Novel tetrahydro-beta-carboline derivative as well as synthesis method and application thereof

Abstract

The invention relates to a novel tetrahydro-beta-carboline derivative as well as a synthesis method and application thereof. The method comprises the following steps: by taking novel tetrahydro-beta-carboline as a substrate, firstly adding inorganic alkali NaH under the protection of nitrogen, then adding an anhydrous N, N-dimethylformamide solvent for dissolving, reacting with a series of benzyl bromide or similar compounds under the condition of ice bath, carrying out intermolecular nucleophilic substitution reaction, adding a quenching agent for quenching reaction, and extracting to remove redundant N, N-dimethyl formamide, so as to obtain the novel tetrahydro-beta-carboline derivative. A series of novel tetrahydro-beta-carboline derivatives are obtained through column chromatography analysis in an N, N-dimethylformamide solvent, and the compounds have the application of inhibiting phytopathogen. The phytopathogens comprise rhizoctonia solani, sclerotinia sclerotiorum, botrytis cinerea, fusarium graminearum, colletotrichum capsici and pyricularia oryzae. The synthesis process is simple, and the product purity is high.

Description

Technical Field

[0001] The present invention belongs to the field of pesticide synthesis, and in particular relates to a novel tetrahydro-β-carboline derivative, a synthesis method thereof, and use and application thereof for inhibiting plant pathogens. Background Art

[0002] Agricultural production in my country is facing an increasingly challenging situation, and ensuring crop yields has become a critical issue that demands urgent attention. With the continued expansion of crop cultivation, the onslaught of pests, diseases, weeds, and other harmful organisms has inevitably led to reduced grain production and declining returns from cash crops. As a crucial agricultural production tool for ensuring high crop yields, pesticides have long been a key area of ​​agricultural research and development.

[0003] While the extensive use of pesticides has brought significant economic benefits, it has also raised a series of issues that cannot be ignored. From a safety risk perspective, the acute toxicity of pesticides increases the probability of poisoning in humans and animals and can also cause damage to plants. Regarding the ecological environment, their extensive use poses a potential risk of disrupting the balance of the ecosystem and causing environmental pollution. Furthermore, pesticide residues can enter the human body through bioaccumulation, creating potential chronic toxicity hazards. Furthermore, long-term pesticide use can lead to the development of resistance in the target species. To achieve effective control, pesticide use must be increased, creating a vicious cycle of "increased use leading to increased resistance." At a time when ecological and food safety are of paramount concern, these issues have sparked widespread concern across society and seriously impacted the sustainable development of the pesticide industry.

[0004] Tetrahydro-β-carboline belongs to the indole family of compounds, which are among the most widespread heterocyclic compounds in nature. Numerous studies have demonstrated that numerous compounds containing indole structures exhibit significant biological activity. The development of new pesticides based on natural indole compounds offers the distinct advantages of low toxicity and environmental friendliness. However, the extremely limited availability of indole alkaloids in natural products makes it difficult to meet the quantity and variety requirements for in-depth research. Therefore, the chemical synthesis of indole alkaloids and their analogs is crucial and urgent. By selecting simple starting materials, cleverly combining building blocks, precisely controlling reaction conditions, and designing diverse branching reaction pathways, a rich and diverse collection of compounds can be flexibly constructed, which can then be screened for biological activity. This synthetic strategy, due to its simplicity, rapidity, efficiency, and wide applicability, plays a vital role in the discovery and optimization of active drug leads. Summary of the Invention

[0005] In order to overcome the deficiencies of the prior art, the present invention aims to provide a novel tetrahydro-β-carboline derivative, a synthesis method and use thereof. The hybrid compound has good inhibitory activity against rice sheath blight, rapeseed sclerotinia, tomato gray mold, wheat fusarium, pepper anthracnose or rice blast.

[0006] In order to achieve the above-mentioned object of the invention, the present invention adopts the following technical solutions:

[0007] A novel tetrahydro-β-carboline derivative having the general formula (I):

[0008]

[0009] The synthetic route of a novel tetrahydro-β-carboline derivative having formula (I) is as follows:

[0010]

[0011] The R is any one of the following H1 to H20 groups:

[0012]

[0013] The above-mentioned group R (H1-H20) is grafted onto compound B to obtain compounds C1 to C20. The corresponding raw materials used are benzyl bromide or its analogues, specifically: benzyl bromide, methyl iodide, ethyl iodide, propyl iodide, butyl iodide, pentane iodide, 2-methylbenzyl bromide, 3-methylbenzyl bromide, 4-methylbenzyl bromide, 2-fluorobenzyl bromide, 3-fluorobenzyl bromide, 4-fluorobenzyl bromide, 2-(trifluoromethyl)benzyl bromide, 3-(trifluoromethyl)benzyl bromide, 4-(trifluoromethyl)benzyl bromide, 2-chlorobenzyl bromide, 3-chlorobenzyl bromide, 4-chlorobenzyl bromide, 4-methoxybenzyl bromide, 3,4-dichlorobenzyl bromide, and 3,5-dimethoxybenzyl bromide.

