CN109651227B - 1-methyl-5-bromine arundoin derivative and preparation method and application thereof - Google Patents

1-methyl-5-bromine arundoin derivative and preparation method and application thereof Download PDF

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CN109651227B
CN109651227B CN201910078416.8A CN201910078416A CN109651227B CN 109651227 B CN109651227 B CN 109651227B CN 201910078416 A CN201910078416 A CN 201910078416A CN 109651227 B CN109651227 B CN 109651227B
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bromoarundoin
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卢爱党
杨珊
王铁男
李红岩
汪清民
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Hebei University of Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
    • 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
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/36—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings
    • A01N43/38—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings condensed with carbocyclic rings

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Abstract

The invention relates to a 1-methyl-5-bromine arundoin derivative, a preparation method and application thereof, in particular to a biocide containing a five-membered ring heterocyclic compound with 1 nitrogen atom as the only ring heteroatom, the 1-methyl-5-bromine arundoin derivative has the following chemical structural formula I,
Figure DDA0001959631150000011
the preparation method comprises the following steps of as shown in a chemical reaction equation,

Description

1-methyl-5-bromine arundoin derivative and preparation method and application thereof
Technical Field
The technical scheme of the invention relates to a biocide containing a five-membered ring heterocyclic compound with 1 nitrogen atom as the only ring heteroatom, in particular to a 1-methyl-5-bromoarundoin derivative and a preparation method and application thereof.
Background
The arundoin is natural alkaloid containing an indole skeleton, the basic structure skeleton of the arundoin is a tertiary amine structure and an indole structure, and the chemical structural formula of the arundoin is as follows:
Figure BDA0001959631140000011
the obtained donaxine has high bioactivity. Is widely distributed in nature, and is an alkaloid with chemosensory effect generated by gramineous plants such as wheat, barley, arundo donax and the like in the evolution process (Phytochemistry,1984,23(3), 539-541; Phytochemistry,1985,24(5), 945-947; exp.appl.,1986,40(3), 259-262), and has growth inhibition effect on environmental plants, insects, microorganisms and the like (Shaoyang institute of academic report, 2003,2(2), 131-135). People develop biological pesticides with different purposes by utilizing different biological activities of the arundoin. For example, the graminine secreted by barley has strong inhibiting effect on chickweed weeds (world agriculture, 2002,279(7), 41-44.), has 77 percent inhibiting effect on the growth at the concentration of 10mg/Kg, and can be developed into a biological herbicide (J.org.chem.,1959,24, 1285-. The arundoin can generate the insect food repellency (insect knowledge, 2003,40(1), 24-27; Shenyang university of agriculture, 2002,33(4),309 and 314.), and can be used for developing related pesticides for crop insecticides. The arundoin and the derivatives thereof become a biological pesticide with wide development prospect due to the characteristics of high efficiency, low toxicity, resistance and low residue (pesticides, 2004,43(2), 76-77).
The concentration of the arundoin in barley is about 8mg/g (dry weight), so that the concentration has a certain defense effect on pests in the growth process, but the concentration has a certain toxic and side effect on mammals (Plant Physiol.1983,71, 896-904; pharm.chem.J.2004,38, 287-310; Mat.Sci.Eng.C 2016,65, 400-407), so that the activity is improved and the toxicity to the environment is reduced through modification and reconstruction of the structure, and the method has a very important application value.
The prior art for the preparation of arundoin derivatives is reported in the following documents:
indole, dimethylamine and formaldehyde are used as raw materials, and the method for preparing the gramine and derivatives through the classical Mannich reaction under the catalysis of glacial acetic acid is a commonly used method (chemical time publication, 2002,6(3), 49-50; pesticides, 2004,43(2), 76-77; Open Org. chem. J.2007,1, 1-12; J.Med. chem.2016,59,6265 and 6280.), and is shown in the following reaction formula (1). The preparation method of the gramine and the derivatives reported in the document generally has the defects of large solvent requirement, high requirement on substrate substituent groups and low universality, and experiments prove that when the substrate designed by the invention is adopted, the raw materials are always incompletely reacted by the synthesis method, and the yield is only about 50%.
Figure BDA0001959631140000021
In 2006, Dai et al, North and Hei university reported that the synthesis of gramines and derivatives in absolute ethanol solvent was performed efficiently using Lewis acid zinc chloride as a catalyst (Synth. Commun.2006,36(13), 1829-1835.), as shown in the following reaction formula (2). The method also needs a large amount of solvent, has single substitution site, has undesirable reaction result when other aldehydes are used, and brings great difficulty to the development of green process due to the addition of zinc chloride.
