reaction to obtain an aminothiourea matrine intermediate, and the reaction equation is as follows:

[0012]

[0013] Step S3, adding a dissolving solvent ethanol into the obtained aminothiourea matrine intermediate in a second reaction container to dissolve the aminothiourea matrine intermediate; and then adding α-bromo R-based acetophenone to perform a reaction to obtain a fungistatic matrine hydrazine thiazole derivative 5, and the reaction equation is as follows:

[0014]

[0015] Preferably, after the reaction in step S2 is completed, a quenching reaction is performed, and after the quenching reaction, the aqueous phase is extracted with ethyl acetate, the organic phases are combined, and then concentrated and dried to obtain the aminothiourea matrine intermediate.

[0016] Preferably, acetic acid is used for the quenching reaction in step S2.

[0017] Preferably, the reaction is monitored by using a TLC plate until the reaction is completed.

[0018] Preferably, the molar ratio of sophoridine to aminothiourea is 1:1-1.2 in mmol:mmol; and the molar ratio of the aminothiourea matrine to α-bromoacetophenone is 1:1.1-1.3 in mmol:mmol.

[0019] Preferably, the α-bromo R-based acetophenone includes α-bromo-3,4-dichloroacetophenone, α-bromo-4-hydroxyacetophenone, α-bromoacetophenone, α-bromo-4-chloroacetophenone, α-bromo-4-trifluoromethylacetophenone, α-bromo-4-methoxyacetophenone, α-bromo-4-methylacetophenone, α-bromo-4-iodoacetophenone, α-bromo-acetophenone, and α-bromo-4-benzyloxyacetophenone.

[0020] Preferably, the fungistatic matrine hydrazine thiazole derivative 5 includes fungistatic matrine-C13 hydrazine thiazole derivative 5-1, fungistatic matrine-C13 hydrazine thiazole derivative 5-3, fungistatic matrine-C13 hydrazine thiazole derivative 5-4, fungistatic matrine-C13 hydrazine thiazole derivative 5-5, fungistatic matrine-C13 hydrazine thiazole derivative 5-6, fungistatic matrine-C13 hydrazine thiazole derivative 5-9, fungistatic matrine-C13 hydrazine thiazole derivative 5-10, fungistatic matrine-C13 hydrazine thiazole derivative 5-12, fungistatic matrine-C13 hydrazine thiazole derivative 5-14, and fungistatic matrine-C13 hydrazine thiazole derivative 5-19.

[0021] Another object of the present application is the use of the fungistatic matrine hydrazine thiazole derivatives in the preparation of plant fungus inhibitors.

[0022] Preferably, the plant fungus is Sclerotinia sclerotiorum, Tapesia acuformis, Nectria galligena, and Valsa mali.

[0023] Compared with the prior art, the present application has the following beneficial effects:

[0024] (1) The fungistatic matrine hydrazine thiazole derivatives of the present application have novel molecular structures, are new compounds, have distinct chemical structural characteristics, contain hydrazine structures, and have simple preparation methods, readily available raw materials, and easily controlled reaction conditions, especially in the synthesis of matrine-C13 hydrazine thiazole derivatives, the product can be obtained by column chromatography.

[0025] (2) The compound of the present application is a fungicide for preventing and treating plant fungi in the field of agriculture or forestry, and has good prevention and treatment effects on Sclerotinia sclerotiorum, Tapesia acuformis, Nectria galligena, and Valsa mali. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 The structure of the fungistatic matrine hydrazine thiazole derivative 5 in the embodiments of the present application is shown in the figure.

[0027] Figure 2 The nuclear magnetic resonance hydrogen spectrum of compound 5-1 in the embodiments of the present application is shown in the figure.

[0028] Figure 3 The nuclear magnetic resonance carbon spectrum of compound 5-1 in the embodiments of the present application is shown in the figure.

[0029] Figure 4 The nuclear magnetic resonance hydrogen spectrum of compound 5-6 in the embodiments of the present application is shown in the figure.