[0014] Specifically, the synthesis process of a novel tetrahydro-β-carboline derivative having formula (I) comprises the following steps:

[0015] Step 1: Prepare the substrate: 5-methoxytryptamine was added as a raw material to dichloromethane and N,N-dimethylformamide (DMF) solvents, stirred and dissolved, and the reaction system was placed in a 0°C ice-water bath. Trifluoroacetic acid was added dropwise with stirring, and then acetaldehyde was added dropwise. The ice bath was removed, and the reaction was carried out at room temperature to obtain a novel tetrahydro-β-carboline substrate (Compound B).

[0016] Step 2: The novel tetrahydro-β-carboline substrate obtained in step 1 undergoes a nucleophilic substitution reaction with a series of benzyl bromides or analogs under nitrogen protection, and TLC tracking detection is performed. After the reaction is complete, water is added dropwise to the reaction solution to quench the reaction, and the N,N-dimethylformamide solvent is removed by extraction. The organic phases are combined and concentrated under reduced pressure. The crude product is separated by column chromatography to obtain a novel tetrahydro-β-carboline derivative.

[0017] Specifically, an anhydrous N,N-dimethylformamide solution is added to a reaction bottle containing a novel tetrahydro-β-carboline substrate (compound B), NaH is added under nitrogen protection, and finally benzyl bromide or the like is added dropwise to undergo a nucleophilic substitution reaction to generate a series of novel tetrahydro-β-carboline derivatives.

[0018] The novel tetrahydro-β-carboline derivatives are used to inhibit plant pathogens, including rice sheath blight, rapeseed sclerotinia, tomato gray mold, wheat head blight, pepper anthracnose, or rice blast.

[0019] Beneficial effects: The novel tetrahydro-β-carboline derivative provided by the present invention has the characteristics of simple structure, readily available raw materials, mild reaction conditions, and simple process, and has the activity of inhibiting plant pathogens.

[0020] Activity test results showed that compounds C4, C5, C6, and C8 had inhibition rates of 100%, 100%, 95.82%, and 99.17% against Sclerotinia sclerotiorum, respectively, which were superior to the positive control, kresoxim-methyl (75.92%), and comparable to the positive control, carbendazim (100%). Compounds C4, C5, C6, and C8 had inhibition rates of 72.35%, 81.94%, 98.76%, and 100% against Botrytis cinerea, respectively. Compounds C6 and C8 exhibited inhibition activities superior to the positive controls, kresoxim-methyl (82.70%) and carbendazim (77.08%). Compounds C4 and C5 had inhibition rates of 82.97% and 90.10% against Magnaporthe grisea, respectively, which were superior to the positive control, kresoxim-methyl (75.83%), but slightly inferior to carbendazim (100%). DETAILED DESCRIPTION

[0021] The present invention will be described in detail below in conjunction with the embodiments.

[0022] Example 1 Synthesis

[0023] Step 1: Novel tetrahydro-β-carboline (Compound B).

[0024]

[0025] The preparation method is as follows: 5-methoxytryptamine (5.0 mmol, 0.95 g) was weighed into a 100 ml flask, dichloromethane (30.0 mL) and N,N-dimethylformamide (DMF, 5.0 mL) were added and stirred to dissolve, and the reaction system was placed in an ice-water bath at 0°C. Trifluoroacetic acid (TFA, 7.5 mmol, 0.6 mL) was added dropwise and stirred for 30 minutes, followed by the addition of acetaldehyde (20.0 mmol, 1.2 mL). The ice bath was removed, and the reaction was monitored by TLC at room temperature until completion. The reaction mixture was transferred to a 0°C ice-water bath, and a saturated sodium hydroxide solution was added to adjust the pH to 9. After distilling off the DCM under reduced pressure, the organic phase was extracted with ethyl acetate and washed with a saturated sodium chloride solution (20 mL × 2), dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure. The residue was separated and purified by column chromatography (eluent: V dichloromethane: V petroleum ether: V methanol = 20:10:1) to obtain intermediate B (0.76 g, 3.4 mmol, 67.3%).

[0026] Step 2: Compound C1 Synthesis

[0027] Weigh NaH (sodium hydride, 0.36 g, 15.0 mmol) and Intermediate B (1.08 g, 5.0 mmol) into a pre-dried 100 mL reaction flask (or double-necked round-bottom flask) under nitrogen protection. Transfer the reaction apparatus to a 0°C ice-water bath. Add anhydrous N,N-dimethylformamide (10.0 mL) dropwise to the reaction flask. After the addition is complete, continue stirring in the 0°C ice-water bath for 30 min. Add benzyl bromide (11.0 mmol, 1.31 mL) dropwise. Monitor the reaction at room temperature by TLC until completion. Transfer the reaction to a 0°C ice-water bath and slowly add excess water (approximately 10.0 mL) to quench any remaining NaH until bubbles cease, indicating completion. The organic phase was extracted with ethyl acetate, washed with saturated sodium chloride solution (20 mL × 2), dried over anhydrous sodium sulfate, filtered, and distilled under reduced pressure. The product was separated and purified by column chromatography (eluent: V petroleum ether: V ethyl acetate: V triethylamine = 20:1:1) to obtain the target product C1 (1.54 g, 3.9 mmol, 78.0%).

