Bilobaine salt derivatives and their applications in preventing and controlling plant viruses and sterilization

Abstract

The present invention relates to the field of agricultural protection technology, in particular to a leucine salt derivative and its application in preventing and controlling plant viruses and sterilizing. The leucine salt derivative includes a compound represented by formula (I): #imgabs0# wherein R 1 Includes at least one of hydrogen, methyl, methoxy, F, Cl, Br, I and cyano; R 2 Includes at least one of hydrogen, methyl, methoxy, F, Cl, Br, I, trifluoromethyl and methoxycarbonyl; R 3 including at least one of methyl, cyclopropylmethyl, cyclohexylmethyl, 2,2-dimethylpropyl and benzyl; R 4 The leucophylline salt derivatives have good plant virus prevention and control and good fungicidal activity.

Description

Technical Field

[0001] The present invention relates to the technical field of agricultural protection, in particular to a cephalosporin salt derivative and its application in preventing and controlling plant viruses and sterilizing. Background Art

[0002] Current research has found that leucophylline has activity comparable to chloroquine against Plasmodium falciparum. Studies have also shown that leucophylline derivatives have certain pharmaceutical effects. Specifically: 1. Studies have synthesized 11-anilinoquinoline derivatives and demonstrated potential anti-tumor activity through in vivo and in vitro experiments. 2. Studies have found that leucophylline salt derivatives containing an aniline structure have significant inhibitory effects on methicillin-resistant Staphylococcus aureus. Although there are many methods for synthesizing leucophylline structures, they generally have disadvantages such as long reaction routes, low yields, and harsh reaction conditions. The present invention successfully constructs leucophylline salt derivatives in a single step by introducing an imine salt intermediate as a C1 synthon. The experimental operation is simple and the yield can reach equivalent. Moreover, to date, there is no application of leucophylline salt derivatives in the prevention and treatment of plant viruses and sterilization. Summary of the Invention

[0003] The present invention aims to solve at least one of the technical problems existing in the related art. To this end, the present invention provides a cephalaine salt derivative having good plant virus prevention and control and good fungicidal activity.

[0004] In one aspect of the present invention, the present invention provides a leucophylline salt derivative, wherein the leucophylline salt derivative includes a compound represented by formula (I):

[0005] (I)

[0006] Among them, R 1 including at least one of hydrogen, methyl, methoxy, F, Cl, Br, I and cyano;

[0007] R 2 including at least one of hydrogen, methyl, methoxy, F, Cl, Br, I, trifluoromethyl and methoxycarbonyl;

[0008] R 3 including at least one of methyl, cyclopropylmethyl, cyclohexylmethyl, 2,2-dimethylpropyl and benzyl;

[0009] R 4 Includes at least one of hydrogen, p-toluenesulfonyl and benzenesulfonyl.

[0010] Furthermore, the cephalaenopsis alkaloid salt derivative includes at least one of the compounds represented by formula (I-1) to formula (I-22):

[0011] .

[0012] In another aspect of the present invention, the present invention provides a method for preparing the leucoderma salt derivative as described above, the preparation method comprising the following steps:

[0013] In the presence of a catalyst and a formylating agent, compound A is subjected to an electrophilic substitution reaction with an imine salt in an organic solvent to obtain the leucoderma salt derivative;

[0014] The structural formula of the compound A includes ,in,

[0015] R 1 including at least one of hydrogen, methyl, methoxy, F, Cl, Br, I and cyano;

[0016] R 2 including at least one of hydrogen, methyl, methoxy, F, Cl, Br, I, trifluoromethyl and methoxycarbonyl;

[0017] R 3 including at least one of methyl, cyclopropylmethyl, cyclohexylmethyl, 2,2-dimethylpropyl and benzyl;

[0018] R 4 Includes at least one of hydrogen, p-toluenesulfonyl and benzenesulfonyl.

[0019] Further, the catalyst includes POCl3 and / or SOCl2;

[0020] And / or, the molar ratio of the compound A to the catalyst is 1:1.2-3.0.

[0021] Further, the formylating agent includes N,N-dimethylformamide and / or N-methylformanilide;

[0022] The imide salt includes and / or .

[0023] Furthermore, the concentration of compound A is 0.4-0.6 mmol / mL.

[0024] Furthermore, the organic solvent includes at least one of N,N-dimethylformamide, dichloromethane, 1,2-dichloroethane, 1,4-dioxane and tetrahydrofuran.

[0025] Furthermore, the temperature of the electrophilic substitution reaction is -16°C-25°C, and the time is 1-2 h.

[0026] In another aspect of the present invention, the present invention provides a use of the leucoderma salt derivative as described above in preventing and treating plant viral diseases.

[0027] In another aspect of the present invention, the present invention provides a use of the cephalaenopsis alkaloid derivative as described above in sterilization.

[0028] The above one or more technical solutions in the embodiments of the present invention have at least one of the following technical effects:

[0029] The leucine salt derivatives of the present invention are prepared by introducing different substitutions on the quinoline benzene ring and quinoline nitrogen, and utilizing the substituents to regulate the electrical properties and solubility of the leucine salt derivatives, so that the obtained leucine salt derivatives have good plant virus prevention and control and good bactericidal activity.

[0030] Additional aspects and advantages of the present invention will be set forth in part in the description which follows and, in part, will be obvious from the description which follows, or may be learned by practice of the present invention. DETAILED DESCRIPTION

[0031] To make the purpose, technical solutions and advantages of the present invention clearer, the technical solutions in the present invention will be clearly and completely described below. Obviously, the embodiments described are part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention. The following embodiments are used to illustrate the present invention, but are not used to limit the scope of the present invention.

[0032] In the description of this specification, the reference terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" mean that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the embodiment of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art can combine and combine different embodiments or examples described in this specification and features of different embodiments or examples without contradiction.

[0033] In one aspect of the present invention, the present invention provides a leucophylline salt derivative, wherein the leucophylline salt derivative includes a compound represented by formula (I):

[0034] (I)

[0035] Among them, R 1 Including at least one of hydrogen, methyl, methoxy, F (fluorine), Cl (chlorine), Br (bromine), I (iodine) and cyano; R 2 Includes at least one of hydrogen, methyl, methoxy, F, Cl, Br, I, trifluoromethyl and methoxycarbonyl; R 3 Including at least one of methyl, cyclopropylmethyl, cyclohexylmethyl, 2,2-dimethylpropyl and benzyl; R 4 Includes at least one of hydrogen, p-toluenesulfonyl and benzenesulfonyl.

