Azacyclo-alkaloid and application of azacyclo-alkaloid in prevention and treatment of plant viruses

Abstract

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

Description

[0001] This application is a divisional application of the Chinese invention patent application with the application date of August 28, 2025, the application number of 202511213258.4, and the invention name of "Aza heterocyclic alkaloid and its application in preventing and treating plant viruses". TECHNICAL FIELD

[0002] The present application relates to the technical field of aza heterocyclic compounds, in particular to an aza heterocyclic alkaloid and its application in preventing and treating plant viruses. BACKGROUND

[0003] The prevention of plant viruses is an important issue in global agricultural production, but due to the complexity of viruses and the diversity of transmission mechanisms, its prevention faces many challenges. At present, the prevention methods of plant virus diseases include agricultural prevention, biological prevention, chemical prevention and genetic engineering, etc. Chemical prevention is widely used in agricultural production due to its simple operation, quick effect and other advantages.

[0004] 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 effect in actual application, but due to their drug resistance problem, it seriously affects their prevention effect.

[0005] Aza heterocyclic alkaloids are a class of nitrogen-containing secondary metabolites formed by plants in long-term evolution. Due to their unique chemical structure and biological activity, they have universal antitumor, antibacterial and immunosuppressive activity. However, the biological activity research of this class of compounds mainly focuses on the research of medicinal activity, and the application in the field of agriculture is rarely reported, especially the research on plant antiviral is not reported. SUMMARY

[0006] The present application aims to at least solve one of the technical problems in the related art. To this end, the first object of the present application is to provide an aza heterocyclic alkaloid, and the second object of the present application is to provide an application of the aza heterocyclic alkaloid in preventing and treating plant viruses.

[0007] In order to achieve the first object, the technical solution adopted by the present application is as follows: An aza heterocyclic alkaloid, the structural formula of which is as follows: , Among them, X is selected from any one of -OCH3, -OCH2CH3 and -O(CH2)2CH3; R is selected from any one of the following groups: , , ; -(CH2) n CH3, n is selected from any integer from 1 to 17; -(CH2) m CH(CH3)2, m is selected from 1 or 2; -CH2C(CH3)3, -CH(CH2CH3)(CH2CH2CH3); a is selected from any integer from 1 to 8; b is selected from any integer from 1 to 3; R1is selected from H, a halogen, and -C(CH3)3; R2is selected from H, -CH3, a halogen, -C(CH3)3, -CF3, or -OCH3.

[0008] Preferably, X is selected from -OCH3; and R is selected from -(CH2) n CH3, n is selected from 1, 3, 7, 11, or 17.

[0009] Preferably, X is selected from -OCH3; and R is selected from .

[0010] Preferably, X is selected from -OCH3; and R is selected from .

[0011] Preferably, X is selected from -OCH3; and R is selected from R1is selected from Cl or Br of a halogen.

[0012] Preferably, X is selected from -OCH3; and R is selected from R2is selected from F, Cl, or Br of a halogen.

[0013] To achieve the second object, the technical scheme adopted by the present application is: Use of an azacyclic alkaloid in the prevention and treatment of plant viruses, the azacyclic alkaloid as claimed in any one of the preceding items.

[0014] Preferably, the virus is selected from tobacco mosaic virus.

[0015] Preferably, the plant is selected from one or more of Solanaceae plants, Cruciferae plants, Chenopodiaceae plants, Cucurbitaceae plants, and Leguminosae plants.

[0016] 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.

[0017] The one or more technical solutions in the embodiments of the present application have at least one of the following technical effects: 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.

[0018] 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 having ordinary skill in the art upon examination of the following or can be learned from practice of the application. DETAILED DESCRIPTION

[0019] In order to make the objects, technical solutions and advantages of the present application clearer, the technical solutions in the present application will be described clearly and completely below in conjunction with specific embodiments. Obviously, the described embodiments are only some 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 work 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.