[0028] Property identification: colorless oil, 1H NMR(400MHz,DMSO-d6)δ7.28–7.12(m,9H,H-20,24,21,23,25,29,26,28,22),6.96( d,J=2.4Hz,1H,H-27),6.88–6.81(m,1H,H-3,2),6.67(dd,J=8.8,2.4Hz,1H),5.37–5 .07(m,2H,H-16),3.79(d,J=6.7Hz,1H,H-12),3.76(s,3H,H-11),3.74–3.55(m,2H,H -17),3.25–2.52(m,2H,H-14),2.96–2.79(m,2H,H-15),1.27(d,J=6.7Hz,3H,H-30). 13 C NMR(101MHz,DMSO-d6)δ153.42,139.53,138.44,131.65,128.43,128.27,128.09,127.13,126.91, 126.70,125.88,110.43,110.37,105.73,100.31,56.54,55.40,49.69,45.77,42.66,19.38,18.02.

[0029] Examples 2 to 20 The difference between Example 1 and Example 1 is that the reagents used are different (the benzyl bromide in Example 1 is replaced by other raw materials in Table 1), as shown in Table 1:

[0030] Table 1

[0031]

[0032]

[0033] Example 2

[0034]

[0035] Yellow oily, 1H NMR (400MHz, DMSO-d6) δ7.24 (d, J=8.8Hz, 1H, H-3), 6.88 (d, J=2.4Hz, 1H, H-2), 6.71 (dd, J= 8.8,2.5Hz,1H,H-6),4.07(dq,J=14.3,7.1Hz,1H,H-12),3.96(dt,J=13.0,6.7Hz,2H,H-17 ),3.74(s,3H,H-15),3.06–2.84(m,2H,H-12),2.74–2.38(m,2H,H-13),2.61–2.48(m,2H,H -18),1.29(d,J=6.7Hz,3H,H-16),1.20(t,J=7.1Hz,3H,H-19),1.07(t,J=7.1Hz,3H,H-20). 13 C NMR(101MHz,DMSO-d6)δ153.20,138.40,130.74,127.14,109.92,109.91,105 .15,100.21,55.38,49.92,46.32,41.87,37.25,18.45,17.93,15.19,13.45.

[0036] Example 3

[0037]

[0038] Yellow oily, 1 H NMR (400MHz, DMSO-d6) δ7.23 (d, J=8.8Hz, 1H, H-3), 6.89 (d, J=2.4Hz, 1H, H-2), 6.71 (dd, J=8.8, 2.5Hz, 1H, H-6),3.91(dddd,J=80.7,15.0,8.6,6.1Hz,2H,H-18),6.71(dd,J=8.8,2.5Hz,1H,H-12),3.75(s,3H,H-11 ),3.09–2.81(m,2H,H-14),2.76–2.47(m,2H,H-15),2.46–2.37(m,2H,H-16),1.77–1.53(m,2H,H-19),1.5 3–1.43(m,2H,H-20),1.29(d,J=6.6Hz,3H,H-17),0.87(t,J=7.4Hz,3H,H-22),0.82(t,J=7.4Hz,3H,H-21). 13C NMR(101MHz,DMSO-d6)δ153.21,138.78,131.08,127.11,110.14,109.90,104.92,10 0.07,55.32,54.40,50.35,44.11,42.37,23.01,20.96,18.43,18.23,11.79,11.05.

[0039] Example 4

[0040]

[0041] Yellow oily, 1 H NMR (400MHz, DMSO-d6) δ7.35(td,J=7.8,1.9Hz,1H),7.31–7.05(m,6H),7.02–6.93(m,2H),6.70(dd,J=8.8,2.5Hz,1H),6.39(td,J= 7.7,1.7Hz,1H),3.82(q,J=6.6Hz,1H),3.76(s,3H),3.80–3.59(m,2H),3.24–2.51(m,2H),2.94–2.80(m,2H),1.28(d,J=6.7Hz,3H). 13 C NMR(101MHz,DMSO-d6)δ153.14,138.71,131.02,127.04,110.10,109.90,104.94,100.13,5 5.38,52.04,50.18,42.42,42.36,31.87,29.90,20.03,19.54,18.43,18.21,13.93,13.69.