[0036] The leucine salt derivatives of the present invention are prepared by introducing different substitutions on the quinoline benzene ring and quinoline nitrogen, and utilizing the substituents to regulate the electrical properties and solubility of the leucine salt derivatives, so that the obtained leucine salt derivatives have good plant virus prevention and control and good bactericidal activity.

[0037] In some embodiments of the present invention, the leucoderma salt derivative includes at least one compound represented by formula (I-1) to formula (I-22):

[0038] .

[0039] In another aspect of the present invention, a method for preparing the aforementioned leucophylline salt derivative is provided, the method comprising the following steps: in the presence of a catalyst and a formylating agent, allowing compound A to undergo electrophilic substitution reaction with an imine salt in an organic solvent to obtain the leucophylline salt derivative; the structural formula of compound A includes , where R 1 Includes at least one of hydrogen, methyl, methoxy, F, Cl, Br, I and cyano; R 2 Includes at least one of hydrogen, methyl, methoxy, F, Cl, Br, I, trifluoromethyl and methoxycarbonyl; R 3 Including at least one of methyl, cyclopropylmethyl, cyclohexylmethyl, 2,2-dimethylpropyl and benzyl; R 4 Includes at least one of hydrogen, p-toluenesulfonyl and benzenesulfonyl.

[0040] In some embodiments of the present invention, the catalyst comprises POCl3 and / or SOCl2.

[0041] In some specific embodiments of the present invention, the molar ratio of compound A to the catalyst is 1:1.2-3.0, for example, 1:1.2, 1:1.5, 1:2, 1:2.5, or 1:3.0. Relative to the above molar ratio range, when the molar ratio of compound A to the catalyst is greater than 1:3.0, the yield of the leucophylline salt derivative is significantly reduced; when the molar ratio of compound A to the catalyst is less than 1:1.2, the yield of the leucophylline salt derivative is also significantly reduced.

[0042] In some preferred embodiments of the present invention, the molar ratio of compound A to catalyst is 1:1.5-2.5.

[0043] In some embodiments of the present invention, the formylating agent comprises N,N-dimethylformamide and / or N-methylformanilide.

[0044] In some embodiments of the present invention, the concentration of Compound A is 0.4-0.6 mmol / mL. In some specific embodiments of the present invention, the amount of organic solvent used is such that the concentration of Compound A is 0.5 mmol / mL.

[0045] In some embodiments of the present invention, the organic solvent includes at least one of N,N-dimethylformamide, dichloromethane, 1,2-dichloroethane, 1,4-dioxane and tetrahydrofuran.

[0046] In some embodiments of the present invention, the temperature of the electrophilic substitution reaction is -16-25°C (for example, -16°C, -10°C, -5°C, 0°C, 5°C, 10°C, 15°C, 20°C or 25°C), and the time is 1-2 h (for example, 1 h, 1.5 h or 2 h).

[0047] In some embodiments of the present invention, the imide salt comprises and / or .

[0048] In another aspect of the present invention, the present invention provides a use of the aforementioned leucophylline salt derivative in preventing and treating plant viral diseases. The leucophylline salt derivative provided by the present invention has excellent anti-plant viral activity.

[0049] In some specific embodiments of the present invention, the cephalaenopsis salt derivatives of the present invention exhibit good anti-tobacco mosaic virus activity.

[0050] In some specific embodiments of the present invention, the leucophylline salt derivatives of the present invention can be used as anti-plant virus agents to kill insects.

[0051] In another aspect of the present invention, the present invention provides a use of the aforementioned leucophylline salt derivative in sterilization. The leucophylline salt derivative provided by the present invention has high sterilization activity.

[0052] In some specific embodiments of the present invention, the leucoderma salt derivatives of the present invention have excellent fungicidal activity against pathogens that cause rice sheath blight.

[0053] The present invention will be further described below with reference to specific examples. It should be noted that the following examples are only used to explain the present invention and are not intended to limit the present invention.

[0054] Example

[0055] Example 1

[0056] The preparation method of the leucoderma salt derivative of the compound represented by formula (I-1) comprises the following steps:

[0057] 1. Preparation of Compound A

[0058]

[0059] Indole (3.51 g, 30 mmol) was dissolved in acetonitrile (30 mL), and 60% sodium hydride (1.01 g, 40 mmol) was slowly added in batches at 0 °C. After stirring for 10 min, the mixture was returned to room temperature and p-toluenesulfonyl chloride (6.29 g, 33 mmol) was added until the reaction was complete. Saturated aqueous ammonium chloride was added to quench the reaction, and the mixture was extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and evaporated under reduced pressure. The mixture was purified by column chromatography to obtain compound 1 as a white solid.

[0060] Compound 1 (2.98 g, 11 mmol) and high-purity water (110 mmol) were dissolved in acetone (110 mL). NBS (2.14 g, 12 mmol) was added until the reaction was complete. Triethylamine (12 mmol) was then added and stirred for 1 h. A large amount of white solid precipitated. The solid was filtered, washed several times with acetone, and air-dried to obtain intermediate 2.

[0061] Intermediate 2 (2.35 g, 5 mmol), N-methylaniline (5.5 mmol) and triethylamine (10 mmol) were dissolved in ethyl acetate (100 mL) and heated under reflux for 6 h. After the reaction was completed, water was added and the mixture was extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and distilled under reduced pressure. The mixture was then dissolved in ethyl acetate and a solution of boron trifluoride in ether (25 mmol) was added. The mixture was reacted at 50 °C for 3 h. After the reaction was completed, the mixture was cooled to room temperature, and a saturated sodium bicarbonate solution was slowly added. The mixture was extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and distilled under reduced pressure. The mixture was purified by column chromatography to obtain compound A as a white solid.

[0062] 2. Preparation of the compound represented by formula (I-1).

