A kind of antifungal matrine derivative and preparation method and application

Abstract

The application discloses a kind of antifungal matrine derivatives and preparation method and application, with sophocarpine and thiourea reaction;The lone pair of electrons on the nitrogen atom of thiourea attacks C13 in matrine, and a series of antifungal matrine derivatives are synthesized by nucleophilic addition of thiourea matrine intermediate, with thiourea matrine and alpha-brominated R group ketone as reactant to synthesize a series of antifungal matrine derivatives with ethanol as solvent.The application not only enhances the bacteriostatic activity of matrine derivatives, but also has simple preparation method and easy control of reaction conditions.

Description

Technical Field

[0001] This invention belongs to the field of pesticide synthesis technology, specifically relating to an antifungal matrine derivative, its preparation method, and its application. Background Technology

[0002] Matrine alkaloids, extracted from the traditional Chinese medicine Sophora flavescens Ait, Sophora subprostrata, and Sophora alopecuroides L., have garnered attention for decades. Matrine-type alkaloids belong to the quinolone analogue family and are composed of matrine, allostrine, sophoridine, sophoridine, oxymatrine, sophoridine, and sophorol, among others. They possess numerous biological activities and therapeutic properties. For example, matrine exhibits various effective effects, including anti-inflammatory, antiviral, antitumor, antiparasitic, antimicrobial, immunosuppressive, neuroprotective, and cardioprotective effects. Matrine is also used to prepare surface-imprinted materials for molecularly selective recognition.

[0003] Due to its low bioavailability, poor chemical stability, and toxicity to the central nervous system, it is necessary to modify its structure to find antifungal matrine derivatives with higher biological activity and safety. Summary of the Invention

[0004] Purpose of the invention: To address the problem of low bioavailability of matrine, this invention provides a matrine derivative that inhibits plant fungi.

[0005] Technical solution: To achieve the above objectives, the technical solution adopted by this invention is as follows:

[0006] An antifungal matrine derivative, the structural formula of which is 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 an antifungal matrine derivative, comprising the following steps:

[0011] Step 1: Sophoridine reacts with thiourea; the lone pair electrons on the nitrogen atom of thiourea attack the C13 position of matrine, synthesizing the thiourea-matrine intermediate through nucleophilic addition;

[0012] Step 2: Using thiourea matrine intermediate and α-bromo-R-ethyl ketone as reactants and ethanol as solvent, an antifungal matrine derivative is synthesized.

[0013] Preferred method: In step 1, NaH is added to the flask, followed by DMF solution. Thiourea is weighed and added to the flask. After stirring at room temperature, the weighed sophoridine 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. Then, after extraction, concentration and drying, column chromatography is used to separate and purify the intermediate thiourea matrine.

[0014] Preferred method: In step 2, thiourea matrine intermediate is added to a round-bottom flask, then dissolved in ethanol, followed by the addition of α-bromo-R-methyl ethyl ketone. The reaction is carried out at room temperature, and the reaction is monitored by TLC plate until the reaction is completed. The reaction solution is concentrated and dried, and separated by column chromatography to obtain matrine aminethiazole derivative 5.

[0015] Preferred method: Monitor the reaction using a TLC plate until the reaction is complete.

[0016] Preferred method: Step 2 includes 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 derivative 5-11 was synthesized by reacting thiourea matrine intermediate 3 with α-bromo-3,4-dichloroacetophenone.

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

[0023] Another object of the present invention is to provide the application of the antifungal matrine derivative as described above in the preparation of plant fungal inhibitors.

[0024] Preferably, the plant fungi are Sclerotinia sclerotiorum, pineapple sclerotiorum, Aureobasidium aurantiatum, and apple rot fungus.

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

[0026] (1) The antifungal matrine derivatives of the present invention have novel molecular structures and are all new compounds; they have distinct chemical structural characteristics; the preparation method of the compounds is simple; the reaction conditions are easy to control; and the products can be obtained by column chromatography.

[0027] (2) The antifungal matrine derivative of the present invention overcomes the defect that most clinical antibacterial drugs have only one target, can exert pharmacological effects through multiple pathways and systems, and also has the advantages of high efficiency and low toxicity. Attached Figure Description

[0028] Figure 1 This is a schematic diagram illustrating the preparation method of the antifungal matrine derivative series 5 in this embodiment of the invention.

