CN116210706A - Application of alkaloid polyaurine B derivative in resisting plant virus and germ - Google Patents

Application of alkaloid polyaurine B derivative in resisting plant virus and germ Download PDF

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CN116210706A
CN116210706A CN202310053505.3A CN202310053505A CN116210706A CN 116210706 A CN116210706 A CN 116210706A CN 202310053505 A CN202310053505 A CN 202310053505A CN 116210706 A CN116210706 A CN 116210706A
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polyaurine
alkaloid
nmr
plant
cdcl
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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

Abstract

The invention discloses application of alkaloid polyaurine B derivatives in resisting plant viruses and pathogens, relates to biocides containing alkaloid polyaurine B derivatives of 3-amino-5-phenyl-1, 2, 4-thiadiazole, in particular relates to application of twenty-eight alkaloid polyaurine B derivatives in resisting plant viruses and pathogens as plant viruses and plant pathogens, wherein the application of the alkaloid polyaurine B derivatives is used for resisting plant viruses and tobacco mosaic viruses; 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 virus and germ
Technical Field
The technical scheme of the invention relates to a biocide containing an alkaloid polyaurine B derivative of 3-amino-5-phenyl-1, 2, 4-thiadiazole, in particular to application of the alkaloid polyaurine B derivative in resisting plant viruses and germs.
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. The compounds containing the core skeleton extracted from natural or artificially synthesized are 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) such as polyaurines B, dendrodoine, P Y2 Receptor Inhibitor, dendrodoine cytotoxic, SCH-202676 and Neuropeptide Y Receptor Antagonit, as shown in the structural formula I.
Figure BDA0004059358170000011
Since Marcello et al in 2019 reported that polyaurene alkaloids were isolated from the metabolic components of marine capsular polysaccharides for the first time (Mar. Drugs.,2019,19,278), it was subsequently demonstrated that polyaurene alkaloids have a significant effect on mammalian cell growth and parasite viability, as well as bactericidal, anticancer, antiviral effects (Russ Chem Bull,2021,3,27,3114-3116).
Through literature research, as the polyaurine alkaloid has low natural content, low synthesis yield and high cost, the application research of researchers is mainly focused on medicines, particularly on anti-tumor aspects, and has few reports on controlling plant diseases and insect pests. With the continuous exploration of new methods for synthesizing polyaurine alkaloids, daniel G et al (J. Nat. Prod.,2020,83,1721-1724; see reaction formula I) report new methods for synthesizing pityriacillin and derivatives thereof, greatly reducing the difficulty and cost of synthesis. Therefore, by modifying and reforming the structure, the polyaurine derivative can be applied to controlling plant diseases and insect pests in agricultural production, so that the biological activity spectrum of the polyaurine derivative can be widened, and the polyaurine derivative has very important application value for protecting crops.
Figure BDA0004059358170000012
Disclosure of Invention
The invention aims to provide the application of the alkaloid polyaurine B derivative in resisting plant viruses and pathogens, and discovers that the alkaloid polyaurine B derivative has good activity in resisting plant viruses and pathogens for the first time, and expands the application range of the alkaloid polyaurine B derivative as a biological pesticide.
The technical scheme adopted by the invention for solving the technical problems is as follows:
the application of alkaloid polyaurine B derivative in resisting plant virus and germ, in particular to the application of alkaloid polyaurine B derivative with the following chemical structural formulas of 1-28 as plant virus resisting agent and plant germ killing agent,
Figure BDA0004059358170000021
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 the highly toxic chemical methyl chloroformate is needed in the preparation process of the polyaurine B, the invention ensures the biological activity of the polyaurine B, and simultaneously uses cheap and easily available acyl chloride as a raw material to obtain the alkaloid polyaurine derivative through amidation, thereby avoiding the use of highly toxic reagents;
(2) The alkaloid polyaurine derivatives are found to have good anti-plant virus activity for the first time, under the same test condition, most of the alkaloid polyaurine derivatives are better than commercial variety ribavirin, and the compounds 19 and 23 show higher anti-TMV activity than Ningnan mycin at the concentration of 100 mug/mL; in addition, the 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 of the compounds on some fungi exceeds 90 percent, and the application range of the alkaloid polyaurine B derivatives as biological pesticides is enlarged.
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:
Figure BDA0004059358170000031
the specific operation steps are as follows:
in the first step, methyl 4-methoxybenzoate (498.5 mg,3.0 mmol), P 4 S 10 (513 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 parameters of the reddish brown solid matter are: 1 H NMR(400MHz,DMSO-d 6 )δ8.12(d,J＝8.9Hz,2H),7.01(d,J＝8.9Hz,2H),4.23(s,3H),3.84(s,3H)； 13 C NMR(101MHz,DMSO-d 6 ) Delta 211.2,164.1,131.3,131.0,114.3,59.8,56.2 the intermediate product was identified as 4-methoxyphenylthioMethyl benzoate.
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 10 min, 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 with anhydrous Na 2 SO 4 Drying, filtering, concentrating under vacuum, and purifying by column chromatography (petroleum ether: ethyl acetate=1:1 as eluent) to obtain 294.7mg pale yellow solid product with yield of 60%; the relevant parameters of the pale yellow solid substance are: 1 HNMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,DMSO-d 6 ) Delta 198.0,164.3,161.5,130.3,112.8,55.7,28.2; the intermediate product was identified as 4-methoxy-N- (N-methylcarbamoylamino) benzothiamide.
In the 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 Cu (OAc) dissolved therein 2 ·H 2 In a solution of O (30 mg,0.2 mmol) in DMF (3 mL), the reaction mixture was stirred in an open flask at 80deg.C for 3h, cooled to room temperature and concentrated in vacuo. The residue was dissolved in ethyl acetate (10 mL), washed with water (2X 10 mL), and the organic layer was collected using anhydrous Na 2 SO 4 Drying, filtering, concentrating under vacuum, and purifying by column chromatography (petroleum ether: ethyl acetate=3:1 as eluent) to obtain 238.9mg of white solid compound 1 with a yield of 60%; the relevant parameters for the white solid material are: 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,DMSO-d 6 )δ185.6,171.8,162.6,128.9,123.5,115.3,56.0,30.0；HRMS(ESI):calcd for C 10 H 11 N 3 OS: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 relevant parameters of the substance are as follows: 1 H NMR(400MHz,CDCl 3 )δ7.84(d,J＝8.7Hz,2H),6.95(d,J＝8.6Hz,2H),3.87(s,3H),3.24(s,6H)； 13 C NMR(100MHz,CDCl 3 )δ186.2,172.3,162.3,128.7,124.1,114.4,55.5,39.1；HRMS(ESI):calcd for C 11 H 13 N 3 OS:m/z[M+H] + ,236.0858；found(ESI + ):236.0852。
compound 3, yellow oil, yield 85%; the relevant parameters of the substance are as follows: 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 )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 C 14 H 19 N 3 OS:m/z[M+H] + ,278.1326；found(ESI + ):277.1322。
compound 4, white solid in 90% yield; the relevant parameters of the substance are as follows: 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 )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 C 17 H 17 N 3 OS:m/z[M+H] + ,312.1160；found(ESI + ):312.1165。
compound 5, brown solid in 90% yield; the relevant parameters of the substance are as follows: 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(101MHz,DMSO-d 6 )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 C 14 H 17 N 3 O 3 S:m/z[M+H] + ,222.0692；found:222.0696。
compound 6, yellow solid in 92% yield; the relevant parameters of the substance are as follows: 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,CDCl 3 )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 C 15 H 19 N 3 O 3 S:m/z[M+H] + ,308.1069；found:308.1064。
compound 7, white solid in 90% yield; the relevant parameters of the substance are as follows: 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(101MHz,CDCl 3 )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 C 18 H 17 N 3 O 3 S:m/z[M+H] + ,322.1223；found:322.1220。
compound 8, white solid in 80% yield; the relevant parameters for the white solid material are: 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(101MHz,CDCl 3 )δ187.5,171.8,167.1,162.9,128.9,123.0,114.7,55.6,34.6,25.2；
HRMS(ESI):calcd for C 12 H 13 N 3 O 2 S:m/z[M+H] + ,264.0807；found:264.0801。
compound 9, a pale yellow solid, yield 85%; the relevant parameters of the substance are as follows: 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(101MHz,CDCl 3 )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 C 13 H 15 N 3 O 2 S:m/z[M+H] + ,278.0960；found:278.0958。