[0020] A nitrogen heterocyclic alkaloid has the following structural formula: In the following examples, the experimental methods used are conventional methods, and the materials, reagents, etc. used are obtained from commercial channels according to the techniques or conditions described in the literature in the art or according to the product instructions, unless otherwise specified.

[0021] Example 1 The synthesis route of the nitrogen heterocyclic alkaloid (a, b, c and d) is as follows: ; The preparation process is as follows: I. Preparation of intermediate I.

[0022] 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: 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); 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; HRMS (ESI) m / z: [M + H] ＋ C 10 H 16 BrN2O + Calculated value was 259.0440, actual value was 259.0443.

[0023] II. Preparation of intermediate II.

[0024] 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, then 10 wt% aqueous solution of dioxane (70 mL) was added into the flask, the solution was stirred and dissolved, then the temperature was raised to 100 °C, after 3 h, the temperature was lowered to room temperature, then sodium methoxide (3.21 g, 59.4 mmol) was slowly added into the reaction system. Then the temperature was raised to 100 °C, after 2.5 h, the reaction was monitored by TLC. After the reaction was completed, the solution was adjusted to neutral by 2 mol / L HCl, after 15 min, the reaction was filtered, the filter cake was washed by water and acetone, then dried, to obtain intermediate II, the yield was 70%, the melting point was 224-227 °C, the spectral data of1H NMR,13C NMR and HRMS were as follows: 1 H NMR、 13 C NMR and HRMS are as follows: 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); 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; HRMS(ESI)m / z:[M-H] － C 10 H9N2O2 - Calculated value was 189.0670; actual value was 189.0669.

[0025] III. Preparation of azacyclic alkaloid a .

[0026] 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: 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); 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.

[0027] Four, preparation of azacyclic alkaloid b .

[0028] 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, followed by the addition of ethylamine (0.3 mL, 5.2 mmol), glacial acetic acid (0.3 mL, 5.2 mmol) in sequence, and the reaction was allowed to proceed at 50 °C for 6 h, with TLC monitoring. 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 previously obtained organic phase, washed with saturated brine, dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated. The yellow oil of the azacyclic alkaloid b was obtained by column chromatography using a mixture of PE and EA (volume ratio of PE to EA was 2:1) as the eluent, with a yield of 85%. The spectral data of1H NMR,13C NMR and HRMS are as follows: 1 H NMR, 13 C NMR and HRMS are as follows: 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); 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; HRMS (ESI) m / z: [M + H] ＋ C 12 H 16 N3O + Calculated value: 218.1288; actual value: 218.1285.

[0029] V. Preparation of azacyclic alkaloid c .

[0030] 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, with TLC monitoring. 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 separate the yellow oil of azacyclic alkaloid b, with a yield of 85%, and its structure was confirmed by1H NMR,13C NMR and HRMS. 1 H NMR、 13 C NMR and HRMS spectral data are as follows: 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); 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; HRMS (ESI) m / z: [M + H] ＋ H 20 N3O + Calculated value is 294.1601; actual value is 294.1602.

[0031] Six, preparation of azacyclic alkaloid d .

[0032] 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, and the reaction was allowed to proceed at 50 °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 to extract the reaction mixture, and the organic phase was collected, and the aqueous phase was extracted with dichloromethane, and then the obtained organic phase was combined with the previously obtained organic phase, and then saturated brine was used to wash, and anhydrous Na2SO4 was used for drying, and then the filtrate was concentrated, and then a mixed solvent of PE and EA (the volume ratio of PE to EA was 1:2) was used as an eluent for column chromatography separation, and then azacyclic alkaloid b in yellow oil was obtained, and the yield was 54%, and its structure was confirmed by1H NMR,13C NMR and HRMS. 1 H NMR、 13 C NMR and HRMS spectral data are as follows: 1 H NMR(400MHz,CDCl3) δ 10.69(s,1H),7.31(s,1H),7.03(s,1H),6.72(d, J =2.8Hz,1H),6.31–6.20(m,1H),5.93(s,1H),3.89(s,3H),3.45(t, J =7.2Hz,2H),1.84–1.64(m,2H),1.52–1.25(m,18H),0.86(t, J =6.8Hz,3H); 13 C NMR(100MHz,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; HRMS(ESI)m / z:[M+H] ＋ C 22 H 36 N3O + Calculated value is 358.2853; actual value is 358.2853.