[0030] Figure 5 The nuclear magnetic resonance carbon spectrum of compound 5-6 in the embodiments of the present application is shown in the figure.

[0031] Figure 6 The nuclear magnetic resonance fluorine spectrum of compound 5-6 in the embodiments of the present application is shown in the figure.

[0032] Figure 7 The nuclear magnetic resonance hydrogen spectrum of compound 5-12 in the embodiments of the present application is shown in the figure.

[0033] Figure 8 The nuclear magnetic resonance carbon spectrum of compound 5-12 in the embodiments of the present application is shown in the figure.

[0034] Figure 9 The nuclear magnetic resonance hydrogen spectrum of compound 5-14 in the embodiments of the present application is shown in the figure.

[0035] Figure 10 The nuclear magnetic resonance spectrum of the compound 5-14 in the embodiment of the present application. DETAILED DESCRIPTION

[0036] The present application will be further clarified by the following examples, which should not be construed as limiting the scope of the present application. After reading the present application, those skilled in the art will be able to modify the present application in various ways, which should be construed as falling within the scope of the appended claims.

[0037] Example 1

[0038] A kind of antifungal matrine hydrazine thiazole derivative, the structural formula of the antifungal matrine hydrazine thiazole derivative is as shown in Figure 1 :

[0039]

[0040] Wherein, R is one of the following groups: 3,4-dichlorophenyl 55-1, 4-hydroxyphenyl 55-3, phenyl 55-4, 4-chlorophenyl 55-5, 4-trifluoromethylphenyl 55-6, 4-methoxyphenyl 55-9, 4-methylphenyl 55-10, 4-iodophenyl 55-12, naphthyl 55-14, 3-nitro-4-benzyloxyphenyl 55-19.

[0041]

[0042] The antifungal matrine hydrazine thiazole derivative of the present embodiment not only retains the structure of matrine, but also obtains matrine derivatives with hydrazine thiazole structure, which enhances the antibacterial activity of matrine derivatives.

[0043] Example 2

[0044] The present embodiment provides a preparation method of an antifungal matrine hydrazine thiazole derivative, comprising the following steps:

[0045] Step S1, NaH is added to reaction container one, DMF solution is added, and aminothiourea is added to the solution in reaction container one and stirred. Specifically, 60% pure NaH is added to a round-bottom flask, DMF solution is then added, aminothiourea is weighed and added to the flask, and stirring is carried out at 0°C for 10 min.

[0046] Step S2, sophoridine is added to the solution of step S1 for reflux reaction, quenching reaction is carried out after the reaction is completed, and then extraction, concentration and drying are carried out, and column chromatography separation is carried out to obtain aminothiourea matrine intermediate, and the reaction equation is as follows:

[0047]

[0048] Specifically, the weighed sophoridine was added into a flask, and the reaction was carried out under reflux. The reaction was monitored by TLC until the reaction was completed. Then, an appropriate amount of acetic acid was added to quench the reaction. After extraction, concentration, drying and column chromatography separation (dichloromethane:methanol = 10:1-8:1), the aminothiourea matrine intermediate was obtained.

[0049] In this embodiment, the lone pair of electrons on the nitrogen atom of the aminothiourea attacks the C13 position of the sophoridine to synthesize the aminothiourea matrine intermediate 3 by nucleophilic addition.

[0050] In step S3, the aminothiourea matrine intermediate obtained in step S2 was added into a reaction container II, and dissolved in ethanol. After the solution was dissolved, the reaction was carried out by adding α-bromo R-ethyl ketone. After the reaction was completed, concentration, drying and column chromatography separation were carried out to obtain the fungistatic matrine hydrazine thiazole derivative 5. The reaction equation is as follows:

[0051]

[0052] Specifically, the aminothiourea matrine intermediate was added into a round-bottom flask, and then dissolved in ethanol. Then, α-bromo R-ethyl ketone was added, and the reaction was carried out at room temperature. The reaction was monitored by TLC until the reaction was completed. After concentration, drying and column chromatography separation (dichloromethane:methanol = 30:1-20:1), the fungistatic matrine hydrazine thiazole derivative 5 was obtained.

