Aza-cyclic alkaloid and its use in the control of plant viruses

Abstract

The application relates to the technical field of nitrogen heterocyclic compounds, in particular to a nitrogen heterocyclic alkaloid and application thereof in preventing and treating plant viruses. The structural formula of the nitrogen heterocyclic alkaloid is shown in the description, X is selected from any one of -OCH3, -OCH2CH3 and -O(CH2)2CH3. The anti-virus activity test result shows that the nitrogen heterocyclic alkaloid series compounds provided by the application all have anti-virus activity, wherein the anti-virus activity level of part of the nitrogen heterocyclic alkaloids reaches or even exceeds that of a positive control drug. Therefore, the nitrogen heterocyclic alkaloid can be expected to be applied to the prevention and treatment of plant viruses.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of nitrogen heterocyclic compounds, in particular to a nitrogen heterocyclic alkaloid and its application in preventing and treating plant viruses. BACKGROUND

[0002] The prevention and treatment of plant viruses is an important issue in global agricultural production, but due to the complexity of viruses and the diversity of transmission mechanisms, the prevention and treatment thereof faces many challenges. At present, the prevention and treatment methods of plant virus diseases include agricultural prevention and treatment, biological prevention and treatment, chemical prevention and treatment, and genetic engineering, etc. Chemical prevention and treatment is widely used in agricultural production due to its simple operation and quick effect.

[0003] At present, the chemical agents registered on the market for preventing and treating plant virus diseases mainly include ribavirin, moroxydine hydrochloride, chlorobromoisocyanuric acid, dimethomorph, lentinan, and some copper preparations, etc. These agents show certain prevention and treatment effect in actual application, but due to the problem of drug resistance, the prevention and treatment effect thereof is seriously affected.

[0004] Nitrogen heterocyclic alkaloids are a kind of nitrogen-containing secondary metabolites formed by plants in long-term evolution. Due to its unique chemical structure and biological activity, it has the effects of universal anti-tumor, anti-bacterial and immunosuppressive activity. However, the biological activity research of this kind of compound mainly focuses on the medical activity research, and the application thereof in the field of agriculture is rarely reported, especially the research on plant antiviral aspect is not reported. SUMMARY

[0005] The present application aims at at least solving one of the technical problems in the related art. To this end, the first object of the present application is to provide a nitrogen heterocyclic alkaloid, and the second object of the present application is to provide the application of the nitrogen heterocyclic alkaloid in preventing and treating plant viruses.

[0006] In order to achieve the first object, the technical solution adopted by the present application is as follows:

[0007] A nitrogen heterocyclic alkaloid, the structural formula of which is as follows:

[0008] ;

[0009] wherein X is selected from any one of -OCH3, -OCH2CH3 and -O(CH2)2CH3;

[0010] R is selected from any one of the following groups:

[0011] 、 、 ;

[0012] -(CH2) nCH3, n is selected from any integer from 1 to 17;

[0013] -(CH2) m CH(CH3)2, m is selected from 1 or 2;

[0014] -CH2C(CH3)3, -CH(CH2CH3)(CH2CH2CH3);

[0015] a is selected from any integer from 1 to 8;

[0016] b is selected from any integer from 1 to 3;

[0017] R1is selected from H, a halogen element, and -C(CH3)3;

[0018] R2is selected from H, -CH3, a halogen element, -C(CH3)3, -CF3, or -OCH3.

[0019] Preferably, X is selected from -OCH3; and R is selected from -(CH2) n CH3, n is selected from 1, 3, 7, 11, or 17.

[0020] Preferably, X is selected from -OCH3; and R is selected from .

[0021] Preferably, X is selected from -OCH3; and R is selected from .

[0022] Preferably, X is selected from -OCH3; and R is selected from R1is selected from Cl or Br in a halogen element.

[0023] Preferably, X is selected from -OCH3; and R is selected from R2is selected from F, Cl, or Br in a halogen element.

[0024] To achieve the second object, the technical solution adopted by the present application is:

[0025] Use of an azacyclic alkaloid in the prevention and treatment of plant viruses, the azacyclic alkaloid as described in any of the above.

[0026] Preferably, the virus is selected from tobacco mosaic virus.

[0027] Preferably, the plant is selected from one or several of Solanaceae plants, Cruciferae plants, Chenopodiaceae plants, Cucurbitaceae plants, and Leguminosae plants.

[0028] Preferably, the Solanaceae plant is selected from one or more of tobacco, tomato, pepper and eggplant; the Cruciferae plant is selected from one or more of Chinese cabbage, cabbage and rape; the Chenopodiaceae plant is selected from one or both of spinach and amaranth; the Cucurbitaceae plant is selected from cucumber; and the Leguminosae plant is selected from one or both of kidney bean and cowpea.

[0029] The one or more technical solutions in the embodiments of the present application have at least one of the following technical effects:

[0030] The present application provides a kind of nitrogen heterocyclic alkaloid, and the antiviral activity test result shows that series compound all has antiviral activity, and the antiviral activity level of part nitrogen heterocyclic alkaloid reaches, even exceeds the antiviral activity of positive control drug product.Therefore, the nitrogen heterocyclic alkaloid is expected to be applied in the prevention and treatment of plant virus.

[0031] Additional aspects and advantages of the application will be set forth in part in the description which follows, and in part will become apparent to those skilled in the art upon examination of the following and / or can be learned by practice of the application. DETAILED DESCRIPTION

[0032] So that the objects, technical solutions and advantages of the present application are more apparent, the technical solutions in the present application will be described clearly and completely below in connection with specific embodiments. Obviously, the described embodiments are only a part of the embodiments of the present application, but not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application. The following embodiments are used to illustrate the present application, but cannot be used to limit the scope of the present application.

[0033] A nitrogen heterocyclic alkaloid has the following structural formula:

[0034]

[0035] In the following examples, the experimental methods used are conventional methods, and the used materials, reagents, etc. are commercially available unless otherwise specified, and are performed according to the techniques or conditions described in the literature in the art or according to the product instructions unless otherwise specified.

[0036] Example 1

[0037] The synthesis route of the nitrogen heterocyclic alkaloids (a, b, c and d) is as follows:

[0038] ;

[0039] The preparation process is as follows:

[0040] I. Preparation of intermediate I.