Figure BDA0001959631140000022
The synthesis of the heterocyclic aromatic amine-containing gramine analogs using a solvent-free, catalyst-free one-pot method was reported by Olyaei (Tetrahedron Lett.2010,51, 6086-. With the reactions at 75 ℃ or 80 ℃ reported in the above documents, the starting materials are not always completely converted, and it is most critical that the post-treatment does not precipitate solids as described in the above documents, often a black viscous material is precipitated to stick to the walls of the vessel, and the post-treatment brings about difficulties.
In 2014, Chinna Rajesh et al reported the synthesis of a gramine-containing analog by a one-pot method with the addition of a one-fold amount of ethylene glycol without the use of a catalyst (Tetrahedron Lett.2014,55, 2977-. The method has the defects of high production cost and environmental pollution caused by the addition of glycol which is a solvent.
Disclosure of Invention
The technical problem to be solved by the invention is as follows: the 1-methyl-5-bromoarundoin derivative and the preparation method and the application thereof are provided, wherein the 1-methyl-5-bromoarundoin derivative is a brand new arundoin derivative, the preparation method overcomes the defects of low yield, high production cost and environmental pollution in the process of preparing the arundoin derivative in the prior art, and the 1-methyl-5-bromoarundoin derivative is found to have good activity against plant viruses and germs for the first time.
The technical scheme adopted by the invention for solving the technical problem is as follows: the 1-methyl-5-bromine arundoin derivative has the following chemical structural formula I,
Figure BDA0001959631140000023
in the general formula I, HX represents inorganic acid or organic acid, and when HX represents inorganic acid, it is HCl, HBr, HI, H2SO4Or H3PO4When HX represents an organic acid, dichloroacetic acid, trifluoroacetic acid, propionic acid, butyric acid, malonic acid, oxalic acid, adipic acid, camphorsulfonic acid, methanesulfonic acid, p-toluenesulfonic acid, trans-ferulic acid, salicylic acid, malic acid, succinic acid, p-hydroxybenzoic acid, lactic acid, caffeic acid, chlorogenic acid, sulfanilic acid, 5-sulfosalicylic acid, fumaric acid, gluconic acid, itaconic acid, or sorbic acid.
The 1-methyl-5-bromoarundoin derivative is preferably a compound having the following chemical structural formulas I-1 to I-10:
Figure BDA0001959631140000031
the preparation method of the 1-methyl-5-bromoarundoin derivative comprises the following specific steps of:
Figure BDA0001959631140000032
1-methyl-5-bromoindole shown in a chemical structural formula 1 is used as a raw material to react with formaldehyde aqueous solution and dimethylamine aqueous solution to generate a 1-methyl-5-bromoarundoin intermediate product shown in a chemical structural formula 2, the intermediate product is dissolved in methanol, and inorganic acid or organic acid HX is added to react to prepare the 1-methyl-5-bromoarundoin derivative shown in a chemical structural formula I.
The 1-methyl-5-bromoarundoin derivative is used as an anti-plant virus agent, and the 1-methyl-5-bromoarundoin derivative is a compound shown as the following chemical structural formulas I-1 to I-10:
Figure BDA0001959631140000033
the plant virus is tobacco mosaic virus, pepper virus, rice virus, tomato virus, sweet potato virus, melon virus and maize dwarf mosaic virus.
The 1-methyl-5-bromoarundoin derivative is used as a plant pathogenic fungicide, and the 1-methyl-5-bromoarundoin derivative is a compound shown as the following chemical structural formulas I-1 to I-10:
Figure BDA0001959631140000041
the plant pathogenic fungi are 14 plant pathogenic fungi including cucumber fusarium wilt, peanut brown spot fungus, apple ring spot fungus, tomato early blight fungus, wheat gibberella, rice bakanae fungus, rape sclerotinia sclerotiorum, pepper phytophthora capsici, wheat sharp eyespot fungus, corn small spot fungus, watermelon anthracnose fungus, potato late blight fungus, rice sharp eyespot fungus and cucumber gray mold fungus.
In the preparation method of the 1-methyl-5-bromoarundoin derivative, the related raw material 1-methyl-5-bromoindole, the formaldehyde aqueous solution, the dimethylamine aqueous solution, the methanol, the inorganic acid or the organic acid HX are all obtained from commercial sources, and the chemical reaction process can be mastered by those skilled in the art.
