CN116210706B - Application of alkaloid polyaurine B derivative in resisting plant viruses and pathogens - Google Patents

Application of alkaloid polyaurine B derivative in resisting plant viruses and pathogens Download PDF

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CN116210706B
CN116210706B CN202310053505.3A CN202310053505A CN116210706B CN 116210706 B CN116210706 B CN 116210706B CN 202310053505 A CN202310053505 A CN 202310053505A CN 116210706 B CN116210706 B CN 116210706B
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polyaurine
alkaloid
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CN116210706A (en
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卢爱党
赵波波
高济璇
袁欣雨
张玉菲
王佳莉
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Hebei University of Technology
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/82—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with three ring hetero atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
    • A01N47/18—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof containing a —O—CO—N< group, or a thio analogue thereof, directly attached to a heterocyclic or cycloaliphatic ring
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P3/00—Fungicides
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Life Sciences & Earth Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Environmental Sciences (AREA)
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Abstract

The invention discloses application of alkaloid polyaurine B derivatives in resisting plant viruses and pathogens, relates to a biocide containing alkaloid polyaurine B derivatives of 3-amino-5-phenyl-1, 2, 4-thiadiazole, in particular to application of twenty-eight alkaloid polyaurine B derivatives in resisting plant viruses and pathogens as an anti-plant virus agent and an anti-plant pathogen agent, wherein the application of the alkaloid polyaurine B derivatives as the anti-plant virus agent is used for tobacco mosaic virus; the plant pathogen killing agent is used for inhibiting 8 plant pathogens such as sclerotinia sclerotiorum, peanut brown spot pathogen, cucumber fusarium wilt, rice sheath blight pathogen, tomato early blight pathogen, apple ring rot pathogen, wheat sheath blight pathogen or rice blast pathogen and the like.

Description

Application of alkaloid polyaurine B derivative in resisting plant viruses and pathogens
Technical Field
The technical scheme of the invention relates to a biocide containing alkaloid polyaurine B derivatives of 3-amino-5-phenyl-1, 2, 4-thiadiazole, in particular to application of alkaloid polyaurine B derivatives in resisting plant viruses and pathogens.
Background
Polyaurine alkaloids are thiadiazole alkaloids with novel structures, and an amide structure is connected to the C-5 position of the thiadiazole through an amino functional group. Compounds extracted from nature or synthesized and containing the core skeleton have polyaurine B, dendrodoine, P Y2 Receptor Inhibitor, dendrodoine cytotoxic, SCH-202676, neuropeptide Y Receptor Antagonit and other polyaurines alkaloids (Org.Lett.,2013,15,9,2230-2233;Org.Lett.,2009,11,24,5666-5669;Mar.Drugs.,2019,19,278;J.Nat.Prod.2020,83,1721-1724), shown in structural formula I.
Since 2019 Marcello et al reported that polyaurine type alkaloids were isolated from the metabolic components of marine capsular polysaccharides for the first time (mar. Drugs, 2019,19,278), polyaurine type alkaloids were subsequently demonstrated to have a significant effect on cell growth and parasite viability in mammals, as well as bactericidal, anticancer, antiviral effects (Russ Chem Bull,2021,3,27,3114-3116).
Through literature investigation, researchers mainly concentrate on medicine, especially anti-tumor aspects, and have few reports on controlling plant diseases and insect pests due to low natural content of polyaurine alkaloids, low synthesis yield and high cost. With the continuous exploration of new methods for synthesizing polyaurine-class alkaloids, daniel G et al (J.Nat. Prod.,2020,83,1721-1724; see equation one) report new methods for synthesizing PITYRIACITRIN and derivatives thereof, which greatly reduce the difficulty and cost of synthesis. Therefore, by modifying and reforming the structure, the derivative can be applied to controlling plant diseases and insect pests in agricultural production, the biological activity spectrum of polyaurine derivatives can be widened, and the derivative has very important application value for protecting crops.
Disclosure of Invention
The invention aims to provide the application of the alkaloid polyaurine B derivative in resisting plant viruses and pathogens, and the alkaloid polyaurine B derivative is found to have good activity in resisting plant viruses and pathogens for the first time, so that the application range of the alkaloid polyaurine B derivative as a biological pesticide is widened.