[0041] In a 100 mL round bottom flask, diethylformamide (5.9 mL, 53.1 mmol), chloroform (5 mL) were added under ice water bath condition, then phosphorous oxybromide (POBr3) (12.7 g, 44.3 mmol) was added dropwise slowly, the reaction was carried out for 30 min, then the solvent was removed under reduced pressure to obtain a white complex, which was cooled to room temperature, chloroform (10 mL) was added, 4-methoxy-3-pyrroline-2-one (2 g, 17.7 mmol) was added dropwise slowly into the reaction system under ice water bath condition, then the temperature was increased to 60 °C, the reaction was carried out for 5 h, which was monitored by thin layer chromatography (TLC). After the reaction was completed, 50 mL ice water was added into the reaction mixture, then the pH was adjusted to neutral with 2 mol / L NaOH solution, the mixture was divided into two layers, the organic phase was collected, the water layer was extracted with ethyl acetate, then the organic phase was combined with the previous one, washed with saturated brine, dried over anhydrous Na2SO4, filtered, the filtrate was concentrated, then column chromatography was carried out with a mixture of petroleum ether (PE) and ethyl acetate (EA) (volume ratio of PE to EA was 5:1) as eluent to obtain yellow solid intermediate I, yield was 76%, melting point was 38-40 °C, the spectral data of1H NMR,13C NMR and HRMS were as follows: 1 H NMR、 13 C NMR and HRMS were as follows:

[0042] 1 H NMR (400 MHz, CDCl3) δ 6.98 (s, 1H), 5.56 (s, 1H), 4.08 (q, J = 7.1 Hz, 2H), 3.73 (s, 3H), 3.36 (q, J = 7.2 Hz, 2H), 1.26 (td, J = 7.2, 4.9 Hz, 6H);

[0043] 13 C NMR (100 MHz, CDCl3) δ 165.3, 138.7, 133.5, 120.7, 96.4, 58.0, 51.2, 44.6, 14.7, 12.5;

[0044] HRMS (ESI) m / z: [M + H] ＋ C 10 H 16 BrN2O + Calculated value was 259.0440, actual value was 259.0443.

[0045] II.

[0046] At room temperature, 1-Boc-pyrrole-2-boronic acid (6.27 g, 29.7 mmol), Na2CO3(6.3 g, 59.4 mmol), Pd(PPh3)4(2.29 g, 1.98 mmol) were added into a round bottom flask containing intermediate I (5.12 g, 19.8 mmol) in sequence, and then 10 wt% aqueous solution of dioxane (70 mL) was added into the flask, and the solution was stirred and dissolved, and then the temperature was raised to 100°C, and after 3 h of reaction, the temperature was lowered to room temperature, and then sodium methoxide (3.21 g, 59.4 mmol) was slowly added into the reaction system. Then the temperature was raised to 100°C, and after 2.5 h of reaction, the reaction was monitored by TLC. After the reaction was completed, the pH of the solution was adjusted to neutral with 2 mol / L HCl, and the reaction was carried out for 15 min, and then the solution was filtered, and the filter cake was washed with water and acetone, and then dried to obtain intermediate II, with a yield of 70%, and a melting point of 224-227°C. 1 H NMR, 13 The spectral data of1H NMR,13C NMR and HRMS are as follows:

[0047] 1 H NMR(400MHz,DMSO- d 6) δ 11.39(s,1H),11.28(s,1H),9.31(s,1H),6.91(s,1H),6.75(d, J =2.1Hz,1H),6.27(s,1H),6.16–6.03(m,1H),3.84(s,3H);

[0048] 13 C NMR(100MHz,DMSO- d 6) δ 172.1,159.1,133.7,123.9,120.8,117.9,109.8,108.8,91.4,58.2;

[0049] HRMS(ESI)m / z:[M-H] － C 10 H9N2O2 - Calculated value: 189.0670; actual value: 189.0669.

[0050] III. Preparation of azacyclic alkaloid a .

[0051] At room temperature, intermediate II (0.1 g, 0.52 mmol) was taken in a 25 mL reaction vessel, then 1,2-dichloroethane (10 mL) was added to dissolve intermediate II, then isobutylamine (0.52 mL, 5.2 mmol), glacial acetic acid (0.3 mL, 5.2 mmol) were added in turn, and the reaction was carried out at 25°C for 6 h, and TLC was used for monitoring. After the reaction was completed, water was added to quench the reaction, and dichloromethane was used for extraction, and the organic phase was collected, and the aqueous phase was extracted with dichloromethane, and then the obtained organic phase was combined with the aforementioned organic phase, and then washed with saturated brine, dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated, and then column chromatography was used for separation with a mixed solvent of PE and EA (the volume ratio of PE to EA was 2:1) as the eluent, and then yellow oil of azacyclic alkaloid a was obtained, the yield was 75%, and its structure was identified by1H NMR and13C NMR. 1 H NMR and 13 The spectral data of1H NMR and13C NMR are as follows:

[0052] 1 H NMR (400 MHz, CDCl3) δ 10.72 (s, 1H), 7.30 (s, 1H), 7.04 (s, 1H), 6.77 (s, 1H), 6.27 (s, 1H), 5.98 (s, 1H), 3.91 (s, 3H), 3.29 (d, J = 6.7 Hz, 2H), 2.02 (dt, J = 13.3, 6.7 Hz, 1H), 1.02 (d, J = 6.7 Hz, 6H);

[0053] 13 C NMR (100 MHz, CDCl3) δ 163.9, 142.3, 140.7, 124.0, 122.7, 113.2, 110.7, 110.7, 91.2, 58.6, 29.5, 19.8.

[0054] Four, preparation of azacyclic alkaloid b .

[0055] Intermediate II (0.1 g, 0.52 mmol) was taken in a 25 mL reaction vessel, then 1,2-dichloroethane (10 mL) was added to dissolve intermediate II, then ethylamine (0.3 mL, 5.2 mmol), glacial acetic acid (0.3 mL, 5.2 mmol) were added successively, and the reaction was allowed to proceed at 50 °C for 6 h, which was monitored by TLC. After the reaction was completed, the reaction was quenched with water, extracted with dichloromethane, and the organic phase was collected. The aqueous phase was extracted with dichloromethane, and the obtained organic phase was combined with the aforementioned organic phase, washed with saturated brine, dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated, and column chromatography was performed using a mixed solvent of PE and EA (volume ratio of PE to EA was 2:1) as the eluent to obtain yellow oily azacyclic alkaloid b in a yield of 85%, which had the following spectral data: 1 H NMR, 13 C NMR and HRMS as follows:

[0056] 1 H NMR (400 MHz, CDCl3) δ 7.51 (s, 1H), 7.37-7.30 (m, 1H), 7.08-7.02 (m, 1H), 6.22 (s, 1H), 6.08 (s, 1H), 3.86 (s, 3H), 3.54 (q, J = 7.3 Hz, 2H), 1.53 (s, 9H), 1.37 (t, J = 7.3 Hz, 3H);

[0057] 13 C NMR (100 MHz, CDCl3) δ 162.1, 148.4, 142.6, 140.3, 126.1, 124.7, 119.8, 111.9, 110.6, 96.5, 84.9, 58.3, 45.9, 27.9, 15.2;

[0058] HRMS (ESI) m / z: [M + H] ＋ C 12 H 16 N3O + Calculated value: 218.1288; actual value: 218.1285.