[0033] Example 2 The synthetic route of azacyclic alkaloids 3a-3z is as follows: .

[0034] I. Preparation of azacyclic alkaloid 3a .

[0035] 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: 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); 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; HRMS (ESI) m / z: [M + H] ＋ C 14 H 20 N3O + Calculated value is 246.1601; actual value is 246.1600.

[0036] II. Preparation of azacyclic alkaloid 3b .

[0037] 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 melting point is 121-123 °C, and the spectral data of H NMR, C NMR and HRMS are as follows: 1 H NMR, 13 C NMR and HRMS are as follows: 1 H NMR (400MHz, CDCl3) δ 7.22 (m, 1H), 7.01 (s, 1H), 6.72 (s, 1H), 6.24 (dt, J =4.8, 2.4Hz, 1H), 5.93 (s, 1H), 3.87 (s, 3H), 3.19 (d, J =6.4Hz, 2H), 1.01 (s, 9H); 13 C NMR (100MHz, 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; HRMS (ESI) m / z: [M + H] ＋ C 15 H 22 N3O + The calculated value is 260.1757; the actual value is 260.1755.

[0038] III. Preparation of azacyclic alkaloid 3c .

[0039] 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%, and the melting point is 121-123 °C, and the spectral data of H NMR, C NMR and HRMS are as follows: 1 H NMR, 13 C NMR and HRMS are as follows: 1 H NMR (400MHz, 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). 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; HRMS (ESI) m / z: [M+H] ＋ C 15 H 22 N3O + The calculated value is 260.1757; the actual value is 260.1756.

[0040] IV. Preparation of nitrogen heterocyclic alkaloids (3 days) .

[0041] 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: 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); 13 C NMR (100MHz, CDCl3) δ 163.8, 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; HRMS (ESI) m / z: [M+H] ＋ C 18 H 28 N3O + The calculated value is 302.2227; the actual value is 302.2223.

[0042] V. Preparation of nitrogen heterocyclic alkaloid 3e .

[0043] 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℃, and the 1 H NMR, 13 C NMR and HRMS spectral data are as follows: 1 H NMR (400MHz, CDCl3) δ 7.29 (s, 1H), 6.96 (d, J = 0.9Hz, 1H), 6.70 (d, J = 2.7Hz, 1H), 6.23 (dd, J = 3.4, 2.8Hz, 1H), 5.95 (s, 1H), 3.86 (s, 3H), 3.39 (t, J = 7.2Hz, 2H), 1.77-1.60 (m, 2H), 1.44-1.14 (m, 12H), 0.84 (t, J = 6.8Hz, 3H); 13 C NMR (100MHz, CDCl3) 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; HRMS (ESI) m / z: [M + H] ＋ C 18 H 28 N3O + Calculated value is 302.2227; actual value is 302.2222.

[0044] Six, preparation of azacyclic alkaloid 3f .

[0045] 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 43%, the melting point is 142-144℃, and the 1 H NMR, 13 C NMR and HRMS spectral data are as follows: 1 H NMR (400MHz, CDCl3) δ 7.31 (d, J = 10.7Hz, 1H), 7.00 (s, 1H), 6.74 (d,J = 3.4 Hz, 1H), 6.32 - 6.19 (m, 1H), 5.97 (s, 1H), 3.89 (s, 3H), 3.43 (t, J = 7.2 Hz, 2H), 1.79 - 1.62 (m, 2H), 1.25 (s, 30H), 0.88 (t, J = 6.7 Hz, 3H); 13 C NMR (100 MHz, CDC13) 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; HRMS (ESI) m / z: [M + H] ＋ C 28 H 48 N3O + Calculated 442.3792; Found 442.3788.

