CN113999231B - Camelin A derivative, preparation thereof and application thereof in preventing and treating plant virus germ diseases - Google Patents
Camelin A derivative, preparation thereof and application thereof in preventing and treating plant virus germ diseases Download PDFInfo
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- CN113999231B CN113999231B CN202010727670.9A CN202010727670A CN113999231B CN 113999231 B CN113999231 B CN 113999231B CN 202010727670 A CN202010727670 A CN 202010727670A CN 113999231 B CN113999231 B CN 113999231B
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- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 241000700605 Viruses Species 0.000 title abstract description 19
- 201000010099 disease Diseases 0.000 title abstract description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 5
- 241000723873 Tobacco mosaic virus Species 0.000 claims abstract description 8
- 239000003513 alkali Substances 0.000 claims abstract description 6
- 244000052769 pathogen Species 0.000 claims abstract description 3
- VQQVWGVXDIPORV-UHFFFAOYSA-N Tryptanthrine Chemical class C1=CC=C2C(=O)N3C4=CC=CC=C4C(=O)C3=NC2=C1 VQQVWGVXDIPORV-UHFFFAOYSA-N 0.000 claims abstract 5
- 230000001717 pathogenic effect Effects 0.000 claims abstract 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- PXBFMLJZNCDSMP-UHFFFAOYSA-N 2-Aminobenzamide Chemical compound NC(=O)C1=CC=CC=C1N PXBFMLJZNCDSMP-UHFFFAOYSA-N 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 8
- BWWHTIHDQBHTHP-UHFFFAOYSA-N 2-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=CC=C1C(Cl)=O BWWHTIHDQBHTHP-UHFFFAOYSA-N 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- 240000007594 Oryza sativa Species 0.000 claims description 6
- 235000007164 Oryza sativa Nutrition 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 238000010992 reflux Methods 0.000 claims description 6
- 235000009566 rice Nutrition 0.000 claims description 6
- 239000000243 solution Substances 0.000 claims description 6
- 238000003786 synthesis reaction Methods 0.000 claims description 6
- 241000209140 Triticum Species 0.000 claims description 5
- 235000021307 Triticum Nutrition 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 240000008067 Cucumis sativus Species 0.000 claims description 4
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 claims description 4
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 claims description 4
- 241000233616 Phytophthora capsici Species 0.000 claims description 3
- 241001558929 Sclerotium <basidiomycota> Species 0.000 claims description 3
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 244000000003 plant pathogen Species 0.000 claims description 3
- IQQRAVYLUAZUGX-UHFFFAOYSA-N 1-butyl-3-methylimidazolium Chemical compound CCCCN1C=C[N+](C)=C1 IQQRAVYLUAZUGX-UHFFFAOYSA-N 0.000 claims description 2
- 235000017060 Arachis glabrata Nutrition 0.000 claims description 2
- 244000105624 Arachis hypogaea Species 0.000 claims description 2
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- 235000018262 Arachis monticola Nutrition 0.000 claims description 2
- 241000193738 Bacillus anthracis Species 0.000 claims description 2
- 244000241235 Citrullus lanatus Species 0.000 claims description 2
- 235000012828 Citrullus lanatus var citroides Nutrition 0.000 claims description 2
- 241000223218 Fusarium Species 0.000 claims description 2
- 235000007688 Lycopersicon esculentum Nutrition 0.000 claims description 2
- 240000003768 Solanum lycopersicum Species 0.000 claims description 2
- 240000008042 Zea mays Species 0.000 claims description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 claims description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 235000005822 corn Nutrition 0.000 claims description 2
- 239000002608 ionic liquid Substances 0.000 claims description 2
- 235000020232 peanut Nutrition 0.000 claims description 2
- 241001465180 Botrytis Species 0.000 claims 1
- 230000003197 catalytic effect Effects 0.000 claims 1
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- 230000000694 effects Effects 0.000 abstract description 19
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- 239000007787 solid Substances 0.000 description 15
- 150000001875 compounds Chemical class 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 238000012360 testing method Methods 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 4
