Aminogroup-containing pauciflorine derivatives, preparation method and application thereof

Abstract

The present application relates to the field of agricultural technology, and particularly relates to an amine group-containing alstoniascholaris alkaloid derivative, a preparation method and application thereof. The amine group-containing alstoniascholaris alkaloid derivative comprises a compound as shown in formula (I): wherein R comprises at least one of C3-C12 linear alkyl, C3-C12 branched alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl, C2-C6 aminoalkyl, tetrahydropyrrole group, piperidine group, piperidinylmethyl, N-methylpiperidine group and N-methylpiperidinylmethyl. The amine group-containing alstoniascholaris alkaloid derivative has good plant virus control and good fungicidal activity.

Description

Technical Field

[0001] This invention relates to the field of agricultural technology, and in particular to leucocele alkaloid derivatives containing amine groups, their preparation methods, and applications. Background Technology

[0002] In 1951, Gellert first isolated the alkaloid cryptolepine, an indole-quinoline structure, from *Cryptolepis sanguinolenta*. Current research has found that cryptolepine derivatives exhibit antibacterial activity against chloroquine-resistant strain K1 and chloroquine-sensitive strain HB3; the combination of cryptolepine and artemisinin derivatives shows synergistic antimalarial activity against *Bacillus burgdorferi* NK-65 and *Plasmodium falciparum* 3D7 in vivo and in vitro; and cryptolepine analogs have the ability to induce and stabilize the c-myc gene and downregulate its expression in HepG2 cells. However, to date, there are no reports on the application of cryptolepine derivatives in the control of plant viruses and for fungicides. Summary of the Invention

[0003] The present invention aims to at least solve one of the technical problems existing in the related art. To this end, the present invention provides a white vine alkaloid derivative containing an amino group structure, which has good antiviral activity against plant viruses and good bactericidal activity.

[0004] In one aspect of the invention, a leucocephaline derivative containing an amino group is provided, the leucocephaline derivative comprising compounds as shown in formula (I):

[0005]

[0006] Wherein, R includes at least one of the following: a straight-chain alkyl group of C3-C12, a branched alkyl group of C3-C12, a cycloalkyl group of C3-C6, a cycloalkylmethyl group of C3-C6, an aminoalkyl group of C2-C6, a tetrahydropyrrolyl group, a piperidinyl group, a piperidinylmethyl group, an N-methylpiperidinyl group, and an N-methylpiperidinylmethyl group.

[0007] Furthermore, the N- group of the C2-C6 aminoalkyl group is substituted with a substituent, said substituent including methyl, ethyl, and... At least one of them.

[0008] Furthermore, the C3-C12 straight-chain alkyl group includes at least one or more of n-propyl, n-pentyl, n-dodecyl, isopentyl, and 3-ethylhexyl;

[0009] C3-C6 cycloalkyl groups include at least one of cyclopropyl, cyclopentyl, and cyclohexyl;

[0010] C3-C6 cycloalkylmethyl groups include at least one of cyclopropylmethyl, cyclopentylmethyl, and cyclohexylmethyl;

[0011] C2-C6 aminoalkyl groups include at least one of aminoethyl, aminopropyl, aminobutyl, β-methylaminoethyl, β,β-dimethylaminoethyl, N-methylaminoethyl, N-ethylaminoethyl, N-methylaminopropyl, N,N-dimethyl-α,α-dimethylaminopropyl, and γ-piperidinylpropyl.

[0012] Furthermore, the amine-containing leucocele alkaloid derivative includes at least one of the compounds shown in formulas (I-1) to (I-25):

[0013]

[0014] In another aspect of the present invention, the present invention provides a method for preparing the leucocele alkaloid derivative containing an amino group as described above, the method comprising the following steps:

[0015] In ethyl acetate as solvent, under reflux conditions... A nucleophilic substitution reaction of the aromatic ring with RNH2 yields a leucocele alkaloid derivative containing an amino group.

[0016] Wherein, R includes at least one of the following: a straight-chain alkyl group of C3-C12, a branched alkyl group of C3-C12, a cycloalkyl group of C3-C6, a cycloalkylmethyl group of C3-C6, an aminoalkyl group of C2-C6, a tetrahydropyrrolyl group, a piperidinyl group, a piperidinylmethyl group, an N-methylpiperidinyl group, and an N-methylpiperidinylmethyl group.

[0017] Furthermore, the reflux temperature is 110–130°C, and the reflux time is 15–17 h.

[0018] Furthermore, The molar ratio of RNH2 to RNH2 is 1:(1-3).

[0019] Furthermore, the solid product obtained after the nucleophilic substitution reaction was washed multiple times with ethyl acetate to obtain a leucocele alkaloid derivative containing an amino group.

[0020] In another aspect of the invention, the invention provides the application of the aforementioned amine-containing leucocele alkaloid derivative in its antiviral activity against plant viruses.

[0021] In another aspect of the present invention, the present invention provides the application of the aforementioned amine-containing leucocele alkaloid derivative in bactericidal applications.

[0022] The above-described one or more technical solutions in the embodiments of the present invention have at least one of the following technical effects:

[0023] This invention relates to a amine-containing derivative of *Gynostemma pentaphyllum*, using 11-chloro-Gynostemma pentaphyllum iodide as the parent compound. Primary amines with different substituents are selectively introduced at the C-11 position. These primary amines act as both hydrogen bond donors and acceptors, increasing the number of hydrogen bond sites between the molecule and target proteins, thereby enhancing the compound's biological activity. The *Gynostemma pentaphyllum* derivative of this invention exhibits good activity against plant viruses and good bactericidal activity.

[0024] Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. Detailed Implementation

[0025] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention are described clearly and completely below. Obviously, the described embodiments are only some, not all, of the embodiments of this invention. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention. The following embodiments are used to illustrate this invention but cannot be used to limit the scope of this invention.

[0026] In the description of the embodiments of the present invention, it should be noted that the terms "center," "longitudinal," "lateral," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," and "outer," etc., indicating orientation or positional relationships, are only for the convenience of describing the embodiments of the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation on the embodiments of the present invention. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and should not be construed as indicating or implying relative importance.

[0027] In the description of the embodiments of the present invention, it should be noted that, unless otherwise explicitly specified and limited, the terms "connected" and "linked" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium. Those skilled in the art can understand the specific meaning of the above terms in the embodiments of the present invention based on the specific circumstances.

