Amino acid fragment-containing arecoline derivatives, methods of making and using the same

Abstract

The application discloses an arecoline derivative containing an amino acid fragment, a preparation method of the arecoline derivative, and application of the arecoline derivative as an agricultural fungicide. The arecoline derivative containing the amino acid fragment has a novel molecular structure and excellent inhibitory activity on plant pathogenic bacteria, is suitable for prevention and treatment of agricultural plant pathogenic bacteria, can be used for development and use of effective components of agricultural fungicides or adjuvants, and has the potential of development and application as a new agricultural fungicide.

Description

Technical Field

[0001] This invention belongs to the field of chemical pesticide synthesis, specifically relating to an arecoline derivative containing amino acid fragments and its preparation method, as well as the application of the arecoline derivative containing amino acid fragments as an agricultural fungicide. Background Technology

[0002] Natural products are diverse in nature, possess good biocompatibility, unique mechanisms of action, and are easily degraded, making them widely used in drug development. Alkaloids, as an important component of natural products, have complex chemical structures, and their instability and volatility in nature make them difficult to apply directly in practice. Modification using natural products as lead compounds is a research hotspot in pesticide development, with many successful examples. Examples include neonicotinoid insecticides such as imidacloprid developed using nicotine from tobacco as a lead compound, and carbamate fungicides such as dimethoate developed using physostigmine as a lead compound.

[0003] Areca nut is a traditional medicinal plant found in southern China. Arecoline, a representative alkaloid found in areca nut, possesses rich biological activities, with research focusing on its effects on the nervous system, treatment of cardiovascular diseases, anthelmintic activity, and antimicrobial activity. Studies have demonstrated that arecoline exhibits inhibitory activity against Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, and Escherichia coli. The minimum inhibitory concentrations (MICs) against Staphylococcus aureus and Bacillus subtilis are 12.50 and 6.25 mg / mL, respectively, while the MICs against Bacillus cereus and Escherichia coli are both 25.00 mg / mL. In terms of anthelmintic activity, arecoline functions similar to acetylcholine, affecting the nervous system of liver flukes and Schistosoma mansoni, thus paralyzing the worms and leading to their death. It also has a killing effect on pork roundworms, Echinococcus granulosus larvae, and Oncomelania snails. Furthermore, arecoline also exhibits insecticidal activity against cattle ticks, golden apple snails, and diamondback moth larvae. The LC50 after 24 hours of treatment showed significant toxicity. 50 The concentrations were 4.16 mg / L, 5.64 mg / L, and 70.28 mg / L, respectively.

[0004] Small molecule peptide derivatives, such as amino acids, possess advantages as antibacterial compounds, including high safety, good antibacterial activity, broad antibacterial spectrum, and low likelihood of inducing drug resistance. Furthermore, their easy degradation, low residue, and environmentally friendly properties give them unique advantages in antibacterial drug design. Small amino acid molecules, as active fragments, have wide applications in pesticide structures; for example, commercial pesticides such as valacyclophosphamide, valerate, benomyl, and lambda-cyhalothrin all contain amino acid structural fragments. Summary of the Invention

[0005] In response to the aforementioned technical problems in related technologies, this invention utilizes the principles of bioisosterism and active group splicing to design and synthesize a series of arecoline derivatives containing amino acid fragments, and provides their preparation methods and applications, which can solve the above problems.

[0006] To achieve the above-mentioned technical objectives, the technical solution of the present invention is implemented as follows:

[0007] A arecoline derivative containing amino acid fragments, with the general structural formula (1),

[0008]

[0009] The X group represents O or NH; the value of n is 0, 1, 2 or 3.

[0010] Furthermore, in the structural formula (Ⅰ) of an arecoline derivative containing an amino acid fragment, R 1 Selected from hydrogen atom, methyl, ethyl, cyclopropyl, isopropyl, tert-butyl.

[0011] Furthermore, in the structural formula (Ⅰ) of an arecoline derivative containing an amino acid fragment, R 2 Selected from hydrogen atom, methyl, isopropyl, isobutyl, sec-butyl, benzyl and CH3SCH2CH2.

[0012] Furthermore, in the structural formula (Ⅰ) of an arecoline derivative containing an amino acid fragment, R 3 Selected from aryl, aliphatic heterocycles, oxygen heterocycles, nitrogen heterocycles, sulfur heterocycles, aromatic heterocycles, benzo[a] heterocycles, or fused rings with substituents, wherein R 3 The substituents on it are halogen atoms such as fluorine, chlorine and bromine, as well as mono- or poly-substituted groups such as methyl, isopropyl, tert-butyl, methoxy, nitro, cyano, trifluoromethoxy, and trifluoromethyl.

[0013] Furthermore, a method for preparing arecoline derivatives containing amino acid fragments involves the following reaction steps:

[0014]

[0015] Furthermore, the arecoline derivatives containing amino acid fragments described in any of the above-mentioned embodiments can be used as agricultural fungicides.

[0016] Furthermore, the agricultural fungicide is used as a technical material to prepare formulations and compositions, wherein the agricultural fungicide is at least one of the arecoline derivatives containing amino acid fragments mentioned above.

[0017] Furthermore, the formulation of agricultural fungicides is at least one of emulsifiable concentrates, water-in-oil emulsions, microemulsions, wettable powders, water-dispersible granules, suspensions, or other suitable formulations.

[0018] Furthermore, the content of arecoline derivatives containing amino acid fragments in the fungicidal composition made from agricultural fungicides is 1-99.9% by weight.

[0019] Furthermore, the application of the arecoline derivatives or combination formulations containing amino acid fragments as agricultural fungicides is characterized in that the agricultural fungicide is used to control plant pathogenic fungal diseases; wherein the plant pathogenic fungi include: Oomycetes, such as downy mildew, white rust, damping-off, cottony rot, Phytophthora, and late blight; Basidiomycetes, such as stripe rust, smut, and sheath blight; Ascomycetes, such as powdery mildew, sclerotinia, black spot, and Fusarium head blight; Deuteromycetes, such as wilt, root rot, damping-off, anthracnose, verticillium wilt, gray mold, brown spot, black spot, black rot, stem rot, leaf spot, early blight, ring spot, leaf blight, and pseudostem spot, etc.

[0020] Beneficial effects:

[0021] The arecoline derivative containing amino acid fragments provided by this invention has a novel molecular structure and significantly enhanced antibacterial activity compared with the lead compound arecoline. It exhibits good inhibitory effects on plant pathogens such as rice blast fungus, dragon fruit black spot fungus, mango stem rot fungus, wheat stem base rot fungus, banana anthracnose fungus, rice sheath blight fungus, apple ring rot fungus, rapeseed sclerotium rot fungus, and pepper blight fungus. It can be used for the development and application of effective components in the preparation of agricultural fungicides or adjuvants. Attached Figure Description

[0022] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0023] The present invention will now be described in further detail with reference to the accompanying drawings.