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- 238000011081 inoculation Methods 0.000 description 4
- AMNAZJFEONUVTD-KEWDHRJRSA-N (2s,3s,4s,5r,6r)-6-(4-amino-2-oxopyrimidin-1-yl)-4,5-dihydroxy-3-[[(2s)-3-hydroxy-2-[[2-(methylamino)acetyl]amino]propanoyl]amino]oxane-2-carboxamide Chemical compound O1[C@H](C(N)=O)[C@@H](NC(=O)[C@H](CO)NC(=O)CNC)[C@H](O)[C@@H](O)[C@@H]1N1C(=O)N=C(N)C=C1 AMNAZJFEONUVTD-KEWDHRJRSA-N 0.000 description 3
- FEACDOXQOYCHKU-UHFFFAOYSA-N Gougerotin Natural products CNCC(=O)NC1=NC(=O)N(C=C1)C2OC(C(O)C(NC(=O)C(N)CO)C2O)C(=O)N FEACDOXQOYCHKU-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
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- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 239000000287 crude extract Substances 0.000 description 2
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- 238000000746 purification Methods 0.000 description 2
- 238000003828 vacuum filtration Methods 0.000 description 2
- KYCQOKLOSUBEJK-UHFFFAOYSA-M 1-butyl-3-methylimidazol-3-ium;bromide Chemical compound [Br-].CCCCN1C=C[N+](C)=C1 KYCQOKLOSUBEJK-UHFFFAOYSA-M 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
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- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 1
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- 230000000415 inactivating effect Effects 0.000 description 1
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- 238000005259 measurement Methods 0.000 description 1
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- 229920001223 polyethylene glycol Polymers 0.000 description 1
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- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000007430 reference method Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229960000329 ribavirin Drugs 0.000 description 1
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 1
- HBMJWWWQQXIZIP-UHFFFAOYSA-N silicon carbide Chemical compound [Si+]#[C-] HBMJWWWQQXIZIP-UHFFFAOYSA-N 0.000 description 1
- 229910010271 silicon carbide Inorganic materials 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Dentistry (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Saccharide Compounds (AREA)
Abstract
The invention relates to camelning alkali A derivatives I-1-I-12, a preparation method thereof and application thereof in preventing and treating plant virus and germ diseases. The tryptanthrin derivatives I-1 to I-12 show anti-plant virus activity, can well inhibit tobacco mosaic virus, and also show broad-spectrum anti-plant pathogen activity, and have outstanding inhibition activity on apple ring rot.
Description
Technical Field
The invention relates to a camelning alkali A derivative, a preparation method thereof and application thereof in preventing and treating plant virus germ diseases, and belongs to the technical field of agricultural protection.
Background
In 2007, jason Herr (bioorg. Med. Chem.2007, 15, 4237-4246) and the like, an Albany molecular research company, U.S. had found that 3-flupeganine A had a strong inhibitory activity on Topo I, comparable to that of CPT, but not directly related to the cytotoxicity of CPT. 3-N, N-diethylamine ethoxy and 3-N, N-dimethylaminoethoxy camelinine A have an improving effect on the toxicity of HCT-116 tumor cells (human colon cancer cell line). Notably, in 2004, the Dallavalle group of university of Milan (Bioorg. Med. Chem. Lett.2004, 14, 5757-5761.) found that 2, 3-dimethoxy camelin A was strongly cytotoxic to H460 (human non-small lung cancer cell line) via topo-I mediated DNA division, potentially providing a new idea for structural engineering of camelin. On the other hand, in 2004, 14-ethyl camelin a was found to have slightly improved cytotoxicity compared to camelin a, as found by the Chavan task group (Tetrahedron lett.2004, 60, 9931-9935). Furthermore, the Golubev group of the russian institute for organic element compounds, mei Yanuo, 2010 (russ. Chem. Bull.2010, 59, 209-218.) found that 14-trifluoromethyl camelinine a caused apoptosis of colon adenocarcinoma cells and leukemia cells cultured in vitro, and also showed activity in inhibiting Topo I.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a camelning alkali A derivative, a preparation method thereof and application thereof in preventing and treating plant virus and germ diseases. The camelnine A derivative of the patent has good activity of resisting plant viruses and pathogens.
