Fungus-inhibiting matrine hydrazine thiazole derivative as well as preparation method and application thereof

Abstract

The invention discloses an antifungal matrine hydrazine thiazole derivative as well as a preparation method and application thereof, the antifungal matrine hydrazine thiazole derivative is shown in figure 1, and during preparation, thiosemicarbazide is dissolved and then subjected to reflux reaction with sophocarpine to obtain a thiosemicarbazide matrine intermediate; and reacting the obtained thiosemicarbazide matrine intermediate with alpha-bromo-R-ethyl ketone, concentrating and drying after the reaction is finished, and carrying out column chromatography separation to obtain the antifungal matrine hydrazine thiazole derivative 5. The obtained anti-fungal matrine hydrazine thiazole derivative is high in anti-bacterial activity, the preparation method is simple and convenient, and reaction conditions are easy to control.

Description

Technical Field

[0001] The invention belongs to the technical field of pesticide synthesis and relates to a preparation method and application of a fungicide-inhibiting matrine hydrazine thiazole derivative. Background Art

[0002] Matrine alkaloids are extracted from the traditional Chinese medicine Sophora flavescens and have been attracting attention in the past few decades. Matrine-type alkaloids belong to quinolizidine analogs and are composed of matrine, allomatrine, sophorocarpine, sophoridine, oxymatrine, sophoramine, sophorol, etc. and have many biological activities and therapeutic properties. For example, matrine exhibits a variety of effective effects, 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 selective molecular 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 semisynthetic strategies have attracted great interest of medical scientists and have made challenging progress in the past few years. Summary of the invention

[0004] Purpose of the invention: To address the problem of low bioavailability of matrine, the present invention provides an antifungal matrine hydrazine thiazole derivative that has inhibitory properties against plant fungi.

[0005] Technical solution: To achieve the above purpose, the technical solution adopted by the present invention is:

[0006] A fungi-inhibiting matrine hydrazine thiazole derivative, the fungi-inhibiting matrine hydrazine thiazole derivative has a structural formula as shown below:

[0007]

[0008] Wherein, 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 present invention is a method for preparing a fungistatic matrine hydrazine thiazole derivative, comprising the following steps:

[0010] Step S1, adding NaH into a reaction container 1, then adding a DMF solution, and then adding thiosemicarbazide into the reaction container 1 and stirring the solution to obtain a thiosemicarbazide pre-reaction solution.

[0011] Step S2, adding sophocarpine to the pre-reaction solution of thiosemicarbazide in step S1 for reflux reaction to obtain thiosemicarbazide matrine intermediate, the reaction equation is as follows:

[0012]

[0013] Step S3, adding ethanol as a dissolving solvent to the reaction container 2 to dissolve the obtained semicarbazide matrine intermediate; then adding α-bromo R-ethyl ketone to react to obtain the antifungal matrine hydrazine thiazole derivative 5, the reaction equation is as follows:

[0014]

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

[0016] Preferably, acetic acid is used to quench the reaction in step S2.

[0017] Preferably, the reaction is monitored by TLC plate until the reaction is complete.

[0018] Preferably, the molar ratio of sophocarpine to thiosemicarbazide is 1:1-1.2 in mmol:mmol; the molar ratio of thioureamatrine to α-bromoacetophenone is 1:1.1-1.3 in mmol:mmol.

[0019] Preferably: the α-bromo R-based acetone 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-bromonaphthylacetophenone, and α-bromo-4-benzyloxyacetophenone.

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

[0021] Another object of the present invention is the use of a fungistatic matrine hydrazine thiazole derivative in the preparation of plant fungal inhibitors.

[0022] Preferably, the plant fungi are Sclerotinia sclerotiorum, Cystosporium aureum, Psoralea corylifolia, and Psoralea corylifolia.

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

[0024] (1) The antifungal matrine hydrazine thiazole derivatives of the present invention have novel molecular structures and are all new compounds; they have distinct chemical structure characteristics and contain hydrazine structures; the preparation method of the compounds is simple, the raw materials are easily available, and the reaction conditions are easily controlled. In particular, in the step of synthesizing the matrine-C13 hydrazine thiazole derivative, the product can be obtained by column chromatography.