[0046] Seven, preparation of azacyclic alkaloid 3g .

[0047] 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 129-131℃, the 1 H NMR and 13 C NMR spectrum data are as follows: 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); 13 C NMR (100 MHz, CDC13) δ163.5, 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.

[0048] EIGHT, PREPARATION OF AZACYCLIC ALKALOID 3h .

[0049] 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 43%, the melting point is 115-117°C, and the 1 H NMR, 13 C NMR and HRMS spectrum data are as follows: 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); 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; HRMS (ESI) m / z: [M + H] ＋ C 16 H 16 N3O + Calculated value is 266.1288; actual value is 266.1286.

[0050] NINTH, PREPARATION OF AZACYCLIC ALKALOID 3i .

[0051] 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 43%, the melting point is 115-117°C, and the 1 H NMR, 13 C NMR and HRMS spectrum data are as follows: 1 H NMR (400 MHz, CDC13) 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); 13 C NMR (100 MHz, CDC13) 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; HRMS (ESI) m / z: [M + H] ＋ C 16 H 15 BrN3O + Calculated 344.0393; Found 344.0388.

[0052] X. Preparation of azacyclic alkaloid 3j .

[0053] 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°C, and the 1 H NMR, 13 C NMR and HRMS spectral data are as follows: 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); 13 C NMR (100 MHz, CDC13) δ158.7, 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; HRMS (ESI) m / z: [M + H] ＋ C 16 H 15 ClN3O + Calculated 300.0898; Found 300.0897.

[0054] Eleven, preparation of azacyclic alkaloid 3k .

[0055] 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 39%, the melting point is 122-124°C, and the 1 H NMR and 13 C NMR spectrum data are as follows: 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); 13 C NMR (100 MHz, CDC13) 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.

[0056] Twelve, preparation of azacyclic alkaloid 3l .

[0057] 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 51%, the melting point is 157-159°C, and the 1 H NMR, 13 C NMR and HRMS spectrum data are as follows: 1H NMR (400 MHz, CDC13) δ 7.37 (s, 1 H), 7.32 - 7.19 (m, 5 H), 6.81 (s, 1 H), 6.62 (d, J = 2.7 Hz, 1 H), 6.23 - 6.16 (m, 1 H), 5.94 (s, 1 H), 4.42 (s, 2 H), 3.80 (s, 3 H); 13 C NMR (100 MHz, CDC13) 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; HRMS (ESI) m / z: [M + H] ＋ C 17 H 17 FN3O + Calculated 298.1350; Found 298.1349.

[0058] Thirteen, preparation of azacyclic alkaloid 3m .

[0059] 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 56%, the melting point is 136-138℃, and the 1 H NMR, 13 C NMR and 19 F NMR spectrum data are as follows: 1 H NMR (400 MHz, CDC13) δ 7.36 - 7.27 (m, 3 H), 7.01 (dd, J = 14.5, 5.5 Hz, 3 H), 6.75 (d, J = 3.0 Hz, 1 H), 6.26 - 6.20 (m, 1 H), 5.93 (s, 1 H), 4.54 (s, 2 H), 3.82 (s, 3 H); 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; 19F NMR (376 MHz, CDC13) δ -113.25 (s).

[0060] XIV. Preparation of azacyclic alkaloid 3n .

[0061] 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 of 1 H NMR, 13 C NMR and HRMS are as follows: 1 H NMR (400 MHz, CDC13) δ 7.35 (m, 3H), 7.04 (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); 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; HRMS (ESI) m / z: [M + H] ＋ C 17 H 17 ClN3O + Calculated value is 314.1055; actual value is 314.1051.