compound 10, white solid in 83% yield; the relevant parameters of the substance are as follows: 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(101MHz,CDCl 3 )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 C 14 H 17 N 3 O 2 S: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 follows: 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(101MHz,CDCl 3 )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 C 14 H 17 N 3 O 2 S:m/z[M+H] + ,292.1116；found:292.1114。
compound 12, white solid in 87% yield; the relevant parameters of the substance are as follows: 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(101MHz,CDCl 3 )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 C 15 H 19 N 3 O 2 S:m/z[M+H] + ,306.1274；found:306.1271。
compound 13, white solid in 85% yield; the relevant parameters of the substance are as follows: 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(101MHz,CDCl 3 )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 C 15 H 19 N 3 O 2 S:m/z[M+H] + ,306.1276；found:306.1271。
compound 14, yellow solid in 78% yield; the relevant parameters of the substance are as follows: 1 H 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)； 13 C NMR(101MHz,CDCl 3 )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 C 17 H 15 N 3 O 2 S:m/z[M+H] + ,326.0955；found:326.0958。
compound 15, white solid in 88% yield; the relevant parameters of the substance are as follows: 1 H NMR(400MHz,CDCl 3 )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)； 13 CNMR(101MHz,CDCl 3 )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 C 17 H 14 ClN 3 O 2 S:m/z[M+H] + ,360.0573；found:360.0568。
compound 16, brown solid in 85% yield; the relevant parameters of the substance are as follows: 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(101MHz,CDCl 3 )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 C 17 H 14 ClN 3 O 2 S:m/z[M+H] + ,360.0570；found:360.0568。
compound 17, brown solid in 87% yield; the relevant parameters of the substance are as follows: 1 H NMR(400MHz,CDCl 3 )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)； 13 C 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 C 17 H 14 BrN 3 O 2 S:m/z[M+H] + ,404.0067；found:404.0063。
compound 18, white solid in 82% yield; the relevant parameters of the substance are as follows: 1 H 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)； 13 C NMR(101MHz,CDCl 3 )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 relevant parameters of the substance are as follows: 1 H 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)； 13 C NMR(101MHz,CDCl 3 )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 C 18 H 17 N 3 O 2 S:m/z[M+H] + ,340.1116；found:340.1114。
compound 20, reddish brown solid, yield 70%; the relevant parameters of the substance are as follows: 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(101MHz,CDCl 3 )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 C 18 H 17 N 3 O 2 S:m/z[M+H] + ,340.1119；found:340.1114。
compound 21, brown solid, yield 83%; the relevant parameters of the substance are as follows: 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(101MHz,CDCl 3 )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 C 15 H 13 N 3 O 2 S 2 :m/z[M+H] + ,332.0520；found:332.0522。
compound 22, pale yellow oil, yield 82%; the relevant parameters of the substance are as follows: 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(101MHz,CDCl 3 )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 C 14 H 15 N 3 O 2 S:m/z[M+H] + ,290.0955；found:290.0958。
compound 23, white solid in 80% yield; the relevant parameters of the substance are as follows: 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(101MHz,CDCl 3 )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 C 16 H 19 N 3 O 2 S:m/z[M+H] + ,236.0858；found:236.0852。
compound 24, white solid in 70% yield; the relevant parameters of the substance are as follows: 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(101MHz,CDCl 3 )δ186.1,166.5,163.7,153.9,129.4,126.9,116.4,70.5,35.9,22.1；HRMS(ESI):calcd for C 13 H 14 FN 3 O 2 S:m/z[M+H] + ,296.0870；found:296.0864。
compound 25, a pale yellow solid, in 86% yield; the relevant parameters of the substance are as follows: 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(101MHz,CDCl 3 )δ186.1,166.6,153.8,138.2,129.6,128.9,128.4,22.1；HRMS(ESI):calcd for C 13 H 14 ClN 3 O 2 S:m/z[M+H] + ,312.0571；found:312.0568。
compound 26, white solid in 85% yield; the relevant parameters of the substance are as follows: 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(101MHz,CDCl 3 )δ186.2,166.7,153.9,132.6,129.4,128.5,126.6,70.5,35.9,22.1；HRMS(ESI):calcd for C 13 H 14 BrN 3 O 2 S:m/z[M+H] + ,356.0067；found:356.0063。
compound 27, yellow solid in 85% yield; the relevant parameters of the substance are as follows: 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(101MHz,CDCl 3 )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 C 14 H 17 N 3 O 2 S:m/z[M+H] + ,292.1110；found:292.1114。
compound 28, white solid in 85% yield; the relevant parameters of the substance are as follows: 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(101MHz,CDCl 3 )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 C 14 H 17 N 3 O 3 S: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 procedures:
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 materials, respectively, and adding 0.4mL of DMF into each raw material for dissolving to obtain 1×10 5 The mother solution with the concentration of mu g/mL is diluted to the test concentration of 500 mu g/mL or 100 mu g/mL by using a Tween 80 aqueous solution with the mass percent concentration of 1 per mill, so that the individual compound medicament solution shown by the alkaloid polyaurine B derivatives 1-28 is prepared, and a Ningnanmycin preparation is directly diluted by adding water to be used as a comparison object;
thirdly, living body protection:
respectively selecting ten parts of 3-5 She Qishan Western cigarettes with uniform growth vigor, spraying the second step of spraying the prepared alkaloid polyaurine B derivative 1-28 into the whole plant, repeating for 3 times, setting Tween 80 water solution with the mass percent concentration of 1%for comparison, spreading 500 meshes of silicon carbide on the leaf surface after 24 hours, dipping a virus solution by using a writing brush, lightly wiping the whole leaf surface for 2 times along the pulse supporting 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 1 time for 3 times for each 3 leaves, recording the number of lesions after 3 days, and calculating the prevention effect; the method comprises the steps of carrying out a first treatment on the surface of the
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, flushing with running water after inoculation, collecting and drying leaf surfaces, spraying the individual compound medicament solution shown in the alkaloid polyaurine B derivatives 1-28 prepared in the second step on the whole plant, 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 Western cigarettes with uniform growth vigor, respectively mixing and passivating 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 for 30min, performing friction inoculation, wherein the virus concentration is 20 mug/mL, washing with running water immediately after inoculation, repeating for 3 times, setting a Tween 80 aqueous solution with the mass percent concentration of 1%o for comparison, calculating the number of lesions after 3 days;
the results of the measurement of the tobacco mosaic virus resistance of 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 in alkaloid polyaurine B derivatives 1 to 28:
Figure BDA0004059358170000081
/>
Figure BDA0004059358170000091
table 1 results of biological activity tests show that alkaloid polyaurines and derivatives thereof have good 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 polyaucine B derivatives in 0.03mL of acetone respectively, diluting to a test concentration of 50mg/kg by using an aqueous solution containing 200 mug/mL of Tween 80, then sucking 1mL of liquid medicine respectively, injecting into a corresponding culture dish, adding 9mL of culture medium respectively, shaking uniformly to prepare a 50 mug/mL medicine-containing flat plate, taking the flat plate with 1mL of sterilized purified water as a blank control, cutting a bacterial disc along the outer edge of hypha by using a puncher with the diameter of 4mm, moving the bacterial disc onto the medicine-containing flat plate, repeating each treatment for three times, placing the culture dish in a constant temperature incubator with the temperature of 24+/-1 ℃ for culturing, investigating the expansion diameter of each treated bacterial disc after 48 hours, averaging, and comparing with the blank control to calculate the relative antibacterial rate.
Figure BDA0004059358170000101
The results of the in vitro fungicidal activity of the individual compounds in the 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
Figure BDA0004059358170000102
/>
Figure BDA0004059358170000111
Table 2 shows 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 (3)