[0063] Phosphorus oxychloride (2 mmol, 186 μL) was slowly added dropwise to ultra-dry DMF (N,N-dimethylformamide) (1 mL) at -16 °C and stirred for 0.5 hours. Compound A (1 mmol, 376 mg) dissolved in ultra-dry DMF (2 mL) was then added dropwise at 0 °C and allowed to react at room temperature for 1 hour. After the reaction, the reaction mixture was poured into ice water and stirred to precipitate a solid. 10% sodium hydroxide solution was added, and the pH was adjusted to approximately 10. The mixture was allowed to stand for 1 hour and then filtered to obtain 393 mg of the leucophylline salt derivative as a yellow solid in a 93% yield with a melting point of 148-149 °C. 1 H NMR (400 MHz, DMSO-d6) δ 9.98 (d, J = 10.7 Hz,1H), 8.96 – 8.84 (m, 3H), 8.56 – 8.46 (m, 1H), 8.34 – 8.27 (m, 1H), 8.16 –8.04 (m, 4H), 7.81 – 7.75 (m, 1H), 7.39 (d, J = 8.4 Hz, 2H), 5.03 (s, 3H), 2.27 (s, 3H). 13 C NMR (100 MHz, DMSO-d6) δ 147.5, 142.1, 137.6, 136.0, 135.2,133.0, 131.7, 131.6, 131.1, 129.1, 128.3, 127.7, 127.4, 126.3, 118.9, 118.2,115.2, 41.7, 21.5.HRMS, calculated for C 23 H 19 N2O2S + [M-Cl]+ 387.1162, found387.1160.

[0064] Example 2

[0065] The preparation method of the cephalaenoic acid salt derivative of the compound represented by formula (I-2) is basically the same as that of Example 1, except that the raw material in step 1 has a methyl substituent at the 5-position of the indole ring.

[0066] In this example, 402 mg of a cephalaenoic acid salt derivative was obtained as a yellow solid with a yield of 92% and a melting point of 151-152 °C. 1 H NMR (400 MHz, DMSO-d6) δ 9.98 (s, 1H), 8.84 (d, J = 8.8 Hz, 2H), 8.71 (s,1H), 8.46 (d, J = 8.7 Hz, 1H), 8.34 – 8.25 (m, 1H), 8.12 – 8.01 (m, 3H), 7.95 (d, J = 8.8 Hz, 1H), 7.37 (d, J = 8.1 Hz, 2H), 4.96 (s, 3H), 2.60 (s, 3H), 2.27 (s, 3H). 13 C NMR (100 MHz, DMSO-d6)δ 147.4, 142.3, 140.6, 137.6, 137.2,136.2, 135.1, 133.0, 132.0, 131.7, 131.0, 129.1, 129.0, 128.5, 127.7, 127.4,126.0, 118.8, 118.5, 115.1, 41.5, 21.5, 21.2. HRMS, calculated for C 24 H 21 N2O2S + [M-Cl] + 401.1318, found 401.1315.

[0067] Example 3

[0068] The preparation method of the leucoderma salt derivative of the compound represented by formula (I-3) is basically the same as that of Example 1, except that the raw material in step 1 has a methoxy substituent at the 5-position of the indole ring.

[0069] In this example, 448 mg of a cephalaenoic acid salt derivative was obtained as a bright orange solid with a yield of 99% and a melting point of 162-163°C. 1H NMR (400 MHz, DMSO-d6) δ 9.94 (s, 1H), 8.91 – 8.82 (m, 2H), 8.42 (d, J =9.3 Hz, 1H), 8.34 – 8.27 (m, 1H), 8.17 (s, 1H), 8.10 – 8.05 (m, 1H), 8.00 (d,J = 8.3 Hz, 2H), 7.74 – 7.68 (m, 1H), 7.35 (d, J = 8.1 Hz, 2H), 5.01 (s, 3H), 4.02 (s, 3H), 2.26 (s, 3H). 13 C NMR (100 MHz, DMSO-d6) δ 157.4, 147.4, 141.9,137.7, 136.7, 135.3, 132.9, 132.1, 131.7, 131.0, 129.4, 129.1, 127.6, 127.4,124.5, 119.2, 118.9, 116.4, 110.1, 56.9, 41.5, 21.5. HRMS, calculated forC 24 H 21 N2O3S + [M-Cl] + 417.1267, found 417.1265.

[0070] Example 4

[0071] The preparation method of the cephalaenoic acid salt derivative of the compound represented by formula (I-4) is basically the same as that of Example 1, except that the raw material in step 1 has a fluorine atom substituent at the 5-position of the indole ring.

[0072] In this example, 379 mg of a cephalaenoic acid salt derivative was obtained as a bright yellow solid with a yield of 86% and a melting point of 160-161°C. 1 H NMR (400 MHz, DMSO-d6) δ 10.04 (s, 1H), 8.92 – 8.79 (m, 3H), 8.60 (dd, J= 9.3, 4.3 Hz, 1H), 8.38 – 8.28 (m, 1H), 8.15 – 7.99 (m, 4H), 7.39 (d, J =8.2 Hz, 2H), 4.97 (s, 3H), 2.29 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 147.6,141.7, 138.6, 137.7, 135.6, 132.9, 132.3, 131.7, 131.1, 129.8, 129.3, 127.7,123.9, 123.6, 119.4, 118.9, 117.1, 114.2, 114.0, 41.4, 21.5. HRMS, calculated for C 23 H 18 FN2O2S + [M-Cl] + 405.1068, found 405.1066.

[0073] Example 5

[0074] The preparation method of the cephalaenoic acid salt derivative of the compound represented by formula (I-5) is basically the same as that of Example 1, except that the raw material in step 1 has a chlorine atom substituent at the 5-position of the indole ring.

[0075] In this example, 453 mg of a cephalaenoic acid salt derivative was obtained as a bright yellow solid with a yield of 99% and a melting point of 158-159°C. 1 H NMR (400 MHz, DMSO-d6) δ 10.05 (s, 1H), 8.97 (s, 1H), 8.87 (d, J = 8.2Hz, 2H), 8.59 (d, J = 9.1 Hz, 1H), 8.36 – 8.29 (m, 1H), 8.21 – 8.04 (m, 4H), 7.40 (d, J = 8.1 Hz, 2H), 4.98 (s, 3H), 2.29 (s, 3H). 13 C NMR (100 MHz, DMSO-d6) δ 147.7, 141.2, 140.6, 137.7, 135.6, 135.5, 132.9, 132.1, 131.8, 131.2,130.8, 129.8, 129.4, 127.8, 127.2, 119.8, 118.9, 116.9, 110.0, 41.6, 21.5.HRMS, calculated for C 23 H 18 ClN2O2S + [M-Cl] + 421.0772, found 421.0771.

[0076] Example 6

[0077] The preparation method of the cephalaenoic acid salt derivative of the compound represented by formula (I-6) is basically the same as that in Example 1, except that the raw material in step 1 has a bromine atom substituent at the 5-position of the indole ring.