[0053] In this embodiment, the aminothiourea matrine was synthesized by using sophoridine and aminothiourea as starting materials, and N,N-dimethylformamide as a solvent. Then, a series of fungistatic matrine hydrazine thiazole derivatives were synthesized by using the aminothiourea matrine and α-bromo R-ethyl ketone as reactants, and ethanol as a solvent. While the structure of matrine was completely retained, the fungistatic matrine hydrazine thiazole derivative with hydrazine thiazole structure was formed, which enhanced the antibacterial activity of the fungistatic matrine hydrazine thiazole derivative.

[0054] Example 3

[0055] The difference between this embodiment and example 2 is that the fungistatic matrine-C13 amine thiazole derivative 5-1 was synthesized by reacting the aminothiourea matrine intermediate 3 with α-bromo-3,4-dichloroacetophenone.

[0056] In a round bottom flask, add matrine aminothiazole intermediate 3, add solvent ethanol to dissolve, then add α-bromo-3,4-dichloroacetophenone, the molar ratio of matrine aminothiazole intermediate 3 and α-bromo-3,4-dichloroacetophenone is mmol: mmol: 0.3:0.36; react at room temperature, monitor the reaction with TLC plate until the reaction is completed, reaction time: 1 h. Concentrate the reaction solution to dryness, separate by column chromatography (dichloromethane:methanol = 30:1~20:1) to obtain the product fungistatic matrine C13 hydrazine thiazole derivative 5-1:

[0057]

[0058] As shown in Figure 2 , 3 , the spectrum data of fungistatic matrine C13 hydrazine thiazole derivative 5-1 is analyzed as follows:

[0059] White solid, R f :0.60 (DCE:MeOH = 10:1), 125.2 mg (82.4% yield)

[0060] 1 H NMR (600 MHz, Chloroform-d) δ 7.97 (s, 1H), 7.85 (s, 1H), 7.55 (d, J = 8.5 Hz, 1H), 7.43 (d, J = 8.3 Hz, 1H), 6.78 (s, 1H), 4.46-4.29 (m, 2H), 4.10-3.98 (m, 1H), 3.27 (s, 1H), 3.14 (t, J = 12.7 Hz, 1H), 2.88-2.78 (m, 2H), 2.51-2.40 (m, 2H), 2.14 (s, 1H), 2.04-1.91 (m, 3H), 1.80-1.62 (m, 5H), 1.59-1.49 (m, 2H), 1.46-1.33 (m, 4H).

[0061] 13 C NMR (101 MHz, CDCl3) δ 175.0, 167.2, 148.8, 135.2, 132.6, 131.2, 130.5, 127.6, 125.0, 104.6, 63.7, 57.1 (2C), 51.6, 50.1, 42.8, 41.6, 36.0, 35.4, 29.4, 27.6, 26.3, 21.0, 20.6.

[0062] HRMS (ESI) Calcd for C 24 H 29 Cl2N5OS [M+H] +m / z 506.1543, found 506.1539.

[0063] Example 4

[0064] The difference between this example and Example 2 is that the fungistatic matrine C13 hydrazine thiazole derivative 5-3 was synthesized by reacting the aminothiourea matrine intermediate 3 with α-bromo-4-hydroxyacetophenone.

[0065]

[0066] Example 5

[0067] The difference between this example and Example 2 is that the fungistatic matrine C13 hydrazine thiazole derivative 5-4 was synthesized by reacting the aminothiourea matrine intermediate 3 with α-bromoacetophenone.

[0068]

[0069] Example 6

[0070] The difference between this example and Example 2 is that the fungistatic matrine C13 hydrazine thiazole derivative 5-5 was synthesized by reacting the aminothiourea matrine intermediate 3 with α-bromo-4-chloroacetophenone.

[0071]

[0072] Example 7

[0073] The difference between this example and Example 2 is that the fungistatic matrine C13 hydrazine thiazole derivative 5-6 was synthesized by reacting the aminothiourea matrine intermediate 3 with α-bromo-4-trifluoromethylacetophenone.