[0024] Figure 1 This is the general structural formula of an arecoline derivative containing an amino acid fragment according to the present invention;

[0025] Figure 2a This is a structural description table of some compounds (Ⅰ-1~Ⅰ-22) of the arecoline derivative containing amino acid fragments of the present invention after the general structural formula is replaced by substituents;

[0026] Figure 2bThis is a structural description table of some compounds (I-23 to I-54) of a arecoline derivative containing an amino acid fragment, after the general structural formula of the present invention has been replaced by substituents;

[0027] Figure 2c This is a structural description table of some compounds (I-55 to I-86) of a arecoline derivative containing an amino acid fragment, after the general structural formula of the present invention has been replaced by substituents;

[0028] Figure 2d This is a table illustrating the structures of some compounds (I-87 to I-106) of a arecoline derivative containing an amino acid fragment, after the general formula of the structure has been replaced by substituents.

[0029] Figure 3a This is a table showing the antibacterial activity test results (100 mg / L) of some compounds (Ⅰ-1~Ⅰ-6) of the arecoline derivative containing amino acid fragments after substituent substitution.

[0030] Figure 3b This is a table showing the antibacterial activity test results (100 mg / L) of some compounds (Ⅰ-6~Ⅰ-34) of a arecoline derivative containing amino acid fragments after substituent replacement.

[0031] Figure 3c This is a table showing the antibacterial activity test results (100 mg / L) of some compounds (Ⅰ-35~Ⅰ-62) of the arecoline derivative containing amino acid fragments of the present invention after substituents were replaced;

[0032] Figure 3d This is a table showing the antibacterial activity test results (100 mg / L) of some compounds (Ⅰ-63~Ⅰ-91) of a arecoline derivative containing an amino acid fragment after being replaced by substituents according to the present invention.

[0033] Figure 3e Table of antibacterial activity test results (100 mg / L) of some compounds (Ⅰ-92~Ⅰ-106) of arecoline derivative containing amino acid fragments after substituent substitution;

[0034] Figure 3f Table showing the antibacterial activity test results (100 mg / L) of arecoline, chlorothalonil, and prochloraz. Detailed Implementation

[0035] To enable those skilled in the art to better understand the technical solution of the present invention, the technical solution of the arecoline derivative containing amino acid fragments, its preparation method, and its application will be further described below with reference to the accompanying drawings and specific embodiments.

[0036] A arecoline derivative containing amino acid fragments, with the general structural formula (1),

[0037]

[0038] Where the X group represents O or NH; n can take the value of 0, 1, 2 or 3;

[0039] In the structural formula (Ⅰ) of the arecoline derivative containing an amino acid fragment described above, R 1 Selected from hydrogen atom, methyl, ethyl, cyclopropyl, isopropyl, tert-butyl.

[0040] In the structural formula (Ⅰ) of the arecoline derivative containing an amino acid fragment described above, R 2 Selected from hydrogen atom, methyl, isopropyl, isobutyl, sec-butyl, benzyl and CH3SCH2CH2.

[0041] In the structural formula (Ⅰ) of the arecoline derivative containing an amino acid fragment described above, R 3 Selected from aryl, aliphatic heterocycles, oxygen heterocycles, nitrogen heterocycles, sulfur heterocycles, aromatic heterocycles, benzo[a] heterocycles, or fused rings with substituents, wherein R 3 The substituents on it are halogen atoms such as fluorine, chlorine and bromine, as well as mono- or poly-substituted groups such as methyl, isopropyl, tert-butyl, methoxy, nitro, cyano, trifluoromethoxy, and trifluoromethyl.

[0042] The above-described method for preparing arecoline derivatives containing amino acid fragments comprises the following steps:

[0043]

[0044] The reaction yielded:

[0045] The preparation method described above uses trifluoroacetic acid for deprotection under ice bath conditions. Other reactions can be carried out at room temperature, and post-processing can be performed according to conventional methods.

[0046] The application of arecoline derivatives containing amino acid fragments as agricultural fungicides as described above.

[0047] The specific preparation method of the compound of the present invention is illustrated below through implementation examples:

[0048] Example 1

[0049] The structural formula of the arecoline derivative containing amino acid fragments in this embodiment is shown in formula (Ⅰ-11).

[0050]

[0051] Its synthesis method is as follows:

[0052] In a round-bottom flask, 2-fluorobenzyl alcohol (1.2 mmol, 151 mg), BOC-Val-OH (1.5 mmol, 325 mg), DMAP (0.5 mmol, 61 mg), and 5 mL of dichloromethane were added sequentially and stirred until homogeneous. Then, EDCI (1.5 mmol, 285 mg) was added. The reaction was stirred at room temperature for 3 h, and the reaction was monitored by TLC. After the reaction was complete, ethyl acetate (30 mL) was added, and the mixture was washed successively with water, saturated sodium bicarbonate, and saturated brine, and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain intermediate 2, which could be used directly in subsequent reactions without purification.

[0053] Transfer intermediate 2 to a 25 mL round-bottom flask, add 4 mL of dichloromethane, and place in an ice bath. Add 2 mL of trifluoroacetic acid dropwise to the flask using a dropping funnel. After reacting for 2 hours, adjust the pH to weakly alkaline (8-9) using saturated sodium carbonate. Extract the mixture with dichloromethane (×20), combine the organic phases, wash with saturated brine, dry to anhydrous sodium sulfate, filter, and concentrate under reduced pressure to obtain a colorless oily liquid or a white solid. Transfer the product to a 25 mL reaction flask, add arecoline (1 mmol, 141 mg), DMAP (0.5 mmol, 61 mg), and 5 mL of dichloromethane sequentially, and stir until homogeneous. Then add EDCI (2 mmol, 383 mg). Stir the reaction overnight at room temperature, monitoring the reaction progress by TLC. After the reaction is complete, add 30 mL of ethyl acetate, wash successively with water, saturated sodium bicarbonate, and saturated brine, and dry to anhydrous sodium sulfate. Compound I-1 was obtained by vacuum filtration, concentration under reduced pressure, and column chromatography (eluent: DCM / MeOH = 15 / 1).

[0054] The hydrogen NMR spectrum of the compound 1 H NMR(400MHz, CDCl3)δ0.87(d,J=6.86Hz,6H),2.12–2.22(m,1H),2.29–2.35(m,2H),2.38(s,3H),2.43–2.55(m,2H),3.06–3.23(m,2H) ), 4.65(dd,J=4.77,8.69Hz,1H),5.13–5.30(m,2H),6.17(d,J=8.70Hz,1H),6.50–6.59(m,1H),6.99–7.16(m,2H),7.28–7.41(m,2H).

[0055] Example 2

[0056] The structural formula of the arecoline derivative containing amino acid fragments in this embodiment is shown in formula (Ⅰ-13).