[0078] In this example, 472 mg of a cephalaenoic acid salt derivative was obtained as a yellow solid with a yield of 94% and a melting point of 154-155 °C. 1 H NMR (400 MHz, DMSO-d6) δ 10.04 (s, 1H), 9.06 (s, 1H), 8.87 (d, J = 8.2Hz, 2H), 8.52 (d, J = 9.0 Hz, 1H), 8.35 – 8.29 (m, 1H), 8.27 (d, J = 9.1 Hz,1H), 8.14 – 8.07 (m, 3H), 7.39 (d, J = 8.3 Hz, 2H), 4.98 (s, 3H), 2.29 (s,3H). 13 C NMR (100 MHz, DMSO-d6) δ 147.7, 141.1, 141.0, 138.3, 137.7, 135.6,132.9, 131.9, 131.7, 131.2, 130.0, 129.7, 129.4, 127.8, 120.2, 118.9, 118.8,117.1, 41.7, 21.5. HRMS, calculated for C 23 H 18 BrN2O2S + [M-Cl] + 465.0267, found465.0269.

[0079] Example 7

[0080] The preparation method of the cephalaenoic acid salt derivative of the compound represented by formula (I-7) is basically the same as that of Example 1, except that the raw material in step 1 has an iodine atom substituent at the 5-position of the indole ring.

[0081] In this example, 505 mg of a cephalaenoic acid salt derivative was obtained as an orange-yellow solid with a yield of 92% and a melting point of 138-139 °C. 1H NMR (400 MHz, CDCl3) δ 8.79 (s, 1H), 8.57 – 8.46 (m, 2H), 8.07 (t, J =7.8 Hz, 1H), 7.96 (d, J = 8.0 Hz, 2H), 7.83 (d, J = 8.1 Hz, 1H), 7.65 (t, J =7.5 Hz, 1H), 7.54 (d, J = 8.7 Hz, 1H), 7.33 (d, J = 8.8 Hz, 1H), 7.30 – 7.18(m, 3H), 4.96 (s, 3H), 2.38 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 144.4, 142.9,141.6, 140.0, 135.2, 134.7, 133.4, 132.7, 132.5, 129.7, 128.9, 127.3, 126.2,126.1, 125.8, 117.5, 115.5, 114.4, 40.5, 21.4. HRMS, calculated forC 23 H 18 IN2O2S + [M-Cl] + 513.0128, found 513.0129.

[0082] Example 8

[0083] The preparation method of the cephalaenoic acid salt derivative of the compound represented by formula (I-8) is basically the same as that of Example 1, except that the raw material in step 1 has a cyano substituent at the 5-position of the indole ring.

[0084] In this example, 237 mg of a cephalaenoic acid salt derivative was obtained as a light yellow solid with a yield of 92% and a melting point of 112-113 °C. 1 H NMR (400 MHz, CDCl3) δ 8.07 (d, J = 8.6 Hz, 1H), 7.88 (s, 1H), 7.77 (d, J= 8.3 Hz, 2H), 7.69 (d, J = 3.7 Hz, 1H), 7.59 – 7.53 (m, 1H), 7.28 (s, 1H), 6.72 (d, J = 3.7 Hz, 1H), 2.37 (s, 3H). 13HRMS, calculated for C 24 H 18 N3O2S + [M-Cl] + 412.1114, found 412.1117.

[0085] Example 9

[0086] The preparation method of the cephalaenoic acid salt derivative of the compound represented by formula (I-9) is basically the same as that of Example 1, except that the raw material in step 3 has a methyl substituent at the 4-position of the aniline ring.

[0087] In this example, 424 mg of a cephalaenoic acid salt derivative was obtained as a yellow-green solid with a yield of 97% and a melting point of 152-153 °C. 1 H NMR (400 MHz, DMSO-d6) δ 9.88 (s, 1H), 8.86 (d, J = 8.4 Hz, 1H), 8.72 (d,J = 7.9 Hz, 1H), 8.58 (d, J = 9.2 Hz, 2H), 8.15 (d, J = 9.3 Hz, 1H), 8.13 –8.09 (m, 1H), 8.07 (d, J = 8.0 Hz, 2H), 7.81 – 7.74 (m, 1H), 7.38 (d, J = 8.1Hz, 2H), 4.94 (s, 3H), 2.68 (s, 3H), 2.28 (s, 3H). 13 C NMR (100 MHz, DMSO-d6) δ147.5, 142.1, 141.6, 139.4, 137.2, 136.2, 135.7, 133.1, 131.9, 131.7, 131.1,130.1, 130.0, 128.3, 128.1, 127.7, 127.7, 126.3, 118.5, 118.5, 115.4, 41.4,21.5, 21.3. HRMS, calculated for C 24 H 21 N2O2S + [M-Cl] +401.1318, found 401.1318.

[0088] Example 10

[0089] The preparation method of the cephalaenoic acid salt derivative of the compound represented by formula (I-10) is basically the same as that in Example 1, except that the raw material in step 3 has a methoxy substituent at the 4-position of the aniline ring.

[0090] In this example, 448 mg of a cephalaenoic acid salt derivative was obtained as a yellow solid with a yield of 99% and a melting point of 188-189 °C. 1 H NMR (400 MHz, DMSO-d6) δ 9.86 (s, 1H), 8.84 (d, J = 8.3 Hz, 1H), 8.77 (d, J= 9.8 Hz, 1H), 8.54 (d, J = 8.6 Hz, 1H), 8.31 (d, J = 2.8 Hz, 1H), 8.06 (d, J= 8.4 Hz, 3H), 7.93 – 7.88 (m, 1H), 7.78 – 7.72 (m, 1H), 7.39 (d, J = 8.3 Hz, 2H), 4.95 (s, 3H), 4.07 (s, 3H), 2.29 (s, 3H). 13 C NMR (100 MHz, DMSO-d6) δ159.0, 147.5, 141.7, 140.0, 135.3, 133.4, 133.1, 132.2, 131.1, 129.6, 127.8,127.6, 127.4, 127.2, 126.2, 120.5, 118.5, 115.3, 109.2, 56.8, 41.7,21.5.HRMS, calculated for C 24 H 21 N2O3S + [M-Cl] + 417.1267, found 417.1268.