[0042] Example 5

[0043]

[0044] Yellow oily, 1H NMR (400MHz, DMSO-d6) δ7.23 (d, J=8.8Hz, 1H, H-3), 6.87 (d, J=2.5Hz, 1H, H-6), 6.70 (dd, J=8 .8,2.5Hz,1H,H-2),4.12–3.80(m,2H,H-17),3.92(q,J=6.3Hz,1H,H-10),3.74(s,3H,H-15), 3.11–2.35(m,4H,H-12,13),2.59–2.42(m,2H,H-18),1.73–1.43(m,4H,H-19,20),1.30(d,J= 6.8Hz,3H,H-16),1.35–1.12(m,8H,H-21,22,23,24),0.84(dt,J=15.6,6.9Hz,6H,H-25,26). 13 C NMR(101MHz,DMSO-d6)δ153.63,139.17,131.48,127.54,110.55,110.38,105.40,100.62,55.85, 52.84,50.63,43.05,42.96,29.87,29.64,29.01,27.92,22.57,22.38,18.99,18.64,14.44,14.29

[0045] Example 6

[0046]

[0047] Yellow oily, 1 H NMR(400MHz,DMSO-d6)δ7.16(d,J=7.5Hz,1H,H-30),7.12–6.97(m,7H,H-24,29,3,28,23,25,27),6.94 (t,J=7.5Hz,1H,22),6.66(dd,J=8.8,2.4Hz,1H,H-2),6.01(d,J=7.6Hz,1H,H-6),5.34–5.08(m,2H,H-1 7),3.77(s,3H,H-15),3.74(d,J=6.8Hz,1H,H-10),3.61(dd,J=68.3,13.7Hz,2H,H-18),3.23–2.47(m, 2H,H-12),2.94–2.84(m,2H,H-13),2.33(s,3H,H-32),2.25(s,3H,H-31),1.23(d,J=6.7Hz,3H,H-16F). 13C NMR(101MHz,DMSO-d6)δ153.43,138.88,137.23,136.97,136.44,134.71,131.66,129.98,129.91,128.87,127.05,126.67,126 .62,125.76,125.28,124.52,110.42,110.38,105.75,100.31,55.38,54.83,50.25,43.93,42.06,19.28,18.68,18.63,18.05.

[0048] Example 7

[0049]

[0050] Yellow oily, 1 H NMR(400MHz,DMSO-d6)δ7.16–6.94(m,8H,H-30,29,25,24,3,28,26,23),6.75(s,1H,H-21) ,6.68(dd,J=8.8,2.4Hz,1H,H-2),6.57(d,J=7.6Hz,1H,H-6),5.30–5.03(m,2H,H-17),3.8 0–3.73(m,1H,H-10),3.75(s,3H,H-15),3.73–3.52(m,2H,H-18),3.25–2.51(m,2H,H-12), 2.95–2.79(m,2H,H-13),2.23(s,3H,H-31),2.18(s,3H,H-32),1.27(d,J=6.7Hz,3H,H-16). 13 C NMR(101MHz,DM-SO-d6)δ153.40,139.47,138.47,138.39,137.45,137.05,131.64,128.83,128.33,127.93,127.57,127.36,12 7.11,126.39,125.30,122.89,110.37,110.32,105.62,100.29,56.54,55.35,49.69,45.74,42.69,20.99,20.94,19.33,18.03.

[0051] Example 8

[0052]

[0053] Yellow oily, 1H NMR (400MHz, DMSO-d6) δ7.17–6.98(m,7H,H-26,30,3,27,29,22,24),6.94(d,J=2.5Hz,1H,H -21),6.74(d,J=7.6Hz,2H,H-25,2),6.66(dd,J=8.8,2.4Hz,1H,H-6),5.30–5.00(m,2H,H-1 7),3.77(s,1H,H-10),3.75(s,3H,H-15),3.72–3.48(m,2H,H-18),3.23–2.51(m,2H,H-12), 2.96–2.74(m,2H,H-13),2.26(s,3H,H-32),2.23(s,3H,H-31),1.25(d,J=7.0Hz,3H,H-16). 13 C NMR(101MHz,DMSO-d6)δ153.37,138.46,136.41,135.99,135.64,135.35,131.63,128.96,128.66,128.24,127 .09,125.87,110.42,110.30,105.65,100.27,56.25,55.39,49.54,45.57,42.64,20.68,20.59,19.29,18.03.

[0054] Example 9

[0055]

[0056] Yellow oily, 1 H NMR(400MHz,DMSO-d6)δ7.35(td,J=7.8,1.9Hz,1H,h-30),7.31–7.05(m,6H,H-23,28,25,3,2 9,27),7.02–6.93(m,2H,H-24,22),6.70(dd,J=8.8,2.5Hz,1H,H-2),6.39(td,J=7.7,1.7Hz, 1H,H-6),5.42–5.18(m,2H,H-17),3.82(q,J=6.6Hz,1H,H-10),3.76(s,3H,H-15),3.80–3.59 (m,2H,H-18),3.24–2.51(m,2H,H-12),2.94–2.80(m,2H,H-13),1.28(d,J=6.7Hz,3H,H-16). 13CNMR(101MHz,DMSO-d6)δ161.17(d,J=244.4Hz),159.87(d,J=244.5Hz),154.05,138.86,132.11,130 .80(d,J=4.6Hz),129.55(d,J=8.1Hz),129.05(d,J=8.2Hz),128.06(d,J=4.3Hz),127.64,126.65(d,J =13.6Hz),125.65(d,J=14.4Hz),124.93(d,J=3.3Hz),124.62(d,J=3.4Hz),115.68(d,J=20.9Hz),115 .53(d,J=21.7Hz),111.06,110.76,106.49,100.91,55.87,50.68,49.86,49.83,42.89,19.81,18.47. 19 F NMR (376MHz, DMSO-d6) δ-118.28.