[0057]

[0058] Its synthesis method is as follows:

[0059] In a round-bottom flask, 2-chloro-5-hydroxymethylpyridine (1.2 mmol, 172 mg), BOC-Val-OH (1.5 mmol, 325 mg), DMAP (0.5 mmol, 61 mg), and 5 mL of dichloromethane were added sequentially and stirred until homogeneous. Then, EDCI (1.5 mmol, 285 mg) was added. The reaction was stirred at room temperature for 3 h, and the reaction was monitored by TLC. After the reaction was complete, ethyl acetate (30 mL) was added, and the mixture was washed successively with water, saturated sodium bicarbonate, and saturated brine, and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain intermediate 2, which could be used directly in subsequent reactions without purification.

[0060] Transfer intermediate 2 to a 25 mL round-bottom flask, add 4 mL of dichloromethane, and place in an ice bath. Add 2 mL of trifluoroacetic acid dropwise to the flask using a dropping funnel. After reacting for 2 hours, adjust the pH to weakly alkaline (8-9) using saturated sodium carbonate. Extract the mixture with dichloromethane (×20), combine the organic phases, wash with saturated brine, dry to anhydrous sodium sulfate, filter, and concentrate under reduced pressure to obtain a colorless oily liquid or a white solid. Transfer the product to a 25 mL reaction flask, add arecoline (1 mmol, 141 mg), DMAP (0.5 mmol, 61 mg), and 5 mL of dichloromethane sequentially, and stir until homogeneous. Then add EDCI (2 mmol, 383 mg). Stir the reaction overnight at room temperature, monitoring the reaction progress by TLC. After the reaction is complete, add 30 mL of ethyl acetate, wash successively with water, saturated sodium bicarbonate, and saturated brine, and dry to anhydrous sodium sulfate. Compound I-13 was obtained by vacuum filtration, concentration under reduced pressure, and column chromatography (eluent: DCM / MeOH = 15 / 1).

[0061] The 1H NMR spectrum of compound I-13 1 H NMR(400MHz, CDCl3)δ0.87(d,J=6.90Hz,3H),0.91(d,J=6.85Hz,3H),2.16(pd,J=5.02, 6.85Hz,1H),2.30–2.37(m,2H),2.39(s,3H),2.50(td,J=3.00,5.70Hz,2H),3.06–3.25( m,2H),4.61(dd,J=5.02,8.57Hz,1H),5.08–5.25(m,2H),6.15(d,J=8.57Hz,1H),6.55( m,1H),7.33(dd,J=0.74,8.28Hz,1H),7.67(dd,J=2.53,8.20Hz,1H),8.35–8.43(m,1H).

[0062] Example 3

[0063] The structural formula of the arecoline derivative containing amino acid fragments in this embodiment is shown in formula (Ⅰ-27).

[0064]

[0065] Its synthesis method is as follows:

[0066] In a round-bottom flask, 1.2 mmol (137 mg) of 2-thiophene methanol, 1.5 mmol (325 mg) of BOC-Val-OH, 0.5 mmol (61 mg) of DMAP, and 5 mL of dichloromethane were added sequentially and stirred until homogeneous. Then, 1.5 mmol (285 mg) of EDCI was added. The reaction was stirred at room temperature for 3 h, and the reaction was monitored by TLC. After the reaction was complete, 30 mL of ethyl acetate was added, and the mixture was washed successively with water, saturated sodium bicarbonate, and saturated brine, and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain intermediate 2, which could be used directly in subsequent reactions without purification.

[0067] Transfer intermediate 2 to a 25 mL round-bottom flask, add 4 mL of dichloromethane, and place in an ice bath. Add 2 mL of trifluoroacetic acid dropwise to the flask using a dropping funnel. After reacting for 2 hours, adjust the pH to weakly alkaline (8-9) using saturated sodium carbonate. Extract the mixture with dichloromethane (×20), combine the organic phases, wash with saturated brine, dry to anhydrous sodium sulfate, filter, and concentrate under reduced pressure to obtain a colorless oily liquid or a white solid. Transfer the product to a 25 mL reaction flask, add arecoline (1 nmol, 141 mg), DMAP (0.5 mmol, 61 mg), and 5 mL of dichloromethane sequentially, and stir until homogeneous. Then add EDCI (2 nmol, 383 mg). Stir the reaction overnight at room temperature, monitoring the reaction progress by TLC. After the reaction is complete, add 30 mL of ethyl acetate, wash successively with water, saturated sodium bicarbonate, and saturated brine, and dry to anhydrous sodium sulfate. Compound I-27 was obtained by vacuum filtration, concentration under reduced pressure, and column chromatography (eluent: DCM / MeOH = 15 / 1).

[0068] The 1H NMR spectrum of compound I-27 1H NMR(400MHz, CDCl3)δ0.89(dd,J=6.8,1.5Hz,3H),0.93(dd,J=6.7,1.5Hz,3H),2.13–2.03(m,1H),2.27–2.14(m,2H),2.36(s,3H),2.8 3(t,J=4.8Hz,2H),3.58(m,2H),4.33–4.24(m,1H),5.32–5.20(m,2H),6.76(m,1H),6.95(m,1H),7.02–6.98(m,1H)7.28–7.25(m,2H).

[0069] Example 4

[0070] The structural formula of the arecoline derivative containing amino acid fragments in this embodiment is shown in formula (I-31).

[0071]

[0072] Its synthesis method is as follows:

[0073] In a round-bottom flask, 3-phenoxybenzyl alcohol (1.2 mmol, 240 mg), BOC-Leu-OH (1.5 mmol, 347 mg), DMAP (0.5 mmol, 61 mg), and 5 mL of dichloromethane were added sequentially and stirred until homogeneous. Then, EDCI (1.5 mmol, 285 mg) was added. The reaction was stirred at room temperature for 3 h, and the reaction was monitored by TLC. After the reaction was complete, ethyl acetate (30 mL) was added, and the mixture was washed successively with water, saturated sodium bicarbonate, and saturated brine, and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain intermediate 2, which could be used directly in subsequent reactions without purification.

[0074] Transfer intermediate 2 to a 25 mL round-bottom flask, add 4 mL of dichloromethane, and place in an ice bath. Add 2 mL of trifluoroacetic acid dropwise to the flask using a dropping funnel. After reacting for 2 hours, adjust the pH to weakly alkaline (8-9) using saturated sodium carbonate. Extract the mixture with dichloromethane (×20), combine the organic phases, wash with saturated brine, dry to anhydrous sodium sulfate, filter, and concentrate under reduced pressure to obtain a colorless oily liquid or a white solid. Transfer the product to a 25 mL reaction flask, add arecoline (1 mmol, 141 mg), DMAP (0.5 mmol, 61 mg), and 5 mL of dichloromethane sequentially, and stir until homogeneous. Then add EDCI (2 mmol, 383 mg). Stir the reaction overnight at room temperature, monitoring the reaction progress by TLC. After the reaction is complete, add 30 mL of ethyl acetate, wash successively with water, saturated sodium bicarbonate, and saturated brine, and dry to anhydrous sodium sulfate. Compound I-31 was obtained by vacuum filtration, concentration under reduced pressure, and column chromatography (eluent: DCM / MeOH = 15 / 1).