[0091] Example 11

[0092] The preparation method of the cephalaenoic acid salt derivative of the compound represented by formula (I-11) is basically the same as that in Example 1, except that the raw material in step 3 has a fluorine atom substituent at the 4-position of the aniline ring.

[0093] In this example, 410 mg of a cephalaenoic acid salt derivative was obtained as a yellow solid with a yield of 93% and a melting point of 153-154 °C.1 H NMR (400 MHz, DMSO-d6) δ 10.00 (s, 1H), 8.95 (d, J = 22.6 Hz, 2H), 8.75 (s,1H), 8.57 (d, J = 7.1 Hz, 1H), 8.27 (s, 1H), 8.10 (s, 3H), 7.79 (s, 1H), 7.41 (s, 2H), 5.00 (s, 3H), 2.29 (s, 3H). 13 C NMR (100 MHz, DMSO-d6) δ 147.6, 142.4,142.3, 136.2, 134.8, 133.0, 132.6, 131.1, 128.4, 128.2, 127.8, 126.4, 124.8,124.5, 122.4, 118.2, 115.4, 114.9, 114.7, 42.1, 21.5. 19 F NMR (376 MHz, DMSO) δ-110.17 – -110.42 (m). HRMS, calculated for C 23 H 18 FN2O2S + [M-Cl] + 405.1068, found405.1068.

[0094] Example 12

[0095] The preparation method of the cephalaenoic acid salt derivative of the compound represented by formula (I-12) is basically the same as that in Example 1, except that the raw material in step 3 has a chlorine atom substituent at the 4-position of the aniline ring.

[0096] In this example, 398 mg of a cephalaenoic acid salt derivative was obtained as a green solid with a yield of 87% and a melting point of 178-179 °C. 1H NMR (400 MHz, DMSO-d6) δ 9.98 (s, 1H), 9.03 (s, 1H), 8.95 – 8.86 (m, 2H), 8.58 (d, J = 8.6 Hz, 1H), 8.32 (d, J = 9.6 Hz, 1H), 8.15 (t, J = 8.0 Hz, 1H), 8.10 (d, J = 8.0 Hz, 2H), 7.79 (t, J = 7.8 Hz, 1H), 7.40 (d, J = 8.1 Hz, 2H), 4.98 (s, 3H), 2.29 (s, 3H). 13 C NMR (100 MHz, DMSO-d6) δ 147.6, 142.8, 142.5,136.4, 136.2, 134.9, 133.6, 133.0, 132.6, 131.1, 129.9, 128.5, 128.3, 128.0,127.8, 126.4, 121.3, 118.2, 115.4, 100.0, 41.9, 21.5. HRMS, calculated forC 23 H 18 ClN2O2S + [M-Cl] + 421.0772, found 421.0773.

[0097] Example 13

[0098] The preparation method of the cephalaenoic acid salt derivative of the compound represented by formula (I-13) is basically the same as that in Example 1, except that the raw material in step 3 has a bromine atom substituent at the 4-position of the aniline ring.

[0099] In this example, 478 mg of a yellow solid of a cephalaenoic acid salt derivative was obtained with a yield of 95% and a melting point of 167-168 °C. 1HNMR (400 MHz, DMSO-d6) δ 9.97 (s, 1H), 9.18 (d, J = 2.1 Hz, 1H), 8.91 (d, J =8.3 Hz, 1H), 8.83 (d, J = 9.6 Hz, 1H), 8.58 (d, J = 8.6 Hz, 1H), 8.41 (d, J =9.5 Hz, 1H), 8.17 – 8.12 (m, 1H), 8.10 (d, J = 8.4 Hz, 2H), 7.82 – 7.74 (m,1H), 7.39 (d, J = 8.3 Hz, 2H), 4.97 (s, 3H), 2.29 (s, 3H). 13 C NMR (100 MHz, DMSO-d6) δ 147.6, 142.7, 142.5, 137.4, 136.5, 136.4, 133.2, 133.0, 132.4,131.1, 128.7, 128.5, 127.9, 127.8, 126.4, 122.2, 121.2, 118.2, 115.4, 41.9,21.5. HRMS, calculated for C 23 H 18 BrN2O2S + [M-Cl] + 465.0267, found 465.0268.

[0100] Example 14

[0101] The preparation method of the cephalaenoic acid salt derivative of the compound represented by formula (I-14) is basically the same as that in Example 1, except that the raw material in step 3 has a trifluoromethyl substituent at the 4-position of the aniline ring.

[0102] In this example, 481 mg of a cephalaenoic acid salt derivative was obtained as a bright yellow solid with a yield of 98% and a melting point of 165-166 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.23 (s, 1H), 9.45 (s, 1H), 9.09 (d, J = 9.4Hz, 1H), 8.97 (d, J = 8.3 Hz, 1H), 8.63 (d, J = 8.6 Hz, 1H), 8.59 – 8.52 (m,1H), 8.19 (t, J = 8.0 Hz, 1H), 8.14 (d, J = 8.5 Hz, 2H), 7.82 (t, J = 7.7 Hz,1H), 7.41 (d, J = 8.2 Hz, 2H), 5.03 (s, 3H), 2.30 (s, 3H). 13 C NMR (100 MHz, DMSO-d6) δ 147.7, 144.2, 142.8, 138.8, 136.9, 133.0, 132.7, 131.2, 129.9,128.8, 127.8, 126.7, 126.5, 121.0, 118.1, 115.4, 42.0, 21.5. 19 F NMR (376 MHz, DMSO) δ -61.03 (s). HRMS, calculated for C 24 H 18 F3N2O2S + [M-Cl] + 455.1036, found455.1039.

[0103] Example 15

[0104] The preparation method of the cephalaenoic acid salt derivative of the compound represented by formula (I-15) is basically the same as that in Example 1, except that the raw material in step 3 has a methoxycarbonyl substituent at the 4-position of the aniline ring.

[0105] In this example, 438 mg of a cephalaenoic acid salt derivative was obtained as a yellow-green solid with a yield of 91% and a melting point of 157-158 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.21 (s, 1H), 9.54 (s, 1H), 8.94 (t, J = 7.8Hz, 2H), 8.63 (d, J = 8.4 Hz, 2H), 8.18 (t, J = 8.0 Hz, 3H), 7.81 (t, J = 7.6Hz, 1H), 7.40 (d, J = 8.2 Hz, 2H), 4.99 (s, 3H), 4.04 (s, 3H), 2.29 (s, 3H). 13 C NMR (100 MHz, DMSO-d6) δ 165.3, 147.7, 143.7, 142.8, 139.2, 136.7, 133.9,133.3, 133.1, 132.3, 131.1, 130.2, 129.4, 128.6, 127.8, 127.0, 126.4, 119.8,118.1, 115.4, 53.5, 41.9, 21.5. HRMS, calculated for C 25 H 21 N2O4S + [M-Cl] + 445.1217, found 445.1216.