1. The application of alkaloid polyaurine B derivatives in resisting plant viruses and pathogens is characterized in that: in particular to an alkaloid polyaurine B derivative with the following chemical structural formulas of 1-28, which is used as an anti-plant virus agent or a plant pathogen killing agent,
Figure FDA0004059358160000011
2. use of the alkaloid polyaurine B derivative according to claim 1, characterized in that: the plant virus is tobacco mosaic virus.
3. Use of the alkaloid polyaurine B derivative according to claim 1, characterized in that: 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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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20050060624A (en) * 2003-12-17 2005-06-22 주식회사 케이티앤지 The novel bacillus amyloliquefaciens ktgb0202 and control method of plant pathogenic fungi using that
US20090163545A1 (en) * 2007-12-21 2009-06-25 University Of Rochester Method For Altering The Lifespan Of Eukaryotic Organisms
CN107614491A (en) * 2014-06-26 2018-01-19 蒙纳什大学 Enzyme interacting agent
CN113287619A (en) * 2021-06-02 2021-08-24 河北工业大学 Application of Pityriacitrin alkaloid and derivative thereof in resisting plant viruses and germs
CN115462383A (en) * 2022-09-28 2022-12-13 河北工业大学 Application of Almazole D alkaloid and derivatives thereof in resisting plant viruses and pathogenic bacteria