[0025] (2) The compound described in the present invention is an agent for preventing and controlling plant fungi in the field of agriculture or forestry. This agent has a good control effect on rapeseed sclerotinia, golden shell cystsporium, sugarcane pineapple pathogen and apple rot pathogen. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 Schematic diagram of the structure of the antifungal matrine hydrazine thiazole derivative 5 in the embodiment of the present invention.

[0027] Figure 2 It is the hydrogen nuclear magnetic resonance spectrum of compound 5-1 in the example of the present invention.

[0028] Figure 3 It is the carbon nuclear magnetic resonance spectrum of compound 5-1 in the example of the present invention.

[0029] Figure 4 It is the hydrogen nuclear magnetic resonance spectrum of compound 5-6 in the example of the present invention.

[0030] Figure 5 It is the carbon nuclear magnetic resonance spectrum of compound 5-6 in the example of the present invention.

[0031] Figure 6 It is the nuclear magnetic resonance fluorine spectrum of compound 5-6 in the example of the present invention.

[0032] Figure 7 It is the hydrogen nuclear magnetic resonance spectrum of compound 5-12 in the example of the present invention.

[0033] Figure 8 It is the carbon nuclear magnetic resonance spectrum of compound 5-12 in the example of the present invention.

[0034] Fig. 9 It is the hydrogen nuclear magnetic resonance spectrum of compound 5-14 in the example of the present invention.

[0035] Fig.10 It is the carbon nuclear magnetic resonance spectrum of compound 5-14 in the example of the present invention. DETAILED DESCRIPTION

[0036] The present invention is further explained below in conjunction with the accompanying drawings and specific embodiments. It should be understood that these examples are only used to illustrate the present invention and are not used to limit the scope of the present invention. After reading the present invention, various equivalent forms of modifications to the present invention by those skilled in the art all fall within the scope defined by the claims attached to this application.

[0037] Example 1

[0038] A fungi-inhibiting matrine hydrazine thiazole derivative, the fungi-inhibiting matrine hydrazine thiazole derivative has a structural formula as shown in Figure 1 As shown:

[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 this embodiment not only completely retains the structure of matrine, but also obtains a matrine derivative with a hydrazine thiazole structure, which enhances the antibacterial activity of the matrine derivative.

[0043] Example 2

[0044] This embodiment provides a method for preparing a fungi-inhibiting matrine hydrazine thiazole derivative, comprising the following steps:

[0045] Step S1, add NaH to reaction vessel 1, then add DMF solution, then add thiosemicarbazide to reaction vessel 1 and stir the solution. Specifically, add 60% pure NaH to a round-bottom flask, then add DMF solution, weigh thiosemicarbazide and add it to the flask, and stir at 0°C for 10 minutes.

[0046] Step S2, adding sophoracarpine to the solution of step S1 for reflux reaction, quenching the reaction after the reaction is completed, and then extracting, concentrating and drying, and separating by column chromatography to obtain a semicarbazide matrine intermediate, the reaction equation is as follows:

[0047]

[0048] Specifically, the weighed sophoracarpine is added into a flask, refluxed, and the reaction is detected by TLC plate until the reaction is completed. After the reaction is completed, an appropriate amount of acetic acid is added to quench the reaction, and then extracted, concentrated and dried, and purified by column chromatography (dichloromethane: methanol = 10: 1-8: 1) to obtain a semicarbazide matrine intermediate.

[0049] In this example, the lone pair of electrons on the nitrogen atom of thiosemicarbazide attacks the C13 position in sophocarpine to synthesize thiosemicarbazide matrine intermediate 3 through nucleophilic addition.

[0050] Step S3, add the semicarbazide matrine intermediate obtained in step S2 into the reaction container 2, and add the dissolving solvent ethanol to dissolve it. Add α-bromo R-ethyl ketone to the dissolved solution to react, concentrate and dry after the reaction, and separate by column chromatography to obtain the antifungal matrine hydrazine thiazole derivative 5, and the reaction equation is as follows:

[0051]

[0052] Specifically, a semicarbazide matrine intermediate was added to a round-bottom flask, and then a solvent ethanol was added to dissolve it, and then α-bromo R-methyl ethyl ketone was added to react at room temperature. The reaction was monitored by a TLC plate until the reaction was completed. The reaction solution was concentrated and dried, and separated by column chromatography (dichloromethane: methanol = 30:1 to 20:1) to obtain an antifungal matrine hydrazine thiazole derivative 5.

