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

Abstract

The invention discloses an antifungal matrine derivative as well as a preparation method and application thereof. The preparation method comprises the following steps: reacting sophocarpine with thiourea; a lone pair electron on a thiourea nitrogen atom attacks a C13 site in sophocarpidine, a thiourea sophocarpidine intermediate is synthesized through nucleophilic addition, and a series of antifungal sophocarpidine derivatives are synthesized by taking thiourea sophocarpidine and alpha-bromo-R-ethyl ketone as reactants and taking ethanol as a solvent. The antibacterial activity of the matrine derivative is enhanced, 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 specifically relates to a fungus-inhibiting matrine derivative and a preparation method and application thereof. Background Art

[0002] Matrine alkaloids are extracted from the traditional Chinese medicine Sophora flavescens Ait, Sophora subprostrata and Sophora alopecuroides L., and have been receiving attention for the past few decades. Matrine-type alkaloids belong to quinolizidine analogs, and are composed of matrine, allomatrine, sophoracarpine, 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. Matrine is also used to prepare surface imprinted materials for selective molecular recognition.

[0003] Due to its low bioavailability, poor chemical stability and toxicity to the central nervous system, it is necessary to find antifungal matrine derivatives with higher biological activity and safety by modifying its structure. 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 derivative that has inhibitory activity against plant fungi.

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

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

[0007]

[0008] Wherein, R is one of the following groups;

[0009]

[0010] Another object of the present invention is to provide a method for preparing a fungistatic matrine derivative, comprising the following steps:

[0011] Step 1, using sophoracarpine to react with thiourea; the lone pair of electrons on the nitrogen atom of thiourea attacks the C13 position of matrine, and a thiourea matrine intermediate is synthesized by nucleophilic addition;

[0012] Step 2, using the thiourea matrine intermediate and α-bromo R-ethyl ketone as reactants and ethanol as solvent to synthesize the antifungal matrine derivative.

[0013] Preferably: in step 1, NaH is added to the flask, and then the DMF solution is added, thiourea is weighed and added to the flask, and after stirring at room temperature, the weighed sophoracarpine is added to the flask, and reacted at room temperature. 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 to obtain the thiourea matrine intermediate.

[0014] Preferably: in step 2, the thiourea matrine intermediate is added to a round-bottom flask, and then the solvent ethanol is added to dissolve it, and then α-bromo R-methyl ethyl ketone is added, and the reaction is reacted at room temperature. The reaction is monitored by a TLC plate until the reaction is completed, and the reaction solution is concentrated and dried, and separated by column chromatography to obtain the matrine amine thiazole derivative 5.

[0015] Preferably, the reaction is monitored by TLC plate until the reaction is complete.

[0016] Preferably: the method of step 2 comprises the following steps:

[0017] Matrine-C13 aminothiazole derivative 5-2 was synthesized by reacting thiourea matrine intermediate 3 with α-bromo-2,4-dichloroacetophenone.

[0018] Matrine-C13 aminothiazole derivative 5-3 was synthesized by reacting thiourea matrine intermediate 3 with α-bromo-4-chloroacetophenone.

[0019] Matrine-C13 aminothiazole derivatives 5-7 were synthesized by reacting thiourea matrine intermediate 3 with α-bromo-4-trifluoromethylacetophenone.

[0020] Matrine-C13 aminothiazole derivatives 5-9 were synthesized by reacting thiourea matrine intermediate 3 with α-bromo-4-bromoacetophenone.

[0021] Matrine-C13 aminothiazole derivatives 5-11 were synthesized by reacting thiourea matrine intermediate 3 with α-bromo-3,4-dichloroacetophenone.

[0022] Matrine-C13 aminothiazole derivatives 5-12 were synthesized by reacting thiourea matrine intermediate 3 with α-bromo-4-phenylacetophenone.

[0023] Another object of the present invention is to provide a use of the fungistatic matrine derivatives described above in the preparation of plant fungi inhibitors.

[0024] Preferably, the plant fungi are rapeseed sclerotinia pathogen, sugarcane pineapple pathogen, golden cystosporium, and apple rot pathogen.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] (1) The antifungal matrine derivatives of the present invention have novel molecular structures and are all new compounds; their chemical structures have distinct characteristics; the preparation methods of the compounds are simple, the reaction conditions are easily controlled, and the products can be obtained by column chromatography.