[0029] Figure 2 This is the hydrogen nuclear magnetic resonance spectrum of compound 5-2 in the embodiments of the present invention.

[0030] Figure 3 This is the carbon NMR spectrum of compound 5-2 in the embodiments of the present invention.

[0031] Figure 4 This is the 1H NMR spectrum of compound 5-3 in the embodiments of the present invention.

[0032] Figure 5 This is the carbon NMR spectrum of compound 5-3 in the embodiments of the present invention.

[0033] Figure 6 The above are the proton NMR spectra of compounds 5-7 in the embodiments of the present invention.

[0034] Figure 7 The images show the carbon NMR spectra of compounds 5-7 from the embodiments of this invention.

[0035] Figure 8 The NMR fluorine spectra of compounds 5-7 in the embodiments of the present invention are shown.

[0036] Figure 9 The above are the proton NMR spectra of compounds 5-9 in the embodiments of the present invention.

[0037] Figure 10 The images show the carbon NMR spectra of compounds 5-9 from the embodiments of this invention.

[0038] Figure 11 The above are the proton NMR spectra of compounds 5-11 in the embodiments of the present invention.

[0039] Figure 12 The image shows the carbon NMR spectra of compounds 5-11 in the embodiments of this invention.

[0040] Figure 13 The above are the proton NMR spectra of compounds 5-12 in the embodiments of the present invention.

[0041] Figure 14 The image shows the carbon NMR spectra of compounds 5-12 in the embodiments of this invention. Detailed Implementation

[0042] The present invention will be further illustrated below with reference to the accompanying drawings and specific embodiments. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the invention. After reading this invention, any modifications of the invention in various equivalent forms by those skilled in the art will fall within the scope defined by the appended claims.

[0043] Example 1

[0044] An antifungal matrine derivative, the structural formula of which is 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 complete matrine structure, 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 an antifungal matrine derivative, comprising the following steps:

[0051] Step 1 involves reacting sophoridine 1 with thiourea 2; the lone pair electrons on the nitrogen atom of thiourea attack the C13 position of matrine, synthesizing thiourea-matrine intermediate 3 via nucleophilic addition. The reaction process is as follows: Figure 1 As shown.

[0052] Add 60% pure NaH to a round-bottom flask, then add DMF solution. Weigh out thiourea and add it to the flask. Stir at room temperature for 10 minutes, then add the weighed sophoridine to the flask. Let it react at room temperature and monitor the reaction with a TLC plate until the reaction is complete. After the reaction is complete, 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 the thiourea matrine intermediate.

[0053] Step 2 involves synthesizing a series of matrine derivatives 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 As shown.

[0054] Thiourea matrine intermediate was added to a round-bottom flask, then dissolved in ethanol, followed by the addition of α-bromo-R-methyl ethyl ketone. The reaction was carried out at room temperature, and the reaction was monitored by TLC until the reaction was completed. The reaction solution was concentrated and dried, and separated by column chromatography to obtain matrine aminethiazole derivative 5.

[0055] First, thiourea matrine was synthesized using sophoridine and thiourea as starting substrates and N,N-dimethylformamide as solvent. 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 complete structure of matrine, antifungal matrine derivatives with an aminothiazole structure were formed, enhancing the antifungal activity of the antifungal matrine derivatives.

[0056] Example 3

[0057] The difference between this embodiment and Example 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] Thiourea matrine intermediate 3 was added to a round-bottom flask and dissolved in ethanol. Then, α-bromo-2,4-dichloroacetophenone was added. The molar ratio of thiourea matrine intermediate 3 to α-bromo-2,4-dichloroacetophenone was mmol:mmol:0.3:0.36. The reaction was carried out at room temperature, and the reaction was monitored by TLC plate until completion. The reaction time was 1 h. The reaction solution was 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 spectral data analysis of matrine-C13 thiazole derivative 5-2 is as follows:

[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 embodiment and Example 3 is that: matrine-C13 aminothiazole derivative 5-3 is synthesized by reacting thiourea matrine intermediate 3 with α-bromo-4-chloroacetophenone.