[0057] Example 10

[0058]

[0059] Yellow oily, 1 H NMR (400MHz, DMSO-d6) δ7.26 (ddq, J=10.9, 5.9, 2.8Hz, 2H, H-27, 22), 7.19 (d, J=8.8Hz, 1H, H-3) ,7.08–6.95(m,5H,H-26,21,20,28,25),6.70(dd,J=8.8,2.5Hz,1H,H-23),6.66–6.57(m,2H,H-2 ,6),5.25(dd,J=93.2,17.5Hz,2H,H-16),3.76(s,3H,H-15),3.79–3.55(m,2H,H-19),3.69(q,J= 6.7Hz,1H,H-10),2.97–2.78(m,2H,H-12),3.28–2.51(m,2H,H-13),1.29(d,J=6.7Hz,3H,H-18). 13CNMR(101MHz,DMSO-d6)δ162.27(d,J=242.6Hz,C,C-24),162.25(d,J=243.8Hz,C,C-29),153.55(C,C-1),1 42.79(d,J=7.0Hz),141.58(d,J=6.8Hz),138.18,131.63,130.45(d,J=8.3Hz),129.90(d,J=8.3Hz),127.15 ,123.95(d,J=2.5Hz),121.78(d,J=2.6Hz),114.49(d,J=21.2Hz),113.60(d,J=2.8Hz),113.59(d,J=44.7Hz ),112.58(d,J=21.8Hz),110.58,110.35,106.02,100.41,55.95,55.38,49.64,45.24,42.80,19.46,18.00. 19 F NMR (376MHz, DMSO-d6) δ-114.83.

[0060] Example 11

[0061]

[0062] Yellow oily, 1 H NMR (400MHz, DMSO-d6) δ7.28–7.20(m,2H,H-30,26),7.18(d,J=8.8Hz,1H,H-3),7.05(td,J=8.9,3.2 Hz,4H,H-21,25,24,22),6.97(d,J=2.5Hz,1H,H-2),6.89–6.81(m,2H,H-29,27),6.70(dd,J=8.8,2.5 Hz,1H,H-6),5.21(dd,J=95.0,17.1Hz,2H,H-18),3.76(s,3H,H-15),3.73–3.52(m,2H,H-16),3.69( q,J=6.6Hz,1H,H-10),3.25–2.51(m,2H,H-12),2.94–2.78(m,2H,H-13),1.27(d,J=6.7Hz,3H,H-17). 13C NMR(101MHz,DMSO-d6)δ161.66(d,J=242.7Hz),161.58(d,J=242.2Hz).153.50, 138.23,135.57(d,J=2.9Hz),134.56(d,J=3.0Hz),131.62,129.90(d,J=8.0Hz) ,127.76(d,J=8.1Hz),127.15,115.56(d,J=50.2Hz).115.35(d,J=49.7Hz,),11 0.47,110.35,105.90,100.36,55.62,55.37,49.48,45.08,42.61,19.30,18.01. 19 F NMR (376MHz, DMSO-d6) δ-115.80.

[0063] Example 12

[0064]

[0065] Yellow oily, 1 H NMR (400MHz, DMSO-d6) δ7.71(dd,J=5.6,3.7Hz,1H,H-28),7.67(d,J=7.8Hz,1H,H-23),7.63(d,J=7.8Hz,1H,H-22 ),7.55(t,J=7.6Hz,1H,H-27),7.44–7.34(m,3H,H-20,21,25),7.08(d,J=8.8Hz,1H,H-26),7.02(d,J=2.4Hz,1H, H-3),6.71(dd,J=8.9,2.4Hz,1H,H-2),6.23(dd,J=5.5,3.6Hz,1H,H-6),5.52–5.25(m,2H,H-16),3.96–3.72(m,2 H,H-17),3.77(s,3H,H-11),3.70(d,J=6.9Hz,1H,H-12),3.28–2.51(m,4H,H-14,15),1.24(d,J=6.7Hz,3H,H-38). 13C NMR(101MHz,DMSO-d6)δ153.72,138.36,138.23,136.86,132.80,132.28,131.65,129.74,128.74–119.97(m),127.61,127.45–126.45(m),127. 18,127.12,126.55,126.06–125.12(m),125.92–125.66(m).110.95,11 0.09,106.50,100.57,55.36,52.69,50.37,42.62,42.34,19.00,18.07. 19 F NMR (376MHz, Chloroform-d) δ-62.76.