[0028] In embodiments of the present invention, unless otherwise explicitly specified and limited, "above" or "below" the second feature can mean that the first feature is in direct contact with the second feature, or that the first feature is in indirect contact with the second feature through an intermediate medium. Furthermore, "above," "on top of," and "over" the second feature can mean that the first feature is directly above or diagonally above the second feature, or simply that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature can mean that the first feature is directly below or diagonally below the second feature, or simply that the first feature is at a lower horizontal level than the second feature.

[0029] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., refer to specific features, structures, materials, or characteristics described in connection with that embodiment or example, which are included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.

[0030] In one aspect of the invention, a leucocephaline derivative containing an amino group is provided, the leucocephaline derivative comprising compounds as shown in formula (I):

[0031]

[0032] Wherein, R includes at least one of the following: a straight-chain alkyl group of C3-C12, a branched alkyl group of C3-C12, a cycloalkyl group of C3-C6, a cycloalkylmethyl group of C3-C6, an aminoalkyl group of C2-C6, a tetrahydropyrrolyl group, a piperidinyl group, a piperidinylmethyl group, an N-methylpiperidinyl group, and an N-methylpiperidinylmethyl group.

[0033] This invention relates to a amine-containing derivative of *Gynostemma pentaphyllum*, using 11-chloro-Gynostemma pentaphyllum iodide as the parent compound. Primary amines with different substituents are selectively introduced at the C-11 position. These primary amines act as both hydrogen bond donors and acceptors, increasing the number of hydrogen bond sites between the molecule and target proteins, thereby enhancing the compound's biological activity. The *Gynostemma pentaphyllum* derivative of this invention exhibits good activity against plant viruses and good bactericidal activity.

[0034] In some embodiments of the present invention, the N-terminus of the C2-C6 aminoalkyl group is substituted with a substituent, said substituent including methyl, ethyl, and... At least one of them.

[0035] In some embodiments of the present invention, the C3-C12 straight-chain alkyl group includes at least one or more of n-propyl, n-pentyl, n-dodecyl, isopentyl, and 3-ethylhexyl; the C3-C6 cycloalkyl group includes at least one of cyclopropyl, cyclopentyl, and cyclohexyl; the C3-C6 cycloalkylmethyl group includes at least one of cyclopropylmethyl, cyclopentylmethyl, and cyclohexylmethyl; and the C2-C6 aminoalkyl group includes at least one of aminoethyl, aminopropyl, aminobutyl, β-methylaminoethyl, β,β-dimethylaminoethyl, N-methylaminoethyl, N-ethylaminoethyl, N-methylaminopropyl, N,N-dimethyl-α,α-dimethylaminopropyl, and γ-piperidinylpropyl.

[0036] In some preferred embodiments of the present invention, R includes n-propyl, n-pentyl, n-dodecyl, isopentyl, 3-ethylhexyl, cyclopropylmethyl, cyclopentyl, cyclohexylmethyl, aminoalkyl, substituted aminoalkyl, pyrrole, piperidinyl, piperidinylmethyl, N-methylpiperidinyl; said substituted aminoalkyl includes those substituted with methyl, ethyl and / or Substituted aminoalkyl groups.

[0037] In some embodiments of the present invention, the amine-containing leucocele alkaloid derivative comprises at least one of the compounds shown in formulas (I-1) to (I-25):

[0038]

[0039] In another aspect of the present invention, the present invention provides a method for preparing the leucocele alkaloid derivative containing an amino group as described above, the method comprising the following steps:

[0040] In ethyl acetate as solvent, under reflux conditions... A nucleophilic substitution reaction of the aromatic ring with RNH2 yields a leucopicine derivative containing an amino group; wherein R includes at least one of the following: a straight-chain alkyl group of C3-C12, a branched alkyl group of C3-C12, a cycloalkyl group of C3-C6, a cycloalkylmethyl group of C3-C6, an aminoalkyl group of C2-C6, a tetrahydropyrrolyl group, a piperidinyl group, a piperidinylmethyl group, an N-methylpiperidinyl group, and an N-methylpiperidinylmethyl group.

[0041] In some embodiments of the present invention, the temperature of the heating reflux is 110-130°C (e.g., 110°C, 120°C, or 130°C), and the heating reflux time is 15-17 hours (e.g., 15 hours, 16 hours, or 17 hours).

[0042] In some embodiments of the present invention The molar ratio with RNH2 is 1:

[0043] (1~3), for example, it can be 1:1, 1:2 or 1:3, etc.

[0044] In some embodiments of the present invention, the solid product obtained after the nucleophilic substitution reaction is washed multiple times with ethyl acetate to obtain a leucocele alkaloid derivative containing an amino group.

[0045] In some specific embodiments of the present invention, the preparation method of the amine-containing leucocele alkaloid derivative includes the following steps: 11-chloroleucocele alkaloid iodide compound ( 197 mg (0.5 mmol) was dissolved in ethyl acetate (20 mL). An alkylamine (RNH2, 1 mmol) was added, and the mixture was heated under reflux for 16 h. After the reaction was complete, the mixture was cooled to room temperature, and a solid precipitated. The solid was filtered, washed several times with ethyl acetate, and dried to obtain the leucopicrin derivative with an amino group. The specific synthetic route is shown below:

[0046]

[0047] R is consistent with the previous description and will not be elaborated further here.

[0048] In another aspect of the invention, the invention provides the application of the aforementioned amine-containing leucocele alkaloid derivative in its antiviral activity against plant viruses.

[0049] In some specific embodiments of the present invention, the amine-containing leucocele alkaloid derivative of the present invention exhibits good anti-tobacco mosaic virus activity.

[0050] In another aspect of the present invention, the present invention provides the application of the aforementioned amine-containing leucocele alkaloid derivative in bactericidal applications.

[0051] In some specific embodiments of the present invention, the amine-containing cypermethrin derivative of the present invention exhibits bactericidal activity against pathogens that cause rice sheath blight.

[0052] The present invention will be further described below with reference to specific embodiments. It should be noted that the following embodiments are only used to explain the present invention and should not be construed as limiting the present invention.