The invention has the beneficial effects that: compared with the prior art, the invention has the prominent substantive characteristics and remarkable progress as follows:
(1) the invention synthesizes the 1-methyl-5-bromine arundoin derivatives shown in the chemical structural formula I for the first time, in particular to the arundoin derivative compounds shown in the chemical structural formulas I-1 to I-10, provides the preparation methods of the compounds for the first time, and discovers that the arundoin has good activity of resisting plant viruses and germs for the first time.
(2) Compared with the prior art that the aromatic amine-containing gramine analogue is synthesized by using a solvent-free and catalyst-free one-pot method respectively reported by Olyaei (Tetrahedron Lett.2010,51, 6086-. The invention has the obvious advantages that 80 ℃ charging is adopted, the 90 ℃ reaction effect is good, and the column chromatography can obtain a very pure product.
(3) Compared with the prior art that Chinna Rajesh et al reports that the gramine-containing analogue is synthesized by adding a one-pot method of one time of ethylene glycol without using a catalyst in 2014,55, 2977-2981), the method needs the addition of ethylene glycol in the prior art, and the method has the remarkable improvement that the method can be completed under the condition of no solvent.
Detailed Description
Example 1
The preparation method of the 1-methyl-5-bromine arundoin derivative with the chemical structural formula I is as follows:
the prepared 1-methyl-5-bromine arundoin derivative has the following chemical structural formula I:
Figure BDA0001959631140000051
in the general formula I, HX represents inorganic acid or organic acid, and when HX represents inorganic acid, it is HCl, HBr, HI, H2SO4Or H3PO4When HX represents an organic acid, dichloroacetic acid, trifluoroacetic acid, propionic acid, butyric acid, malonic acid, oxalic acid, adipic acid, camphorsulfonic acid, methanesulfonic acid, p-toluenesulfonic acid, trans-ferulic acid, salicylic acid, malic acid, succinic acid, p-hydroxybenzoic acid, lactic acid, caffeic acid, chlorogenic acid, sulfanilic acid, 5-sulfosalicylic acid, fumaric acid, gluconic acid, itaconic acid, or sorbic acid.
The preparation method of the 1-methyl-5-bromine arundoin derivative with the chemical structural formula I comprises the following specific steps of a chemical reaction equation:
Figure BDA0001959631140000052
1-methyl-5-bromoindole shown in a chemical structural formula 1 is used as a raw material to react with formaldehyde aqueous solution and dimethylamine aqueous solution to generate a 1-methyl-5-bromoarundoin intermediate product shown in a chemical structural formula 2, the intermediate product is dissolved in methanol, and inorganic acid or organic acid HX is added to react to prepare the 1-methyl-5-bromoarundoin derivative shown in a chemical structural formula I.
Example 2
The preparation method of the 1-methyl-5-bromoarundoin benzoate shown in the chemical structural formula I-1 comprises the following steps:
the chemical structural formula I-1 of the 1-methyl-5-bromine arundoin benzoate is
Figure BDA0001959631140000053
The preparation method comprises the following specific steps:
step one, under the conditions of magnetic stirring at the temperature of 0-5 ℃ and 600 revolutions per minute, adding 5mL of mixed solution of formaldehyde with the mass percent concentration of 37%, namely 61.5mmol of formaldehyde, and dimethylamine with the mass percent concentration of 5mL of dimethylamine, namely 33.5mmol of dimethylamine into a 150mL reactor, dropwise adding 2.855mL of glacial acetic acid after 1 hour, reacting for 15 minutes, adding 3.20g of raw material 1-methyl-5-bromoindole with the mass percent concentration of 15.23mmol, reacting for 1.5 hours, transferring to room temperature, continuing to react for 12 hours, detecting