[0067]

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

[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 Example 3 is that matrine-C13 aminothiazole derivatives 5-7 are synthesized by reacting thiourea matrine intermediate 3 with α-bromo-4-trifluoromethylacetophenone.

[0075]

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

[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 (377MHz, 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 Example 3 is that matrine-C13 aminothiazole derivatives 5-9 are synthesized by reacting thiourea matrine intermediate 3 with α-bromo-4-bromoacetophenone.

[0083] like Figure 9 , 10 As shown, the spectral data analysis of matrine-C13 aminothiazole derivatives 5-9 is as follows:

[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 Example 3 is that the matrine-C13 aminothiazole derivative 5-11 was synthesized by reacting thiourea matrine intermediate 3 with α-bromo-3,4-dichloroacetophenone.

[0090]

[0091] like Figure 11 , 12 As shown, the spectral data analysis of matrine-C13 aminothiazole derivative 5-11 is as follows:

[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 Example 3 is that matrine-C13 aminothiazole derivative 5-12 is synthesized by reacting thiourea matrine intermediate 3 with α-bromo-4-phenylacetophenone.

[0098] like Figure 13 , 14 As shown, the spectral data analysis of matrine-C13 aminothiazole derivative 5-3 is as follows:

[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, and solvent, and found the optimal scheme for synthesizing thiourea intermediates.

[0104] Example 9

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

[0106] The fungal species included were four plant fungi: Sclerotinia sclerotiorum var. sclerotiorum, rot fungus of apple, pineapple rot fungus of sugarcane, and Aureobasidium aureum.

[0107] The specific process is as follows:

[0108] The plant fungi used in this experiment were strains preserved in the laboratory at 4℃, namely *Sclerotinia sclerotiorum*, *Pseudomonas aeruginosa*, *Pseudomonas canaliculata*, and *Cyclocarya pallida*. The culture medium used was Potato Agar-Dextrose Agar (PDA, Haibo Biotechnology Co., Ltd.), and the solvent was dimethyl sulfoxide (Anhui Zesheng Technology Co., Ltd.). Experimental method: Mycelial growth rate method.

[0109] Activation: First, incubate the four plant fungi on PDA plates at 25℃ for about 3-6 days before use;

[0110] PDA preparation: Mix 46g of PDA powder with 1000mL of water, boil and bottle (50mL / bottle), then sterilize and set aside for use.

[0111] Preparation of compound stock solution: Dissolve 10 mg of the compound in 1 mL of dimethyl sulfoxide to prepare a 10 g / L stock solution. Take 250 μL of the stock solution each time and add it to 50 mL of PDA.

[0112] Sterilization: PDA culture medium, pipette tips sterilized, operating table sterilized, and aseptic operation throughout the experiment;

[0113] Sample addition: Take 250 μL of the 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. Pour the medium into petri dishes and cool. Perform three parallel controls for each compound. The medium with an equal amount of dimethyl sulfoxide is used as a blank control, azoxystrobin is used as a positive control, and matrine is used as a negative control.

[0114] Inoculation: After the culture medium plate has solidified, under aseptic conditions, use a punch to make round mycelial cakes (0.50 cm in diameter) at the edge of the mycelia of each strain after 6 days of culture (with the growth status as uniform as possible). Then, use an inoculation needle to pick them up and transfer them to the center of the drug-containing plate. Finally, invert the petri dish and incubate it in an incubator (28℃).

[0115] Data processing: The growth of mycelium was observed and measured at different time points after treatment. When the blank control mycelium grew to more than 2 / 3 of the plate diameter, it was measured using the cross-cross method. The diameter was measured and the data was processed to calculate the inhibition rate.

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

[0117] Each treatment was repeated 3 times.

[0118] Table 1 shows the antifungal inhibition rate (50 mg / L) of matrine-C13 aminethiazole derivative.