[0053] Example

[0054] Example 1

[0055] The preparation method of the leucocele alkaloid derivative containing an amino group includes the following steps:

[0056] 1. Dissolve 2.74 g (20 mmol) of anthranilic acid in an equal volume of a mixed solution of DMF (N,N-dimethylformamide, 8 mL) and THF (tetrahydrofuran, 8 mL). Slowly add 24 mmol of bromoacetyl bromide at 0 °C and stir overnight at room temperature. After the reaction is complete, pour the reaction solution into an appropriate amount of ice water, and a large amount of white solid precipitates. Filter the solid, wash it five times with plenty of water, and air dry to obtain 2-(bromoacetylamino)benzoic acid.

[0057] 2. Dissolve 2-(bromoacetamido)benzoic acid (5g, 19.4mmol) in DMF (10mL), add aniline (69.4mmol), and heat under reflux at 120℃ for 18h. After the reaction is complete, cool to room temperature, slowly add 5% potassium hydroxide solution to adjust the pH to 11, extract several times with dichloromethane, collect the aqueous phase, adjust the pH to 2-3 with 5% hydrobromic acid solution, let stand overnight at room temperature, and a large amount of white solid precipitates. Filter and dry to obtain 2-(2-(anilino)acetamidobenzoic acid).

[0058] 3. Polyphosphoric acid (150g) was added to 2-(2-(aniline)acetaminobenzoic acid (4.27g, 15.8mmol), and heated at 130℃ for 2h. After the reaction was completed, the mixture was cooled to room temperature, and the reaction solution was poured into an appropriate amount of ice water. The pH was adjusted to neutral with saturated potassium hydroxide solution, extracted with ethyl acetate, and the organic phases were combined. The mixture was washed with saturated brine, dried over anhydrous sodium sulfate, and then distilled under reduced pressure. The solution was purified by column chromatography to obtain 5,11-dihydro-11H-indolo[3,2-b]quinoline-11one.

[0059] 4. Phosphorus oxychloride (33 mL) was slowly added dropwise to 5,11-dihydro-11H-indolo[3,2-b]quinoline-11 one (3.05 g, 13 mmol). The mixture was heated under reflux at 120 °C for 2 h. After the reaction was completed, the mixture was cooled to room temperature. The reaction solution was slowly poured into an appropriate amount of ice water. The pH was adjusted to neutral with saturated potassium hydroxide solution. The mixture was extracted with ethyl acetate, and the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and then distilled under reduced pressure. The solution was purified by column chromatography to obtain 11-chloro-10H-indolo[3,2-b]quinoline.

[0060] 5. Dissolve 11-chloro-10H-indolo[3,2-b]quinoline (126 mg, 0.5 mmol) in DMF (2 mL), add iodomethane (1.5 mmol), and heat at 100 °C for 8 h. After the reaction is complete, cool to room temperature, add ethyl acetate, and a large amount of solid precipitates out. Filter, wash several times with ethyl acetate, and dry to obtain 11-chloro-Baiye Teng alkaloid iodide compound.

[0061] 6. Weigh 197 mg (0.5 mmol) of 11-chloro-Baiyetangine iodide salt and dissolve it in 20 mL of ethyl acetate. Add 1 mmol of amine and heat under reflux for 16 h. After the reaction is complete, cool to room temperature. A solid precipitates out. Filter the solid and wash it several times with ethyl acetate. Dry it. The resulting Baiyetangine derivative containing an amino group has the following structural formula: 124 mg of yellow-green solid, yield 59%, melting point: greater than 250℃. 1 H NMR (400MHz, DMSO-d6) δ11.64(s,1H),8.69(d,J=8.5Hz,2H),8.51(d,J=8.4Hz,1H),8.30(d,J=8.9Hz,1H),8.04-7.96(m,1H),7.84( d,J=8.4Hz,1H),7.75-7.65(m,2H),7.41-7.31(m,1H),4.55(s,3H),4.04(t,J=6.4Hz,2H),1.94-1.79(m,2H),1.04(t,J=7.3Hz,3H). 13 C NMR(100MHz,DMSO-d6)δ144.0,142.9,137.5,135.8,132.7,130.9,124.7,124.4,124.4,1 21.2,117.8,116.6,115.5,114.8,113.9,47.4,38.5,23.5,11.7.HRMS(ESI),calculated for C 19 H 20 N3 + [MI] + 290.1652, found 290.1651.

[0062] Example 2

[0063] The preparation method of the amine-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with n-pentylamine. The resulting amine-containing leucocele alkaloid derivative has the following structural formula: 133 mg of yellow solid, yield 60%, melting point: 230-231℃. 1H NMR (400MHz, DMSO-d6) δ11.61(s,1H),8.69(d,J=7.7Hz,2H),8.50(d,J=7.9Hz,1H),8.29(d,J=8.5Hz,1H),8.06-7.95(m,1H),7.84(d,J= 7.8Hz,1H),7.76-7.61(m,2H),7.42-7.28(m,1H),4.54(s,3H),4.06(s,2H),1.93-1.69(m,2H),1.53-1.30(m,4H),0.90(t,J=6.4Hz,3H). 13 C NMR(100MHz,DMSO-d6)δ143.5,142.4,137.0,135.3,132.2,130.4,124.2,123.9,120.7,117 .3,116.1,115.0,114.3,113.4,45.4,38.0,29.3,28.4,21.9,13.9.HRMS(ESI),calculated for C 21 H 24 N3 + [MI] + 318.1965, found 318.1964.

[0064] Example 3

[0065] The preparation method of the amine-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with n-dodecylamine. The resulting amine-containing leucocele alkaloid derivative has the following structural formula: 157 mg of yellow solid, yield 57%, melting point: 171-172 °C. 1 H NMR (400MHz, DMSO-d6) δ11.62(s,1H),8.69(d,J=7.8Hz,2H),8.51(d,J=8.1Hz,1H),8.31(d,J=8.5Hz,1H),8.05-7.96(m,1H),7.84(d,J= 7.9Hz,1H),7.75-7.64(m,2H),7.41-7.30(m,1H),4.55(s,3H),4.07(s,2H),1.44(s,2H),1.24(d,J=52.3Hz,18H),0.82(t,J=6.3Hz,3H). 13C NMR(100MHz,DMSO-d6)δ144.0,143.0,137.6,135.8,132.7,130.9,124.7,124.4,121.2,117.8,116.6,1 15.6,114.9,113.9,45.9,38.5,31.7,30.1,29.5,29.4,29.2,26.7,22.5,14.4.HRMS(ESI),calculated for C 28 H 38 N3 + [MI] + 416.3060, found 416.3060.