the reaction by a TLC point plate, adding saturated salt solution, adding aqueous solution of NaOH with the mass percent concentration of 30%, adjusting the pH of the system to 12-14, and using 30mL of CH (CH) (-12-14)2Cl2Extracting for three times, washing the organic phase with water and saturated sodium chloride sequentially, mixing the organic phases, drying with anhydrous sodium sulfate, removing solvent from the filtered organic phase with a rotary evaporator, purifying the obtained crude product with column chromatography, wherein the eluent is petroleum ether and ethyl acetate 15: 1 to obtain a light yellow liquid intermediate product with the yield of 85 percent; the relevant parameters of the yellowish liquid material were determined to be:1H NMR(400MHz,CDCl3)δ7.81(d,J＝2.0Hz,1H,Ar-H),7.29(dd,J＝2.0and 8.8Hz,1H,Ar-H),7.15(d,J＝8.4Hz,1H,Ar-H),6.98(s,1H,Ar-H),3.74(s,3H,N-CH3),3.54(s,2H,Ar-CH2),2.26(s,6H,N-(CH3)2)；13C NMR(100MHz,CDCl3)δ135.7,130.0,129.4,124.4,122.0,112.6,111.7,110.6,54.4,45.4,32.9；HRMS(ESI)calcd forC12H16BrN2(M+H)+267.0491, found 267.0496, which confirmed the intermediate product to be 1-methyl-5-bromoarundoin;
secondly, dissolving 0.17g, namely 0.65mmol of 1-methyl-5-bromoarundoin prepared in the first step into a mixed solution of 20mL of methanol, adding 0.15g, namely 0.65mmol of benzoic acid, heating and refluxing for 2h, and after desolventizing, purifying by column chromatography to obtain 0.24g of yellow oily matter with the yield of 95%;1H NMR(400MHz,DMSO-d6)δ7.96(d,J＝7.3Hz,2H,Ar-H),7.91(d,J＝1.5Hz,1H,Ar-H),7.55(t,J＝7.2Hz,1H,Ar-H),7.40–7.47(m,4H,Ar-H),7.56(dd,J＝8.7,1.7Hz,1H,Ar-H),3.83(s,2H,Ar-CH2),3.77(s,3H,N-CH3),3.18(s,1H,CO2H),2.35(s,6H,N-(CH3)2)；13C NMR(100MHz,DMSO-d6) Delta 168.2,135.7,133.0,131.8,131.6,129.5,129.2,128.2,123.7,121.5,111.9,111.8,107.7,52.3,43.2,32.6, and the product was determined to be 1-methyl-5-bromoarundoin benzoate.
Example 3
The preparation method of the 1-methyl-5-bromine arundoin L malate shown in the chemical structural formula I-2 comprises the following steps:
the chemical structural formula I-2 of the 1-methyl-5-bromine arundoin L malate is
Figure BDA0001959631140000061
The preparation method comprises the following specific steps:
the first step, same as example 1;
second, column chromatography purification as in example 1 except substituting L malic acid for benzoic acidObtaining light yellow oily matter with the yield of 94 percent;1H NMR(400MHz,DMSO-d6)δ7.94(d,J＝1.7Hz,1H,Ar-H),7.46(s,1H,Ar-H),7.44(d,J＝8.7Hz,1H,Ar-H),7.30(dd,J＝1.8,8.7Hz,1H,Ar-H),4.00(s,2H,Ar-CH2),3.86–3.92(m,1H,CH2-CH),3.79(s,3H,N-CH3),3.18(s,3H,CO2H,OH),2.49–2.56(m,1H,CH-CH2),2.46(s,6H,N-(CH3)2),2.31–2.38(m,1H,CH-CH2)；13C NMR(100MHz,DMSO-d6) δ 177.2,172.7,135.8,132.8,129.9,124.4,121.9,112.6,106.5,66.5,52.5,49.1,43.2,42.2,33.2, the product was determined to be 1-methyl-5-bromoarundoin L malate.
Example 4
The preparation method of 1-methyl-5-bromoarundoin D malate shown in the chemical structural formula I-3 comprises the following steps:
the chemical structural formula I-3 of the 1-methyl-5-bromine arundoin D malate is
Figure BDA0001959631140000071
The preparation method comprises the following specific steps:
the first step, same as example 1;
step two, except that the benzoic acid is replaced by the D malic acid, other steps are carried out in the same way as the example 1, and the light yellow oily matter is obtained by column chromatography purification, with the yield of 93 percent;1H NMR(400MHz,DMSO-d6)δ7.94(d,J＝1.7Hz,1H,Ar-H),7.46(s,1H,Ar-H),7.44(d,J＝8.7Hz,1H,Ar-H),7.30(dd,J＝1.8,8.7Hz,1H,Ar-H),4.00(s,2H,Ar-CH2),3.86–3.92(m,1H,CH2-CH),3.79(s,3H,N-CH3),3.18(s,3H,CO2H,OH),2.49–2.56(m,1H,CH-CH2),2.46(s,6H,N-(CH3)2),2.31–2.38(m,1H,CH-CH2)；13C NMR(100MHz,DMSO-d6) δ 177.2,172.7,135.8,132.8,129.9,124.4,121.9,112.6,106.5,66.5,52.5,49.1,43.2,42.2,33.2, the product was determined to be 1-methyl-5-bromoarundoin D malate.