[0106] Example 16

[0107] The preparation method of the cephalaenoic acid salt derivative of the compound represented by formula (I-16) is basically the same as that in Example 1, except that the raw material in step 3 has a methyl substituent at the 3-position of the aniline ring.

[0108] In this example, 433 mg of a cephalaenoic acid salt derivative was obtained as a yellow-green solid with a yield of 99% and a melting point of 141-142°C. 1HNMR (400 MHz, DMSO-d6) δ 9.95 (s, 1H), 8.89 (d, J = 8.2 Hz, 1H), 8.72 (d, J =8.4 Hz, 1H), 8.68 (s, 1H), 8.57 (d, J = 8.6 Hz, 1H), 8.12 (d, J = 7.8 Hz,1H), 8.07 (d, J = 8.4 Hz, 2H), 7.93 (d, J = 8.4 Hz, 1H), 7.77 (t, J = 7.7 Hz,1H), 7.38 (d, J = 8.2 Hz, 2H), 4.94 (s, 3H), 2.76 (s, 3H), 2.28 (s, 3H). 13 CNMR (100 MHz, DMSO-d6) δ 147.5, 147.1, 142.0, 141.7, 137.9, 135.6, 133.1,131.2, 131.1, 129.1, 128.1, 127.7, 126.2, 125.9, 118.5, 117.7, 115.4, 41.3,22.8, 21.5. HRMS, calculated for C 24 H 21 N2O2S + [M-Cl] + 401.1318, found 401.1318.

[0109] Example 17

[0110] The preparation method of the cephalaenoic acid salt derivative of the compound represented by formula (I-17) is basically the same as that in Example 1, except that the raw material in step 3 has a chlorine atom substituent at the 3-position of the aniline ring.

[0111] In this example, 430 mg of a cephalaenoic acid salt derivative was obtained as a yellow solid with a yield of 94% and a melting point of 154-155 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.05 (s, 1H), 9.02 (s, 1H), 8.96 – 8.85 (m, 2H), 8.59 (d, J = 8.6 Hz, 1H), 8.20 – 8.13 (m, 2H), 8.10 (d, J = 8.4 Hz, 2H), 7.79(t, J = 7.8 Hz, 1H), 7.40 (d, J = 8.3 Hz, 2H), 4.95 (s, 3H), 2.29 (s, 3H). 13 CNMR (100 MHz, DMSO-d6) δ 147.1, 142.4, 142.0, 139.8, 137.6, 135.9, 132.9,132.6, 131.5, 130.6, 129.3, 128.6, 127.9, 127.3, 125.9, 125.7, 117.9, 117.7,114.9, 41.3, 21.0. HRMS, calculated for C 23 H 18 ClN2O2S + [M-Cl] + 421.0772, found421.0773.

[0112] Example 18

[0113] The preparation method of the cephalaenoic acid salt derivative of the compound represented by formula (I-18) is basically the same as that of Example 1, except that there is a cyclopropylmethyl substituent on the nitrogen atom of aniline in step 3.

[0114] In this example, 458 mg of a cephalaenoic acid salt derivative was obtained as a yellow solid with a yield of 99% and a melting point of 113-114 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.06 (s, 1H), 8.86 (t, J = 9.8 Hz, 2H), 8.79 (d,J = 8.1 Hz, 1H), 8.59 (d, J = 8.3 Hz, 1H), 8.32 (t, J = 7.7 Hz, 1H), 8.19 –8.05 (m, 4H), 7.84 (t, J = 7.3 Hz, 1H), 7.41 (d, J = 7.3 Hz, 2H), 5.52 (d, J= 4.9 Hz, 2H), 2.30 (s, 3H), 1.51 (s, 1H), 0.82 (s, 2H), 0.66 (d, J = 7.2 Hz,2H). 13 C NMR (100 MHz, DMSO-d6) δ 147.5, 142.5, 141.5, 137.2, 136.0, 135.3,133.3, 132.3, 131.9, 131.1, 129.7, 129.2, 127.8, 127.4, 126.6, 119.0, 117.5,115.6, 54.7, 21.6, 10.6, 4.6. HRMS, calculated for C 26 H 23 N2O2S + [M-Cl] + 427.1475, found 427.1474.

[0115] Example 19

[0116] The preparation method of the cephalaenoic acid salt derivative of the compound represented by formula (I-19) is basically the same as that of Example 1, except that in step 3, there is a cyclohexylmethyl substituent on the nitrogen atom of aniline.

[0117] In this example, 495 mg of a cephalaenoic acid salt derivative was obtained as a yellow solid with a yield of 98% and a melting point of 142-143 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.07 (s, 1H), 8.96 (d, J = 9.2 Hz, 1H), 8.87 (d,J = 7.9 Hz, 1H), 8.64 – 8.56 (m, 2H), 8.32 – 8.25 (m, 1H), 8.17 – 8.06 (m,4H), 7.83 (t, J = 7.8 Hz, 1H), 7.40 (d, J = 8.3 Hz, 2H), 5.44 (d, J = 92.5Hz, 2H), 2.89 (s, 1H), 2.72 (s, 1H), 2.51 (s, 1H), 2.30 (s, 3H), 2.09 (s,1H), 1.83 (s, 1H), 1.62 – 1.53 (m, 2H), 1.43 – 1.34 (m, 2H), 1.19 – 1.04 (m,2H). 13 C NMR (100 MHz, DMSO-d6) δ 147.5, 142.4, 141.7, 137.7, 135.8, 135.1,133.2, 132.4, 131.8, 131.1, 129.8, 129.2, 127.8, 127.7, 127.2, 126.6, 119.4,117.7, 115.6, 56.2, 38.0, 36.3, 31.2, 26.0, 21.5. HRMS, calculated forC 29 H 29 N2O2S + [M-Cl] + 469.1944, found 469.1946.

[0118] Example 20

[0119] The preparation method of the cephalaenoic acid salt derivative of the compound represented by formula (I-20) is basically the same as that of Example 1, except that there is a tert-butylmethyl substituent on the nitrogen atom of aniline in step 3.