[0053] In this embodiment, thiosemicarbazide matrine is first synthesized using sophoracarbine and thiosemicarbazide as starting substrates and N,N-dimethylformamide as solvent, and then a series of antifungal matrine hydrazine thiazole derivatives are synthesized using thiosemicarbazide matrine and α-bromo R-ethyl ketone as reactants and ethanol as solvent. While the structure of matrine is completely retained, antifungal matrine hydrazine thiazole derivatives with hydrazine thiazole structure are formed, thereby enhancing the antibacterial activity of antifungal matrine hydrazine thiazole derivatives.

[0054] Example 3

[0055] The difference between this embodiment and embodiment 2 is that the antifungal matrine-C13 aminothiazole derivative 5-1 is synthesized by reacting the semicarbazide thiourea matrine intermediate 3 with α-bromo-3,4-dichloroacetophenone.

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

[0057]

[0058] like Figure 2 , 3 As shown, the spectrum data analysis of the antifungal matrine-C13 hydrazine thiazole derivative 5-1:

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

[0060] 1 H NMR(600MHz,Chloroform-d)δ7.97(s,1H),7.85(s,1H),7.55(d,J=8.5Hz,1H), 7.43(d,J=8.3Hz,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=12.7Hz,1H),2.88-2.78(m,2H),2.51-2.40(m,2H),2.14(s,1 H),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, CDCl 3 )δ175.0,167.2,148.8,135.2,132.6,131.2,130.5,127.6,125.0,104.6,63. 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 Cl 2 N 5OS[M+H] + m / z 506.1543, found 506.1539.

[0063] Implementation 4

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

[0065]

[0066] Implementation 5

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

[0068]

[0069] Implementation List 6

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

[0071]

[0072] Implementation List 7

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

[0074]

[0075] like Figure 4 , 5 , 6, the spectrum data analysis of the thiazole derivative 5-6 at the C13 position of matrine:

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

[0077] 1 H NMR (400 MHz, CDCl 3)δ7.87(d,J=7.7Hz,2H),7.63(d,J=8.4Hz,2H),7.16(s,1H),6.92(s,1H),4. 43(dd,J=12.8,4.4Hz,1H),4.34(s,1H),4.22-4.06(m,1H),3.43(s,1H),3.1 9(t,J=12.8Hz,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, CDCl 3 )δ174.3,167.0,150.0,138.2,129.3,126.0(4C),δ125.54(dd,J=7.6,3.7Hz),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, CDCl 3 )δ-62.4.

[0080] HRMS(ESI)Calcd for C 25 H 30 F 3 N 5 OS[M+H] + m / z 506.2196, found 506.2203.

[0081] Implementation 8

[0082] The difference between this example and example 2 is that the antifungal matrine-C13 hydrazine thiazole derivative 5-9 is synthesized by reacting the semicarbazide thiourea matrine intermediate 3 with α-bromo-4-methoxyacetophenone.

[0083]

[0084] Implementation List 9

[0085] The difference between this example and example 2 is that the antifungal matrine-C13 hydrazine thiazole derivative 5-10 is synthesized by reacting the semicarbazide thiourea matrine intermediate 3 with α-bromo-4-methylacetophenone.

[0086]

[0087] Implementation 10

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

[0089]

[0090] like Figure 7 , 8 As shown, the spectrum data analysis of hydrathiazole derivatives 5-12 at C13 position of matrine:

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

[0092] 1 H NMR(400MHz,Chloroform-d)δ7.69(d,J=7.8Hz,2H),7.48(d,J=7.9Hz,2H),6.78(s,1H),4.45-4.28(m,2H),4.10(s,1H),3.30(s,1H),3. 17(t,J=12.9Hz,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, CDCl 3 )δ174.7,167.2,150.2,137.6(2C),134.6,127.7(2C),103.9,93.0,63.9,5 7.1,51.4,50.1,42.6,41.6,36.1,35.4,29.7,29.3,27.5,26.2,20.9,20.4.