[0059] V. Preparation of azacyclic alkaloid c .

[0060] At room temperature, intermediate II (0.1 g, 0.52 mmol) was taken in a 25 mL reaction vessel, followed by 1,2-dichloroethane (10 mL) to dissolve intermediate II, then phenethylamine (0.6 mL, 5.2 mmol), glacial acetic acid (0.3 mL, 5.2 mmol) were added in sequence, and the reaction was allowed to proceed at 50 °C for 6 h, which was monitored by TLC. After the reaction was completed, the reaction was quenched with water, extracted with dichloromethane, and the organic phase was collected. The aqueous phase was extracted with dichloromethane, and the obtained organic phase was combined with the aforementioned organic phase, washed with saturated brine, dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated, and column chromatography was performed using a mixed solvent of PE and EA (volume ratio of PE to EA was 1:2) as the eluent to obtain yellow oil of azacyclic alkaloid b in a yield of 85%, which had the following spectral data: 1 H NMR, 13 C NMR and HRMS spectral data are as follows:

[0061] 1 H NMR (400 MHz, CDCl3) δ 10.61 (s, 1H), 9.56 (s, 1H), 7.29 (m, 5H), 7.16-6.99 (m, 2H), 6.75 (s, 1H), 6.29 (s, 1H), 5.92 (s, 1H), 3.88 (s, 3H), 3.80-3.62 (m, 2H), 3.07 (t, J = 7.3 Hz, 2H);

[0062] 13 C NMR (100 MHz, CDCl3) δ 163.9, 142.5, 140.2, 137.1, 129.0, 128.9, 127.0, 124.3, 122.7, 113.4, 110.8, 91.2, 58.5, 52.4, 36.6, 29.7;

[0063] HRMS (ESI) m / z: [M + H] ＋ H 20 N3O + Calculated value is 294.1601; actual value is 294.1602.

[0064] Six, preparation of azacyclic alkaloid d .

[0065] Intermediate II (0.1 g, 0.52 mmol) was taken in a 25 mL reaction vessel, then 1,2-dichloroethane (10 mL) was added to dissolve intermediate II, then dodecylamine (0.96 g, 5.2 mmol), glacial acetic acid (0.3 mL, 5.2 mmol) were added in sequence, the reaction was heated to 50 °C for 6 h, TLC monitoring. After the reaction was completed, the reaction was quenched with water, extracted with dichloromethane, the organic phase was collected, the aqueous phase was extracted with dichloromethane, and then the obtained organic phase was combined with the aforementioned organic phase, washed with saturated brine, dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated, then column chromatography was performed using a mixed solvent of PE and EA (volume ratio of PE to EA was 1:2) as the eluent to separate the yellow oily azacyclic alkaloid b, yield 54%, which 1 H NMR, 13 C NMR and HRMS spectral data are as follows:

[0066] 1 H NMR (400 MHz, CDCl3) δ 10.69 (s, 1H), 7.31 (s, 1H), 7.03 (s, 1H), 6.72 (d, J = 2.8 Hz, 1H), 6.31-6.20 (m, 1H), 5.93 (s, 1H), 3.89 (s, 3H), 3.45 (t, J = 7.2 Hz, 2H), 1.84-1.64 (m, 2H), 1.52-1.25 (m, 18H), 0.86 (t, J = 6.8 Hz, 3H);

[0067] 13 C NMR (100 MHz, CDCl3) δ 163.7, 142.2, 140.3, 124.0, 122.7, 113.1, 110.8, 110.7, 91.1, 58.5, 51.0, 31.9, 30.3, 29.6, 29.6, 29.4, 29.4, 29.1, 26.5, 22.7, 14.1;

[0068] HRMS (ESI) m / z: [M + H] ＋ C 22 H 36 N3O + Calculated value is 358.2853; actual value is 358.2853.

[0069] Example 2

[0070] The synthetic route of azacyclic alkaloids 3a-3z is as follows:

[0071] .

[0072] I. Preparation of azacyclic alkaloid 3a .

[0073] At room temperature, intermediate II (0.2 g, 1.04 mmol), n-butylamine (206 μL, 2.08 mmol) were put into a 30 mL reaction vessel, then methanol (10 mL) was added to dissolve them, finally 2 mol / L HCl (60 μL) was added, the temperature was raised to 60 °C, and the reaction was carried out for 7 h, and TLC was used to monitor the reaction. After the reaction was completed, the solvent was removed under reduced pressure, and the organic phase was extracted with ethyl acetate and water, and the organic phase was washed with saturated brine and dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated and separated by column chromatography using a mixed solvent of PE, EA and acetone (ACE) (the volume ratio of PE, EA and ACE was 2.5:1:1) as the eluent, and yellow solid azacyclic alkaloid 3a was obtained, the yield was 62%, the melting point was 112-114 °C, and the spectral data of its 1 H NMR, 13 C NMR and HRMS are as follows:

[0074] 1 H NMR (400 MHz, CDCl3) δ 7.31 (s, 1H), 6.98 (dd, J = 2.2, 1.2 Hz, 1H), 6.76-6.59 (m, 1H), 6.24 (dd, J = 3.6, 2.7 Hz, 1H), 5.94 (s, 1H), 3.88 (s, 3H), 3.41 (t, J = 7.61 Hz, 2H), 1.75-1.61 (m, 2H), 1.39 (m, 2H), 0.92 (t, J = 7.4 Hz, 3H);

[0075] 13 C NMR (100 MHz, CDCl3) δ 163.5, 142.4, 140.5, 123.5, 123.2, 112.5, 111.5, 110.5, 91.3, 58.4, 50.8, 32.3, 19.7, 13.6;

[0076] HRMS (ESI) m / z: [M + H] ＋ C 14 H 20 N3O + Calculated value: 246.1601; actual value: 246.1600.

[0077] II. Preparation of azacyclic alkaloid 3b .

[0078] Except that n-butylamine is replaced by The rest of the preparation process is the same as that of azacyclic alkaloid 3a, and the yield is 62%, and the 1 H NMR, 13 C NMR and HRMS spectral data are as follows:

[0079] 1 H NMR (400 MHz, CDCl3) δ 7.22 (m, 1H), 7.01 (s, 1H), 6.72 (s, 1H), 6.24 (dt, J = 4.8, 2.4 Hz, 1H), 5.93 (s, 1H), 3.87 (s, 3H), 3.19 (d, J = 6.4 Hz, 2H), 1.01 (s, 9H);

[0080] 13 C NMR (100 MHz, CDCl3) δ 164.0, 142.5, 141.0, 124.1, 122.7, 113.2, 110.7, 110.7, 91.2, 63.3, 58.5, 32.8, 27.1;

[0081] HRMS (ESI) m / z: [M + H] ＋ C 15 H 22 N3O + Calculated value is 260.1757; actual value is 260.1755.