[0075] The 1H NMR spectrum of compound I-31 1 H NMR (400MHz, CDCl3) δ0.85–0.98(m,6H),1.45–1.73(m,3H),2.28–2.36(m,2H),3.39(s,3H),2.44–2.54(m,2H),3.07–3.24(m ,2H),4.68–4.77(m,1H),5.06–5.20(m,2H),6.10(d,J=8.28Hz,1H),6.51–6.57(m,1H),6.93–7.13(m,6H),7.27–7.40(m,3H).

[0076] Example 5

[0077] The structural formula of the arecoline derivative containing amino acid fragments in this embodiment is shown in formula (I-36).

[0078]

[0079] Its synthesis method is as follows:

[0080] In a round-bottom flask, 3,5-dichlorobenzyl alcohol (1.2 mmol, 240 mg), BOC-Ile-OH (1.5 mmol, 347 mg), DMAP (0.5 mmol, 61 mg), and 5 mL of dichloromethane were added sequentially and stirred until homogeneous. Then, EDCI (1.5 mmol, 285 mg) was added. The reaction was stirred at room temperature for 3 h, and the reaction was monitored by TLC. After the reaction was complete, ethyl acetate (30 mL) was added, and the mixture was washed successively with water, saturated sodium bicarbonate, and saturated brine, and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain intermediate 2, which could be used directly in subsequent reactions without purification.

[0081] Transfer intermediate 2 to a 25 mL round-bottom flask, add 4 mL of dichloromethane, and place in an ice bath. Add 2 mL of trifluoroacetic acid dropwise to the flask using a dropping funnel. After reacting for 2 hours, adjust the pH to weakly alkaline (8-9) using saturated sodium carbonate. Extract the mixture with dichloromethane (×20), combine the organic phases, wash with saturated brine, dry to anhydrous sodium sulfate, filter, and concentrate under reduced pressure to obtain a colorless oily liquid or a white solid. Transfer the product to a 25 mL reaction flask, add arecoline (1 mmol, 141 mg), DMAP (0.5 mmol, 61 mg), and 5 mL of dichloromethane sequentially, and stir until homogeneous. Then add EDCI (2 mmol, 383 mg). Stir the reaction overnight at room temperature, monitoring the reaction progress by TLC. After the reaction is complete, add 30 mL of ethyl acetate, wash successively with water, saturated sodium bicarbonate, and saturated brine, and dry to anhydrous sodium sulfate. Compound I-36 was obtained by vacuum filtration, concentration under reduced pressure, and column chromatography (eluent: DCM / MeOH = 15 / 1).

[0082] The 1H NMR spectrum of compound I-36 1 H NMR(400MHz, CDCl3)δ0.75–0.91(m,6H),1.01–1.15(m,1H),1.24–1.40(m,1H),1.79–1.92(m,1H),2.20–2.28(m,2H),2.31(s,3H),2.36–2.46(m ,2H),2.98–3.16(m,2H),4.55–4.66(m,1H),4.92–5.11(m,2H),6.16(d, J=8.77Hz,1H),6.42–6.53(m,1H),7.12–7.17(m,2H),7.19–7.24(m,1H).

[0083] Example 6

[0084] The structural formula of the arecoline derivative containing amino acid fragments in this embodiment is shown in formula (I-56).

[0085]

[0086] Its synthesis method is as follows:

[0087] In a round-bottom flask, 2-amino-4-trifluoromethylpyridine (1.2 mmol, 195 mg), BOC-Val-OH (1.5 mmol, 325 mg), DMAP (0.5 mmol, 61 mg), and 5 mL of dichloromethane were added sequentially and stirred until homogeneous. Then, EDCI (1.5 mmol, 285 mg) was added. The reaction was stirred at room temperature for 1 h, and the reaction was monitored by TLC. After the reaction was complete, CH2Cl2 (20 mL) was added, and the mixture was washed successively with saturated sodium bicarbonate and saturated brine, and dried over anhydrous magnesium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain a pale yellow solid, which could be used directly in subsequent reactions without purification.

[0088] Intermediate 2 was transferred to a 20 mL round-bottom flask and dissolved in 4 mL of dichloromethane. Trifluoroacetic acid (2 mL) was slowly added dropwise to the flask using a dropping funnel. The mixture was stirred at room temperature, and the reaction was monitored by TLC. After the reaction was complete, the mixture was transferred to a separatory funnel, and 10 mL of water was added for extraction. The aqueous layer was collected, and the pH was adjusted to alkaline (9–10) using saturated sodium carbonate. The aqueous layer was then extracted with 30 mL of dichloromethane. The organic phases were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to obtain a pale yellow oily liquid. The product was transferred to a 25 mL reaction flask, and arecoline (1 mmol, 141 mg), DMAP (0.5 mmol, 61 mg), and 5 mL of dichloromethane were added sequentially. The mixture was stirred until homogeneous, and then EDCI (2 mmol, 383 mg) was added. The mixture was stirred overnight at room temperature, and the reaction was monitored by TLC. After the reaction was complete, dichloromethane (20 mL) was added, and the mixture was washed successively with saturated sodium bicarbonate and saturated brine, and dried over anhydrous sodium sulfate. The mixture was then filtered, concentrated under reduced pressure, and separated by column chromatography (eluent: dichloromethane: methanol = 15:1) to obtain the target compound I-56.

[0089] The compound's I-56 proton NMR spectrum, 1H NMR(400MHz, CDCl3)δ9.44(d,J=46.6Hz,1H),8.58–8.53(m,1H),8.34(d,J=8.8Hz, 1H),7.92(dd,J=8.9,2.5Hz,1H),6.74–6.68(m,J=1.9Hz,1H),6.56–6.45(m,1H),4 .85–4.71(m,1H),3.37–3.15(m,2H),2.59–2.49(m,2H),2.44(s,3H),2.41–2.34(m ,2H),2.30–2.20(m,1H),1.04(dd,J=6.7,1.7Hz,3H),1.01(dd,J=6.8,1.7Hz,3H).

[0090] Example 7

[0091] The structural formula of the arecoline derivative containing amino acid fragments in this embodiment is shown in formula (I-61).

[0092]

[0093] Its synthesis method is as follows:

[0094] In a round-bottom flask, 3-phenoxyaniline (1.2 mmol, 222 mg), BOC-Val-OH (1.5 mmol, 325 mg), DMAP (0.5 mmol, 61 mg), and 5 mL of dichloromethane were added sequentially and stirred until homogeneous. Then, EDCI (1.5 mmol, 285 mg) was added. The reaction was stirred at room temperature for 1 h, and the reaction was monitored by TLC. After the reaction was complete, CH2Cl2 (20 mL) was added, and the mixture was washed successively with saturated sodium bicarbonate and saturated brine, and dried over anhydrous magnesium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain a pale yellow solid, which could be used directly in subsequent reactions without purification.