[0120] In this example, 455 mg of a cephalaenoic acid salt derivative was obtained as a yellow solid with a yield of 95% and a melting point of 127-128 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.12 (s, 1H), 9.09 (d, J = 7.6 Hz, 1H), 9.01 –8.83 (m, 2H), 8.56 (d, J = 7.9 Hz, 1H), 8.26 (s, 1H), 8.11 – 7.94 (m, 4H), 7.77 (s, 1H), 7.35 (d, J = 7.0 Hz, 2H), 5.77 (s, 1H), 5.55 (d, J = 14.7 Hz, 1H), 2.27 (s, 3H), 0.85 (s, 9H). 13 C NMR (100 MHz, DMSO-d6) δ 147.5, 142.9,142.4, 138.7, 135.9, 134.5, 132.9, 132.6, 131.7, 131.0, 129.3, 128.2, 127.9,127.7, 126.2, 120.7, 118.6, 115.9, 59.0, 37.4, 28.6, 21.5. HRMS, calculated for C 27 H 27 N2O2S + [M-Cl] + 443.1788, found 443.1790.

[0121] Example 21

[0122] The preparation method of the cephalaenoic acid salt derivative of the compound represented by formula (I-21) is basically the same as that of Example 1, except that there is a benzyl substituent on the nitrogen atom of aniline in step 3.

[0123] In this example, 494 mg of a cephalaenoic acid salt derivative was obtained as a yellow solid with a yield of 99% and a melting point of 156-157 °C. 1H NMR (400 MHz, CDCl3) δ 9.87 (s, 1H), 8.61 (d, J = 9.1 Hz, 1H), 8.55 (d, J =8.6 Hz, 1H), 8.50 (d, J = 8.1 Hz, 1H), 8.29 (d, J = 8.3 Hz, 1H), 8.17 (t, J =7.5 Hz, 1H), 7.99 – 7.92 (m, 2H), 7.83 (d, J = 8.4 Hz, 2H), 7.57 (t, J = 7.8Hz, 1H), 7.33 (d, J = 5.2 Hz, 3H), 7.31 – 7.26 (m, 6H), 2.33 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 147.5, 143.3, 141.9, 137.7, 136.0, 133.0, 132.1, 131.9,130.8, 130.7, 130.0, 129.7, 129.5, 128.8, 127.2, 127.0, 126.7, 126.6, 125.9,119.3, 116.9, 115.7, 57.5, 21.7. HRMS, calculated for C 29 H 23 N2O2S + [M-Cl] + 463.1475, found 463.1476.

[0124] Example 22

[0125] The preparation method of the cephalaenoic acid salt derivative of the compound represented by formula (I-22) is basically the same as that in Example 1, except that in step 2, there is a benzenesulfonic acid substituent on the indole nitrogen atom.

[0126] In this example, 466 mg of a cephalaenoic acid salt derivative was obtained as a bright yellow solid with a yield of 97% and a melting point of 140-141 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.03 (s, 1H), 8.92 (d, J = 8.2 Hz, 1H), 8.85 (d, J = 8.6 Hz, 2H), 8.58 (d, J = 8.5 Hz, 1H), 8.31 (t, J = 7.6 Hz, 1H), 8.21(d, J = 7.7 Hz, 2H), 8.16 – 8.07 (m, 2H), 7.79 (t, J = 7.7 Hz, 1H), 7.74 (t,J = 7.4 Hz, 1H), 7.60 (t, J = 7.7 Hz, 2H), 4.98 (s, 3H). 13 C NMR (100 MHz, DMSO-d6) δ 142.4, 142.2, 137.6, 136.4, 136.0, 135.2, 131.8, 131.7, 130.7,129.2, 129.1, 128.4, 127.7, 127.5, 126.4, 118.8, 118.4, 115.4, 110.0, 41.5.HRMS, calculated for C 22 H 17 N2O2S + [M-Cl] + 373.1005, found 373.1004.

[0127] Comparative Example 1

[0128] Synthesis of 5-methyl-7-bromo-5H-indolo[3,2-b]quinoline:

[0129] Phosphorus oxychloride (2 mmol) was added dropwise to DMF (1 mL) at -16°C and stirred for 0.5 hours. Intermediate A with bromine substitution at the 5-position of indole was then added and stirred at room temperature for 1 hour. Saturated sodium bicarbonate solution was then added to the reaction solution, extracted with ethyl acetate, and the organic layer was rinsed with saturated sodium bicarbonate solution. The organic phases were combined, dried over magnesium sulfate, and concentrated under reduced pressure to obtain a solid residue, which was purified by column chromatography using dichloromethane / methanol as eluent to obtain a yellow solid product.

[0130] Dissolve dimethylamine hydrochloride (0.1 mol) in DMF (1 mL). Add the yellow solid product (0.05 mol) obtained in the previous step to the reaction system and heat under reflux for 1.5 hours. After the reaction is complete, cool the reaction mixture and add 5% sodium carbonate (5 mL). Stir at room temperature for 10 minutes. Extract with ethyl acetate three times, rinse with saturated sodium carbonate, combine the organic phases, dry over magnesium sulfate, and concentrate under reduced pressure to obtain a solid residue. Purify the residue by column chromatography using dichloromethane / methanol as the eluent to obtain a purple solid product. Yield: 35%; purple powdery solid. 1 H NMR (400MHz, DMSO-d6) δ 9.05 (s, 1H), 8.70 (s, 1H), 8.58 (d, J = 9.0 Hz, 1H), 8.44 (d, J = 8.3 Hz, 1H), 8.02 – 7.87 (m, 1H), 7.74(t, J = 7.5 Hz, 1H), 7.69–7.60 (m, 2H), 4.92 (s, 3H).

[0131] Experimental Example 1

[0132] The assay procedure for anti-tobacco mosaic virus (TMV) activity is as follows:

[0133] 1. Virus purification and concentration determination:

[0134] The crude viral extract was treated with polyethylene glycol twice by centrifugation and then refrigerated at 4°C until use. The absorbance at a wavelength of 260 nm was measured using a UV spectrophotometer, and the viral concentration was calculated according to the formula.

[0135] Virus concentration (mg / ml) = (A 260 × dilution factor) / E 0.1% 1cm 260nm .

[0136] Where E represents the extinction coefficient, that 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 of 1 cm.