[0082] III. Preparation of azacyclic alkaloid 3c .

[0083] Except that n-butylamine is replaced by The rest of the preparation process is the same as that of azacyclic alkaloid 3a, and the yield is 55%, melting point: 121-123℃, and the 1 H NMR, 13 C NMR and HRMS spectral data are as follows:

[0084] 1 H NMR (400 MHz, CDCl3) δ 7.30 (s, 1H), 6.98 (s, 1H), 6.76-6.62 (m, 1H), 6.41-6.16 (m, 1H), 5.94 (s, 1H), 3.87 (d, J=3.7Hz, 3H), 3.43 (dd, J =9.9, 4.8Hz, 2H), 1.75–1.63(m, 1H), 1.59(dd, J =13.6, 7.8Hz, 2H), 0.91(dd, J =6.1, 2.5Hz, 6H);

[0085] 13 C NMR (100MHz, CDCl3) δ 163.5, 142.4, 140.4, 123.7, 123.0, 112.7, 111.3, 110.6, 91.2, 58.4, 49.3, 39.0, 25.5, 22.3;

[0086] HRMS (ESI) m / z: [M+H] ＋ C 15 H 22 N3O + The calculated value is 260.1757; the actual value is 260.1756.

[0087] IV. Preparation of nitrogen heterocyclic alkaloids (3 days) .

[0088] Besides replacing n-butylamine with The remaining preparation process is the same as that for nitrogen heterocyclic alkaloid 3a, with a yield of 58% and a melting point of 146–148 °C. 1 H NMR, 13 The spectral data of C NMR and HRMS are as follows:

[0089] 1 H NMR (400MHz, CDCl3) δ 7.29(s, 1H), 7.04(s, 1H), 6.84–6.68(m, 1H), 6.27(d, J =2.6Hz, 1H), 5.97(s, 1H), 3.91(s, 3H), 3.55–3.32(m, 2H), 1.67(d, J =5.7Hz, 1H), 1.50–1.17(m, 8H), 0.93(dt, J =14.6, 4.6 Hz, 6H);

[0090] 13 C NMR (100MHz, CDCl3) δ163.8, 142.3, 140.7, 124.0, 122.7, 113.1, 110.7, 110.7, 91.1, 58.5, 54.3, 40.2, 30.3, 28.6, 23.6, 22.9, 14.1, 10.7;

[0091] HRMS (ESI) m / z: [M + H]+calcd for C26H32N2O4, 440.2457; found, 440.2457. ＋ C 18 H 28 N3O + calcd 302.2227; found 302.2223.

[0092] V. Preparation of azacyclic alkaloid 3e .

[0093] Except that n-butylamine is replaced by , the rest of the preparation process is the same as that of azacyclic alkaloid 3a, the yield is 68%, the melting point is 133-135°C, and the 1 H NMR, 13 C NMR and HRMS spectral data are as follows:

[0094] 1 H NMR (400 MHz, CDC13) δ 7.29 (s, 1H), 6.96 (d, J = 0.9 Hz, 1H), 6.70 (d, J = 2.7 Hz, 1H), 6.23 (dd, J = 3.4, 2.8 Hz, 1H), 5.95 (s, 1H), 3.86 (s, 3H), 3.39 (t, J = 7.2 Hz, 2H), 1.77-1.60 (m, 2H), 1.44-1.14 (m, 12H), 0.84 (t, J = 6.8 Hz, 3H);

[0095] 13 C NMR (100 MHz, CDC13) δ 163.5, 142.3, 140.5, 123.6, 123.1, 112.6, 110.6, 91.3, 58.4, 51.1, 31.8, 30.4, 29.1, 26.5, 22.6, 14.1;

[0096] HRMS (ESI) m / z: [M + H]+calcd for C26H32N2O4, 440.2457; found, 440.2457. ＋ C 18 H 28 N3O + calcd 302.2227; found 302.2222.

[0097] Six, preparation of azacyclic alkaloid 3f .

[0098] Except that n-butylamine is replaced by , the rest of the preparation process is the same as the preparation process of azacyclic alkaloid 3a, the yield is 43%, the melting point is 142-144℃, and the 1 H NMR, 13 C NMR and HRMS spectrum data are as follows:

[0099] 1 H NMR (400MHz, CDCl3) δ 7.31(d, J =10.7Hz, 1H), 7.00(s, 1H), 6.74(d, J =3.4Hz, 1H), 6.32-6.19(m, 1H), 5.97(s, 1H), 3.89(s, 3H), 3.43(t, J =7.2Hz, 2H), 1.79-1.62(m, 2H), 1.25(s, 30H), 0.88(t, J =6.7Hz, 3H);

[0100] 13 C NMR (100MHz, CDCl3) δ 163.5, 142.2, 140.5, 123.5, 123.0, 112.7, 111.2, 110.6, 91.2, 58.4, 51.1, 31.9, 30.4, 29.7, 29.7, 29.6, 29.6, 29.5, 29.4, 29.1, 26.5, 22.7, 14.1;

[0101] HRMS (ESI) m / z: [M+H] ＋ C 28 H 48 N3O + The calculated value is 442.3792; the actual value is 442.3788.

[0102] Seven, preparation of azacyclic alkaloid 3g .

[0103] Except that n-butylamine is replaced by , the rest of the preparation process is the same as the preparation process of azacyclic alkaloid 3a, the yield is 43%, the melting point is 142-144℃, and the 1 H NMR and 13 C NMR spectrum data are as follows:

[0104] 1 H NMR (400 MHz, CDC13) δ 8.52 (d, J = 4.9 Hz, 2H), 7.64 (d, J = 7.8 Hz, 1H), 7.55 (s, 1H), 7.31 - 7.17 (m, 1H), 6.88 (s, 1H), 6.61 (dd, J = 3.6, 1.1 Hz, 1H), 6.32 - 6.17 (m, 1H), 5.95 (s, 1H), 4.53 (s, 2H), 3.87 (s, 3H); J J = 7.8 Hz, 1H), 7.55 (s, 1H), 7.31 - 7.17 (m, 1H), 6.88 (s, 1H), 6.61 (dd, J = 3.6, 1.1 Hz, 1H), 6.32 - 6.17 (m, 1H), 5.95 (s, 1H), 4.53 (s, 2H), 3.87 (s, 3H); J = 3.6, 1.1 Hz, 1H), 6.32 - 6.17 (m, 1H), 5.95 (s, 1H), 4.53 (s, 2H), 3.87 (s, 3H);

[0105] 13 C NMR (100 MHz, CDC13) δ 163.5, 149.4, 148.8, 140.7, 135.7, 132.2, 123.9, 123.7, 123.4, 122.8, 113.0, 111.9, 110.7, 91.6, 58.4, 52.0.