[0095] Intermediate 2 was transferred to a 20 mL round-bottom flask and dissolved in 4 mL of dichloromethane. Trifluoroacetic acid (2 mL) was slowly added dropwise to the flask using a dropping funnel. The mixture was stirred at room temperature, and the reaction was monitored by TLC. After the reaction was complete, the mixture was transferred to a separatory funnel, and 10 mL of water was added for extraction. The aqueous layer was collected, and the pH was adjusted to alkaline (9–10) using saturated sodium carbonate. The aqueous layer was then extracted with 30 mL of dichloromethane. The organic phases were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to obtain a pale yellow oily liquid. The product was transferred to a 25 mL reaction flask, and arecoline (1 mmol, 141 mg), DMAP (0.5 mmol, 61 mg), and 5 mL of dichloromethane were added sequentially. The mixture was stirred until homogeneous, and then EDCI (2 mmol, 383 mg) was added. The mixture was stirred overnight at room temperature, and the reaction was monitored by TLC. After the reaction was complete, dichloromethane (20 mL) was added, and the mixture was washed successively with saturated sodium bicarbonate and saturated brine, and dried over anhydrous sodium sulfate. The mixture was then filtered, concentrated under reduced pressure, and separated by column chromatography (eluent: dichloromethane: methanol = 15:1) to obtain the target compound I-61.

[0096] The compound's NMR I-61 1H spectrum, 1 H NMR (400MHz, CDCl3) δ0.88 (dd, J=1.46, 6.58Hz, 3H), 0.92 (dd, J=1.46, 6.59Hz, 3H),2.05(m,1H),2.22(m,2H),2.35(s,3H),2.71–2.78(m,2H),3.58(m,2H),4. 39(m,1H),6.66–6.72(m,1H),6.76(m,1H),6.98–7.03(m,2H),7.10(m,1H),7.2 4–7.27(m,1H),7.27–7.30(m,2H),7.32–7.37(m,2H),8.01(m,1H),9.01(s,1H).

[0097] Example 8

[0098] The structural formula of the arecoline derivative containing amino acid fragments in this embodiment is shown in formula (I-65).

[0099]

[0100] Its synthesis method is as follows:

[0101] In a round-bottom flask, 5-thiazolamide (1.2 mmol, 120 mg), BOC-Val-OH (1.5 mmol, 325 mg), DMAP (0.5 mmol, 61 mg), and 5 mL of dichloromethane were added sequentially and stirred until homogeneous. Then, EDCI (1.5 mmol, 285 mg) was added. The reaction was stirred at room temperature for 1 h, and the reaction was monitored by TLC. After the reaction was complete, CH2Cl2 (20 mL) was added, and the mixture was washed successively with saturated sodium bicarbonate and saturated brine, and dried over anhydrous magnesium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain a pale yellow solid, which could be used directly in subsequent reactions without purification.

[0102] Intermediate 2 was transferred to a 20 mL round-bottom flask and dissolved in 4 mL of dichloromethane. Trifluoroacetic acid (2 mL) was slowly added dropwise to the flask using a dropping funnel. The mixture was stirred at room temperature, and the reaction was monitored by TLC. After the reaction was complete, the mixture was transferred to a separatory funnel, and 10 mL of water was added for extraction. The aqueous layer was collected, and the pH was adjusted to alkaline (9–10) using saturated sodium carbonate. The aqueous layer was then extracted with 30 mL of dichloromethane. The organic phases were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to obtain a pale yellow oily liquid. The product was transferred to a 25 mL reaction flask, and arecoline (1 mmol, 141 mg), DMAP (0.5 mmol, 61 mg), and 5 mL of dichloromethane were added sequentially. The mixture was stirred until homogeneous, and then EDCI (2 mmol, 383 mg) was added. The mixture was stirred overnight at room temperature, and the reaction was monitored by TLC. After the reaction was complete, 20 mL of dichloromethane was added, and the mixture was washed successively with saturated sodium bicarbonate and saturated brine, and dried over anhydrous sodium sulfate. The mixture was then filtered, concentrated under reduced pressure, and separated by column chromatography (eluent: dichloromethane: methanol = 15:1) to obtain the target compound I-65.

[0103] The compound's NMR I-65 1H spectrum, 1 H NMR (400MHz, CDCl3) δ9.51(s,1H),8.33(d,J=1.8Hz,1H),8.13(d,J=1.8Hz,1H),8.01(m,1H),6.77(m,1H),4.54(m,1H),3.59(m,2H),2.84(m ,2H),2.36(s,3H),2.23(tdt,J=5.2,3.5,1.0Hz,2H),2.12–2.01(m,J=6.5Hz,1H),0.93(dd,J=6.6,1.5Hz,3H),0.89(dd,J=6.6,1.5Hz,3H).

[0104] Example 9

[0105] The structural formula of the arecoline derivative containing amino acid fragments in this embodiment is shown in formula (I-73).

[0106]

[0107] Its synthesis method is as follows:

[0108] In a round-bottom flask, 2-amino-6-chloropyridine (1.2 mmol, 154 mg), BOC-Leu-OH (1.5 mmol, 347 mg), DMAP (0.5 mmol, 61 mg), and 5 mL of dichloromethane were added sequentially and stirred until homogeneous. Then, EDCI (1.5 mmol, 285 mg) was added. The reaction was stirred at room temperature for 1 h, and the reaction was monitored by TLC. After the reaction was complete, CH2Cl2 (20 mL) was added, and the mixture was washed successively with saturated sodium bicarbonate and saturated brine, and dried over anhydrous magnesium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain a pale yellow solid, which could be used directly in subsequent reactions without purification.

[0109] Intermediate 2 was transferred to a 20 mL round-bottom flask and dissolved in 4 mL of dichloromethane. Trifluoroacetic acid (2 mL) was slowly added dropwise to the flask using a dropping funnel. The mixture was stirred at room temperature, and the reaction was monitored by TLC. After the reaction was complete, the mixture was transferred to a separatory funnel, and 10 mL of water was added for extraction. The aqueous layer was collected, and the pH was adjusted to alkaline (9–10) using saturated sodium carbonate. The aqueous layer was then extracted with 30 mL of dichloromethane. The organic phases were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to obtain a pale yellow oily liquid. The product was transferred to a 25 mL reaction flask, and arecoline (1 mmol, 141 mg), DMAP (0.5 mmol, 61 mg), and 5 mL of dichloromethane were added sequentially. The mixture was stirred until homogeneous, and then EDCI (2 mmol, 383 mg) was added. The mixture was stirred overnight at room temperature, and the reaction was monitored by TLC. After the reaction was complete, dichloromethane (20 mL) was added, and the mixture was washed successively with saturated sodium bicarbonate and saturated brine, and dried over anhydrous sodium sulfate. The mixture was then filtered, concentrated under reduced pressure, and separated by column chromatography (eluent: dichloromethane: methanol = 15:1) to obtain the target compound I-73.