The technical scheme adopted by the invention for solving the technical problems is as follows:
the application of alkaloid polyaurine B derivatives in resisting plant virus and germ, in particular to the application of alkaloid polyaurine B derivatives shown in the following 1-28 chemical structural formulas as plant virus resisting agents and plant germ killing agents,
The application of the alkaloid polyaurine B derivative is characterized in that: as an anti-plant virus agent, said plant virus being a tobacco mosaic virus.
The application of the alkaloid polyaurine B derivative is characterized in that: the plant pathogenic bacteria are 8 plant pathogenic bacteria such as sclerotinia rot, brown spot of peanut, fusarium oxysporum, banded sclerotial blight of rice, early blight of tomato, ring spot of apple, banded sclerotial blight of wheat or rice blast of rice, etc.
Compared with the prior art, the invention has the outstanding substantial characteristics and remarkable progress as follows:
(1) Aiming at the problem that a virulent chemical methyl chloroformate is needed in the polyaurine B preparation process, the alkaloid polyaurine derivative is obtained by amidation by taking cheap and easily available acyl chloride as a raw material through the replacement of the raw material while ensuring the bioactivity of the alkaloid, and avoiding the use of a high-toxicity reagent;
(2) The alkaloid polyaurine derivatives are found to have good anti-plant virus activity for the first time, and most of the derivatives are better than commercial variety ribavirin under the same test condition, and the compounds 19 and 23 show higher anti-TMV activity than Ningnan mycin at the concentration of 100 mug/mL; in addition, polyaurine B derivatives have broad-spectrum inhibitory activity against 8 common agricultural pathogens. The compounds 5, 11, 12 and 27 show moderate to good bactericidal activity, the activity on some fungi exceeds 90%, and the application range of the alkaloid polyaurine B derivative as biological pesticide is widened.
The invention discovers that the alkaloid polyaurine B derivative has good anti-plant virus activity and broad-spectrum plant pathogen killing activity for the first time, and the obtained polyaurine B derivative shows excellent biological activity, and part of compounds have unexpected effects and breakthrough progress on antiviral activity and bactericidal activity.
Detailed Description
Example 1
The preparation method of the alkaloid polyaurine B derivative shown in the chemical structural formulas 1-28 is shown in a reaction formula II:
the specific operation steps are as follows:
In the first step, methyl 4-methoxybenzoate (498.5 mg,3.0 mmol), P 4S10 (313 mg,0.7 mmol) and disiloxane (5 mL) were refluxed in paraxylene (10 mL). The reaction was stirred continuously until complete according to TLC monitoring. After the reaction was completed, the solvent was evaporated to dryness using a rotary evaporator. The residue was added with methanol several times to extract the product. The solvent was removed in vacuo and purified by column chromatography (petroleum ether: ethyl acetate=60:1 as eluent) to give 492.0mg of product as a brown solid in 89% yield; the relevant parameter for the reddish brown solid material is ：1H NMR(400MHz,DMSO-d6)δ8.12(d,J＝8.9Hz,2H),7.01(d,J＝8.9Hz,2H),4.23(s,3H),3.84(s,3H);13C NMR(101MHz,DMSO-d6)δ211.2,164.1,131.3,131.0,114.3,59.8,56.2. to determine that the intermediate product is methyl 4-methoxyphenylthiobenzoate.
In the second step, sodium hydride (60% mineral oil, 140mg,3.5 mmol) was added to a solution of methylguanidine hydrochloride (264 mg,2.4 mmol) in THF-DMF (2:1, 12 mL) at 0deg.C, after stirring the solution for 10min, a solution of methyl 4-methoxyphenylthiobenzoate (400 mg,2.2 mmol) in THF (4 mL) was added dropwise and the mixture stirred for 18h at 50deg.C. After the reaction was completed, the mixture was cooled to 0 ℃, quenched with water (20 mL), and the aqueous layer was extracted with ethyl acetate (3×10 mL). The organic layer was collected, dried over anhydrous Na 2SO4, filtered, concentrated in vacuo, and purified by column chromatography (petroleum ether: ethyl acetate=1:1 as eluent) to give 294.7mg of a pale yellow solid product in 60% yield; the relevant parameter for the pale yellow solid material was ：1HNMR(400MHz,DMSO-d6)δ9.11(s,1H),8.21(d,J＝8.6Hz,2H),6.86(d,J＝8.7Hz,2H),3.78(s,3H),2.83(s,3H);13C NMR(101MHz,DMSO-d6)δ198.0,164.3,161.5,130.3,112.8,55.7,28.2; to determine that the intermediate was 4-methoxy-N- (N-methylcarbamoyl) benzsulfamide.