[0066] Example 13

[0067]

[0068] Yellow oily, 1 H NMR(400MHz,DMSO-d6)δ7.58(s,1H,H-21),7.56–7.39(m,5H,H-27,29,24,22,26),7.26(s,1H,H-25) ,7.19(d,J=8.8Hz,1H,H-20),7.00(d,J=2.4Hz,1H,H-3),6.94(d,J=7.7Hz,1H,H-2),6.70(dd,J=8.8 ,2.5Hz,1H,H-6),5.48(d,J=17.6Hz,1H),5.25(d,J=17.6Hz,2H,H-16),3.76(s,3H,H-11),3.88–3.6 1(m,2H,H-17),3.66(d,J=2.4Hz,1H,H-12),3.31–2.47(m,3H,H-14,15),1.29(d,J=6.6Hz,3H,H-30). 13C NMR(101MHz,DMSO-d6)δ153.61,141.22,140.18,138.10,131.94,131.64,129.5 9,129.53,129.07,128.93(td,J=31.5,11.5Hz),127.19,124.20(q,J=3.8Hz),12 4.17(qd,J=272.3,21.3Hz),123.56(dd,J=18.7,3.9Hz),122.38(q,J=3.9Hz),11 0.70,110.35,106.21,100.44,55.89,55.34,49.89,45.24,42.77,19.56,18.03. 19 F NMR (376MHz, DMSO-d6) δ-61.00.

[0069] Example 14

[0070]

[0071] Yellow oily, 1 H NMR (400MHz, DMSO-d6) δ7.57(d,J=8.2Hz,2H,H-26,28),7.52(d,J=8.1Hz,2H,H-21,23),7.41(d,J=8. 0Hz,2H,H-25,29),7.20(d,J=8.8Hz,1H,H-3),7.00(d,J=2.4Hz,1H,H-2),6.96(d,J=8.1Hz,2H,H-20,2 4),6.71(dd,J=8.8,2.5Hz,1H,H-6),5.34(dd,J=113.3,17.8Hz,2H,H-16),3.77(s,3H,H-11),3.86–3. 63(m,2H,H-17),3.59(d,J=6.7Hz,1H,H-12),3.32–2.52(m,2H,H-14,15),1.29(d,J=6.7Hz,3H,H-30). 13C NMR (101MHz, DMSO-d6) δ153.63,144.55,143.41,138.03,131.69,128.60,127.47(q,J=31.7Hz),127.41(q,J=31.7Hz).127.14,126.39,125.34(q, J=3.7Hz),124.78(d,J=3.9Hz),124.24(qd,J=271.8,11.8Hz),110.68,1 10.28,106.14,100.45,55.88,55.38,49.47,45.30,42.98,19.37,18.05. 19 F NMR (376MHz, DMSO-d6) δ-60.86.

[0072] Example 15

[0073]

[0074] Colorless oil, 1 H NMR (400MHz, DMSO-d6) δ7.46–7.32(m,3H,H-29,26,24),7.23(dtd,J=9.3,7.4,3.6Hz,3H,H-27,28,2 2),7.15–7.07(m,2H,H-23,3),7.00(d,J=2.4Hz,1H,H-21),6.69(dd,J=8.8,2.5Hz,1H,H-2),6.17(dd ,J=7.7,1.7Hz,1H,H-6),5.43–5.19(m,2H,H-17),3.80(d,J=14.9Hz,1H,H-10),3.77(s,3H,H-15),3. 76–3.63(m,2H,H-18),3.27–2.52(m,2H,H-12),2.97–2.84(m,2H,H-13),1.27(d,J=6.7Hz,3H,H-16). 13 C NMR (101MHz, DMSO-d6) δ153.61,138.42,136.78,135.52,132.99,131.54,131.05,129.83,129.27,129.16,128.75,128. 26,127.32,127.15,126.95,126.90,110.73,110.25,106.20,100.48,55.39,53.67,50.36,43.78,42.49,19.43,18.10.

[0075] Example 16

[0076]

[0077] Colorless oil, 1 H NMR(400MHz,DMSO-d6)δ7.24(d,J=1.9Hz,1H,H-30),7.23–7.09(m,6H,H-21,22,23,25,27,28) ,6.94(d,J=2.4Hz,1H,H-26),6.81(dt,J=2.5,1.1Hz,1H,H-3),6.66(ddd,J=9.1,3.6,2.0Hz,2 H,H-2,6),5.21(dd,J=92.6,17.5Hz,2H,H-16),3.71(s,3H,H-15),3.61(q,J=6.6Hz,1H,H-10) ,3.61(dd,J=83.2,14.3Hz,2H,H-18),3.24–2.46(m,4H,H-12,13),1.23(d,J=6.7Hz,3H,H-17). 13 CNMR(101MHz,DMSO-d6)δ153.59,142.40,141.24,138.12,133.23,133.02,131.60,130.40,129.96,127.79,127.17,126 .99,126.78,126.69,125.61,124.43,110.68,110.42,106.07,100.40,55.92,55.39,49.68,45.13,42.87,19.67,18.01.

[0078] Example 17

[0079]

[0080] Colorless oil, 1H NMR(400MHz,DMSO-d6)δ7.28(dd,J=8.5,3.2Hz,4H,H-28,26,25,29),7.24–7.15(m,3H,H-20,24,21 ),6.97(d,J=2.4Hz,1H,H-23),6.81(d,J=2.0Hz,1H,H-3),6.80(s,1H,H-2),6.69(dd,J=8.8,2.4Hz, 1H,H-6),5.22(dd,J=102.1,17.4Hz,2H,H-16),3.76(s,3H,H-11),3.64(q,J=6.6Hz,1H,H-12),3.7 5–3.49(m,2H,H-17),3.27–2.51(m,2H,H-14),2.97–2.76(m,2H,H-15),1.26(d,J=6.7Hz,3H,H-30). 13 C NMR (101MHz, DMSO-d6) δ153.51,138.56,138.12,137.53,131.62,131.51,131.11,129.90,128.42,127. 98,127.66,127.10,110.54,110.33,105.97,100.37,55.65,55.39,49.44,45.10,42.76,19.38,18.01.