[0094] HRMS(ESI)Calcd for C 24 H 30 IN 5 OS[M+H] + m / z 564.1289, found 564.1280.

[0095] Implementation 11

[0096] The difference between this example and example 2 is that the antifungal matrine-C13 hydrazine thiazole derivative 5-14 is synthesized by reacting the semicarbazide thiourea matrine intermediate 3 with α-bromonaphthaleneacetone.

[0097]

[0098] like Fig. 9 , 10 As shown, the spectrum data analysis of hydrathiazole derivatives 5-12 at C13 position of matrine:

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

[0100] 1 H NMR (400 MHz, CDCl 3 )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 (151 MHz, CDCl 3 )δ175.6,167.2,151.0,133.6,132.9,132.7,128.2,128.0,127.7,126.5,126.0,124.6,124. 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 N 5 OS[M+H] + m / z 488.2479, found 488.2470.

[0103] Implementation 12

[0104] The difference between this example and example 2 is that the antifungal matrine-C13 hydrazine thiazole derivative 5-19 is synthesized by reacting the semicarbazide thiourea matrine intermediate 3 with α-bromo-4-benzyloxyacetophenone.

[0105]

[0106] Implementation 13

[0107] This embodiment provides an application of a fungi-inhibiting matrine hydrazine thiazole derivative in the preparation of a plant fungus inhibitor, wherein the plant fungi are Sclerotinia sclerotiorum, Cystosporium aureum, Psoralea corylifolia, and Psoralea corylifolia.

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

[0109] Species: 4 plant fungi, namely rapeseed sclerotinia pathogen, apple rot pathogen, sugarcane pineapple pathogen and golden shell cystsporium.

[0110] The specific process is as follows:

[0111] The plant fungi used in this experiment were strains stored at 4°C in the laboratory, including rapeseed sclerotinia, apple rot, sugarcane pineapple pathogen and golden shell cystspore. The culture medium used was potato agar glucose medium (PDA, Haibo Biotechnology Co., Ltd.), and the solvent was dimethyl sulfoxide (Anhui Zesheng Technology Co., Ltd.). Experimental method: hyphae growth rate method.

[0112] Activation: First, culture the four plant fungi on a PDA plate at 25°C for about 3-6 days for later use;

[0113] Preparation of PDA: Prepare 46g of PDA powder with 1000mL of water, boil and bottle, 50mL / bottle, then sterilize and set aside.

[0114] Preparation of compound mother solution: Dissolve 10 mg of compound in 1 mL of dimethyl sulfoxide to prepare a 10 g / L compound mother solution. Take 250 μL of the mother solution each time and add it to 50 mL of PDA.

[0115] Sterilization: PDA culture medium, gun tip sterilization, operating table sterilization, the whole experiment is sterile operation;

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

[0117] Inoculation: After the culture medium plate solidifies, under sterile operation, use a puncher to punch a round bacterial cake (diameter 0.50 cm) at the edge of the hyphae of each strain that has been cultured for 6 days (the growth conditions should be as consistent as possible), then use an inoculation needle to pick it to the center of the drug-containing plate, and then place the culture dish upside down in an incubator (28°C) for culture.

[0118] Data processing: The growth of mycelium was observed at different times after treatment. When the blank control bacteria grew to more than 2 / 3 of the plate diameter, it could be measured. 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) × 100.

[0120] Each treatment was repeated 3 times.

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

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

[0123]

[0124]

[0125] The results of the bactericidal activity determination of the experimental group 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 showed different degrees of antibacterial activity against four plant fungi, and most of the compounds had certain inhibitory activity against rapeseed sclerotinia, golden shell cystspore, sugarcane pineapple pathogen and apple rot pathogen; compound 5-6 had obvious inhibitory effects on these four plant fungi, among which it was particularly obvious against golden shell cystspore, with an inhibition rate of up to 92.8% at a concentration of 50 mg / L, which was higher than the inhibition rate of the positive drug azoxystrobin on golden shell cystspore. The inhibitory effects of the compounds in the example experimental group on sugarcane pineapple pathogen were better than the inhibitory effects of the positive drug azoxystrobin on sugarcane pineapple pathogen; among them, compound 5-6 had the best effect, with an inhibition rate of 50.9%. From the data in the table, it can be seen that the inhibitory effects of the experimental group compounds 5-1, 5-6, 5-12, and 5-14 on rapeseed sclerotinia, golden cystosporium, and apple rot pathogens are better than those of the parent structure matrine. It can be seen that the hydrazine-thiazole antifungal matrine derivatives containing hydrazine thiazoles constructed by semicarbazide can greatly improve the inhibitory effect of the parent structure on plant fungi, providing a reference for the research direction of agricultural and forestry fungicides.