[0027] (2) The antifungal matrine derivatives of the present invention overcome the defect that most clinical antibacterial drugs have only one target, can exert pharmacological effects in multiple pathways and systems, and also have the advantages of high efficiency and low toxicity. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 Schematic diagram of the preparation method of 5 series of antifungal matrine derivatives in the embodiments of the present invention.

[0029] Figure 2 This is the hydrogen nuclear magnetic resonance spectrum of Example Compound 5-2 of the present invention.

[0030] Figure 3 This is the carbon nuclear magnetic resonance spectrum of Example Compound 5-2 of the present invention.

[0031] Figure 4 This is the hydrogen nuclear magnetic resonance spectrum of Example Compound 5-3 of the present invention.

[0032] Figure 5 This is the carbon nuclear magnetic resonance spectrum of Example Compound 5-3 of the present invention.

[0033] Figure 6 The hydrogen nuclear magnetic resonance spectrum of Example Compound 5-7 of the present invention.

[0034] Figure 7 The carbon nuclear magnetic resonance spectrum of Example Compound 5-7 of the present invention.

[0035] Figure 8 The nuclear magnetic resonance fluorine spectrum of Example Compound 5-7 of the present invention.

[0036] Fig. 9 The hydrogen nuclear magnetic resonance spectrum of Example Compound 5-9 of the present invention.

[0037] Fig.10 The carbon nuclear magnetic resonance spectrum of Example Compound 5-9 of the present invention.

[0038] Fig.11 The hydrogen nuclear magnetic resonance spectrum of Example Compound 5-11 of the present invention.

[0039] Fig.12 The carbon nuclear magnetic resonance spectrum of Example Compound 5-11 of the present invention.

[0040] Fig.13 The hydrogen nuclear magnetic resonance spectrum of Example Compound 5-12 of the present invention.

[0041] Fig.14 The carbon nuclear magnetic resonance spectrum of Example Compound 5-12 of the present invention. DETAILED DESCRIPTION

[0042] 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.

[0043] Example 1

[0044] A fungus-inhibiting matrine derivative, the fungus-inhibiting matrine derivative has a structural formula as shown below:

[0045]

[0046] Wherein, R is one of the following groups;

[0047]

[0048] The antifungal matrine derivative of this embodiment not only retains the matrine structure completely, but also has an aminothiazole structure, which enhances the antibacterial activity of the matrine derivative.

[0049] Example 2

[0050] This embodiment provides a method for preparing a fungus-inhibiting matrine derivative, comprising the following steps:

[0051] Step 1, sophoracarpine 1 is reacted with thiourea 2; the lone pair of electrons on the nitrogen atom of thiourea attacks the C13 position of matrine, and thiourea matrine intermediate 3 is synthesized by nucleophilic addition. The reaction process is as follows: Figure 1 shown.

[0052] Add 60% pure NaH to a round-bottom flask, then add DMF solution, weigh thiourea and add it to the flask, stir at room temperature for 10 minutes, then add the weighed sophoracarpine to the flask, react at room temperature, and use TLC plate to detect the reaction until the reaction is completed. After the reaction is completed, add an appropriate amount of acetic acid to quench the reaction, then extract, concentrate and dry, and purify by column chromatography (dichloromethane: methanol = 10: 1-8: 1) to obtain thiourea matrine intermediate.

[0053] Step 2, a series of matrine derivatives are synthesized by using thiourea matrine intermediate 3 and α-bromo R-ethyl ketone as reactants and ethanol as solvent. The reaction process is as follows: Figure 1 shown.

[0054] The thiourea matrine intermediate was added into a round-bottom flask, and then the 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 TLC plate until the reaction was completed. The reaction solution was concentrated and dried, and separated by column chromatography to obtain the matrine amine thiazole derivative 5.