The camelnine A derivative I of the present invention is a compound represented by the following I-1 to I-12 (structural formula I). The synthetic method of the structural formulas I-1 to I-12 is as follows:
synthesis of camelning A derivatives I-1 to I-11: the preparation method is characterized in that firstly, chloroform is used as a solvent, triethylamine is used as alkali, anthranilamide (1) and o-nitrobenzoyl chloride (2) are used for generating an intermediate 3 at room temperature, then, the intermediate 3 is dissolved in a 10% KOH aqueous solution, ethanol=2:1 solution, heating reflux is carried out at 80 ℃ to generate an intermediate 4, then, ethanol is used as a solvent, under the action of stannous chloride dihydrate (5), heating reflux is carried out at 90 ℃ to generate an intermediate 6, and finally, under the action of ionic liquid [ BmIm ] Br, the intermediate 6 reacts with corresponding aldehyde to generate I-1 to I-11.
Structural I
Equation one
Synthesis of camelning a derivative I-12: prepared according to the method shown in the second equation, using DMF as solvent, under the action of oxygen, the compound 8 generates I-12 under the heating condition of 100 ℃.
Equation two
The camelnine A derivatives I-1 to I-12 of the invention show good activity of resisting plant viruses and germs, and can well inhibit Tobacco Mosaic Virus (TMV) and cucumber wilt, peanut brown spots, apple ring, wheat sheath blight, corn small spots, watermelon anthrax, rice bakanae, tomato early blight, wheat gibberella, rice blast, phytophthora capsici, rape sclerotium, cucumber gray mold and rice sheath blight 14 plant germs.
Detailed Description
Example 1: synthesis of camelning A derivatives I-1 to I-12
In a first step, intermediate 3 is synthesized. O-aminobenzamide (1) (5 g,37 mmol) is dissolved in chloroform, triethylamine (14 mL) is added, o-nitrobenzoyl chloride (2) (7 mL,52 mmol) is slowly added under stirring, the reaction is carried out for four hours at room temperature, TLC detects the end of the reaction, white solid 4.2g is obtained through vacuum filtration, the yield is 80%, the melting point is 195-197 ℃, 1 H NMR(400MHz，DMSO-d 6 )δ12.52(s，1H)，8.48(d，J＝8.2Hz，1H)，8.38(brs，1H)，8.11(d，J＝8.1Hz，1H)，7.92-7.75(m，5H)，7.59(t，J＝7.7Hz，1H)，7.23(t，J＝7.6Hz，1H).
in the second step, intermediate 4 is synthesized. Intermediate 3 (4 g,14 mmol) was dissolved in 10% aqueous KOH (40 mL) and absolute ethanol (20 mL), heated to reflux at 90℃and the reaction was checked by TLC to completion, most of the solvent was spun dry, extracted with ethyl acetate, dried over anhydrous sodium sulfate, suction filtered and desolventized under reduced pressure to give a light brown solid 3.4g, yield 92%, melting point 178-180 ℃, 1 H NMR(400MHz，DMSO-d 6 )δ12.89(s，1H)，8.33-8.19(m，2H)，8.00-7.83(m，4H)，7.71(d，J＝8.2Hz，1H)，7.64(t，J＝7.5Hz，1H). 13 C NMR(100MHz，DMSO-d 6 )δ161.6，151.8，148.4，147.4，134.7，133.9，131.5，131.4，129.2，127.3，127.1，125.9，124.5，121.1.