[0062] XV. Preparation of azacyclic alkaloid 3o .

[0063] 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 of 1 H NMR, 13 C NMR and HRMS are as follows: 1 H NMR (400 MHz, CDC13) δ 7.36 (m, 3H), 7.04 (d, J8.2 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); 13 C NMR (100 MHz, CDC13) 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; HRMS (ESI) m / z: [M + H] ＋ C 17 H 17 BrN3O + Calculated 358.0550; Found 358.0548.

[0064] Sixteen, preparation of azacyclic alkaloid 3p .

[0065] 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 60%, the melting point is 142-144℃, and the 1 H NMR, 13 C NMR and HRMS spectral data are as follows: 1 H NMR (400 MHz, CDC13) 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); 13 C NMR (100 MHz, CDC13) 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; HRMS (ESI) m / z: [M + H] ＋ C 18 H 20 N3O + Calculated 294.1601; Found 294.1598.

[0066] Seventeen, preparation of azacyclic alkaloid 3q .

[0067] 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 spectral data of 1 H NMR, 13 C NMR and HRMS are as follows: 1 H NMR (400MHz, CDCl3) δ 7.35 (s, 1H), 7.12 (d, J =8.1Hz, 2H), 6.80 (d, J =7.9Hz, 3H), 6.60 (dd, J =3.5, 1.0Hz, 1H), 6.19 (t, J =2.9Hz, 1H), 5.93 (s, 1H), 4.35 (s, 2H), 3.80 (s, 3H), 3.74 (s, 3H); 13 C NMR (100MHz, CDCl3) 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; HRMS (ESI) m / z: [M+H] ＋ C 18 H 20 N3O2 + Calculated value is 310.1550; actual value is 310.1546.

[0068] Eighteen, preparation of azacyclic alkaloid 3r .

[0069] 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℃, and the spectral data of 1 H NMR, 13 C NMR, 19 F NMR and HRMS are as follows: 1 H NMR (400MHz, CDCl3) δ 7.50 (d, J=7.9Hz, 2H), 7.43(s, 1H), 7.32–7.23(m, 2H), 6.78(s, 1H), 6.59(d, J =2.9Hz, 1H), 6.23–6.15 (m, 1H), 5.92 (s, 1H), 4.44 (s, 2H), 3.84 (s, 3H); 13 C NMR (100MHz, CDCl3) 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; 19 F NMR (376MHz, CDCl3) δ -62.55; HRMS (ESI) m / z: [M+H] ＋ C 18 H 17 F3N3O + The calculated value is 348.1318; the actual value is 348.1314.

[0070] 19. Preparation of nitrogen heterocyclic alkaloids 3s .

[0071] Besides replacing n-butylamine with The remaining preparation process is the same as that for nitrogen heterocyclic alkaloid 3a, with a yield of 45% and a melting point of 122–124 °C. 1 H NMR, 13 The spectral data of C NMR and HRMS are as follows: 1 H NMR (400MHz, CDCl3) δ 7.38(s, 1H), 7.17(s, 4H), 6.84(s, 1H), 6.65(d, J =2.9Hz, 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, 6.9Hz, 1H), 1.21(d, J =6.9Hz, 6H); 13 C NMR (100MHz, CDCl3) δ162.5, 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; HRMS (ESI) m / z: [M + H] ＋ Calculated for C 20 H 24 N3O ＋ 322.1914; Found 322.1917.

[0072] XX. Preparation of azacyclic alkaloid 3t .

[0073] 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 133-135°C, and the 1 H NMR, 13 C NMR and HRMS spectral data are as follows: 1 H NMR (400 MHz, CDC13) 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); 13 C NMR (100 MHz, CDC13) 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; HRMS (ESI) m / z: [M + H] ＋ C 15 H 20 N3O ＋ Calculated for C258.1601; Found 258.1600.

[0074] XXI. Preparation of azacyclic alkaloid 3u .