[0055] First, thiourea matrine was synthesized using sophoracarpine and thiourea as starting substrates and N,N-dimethylformamide as solvent, and then a series of antifungal matrine derivatives were synthesized using thiourea matrine and α-bromo-R-ethyl ketone as reactants and ethanol as solvent. While retaining the structure of matrine, antifungal matrine derivatives with aminothiazole structure were formed, which enhanced the antibacterial activity of antifungal matrine derivatives.

[0056] Example 3

[0057] The difference between this embodiment and embodiment 2 is that the matrine-C13 aminothiazole derivative 5-2 is synthesized by reacting the thiourea matrine intermediate 3 with α-bromo-2,4-dichloroacetophenone.

[0058] Add thiourea matrine intermediate 3 into a round-bottom flask, add solvent ethanol to dissolve, then add α-bromo-2,4-dichloroacetophenone, the molar ratio of thiourea matrine intermediate 3 to α-bromo-2,4-dichloroacetophenone is mmol:mmol:0.3:0.36; react at room temperature, monitor the reaction with a TLC plate until the reaction is completed, reaction time: 1h. The reaction solution is concentrated and dried, and separated by column chromatography (dichloromethane:methanol=30:1~20:1) to obtain the product matrine-C13 aminothiazole derivative 5-2:

[0059]

[0060] like Figure 2 , 3 As shown, the spectrum data analysis of matrine-C13 aminothiazole derivative 5-2:

[0061] White solid, R f :0.65 (DCM:MeOH=10:1), 145.9mg (99.0% yield).

[0062] 1H NMR (600MHz, CDCl3) δ7.84(d,J=8.5Hz,1H),7.39(d,J=2.2Hz,1H),7.22(dd,J=8.5,2.2Hz,1H),7.01(s,1H),6.23(d,J=6.6H z,1H),4.38(dd,J=12.7,4.5Hz,1H),4.20(q,J=5.1Hz,1H),4.11–4.04(m,1H),3.16(t,J=12.7Hz,1H),2.82(dd,J=21.2,11.4 Hz,2H),2.71(dd,J=17.2,4.9Hz,1H),2.55(dd,J=17.0,5.5Hz,1H),2.37(dt,J=12.5,6.4Hz,1H),2.19(s,1H),2.03–1.93(m ,3H),1.87–1.81(m,1H),1.74(d,J=14.4Hz,2H),1.69–1.64(m,1H),1.61–1.56(m,2H),1.55–1.48(m,1H),1.45–1.36(m,3H).

[0063] 13 C NMR (400MHz, CDCl3) δ166.9,166.1,146.5,133.3,132.3,132.2,132.1,130.1,127.0,10 7.0,63.8,57.1,57.1,50.2,46.7,42.6,41.7,38.2,35.3,30.7,27.5,26.3,20.9,20.4.

[0064] HRMS(ESI)Calcd for C 24 H 28 Cl2N4OS[M+H] + m / z 491.1434, found 491.1425.

[0065] Example 4

[0066] The difference between this example and example 3 is that the matrine-C13 aminothiazole derivative 5-3 is synthesized by reacting the thiourea matrine intermediate 3 with α-bromo-4-chloroacetophenone:

[0067]

[0068] like Figure 4 , 5 As shown, the spectrum data analysis of matrine-C13 aminothiazole derivative 5-3:

[0069] White solid, R f :0.65 (DCM:MeOH=10:1), 135.7 mg (99.0% yield).

[0070] 1 H NMR (400MHz, CDCl3) δ7.71(d,J=8.3Hz,2H),7.31(d,J=8.2Hz,2H),6.65(s,1H),5.80(d,J =6.3Hz,1H),4.39(dd,J=12.9,4.6Hz,1H),4.22(s,1H),4.13–3.99(m,1H),3.15(t,J=12. 8Hz,1H),2.88–2.68(m,3H),2.61–2.49(m,1H),2.38–2.24(m,1H),2.17(s,1H),2.04–1.8 6(m,4H),1.71(dd,J=26.3,13.1Hz,3H),1.63–1.51(m,3H),1.48–1.36(d,J=16.6Hz,3H).

[0071] 13 C NMR (101MHz, CDCl3) δ167.3,166.7,150.2,133.4,133.2,128.6(2C),127.3(2C),1 01.6,63.8,57.1,50.1,46.8,42.5,41.7,38.3,35.4,30.7,27.5,26.4,20.9,20.5.