[0066] Example 4

[0067] The preparation method of the amine-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with isopentylamine. The resulting amine-containing leucocele alkaloid derivative has the following structural formula: 173 mg of yellow solid, yield 78%, melting point: 238-239℃. 1 H NMR (400MHz, MeOH-d4) δ8.57(d,J=8.6Hz,1H),8.49(d,J=8.5Hz,1H),8.24(d,J=8.9Hz,1H),8.04-7.97(m,1H),7.83(d,J=8. 4Hz,1H),7.75-7.66(m,2H),7.45-7.37(m,1H),4.61(s,3H),4.17(t,J=7.1Hz,2H),1.89-1.78(m,3H),1.03(d,J=6.3Hz,6H). 13 C NMR(100MHz,MeOH-d4)δ144.1,143.1,137.7,136.1,132.3,130.7,124.2,123.7,123.3,121 .0,116.7,115.6,114.8,113.1,110.0,44.1,38.7,37.3,25.6,21.5.HRMS(ESI),calculated for C 21 H 24 N3 + [MI] + 318.1965, found 318.1966.

[0068] Example 5

[0069] The preparation method of the amine-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with 3-ethylhexylamine. The resulting amine-containing leucocele alkaloid derivative has the following structural formula: 175 mg of yellow solid, yield 72%, melting point: 200-201℃. 1 H NMR (400MHz, DMSO-d6) δ11.75(s,1H),8.75(d,J=8.1Hz,1H),8.59(d,J=8.5Hz, 2H),8.38(d,J=8.8Hz,1H),8.09-7.99(m,1H),7.85(d,J=8.4Hz,1H),7.81-7.6 8(m,2H),7.46-7.35(m,1H),4.63(s,3H),4.02(s,2H),1.94-1.85(m,1H),1.52 -1.33(m,4H),1.32-1.19(m,4H),0.87(t,J=7.4Hz,3H),0.82(t,J=7.1Hz,3H). 13 C NMR(100MHz,DMSO-d6)δ144.4,143.1,137.7,136.3,132.8,131.2,125.0,124.6,124.3,121.4,118.0 ,117.3,115.9,115.3,114.0,49.6,38.6,30.5,28.5,23.9,22.9,14.3,10.9.HRMS(ESI),calculated for C 24 H 30 N3 + [MI] + 360.2434, found 360.2433.

[0070] Example 6

[0071] The preparation method of the amine-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with cyclopropylmethylamine. The resulting amine-containing leucocele alkaloid derivative has the following structural formula: 134 mg of yellow solid, yield 62%, melting point: greater than 250℃. 1H NMR (400MHz, DMSO-d6) δ11.70(s,1H),8.87(s,1H),8.73(d,J=8.5Hz,1H),8.52(d,J=8.4Hz,1H),8.32(d,J=8.9Hz,1H),8.05-7.97(m,1H),7.85(d ,J=8.3Hz,1H),7.74-7.66(m,2H),7.40-7.32(m,1H),4.57(s,3H),3.97( d,J=6.7Hz,2H),1.38-1.26(m,1H),0.63-0.54(m,2H),0.52-0.42(m,2H). 13 C NMR(100MHz,DMSO-d6)δ143.9,143.0,137.6,135.8,132.8,131.0,124.7,124.5,124.4, 121.2,117.8,116.7,115.6,114.9,114.0,50.2,38.5,12.0,4.3.HRMS(ESI),calculated for C 20 H 20 N3 + [MI] + 302.1652, found 302.1650.

[0072] Example 7

[0073] The preparation method of the amine-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with cyclopentylamine. The resulting amine-containing leucocele alkaloid derivative has the following structural formula: 133 mg of brownish-yellow solid, yield 60%, melting point: 248-249℃. 1 H NMR (400MHz, DMSO-d6) δ11.63(s,1H),8.76(d,J=8.4Hz,1H),8.55(d,J=8.3Hz,1H),8.46-8.29(m,2H),8.06-7.97(m,1H),7.88(d,J=8.3Hz,1H), 7.78-7.66(m,2H),7.44-7.33(m,1H),5.02(s,1H),4.60(s,3H),2.29-2 .14(m,2H),1.98-1.89(m,2H),1.88-1.78(m,2H),1.73(d,J=6.1Hz,2H). 13C NMR(100MHz,DMSO-d6)δ143.5,143.0,137.6,136.0,132.8,131.1,124.9,124.8,124.3,1 21.2,117.8,116.8,115.7,114.9,114.0,57.0,38.6,34.2,24.5.HRMS(ESI),calculated for C 21 H 22 N3 + [MI] + 316.1808, found 316.1808.

[0074] Example 8

[0075] The preparation method of the amine-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with cyclohexylmethylamine. The resulting amine-containing leucocele alkaloid derivative has the following structural formula: 186 mg of yellow solid, yield 79%, melting point: 243-244℃. 1 H NMR (400MHz, DMSO-d6) δ11.86(s,1H),8.77(d,J=8.5Hz,2H),8.56(d,J=8.4H z,1H),8.35(d,J=8.9Hz,1H),8.02(t,J=7.8Hz,1H),7.88(d,J=8.4Hz,1H),7 .79-7.67(m,2H),7.39(t,J=7.6Hz,1H),4.61(s,3H),3.98(s,2H),1.85(d,J =10.3Hz,3H),1.64(d,J=23.4Hz,3H),1.23-1.11(m,3H),1.10-0.99(m,2H). 13 C NMR(100MHz,DMSO-d6)δ144.3,143.0,137.7,136.0,132.8,131.0,124.8,124.5,124.5,121.3, 118.0,117.1,115.8,115.1,114.1,54.8,52.0,38.5,30.7,26.4,25.8.HRMS(ESI),calculated for C 23 H 26 N3 + [MI] + 344.2121, found 344.2122.