and a third step of: synthesis of intermediate 6. Intermediate 4 (1.2 g,4.5 mmol) and SnCl 2 ·2H 2 O (5) (5.1 g,22.5 mmol) is dissolved in ethanol (20 mL), heated to reflux at 90 ℃, TLC detects the end of the reaction, most of the solvent is spin-dried, extracted with ethyl acetate, dried with anhydrous sodium sulfate, filtered by suction, desolventized under reduced pressure to obtain yellow solid 1g, yield 80%, melting point 155-157 ℃, 1 H NMR(400MHz，DMSO-d 6 )δ12.18(brs，1H)，8.19(d，J＝7.9Hz，1H)，7.88(t，J＝7.6Hz，1H)，7.84-7.73(m，2H)，7.55(t，J＝7.5Hz，1H)，7.26(t，J＝7.6Hz，1H)，7.12(brs，1H)，6.89(d，J＝8.3Hz，1H)，6.66(t，J＝7.5Hz，1H). 13 C NMR(100MHz，DMSO-d 6 )δ162.6，154.1，149.9，148.5，135.0，132.3，129.3，127.4，126.7，126.2，120.9，117.1，115.5，112.8.
fourth, camelning alkali A derivatives I-1 to I-11. Intermediate 6 (500 mg,2.11 mmol), the corresponding aldehyde (7) (63 mg,2.11 mmol), I 2 (27 mg,0.11 mmol) in [ BmIm ]]Br (4 mL), heating TLC at 80 ℃ to detect the end of the reaction, adding water for quenching, and carrying out vacuum filtration to obtain I-1 to I-11.
I-1: 330mg of yellow solid, 63% yield, melting point 178-180 ℃, 1 H NMR(400MHz，MeOD-d 4 )δ8.27-8.16(m，2H)，7.81-7.76(m，1H)，7.71(d，J＝8.0Hz，1H)，7.48-7.42(m，1H)，7.40-7.34(m，1H)，6.99-6.92(m，1H)，6.88(d，J＝8.1Hz，1H)，5.31(s，2H). 13 C NMR(100MHz，DMSO-d 6 )δ159.8，148.6，148.4，148.2，135.1，133.7，127.7，127.5，126.8，126.4，120.8，119.5，116.6，116.1，52.9.HRMS(ESI)calcd for C 15 H 12 N 3 O[M+H] + 250.0975，found 250.0974.
i-2: yellow solid, yield 65%, melting point 116-118 ℃, 1 H NMR(400MHz，MeOD-d 4 )δ8.27-8.16(m，2H)，7.83-7.76(m，1H)，7.72(d，J＝8.1Hz，1H)，7.46(t，J＝7.5Hz，1H)，7.40-7.33(m，1H)，6.90(t，J＝7.6Hz，1H)，6.84(d，J＝8.1Hz，1H)，6.32(q，J＝6.1Hz，1H)，1.43(d，J＝6.1Hz，3H). 13 C NMR(100MHz，DMSO-d 6 )δ159.5，148.1，147.3，145.7，135.1，134.1，127.5，127.4，126.8，126.4，120.5，118.9，116.4，115.1，59.3，19.9.HRMS(ESI)calcd for C 16 H 14 N 3 O[M+H] + 264.1131，found 264.1131.
i-3: yellow solid, yield 83%, melting point 235-237 ℃, 1 H NMR(400MHz，DMSO-d 6 )δ8.17(d，J＝7.6Hz，2H)，7.83(t，J＝7.6Hz，1H)，7.70(d，J＝8.2Hz，1H)，7.57-7.44(m，2H)，7.37(t，J＝7.6Hz，1H)，6.92(d，J＝8.1Hz，1H)，6.84(t，J＝7.5Hz，1H)，5.96-5.86(m，1H)，1.78(d，J＝10.0Hz，2H)，1.69-1.44(m，3H)，1.22-1.11(m，1H)，1.11-0.88(m，5H). 13 C NMR(100MHz，DMSO-d 6 )δ160.2，148.0，147.6，145.6，135.2，134.1，127.5，127.2，126.3，120.5，118.6，115.9，115.8，65.9，28.7，28.7，26.0，25.5，25.5.HRMS(ESI)calcd for C 21 H 22 N 3 O[M+H] + 332.1757，found 332.1757.