In a third step cesium carbonate (594 mg,1.8 mmol) and 4-methoxy-N- (N-methylcarbamoylamino) benzothiamide (215 mg,1.0 mmol) were dissolved in DMF (5 mL) and added to a solution of Cu (OAc) 2·H2 O (30 mg,0.2 mmol) in DMF (3 mL), the reaction mixture stirred in an open flask at 80℃for 3h, cooled to room temperature and concentrated in vacuo. The residue was dissolved in ethyl acetate (10 mL), washed with water (2×10 mL), the organic layer was collected, dried over anhydrous Na 2SO4, filtered, concentrated in vacuo, and purified by column chromatography (eluent: petroleum ether: ethyl acetate=3:1) to give 238.9mg of compound 1 as a white solid in 60% yield; the related parameters of the white solid matter are ：1H NMR(400MHz,DMSO-d6)δ7.82(d,J＝8.7Hz,2H),7.33(s,1H),7.08(d,J＝8.7Hz,2H),3.84(s,3H),2.86(d,J＝4.7Hz,3H);13C NMR(101MHz,DMSO-d6)δ185.6,171.8,162.6,128.9,123.5,115.3,56.0,30.0;HRMS(ESI):calcd for C10H11N3OS:m/z[M+H]+,222.0692;found:222.0696.
Fourthly, methyl iodide, bromoalkane or chloroformate or (1.5 mL) is dripped into 5- (4-methoxyphenyl) -N-methyl-1, 2, 4-thiadiazole-3-amine (221.0 mg,1.0 mmol) at the temperature of 0 ℃, the mixture is refluxed and stirred for 12h, and the mixture is purified by column chromatography (petroleum ether is used as eluent: ethyl acetate=20:1), thus obtaining the compounds 2-28.
Compound 2, white solid in 83% yield; the related parameters of the substance are ：1H NMR(400MHz,CDCl3)δ7.84(d,J＝8.7Hz,2H),6.95(d,J＝8.6Hz,2H),3.87(s,3H),3.24(s,6H);13C NMR(100MHz,CDCl3)δ186.2,172.3,162.3,128.7,124.1,114.4,55.5,39.1;HRMS(ESI):calcd for C11H13N3OS:m/z[M+H]+,236.0858;found(ESI+):236.0852.
Compound 3, yellow oil, yield 85%; the related parameters of the substance are ：1H NMR(400MHz,CDCl3)δ7.84(d,J＝8.5Hz,2H),6.95(d,J＝8.5Hz,2H),3.87(s,3H),3.66(t,J＝7.3Hz,2H),3.21(s,3H),1.64(q,J＝7.4Hz,2H),1.38(q,J＝7.4Hz,2H),0.96(t,J＝7.3Hz,3H);13C NMR(100MHz,CDCl3)δ185.7,171.5,162.2,128.7,124.0,114.3,55.5,51.4,36.7,29.7,20.0,14.0;HRMS(ESI):calcd for C14H19N3OS:m/z[M+H]+,278.1326;found(ESI+):277.1322.
Compound 4, white solid in 90% yield; the related parameters of the substance are ：1H NMR(400MHz,CDCl3)δ7.86(d,J＝8.2Hz,2H),7.32(s,5H),6.96(d,J＝8.3Hz,2H),4.93(s,2H),3.87(s,3H),3.18(s,3H);13C NMR(100MHz,CDCl3)δ186.3,171.8,162.4,138.3,129.1,128.8,128.6,127.7,127.3,124.0,114.4,55.3,36.3;HRMS(ESI):calcd for C17H17N3OS:m/z[M+H]+,312.1160;found(ESI+):312.1165.