[0076] Example 9

[0077] The preparation method of the amine-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with 3-cyclohexylpropylamine. The resulting amine-containing leucocele alkaloid derivative has the following structural formula: Yellow solid, 90 mg, yield 51%, melting point: 234-235℃. 1 H NMR (400MHz, DMSO-d6) δ11.87(s,1H),8.88(s,1H),8.73(d,J=7.5Hz,1H),8.53( d,J=7.4Hz,1H),8.32(d,J=8.1Hz,1H),8.05-7.97(m,1H),7.87(d,J=7.3Hz,1H), 7.76-7.65(m,2H),7.37(t,J=6.2Hz,1H),4.58(s,3H),4.09(s,2H),1.82(s,2H) ,1.73-1.50(m,6H),1.35(d,J=5.1Hz,2H),1.21-1.10(m,3H),0.91-0.80(m,2H). 13 C NMR(100MHz,DMSO-d6)δ144.1,143.0,137.7,135.7,132.7,130.9,124.7,124.6,124.3,121.2,117.8 ,116.8,115.6,115.0,114.0,46.2,38.5,37.2,34.4,33.2,27.6,26.6,26.2.HRMS(ESI),calculated for C 25 H 30 N3 + [MI] + 372.2434, found372.2437.

[0078] Example 10

[0079] The preparation method of the amine-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with ethylenediamine. The resulting amine-containing leucocele alkaloid derivative has the following structural formula: 180 mg of yellow solid, yield 87%, melting point: 235-236℃. 1H NMR (400MHz, DMSO-d6) δ8.60(d,J=8.4Hz,1H),8.42(d,J=8.4Hz,1H),8.23(d,J=8.9Hz,1H),7.95-7.89(m,1H ),7.72(d,J=8.4Hz,1H),7.63-7.55(m,2H),7.23-7.18(m,1H),4.51(s,3H),4.28-4.21(m,2H),3.20(s,2H). 13 C NMR(100MHz,DMSO-d6)δ145.6,145.0,137.1,135.2,131.8,129.5,124.2,124.1,1 23.4,120.8,119.7,117.3,115.4,115.4,46.6,40.8,38.0.HRMS(ESI),calculated for C 18 H 19 N4 + [MI] + 291.1604, found 291.1602.

[0080] Example 11

[0081] The preparation method of the amine-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with 1,3-propanediamine. The resulting amine-containing leucocele alkaloid derivative has the following structural formula: 230 mg of yellow solid, yield 86%, melting point: 198-199℃. 1 H NMR (400MHz, DMSO-d6) δ8.62(d,J=8.2Hz,1H),8.41(d,J=8.2Hz,1H),8.25(d,J=8.8Hz,1H),7.91(t,J=7.4Hz,1H),7.67(d,J=8.3Hz,1H),7. 59(t,J=7.1Hz,1H),7.50(t,J=7.0Hz,1H),7.14-7.09(m,1H),4.57(s, 3H),4.52(s,2H),3.12(s,1H),2.93(s,2H),2.09(s,2H),1.61(s,2H). 13C NMR(100MHz,DMSO-d6)δ149.5,148.8,145.2,136.6,135.4,131.2,128.2,124.3,124.0,1 22.7,118.1,117.1,116.9,115.3,114.5,42.1,38.6,37.9,30.2.HRMS(ESI),calculated for C 19 H 21 N4 + [MI] + 305.1761, found 305.1759.

[0082] Example 12

[0083] The preparation method of the amine-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with 1,4-butanediamine. The resulting amine-containing leucocele alkaloid derivative has the following structural formula: 282 mg of yellow solid, yield 84%, melting point: 203-204℃. 1 H NMR (400MHz, DMSO-d6) δ8.69(d,J=8.5Hz,1H),8.51(d,J=8.4Hz,1H),8.31(d,J=8.9Hz,1H),8.01-7.95(m,1H),7.81(d,J=8.5Hz,1H),7. 71-7.61(m,2H),7.28(t,J=7.6Hz,1H),4.59(s,3H),4.23(t,J=6.7Hz,2H),2.90(t,J=7.1Hz,2H),1.94-1.83(m,2H),1.78-1.66(m,2H). 13 C NMR(100MHz,DMSO-d6)δ145.6,144.2,137.3,135.7,132.2,129.9,124.5,124.3,123.7,120 .0,119.6,117.6,115.3,115.2,115.0,44.7,39.1,38.3,27.4,24.9.HRMS(ESI),calculated for C 20 H 23 N4 + [MI] + 319.1917, found 319.1918.

[0084] Example 13

[0085] The preparation method of the amine-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with 1,2-propanediamine. The resulting amine-containing leucocele alkaloid derivative has the following structural formula: Yellow solid, 240 mg, yield 87%, melting point: 221-222℃. 1 H NMR (400MHz, DMSO-d6) δ8.64(d,J=8.3Hz,1H),8.41(d,J=8.5Hz,1H),8.21(d,J=8.9Hz,1H),7.91(t,1H),7.71(d,J=8. 4Hz,1H),7.63-7.53(m,2H),7.19(t,1H),4.51(s,3H),3.50(t,J=10.6,6.6Hz,1H),1.85(s,2H),1.33(d,J=6.5Hz,3H). 13 C NMR(100MHz,DMSO-d6)δ170.2,145.2,144.8,136.8,134.5,131.3,128.8,123.8,123.7,1 22.8,120.7,119.1,116.7,115.3,115.0,46.7,37.5,22.6,17.2.HRMS(ESI),calculated for C 19 H 21 N4 + [MI] + 305.1761, found 305.1760.

[0086] Example 14

[0087] The preparation method of the amine-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with 2-methyl-1,2-propanediamine. The resulting amine-containing leucocele alkaloid derivative has the following structural formula: 200 mg of yellow solid, yield 89%, melting point: 252-253℃. 1 H NMR (400MHz, DMSO-d6) δ8.73(d,J=8.4Hz,1H),8.40(d,J=8.4Hz,1H),8.15(d,J=8.8Hz,1H),7.91-7.85(m,1H),7.69(d ,J=8.4Hz,1H),7.59-7.50(m,2H),7.21-7.15(m,1H),4.49(s,3H),4.14(s,2H),1.88(s,1H),1.41(s,6H),1.12(s,2H). 13CNMR(100MHz,DMSO-d6)δ146.2,137.6,131.4,128.5,124.8,123.9,122.7,122.6,119.2,116.9,116.8,115.8,52.7,37.7,26.7,24.9.HRMS(ESI),calculatedfor C 20 H 23 N4 + [MI] + 319.1917, found 319.1917.