[0106] Eighth, preparation of azacyclic alkaloid 3h .

[0107] Except that n-butylamine is replaced by , the rest of the preparation process is the same as the preparation process of azacyclic alkaloid 3a, the yield is 43%, the melting point is 115-117°C, and the 1 H NMR, 13 C NMR and HRMS spectral data are as follows:

[0108] 1 H NMR (400 MHz, CDC13) δ 7.96 (s, 1H), 7.30 (t, J = 7.8 Hz, 2H), 7.15 (d, J = 7.7 Hz, 2H), 7.09 (t, J = 7.3 Hz, 1H), 6.85 (s, 1H), 6.60 (d, J = 2.6 Hz, 1H), 6.29 - 6.18 (m, 1H), 6.01 (s, 1H), 3.90 (s, 3H);

[0109] 13 C NMR (100 MHz, CDC13) δ 159.9, 138.7, 132.3, 132.2, 129.3, 128.7, 128.6, 128.6, 124.3, 121.0, 119.1, 110.0, 109.4, 92.3, 58.2;​

[0110] HRMS (ESI) m / z: [M+H] ＋ C 16 H 16 N3O + Calcd 266.1288; Found 266.1286.

[0111] IX. Preparation of azacyclic alkaloid 3i .

[0112] Except that n-butylamine is replaced by , the rest of the preparation process is the same as that of azacyclic alkaloid 3a, the yield is 40%, the melting point is 122-124℃, and the 1 H NMR, 13 C NMR and HRMS spectral data are as follows:

[0113] 1 H NMR (400 MHz, CDCl3) δ 7.92 (s, 1H), 7.41 (d, J = 8.5 Hz, 2H), 7.05 (d, J = 8.3 Hz, 2H), 6.92 (s, 1H), 6.64 (d, J = 2.8 Hz, 1H), 6.33-6.22 (m, 1H), 6.00 (s, 1H), 3.91 (s, 3H);

[0114] 13 C NMR (100 MHz, CDCl3) δ 159.2, 139.5, 132.2, 132.2, 132.2, 132.1, 131.4, 128.7, 128.6, 121.2, 121.0, 117.2, 110.2, 109.6, 91.9, 58.2;

[0115] HRMS (ESI) m / z: [M+H] ＋ C 16 H 15 BrN3O + Calcd 344.0393; Found 344.0388.

[0116] X. Preparation of azacyclic alkaloid 3j .

[0117] Except that n-butylamine is replaced by , the rest of the preparation process is the same as that of azacyclic alkaloid 3a, the yield is 44%, the melting point is 127-128℃, and the 1 H NMR,13 The spectral data of1H NMR and13C NMR are as follows:

[0118] 1 H NMR (400 MHz, CDC13) δ 7.98 (s, 1H), 7.20 (d, J = 8.2 Hz, 2H), 6.99 (d, J = 7.7 Hz, 2H), 6.76 (s, 1H), 6.55 (d, J = 2.7 Hz, 1H), 6.35 - 6.17 (m, 1H), 6.00 (s, 1H), 3.88 (s, 3H);

[0119] 13 C NMR (100 MHz, CDC13) δ 158.7, 140.3, 132.2, 132.2, 132.1, 131.3, 129.4, 129.1, 128.7, 128.6, 124.6, 120.8, 110.1, 109.1, 91.9, 58.2;

[0120] HRMS (ESI) m / z: [M + H] ＋ C 16 H 15 ClN3O + Calculated value is 300.0898; actual value is 300.0897.

[0121] Eleven, preparation of azacyclic alkaloid 3k .

[0122] Except that n-butylamine is replaced by , the rest of the preparation process is the same as the preparation process of azacyclic alkaloid 3a, the yield is 39%, the melting point is 122-124℃, and the 1 H NMR and 13 The spectral data of1H NMR and13C NMR are as follows:

[0123] 1 H NMR (400 MHz, CDC13) δ 7.70 (s, 1H), 7.37 (d, J = 8.4 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 7.07 (s, 1H), 6.74 (d, J = 3.0 Hz, 1H), 6.25 (s, 1H), 5.93 (s, 1H), 3.87 (s, 3H), 1.31 (s, 9H);

[0124] 13 C NMR (100MHz, CDCl3) δ 164.7, 148.6, 144.6, 137.6, 131.3, 128.6, 128.5, 126.6, 124.9, 122.9, 117.3, 114.2, 113.8, 110.7, 92.1, 58.4, 31.3.

[0125] 12. Preparation of 3l of nitrogen heterocyclic alkaloids .

[0126] Besides replacing n-butylamine with The remaining preparation process is the same as that for nitrogen heterocyclic alkaloid 3a, with a yield of 51% and a melting point of 157–159 °C. 1 H NMR, 13 The spectral data of C NMR and HRMS are as follows:

[0127] 1 H NMR (400MHz, CDCl3) δ 7.37(s, 1H), 7.32–7.19(m, 5H), 6.81(s, 1H), 6.62(d, J =2.7Hz, 1H), 6.23–6.16 (m, 1H), 5.94 (s, 1H), 4.42 (s, 2H), 3.80 (s, 3H);

[0128] 13 C NMR (100MHz, CDCl3) δ 162.5, 141.7, 136.8, 128.9, 128.0, 127.8, 124.3, 122.4, 111.2, 110.2, 91.8, 58.3, 55.2;

[0129] HRMS (ESI) m / z: [M+H] ＋ C 17 H 17 FN3O + The calculated value is 298.1350; the actual value is 298.1349.

[0130] 13. Preparation of nitrogen heterocyclic alkaloids 3m .

[0131] Besides replacing n-butylamine with The remaining preparation process is the same as that for nitrogen heterocyclic alkaloid 3a, with a yield of 56% and a melting point of 136–138 °C. 1 H NMR, 13 C NMR and 19The spectral data of1H NMR are as follows:

[0132] 1 H NMR (400 MHz, CDC13) δ 7.36 - 7.27 (m, 3H), 7.01 (dd, J = 14.5, 5.5 Hz, 3H), 6.75 (d, J = 3.0 Hz, 1H), 6.26 - 6.20 (m, 1H), 5.93 (s, 1H), 4.54 (s, 2H), 3.82 (s, 3H);

[0133] 13 C NMR (100 MHz, CDC13) δ 164.2, 163.9, 161.4, 143.0, 139.7, 131.4, 131.4, 129.8, 129.7, 124.3, 122.6, 116.2, 116.0, 113.7, 111.4, 110.9, 91.4, 58.5, 53.0;

[0134] 19 F NMR (376 MHz, CDC13) δ -113.25 (s).

[0135] Fourteen, preparation of azacyclic alkaloid 3n .