Compound 5, brown solid in 90% yield; the related parameters of the substance are ：1H NMR(400MHz,CDCl3)δ7.88(d,J＝8.1Hz,2H),6.97(d,J＝8.1Hz,2H),5.14–5.04(m,1H),3.87(s,3H),3.53(s,3H),1.33(d,J＝5.6Hz,6H);13C NMR(101MHz,DMSO-d6)δ187.0,166.3,163.1,154.0,129.3,122.9,115.5,70.3,56.1,36.1,22.2;HRMS(ESI):calcd for C14H17N3O3S:m/z[M+H]+,222.0692;found:222.0696.
Compound 6, yellow solid in 92% yield; the related parameters of the substance are ：1H NMR(400MHz,DMSO-d6)δ7.94(d,J＝8.5Hz,2H),7.11(d,J＝8.4Hz,2H),3.94(d,J＝6.4Hz,2H),3.85(s,3H),3.40(s,3H),1.90(dt,J＝13.2,6.6Hz,1H),0.91(d,J＝6.7Hz,6H);13C NMR(101MHz,CDCl3)δ187.1,166.2,162.7,154.5,128.9,123.3,114.6,72.6,55.6,36.0,27.9,19.1;HRMS(ESI):calcd for C15H19N3O3S:m/z[M+H]+,308.1069;found:308.1064.
Compound 7, white solid in 90% yield; the related parameters of the substance are ：1H NMR(400MHz,CDCl3)δ7.86(d,J＝8.2Hz,2H),7.45(d,J＝7.1Hz,1H),7.36(s,2H),7.33(d,J＝8.7Hz,2H),6.97(d,J＝8.2Hz,2H),5.31(s,2H),3.88(s,3H),3.58(s,3H);13C NMR(101MHz,CDCl3)δ187.2,166.0,162.8,154.3,136.1,128.9,128.5,128.1,128.0,123.3,114.6,68.1,55.6,36.1;HRMS(ESI):calcd for C18H17N3O3S:m/z[M+H]+,322.1223;found:322.1220.
Compound 8, white solid in 80% yield; the related parameters of the white solid matter are :1H NMR(400MHz,CDCl3)δ7.88(d,J＝8.7Hz,2H),7.00(d,J＝8.7Hz,2H),3.89(s,3H),3.54(s,3H),2.52(s,3H);13C NMR(101MHz,CDCl3)δ187.5,171.8,167.1,162.9,128.9,123.0,114.7,55.6,34.6,25.2;
HRMS(ESI):calcd for C12H13N3O2S:m/z[M+H]+,264.0807;found:264.0801.
Compound 9, a pale yellow solid, yield 85%; the related parameters of the substance are :1H NMR(400MHz,CDCl3)δ7.88(d,J＝8.1Hz,2H),7.00(d,J＝8.1Hz,2H),3.89(s,3H),3.53(s,3H),2.86(q,J＝6.9Hz,2H),1.20(t,J＝7.1Hz,3H);13C NMR(101MHz,CDCl3)δ187.4,175.3,167.1,162.9,128.9,123.1,114.7,55.6,34.7,29.9,9.7;HRMS(ESI):calcd for C13H15N3O2S:m/z[M+H]+,278.0960;found:278.0958.
Compound 10, white solid in 83% yield; the related parameters of the substance are :1H NMR(400MHz,CDCl3)δ8.00–7.69(m,2H),7.00(d,J＝8.6Hz,2H),3.89(s,3H),3.56(d,J＝30.1Hz,3H),2.80(t,J＝7.4Hz,2H),1.73(dq,J＝14.6,7.1Hz,2H),0.95(t,J＝7.3Hz,3H);13C NMR(101MHz,CDCl3)δ187.4,174.4,167.1,162.9,128.9,123.1,114.7,55.6,38.3,34.7,18.9,14.0;HRMS(ESI):calcd for C14H17N3O2S:m/z[M+H]+,292.1118;found:292.1114.
Compound 11, a pale yellow solid, in 85% yield; the relevant parameters of the substance are determined as :1H NMR(400MHz,CDCl3)δ7.88(d,J＝8.6Hz,2H),7.01(d,J＝8.6Hz,2H),3.89(s,3H),3.50(s,3H),1.59(s,1H),1.20(d,J＝6.7Hz,6H);13C NMR(101MHz,CDCl3)δ187.5,178.9,167.2,163.0,128.9,123.1,114.7,55.6,35.1,33.1,20.0;HRMS(ESI):calcd for C14H17N3O2S:m/z[M+H]+,292.1116;found:292.1114.