[0088] Example 15

[0089] The preparation method of the amine-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with N. 1 -Ethyl-1,2-ethylenediamine. The structural formula of the leucocele alkaloid derivative containing an amino group is: 110 mg of yellow solid, yield 49%, melting point: 233-234℃. 1 H NMR(400MHz,MeOH-d4)δ8.50(d,J=8.5Hz,1H),8.41(d,J=8.5Hz,1H),8.19(d,J=8.9Hz,1H),7.99-7.94(m,1H),7.76(d,J=8.4Hz,1H), 7.68-7.62(m,2H),7.37-7.31(m,1H),4.54(s,3H),4.24-4.17(m,2H),3.23-3.19(m,2H),2.83(q,J=7.2Hz,2H),1.16(t,J=7.2Hz,3H). 13 C NMR(100MHz,MeOH-d4)δ143.4,137.4,136.1,132.1,130.5,124.9,124.1,123.6,123. 1,120.7,116.7,115.5,115.2,113.3,45.2,43.7,37.2,13.2.HRMS(ESI),calculated for C 20 H 23 N4 + [MI] + 319.1917, found 319.1917.

[0090] Example 16

[0091] The preparation method of the amine-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with N.1 -Methyl-1,3-propanediamine. The structural formula of the leucocele alkaloid derivative containing the amino group is: Orange-red solid, 203 mg, yield 74%, melting point: 187-188℃. 1 H NMR (400MHz, MeOH-d4) δ8.48(d,J=8.4Hz,1H),8.38(d,J=8.5Hz,1H),8.16(d,J=8.9Hz,1H),8.00-7.92(m,1H),7.75(d,J=8.4Hz,1H) ,7.70-7.60(m,2H),7.32(t,J=7.7Hz,1H),4.49(s,3H),4.20(t,J=6.3Hz,2H),2.87(t,J=6.0Hz,2H),2.47(s,3H),2.20-2.09(m,2H). 13 C NMR(100MHz,MeOH-d4)δ144.5,144.0,137.3,136.1,132.0,130.3,124.0,123.5,123.0,120 .5,116.6,115.3,114.9,113.4,100.0,46.8,42.9,37.1,34.0,28.7.HRMS(ESI),calculated for C 20 H 23 N4 + [MI] + 319.1917, found 319.1917.

[0092] Example 17

[0093] The preparation method of the amine-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with N. 1 N 1 2,2-Tetramethyl-1,3-propanediamine. The structural formula of the leucocele alkaloid derivative containing an amino group is given. 125 mg of yellow solid, yield 64%, melting point: 242-243℃. 1H NMR (400MHz, DMSO-d6) δ10.76(s,1H),8.57(d,J=8.4Hz,1H),8.36(d,J=8.9Hz,1H),8.19(d,J=8.4Hz,1H),8.07-8.00(m, 1H),7.86-7.71(m,3H),7.42-7.34(m,1H),4.60(s,3H),4.15(s,2H),3.36(s,1H),2.62(s,2H),2.46(s,6H),1.15(s,6H). 13 C NMR(100MHz,DMSO-d6)δ144.5,143.0,137.7,135.8,132.8,130.9,125.0,124.8,123.0,121.2,118 .1,116.7,115.6,115.0,114.0,100.0,69.9,57.3,48.2,38.4,35.4,25.5.HRMS(ESI),calculated for C 23 H 29 N4 + [MI] + 361.2387, found361.2385.

[0094] Example 18

[0095] The preparation method of the amine-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with 3-amino-tetrahydropyrrole. The resulting amine-containing leucocele alkaloid derivative has the following structural formula: 191 mg of brownish-yellow solid, yield 79%, melting point: 184-185℃. 1 H NMR (400MHz, DMSO-d6) δ8.42(d,J=8.3Hz,2H),8.14(d,J=8.7Hz,1H),7.94-7.88(m,1H),7.81(d,J=8.2Hz,1H),7.66-7.60(m,1H),7.55-7.5 1(m,1H),7.34-7.26(m,1H),4.46(s,3H),3.91(d,J=10.2Hz,1H),3.68 (s,1H),2.15(s,1H),1.91(d,J=5.2Hz,2H),1.21(s,1H),0.85(s,1H). 13C NMR(100MHz,DMSO-d6)δ147.5,142.5,139.1,134.4,132.2,129.9,128.1,124.1,122.0,120 .8,119.6,116.8,116.5,114.7,114.2,63.9,53.8,50.8,38.5,33.8.HRMS(ESI),calculated for C 20 H 21 N4 + [MI] + 317.1761, found 317.1761.

[0096] Example 19

[0097] The preparation method of the amino-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with 4-aminopiperidine. The resulting amino-containing leucocele alkaloid derivative has the following structural formula: Orange-yellow solid, 89 mg, yield 81%, melting point: 245-246℃. 1 H NMR (400MHz, DMSO-d6) δ8.74(d,J=8.3Hz,1H),8.52(d,J=7.9Hz,1H),8.33(d,J =8.8Hz,1H),8.00(t,1H),7.86(d,J=8.3Hz,1H),7.73-7.62(m,2H),7.31(t,1H) ,5.05(s,1H),4.60(s,3H),3.49-3.39(m,1H),3.33(d,J=11.9Hz,2H),3.10(t,J =11.7Hz,2H),2.22-2.13(m,2H),1.96-1.88(m,2H).HRMS(ESI),calculatedfor C 21 H 23 N4 + [MI] + 331.1917, found 331.1919.

[0098] Example 20

[0099] The preparation method of the amine-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with 4-aminomethylpiperidine. The resulting amine-containing leucocele alkaloid derivative has the following structural formula: 186 mg of yellow solid, yield 78%, melting point: 217-218℃. 1H NMR (400MHz, DMSO-d6) δ8.77(d,J=8.5Hz,1H),8.53(d,J=8.4Hz,1H),8.33(d,J =8.9Hz,1H),8.03-7.97(m,1H),7.85(d,J=8.4Hz,1H),7.68(t,J=6.9Hz,2H),7. 32(t,J=7.6Hz,1H),4.60(s,3H),4.15(d,J=6.8Hz,2H),3.24(d,J=12.4Hz,2H), 2.76(t,J=11.7Hz,2H),2.13(s,1H),1.95(d,J=12.3Hz,2H),1.53-1.40(m,2H). 13 C NMR(100MHz,DMSO-d6)δ144.3,137.5,135.8,132.4,130.3,124.6,124.5,124.1,120.6,118 .8,118.2,116.6,115.7,115.1,114.9,50.4,43.6,38.4,35.1,27.1.HRMS(ESI),calculated for C 22 H 25 N4 + [MI] + 345.2074, found 345.2073.