i-4: brown solid, yield 67%, melting point 98-100 c, 1 H NMR(400MHz，CDCl 3 )δ8.32-8.26(m，1H)，8.19(d，J＝8.2Hz，1H)，7.74-7.64(m，2H)，7.42-7.31(m，2H)，6.88(t，J＝7.6Hz，1H)，6.64(d，J＝8.2Hz，1H)，5.45-5.38(m，1H)，3.60-3.50(m，1H)，3.38-3.29(m，1H)，3.28-3.18(m，1H)，2.22-1.93(m，3H). 13 C NMR(100MHz，CDCl 3 )δ160.9，146.9，146.9，144.5，133.3，132.5，127.1，126.1，125.4，125.0，120.0，118.0，115.5，111.8，71.0，44.6，31.5，19.8.HRMS(ESI)calcd for C 18 H 16 N 3 O[M+H] + 290.1288，found 290.1287.
i-5: green solid, yield 65%, melting point 193-195 ℃, 1 H NMR(400MHz，DMSO-d 6 )δ8.20(d，J＝7.7Hz，1H)，8.10(d，J＝7.7Hz，1H)，7.86(t，J＝7.1Hz，1H)，7.77(d，J＝8.1Hz，1H)，7.48(t，J＝7.4Hz，1H)，7.33(d，J＝2.6Hz，1H)，7.31-7.24(m，2H)，6.89-6.78(m，2H)，6.61(d，J＝1.9Hz，1H)，6.47(d，J＝8.5Hz，1H)，6.29-6.22(m，1H)，3.90(s，3H)，3.65(s，3H). 13 C NMR(100MHz，DMSO-d 6 )δ160.6，159.1，157.4，148.0，147.7，145.0，134.9，133.4，127.2，126.7，126.5，126.1，125.8，119.9，119.5，118.4，115.8，115.0，104.0，98.9，59.2，55.8，55.1.HRMS(ESI)calcd for C 23 H 20 N 3 O 3 [M+H] + 386.1499，found 386.1500.
i-6: yellow solid, yield 85%, melting point 183-185 ℃, 1 H NMR(400MHz，CDCl 3 )δ8.11(t，J＝6.9Hz，2H)，7.81(d，J＝8.6Hz，2H)，7.58(s，2H)，7.33-7.18(m，4H)，7.16(t，J＝7.5Hz，1H)，6.80(t，J＝7.6Hz，1H)，6.67(d，J＝8.0Hz，1H)，5.13(s，1H). 13 C NMR(100MHz，CDCl 3 )δ160.8，148.2，147.9，146.5，146.2，142.7，135.0，133.8，127.9，127.8，127.3，127.1，126.6，123.9，121.6，120.4，118.2，117.1，62.8.HRMS(ESI)calcd for C 21 H 15 N 4 O 3 [M+H] + 371.1139，found 371.1140.
i-7: yellow solid, yield 84%, melting point 114-116 ℃, 1 H NMR(400MHz，DMSO-d 6 )δ8.54-8.43(m，2H)，8.23(d，J＝7.2Hz，1H)，8.15-8.07(m，2H)，7.89(t，J＝7.7Hz，1H)，7.77(d，J＝8.1Hz，1H)，7.55(t，J＝7.5Hz，1H)，7.36(t，J＝7.1Hz，1H)，7.29(d，J＝3.6Hz，1H)，7.17(d，J＝5.3Hz，2H)，6.98(d，J＝8.1Hz，1H)，6.92-6.81(m，1H). 13 C NMR(100MHz，DMSO-d 6 )δ160.2，150.5，148.6，148.2，147.4，145.3，135.6，134.3，127.8，127.4，127.2，126.9，121.4，120.3，119.7，116.6，116.2，62.2.HRMS(ESI)calcd for C 20 H 15 N 4 O[M+H] + 327.1240，found 327.1239.