Compound 12, white solid in 87% yield; the related parameters of the substance are :1H NMR(400MHz,CDCl3)δ7.88(d,J＝8.6Hz,2H),7.00(d,J＝8.6Hz,2H),3.89(s,3H),3.52(s,3H),2.73(d,J＝6.9Hz,2H),2.17(dt,J＝13.1,6.7Hz,1H),0.95(d,J＝6.6Hz,6H);13C NMR(101MHz,CDCl3)δ187.4,173.9,167.2,162.9,128.9,123.1,114.7,55.6,45.0,34.7,25.8,22.7;HRMS(ESI):calcd for C15H19N3O2S:m/z[M+H]+,306.1274;found:306.1271.
Compound 13, white solid in 85% yield; the related parameters of the substance are :1H NMR(400MHz,CDCl3)δ7.90(d,J＝7.9Hz,2H),7.00(d,J＝8.0Hz,2H),3.89(s,3H),3.35(s,3H),1.15(s,9H);13C NMR(101MHz,CDCl3)δ188.0,179.8,168.2,163.1,128.9,122.9,114.7,55.6,41.3,37.8,28.5;HRMS(ESI):calcd for C15H19N3O2S:m/z[M+H]+,306.1276;found:306.1271.
Compound 14, yellow solid in 78% yield; the related parameters of the substance are :1H NMR(400MHz,Chloroform-d)δ7.63–7.59(m,2H),7.42(d,J＝8.0Hz,2H),7.35(d,J＝7.2Hz,1H),7.29(d,J＝7.5Hz,2H),6.92(d,J＝8.6Hz,2H),3.86(s,3H),3.68(s,3H);13C NMR(101MHz,CDCl3)δ187.2,171.6,167.5,162.9,136.7,133.6,130.4,128.8,127.9,122.9,114.6,55.6,35.5;HRMS(ESI):calcd for C17H15N3O2S:m/z[M+H]+,326.0955;found:326.0958.
Compound 15, white solid in 88% yield; the related parameters of the substance are :1H NMR(400MHz,CDCl3)δ7.49(d,J＝7.5Hz,2H),7.39(s,1H),7.29(s,3H),6.89(s,2H),3.85(s,3H),3.74(s,3H);13CNMR(101MHz,CDCl3)δ168.8,162.8,133.4,132.4,131.5,130.7,130.1,129.2,128.8,128.6,126.6,122.9,114.5,55.5,34.2;HRMS(ESI):calcd for C17H14ClN3O2S:m/z[M+H]+,360.0573;found:360.0568.
Compound 16, brown solid in 85% yield; the related parameters of the substance are :1H NMR(400MHz,CDCl3)δ7.64(d,J＝7.7Hz,2H),7.48(s,1H),7.33(d,J＝7.3Hz,1H),7.20(d,J＝8.3Hz,2H),6.93(d,J＝7.8Hz,2H),3.86(s,3H),3.67(s,3H);13C NMR(101MHz,CDCl3)δ187.5,170.1,167.0,163.0,138.5,134.1,130.3,129.2,128.8,128.2,125.8,122.8,114.6,55.6,35.50;HRMS(ESI):calcd for C17H14ClN3O2S:m/z[M+H]+,360.0570;found:360.0568.
Compound 17, brown solid in 87% yield; the related parameters of the substance are :1H NMR(400MHz,CDCl3)δ7.48(d,J＝8.2Hz,3H),7.35(dd,J＝14.3,7.3Hz,2H),7.21(t,J＝7.5Hz,1H),6.88(d,J＝8.3Hz,2H),3.85(s,3H),3.74(s,3H);13C NMR(101MHz,CDCl3)δ186.9,169.5,165.7,162.8,139.9,132.4,130.2,128.8,128.6,127.1,122.9,119.4,114.5,55.6,34.2;HRMS(ESI):calcd for C17H14BrN3O2S:m/z[M+H]+,404.0067;found:404.0063.