[0072] HRMS(ESI)Calcd for C 24 H 29 ClN4OS[M+H] + m / z 457.1824,found 457.1820.

[0073] Example 5

[0074] The difference between this embodiment and embodiment 3 is that the matrine-C13 aminothiazole derivative 5-7 is synthesized by reacting the thiourea matrine intermediate 3 with α-bromo-4-trifluoromethylacetophenone:

[0075]

[0076] like Figure 6-8 As shown, the spectrum data analysis of matrine-C13 aminothiazole derivatives 5-7:

[0077] White solid, R f:0.65 (DCM:MeOH=10:1), 145.7 mg (99.0% yield).

[0078] 1 H NMR (400MHz, CDCl3) δ7.88(d,J=8.1Hz,2H),7.58(d,J=8.1Hz,2H),6.77(s,1H),6.16( s,1H),4.40(d,J=12.9Hz,1H),4.27(s,1H),4.08(t,J=8.7Hz,1H),3.17(t,J=12.9Hz,1 H),2.91–2.67(m,3H),2.64–2.52(m,1H),2.36(d,J=12.8Hz,1H),2.21(s,1H),2.06–1. 93(m,3H),1.91–1.81(m,1H),1.80–1.70(m,2H),1.68–1.50(m,4H),1.47–1.33(m,3H).

[0079] 13 C NMR (101MHz, CDCl3) δ167.4,167.0,149.7,138.2,129.0,126.1(4C), δ125.46(dd,J=7.4,3.6H z).,103.2,63.9,57.1(2C),50.2,46.7,42.5,41.6,38.2,35.3,30.7,27.4,26.2,20.8,20.3. 19 F NMR (377 MHz, CDCl3) δ -62.4.

[0080] HRMS(ESI)Calcd for C 25 H 29 F3N4OS[M+H] + m / z 491.2087, found 491.2085.

[0081] Example 6

[0082] The difference between this embodiment and embodiment 3 is that the matrine-C13 aminothiazole derivative 5-9 is synthesized by reacting the thiourea matrine intermediate 3 with α-bromo-4-bromoacetophenone.

[0083] like Fig. 9 , 10 As shown, the spectrum data analysis of matrine-C13 position thiazole derivatives 5-9:

[0084] White solid, R f:0.65 (DCM:MeOH=10:1), 142.9 mg (95.0% yield).

[0085] 1 H NMR (400MHz, CDCl3) δ7.67(d,J=8.2Hz,2H),7.48(d,J=8.3Hz,2H),6.68(s,1H),5.92(s,1H) ,4.42(dd,J=12.9,4.5Hz,1H),4.25(t,J=6.7Hz,1H),4.16–4.10(m,1H),3.20(t,J=12.7Hz, 1H),2.94–2.84(m,2H),2.75(dd,J=17.1,4.9Hz,1H),2.58(dd,J=17.2,6.0Hz,1H),2.36–2. 22(m,2H),2.08–1.93(m,4H),1.79(d,J=11.1Hz,2H),1.71–1.54(m,4H),1.50–1.40(m,3H).

[0086] 13 C NMR (101MHz, CDCl3) δ167.4,167.1,150.0,133.9,131.5(2C),127.6(2C),121.3,101. 5,63.7,57.2,57.1,50.4,46.6,42.6,41.9,38.2,35.5,30.7,27.7,26.4,21.1,20.6.

[0087] HRMS(ESI)Calcd for C 24 H 29 BrN4OS[M+H] + m / z 501.1318, found 501.1310.

[0088] Example 7

[0089] The difference between this embodiment and embodiment 3 is that the matrine-C13 aminothiazole derivative 5-11 is synthesized by reacting the thiourea matrine intermediate 3 with α-bromo-3,4-dichloroacetophenone:

[0090]

[0091] like Fig.11 , 12 As shown, the spectrum data analysis of matrine-C13 position thiazole derivatives 5-11:

[0092] White solid, R f:0.65 (DCM:MeOH=10:1), mg (% yield).