Example 5
The preparation method of the 1-methyl-5-bromine arundoin phosphate shown in the chemical structural formula I-4 comprises the following steps:
the chemical structural formula of the 1-methyl-5-bromine arundoin phosphate I-4 is
Figure BDA0001959631140000072
The preparation method comprises the following specific steps:
the first step, same as example 1;
step two, except that the benzoic acid is replaced by the phosphoric acid, other steps are carried out in the same way as the example 1, the light yellow oily substance is obtained by column chromatography purification, and the yield is 96 percent;1H NMR(400MHz,DMSO-d6)δ7.97(s,1H,Ar-H),7.56(s,1H,Ar-H),7.46(d,J＝8.6Hz,1H,Ar-H),7.32(d,J＝8.6Hz,1H,Ar-H),6.86(s,1H,HPO4 2-),4.07(s,2H,Ar-CH2),3.81(s,3H,N-CH3),3.18(s,2H,CO2H),2.50(s,6H,N-(CH3)2)；13C NMR(100MHz,DMSO-d6) δ 135.3,127.8,123.9,121.3,117.9,112.2,109.5,48.6,42.3,32.7, the product was determined to be 1-methyl-5-bromoarundoin phosphate.
Example 6
The preparation method of the 1-methyl-5-bromine arundoin hydrobromide shown in the chemical structural formula I-5 comprises the following steps:
the chemical structural formula of the 1-methyl-5-bromine arundoin hydrobromide I-5 is
Figure BDA0001959631140000073
The preparation method comprises the following specific steps:
the first step, same as example 1;
step two, except that hydrobromic acid is used to replace benzoic acid, other steps are carried out in the same way as the step 1, and purification is carried out by column chromatography to obtain purple solid, wherein the yield is 93%, and the melting point is 212-;1H NMR(400MHz,DMSO-d6)δ9.56(s,1H,HBr),8.11(s,1H,Ar-H),7.65(s,1H,Ar-H),7.45(d,J＝8.7Hz,1H,Ar-H),7.35(d,J＝8.7Hz,1H,Ar-H),4.45(d,J＝4.5Hz,2H,Ar-CH2),3.83(s,3H,N-CH3),2.74(d,J＝4.6Hz,6H,N-(CH3)2)；13C NMR(100MHz,DMSO-d6) δ 135.3,134.1,129.3,124.3,121.4,112.7,112.4,102.1,50.5,41.1,32.9, which identifies the product as 1-methyl-5-bromoarundoin hydrobromide.
Example 7
The preparation method of the 1-methyl-5-bromine arundo donax hydrochloride shown in the chemical structural formula I-6 comprises the following steps:
the chemical structural formula I-6 of the 1-methyl-5-bromine arundo donax hydrochloride is
Figure BDA0001959631140000081
The preparation method comprises the following specific steps:
the first step, same as example 1;
step two, except that the benzoic acid is replaced by hydrochloric acid, the purple solid is obtained by column chromatography purification in the same way as the example 1, the yield is 96 percent, and the melting point is 220-;1H NMR(400MHz,DMSO-d6)δ10.76(s,1H,HCl),8.12(s,1H,Ar-H),7.67(s,1H,Ar-H),7.49(d,J＝8.7Hz,1H,Ar-H),7.33(d,J＝8.7Hz,1H,Ar-H),4.40(d,J＝4.3Hz,2H,Ar-CH2),3.82(s,3H,N-CH3),2.68(d,J＝4.4Hz,6H,N-(CH3)2)；13C NMR(100MHz,DMSO-d6) Delta 135.2,134.1,129.5,124.2,121.3,112.7,112.3,102.2,50.1,40.8,32.9, the product was determined to be 1-methyl-5-bromoarundoin hydrochloride.