Compound 18, white solid in 82% yield; the related parameters of the substance are :1H NMR(400MHz,Chloroform-d)δ7.70(s,3H),7.43(d,J＝8.3Hz,2H),7.33(d,J＝6.4Hz,1H),6.86(d,J＝8.3Hz,2H),3.84(s,3H),3.75(s,3H);13C NMR(101MHz,CDCl3)δ187.1,169.1,165.7,162.8,160.7,132.8,132.1,131.4,131.3,128.8,128.7,127.4,114.5,55.6,34.3.
Compound 19, yellow solid in 85% yield; the related parameters of the substance are :1H NMR(400MHz,Chloroform-d)δ7.51(d,J＝8.1Hz,2H),7.21(t,J＝7.3Hz,1H),7.15(d,J＝10.9Hz,2H),7.07(t,J＝7.1Hz,1H),6.89(d,J＝8.2Hz,2H),3.85(s,3H),3.70(s,3H),2.36(s,3H);13C NMR(101MHz,CDCl3)δ186.9,171.9,1667,162.8,137.7,135.4,130.1,129.0,128.8,126.4,125.3,123.0,114.5,55.5,34.5,19.5;HRMS(ESI):calcd for C18H17N3O2S:m/z[M+H]+,340.1116;found:340.1114.
Compound 20, reddish brown solid, yield 70%; the related parameters of the substance are :1H NMR(400MHz,CDCl3)δ7.85(d,J＝8.1Hz,2H),7.25(s,2H),7.21(d,J＝7.3Hz,3H),6.99(d,J＝8.3Hz,2H),4.26(s,2H),3.89(s,3H),3.55(s,3H);13C NMR(101MHz,CDCl3)δ187.6,172.4,166.9,163.0,135.4,129.4,128.9,128.4,126.7,123.0,114.7,55.6,42.9,35.0;HRMS(ESI):calcd for C18H17N3O2S:m/z[M+H]+,340.1119;found:340.1114.
Compound 21, brown solid, yield 83%; the related parameters of the substance are :1H NMR(400MHz,CDCl3)δ7.78(d,J＝8.4Hz,2H),7.39(d,J＝4.8Hz,1H),7.08–7.04(m,1H),6.97(d,J＝8.4Hz,2H),6.92–6.87(m,1H),3.87(s,3H),3.61(s,3H);13C NMR(101MHz,CDCl3)δ187.9,167.5,164.3,163.0,138.2,130.9,130.3,128.9,126.8,122.9,114.7,55.6,36.2;HRMS(ESI):calcd for C15H13N3O2S2:m/z[M+H]+,332.0520;found:332.0522.
Compound 22, pale yellow oil, yield 82%; the related parameters of the substance are :1H NMR(400MHz,CDCl3)δ7.89(d,J＝7.9Hz,2H),7.00(d,J＝8.1Hz,2H),3.89(s,3H),3.54(s,3H),2.61–2.50(m,1H),1.15(s,2H),0.88–0.84(m,2H);13C NMR(101MHz,CDCl3)δ187.4,175.1,167.4,162.9,128.9,123.1,114.7,55.6,35.2,14.0,9.7;HRMS(ESI):calcd for C14H15N3O2S:m/z[M+H]+,290.0955;found:290.0958.
Compound 23, white solid in 80% yield; the related parameters of the substance are :1H NMR(400MHz,CDCl3)δ7.90–7.87(m,2H),7.01–6.98(m,2H),3.89(s,3H),3.53(s,3H),2.55(s,1H),1.31–0.75(m,8H);13C NMR(101MHz,CDCl3)δ187.5,175.1,167.4,162.9,128.9,123.1,114.7,55.6,35.2,14.0,9.7,9.1;HRMS(ESI):calcd for C16H19N3O2S:m/z[M+H]+,236.0858;found:236.0852.
Compound 24, white solid in 70% yield; the related parameters of the substance are :1H NMR(400MHz,CDCl3)δ7.99–7.91(m,2H),7.17(t,J＝8.0Hz,2H),5.10(p,J＝6.0Hz,1H),3.54(s,3H),1.34(d,J＝6.1Hz,6H);13C NMR(101MHz,CDCl3)δ186.1,166.5,163.7,153.9,129.4,126.9,116.4,70.5,35.9,22.1;HRMS(ESI):calcd for C13H14FN3O2S:m/z[M+H]+,296.0870;found:296.0864.