[0074]

[0075] As shown in Figure 4 , 5 , 6, the spectral data analysis of the matrine C13 hydrazine thiazole derivative 5-6:

[0076] White solid, R f : 0.60 (DCE:MeOH = 10:1), 125.8 mg (83.0% yield)

[0077] 1H NMR (400 MHz, CDC13) δ 7.87 (d, J = 7.7 Hz, 2H), 7.63 (d, J = 8.4 Hz, 2H), 7.16 (s, 1H), 6.92 (s, 1H), 4.43 (dd, J = 12.8, 4.4 Hz, 1H), 4.34 (s, 1H), 4.22 - 4.06 (m, 1H), 3.43 (s, 1H), 3.19 (t, J = 12.8 Hz, 1H), 3.07 - 2.76 (m, 2H), 2.59 - 2.43 (m, 2H), 2.31 - 2.18 (m, 1H), 2.15 - 1.98 (m, 3H), 1.92 - 1.81 (m, 2H), 1.80 - 1.65 (m, 4H), 1.60 - 1.40 (m, 5H).

[0078] 13 C NMR (101 MHz, CDC13) δ 174.3, 167.0, 150.0, 138.2, 129.3, 126.0 (4C), 125.54 (dd, J = 7.6, 3.7 Hz), 105.4, 63.9, 57.1 (2C), 51.5, 50.0, 42.7, 41.5, 37.3, 36.1, 35.3, 29.4, 26.6, 20.9, 20.5.

[0079] 19 F NMR (377 MHz, CDC13) δ -62.4.

[0080] HRMS (ESI) Calcd for C 25 H 30 F3N5OS [M + H] + m / z 506.2196, found 506.2203.

[0081] Example 8

[0082] The difference between this example and Example 2 is that the hydrazine thiazole derivatives 5-9 of the antifungal matrine-C13 position are synthesized by reacting the aminothiourea matrine intermediate 3 with α-bromo-4-methoxyacetophenone.

[0083]

[0084] Example 9

[0085] The difference between this example and Example 2 is that the hydrazine thiazole derivatives 5-10 of the antifungal matrine-C13 position are synthesized by reacting the aminothiourea matrine intermediate 3 with α-bromo-4-methylacetophenone.

[0086]

[0087] Example 10

[0088] The difference between this example and Example 2 is that the hydrazine thiazole derivative 5-12 at C13 position of matrine was synthesized by reacting the intermediate 3 of matrine with α-bromo-4-iodoacetophenone.

[0089]

[0090] As shown in Figure 7 , 8 the spectral data analysis of the hydrazine thiazole derivative 5-12 at C13 position of matrine:

[0091] White solid, R f :0.60 (DCE:MeOH=10:1), 136.9 mg (81.0% yield)

[0092] 1 H NMR (400 MHz, Chloroform-d) δ 7.69 (d, J = 7.8 Hz, 2H), 7.48 (d, J = 7.9 Hz, 2H), 6.78 (s, 1H), 4.45-4.28 (m, 2H), 4.10 (s, 1H), 3.30 (s, 1H), 3.17 (t, J = 12.9 Hz, 1H), 2.94-2.81 (m, 2H), 2.51-2.38 (m, 2H), 2.25-2.17 (m, 1H), 2.09-1.96 (m, 3H), 1.85-1.64 (m, 6H), 1.49-1.38 (m, 5H).

[0093] 13 C NMR (101 MHz, CDCl3) δ 174.7, 167.2, 150.2, 137.6 (2C), 134.6, 127.7 (2C), 103.9, 93.0, 63.9, 57.1, 51.4, 50.1, 42.6, 41.6, 36.1, 35.4, 29.7, 29.3, 27.5, 26.2, 20.9, 20.4.

[0094] HRMS (ESI) Calcd for C 24 H 30 IN5OS[M+H] + m / z 564.1289, found 564.1280.