[0119] Table 1. Antifungal inhibition rate of matrine-C13 aminothiazole derivative (50 mg / L)

[0120]

[0121] The results of the bactericidal activity determination of the experimental group compounds, the positive compound pyraclostrobin, and the parent compound matrine are shown in Table 1. As shown in Table 1, at a concentration of 50 mg / L, compounds 5-2, 5-3, 5-7, 5-9, 5-11, and 5-12 exhibited varying degrees of antifungal activity against four plant fungi. Most compounds showed some inhibitory activity against *Sclerotinia sclerotiorum*, *Pseudomonas aeruginosa*, *Pseudomonas canaliculata*, and *Cyclocarya paliurus*. Compound 5-11 showed significant inhibitory effects against all four plant fungi, with a particularly strong inhibitory effect against *Cyclocarya paliurus*, achieving an inhibition rate of 94.1% at 50 mg / L, higher than the inhibition rate of the positive-area pyraclostrobin against *Cyclocarya paliurus* (65.35%). It also showed a high inhibitory effect against *Pseudomonas aeruginosa*, with an inhibition rate of 86.88%. In the experimental group, the compounds showed better inhibitory effects against *Pseudomonas canaliculata* than the positive-area pyraclostrobin. Compounds 5-11 and 5-12 showed the best effects, with inhibition rates of 69.89% and 64.78%, respectively. The data in the table show that compounds 5-2, 5-3, 5-7, 5-9, 5-11, and 5-12 in the experimental group exhibited better inhibitory effects on these four plant fungi than the parent structure matrine. This demonstrates that the amine-thiazole-containing antifungal matrine derivatives constructed using thiourea can significantly enhance the inhibitory effect of the parent structure on plant fungi, providing valuable insights for research on fungicides in agriculture and forestry.

[0122] The antifungal matrine derivatives of this invention exhibit distinct structures and clear chemical characteristics, demonstrating good efficacy against apple rot fungus, sugarcane pineapple rot fungus, and *Cyclocarya paliurus*. They can be used to control fungal diseases in agricultural or forestry plants. The preparation method of these compounds is simple, and the products are stable. The antifungal matrine derivatives synthesized in this invention possess good activity and medicinal value, providing inspiration for designing novel fungicides for controlling plant fungi based on natural products.

[0123] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A matrine derivative for inhibiting fungi, characterized in that: The structural formula of the antifungal matrine derivative is shown below: Wherein, R is one of the following groups; 。 2. A method for preparing the antifungal matrine derivative as described in claim 1, characterized in that, Includes the following steps: Step 1: Sophoridine reacts with thiourea; the lone pair electrons on the nitrogen atom of thiourea attack the C13 position of matrine, synthesizing the thiourea-matrine intermediate through nucleophilic addition; Add NaH to the flask, then add DMF solution, weigh out thiourea and add it to the flask, stir at room temperature, then add the weighed sophoridine to the flask and react at room temperature. After the reaction is complete, add an appropriate amount of acetic acid to quench the reaction, then extract, concentrate and dry, and separate and purify by column chromatography to obtain the thiourea matrine intermediate. The thiourea matrine intermediate is: Step 2: Using thiourea matrine intermediate and α-bromo-R-methyl ethyl ketone as reactants and ethanol as solvent, an antifungal matrine derivative is synthesized. Thiourea matrine intermediate was added to a round-bottom flask, then dissolved in ethanol, followed by the addition of α-bromo-R-methyl ethyl ketone. The reaction was carried out at room temperature, and the reaction was monitored by TLC until the reaction was completed. The reaction solution was concentrated and dried, and separated by column chromatography to obtain matrine aminethiazole derivative 5.

3. The method for preparing the antifungal matrine derivative according to claim 2, characterized in that: The reaction was monitored using a TLC plate until it was completed.

4. The method for preparing the antifungal matrine derivative according to claim 3, characterized in that: Step 2 includes 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 derivative 5-11 was synthesized by reacting thiourea matrine intermediate 3 with α-bromo-3,4-dichloroacetophenone. Matrine-C13 aminothiazole derivative 5-12 was synthesized by reacting thiourea matrine intermediate 3 with α-bromo-4-phenylacetophenone.

5. The use of the antifungal matrine derivative as described in claim 1 in the preparation of plant fungal inhibitors.

6. The application according to claim 5, characterized in that: The plant fungi mentioned are Sclerotinia sclerotiorum, pineapple sclerotiorum, Aureobasidium aurantiatum, and apple rot fungus.

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