Compound 25, a pale yellow solid, in 86% yield; the related parameters of the substance are :1H NMR(400MHz,CDCl3)δ7.87(d,J＝8.1Hz,2H),7.46(d,J＝8.2Hz,2H),5.17–5.02(m,1H),3.54(s,3H),1.37–1.29(m,6H);13C NMR(101MHz,CDCl3)δ186.1,166.6,153.8,138.2,129.6,128.9,128.4,22.1;HRMS(ESI):calcd for C13H14ClN3O2S:m/z[M+H]+,312.0571;found:312.0568.
Compound 26, white solid in 85% yield; the related parameters of the substance are :1H NMR(400MHz,CDCl3)δ7.84–7.78(m,2H),7.63(d,J＝8.0Hz,2H),5.10(dt,J＝11.8,5.8Hz,1H),3.54(s,3H),1.34(d,J＝6.0Hz,6H);13C NMR(101MHz,CDCl3)δ186.2,166.7,153.9,132.6,129.4,128.5,126.6,70.5,35.9,22.1;HRMS(ESI):calcd for C13H14BrN3O2S:m/z[M+H]+,356.0067;found:356.0063.
Compound 27, yellow solid in 85% yield; the related parameters of the substance are :1H NMR(400MHz,CDCl3)δ7.82(d,J＝7.6Hz,2H),7.29(s,2H),5.17–5.04(m,1H),3.54(s,3H),2.42(s,3H),1.33(d,J＝5.9Hz,6H);13C NMR(101MHz,CDCl3)δ187.5,166.4,154.0,142.7,129.9,127.9,127.1,70.3,35.9,22.1,21.7;HRMS(ESI):calcd for C14H17N3O2S:m/z[M+H]+,292.1110;found:292.1114.
Compound 28, white solid in 85% yield; the related parameters of the substance are :1H NMR(400MHz,CDCl3)δ7.48(s,2H),7.39(t,J＝7.7Hz,1H),7.07(d,J＝7.6Hz,1H),5.14–5.05(m,1H),3.89(s,3H),3.55(s,3H),1.37–1.32(m,6H);13C NMR(101MHz,CDCl3)δ187.3,166.5,160.2,154.0,131.7,130.4,119.7,118.3,111.8,70.4,55.6,35.9,22.1;HRMS(ESI):calcd for C14H17N3O3S:m/z[M+H]+,308.1068;found:308.1064.
Example 2
The anti-tobacco mosaic virus activity of individual compounds shown in the alkaloid polyaurine B derivatives 1 to 28 is measured by the following measurement procedure:
Firstly, tobacco mosaic virus purification and concentration determination:
tobacco mosaic virus purification and concentration determination are carried out according to SOP specification of tobacco mosaic virus prepared by a measuring room of southern university element, virus crude extract is subjected to polyethylene glycol centrifugation for 2 times, the concentration is determined to be 20 mug/mL, and the obtained product is refrigerated at 4 ℃ for later use;
secondly, preparing individual compound medicament solutions shown in alkaloid polyaurine B derivatives 1-28:
weighing 40mg of individual compounds shown as alkaloid polyaurine B derivatives 1-28 as raw medicines, respectively adding 0.4mL of DMF into each raw medicine for dissolution to prepare 1X 10 5 mug/mL mother liquor, and diluting with Tween 80 aqueous solution with mass percent concentration of 1%o to test concentration of 500 mug/mL or 100 mug/mL, thereby preparing individual compound medicament solutions shown as alkaloid polyaurine B derivatives 1-28, and directly diluting with water to prepare Ningnanmycin preparation as a contrast substance;
Thirdly, living body protection:
Respectively selecting ten parts of 3-5 She Qishan Xiyan cigarettes with uniform growth vigor, spraying the prepared individual compound medicament solution shown in the alkaloid polyaurine B derivative 1-28 in the second step by the whole plant, repeating for 3 times, setting tween 80 water solution with the mass percent concentration of 1%o for comparison, spreading 500-mesh silicon carbide on the leaf surface after 24 hours, dipping the virus solution by using a writing brush, lightly wiping the whole leaf surface for 2 times along the branch pulse direction, supporting the lower part of the leaf surface by using palm, flushing the leaf surface with flowing water after inoculation, carrying out moisturizing culture under normal-temperature illumination condition, repeating for 3 times every 3 leaves, recording the number of lesions after 3 days, and calculating the prevention effect; ;
fourth step, living body treatment effect:
Respectively selecting ten parts of 3-5 She Qishan Western cigarettes with uniform growth vigor, inoculating viruses with writing brush whole leaves, wherein the virus concentration is 10 mug/mL, washing with running water after inoculation, spraying the individual compound medicament solution shown in the alkaloid polyaurine B derivative 1-28 prepared in the second step on the whole plant after leaf surface is dried, repeating for 3 times each treatment, setting tween 80 water solution with the mass percent concentration of 1%o for comparison, recording the number of lesions after 3 days, and calculating the control effect;