i-8: yellow solid, yield 72%, melting point 211-213 ℃, 1 H NMR(400MHz，DMSO-d 6 )δ8.20(d，J＝7.8Hz，2H)，7.88(t，J＝7.1Hz，1H)，7.77(d，J＝8.0Hz，1H)，7.59(d，J＝3.6Hz，1H)，7.53(t，J＝7.5Hz，1H)，7.37(t，J＝7.6Hz，1H)，7.26(d，J＝3.7Hz，1H)，6.98-6.83(m，4H). 13 C NMR(100 MHz，DMSO-d 6 )δ159.6，147.8，147.5，144.9，144.4，134.8，133.2，127.2，126.8，126.5，126.0，120.3，119.3，116.4，116.3，58.4.HRMS(ESI)calcd for C 18 H 14 N 5 O 3 [M+H] + 316.1193，found 316.1192.
i-9: brown solid, yield 88%, melting point 153-155 c, 1 H NMR(400MHz，DMSO-d 6 )δ8.23-8.14(m，2H)，7.93(d，J＝3.0Hz，1H)，7.88-7.82(m，1H)，7.73(d，J＝8.1Hz，1H)，7.54-7.48(m，1H)，7.45-7.34(m，2H)，6.98(d，J＝8.0Hz，1H)，6.93-6.85(m，1H)，6.74(d，J＝3.4Hz，1H)，6.57-6.53(m，1H)，2.25(s，3H). 13 C NMR(100MHz，DMSO-d 6 )δ159.1，147.6，146.6，145.0，140.2，139.3，135.0，133.8，127.2，126.9，126.6，126.2，126.0124.6，119.9，119.1，116.1，115.3，59.9，14.7.HRMS(ESI)calcd for C 20 H 16 N 3 OS[M+H] + 346.1009，found 346.1009.
i-10: brown solid, yield 78%, melting point 168-170 ℃, 1 H NMR(400MHz，MeOD-d 4 )δ8.24(d，J＝8.0Hz，2H)，7.86-7.80(m，1H)，7.76(d，J＝8.1Hz，1H)，7.50(t，J＝7.5Hz，1H)，7.38(t，J＝7.1Hz，1H)，7.26(s，1H)，6.96-6.87(m，2H)，6.21(d，J＝3.4Hz，1H)，6.05(d，J＝3.3Hz，1H). 13 C NMR(100MHz，DMSO-d 6 )δ159.6，154.1，148.1，147.2，145.2，135.5，134.1，127.8，127.4，127.1，126.8，121.9，120.4，119.8，116.4，116.0，113.0，111.5，58.2.HRMS(ESI)calcd for C 19 H 13 BrN 3 O 2 [M+H] + 394.0186，found 394.0185.
i-11: yellow green solid with 80 percent of yield and 115-117 ℃ of melting point, 1 H NMR(400MHz，DMSO-d 6 )δ8.62(s，1H)，8.26(d，J＝7.0Hz，1H)，8.13(dd，J＝8.0，1.1Hz，1H)，7.88-7.82(m，1H)，7.78(d，J＝3.0Hz，1H)，7.73(d，J＝7.9Hz，1H)，7.54-7.45(m，2H)，7.45-7.39(m，1H)，6.97(dd，J＝11.2，4.0Hz，1H)，6.88(d，J＝7.9Hz，1H)，2.63(s，3H). 13 C NMR(100MHz，DMSO-d 6 )δ159.0，151.1，150.5，147.4，144.2，135.1，134.0，129.2，127.2，127.0，126.5，119.8，119.5，116.3，115.2，58.2，15.3.HRMS(ESI)calcd for C 19 H 15 N 4 OS[M+H] + 347.0961，found 347.0959.