[0136] Except that n-butylamine is replaced by , the rest of the preparation process is the same as that of azacyclic alkaloid 3a, the yield is 63%, the melting point is 128-130°C, and the spectral data of1H NMR, 1 13 C NMR and HRMS are as follows:

[0137] 1 H NMR (400 MHz, CDC13) δ 7.35 (s, 1H), 7.19 (d, J = 8.3 Hz, 2H), 7.04 (d, J = 8.2 Hz, 2H), 6.68 (s, 1H), 6.53 (d, J = 2.7 Hz, 1H), 6.22 - 6.10 (m, 1H), 5.90 (s, 1H), 4.25 (s, 2H), 3.82 (s, 3H);

[0138] 13 C NMR (100 MHz, CDC13) δ ​162.0, 142.3, 136.2, 133.3, 128.9, 128.8, 125.6, 121.4, 109.9, 92.2, 58.2, 55.3;

[0139] HRMS (ESI) m / z: [M + H]+calcd for C19H16N3O4, 348.1156; found, 348.1158. ＋ C 17 H 17 ClN3O + calcd 314.1055; found 314.1051.

[0140] Fifteen, preparation of azacyclic alkaloid 3o .

[0141] Except that n-butylamine is replaced by , the rest of the preparation process is the same as the preparation process of azacyclic alkaloid 3a, the yield is 70%, the melting point is 150-152℃, and the 1 H NMR, 13 C NMR and HRMS spectral data are as follows:

[0142] 1 H NMR (400 MHz, CDCl3) δ 7.36 (m, 3H), 7.04 (d, J = 8.2 Hz, 2H), 6.68 (s, 1H), 6.53 (d, J = 2.7 Hz, 1H), 6.27-6.10 (m, 1H), 5.90 (s, 1H), 4.25 (s, 2H), 3.82 (s, 3H);

[0143] 13 C NMR (100 MHz, CDCl3) δ 162.0, 142.2, 136.5, 131.8, 129.3, 124.9, 121.9, 121.6, 110.5, 110.1, 92.0, 58.2, 55.3;

[0144] HRMS (ESI) m / z: [M + H]+calcd for C19H16N3O4, 348.1156; found, 348.1158. ＋ C 17 H 17 BrN3O + calcd 358.0550; found 358.0548.

[0145] Sixteen, preparation of azacyclic alkaloid 3p .

[0146] Except that n-butylamine is replaced by The rest of the preparation process is the same as that of the preparation of azacyclic alkaloid 3a, the yield is 60%, the melting point is 142-144°C, and the structure is as follows: 1 H NMR, 13 The spectral data of C NMR and HRMS are as follows:

[0147] 1 H NMR (400MHz, CDCI3) δ 7.36 (s, 1H), 7.07 (s, 4H), 6.74 (s, 1H), 6.57 (d, J = 2.7 Hz, 1H), 6.23-6.14 (m, 1H), 5.94 (s, 1H), 4.33 (s, 2H), 3.81 (s, 3H), 2.30 (s, 3H);

[0148] 13 C NMR (100MHz, CDCI3) δ 162.3, 141.9, 137.5, 134.1, 129.5, 127.7, 125.2, 121.8, 110.3, 110.0, 92.0, 58.2, 55.1, 31.0, 21.1;

[0149] HRMS (ESI) m / z: [M + H] ＋ C 18 H 20 N3O + The calculated value is 294.1601; the actual value is 294.1598.

[0150] Seventeen, preparation of azacyclic alkaloid 3q .

[0151] Except that n-butylamine is replaced by The rest of the preparation process is the same as that of the preparation of azacyclic alkaloid 3a, the yield is 43%, the melting point is 142-144°C, and the structure is as follows: 1 H NMR, 13 The spectral data of C NMR and HRMS are as follows:

[0152] 1 H NMR (400MHz, CDCI3) δ 7.35 (s, 1H), 7.12 (d, J = 8.1 Hz, 2H), 6.80 (d, J = 7.9 Hz, 3H), 6.60 (dd, J = 3.5, 1.0 Hz, 1H), 6.19 (t, J= 2.9 Hz, IH), 5.93 (s, IH), 4.35 (s, 2H), 3.80 (s, 3H), 3.74 (s, 3H);

[0153] 13 C NMR (100 MHz, CDC13) δ 162.4, 159.3, 141.6, 129.2, 128.8, 124.7, 122.2, 114.2, 110.8, 110.1, 91.9, 58.2, 55.3, 54.7;

[0154] HRMS (ESI) m / z: [M + H] ＋ C 18 H 20 N3O2 + Calculated 310.1550; Found 310.1546.

[0155] Eighteen, preparation of azacyclic alkaloid 3r .

[0156] Except that n-butylamine is replaced by , the rest of the preparation process is the same as the preparation process of azacyclic alkaloid 3a, the yield is 62%, the melting point is 133-135°C, and the 1 H NMR, 13 C NMR, 19 F NMR and HRMS spectral data are as follows:

[0157] 1 H NMR (400 MHz, CDC13) δ 7.50 (d, J = 7.9 Hz, 2H), 7.43 (s, IH), 7.32-7.23 (m, 2H), 6.78 (s, IH), 6.59 (d, J = 2.9 Hz, IH), 6.23-6.15 (m, IH), 5.92 (s, IH), 4.44 (s, 2H), 3.84 (s, 3H);

[0158] 13 C NMR (100 MHz, CDC13) δ 161.8, 142.5, 141.5, 130.0, 129.7, 127.8, 125.7, 125.6, 125.4, 124.5, 122.7, 122.1, 114.7, 110.9, 110.3, 91.9, 58.2, 55.7;

[0159] 19F NMR (376 MHz, CDCl3) δ -62.55;

[0160] HRMS (ESI) m / z: [M + H] ＋ C 18 H 17 F3N3O + Calculated: 348.1318; Found: 348.1314.

[0161] Nineteen, preparation of azacyclic alkaloid 3s .

[0162] Except that n-butylamine is replaced by , the rest of the preparation process is the same as that of azacyclic alkaloid 3a, the yield is 45%, the melting point is 122-124℃, and the 1 H NMR, 13 C NMR and HRMS spectral data are as follows:

[0163] 1 H NMR (400 MHz, CDCl3) δ 7.38 (s, 1H), 7.17 (s, 4H), 6.84 (s, 1H), 6.65 (d, J = 2.9 Hz, 1H), 6.26-6.14 (m, 1H), 5.95 (s, 1H), 4.41 (s, 2H), 3.79 (s, 3H), 2.87 (dt, J = 13.8, 6.9 Hz, 1H), 1.21 (d, J = 6.9 Hz, 6H);

[0164] 13 C NMR (100 MHz, CDCl3) δ 162.5, 148.7, 141.6, 134.1, 127.9, 127.0, 126.6, 122.5, 113.5, 111.4, 110.2, 91.7, 58.3, 54.9, 33.8, 24.0;

[0165] HRMS (ESI) m / z: [M + H] ＋ Calculated: C 20 H 24 N3O ＋ 322.1914; Found: 322.1917.