[0095] Example 11

[0096] The difference between this embodiment and Example 2 is that the antifungal matrine-C13 hydrazine derivative 5-14 is synthesized by reacting aminothiourea matrine intermediate 3 with α-bromonaphthyl ethyl ketone.

[0097]

[0098] like Figure 9 , 10 As shown, the spectral data analysis of matrine C13 hydrazine derivative 5-12 is as follows:

[0099] White solid, R f :0.60(DCE:MeOH=10:1),122.8mg(84.0%yield)

[0100] 1 H NMR(400MHz, CDCl3)δ8.25(s,1H),7.91-7.76(m,4H),7.52-7.40(m,2H),6.82(s,1H), 4.30(dd,J=12.7,4.3Hz,1H),4.15-4.06(m,1H),3.83(dd,J=10.7,6.6Hz,1H),3.04(t, J=12.6Hz,1H),2.95-2.85(m,1H),2.74(dd,J=11.7,4.1Hz,2H),2.29-2.26(m,1H),2. 04(s,1H),1.96-1.83(m,3H),1.70-1.54(m,3H),1.47-1.34(m,6H),1.29-1.25(m,3H).

[0101] 13 C NMR (151MHz, CDCl3) δ175.6,167.2,151.0,133.6,132.9,132.7,128.2,128.0,127.7,126.5,126.0,12 4.6,124.3,103.6,63.7,60.4,57.1,51.4,50.1,42.4,41.7,35.4,29.7,29.0,27.6,26.2,21.1,20.6.

[0102] HRMS(ESI)Calcd for C 28 H 33 N5OS[M+H] + m / z 488.2479, found 488.2470.

[0103] Implementation of Column 12

[0104] The difference between this embodiment and embodiment 2 is that the hydrazine thiazole derivative of antifungal matrine C13 is synthesized by reacting the aminothiourea matrine intermediate 3 with α-bromo-4-benzyloxy acetophenone.

[0105]

[0106] Embodiment 13

[0107] The present embodiment provides an application of the hydrazine thiazole derivative of antifungal matrine in preparing a plant fungal inhibitor, wherein the plant fungi are Sclerotinia sclerotiorum, Talaromyces aurantiacus, Nattrassia mangiferae and Valsa mali.

[0108] The antibacterial activity test of the hydrazine thiazole derivative of antifungal matrine is as follows:

[0109] Strains: 4 kinds of plant fungi, which are Sclerotinia sclerotiorum, Valsa mali, Nattrassia mangiferae and Talaromyces aurantiacus.

[0110] The specific process is as follows:

[0111] The plant fungi used in the experiment are strains preserved at 4℃ in the laboratory, which are Sclerotinia sclerotiorum, Valsa mali, Nattrassia mangiferae and Talaromyces aurantiacus. The culture medium used is potato dextrose agar (PDA for short, HIBIOBIOLOGICAL TECHNOLOGY CO., LTD.), and the solvent is dimethyl sulfoxide (Anhui Zesheng Technology Co., Ltd.). The experimental method is mycelial growth rate method.

[0112] Activation: first, the 4 kinds of plant fungi are cultured at 25℃ on PDA plates for about 3-6 days for use;

[0113] PDA preparation: PDA powder 46g and water 1000mL are prepared in a ratio, boiled and bottled, 50mL / bottle, then sterilized and used.

[0114] Preparation of compound stock solution: 10mg of compound is dissolved in 1mL of dimethyl sulfoxide to prepare a 10g / L compound stock solution, and 250μL of the stock solution is taken in 50mL of PDA each time.

[0115] Sterilization: the PDA culture medium is treated with a sterilized gun head, and the operation table is treated with sterilization, and the whole experiment is operated in a sterile environment;

[0116] Sample addition: 250μL of the compound stock solution is taken in the sterilized PDA culture medium each time to prepare a compound-containing culture medium with a concentration of 50mg / L, and then poured into culture dishes for cooling, and three parallel controls are prepared for each compound, wherein the same amount of dimethyl sulfoxide is added to the culture medium as a blank control, azoxystrobin is used as a positive control, and matrine is used as a negative control.