example 2: synthesis of camelning A derivative I-12
Dissolving compound 8 (600 mg,2 mmol) in THF, oxygen protecting, heating TLC at 100deg.C to detect the end of reaction, diluting with water, extracting with methyl tert-butyl ether, drying with anhydrous sodium sulfate, vacuum filtering, removing solvent under reduced pressure, subjecting to column chromatography (V (petroleum ether) to V (ethyl acetate) =10:1) to obtain pale yellow solid 480mg, yield 61%, melting point 131-133 ℃, 1 H NMR(400MHz，CDCl 3 )δ8.82(d，J＝7.9Hz，1H)，8.23(d，J＝8.0Hz，1H)，7.87-7.76(m，4H)，7.65(t，J＝6.8Hz，1H)，7.59(d，J＝7.9Hz，1H)，7.50-7.38(m，3H). 13 C NMR(100MHz，CDCl 3 )δ159.8，146.9，146.6，145.3，142.0，136.1，135.7，135.4，133.7，131.9，129.8，129.3，129.0，128.1，127.6，127.5，127.3，126.7，126.2，121.7，119.8.HRMS(ESI)calcd for C 21 H 12 Cl 2 N 3 O[M+H] + 392.0352，found 392.0353.
example 3: the tobacco mosaic virus resistance activity was measured as follows:
1. virus purification and concentration determination:
the virus purification and concentration measurement are carried out by compiling tobacco mosaic virus SOP standard according to a measuring room generated by elements of university of south China. After 2 times of polyethylene glycol centrifugation treatment, the concentration of the virus crude extract is measured, and the virus crude extract is refrigerated at 4 ℃ for standby.
2. Compound solution preparation:
after weighing, adding DMF to dissolve the raw materials to obtain 1×10 5 Mu g/mL mother liquor, and then diluting the mother liquor to the required concentration by using an aqueous solution containing 1 per mill of Tween 80; the Ningnan mycin preparation is directly diluted by water.
3. Living body protecting action:
3-5 She Qishan Xiyan with uniform growth vigor is selected, the whole plant is sprayed and applied, each treatment is repeated for 3 times, and 1 permillage of Tween 80 aqueous solution is used for comparison. After 24h, the leaf surface is spread with silicon carbide (500 meshes), the whole leaf surface is dipped with a virus liquid by a writing brush, the whole leaf surface is lightly rubbed for 2 times along the branch pulse direction, the lower part of the leaf surface is supported by a palm, the virus concentration is 10 mug/mL, and the leaf surface is washed by running water after inoculation. And after 3d, recording the number of the lesions, and calculating the control effect.
4. In vivo therapeutic action:
3-5 She Qishan Xiyan with uniform growth vigor is selected, the whole leaf of the writing brush is inoculated with virus, the virus concentration is 10 mug/mL, and the whole leaf is washed by running water after inoculation. After leaf surface is dried, spraying and applying the whole plant, repeating for 3 times every treatment, and setting 1%Tween 80 water solution as a control. And after 3d, recording the number of the lesions, and calculating the control effect.
5. In vivo passivation:
selecting 3-5 She Qishan Xie smoke with uniform growth vigor, mixing the medicament with an equal volume of virus juice, inactivating for 30min, performing friction inoculation, wherein the virus concentration is 20 mug/mL, washing with running water after inoculation, repeating for 3 times, and setting 1 milltween 80 water solution for comparison. And counting the number of lesions after 3d, and calculating a result.
Inhibition ratio (%) = [ (control number of dried spots-treated number of dried spots)/control number of dried spots ] ×100%
Firstly, performing in-vivo deactivation, in-vivo treatment and activity protection activity tests on all compounds at a treatment dose of 500 mug/mL, and performing in-vivo deactivation, in-vivo treatment and in-vivo protection activity tests on the compounds with relative inhibition rate of more than 40% at a treatment dose of 500 mug/mL and on the compounds at a treatment dose of 100 mug/mL. The positive control is commercial anti-plant virus agents ribavirin and ningnanmycin.
Table 1 results of tests for activity against Tobacco Mosaic Virus (TMV) of camelnine a derivatives I-1 to I-12:
as can be seen from the data in the table, camelinine A derivatives I-1 to I-12 all showed good anti-TMV activity at a treatment dose of 500. Mu.g/mL, wherein derivatives I-9, I-10 all showed anti-TMV activity comparable to Ningnanmycin.