[0166] Twenty, preparation of azacyclic alkaloid 3t .

[0167] Except that n-butylamine is replaced by The rest of the preparation process is the same as that of the preparation of azacyclic alkaloid 3a, the yield is 54%, the melting point is 133-135°C, and the 1 H NMR, 13 The spectral data of C NMR and HRMS are as follows:

[0168] 1 H NMR (400MHz, CDCI3) δ 7.36 (s, 1H), 6.93 (s, 1H), 6.64 (d, J = 2.6 Hz, 1H), 6.29-6.06 (m, 1H), 5.94 (s, 1H), 3.87 (s, 3H), 3.81 (dd, J = 12.7, 6.5 Hz, 1H), 1.98 (dt, J = 11.9, 9.2 Hz, 2H), 1.78 (ddd, J = 18.7, 10.5, 6.0 Hz, 4H), 1.61 (dt, J = 8.4, 6.7 Hz, 2H);

[0169] 13 C NMR (100MHz, CDCI3) δ 163.2, 142.4, 139.1, 122.9, 111.9, 110.3, 91.3, 62.3, 58.3, 33.6, 29.7, 23.7;

[0170] HRMS (ESI) m / z: [M + H] ＋ C 15 H 20 N3O ＋ The calculated value is 258.1601; the actual value is 258.1600.

[0171] Twenty-one, preparation of azacyclic alkaloid 3u .

[0172] Except that n-butylamine is replaced by The rest of the preparation process is the same as that of the preparation of azacyclic alkaloid 3a, the yield is 54%, the melting point is 133-135°C, and the 1 H NMR, 13 The spectral data of C NMR and HRMS are as follows:

[0173] 1 H NMR (400MHz, CDCI3) δ 7.38 (d, J = 12.3 Hz, 1H), 7.03 (d, J= 1.1 Hz, 1 H), 6.71 (d, J = 1.4 Hz, 1 H), 6.25 (dd, J = 3.5, 2.0 Hz, 1 H), 5.93 (s, 1 H), 3.89 (s, 3 H), 3.51 - 3.18 (m, 1 H), 2.07 - 1.99 (m, 2 H), 1.92 - 1.74 (m, 2 H), 1.70 - 1.50 (m, 3 H), 1.44 - 1.18 (m, 3 H);

[0174] 13 C NMR (100 MHz, CDC13) δ 163.6, 142.1, 138.4, 124.0, 122.8, 112.9, 110.8, 110.6, 91.1, 59.6, 58.4, 33.2, 24.8, 24.5;

[0175] HRMS (ESI) m / z: [M + H] ＋ C 16 H 22 N3O + Calculated 272.1757; Found 272.1756.

[0176] Twenty-two, preparation of azacyclic alkaloid 3v .

[0177] Except that n-butylamine is replaced by , the rest of the preparation process is the same as that of azacyclic alkaloid 3a, the yield is 45%, the melting point is 122-124℃, and the 1 H NMR, 13 C NMR and HRMS spectral data are as follows:

[0178] 1 H NMR (400 MHz, CDC13) δ 7.34 (s, 1 H), 6.95 (s, 1 H), 6.69 (d, J = 3.0 Hz, 1 H), 6.28 - 6.15 (m, 1 H), 5.95 (s, 1 H), 3.85 (s, 3 H), 3.57 - 3.40 (m, 1 H), 1.99 (d, J = 5.8 Hz, 2 H), 1.76 (dd, J = 21.1, 9.4 Hz, 4 H), 1.54 (s, 4 H), 1.43 (s, 2 H);

[0179] 13 C NMR (100 MHz, CDC13) δ163.4, 142.2, 138.6, 123.4, 123.1, 112.4, 111.3, 110.5, 91.3, 62.3, 58.4, 35.5, 27.8, 23.7;

[0180] HRMS (ESI) m / z: [M + H]+calcd for C26H28N4O4, 460.2088; found, 460.2088. ＋ C 18 H 26 N3O ＋ calcd 300.2070; found 300.2070.

[0181] Twenty-Three, Preparation of Azacyclic Alkaloid 3w .

[0182] Except that n-butylamine is replaced by , the rest of the preparation process is the same as that of Azacyclic Alkaloid 3a, the yield is 54%, the melting point is 132-134°C, and the 1 H NMR, 13 C NMR and HRMS spectral data are as follows:

[0183] 1 H NMR (400 MHz, CDCl3) δ 7.33 (s, 1H), 6.92 (s, 1H), 6.65 (d, J = 2.4 Hz, 1H), 6.30-6.10 (m, 1H), 5.94 (s, 1H), 3.86 (s, 3H), 3.59-3.41 (m, 1H), 1.97-1.86 (m, 2H), 1.77 (ddd, J = 23.3, 15.1, 6.4 Hz, 4H), 1.63-1.40 (m, 8H);

[0184] 13 C NMR (100 MHz, CDCl3) δ 163.3, 142.7, 138.7, 123.9, 122.8, 111.7, 110.2, 91.4, 61.5, 58.3, 32.6, 29.7, 27.0, 25.3, 23.4;

[0185] HRMS (ESI) m / z: [M + H]+calcd for C26H28N4O4, 460.2088; found, 460.2088. ＋ C 17 H 24 N3O ＋ calcd 286.1914; found 286.1912.

[0186] Twenty-Four, Preparation of Azacyclic Alkaloid 3x .

[0187] Except that n-butylamine is replaced by The rest of the preparation process is the same as the preparation process of azacyclic alkaloid 3a, the yield is 55%, the melting point is 165-167℃, because of the existence of steric hindrance of the group, there are rotational isomers, the main product obtained 1 H NMR, 13 C NMR and HRMS spectral data are as follows:

[0188] 1 H NMR(400MHz,CDCl3) δ 7.40(s,1H),6.98(s,1H),6.65(d, J =3.0Hz,1H),6.29–6.15(m,1H),5.91(s,1H),3.87(s,3H),2.16(s,3H),1.97(m,6H),1.75–1.47(m,6H);

[0189] 13 C NMR(100MHz,CDCl3) δ 163.7,135.3,132.1,124.4,122.4,113.3,110.7,110.5,91.5,58.3,55.9,42.4,35.7,29.7,29.3;

[0190] HRMS (ESI) m / z: [M+H] ＋ Calculated for C 20 H 26 N3O ＋ 324.2070; actual value is 324.2067.

[0191] Twenty-five, preparation of azacyclic alkaloid 3y .