[0081] Example 18

[0082]

[0083] Brown oily, 1 H NMR(400MHz,DMSO-d6)δ7.20–7.08(m,3H,H-25,29,24),6.95(d,J=2.5Hz,1H,20),6.84–6.75(m,6 H,H-3,2,6,21,23,26),6.68(dd,J=8.8,2.5Hz,1H,28),5.13(dd,J=86.7,16.8Hz,2H,H-16),3.78 (d,J=6.8Hz,1H,H-12),3.75(s,3H,H-11),3.72(s,3H,H-33),3.69(s,3H,H-34),3.58(dd,J=64.0 ,13.5Hz,2H,H-17),3.22–2.45(m,2H,H-14),2.94–2.75(m,2H,H-15),1.26(d,J=6.7Hz,3H,H-30). 13C NMR(101MHz,DMSO-d6)δ158.25,158.09,153.37,138.44,131.63,131.26,130.23,129.43,127.17,127.12,113 .84,113.44,110.42,110.29,105.64,100.27,55.87,55.39,54.98,54.90,49.38,45.28,42.57,19.26,18.02.

[0084] Example 19

[0085]

[0086] Yellow oily, 1 H NMR (400MHz, DMSO-d6) δ7.52–7.43(m,3H,H-21,26,29),7.24–7.16(m,2H,H-24,25),7.10(d,J=2.0Hz ,1H,H-20),6.98(d,J=2.4Hz,1H,H-3),6.71(dd,J=8.8,2.4Hz,1H,H-2),6.63(dd,J=8.3,2.1Hz,1H,H- 6),5.26(dd,J=100.8,17.6Hz,2H,H-16),3.76(s,3H,H-11),3.65(dd,J=86.0,14.3Hz,2H,H-17),3.60 (q,J=6.8Hz,1H,H-12),3.31–2.77(m,2H,H-14),3.00–2.52(m,2H,H-15),1.28(d,J=6.7Hz,3H,H-20). 13 C NMR (101MHz, DMSO-d6) δ154.10,141.53,140.38,138.38,132.01,131.56,131.34,131.22,130.68,130.21,130.01,129. 59,128.68,128.30,127.62,126.44,111.23,110.82,106.66,100.95,55.88,55.66,49.92,45.05,43.40,20.13,18.47.

[0087] Example 20

[0088]

[0089] Brown oily, 1H NMR (400MHz, DMSO-d6) δ7.11(d,J=8.8Hz,1H,H-3),6.97(d,J=2.4Hz,1H,H-2),6.68(dd,J=8.8,2.5Hz,1H,H- 6),6.47(d,J=2.3Hz,2H,H-25,29),6.33(dt,J=8.2,2.3Hz,2H,H-20,24),5.98(d,J=2.2Hz,2H,H-22,27),5.2 7–5.03(m,2H,H-16),3.80(t,J=6.9Hz,1H,H-12),3.76(s,3H,H-11),3.68(s,6H,H-38,37),3.76–3.52(m,2H ,H-11),3.62(s,6H,H-36,35),3.25–2.51(m,2H,H-14),2.97–2.78(m,2H,H-15),1.30(d,J=6.7Hz,3H,H-30). 13 C NMR(101MHz,DMSO-d6)δ160.57,160.38,153.46,142.24,140.94,138.56,131.70,127.15,110.44,110.39,10 5.75,105.67,104.08,100.32,98.69,97.88,56.74,55.36,54.94,54.92,49.89,45.76,42.84,19.36,18.18.

[0090] The inhibitory activities (inhibition rate, %) of the obtained compounds C1 to C20 against six plant pathogenic fungi were determined, and the results are shown in Table 2. Among them, C-1 to C-20 correspond to the compounds obtained in Examples 1 to 20.

[0091] Table 2

[0092]

[0093] Note: Rs: Rhizoctonia solani; Ss: Sclerotinia sclerotiorum; Bc: Botrytis cinerea; Fg: Gibberellic acid; Cc: Colletotrichum sclerotiorum; Mo: Magnaporthe grisea. Each data point represents the average of three replicate experiments. Kresoxim-methyl and carbendazim served as positive controls.