Example 8
The preparation method of the 1-methyl-5-bromine arundoin hydroiodide shown in the chemical structural formula I-7 comprises the following steps:
the chemical structural formula of the 1-methyl-5-bromine arundoin hydroiodide I-7 is
Figure BDA0001959631140000082
The preparation method comprises the following specific steps:
the first step, same as example 1;
second, except that hydroiodic acid is used to replace benzoic acid, other steps are carried out in the same way as in example 1, and the purple solid is obtained by column chromatography purification and then is collectedThe rate is 92 percent, and the melting point is 190-192 ℃;1H NMR(400MHz,DMSO-d6)δ9.36(s,1H,HI),8.10(s,1H,Ar-H),7.65(s,1H,Ar-H),7.49(d,J＝8.7Hz,1H,Ar-H),7.34(d,J＝7.5Hz,1H,Ar-H),4.47(d,J＝4.4Hz,2H,Ar-CH2),3.84(s,3H,N-CH3),2.78(d,J＝4.5Hz,6H,N-(CH3)2)；13C NMR(100MHz,DMSO-d6) Delta 135.3,134.0,129.2,124.4,121.4,112.7,112.4,102.1,50.7,41.3,33.0, the product was determined to be 1-methyl-5-bromoarundoin hydroiodide.
Example 9
The preparation method of the 1-methyl-5-bromine arundoin sulfate shown in the chemical structural formula I-8 comprises the following steps:
the chemical structural formula I-8 of the 1-methyl-5-bromine arundoin sulfate is
Figure BDA0001959631140000091
The preparation method comprises the following specific steps:
the first step, same as example 1;
step two, except that the benzoic acid is replaced by the sulfuric acid, other steps are carried out in the same way as the example 1, and the yellow oily matter is obtained by column chromatography purification, wherein the yield is 97%;1H NMR(400MHz,DMSO-d6)δ9.41(s,1H,HSO4 --H),8.08(d,J＝1.8Hz,1H,Ar-H),7.65(s,1H,Ar-H),7.50(d,J＝8.7Hz,1H,Ar-H),7.35(dd,J＝1.9,8.7Hz,1H,Ar-H),6.57(s,1H,HSO4 -),4.44(d,J＝5.0Hz,2H,Ar-CH2),3.83(s,3H,N-CH3),2.76(d,J＝4.9Hz,6H,N-(CH3)2)；13C NMR(100MHz,DMSO-d6) δ 135.8,134.6,129.8,124.8,121.8,113.2,112.9,102.7,51.1,41.7,33.4, the product was determined to be 1-methyl-5-bromoarundoin sulfate.
Example 10
The preparation method of the 1-methyl-5-bromoarundoin trans-ferulate shown in the chemical structural formula I-9 comprises the following steps:
the chemical structural formula I-9 of the 1-methyl-5-bromine arundoin trans-ferulate is
Figure BDA0001959631140000092
The preparation method comprises the following specific steps:
the first step, same as example 1;
step two, except that trans-ferulic acid is used for replacing benzoic acid, other steps are carried out in the same way as the step 1, and white solid is obtained through column chromatography purification, the yield is 93 percent, and the melting point is 70-71 ℃;1H NMR(400MHz,DMSO-d6)δ9.88(s,2H,CO2H,OH),7.81(s,1H,Ar-H),7.47(d,J＝15.8Hz,1H,Ar-H),7.39(d,J＝8.6Hz,1H,Ar-H),7.29(d,J＝9.2Hz,2H,Ar-H),7.26(d,J＝9.9Hz,1H,Ar-H),6.81(d,J＝8.0Hz,1H,Ar-H),6.39(d,J＝15.8Hz,1H,Ar-H),3.83(s,3H,OCH3),3.76(s,3H,N-CH3),3.57(s,2H,Ar-CH2),2.19(s,6H,N-(CH3)2)；13C NMR(100MHz,DMSO-d6) Delta 168.4,148.9,147.9,143.7,135.5,130.5,129.5,125.9,123.5,122.6,121.5,116.6,115.5,111.8,111.4,111.0,110.1,55.7,53.6,44.4,32.5, the product was determined to be 1-methyl-5-bromoarundoin trans ferulate.
Example 11
The preparation method of the 1-methyl-5-bromine arundoin p-toluenesulfonate shown in the chemical structural formula I-10 comprises the following steps:
the chemical structural formula I-10 of the 1-methyl-5-bromine arundoin p-toluenesulfonate is
Figure BDA0001959631140000101
The preparation method comprises the following specific steps:
the first step, same as example 1;
step two, except that p-toluenesulfonic acid is used for replacing benzoic acid, other steps are carried out in the same way as the example 1, white solid is obtained through column chromatography purification, the yield is 93%, and the melting point is 139-140 ℃;1H NMR(400MHz,DMSO-d6)δ9.59(s,1H,SO3H),8.09(s,1H,Ar-H),7.62(s,1H,Ar-H),7.53(d,J＝7.7Hz,2H,Ar-H),7.50(d,J＝10.0Hz,1H,Ar-H),7.34(d,J＝8.6Hz,1H,Ar-H),7.13(d,J＝7.4Hz,2H,Ar-H),4.40(s,2H,Ar-CH2),3.82(s,3H,N-CH3),2.72(s,6H,N-(CH3)2),2.30(s,3H,Ar-CH3)；13C NMR(100MHz,DMSO-d6) Delta 145.5,137.7,135.3,133.9,129.3,128.1,125.5,124.3,121.3,112.7,112.3,102.5,50.7,41.3,32.9,20.8, and the product was determined to be 1-methyl-5-bromoarundoin p-toluenesulfonate.