[0117] Inoculation: After the medium plate solidified, under sterile operation, punch a round fungus cake (0.50 cm in diameter) at the edge of the mycelium of each strain cultured for 6 days (the growth conditions are as consistent as possible), pick it up with an inoculation needle to the center of the drug-containing plate, and then place the culture dish upside down in the incubator (28°C) for culture.

[0118] Data processing: The growth of mycelium was observed at different times after treatment, and when the control fungus grew to more than 2 / 3 of the diameter of the plate, the measurement could be performed. The cross method was used to measure the diameter and process the data to calculate the inhibition rate.

[0119] Inhibition rate (%) = (control mycelium diameter - treated mycelium diameter) / (control mycelium diameter - 0.5) x 100.

[0120] Each treatment was repeated 3 times.

[0121] Table 1 is the experimental results of the antifungal inhibition rate (50 mg / L) of hydrazine thiazole derivatives of matrine-C13

[0122] Table 1 is the antifungal inhibition rate (50 mg / L) of hydrazine thiazole derivatives of matrine-C13

[0123]

[0124]

[0125] The results of the fungicidal activity determination of the experimental compounds, the positive compound azoxystrobin and the parent compound matrine are shown in Table 1. As can be seen from the results in Table 1, at a concentration of 50 mg / L, compounds 5-1, 5-6, 5-12 and 5-14 show different degrees of inhibition activity against the four plant fungi, and most of the compounds have certain inhibition activity against Sclerotinia sclerotiorum, T. aurantiaca, P. caricae and V. mali. Compound 5-6 has obvious inhibition effect on these four plant fungi, among which the inhibition rate against T. aurantiaca is as high as 92.8% at a concentration of 50 mg / L, which is higher than the inhibition rate of the positive drug azoxystrobin against T. aurantiaca. The inhibition effect of the experimental compounds on P. caricae is better than that of the positive drug azoxystrobin on P. caricae, and the best effect is that of compound 5-6 with an inhibition rate of 50.9%. As can be seen from the data in the table, the inhibition effect of experimental compounds 5-1, 5-6, 5-12 and 5-14 on Sclerotinia sclerotiorum, T. aurantiaca and V. mali is better than that of the parent structure matrine, which shows that the hydrazine thiazole derivatives containing hydrazine thiazole constructed by aminothiourea can greatly improve the inhibition effect of the parent structure on plant fungi, and provide a reference for the research direction of agricultural and forestry fungicides.

[0126] The fungus-inhibiting matrine hydrazine thiazole derivative has obvious structural difference, distinct chemical structural characteristics, and shows good effect on preventing and treating Valsa mali, Ceratocystis paradoxa and Tretosporium aureum. The fungus-inhibiting matrine hydrazine thiazole derivative can be used for preventing and treating fungal diseases of agricultural or forestry plants. The preparation method of the compound is simple, and the product is stable. The synthesized fungus-inhibiting matrine hydrazine thiazole derivative has good activity and medicinal value, which has certain enlightenment for designing new plant fungal prevention and treatment medicaments from natural products.

[0127] The above only describes the preferred embodiments of the present application, and it should be noted that those skilled in the art can make some improvements and refinements without departing from the principles of the present application, and these improvements and refinements should also be considered as the protection scope of the present application.

Claims

1. A fungistatic matrine hydrazine thiazole derivative, characterized in that, The structure of the fungistatic matrine hydrazine thiazole derivative is as follows: ； ； R is any one of 3,4-dichlorophenyl 55-1, 4-hydroxyphenyl 55-3, phenyl 55-4, 4-chlorophenyl 55-5, 4-trifluoromethylphenyl 55-6, 4-methoxyphenyl 55-9, 4-methylphenyl 55-10, 4-iodophenyl 55-12, naphthyl 55-14, 3-nitro-4-benzyloxyphenyl 55-19.