[0094] The experiment used the hyphal growth rate method to conduct an initial screening of activity against six plant pathogenic fungi. The data showed that at a concentration of 100 mg / L, compounds C1-C20 exhibited varying degrees of antifungal activity against the six plant pathogens, with some compounds exhibiting inhibition rates exceeding 50%. Compounds C4, C5, C6, and C8 were particularly potent. Compound C4 exhibited inhibition rates of 63.36%, 100.00%, 72.35%, and 82.97% against Rhizoctonia solani, Sclerotinia sclerotiorum, Botrytis cinerea, and Magnaporthe grisea, respectively. Compound C5 exhibited inhibition rates of 74.98%, 100.00%, 81.94%, and 90.10% against Rhizoctonia solani, Sclerotinia sclerotiorum, Botrytis cinerea, and Magnaporthe grisea, respectively. Compound C6 showed inhibition rates of 50.95%, 95.82% and 98.76% against Rhizoctonia solani, Sclerotinia sclerotiorum and Botrytis cinerea, respectively. Compound C8 showed inhibition rates of 99.17%, 100.00%, 62.43% and 55.75% against Sclerotinia sclerotiorum, Botrytis cinerea, Colletotrichum oxysporum and Magnaporthe oryzae, respectively.

[0095] The results show that this series of compounds has significant inhibitory effects on Sclerotinia sclerotiorum, Botrytis cinerea, and Magnaporthe grisea. Compounds C4, C5, C6, and C8 exhibited inhibition rates of 100%, 100%, 95.82%, and 99.17%, respectively, against Sclerotinia sclerotiorum, superior to the positive control, kresoxim-methyl (75.92%), and comparable to the positive control, carbendazim (100%). Compounds C4, C5, C6, and C8 exhibited inhibition rates of 72.35%, 81.94%, 98.76%, and 100%, respectively, against Botrytis cinerea. Compounds C6 and C8 exhibited inhibitory activity superior to the positive controls, kresoxim-methyl (82.70%) and carbendazim (77.08%). The inhibition rates of compounds C4 and C5 against rice blast fungus were 82.97% and 90.10%, respectively, which were better than the positive control kresoxim-methyl (75.83%) and slightly worse than carbendazim (100%).

[0096] The basic principles, main features, and advantages of the present invention are shown and described above. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The above embodiments and descriptions are merely illustrative of the principles of the present invention. Various changes and modifications may be made to the present invention without departing from the spirit and scope of the present invention. Such changes and modifications are intended to fall within the scope of the present invention. The scope of protection claimed in the present invention is defined by the appended claims and their equivalents.

Claims

1. A novel tetrahydro-β-carboline derivative represented by general formula (I): Formula (I); The R is any one of the following groups H1 to H20: 。 2. The synthesis process of a novel tetrahydro-β-carboline derivative according to claim 1, characterized in that: The reaction formula is as follows: 。 3. The synthesis process of a novel tetrahydro-β-carboline derivative according to claim 2, characterized in that: Here are the steps: Step 1: Prepare the substrate: 5-methoxytryptamine is added as a raw material to dichloromethane and N,N-dimethylformamide solvents, stirred to dissolve, and the reaction system is placed in a 0°C ice-water bath. Trifluoroacetic acid is added dropwise with stirring to react, and acetaldehyde is then added dropwise. The ice bath is removed and the reaction is allowed to proceed at room temperature to obtain a novel tetrahydro-β-carboline substrate. Step 2: The novel tetrahydro-β-carboline substrate obtained in step 1 undergoes a nucleophilic substitution reaction with a series of benzyl bromide or benzyl bromide analogs, followed by TLC monitoring. After the reaction is complete, water is added dropwise to the reaction solution to quench the reaction. The N, N-dimethylformamide solvent is removed by extraction, and the organic phases are combined and concentrated under reduced pressure. The crude product is separated by column chromatography to obtain a novel tetrahydro-β-carboline derivative.

4. The synthesis process of a novel tetrahydro-β-carboline derivative according to claim 3, characterized in that: The second step is to add an anhydrous N, N-dimethylformamide solution of a tetrahydro-β-carboline substrate containing NaH to an anhydrous N, N-dimethylformamide solution of benzyl bromide or a benzyl bromide analog under nitrogen protection to cause a nucleophilic substitution reaction.

5. The synthesis process of a novel tetrahydro-β-carboline derivative according to claim 4, characterized in that: Benzyl bromide or a benzyl bromide analogue is selected from benzyl bromide, methyl iodide, ethyl iodide, propyl iodide, butyl iodide, pentane iodide, 2-methylbenzyl bromide, 3-methylbenzyl bromide, 4-methylbenzyl bromide, 2-fluorobenzyl bromide, 3-fluorobenzyl bromide, 4-fluorobenzyl bromide, 2-(trifluoromethyl)benzyl bromide, 3-(trifluoromethyl)benzyl bromide, 4-(trifluoromethyl)benzyl bromide, 2-chlorobenzyl bromide, 3-chlorobenzyl bromide, 4-chlorobenzyl bromide, 4-methoxybenzyl bromide, 3,4-dichlorobenzyl bromide, 3,5-dimethoxybenzyl bromide.

6. Use of the novel tetrahydro-β-carboline derivative having the general formula (I) according to claim 1 for inhibiting plant pathogens.

7. The use according to claim 6, characterized in that The plant pathogenic bacteria are rice sheath blight, rapeseed sclerotinia, tomato gray mold, wheat fusarium, pepper anthracnose or rice blast.

Images