Example 12
The determination of the anti-tobacco mosaic virus activity of individual compounds shown in chemical structural formulas I-1-I-10 in the 1-methyl-5-bromoarundoin derivative I is carried out by the following procedures:
the first step, tobacco mosaic virus purification and concentration determination:
the purification and concentration determination of the tobacco mosaic virus are carried out according to the specification of tobacco mosaic virus SOP compiled by the institute of elements, institute of southern development university, the virus crude extract is subjected to 2-time polyethylene glycol centrifugation treatment, the concentration is determined to be 20 mug/mL, and the virus crude extract is refrigerated at 4 ℃ for standby;
secondly, preparing individual compound medicament solution shown in chemical structural formulas I-1 to I-10 in the 1-methyl-5-bromoarundoin derivative I:
weighing individual compounds shown in chemical structural formulas I-1-I-10 in the 1-methyl-5-bromoarundoin derivative I by 40mg respectively as raw medicines, and dissolving in 0.4mL of DMF to obtain 1 × 105Diluting the mother solution with mu g/mL by using a Tween 80 aqueous solution with the mass percentage concentration of 1 per mill to the test concentration of 500 mu g/mL or 100 mu g/mL, thus preparing individual compound medicament solution shown in chemical structural formulas I-1-I-10 in the 1-methyl-5-bromoarundoin derivative I, and taking a ningnanmycin preparation to be directly diluted by adding water as a contrast;
step three, in vitro action:
preparing ten friction-inoculated 3-5-leaf-period Sanxi tobacco leaves, respectively washing with running water, wherein the virus concentration is 10 mug/mL, cutting off after drying, splitting along the veins of the leaves, respectively soaking the left and right half leaves in a Tween 80 aqueous solution with the mass percentage concentration of 1 thousandth and an individual compound medicament solution shown in the chemical structural formula I-1-I-10 in the 1-methyl-5-bromoarundoin derivative I prepared in the second step, taking out after 30min, performing moisture preservation culture under the condition of normal-temperature illumination, repeating for 1 time for every 3 leaves, repeating for 3 times, recording the number of disease spots after 3 days, and calculating the prevention effect;
step four, protecting the living body:
respectively selecting ten parts of 3-5-leaf-period Saxifraga, respectively spraying individual compound medicament solution shown by chemical structural formulas I-1-I-10 in the 1-methyl-5-bromoarundoin derivative I prepared in the second step on the whole plant, repeating the treatment for 3 times, setting Tween 80 aqueous solution with the mass percentage concentration of 1 per mill for comparison, spreading 500-mesh carborundum on the leaf surface after 24 hours, taking virus liquid by using a brush pen, lightly wiping the whole leaf surface for 2 times along the branch vein direction, supporting the lower part of the leaf by using a palm, keeping the virus concentration at 10 mu g/mL, washing the leaf surface by using running water after inoculation, recording the number of disease spots after 3 days, and calculating the prevention effect;
the fifth step, the in vivo therapeutic action:
respectively selecting ten 3-5 leaf-period Saxifraga, respectively inoculating viruses with whole leaves of a writing brush, wherein the virus concentration is 10 microgram/mL, washing with running water after inoculation, drying leaf surfaces, spraying whole plants with an individual compound medicament solution shown in chemical structural formulas I-1-I-10 in the 1-methyl-5-bromoarundoin derivative I prepared in the second step, repeating the treatment for 3 times, setting a Tween 80 aqueous solution with the mass percentage concentration of 1 thousandth for comparison, recording the number of disease spots after 3 days, and calculating the prevention effect;
sixthly, in-vivo passivation:
respectively selecting ten parts of 3-5-leaf-period Saxiseng tobacco with uniform growth vigor, respectively mixing and passivating the individual compound medicament solution shown by the chemical structural formula I-1-I-10 in the 1-methyl-5-bromoarundoin derivative I prepared in the second step with virus juice with the same volume for 30min, performing friction inoculation, wherein the virus concentration is 20 mu g/mL, flushing with running water after inoculation, repeating for 3 times, setting a Tween 80 aqueous solution with the mass percentage concentration of 1 per thousand for comparison, counting the number of disease spots after 3 days, and calculating the result;
the results of the determination of the tobacco mosaic virus-resistant activity of individual compounds represented by the chemical structural formulas I-1 to I-10 in the 1-methyl-5-bromoarundoin derivative I are shown in Table 1.