[0110] The compound's NMR I-73 1H spectrum, 1 H NMR(400MHz, CDCl3)δ0.81–0.88(m,6H),1.41(m,1H),1.57(m,1H),1.68(m,1H),2.21(m,2H),2.34(s,3H),2.69–2.79(m,2H),3.5 6(q,J=0.99Hz,2H),4.39(m,1H),6.74(m,1H),7.23–7.27(m,1H),7.35(d,J=8.05Hz,1H),7.40(m,1H),7.67(m,1H),8.78(s,1H).

[0111] Example 10

[0112] The structural formula of the arecoline derivative containing amino acid fragments in this embodiment is shown in formula (I-79).

[0113]

[0114] Its synthesis method is as follows:

[0115] In a round-bottom flask, 2-amino-3,5-dichloropyridine (1.2 mmol, 196 mg), BOC-Ile-OH (1.5 mmol, 347 mg), DMAP (0.5 mmol, 61 mg), and 5 mL of dichloromethane were added sequentially and stirred until homogeneous. Then, EDCI (1.5 mmol, 285 mg) was added. The reaction was stirred at room temperature for 1 h, and the reaction was monitored by TLC. After the reaction was complete, CH2Cl2 (20 mL) was added, and the mixture was washed successively with saturated sodium bicarbonate and saturated brine, and dried over anhydrous magnesium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain a pale yellow solid, which could be used directly in subsequent reactions without purification.

[0116] Intermediate 2 was transferred to a 20 mL round-bottom flask and dissolved in 4 mL of dichloromethane. Trifluoroacetic acid (2 mL) was slowly added dropwise to the flask using a dropping funnel. The mixture was stirred at room temperature, and the reaction was monitored by TLC. After the reaction was complete, the mixture was transferred to a separatory funnel, and 10 mL of water was added for extraction. The aqueous layer was collected, and the pH was adjusted to alkaline (9–10) using saturated sodium carbonate. The aqueous layer was then extracted with 30 mL of dichloromethane. The organic phases were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to obtain a pale yellow oily liquid. The product was transferred to a 25 mL reaction flask, and arecoline (1 mmol, 141 mg), DMAP (0.5 mmol, 61 mg), and 5 mL of dichloromethane were added sequentially. The mixture was stirred until homogeneous, and then EDCI (2 mmol, 383 mg) was added. The mixture was stirred overnight at room temperature, and the reaction was monitored by TLC. After the reaction was complete, dichloromethane (20 mL) was added, and the mixture was washed successively with saturated sodium bicarbonate and saturated brine, and dried over anhydrous sodium sulfate. The mixture was then filtered, concentrated under reduced pressure, and separated by column chromatography (eluent: dichloromethane: methanol = 15:1) to obtain the target compound I-79.

[0117] The compound's NMR I-79 1H spectrum, 1H NMR (400MHz, CDCl3) δ8.19 (s, 1H), 7.42 (m, 1H), 7.30 (d, J = 8.4Hz, 1H), 7.26 (s, 1H), 6.26 (m, 1H), 4.02 (m, 1H), 3.08 (q, J=0.96Hz,2H),2.35–2.13(m,2H),1.85(s,3H),1.72(m,2H),1.43(m,1H),1.01(m,1H),0.70(m,1H),0.33–0.40(m,6H).

[0118] Example 11

[0119] The structural formula of the arecoline derivative containing amino acid fragments in this embodiment is shown in formula (I-91).

[0120]

[0121] Its synthesis method is as follows:

[0122] In a round-bottom flask, 3,5-dichlorobenzyl alcohol (1.2 mmol, 240 mg), BOC-Ala-OH (1.2 mmol, 107 mg), DMAP (0.5 mmol, 61 mg), and 5 mL of dichloromethane were added sequentially and stirred until homogeneous. Then, EDCI (1.5 mmol, 285 mg) was added. The reaction was stirred at room temperature for 1 h, and the reaction was monitored by TLC. After the reaction was complete, CH2Cl2 (20 mL) was added, and the mixture was washed successively with saturated sodium bicarbonate and saturated brine, and dried over anhydrous magnesium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain a pale yellow solid, which could be used directly in subsequent reactions without purification.

[0123] Transfer intermediate 2 to a 25 mL round-bottom flask, add 4 mL of dichloromethane, and place in an ice bath. Add 2 mL of trifluoroacetic acid dropwise to the flask using a dropping funnel. After reacting for 2 hours, adjust the pH to weakly alkaline (8-9) using saturated sodium carbonate. Extract the mixture with dichloromethane (×20), combine the organic phases, wash with saturated brine, dry to anhydrous sodium sulfate, filter, and concentrate under reduced pressure to obtain a colorless oily liquid or a white solid. Transfer the product to a 25 mL reaction flask, add arecoline (1 mmol, 141 mg), DMAP (0.5 mmol, 61 mg), and 5 mL of dichloromethane sequentially, and stir until homogeneous. Then add EDCI (2 mmol, 383 mg). Stir the reaction overnight at room temperature, monitoring the reaction progress by TLC. After the reaction is complete, add 30 mL of ethyl acetate, wash successively with water, saturated sodium bicarbonate, and saturated brine, and dry to anhydrous sodium sulfate. The intermediate was obtained by filtration, concentration under reduced pressure, and column chromatography (eluent: DCM / MeOH = 15 / 1). The intermediate was transferred to a 20 mL Schlenk flask, and 2-iodopropane (1 mmol, 170 mg) and anhydrous potassium carbonate (3 mmol, 414 mg) were added sequentially. 5 mL of LDM was added, and the mixture was heated to 50 °C for 2 h. The reaction was monitored by TLC. After the reaction was complete, ethyl acetate (30 mL) was added, and the mixture was washed successively with water, saturated sodium bicarbonate, and saturated brine, and dried over anhydrous sodium sulfate. The mixture was then filtered, concentrated under reduced pressure, and separated by column chromatography to obtain the target compound I-91.

[0124] The compound's I-91 proton NMR spectrum, 1 H NMR (400MHz, CDCl3) δ7.26(m,2H),7.22(m,1H),6.77–6.73(m,1H),5.27–5.17(m,2H),4.52(q,J=7.5Hz,1H),4.06–3.97(m, 1H), 3.50 (q, J = 1.1Hz, 2H), 2.77–2.73 (m, 2H), 2.17–2.12 (m, 2H), 1.36 (m, 3H), 1.31 (d, J = 7.0Hz, 3H), 1.20 (d, J = 7.0Hz, 3H).

[0125] Example 12

[0126] The structural formula of the arecoline derivative containing amino acid fragments in this embodiment is shown in formula (I-104).