[0075] 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 112-114°C, and the 1 H NMR, 13 C NMR and HRMS spectral data are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.38 (d, J = 12.3 Hz, 1H), 7.03 (d, J = 1.1 Hz, 1H), 6.71 (d, J = 1.4 Hz, 1H), 6.25 (dd, J = 3.5, 2.0 Hz, 1H), 5.93 (s, 1H), 3.89 (s, 3H), 3.51-3.18 (m, 1H), 2.07-1.99 (m, 2H), 1.92-1.74 (m, 2H), 1.70-1.50 (m, 3H), 1.44-1.18 (m, 3H); 13 C NMR (100 MHz, CDCl3) 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; HRMS (ESI) m / z: [M + H] ＋ C 16 H 22 N3O + Calculated value is 272.1757; actual value is 272.1756.

[0076] Twenty-two, preparation of azacyclic alkaloid 3v .

[0077] 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 112-114°C, and the 1 H NMR, 13 C NMR and HRMS spectral data are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.34 (s, 1H), 6.95 (s, 1H), 6.69 (d, J= 2.4 Hz, 1 H), 6.30 - 6.10 (m, 1 H), 5.94 (s, 1 H), 3.86 (s, 3 H), 3.59 - 3.41 (m, 1 H), 1.97 - 1.86 (m, 2 H), 1.77 (ddd, J = 13.7, 9.0, 6.4 Hz, 1 H), 1.64 - 1.42 (m, 4 H), 1.41 - 1.30 (m, 2 H); J = 2.4 Hz, 1 H), 6.30 - 6.10 (m, 1 H), 5.94 (s, 1 H), 3.86 (s, 3 H), 3.59 - 3.41 (m, 1 H), 1.97 - 1.86 (m, 2 H), 1.77 (ddd, J = 13.7, 9.0, 6.4 Hz, 1 H), 1.64 - 1.42 (m, 4 H), 1.41 - 1.30 (m, 2 H); J = 2.4 Hz, 1 H), 6.30 - 6.10 (m, 1 H), 5.94 (s, 1 H), 3.86 (s, 3 H), 3.59 - 3.41 (m, 1 H), 1.97 - 1.86 (m, 2 H), 1.77 (ddd, J = 13.7, 9.0, 6.4 Hz, 1 H), 1.64 - 1.42 (m, 4 H), 1.41 - 1.30 (m, 2 H); 13 C NMR (100 MHz, CDC13) δ 163.4, 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; HRMS (ESI) m / z: [M + H] ＋ C 18 H 26 N3O ＋ Calculated 300.2070; Found 300.2070.

[0078] Twenty-three, preparation of azaheterocyclic alkaloid 3w .

[0079] Except that n-butylamine is replaced by , the rest of the preparation process is the same as that of azaheterocyclic alkaloid 3a, the yield is 54%, the melting point is 132-134℃, and the 1 H NMR, 13 C NMR and HRMS spectral data are as follows: 1 H NMR (400 MHz, CDC13) δ 7.33 (s, 1 H), 6.92 (s, 1 H), 6.65 (d, J = 2.4 Hz, 1 H), 6.30 - 6.10 (m, 1 H), 5.94 (s, 1 H), 3.86 (s, 3 H), 3.59 - 3.41 (m, 1 H), 1.97 - 1.86 (m, 2 H), 1.77 (ddd, J = 2.4 Hz, 1 H), 6.30 - 6.10 (m, 1 H), 5.94 (s, 1 H), 3.86 (s, 3 H), 3.59 - 3.41 (m, 1 H), 1.97 - 1.86 (m, 2 H), 1.77 (ddd, 13 C NMR (100 MHz, CDC13) 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; HRMS (ESI) m / z: [M + H]+calcd for C ＋ C 17 H 24 N3O ＋ calcd 286.1914; found 286.1912.

[0080] Twenty-four, preparation of azacyclic alkaloid 3x .