[0100] Example 21

[0101] The preparation method of the amino-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with 3-aminomethylpiperidine. The resulting amino-containing leucocele alkaloid derivative has the following structural formula: 117 mg of yellow solid, yield 82%, melting point: 200-201℃. 1 H NMR (400MHz, DMSO-d6) δ8.92(s,1H),8.72(d,J=8.4Hz,1H),8.54(d,J=8.4Hz,1H) ,8.35(d,J=8.9Hz,1H),8.07-7.98(m,1H),7.88(d,J=8.3Hz,1H),7.79-7.67(m,2 H),7.43-7.33(m,1H),4.60(s,3H),4.20(s,1H),4.11-3.90(m,2H),3.18(d,J=11 .9Hz,2H),2.92-2.79(m,2H),2.32(s,1H),2.00-1.79(m,2H),1.61-1.34(m,2H). 13C NMR(100MHz,DMSO-d6)δ144.1,137.5,136.2,132.7,132.7,131.0,124.8,124.5,124.4,121.1,11 7.9,115.7,115.0,114.4,100.0,47.9,46.3,44.0,38.6,34.5,26.1,21.6.HRMS(ESI),calculated for C 22 H 25 N4 + [MI] + 345.2074, found 345.2074.

[0102] Example 22

[0103] The preparation method of the amino-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with 4-amino-1-methylpiperidine. The resulting amino-containing leucocele alkaloid derivative has the following structural formula: 121 mg of yellowish-green solid, yield 85%, melting point: 240-241℃. 1 H NMR (400MHz, DMSO-d6) δ11.90(s,1H),8.74(d,J=8.1Hz,1H),8.55(d,J=8.1Hz,1H),8.36(d,J=8.3Hz,2H),8.04(t,J=7.5Hz,1H),7.93( d,J=8.1Hz,1H),7.81-7.68(m,2H),7.39(t,J=7.2Hz,1H),4.86(s,1H),4.62(s,3H),3.28-3.15(m,4H),2.77(s,3H),2.29-2.08(m,4H). 13 C NMR(100MHz,DMSO-d6)δ143.4,143.3,137.5,136.7,132.9,131.4,125.0,124.6,121.5, 117.9,117.4,116.2,115.2,114.1,54.9,52.6,50.1,38.8,30.4.HRMS(ESI),calculated for C 22 H 25 N4 + [MI] + 345.2074, found 345.2074.

[0104] Example 23

[0105] The preparation method of the amino-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with (1-methyl-4-piperidine)methylamine. The resulting amino-containing leucocele alkaloid derivative has the following structural formula: 110 mg of yellow solid, yield 75%, melting point: 246-247℃. 1 H NMR (400MHz, DMSO-d6) δ11.83(s,1H),8.86(s,1H),8.77(d,J=8.6Hz,1H),8.60(d,J=8.6Hz,1H),8.39(d,J=9.0Hz,1H),8.05(t,1H),7.89(d,J= 8.4Hz,1H),7.81-7.72(m,2H),7.41(t,J=7.7Hz,1H),4.65(s,3H),4.07 (s,2H),3.11(s,5H),2.70(s,3H),2.16-1.96(m,3H),1.63-1.47(m,2H). 13 CNMR(100MHz,DMSO-d6)δ144.1,143.3,137.7,136.3,132.9,131.2,124.9,124.7,124.4,121.4 ,118.0,117.0,115.8,115.1,114.1,54.9,49.9,43.1,38.6,34.0,27.2.HRMS(ESI),calculated for C 23 H 27 N4 + [MI] + 359.2230, found 359.2229.

[0106] Example 24

[0107] The preparation method of the amino-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with (1-methyl-3-piperidine)methylamine. The resulting amino-containing leucocele alkaloid derivative has the following structural formula: 192 mg of yellow solid, yield 71%, melting point: 177-178℃. 1H NMR (400MHz, DMSO-d6) δ8.68(d,J=8.5Hz,1H),8.53(d,J=8.4Hz,1H),8.32(d,J=8.9Hz,1H),8 .00(t,1H),7.79(d,J=8.3Hz,1H),7.70(t,J=7.6Hz,2H),7.35(t,J=7.6Hz,1H),4.57(s,3H),4 .50(s,1H),3.69(d,J=15.0Hz,1H),2.47-2.33(m,2H),2.31-2.22(m,1H),2.08(s,3H),1.86-1 .78(m,1H),1.76-1.67(m,1H),1.66-1.56(m,1H),1.54-1.43(m,1H),1.27-1.18(m,1H),0.88-

[0108] 0.79 (m, 1H). 13 C NMR(100MHz,DMSO-d6)δ144.8,143.9,137.5,136.3,132.6,130.8,124.7,124.4,124.1,120.9,11 7.8,115.6,115.5,114.4,55.5,47.8,45.8,38.4,35.1,26.3,22.4,14.4.HRMS(ESI),calculated for C 23 H 27 N4 + [MI] + 359.2230, found359.2231.

[0109] Example 25

[0110] The preparation method of the amino-containing leucocele alkaloid derivative is basically the same as in Example 1, except that in step 5, the amine is replaced with 1-(3-aminopropyl)piperidine. The resulting amino-containing leucocele alkaloid derivative has the following structural formula: 184 mg of yellow solid, yield 73%, melting point: 208-209℃. 1H NMR (400MHz, DMSO-d6) δ8.89(s,1H),8.65(d,J=8.3Hz,1H),8.53(d,J=8.2Hz,1H),8.33(d,J=8.8Hz,1H),8.06-7.98(m,1H),7.88(d,J= 8.2Hz,1H),7.77-7.67(m,2H),7.42-7.33(m,1H),4.56(s,3H),4.18(s,2H),3.14-2.78(m,6H),2.17(s,2H),1.67(s,4H),1.52(s,2H). 13 C NMR(100MHz,DMSO-d6)δ143.4,142.7,137.0,135.5,132.3,130.6,124.3,124.0,123.9,120.8,11 7.4,116.2,115.1,114.4,113.5,54.2,52.7,43.1,38.1,24.7,23.3,21.9.HRMS(ESI),calculated for C 24 H 29 N4 + [MI] + 373.2387, found 373.2383.