[0093] 1 H NMR (400MHz, CDCl3) δ7.92 (s, 1H), 7.59 (d, J = 8.5Hz, 1H), 7.41 (d, J = 8.4Hz, 1H) ,6.71(s,1H),4.47(d,J=11.7Hz,1H),4.27(s,2H),3.19(t,J=13.0Hz,1H),3.05 (s,2H),2.76–2.59(m,2H),2.47(s,1H),2.34–2.13(m,3H),2.08(d,J=13.1Hz,1 H),2.02–1.92(m,1H),1.91–1.80(m,2H),1.77–1.64(m,3H),1.62–1.48(m,4H).

[0094] 13 C NMR (101MHz, CDCl3) δ167.5,167.4,148.6,135.0,132.5,131.0,130.4,127.9,125.0,1 02.7,64.1,56.9(2C),49.9,46.3,42.0,41.1,37.9,34.9,30.8,26.9,25.7,20.3,19.8.

[0095] HRMS(ESI)Calcd for C 24 H 28 Cl2N4OS[M+H] + m / z 491.1434, found 491.1426.

[0096] Example 8

[0097] The difference between this embodiment and embodiment 3 is that the matrine-C13 aminothiazole derivative 5-12 is synthesized by reacting the thiourea matrine intermediate 3 with α-bromo-4-phenylacetophenone.

[0098] like Fig.13 , 14 As shown, the spectrum data analysis of matrine-C13 aminothiazole derivative 5-3:

[0099] White solid, R f :0.65 (DCM:MeOH=10:1), 133.1 mg (89.0% yield).

[0100] 1H NMR (400MHz, CDCl3) δ7.89 (d, J=8.3Hz, 2H), 7.68–7.60 (m, 4H), 7.47 (t, J=7.7Hz, 2H), 7.37 (t, J= 7.4Hz,1H),6.76(s,1H),5.55–5.41(m,1H),4.43(dd,J=12.7,4.4Hz,1H),4.30–4.22(m,1H),4.16 –4.05(m,1H),3.18(t,J=12.7Hz,1H),2.90–2.75(m,3H),2.60(dd,J=17.2,5.9Hz,1H),2.41–2.29 (m,1H),2.20(s,1H),2.07–1.95(m,5H),1.82–1.67(m,4H),1.68–1.53(m,4H),1.54–1.40(m,4H).

[0101] 13 C NMR(151MHz, CDCl3)δ167.2,166.8,151.0,140.8,140.3,133.9,128.8(2C),127.3,127.2(2C),127.0(2C ),126.4(2C),101.3,63.8,57.2,57.2,50.4,46.9,42.6,41.8,38.4,35.5,30.8,27.7,26.5,21.1,20.6.

[0102] HRMS(ESI)Calcd for C 30 H 34 N4OS[M+H] + m / z 499.2526, found 499.2521.

[0103] The experiment explored aspects such as material ratio, catalyst, temperature, solvent, and found the best solution for synthesizing thiourea intermediates.

[0104] Example 9

[0105] This example tests the antifungal activity of fungistatic matrine derivatives.

[0106] Species: 4 plant fungi, namely rapeseed sclerotinia disease, apple rot disease, sugarcane pineapple disease and golden shell cystsporium.

[0107] The specific process is as follows:

[0108] 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.

[0109] Activation: First, culture the four plant fungi on a PDA plate at 25°C for about 3-6 days for later use;

[0110] Preparation of PDA: Prepare 46g of PDA powder with 1000mL of water, boil and bottle, 50mL / bottle, then sterilize and set aside.

[0111] 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.

[0112] Sterilization: PDA culture medium, gun tip sterilization, operating table sterilization, the whole experiment is sterile operation;

[0113] 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.

[0114] 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.

[0115] 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.

[0116] Inhibition rate (%) = (control mycelium diameter - treated mycelium diameter) / (control mycelium diameter - 0.5) × 100.

[0117] Each treatment was repeated 3 times.