[0127]

[0128] Its synthesis method is as follows:

[0129] In a round-bottom flask, 3-phenoxybenzyl alcohol (1.2 mmol, 240 mg), BOC-Ala-OH (1.2 mmol, 107 mg), DMAP (0.5 mmol, 61 mg), and 5 mL of dichloromethane were added sequentially and stirred until homogeneous. Then, EDCI (1.5 mmol, 285 mg) was added. The reaction was stirred at room temperature for 1 h, and the reaction was monitored by TLC. After the reaction was complete, CH2Cl2 (20 mL) was added, and the mixture was washed successively with saturated sodium bicarbonate and saturated brine, and dried over anhydrous magnesium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain a pale yellow solid, which could be used directly in subsequent reactions without purification.

[0130] Transfer intermediate 2 to a 25 mL round-bottom flask, add 4 mL of dichloromethane, and place in an ice bath. Add 2 mL of trifluoroacetic acid dropwise to the flask using a dropping funnel. After reacting for 2 hours, adjust the pH to weakly alkaline (8-9) using saturated sodium carbonate. Extract the mixture with dichloromethane (×20), combine the organic phases, wash with saturated brine, dry to anhydrous sodium sulfate, filter, and concentrate under reduced pressure to obtain a colorless oily liquid or a white solid. Transfer the product to a 25 mL reaction flask, add arecoline (1 mmol, 141 mg), DMAP (0.5 mmol, 61 mg), and 5 mL of dichloromethane sequentially, and stir until homogeneous. Then add EDCI (2 mmol, 383 mg). Stir the reaction overnight at room temperature, monitoring the reaction progress by TLC. After the reaction is complete, add 30 mL of ethyl acetate, wash successively with water, saturated sodium bicarbonate, and saturated brine, and dry to anhydrous sodium sulfate. The intermediate was obtained by filtration, concentration under reduced pressure, and column chromatography (eluent: DCM / MeOH = 15 / 1). The intermediate was transferred to a 20 mL Schlenk flask, and bromocyclopropane (1 mmol, 120 mg) and anhydrous potassium carbonate (3 mmol, 414 mg) were added sequentially. 5 mL of LDM was added, and the mixture was heated to 80 °C for 2 h. The reaction was monitored by TLC. After the reaction was complete, ethyl acetate (30 mL) was added, and the mixture was washed successively with water, saturated sodium bicarbonate, and saturated brine, and dried over anhydrous sodium sulfate. The mixture was then filtered, concentrated under reduced pressure, and separated by column chromatography to obtain the target compound I-104.

[0131] The compound's NMR I-104 proton NMR spectrum, 1H NMR(400MHz, CDCl3)δ7.39–7.33(m,2H),7.26(d,J=15.8Hz,1H),7.15–7.10 (m,2H),7.04–7.01(m,2H),6.95–6.91(m,1H),6.85–6.82(m,1H),6.79–6.7 5(m,1H),5.23–5.11(m,2H),4.53(m,1H),3.52(m,2H),3.47–3.40(m,1H),2 .81–2.74(m,2H),2.19–2.12(m,2H),1.70–1.59(m,2H),1.43–1.36(m,5H).

[0132] The structural descriptions of some compounds (Ⅰ-1 to Ⅰ-106) after the structure of Formula I is replaced by substituents are as follows: Figure 1 As shown, other compounds described in this invention can be prepared using the above method.

[0133] Application examples

[0134] The antibacterial bioactivity of the arecoline derivative containing amino acid fragments prepared by the above steps of the present invention was determined as follows, and the experimental method used was the mycelial growth rate method.

[0135] The tested bacterial strains were *Magnaporthe oryzae* (rice blast fungus), *Botryodipladia theobromae* (mango stem rot fungus), *Bipolaris cactivora* (dragon fruit black spot fungus), *Bothryosphaeria dothidea* (apple ring rot fungus), *Colletotrichum musae* (banana anthracnose fungus), *Fusarium verticillioides* (wheat stem rot fungus), *Rhizoctonia solani* (rice sheath blight fungus), *Sclerotinia sclerotiorum* (rapeseed sclerotinia sclerotiorum), and *Phytophthora capsici* (pepper rot fungus), provided by the College of Tropical Agriculture and Forestry, Hainan University.

[0136] The arecoline derivative test reagent containing amino acid fragments of the present invention was prepared into a solution with a mass concentration of 100 mg / L. Mycelial cakes were collected using a 5 mm diameter punch and inoculated onto potato dextrose agar medium containing the test reagent. A medium containing the same solvent and adjuvants was used as a control. Each group was repeated three times, and colony growth was observed. When the diameter of the blank control colonies reached 2 / 3 of the entire plate, the colony diameter was measured vertically and crosswise to calculate the inhibition rate.

[0137] Result processing:

[0138] Inhibition rate (%) = [(average colony diameter of control group - average colony diameter of treatment group) / (average colony diameter of control group - diameter of mycelial cake)] × 100%

[0139] Based on the inhibition rate against plant pathogenic fungi, five levels are defined: 90≤A≤100%; 80≤B<90%; 70≤C<80%; 60≤D<70%; and E<60%.

[0140] The antibacterial activity test results of some compounds of this invention are shown in Figure 2. As can be seen from the bioassay results in Figure 2, the arecoline derivative containing amino acid fragments provided by this invention has excellent antibacterial activity against plant pathogenic fungi at a concentration of 100 mg / L. It can be used as an active ingredient in chemical pesticides for the control of plant pathogens, and can be mixed with other permitted carriers or adjuvants in plant protection to formulate various formulations usable in agriculture.

[0141] In summary, the arecoline derivative containing amino acid fragments provided by this invention exhibits excellent inhibitory activity against agricultural plant pathogens, is suitable for the prevention and control of agricultural plant pathogens, and can be used for the development and use of effective components in the preparation of agricultural fungicides or adjuvants.

[0142] Obviously, the embodiments described above are merely some embodiments of the present invention, not all embodiments, and are not intended to limit the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention should be included within the protection scope of the present invention.