[0137] TMV's E 0.1% 1cm 260nm It is 3.1.

[0138] 2. Preparation of cephalaenopsis alkaloid solution:

[0139] After weighing, the leucophylline salt compound, ningnanmycin and ribavirin stock drug were dissolved in DMF to prepare a 1 × 105µg / mL stock solution, which was then diluted to the required concentration with an aqueous solution containing 1‰ Tween 80.

[0140] 3. In vivo protection:

[0141] Select uniformly growing Sanxi tobacco plants at the 3–5-leaf stage. Whole-plant spraying was performed, with three replicates per treatment, and a 1‰ Tween 80 aqueous solution was used as a control. After 24 hours, the leaves were sprinkled with emery (500 mesh). A brush dipped in the virus solution was gently rubbed twice along the entire leaf surface along the veins, supporting the underside of the leaf with the palm of your hand. The virus concentration was 10 µg / mL. After inoculation, the leaves were rinsed with running water. Three days later, the number of lesions was recorded and the efficacy was calculated.

[0142] 4. In vivo therapeutic effect:

[0143] Select uniform, 3–5-leaf-long Nicotiana tabacum plants. Use a brush to inoculate the entire leaf with the virus 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 control. After three days, record the number of lesions and calculate the efficacy.

[0144] 5. In vivo passivation activity test:

[0145] Select uniformly growing Sansi tobacco plants at the 3–5-leaf stage. Mix the agent with an equal volume of virus sap and inactivate for 30 minutes. Then, inoculate the plants by friction at a virus concentration of 20 µg / mL. Immediately rinse with running water. Repeat three times. Use a 1‰ Tween 80 aqueous solution as a control. Count the number of lesions three days later and calculate the results.

[0146] Inhibition rate (%) = [(number of control necrosis spots - number of treated necrosis spots) / number of control necrosis spots] × 100%.

[0147] All compounds were first tested for inactivation activity against tobacco mosaic virus at a 500 µg / mL treatment dose. Compounds with a relative inhibition rate greater than 40% were then tested for both therapeutic and protective activity at a 500 µg / mL treatment dose. The commercial antiviral agent ribavirin was used as a positive control.

[0148] The results of the anti-tobacco mosaic virus (TMV) activity tests of the leucine salt derivatives of Formula I-1 to Formula I-22, Ningnanmycin, and Ribavirin are shown in Table 1 below:

[0149] Table 1 Anti-tobacco mosaic virus activity test of cephalaenopsis alkaloids derivatives

[0150]

[0151] As can be seen from the data in Table 1, at 500 μg / mL, the leucophylline salt derivatives exhibited anti-TMV activity. The leucophylline salt derivatives of Formulas I-13 and I-20 had anti-TMV activity comparable to that of commercialized ningnanmycin, while the leucophylline salt derivatives of Formulas I-5, I-6, I-7, I-18, I-19, and I-21 had anti-TMV activity superior to that of ribavirin. At 100 μg / mL, the leucophylline salt derivatives of Formulas I-6, I-7, I-13, I-19, and I-20 had anti-TMV activity superior to that of ribavirin. The activity of the compound in Comparative Example 1 was significantly lower than that of its corresponding leucophylline salt derivative I-6.

[0152] Experimental Example 2

[0153] Bactericidal activity test, the determination procedure is as follows:

[0154] 1. Rice sheath blight potted activity

[0155] Select uniformly growing rice seedlings and apply the designated concentration of foliar spray to the foliage. A blank control sprayed with plain water was also established, with two replicates per treatment. Twenty-four hours after treatment, the plants were inoculated with the rice sheath blight pathogen. After inoculation, the plants were placed in a greenhouse (25 ± 4°C) and maintained normally. Six days after inoculation, the efficacy of the control was visually assessed.

[0156] The in vivo bactericidal activity test results of the leucophylline salt derivatives of Formula I-1 to Formula I-22 and thiofuran are shown in Table 2 below:

[0157] Table 2 In vivo bactericidal activity test results

[0158]

[0159] As can be seen from the data in Table 2, in the in vivo pot experiment, the leucophylline salt derivatives showed certain in vivo fungicidal activity against rice sheath blight, among which the leucophylline salt derivatives having formula I-1 and formula I-16 showed over 95% in vivo fungicidal activity against rice sheath blight.

[0160] It should be noted that in Tables 1 and 2, I-1 is used as an example to illustrate, which represents a sample of a cephalaenopsis alkaloid salt derivative having the formula I-1; the meanings of I-2 to I-22 in Tables 1 and 2 refer to the above explanations.

[0161] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the various embodiments of the present invention.

Claims

1. A cephalaenoic acid salt derivative, characterized in that: At least one of the compounds represented by formula (I-1) to formula (I-22): 。 2. A method for preparing a cephalaenoic acid salt derivative according to claim 1, characterized in that: The preparation method comprises the following steps: In the presence of a catalyst and a formylating agent, compound A is subjected to an electrophilic substitution reaction with an imine salt in an organic solvent to obtain the leucoderma salt derivative; The structural formula of the compound A is ; Among them, R 1 、R 2 、R 3 and R 4 These correspond to the structures of the compounds represented by formula (I-1) to formula (I-22).

3. The method for preparing a cephalaenoic acid salt derivative according to claim 2, wherein: The catalyst is selected from POCl3 and / or SOCl2; And / or, the molar ratio of the compound A to the catalyst is 1:1.2-3.

0.

4. The method for preparing a cephalaenoic acid salt derivative according to claim 2, wherein: The formylating agent is selected from N,N-dimethylformamide and / or N-methylformanilide; The imide salt includes and / or .

5. The method for preparing a cephalaenoic acid salt derivative according to claim 2, wherein: The concentration of the compound A is 0.4-0.6 mmol / mL.

6. The method for preparing a cephalaenoic acid salt derivative according to claim 2, wherein: The organic solvent is selected from at least one of N,N-dimethylformamide, dichloromethane, 1,2-dichloroethane, 1,4-dioxane and tetrahydrofuran.

7. The method for preparing a cephalaenoic acid salt derivative according to claim 2, wherein: The temperature of the electrophilic substitution reaction is -16°C to 25°C, and the time is 1 to 2 hours.

8. Use of the bilobaine salt derivative according to claim 1 in preventing and treating plant viral diseases.

9. A use of the cephalaenoic acid salt derivative according to claim 1 in sterilization, characterized in that: The sterilization application is application in treating rice sheath blight.

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