[0081] 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 there is a bulky group with steric hindrance, there are rotational isomers, the main product obtained 1 H NMR, 13 C NMR and HRMS spectrum data are as follows: 1 H NMR (400MHz, CDCl3) δ 7.40 (s, 1H), 6.98 (s, 1H), 6.65 (d, J = 3.0 Hz, 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); 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; HRMS (ESI) m / z: [M + H]+calcd for C ＋ calcd C 20 H 26 N3O ＋ 324.2070; found 324.2067.

[0082] Twenty-five, preparation of azacyclic alkaloid 3y .

[0083] 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 spectrum data are as follows: 1 H NMR (400MHz, CDCl3) δ7.33 (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); 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; HRMS (ESI) m / z: [M + H] ＋ C 22 H 34 N3O ＋ Calculated 356.2696; Found 356.2693.

[0084] Twenty-six, preparation of azacyclic alkaloid 3z .

[0085] 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: 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); 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.

[0086] Detection Example 1 The detection of anti-tobacco mosaic virus activity is as follows: I. Virus purification and concentration determination.

[0087] The virus purification and concentration determination refer to the SOP standard for tobacco mosaic virus prepared by the Institute of Element Analysis of Nankai University. After 2 PEG centrifugation treatments of the crude virus extract, the concentration is determined, and it is stored at 4°C for standby.

[0088] II. Solution preparation, the process is as follows: After weighing, the nitrogen heterocyclic alkaloids and ribavirin raw drugs are respectively added into DMF for dissolution to prepare 1×10 5 µg / mL mother liquor, which is then diluted to the required concentration with 1‰ Tween 80 aqueous solution.

[0089] III. Detection of in vivo protective effect, the process is as follows: 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.

[0090] IV. Detection of in vivo therapeutic effect, the process is as follows: 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.

[0091] V. Detection of in vivo passivation, the process is as follows: Select 3-5 leaf stage Shanxi 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.

[0092] Among them, the inhibition rate (%) = [(control dead spots - treatment dead spots) / control dead spots] × 100%.

[0093] Under the treatment dose of 500 µg / mL, the in vivo passivation, in vivo treatment, and in vivo protective activity of all the tested substances against tobacco mosaic virus were tested, and the results are shown in Table 1.

[0094] Table 1 Test results of anti-tobacco mosaic virus activity of nitrogen heterocyclic alkaloid series compounds

[0095] From the data provided in Table 1, it can be seen that under the condition of 500 mg / L, the nitrogen heterocyclic alkaloids 3a-3z all have antiviral activity, among which 3b, 3c, a and d have antiviral activity comparable to the positive control drug; the in vivo inactivation, in vivo treatment and in vivo protection activities of nitrogen heterocyclic alkaloids 3d, 3e, 3k, 3v and 3z are higher than those of the positive control drug ribavirin, among which the in vivo inactivation relative inhibition rate of nitrogen heterocyclic alkaloid 3z is as high as 53.7±2.4%, the in vivo treatment relative inhibition rate is as high as 51.0±3.8% and the in vivo protection relative inhibition rate is as high as 50.6±1.9%.

[0096] In summary, under the condition of 500 mg / L, the nitrogen heterocyclic 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.

[0097] Finally, it should be noted that: the above examples are only used to illustrate the technical solutions of the present application, but not to limit it; although the present application has been described in detail with reference to the foregoing examples, those skilled in the art should understand that: it 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. Aza-cyclic alkaloid, characterized in that, The structural formula is shown as follows: ； wherein X is selected from -OCH3; R is selected from or ; wherein a is selected from any integer from 1 to 6.

2. Use of aza-cyclic alkaloids for the control of plant viruses, characterized in that, The nitrogen heterocyclic alkaloid of claim 1, wherein the virus is selected from the group consisting of tobacco mosaic virus.

3. Use of the azacyclic alkaloid according to claim 2 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.

4. Use of the azacyclic alkaloid according to claim 3 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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