Claims

1. A myristicin derivative comprising an amino acid fragment, characterized in that, The structural general formula is formula (I), ， Formula (I) is I-12, I-13, I-14, I-31, I-32, I-33, I-34, I-35, I-36, I-37, I-38, I-39, I-40, I-41, I-42, I-55, I-76, I-81, I-83, I-84, I-85, I-86, I-87, I-88, I-89, I-90, I-91, I-92, I-93, I-94, I-95, I-96, I-97, I-98, I-99, I-100, I-101, I-102, I-103, I-104, I-105, I-106; wherein the X group of I-12 is O, R 1 is H, R 2 is -CH(CH3)2, n has the value 1, R 3 is 3-OC6H5-C6H4; wherein the X group of I-13 is O, R 1 is H, R 2 is -CH(CH3)2, n has the value 1, R 3 is 4-OC6H5-C6H4; wherein the X group of I-14 is O, R 1 is H, R 2 is -CH(CH3)2, n has the value 1, R 3 is 3,5-dichlorophenyl; wherein the X group of I-31 is O, R 1 is H, R 2 is -CH2CH(CH3)2, n has the value 1, R 3 is 3-OC6H5-C6H4; wherein the X group of I-32 is O, R 1 is H, R 2 is -CH2CH(CH3)2, n has the value 1, R 3 is 4-OC6H5-C6H4; wherein the X group of I-33 is O, R 1 is H, R 2 is -CH2CH(CH3)2, n has the value 1, R 3 is 3,5-dichlorophenyl; wherein the X group of I-34 is O, R 1 is H, R 2 is -CH(CH3)CH2CH3, n has the value 1, R 3 is 3-OC6H5-C6H4; wherein the X group of I-35 is O, R 1 is H, R 2 is -CH(CH3)CH2CH3, n has the value 1, R 3 is 4-OC6H5-C6H4; wherein the X group of I-36 is O, R 1 is H, R 2 is -CH(CH3)CH2CH3, n has the value 1, R 3 is 3,5-dichlorophenyl; wherein the X group of I-37 is O, R 1 is H, R 2 is -CH2C6H5, n has the value 1, R 3 is 3-OC6H5-C6H4; wherein the X group of I-38 is O, R 1 is H, R 2 is -CH2C6H5, n has the value 1, R 3 is 4-OC6H5-C6H4; wherein the X group of I-39 is O, R 1 is H, R 2 is -CH2C6H5, n has the value 1, R 3 is 3,5-dichlorophenyl; wherein the X group of I-40 is O, R 1 is H, R 2 is -CH2CH2SCH3, n has the value 1, R 3 is 3-OC6H5-C6H4; wherein the X group of I-41 is O, R 1 is H, R 2 is -CH2CH2SCH3, n has the value 1, R 3 is 4-OC6H5-C6H4; wherein the X group of I-42 is O, R 1 is H, R 2 is -CH2CH2SCH3, n has the value 1, R 3 is 3,5-dichlorophenyl; wherein the X group of I-55 is NH, R 1 is H, R 2 is -CH(CH3)2, n has the value 0, R 3 is 5-Cl-C6H3; wherein the X group of I-76 is NH, R 1 is H, R 2 is -CH2CH(CH3)2, n has the value 0, R 3 is 3,5-dichlorophenyl; wherein the X group of I-81 is NH, R 1 is H, R 2 is -CH(CH3)CH2CH3, n has the value 0, R 3 is 3,5-dichlorophenyl; wherein the X group of I-83 is O, R 1 is CH3, R 2 is -CH3, n has the value 1, R 3 is 3-OC6H5-C6H4; wherein the X group of I-84 is O, R 1 is CH3, R 2 is -CH3, n has the value 1, R 3 is 4-OC6H5-C6H4; wherein the X group of I-85 is O, R 1 is CH3, R 2 is -CH3, n has the value 1, R 3 is 3,5-dichlorophenyl; wherein the X group of I-86 is O, R 1 is -CH2CH3, R 2 is -CH3, n has the value 1, R 3 is 3-OC6H5-C6H4; wherein the X group of I-87 is O, R 1 is -CH2CH3, R 2 is -CH3, n has the value 1, R 3 is 4-OC6H5-C6H4; wherein the X group of I-88 is O, R 1 is -CH2CH3, R 2 is -CH3, n has the value 1, R 3 is 3,5-dichlorophenyl; wherein the X group of I-89 is O, R 1 is -CH(CH3)2, R 2 is -CH3, n has the value 1, R 3 is 3-OC6H5-C6H4; wherein the X group of I-90 is O, R 1 is -CH(CH3)2, R 2 is -CH3, n has the value 1, R 3 is 4-OC6H5-C6H4; wherein the X group of I-91 is O, R 1 is -CH(CH3)2, R 2 is -CH3, n has the value 1, R 3 is 3,5-dichlorophenyl; wherein the X group of I-92 is O, R 1 is -C3H5, R 2 is -CH3, n has the value 1, R 3 is 3-OC6H5-C6H4; wherein the X group of I-93 is O, R 1 is -C3H5, R 2 is -CH3, n has the value 1, R 3 is 4-OC6H5-C6H4; wherein the X group of I-94 is O, R 1 is -C3H5, R 2 is -CH3, n has the value 1, R 3 is 3,5-dichlorophenyl; wherein the X group of I-95 is O, R 1 is CH3, R 2 is -CH3, n has the value 0, R 3 is 3-OC6H5-C6H4; wherein the X group of I-96 is O, R 1 is CH3, R 2 is -CH3, n has the value 0, R 3 is 4-OC6H5-C6H4; wherein the X group of I-97 is O, R 1 is CH3, R 2 is -CH3, n has the value 0, R 3 is 3,5-dichlorophenyl; wherein the X group of I-98 is O, R 1 is -CH2CH3, R 2 is -CH3, n has the value 0, R 3 is 3-OC6H5-C6H4; wherein the X group of I-99 is O, R 1 is -CH2CH3, R 2 is -CH3, n has the value 0, R 3 is 4-OC6H5-C6H4; wherein the X group of I-100 is O, R 1 is -CH2CH3, R 2 is -CH3, n has the value 0, R 3 is 3,5-dichlorophenyl; wherein the X group of I-101 is O, R 1 is -CH(CH3)2, R 2 is -CH3, n has the value 0, R 3 is 3-OC6H5-C6H4; wherein the X group of I-102 is O, R 1 is -CH(CH3)2, R 2 is -CH3, n has the value 0, R 3 is 4-OC6H5-C6H4; wherein the X group of I-103 is O, R 1 is -CH(CH3)2, R 2 is -CH3, n has the value 0, R 3 is 3,5-dichlorophenyl; wherein the X group of I-104 is O, R 1 is -C3H5, R 2 is -CH3, n has the value 0, R 3 is 3-OC6H5-C6H4; wherein the X group of I-105 is O, R 1 is -C3H5, R 2 is -CH3, n has the value 0, R 3 is 4-OC6H5-C6H4; wherein the X group of I-106 is O, R 1 is -C3H5, R 2 is -CH3, n has the value 0, R 3 is 3,5-dichlorophenyl.

2. Use of an amino acid fragment-containing mydriatic agent derivative as claimed in claim 1, characterized in that, The application of the arecoline derivative as an agricultural fungicide, the preparation of the arecoline derivative as an agricultural fungicide into a preparation and a composition.

3. Use according to claim 2, characterized in that, The dosage form of the agricultural fungicide is at least one of emulsifiable concentrate, water emulsion, microemulsion, wettable powder, water dispersible granule, suspension concentrate or other suitable dosage forms.

4. Use according to claim 2, characterized in that, The content of the arecoline derivative containing amino acid fragments in the fungicidal composition prepared from the agricultural fungicide is 1-99.9% by weight.

5. Use according to claim 2, characterized in that, The agricultural fungicide is applied to prevent and treat plant pathogenic diseases.

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