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20050060624A (en) * 2003-12-17 2005-06-22 주식회사 케이티앤지 The novel bacillus amyloliquefaciens ktgb0202 and control method of plant pathogenic fungi using that
US20090163545A1 (en) * 2007-12-21 2009-06-25 University Of Rochester Method For Altering The Lifespan Of Eukaryotic Organisms
CN107614491A (en) * 2014-06-26 2018-01-19 蒙纳什大学 Enzyme interacting agent
CN113287619A (en) * 2021-06-02 2021-08-24 河北工业大学 Application of Pityriacitrin alkaloid and derivative thereof in resisting plant viruses and germs
CN115462383A (en) * 2022-09-28 2022-12-13 河北工业大学 Application of Almazole D alkaloid and derivatives thereof in resisting plant viruses and pathogenic bacteria

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DANIEL G. ANSTIS等: "Synthesis of the 1, 2, 4-Thiadiazole Alkaloid Polyaurine B", 《JOURNAL OF NATURAL PRODUCTS》, 16 April 2020 (2020-04-16), pages 1721 - 1724 *
吴志兵;何雪峰;蔡桦;吴世喜;邝继清;: "1, 2, 3-噻二唑酰胺类化合物的合成与生物活性研究", 化学研究与应用, no. 08, 15 August 2013 (2013-08-15) *

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