[0111] Comparative Example 1

[0112] Synthesis of 11-(4'-(2-aminoethyl)piperazinyl)-substituted leucine iodide salt

[0113] 0.1 mol of compound 7-chloro-11-iodo-methylindole[3,2-b]quinoline and 60 mL of ethylene glycol ether were mixed, and 0.15 mol of 4-(2-aminoethyl)piperazine was added. The mixture was stirred at 120 °C for 0.5 hours, and the solid was cooled to precipitate. The reddish-brown solid was collected by filtration and recrystallized from the ether-ethanol mixture to obtain a yellow powder with a yield of 80% and a melting point greater than 250 °C. 1 HNMR(400Hz,DMSO-d6)δ8.60(d,J=8.4Hz,1H),8.44(s,1H),8.27(d,J=8.8Hz,1H),7.92(dd,J=8.4,7.2Hz,1H) ,7.72(d,J=8.8Hz,1H),7.80(t,J=7.6Hz,1H),7.48(d,J=8.4Hz,1H,),4.55(s,3H),2.85(m,8H),2.65(m,4H).

[0114] Experimental Example 1

[0115] The assay procedure for determining the activity against tobacco mosaic virus is as follows:

[0116] 1. Virus purification and concentration determination:

[0117] After two cycles of polyethylene glycol centrifugation, the absorbance of the crude virus extract at a wavelength of 260 nm was measured using a UV spectrophotometer. 260 The virus concentration is calculated using the formula.

[0118] Virus concentration (mg / ml) = (A 260 (×dilution factor) / E 0.1％ 1cm 260nm

[0119] Where E represents the extinction coefficient, which is the light absorption (optical density) value of a suspension with a concentration of 0.1% (1 mg / ml) at a wavelength of 260 nm and an optical path length of 1 cm.

[0120] TMV's E 0.1％ 1cm 260nm It is 3.1.

[0121] Store at 4℃ for later use.

[0122] 2. Preparation of compound solutions:

[0123] After weighing, the compounds from Examples 1 to 25, ningnanmycin, and ribavirin technical were added to DMF and dissolved to prepare 1×10 5 The stock solution was diluted to the required concentration with an aqueous solution containing 1‰ Tween 80.

[0124] 3. In vivo protection:

[0125] Select uniformly growing *Nicotiana santalinus* plants at the 3-5 leaf stage and spray the entire plant with the pesticide. Each treatment was repeated three times, with a 1‰ Tween 80 aqueous solution as a control. 24 hours later, sprinkle emery (500 mesh) on the leaves. Using a brush dipped in the virus solution, gently rub the entire leaf surface along the veins twice, supporting the underside of the leaf with the palm of your hand. The virus concentration was 10 μg / mL. Rinse with running water after inoculation. Record the number of lesions after 3 days and calculate the control efficacy.

[0126] 4. In vivo therapeutic effects:

[0127] Select uniformly growing *Nicotiana sambac* plants at the 3-5 leaf stage. Inoculate the entire leaf with the virus using a paintbrush at a concentration of 10 μg / mL. Rinse with running water after inoculation. After the leaves have dried, spray the entire plant with the pesticide. Each treatment is replicated three times, with a 1‰ Tween 80 aqueous solution as a control. Record the number of lesions after 3 days and calculate the control efficacy.

[0128] 5. In vivo passivation effect:

[0129] Select uniformly growing 3-5 leaf stage *Nicotiana sambac* plants. Mix the pesticide with an equal volume of virus sap, inactivate for 30 minutes, and then inoculate by friction. The virus concentration is 20 μg / mL. Rinse immediately with running water after inoculation. Repeat 3 times. Include a 1‰ Tween 80 aqueous solution as a control. Count the number of lesions after 3 days and calculate the results.

[0130] Inhibition rate (%) = [(Number of control necrotic spots - Number of treated necrotic spots) / Number of control necrotic spots] × 100%

[0131] The in vivo inactivation, in vivo therapeutic, and protective activities of all compounds against tobacco mosaic virus were tested at a treatment dose of 500 mg / L. The positive control was the commercially available antiviral agent ribavirin.

[0132] The results of the anti-Tobacco Mosaic Virus (TMV) activity tests of the amino-containing leucocele derivatives of Examples 1-25, the compound of Comparative Example 1, ningnanmycin, and ribavirin are shown in Table 1 below:

[0133] Table 1

[0134]

[0135]

[0136] As can be seen from the data in Table 1, at 500 mg / L, most of the amino-containing leucovorin derivatives exhibited good anti-TMV activity, which was better than that of the comparative compounds. Among them, the amino-containing leucovorin derivative of Example 11 had anti-TMV activity comparable to that of commercially available ningnanmycin, while the amino-containing leucovorin derivatives of Examples 4, 5, 12, 13, 18, 19 and 24 had significantly better anti-TMV activity than ribavirin.

[0137] Experiment Example 2

[0138] The antibacterial activity test procedure is as follows:

[0139] Rice sheath blight potted plant activity

[0140] Select uniformly growing rice seedlings and spray them with the prescribed concentration. A blank control was also applied by spraying with water. Each treatment was repeated twice. 24 hours after treatment, inoculate with rice sheath blight pathogens and place the seedlings in a greenhouse (25℃±4℃) under normal management. Visually assess the control efficacy 6 days after inoculation.

[0141] The in vivo bactericidal activity test results of the amino-containing leucopicrin derivatives of Examples 1-25, the compound of Comparative Example 1, and ribavirin are shown in Table 2:

[0142] Table 2

[0143]

[0144] As can be seen from the data in Table 2, in the live pot experiment, the amino-containing cypermethrin derivatives of Examples 1-25 showed live bactericidal activity against rice sheath blight, while the compound of Comparative Example 1 did not show any activity.

[0145] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. The application of a leucocele alkaloid derivative containing an amino group in its antiviral activity against plant viruses, characterized in that, The amine-containing leucocele alkaloid derivatives include at least one of the compounds shown in formulas (I-1) to (I-25): ； The virus in question is tobacco mosaic virus.

2. The application of a leucocele alkaloid derivative containing an amino group in bactericidal activity, characterized in that, The amine-containing leucocele alkaloid derivatives include at least one of the compounds shown in formulas (I-1) to (I-25): ； The bactericidal application is in the treatment of rice sheath blight.

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