[0192] Except that n-butylamine is replaced by The rest of the preparation process is the same as the preparation process of azacyclic alkaloid 3a, the yield is 65%, the melting point is 141-143℃, and its 1 H NMR, 13 C NMR and HRMS spectral data are as follows:

[0193] 1 H NMR(400MHz,CDCl3) δ 7.33(s,1H),6.94(s,1H),6.69(d, J= 2.8 Hz, 1H), 6.21 (s, 1H), 5.98 (s, 1H), 3.88 (s, 3H), 3.60 - 3.30 (m, 1H), 1.81 (m, 2H), 1.55 (m, 2H), 1.45 - 1.21 (m, 18H);

[0194] 13 C NMR (100 MHz, CDC13) δ 163.4, 142.5, 139.1, 123.5, 123.3, 112.2, 111.8, 110.4, 91.3, 58.4, 30.7, 23.6, 23.4, 21.4;

[0195] HRMS (ESI) m / z: [M + H] ＋ C 22 H 34 N3O ＋ Calculated 356.2696; Found 356.2693.

[0196] Twenty-six, preparation of azacyclic alkaloid 3z .

[0197] Except that n-butylamine is replaced by , the rest of the preparation process is the same as the preparation process of azacyclic alkaloid 3a, the yield is 45%, the melting point is 131-133℃, and the 1 H NMR and 13 C NMR spectrum data are as follows:

[0198] 1 H NMR (400 MHz, CDC13) δ 7.10 (s, 1H), 6.78 (s, 1H), 6.31 (s, 1H), 6.03 (d, J = 1.5 Hz, 1H), 5.29 (s, 1H), 4.12 (q, J = 7.2 Hz, 1H), 3.91 (s, 3H), 1.37 - 1.18 (m, 2H), 0.87 (dt, J = 6.1, 5.4 Hz, 4H);

[0199] 13 C NMR (100 MHz, CDC13) δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ δ 163.2, 142.8, 124.3, 122.9, 117.2, 113.9, 111.0, 109.2, 92.3, 58.3, 31.6, 29.7, 22.7, 14.1.

[0200] Test Example 1

[0201] The detection of anti-tobacco mosaic virus activity is as follows:

[0202] I. Virus purification and concentration determination.

[0203] The virus purification and concentration determination refer to the SOP specification prepared by the South University Element Laboratory. After 2 PEG centrifugation treatments of the crude virus extract, the concentration is determined, and it is stored at 4°C for standby.

[0204] II. Solution preparation, the process is as follows:

[0205] After weighing, the nitrogen heterocyclic alkaloid and ribavirin crude drug are respectively added to DMF for dissolution to prepare 1x10 5 µg / mL mother liquor, which is then diluted to the required concentration with 1‰ Tween 80 aqueous solution.

[0206] III. Detection of in vivo protective effect, the process is as follows:

[0207] Select 3-5 leaf stage red flower tobacco with uniform growth, spray the whole plant with the drug, repeat 3 times for each treatment, and set 1‰ Tween 80 aqueous solution as a control. After 24 hours, sprinkle corundum (500 mesh) on the leaf surface, use a brush to dip the virus solution, and gently rub the whole leaf surface along the vein direction for 2 times, support the leaf below with the palm of the hand, the virus concentration is 10 µg / mL, after inoculation, rinse with running water, record the number of lesions after 3 days, and calculate the control effect.

[0208] IV. Detection of in vivo treatment effect, the process is as follows:

[0209] Select 3-5 leaf stage red flower tobacco with uniform growth, use a brush to inoculate the whole leaf with the virus, the virus concentration is 10 µg / mL, after inoculation, rinse with running water. After the leaf surface is dry, spray the whole plant with the drug, repeat 3 times for each treatment, and set 1‰ Tween 80 aqueous solution as a control, record the number of lesions after 3 days, and calculate the control effect.

[0210] V. Detection of in vivo passivation effect, the process is as follows:

[0211] Select 3-5 leaf stage red flower tobacco with uniform growth, mix the drug with an equal volume of virus juice for passivation for 30 minutes, then rub for inoculation, the virus concentration is 20 µg / mL, after inoculation, rinse immediately with running water, repeat 3 times, set 1‰ Tween 80 aqueous solution as a control, count the number of lesions after 3 days, and calculate the results.

[0212] Among them, the inhibition rate (%) = [(control dead spots - treatment dead spots) / control dead spots] x 100%.

[0213] Under the treatment dose of 500 µg / mL, the in vivo passivation, in vivo treatment and in vivo protection activities of all the tested substances against tobacco mosaic virus were tested, and the results are shown in Table 1.

[0214] Table 1 Anti-tobacco mosaic virus activity test results of azacyclic alkaloid series compounds

[0215]

[0216] From the data provided in Table 1, it can be seen that under the condition of 500 mg / L, azacyclic alkaloids 3a-3z all have antiviral activity, among which 3b, 3c, a and d have antiviral activity comparable to the positive control drug; azacyclic alkaloids 3d, 3e, 3k, 3v and 3z have higher activity in vivo passivation, in vivo treatment and in vivo protection than the positive control drug ribavirin, among which azacyclic alkaloid 3z has a relative inhibition rate as high as 53.7±2.4% in vivo passivation, a relative inhibition rate as high as 51.0±3.8% in vivo treatment and a relative inhibition rate as high as 50.6±1.9% in vivo protection.

[0217] In summary, under the condition of 500 mg / L, azacyclic alkaloid series compounds have inhibitory activity on tobacco mosaic virus and are expected to be applied in the prevention and treatment of plant antiviral diseases.

[0218] Finally, it should be noted that the above examples are only used to illustrate the technical solutions of the present application, and are not limited thereto; although the present application has been described in detail with reference to the foregoing examples, those skilled in the art should understand that they can still modify the technical solutions recorded in the foregoing examples, or make equivalent replacement for part of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present application.

Claims

1. Use of aza-cyclic alkaloids for the control of plant viruses, characterized in that, The structural formula of the nitrogen heterocyclic alkaloid is as follows: 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 ； The virus is selected from the group consisting of tobacco mosaic virus.

2. Use of the azacyclic alkaloid according to claim 1 for the control of plant viruses, characterized in that, The plant is selected from one or more of the group consisting of solanaceous plants, cruciferous plants, chenopodiaceous plants, cucurbitaceous plants and leguminous plants.

3. Use of the azacyclic alkaloid according to claim 2 for the control of plant viruses, characterized in that, The solanaceous plant is selected from one or more of the group consisting of tobacco, tomato, pepper and eggplant; the cruciferous plant is selected from one or more of the group consisting of Chinese cabbage, cabbage and rape; the chenopodiaceous plant is selected from one or both of the group consisting of spinach and amaranth; the cucurbitaceous plant is selected from cucumber; and the leguminous plant is selected from one or both of the group consisting of kidney bean and cowpea.

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