Example 4: antibacterial activity was tested, and the assay procedure was as follows:
in vitro sterilization test, cell growth rate assay (plate method):
a certain amount of medicament is dissolved in a proper amount of acetone, then the mixture is diluted to a required concentration by using an aqueous solution containing 200 mu g/mL of emulsifier, then 1mL of liquid medicament is respectively absorbed and injected into a culture dish, 9mL of culture medium is respectively added, and a 50 mu g/mL medicament-containing plate is prepared after shaking uniformly, and a plate added with 1mL of sterilized water is used as a blank control. The trays were cut along the outer edge of the mycelium with a punch of 4mm diameter and transferred to a medicated plate. Each treatment was repeated three times. The dishes were placed in a constant temperature incubator at 24.+ -. 1 ℃. After 48 hours, the expanded diameter of each treatment bacterial disc is investigated, the average value is calculated, and the relative antibacterial rate is calculated compared with a blank control.
Table 2 results of tests of activity against plant pathogens of camelnine a derivatives I-1 to I-12:
the camelnine A derivative shows broad-spectrum inhibition activity on 14 tested bacteria at a test concentration of 50 mug/mL. The inhibition activity on apple ring is good, the inhibition rates of the compounds I-6 and I-11 on apple ring reach 81%, the inhibition rates of the compounds I-3 and I-6 on wheat ring are 87% and 81%, the inhibition rate of the compound I-9 on phytophthora capsici reaches 89%, and the inhibition rates of the compounds I-9 and I-11 on rape sclerotium are 85%.
The endpoints and any values of the ranges disclosed herein are not limited to the precise range or value, and are understood to encompass values approaching those ranges or values. For numerical ranges, one or more new numerical ranges may be found between the endpoints of each range, between the endpoint of each range and the individual point value, and between the individual point value, in combination with each other, and are to be considered as specifically disclosed herein.
The starting materials and reagents referred to in the above examples were prepared by commercial or reference methods and the chemical reaction process is well within the skill of the art.
The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited thereto. Within the scope of the technical idea of the invention, a number of simple variants of the technical solution of the invention are possible, including combinations of the individual technical features in any other suitable way, which simple variants and combinations should likewise be regarded as being disclosed by the invention, all falling within the scope of protection of the invention.
Claims (4)
1. The tryptanthrin derivative is characterized in that the tryptanthrin derivative is one of the following structures I-3 to I-11:
2. the preparation method of I-3 to I-11 in claim 1:
synthesis of camelning A derivatives I-3 to I-11: the preparation method is characterized in that firstly, chloroform is used as a solvent, triethylamine is used as alkali, anthranilamide (1) and o-nitrobenzoyl chloride (2) react for 4 hours at room temperature to generate an intermediate 3, then the intermediate 3 is dissolved in a solution of 10% KOH aqueous solution and ethanol=2:1, heating reflux is carried out at 80 ℃ to generate an intermediate 4, ethanol is used as a solvent, under the action of stannous chloride dihydrate (5), heating reflux is carried out at 90 ℃ to generate an intermediate 6, and finally, the intermediate is treated with ionic liquid [ BmIm]Under the action of Br, intermediate 6 and corresponding aldehyde are reacted at 90 ℃ I 2 Catalytic deliveryGenerating I-3 to I-11 by condensation reaction,
equation one.
3. The use of tryptanthrin derivatives I-3 to I-11 according to claim 1 for controlling tobacco mosaic virus.
4. The use of tryptanthrin derivatives I-3 to I-11 according to claim 1 for controlling plant pathogens, characterized in that it is used as an anti-plant pathogen agent for inhibiting cucumber wilt, peanut brown spots, apple ring, wheat sharp eyespot, corn small spots, watermelon anthrax, rice bakanae, tomato early blight, wheat gibberella, rice blast, phytophthora capsici, rape sclerotium, cucumber botrytis, rice sharp eyespot 14 plant pathogens.
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