fifth step, living body passivation:
Respectively selecting ten parts of 3-5 She Qishan Xiyan cigarettes with uniform growth vigor, respectively mixing the individual compound medicament solution shown in the alkaloid polyaurine B derivative 1-28 prepared in the second step with an equal volume of virus juice, passivating for 30min, performing friction inoculation, wherein the virus concentration is 20 mug/mL, washing with running water after inoculation, repeating for 3 times, setting Tween 80 water solution with the mass percent concentration of 1 per mill for comparison, counting the number of lesions after 3 days, and calculating the result;
The results of the measurement of the anti-tobacco mosaic virus activity of the individual compounds shown in the alkaloid polyaurine B derivatives 1 to 28 are shown in Table 1.
Table 1. Results of anti-TMV activity test of individual compounds shown as alkaloid polyaurine B derivatives 1 to 28:
table 1 shows that alkaloid polyaurines and its derivative have excellent anti-plant virus activity. Under the same test condition, most of the compounds are better than commercial variety ribavirin, and partial compounds have higher TMV resistance than Ningnan mycin at the concentration of 100 mug/mL, so that the compounds have development value.
Example 3
The antibacterial activity test, in vitro sterilization test, and the measurement procedure of the individual compounds in the alkaloid polyaurine B derivatives 1 to 28 are as follows:
Cell growth rate assay, plate method: dissolving 3mg of individual compounds in 1-28 of alkaloid polyaurine B derivatives in 0.03mL of acetone respectively, diluting with water solution containing 200 mug/mL of Tween 80 to test concentration of 50mg/kg, then respectively sucking 1mL of liquid medicine, injecting into corresponding culture dishes, respectively adding 9mL of culture medium, shaking uniformly to prepare 50 mug/mL of medicine-containing flat plates, adding 1mL of sterilized purified water flat plates as blank control, cutting fungus trays along the outer edge of hypha by using a puncher with the diameter of 4mm, transferring to the medicine-containing flat plates, repeating each treatment for three times, placing the culture dishes in a constant temperature incubator at 24+/-1 ℃ for culturing, investigating the expansion diameter of each treated fungus tray after 48 hours, averaging, and comparing with the blank control to calculate the relative antibacterial rate.
The results of the in vitro fungicidal activity of the individual compounds in alkaloid polyaurine B derivatives 1 to 28 described above are shown in Table 2.
TABLE 2 results of in vitro bactericidal Activity test of individual Compounds in alkaloid polyaurine B derivatives 1-28
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Table 2 illustrates that alkaloid polyaurine B derivatives 1-28 have broad-spectrum inhibitory activity against 8 common agricultural pathogens. Some of the compounds showed moderate to good bactericidal activity, in particular the inhibition of compounds 1, 5, 11, 12, 27 to some pathogenic bacteria was more than 90%.
The percentages in the above examples are mass percentages.
The materials and reagents involved in the above examples are all commercially available and the chemical reaction process is well within the skill of the art.
The invention is not a matter of the known technology.

Claims (1)

1. The application of alkaloid polyaurine B derivatives in resisting plant viruses and pathogens is characterized in that: is alkaloid polyaurine B derivatives with the following chemical structural formulas of 1-28, is used as an anti-plant virus agent or a plant pathogen killing agent,
The plant virus is tobacco mosaic virus;
The plant germ is sclerotinia rot, peanut brown spot, cucumber fusarium wilt, rice sheath blight, tomato early blight, apple sheath blight or rice blast.
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