2. A method for preparing the antifungal matrine hydrazine thiazole derivative as described in claim 1, characterized in that, The method comprises the following steps: Step S1, NaH is added to a reaction container one, a DMF solution is added, and the solution is stirred after adding aminothiourea into the reaction container one, to obtain an aminothiourea pre-reaction solution; Step S2, sophoridine is added to the aminothiourea pre-reaction solution of step S1 to perform a reflux reaction to obtain a matrine hydrazine thiazole intermediate, and the reaction equation is as follows: Step S3, the obtained matrine hydrazine thiazole intermediate is dissolved in a dissolving solvent ethanol in a reaction container two, and then α-bromo R group ethanone 4 is added to perform a reaction to obtain a fungistatic matrine hydrazine thiazole derivative 5, and the reaction equation is as follows: 。 3. The method of claim 2, wherein: After the reaction in step S2 is completed, a quenching reaction is performed, and after the quenching reaction, the aqueous phase is extracted with ethyl acetate, the organic phases are combined, and then concentrated and dried to obtain the matrine hydrazine thiazole intermediate.

4. The method of claim 3, wherein: Acetic acid is used for the quenching reaction in step S2.

5. The method of claim 4, wherein: The reaction is monitored by using a TLC plate until the reaction is completed.

6. The method of claim 5, wherein: The molar ratio of sophoridine and aminothiourea is 1:1-1.2 in mmol:mmol, and the molar ratio of the matrine hydrazine thiazole and α-bromoacetophenone is 1:1.1-1.3 in mmol:mmol.

7. The method of claim 3, wherein: The α-bromo R group ethanone 4 is α-bromo-3,4-dichloroacetophenone, α-bromo-4-hydroxyacetophenone, α-bromoacetophenone, α-bromo-4-chloroacetophenone, α-bromo-4-trifluoromethylacetophenone, α-bromo-4-methoxyacetophenone, α-bromo-4-methylacetophenone, α-bromo-4-iodoacetophenone, α-bromoacetophenone, and α-bromo-4-benzyloxyacetophenone.

8. The method of claim 3, wherein: The fungistatic matrine hydrazine thiazole derivative 5 is fungistatic matrine hydrazine thiazole derivative C13 No. 5-1, fungistatic matrine hydrazine thiazole derivative C13 No. 5-3, fungistatic matrine hydrazine thiazole derivative C13 No. 5-4, fungistatic matrine hydrazine thiazole derivative C13 No. 5-5, fungistatic matrine hydrazine thiazole derivative C13 No. 5-6, fungistatic matrine hydrazine thiazole derivative C13 No. 5-9, fungistatic matrine hydrazine thiazole derivative C13 No. 5-10, fungistatic matrine hydrazine thiazole derivative C13 No. 5-12, fungistatic matrine hydrazine thiazole derivative C13 No. 5-14, and fungistatic matrine hydrazine thiazole derivative C13 No. 5-19. The fungistatic matrine hydrazine thiazole derivative C13 No. 5-1 is as follows: The fungistatic matrine hydrazine thiazole derivative C13 No. 5-3 is as follows: The fungistatic matrine hydrazine thiazole derivative C13 No. 5-4 is as follows: The fungistatic matrine hydrazine thiazole derivative C13 No. 5-5 is as follows: The fungistatic matrine hydrazine thiazole derivative C13 No. 5-6 is as follows: The fungistatic matrine C13 hydrazine thiazole derivative 5-6 is: The fungistatic matrine C13 hydrazine thiazole derivative 5-9 is: The fungistatic matrine C13 hydrazine thiazole derivative 5-10 is: The fungistatic matrine C13 hydrazine thiazole derivative 5-12 is: The fungistatic matrine C13 hydrazine thiazole derivative 5-14 is: The fungistatic matrine C13 hydrazine thiazole derivative 5-19 is: 。 9. Use of the fungistatic matrine hydrazine thiazole derivative of claim 1 in the preparation of a plant fungal inhibitor; the plant fungi being Sclerotinia sclerotiorum, Aschersonia aleyrodis, Nattrassia mangiferae, Valsa mali.

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