[0126] The antifungal matrine hydrazine thiazole derivatives of the present invention have obvious structural differences and distinct chemical structure characteristics, and show good effects on preventing and treating apple rot bacteria, sugarcane pineapple pathogens and golden shell cystspores. They can be used to prevent and treat fungal diseases of agricultural or forestry plants. The preparation method of the compound is simple and the product has stable properties. The antifungal matrine hydrazine thiazole derivatives synthesized by the present invention have good activity and medicinal value, which has certain inspiration for designing new agents for preventing and treating plant fungi from natural products.

[0127] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A fungi-inhibiting matrine hydrazine thiazole derivative, characterized in that: The structural formula of the antifungal matrine hydrazine thiazole derivative is as follows: Wherein, 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.

2. A method for preparing the antifungal matrine hydrazine thiazole derivative as claimed in claim 1, characterized in that: The following steps are involved: Step S1, adding NaH to a reaction container 1, then adding a DMF solution, and then adding thiosemicarbazide to the reaction container 1 and stirring the solution to obtain a thiosemicarbazide pre-reaction solution; Step S2, adding sophocarpine to the pre-reaction solution of thiosemicarbazide in step S1 for reflux reaction to obtain thiosemicarbazide matrine intermediate, the reaction equation is as follows: Step S3, adding ethanol as a dissolving solvent to the reaction container 2 to dissolve the obtained semicarbazide matrine intermediate; then adding α-bromo R-ethyl ketone to react to obtain the antifungal matrine hydrazine thiazole derivative 5, the reaction equation is as follows:

3. The preparation method according to claim 2, characterized in that: After the reaction in step S2 is completed, the reaction is quenched. After the reaction is quenched, the aqueous phase is extracted with ethyl acetate, the organic phases are combined, and then concentrated and dried to obtain the semicarbazide matrine intermediate.

4. The preparation method according to claim 3, characterized in that: In step S2, acetic acid is used to quench the reaction.

5. The preparation method according to claim 4, characterized in that: The reaction was monitored by TLC plate until completion.

6. The preparation method according to claim 5, characterized in that: The molar ratio of sophocarpine to thiosemicarbazide is 1:1-1.2 in mmol:mmol; the molar ratio of thioureamatrine to α-bromoacetophenone is 1:1.1-1.3 in mmol:mmol.

7. The preparation method according to claim 3, characterized in that: The α-bromo R-based acetone 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-naphthylacetophenone, and α-bromo-4-benzyloxyacetophenone.

8. The preparation method according to claim 3, characterized in that: The fungistatic matrine hydrazine thiazole derivative 5 includes a fungistatic matrine-C13 hydrazine thiazole derivative 5-1, a fungistatic matrine-C13 hydrazine thiazole derivative 5-3, a fungistatic matrine-C13 hydrazine thiazole derivative 5-4, a fungistatic matrine-C13 hydrazine thiazole derivative 5-5, a fungistatic matrine-C13 hydrazine thiazole derivative 5-6, a fungistatic matrine-C13 hydrazine thiazole derivative 5-9, a fungistatic matrine-C13 hydrazine thiazole derivative 5-10, a fungistatic matrine-C13 hydrazine thiazole derivative 5-12, a fungistatic matrine-C13 hydrazine thiazole derivative 5-14, and a fungistatic matrine-C13 hydrazine thiazole derivative 5-19.

9. Use of the antifungal matrine hydrazine thiazole derivative as claimed in claim 1 in the preparation of plant fungal inhibitors.

10. The use according to claim 7, characterized in that: The plant fungi are rapeseed sclerotinia pathogen, golden cystosporium, sugarcane pineapple pathogen and apple rot pathogen.

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