[0118] Table 1 is the experimental results of the antifungal inhibition rate (50 mg / L) of matrine-C13 amine thiazole derivatives

[0119] Table 1 Antifungal inhibition rate of matrine-C13 amine thiazole derivatives (50 mg / L)

[0120]

[0121] 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 5-2, 5-3, 5-7, 5-9, 5-11, and 5-12 showed different degrees of antibacterial activity against four plant fungi. Most of the compounds had certain inhibitory activity against rapeseed sclerotinia, apple rot pathogen, sugarcane pineapple pathogen, and golden shell cystspore. Compound 5-11 had obvious inhibitory effects on these four plant fungi, especially against golden shell cystspore. The inhibition rate was as high as 94.1% at a concentration of 50 mg / L, which was higher than the inhibition rate of positive drug azoxystrobin on golden shell cystspore (65.35%). It had a high inhibitory effect on apple rot pathogen, with an inhibition rate of 86.88%. The inhibitory effects of the compounds in the example experimental group on sugarcane pineapple pathogen were better than the inhibitory effect of positive drug azoxystrobin on sugarcane pineapple pathogen. Among them, compounds 5-11 and 5-12 had the best effects, with inhibition rates of (69.89% and 64.78%), respectively. From the data in the table, it can be seen that the inhibitory effects of the experimental group compounds 5-2, 5-3, 5-7, 5-9, 5-11, and 5-12 on these four plant fungi are better than those of the parent structure matrine. It can be seen that the aminothiazole-containing antifungal matrine derivatives constructed by thiourea 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.

[0122] The antifungal matrine 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 derivatives synthesized by the present invention have good activity and medicinal value, which has certain implications for designing new agents for preventing and treating plant fungi from natural products.

[0123] 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 fungistatic matrine derivative, characterized in that: The structural formula of the antifungal matrine derivative is as follows: Wherein, R is one of the following groups; 2. A method for preparing a fungistatic matrine derivative, characterized in that: The following steps are involved: Step 1, using sophoracarpine to react with thiourea; the lone pair of electrons on the nitrogen atom of thiourea attacks the C13 position of matrine, and a thiourea matrine intermediate is synthesized by nucleophilic addition; Step 2, using the thiourea matrine intermediate and α-bromo R-ethyl ketone as reactants and ethanol as solvent to synthesize the antifungal matrine derivative.

3. The method for preparing the antifungal matrine derivative according to claim 2, characterized in that: Add NaH to the flask, then add DMF solution, weigh thiourea and add it to the flask. After stirring at room temperature, add the weighed sophoracarpine to the flask and react at room temperature. After the reaction is completed, add an appropriate amount of acetic acid to quench the reaction. After extraction, concentration and drying, column chromatography separation and purification are performed to obtain the thiourea matrine intermediate.

4. The method for preparing the antifungal matrine derivative according to claim 3, characterized in that: The thiourea matrine intermediate was added into a round-bottom flask, and then the 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 TLC plate until the reaction was completed. The reaction solution was concentrated and dried, and separated by column chromatography to obtain the matrine amine thiazole derivative 5.

5. The method for preparing the antifungal matrine derivative according to claim 4, characterized in that: The reaction was monitored by TLC plate until completion.

6. The method for preparing the antifungal matrine derivative according to claim 5, characterized in that: The method of step 2 comprises the following steps: Matrine-C13 aminothiazole derivative 5-2 was synthesized by reacting thiourea matrine intermediate 3 with α-bromo-2,4-dichloroacetophenone; Matrine-C13 aminothiazole derivative 5-3 was synthesized by reacting thiourea matrine intermediate 3 with α-bromo-4-chloroacetophenone; Matrine-C13 aminothiazole derivatives 5-7 were synthesized by reacting thiourea matrine intermediate 3 with α-bromo-4-trifluoromethylacetophenone; Matrine-C13 aminothiazole derivatives 5-9 were synthesized by reacting thiourea matrine intermediate 3 with α-bromo-4-bromoacetophenone; Matrine-C13 aminothiazole derivatives 5-11 were synthesized by reacting thiourea matrine intermediate 3 with α-bromo-3,4-dichloroacetophenone; Matrine-C13 aminothiazole derivatives 5-12 were synthesized by reacting thiourea matrine intermediate 3 with α-bromo-4-phenylacetophenone.

7. Use of the fungistatic matrine derivative according to claim 1 in the preparation of plant fungus inhibitors.

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

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