Table 1.1-methyl-5-bromoarundoin derivatives I individual compounds represented by chemical structural formulae I-1 to I-10 have anti-TMV activity test results:
Figure BDA0001959631140000111
Figure BDA0001959631140000121
from Table 1, the 1-methyl-5-bromoarundoin derivative I shows good anti-TMV activity, and the anti-TMV of the compounds I-1 to I-2 and I-4 to I-10 exceeds that of the commercialized variegated ribavirin in living passivation, living treatment and living protection; the compounds I-4 to I-7 are obviously superior to commercial variety ningnanmycin in vivo tests including in vivo passivation, in vivo treatment and in vivo protection; under the same test conditions, the anti-TMV activity of I-4 to I-5 is superior to that of the compound 2, and the method has great development value.
Example 13
The antibacterial activity test and the in-vitro sterilization test of individual compounds shown in chemical structural formulas I-1-I-10 in the 1-methyl-5-bromoarundoin derivative I are carried out by the following determination procedures:
cell growth rate measurement method, i.e. plate method: respectively dissolving 3mg of individual compounds shown in chemical structural formulas I-1-I-10 in the 1-methyl-5-bromoarundoin derivative I in 0.03mL of acetone, then diluted with an aqueous solution containing 200. mu.g/mL Tween 80 to a test concentration of 50mg/kg, then sucking 1mL of the liquid medicine respectively, injecting into a corresponding culture dish, adding 9mL of culture medium respectively, shaking uniformly to prepare a medicine-containing plate with the concentration of 50 mug/mL, taking a flat plate added with 1mL of sterilized purified water as a blank control, cutting a bacteria disc along the outer edge of hyphae by using a puncher with the diameter of 4mm, moving the bacteria disc to the drug-containing flat plate, repeating the treatment for three times, placing the culture dish in a constant temperature incubator at 24 +/-1 ℃ for culture, investigating the expansion diameter of each treated bacteria disc after 48 hours, calculating an average value, and comparing the average value with the blank control to calculate the relative bacteriostasis rate.
Figure BDA0001959631140000122
The results of the in vitro fungicidal activity of the individual compounds represented by the chemical structural formulae I-1 to I-10 in the above 1-methyl-5-bromoarundoin derivative I are shown in Table 2.
Table 2.1-methyl-5-Bromoarundoline derivative I individual Compounds of chemical structures I-1-I-10 in vitro fungicidal Activity test results
Figure BDA0001959631140000131
As can be seen from the data in Table 2, individual compounds shown in chemical structural formulas I-1 to I-10 in the 1-methyl-5-bromoarundoin derivative I have good activity against plant germs, and part of the compounds have over 50 percent of inhibition rate and broad-spectrum bactericidal activity.
The percentages in the above examples are percentages by mass.
The raw materials and reagents involved in the above examples are commercially available, and the chemical reaction process is within the skill of those in the art.

Claims (5)

1.1-methyl-5-bromoarundoin derivatives characterized by: has the following chemical structural formula I,
Figure FDA0002383880230000011
in the general formula I, HX represents inorganic acid or organic acid, and when HX represents inorganic acid, it is HCl, HBr, HI, H2SO4Or H3PO4When HX represents an organic acid, dichloroacetic acid, trifluoroacetic acid, propionic acid, butyric acid, malonic acid, oxalic acid, adipic acid, camphorsulfonic acid, methanesulfonic acid, p-toluenesulfonic acid, trans-ferulic acid, salicylic acid, malic acid, succinic acid, p-hydroxybenzoic acid, lactic acid, caffeic acid, chlorogenic acid, sulfanilic acid, 5-sulfosalicylic acid, fumaric acid, gluconic acid, itaconic acid, or sorbic acid.
2. The 1-methyl-5-bromoarundoin derivative according to claim 1, wherein: is a compound shown in the following chemical structural formulas I-1 to I-10:
Figure FDA0002383880230000012
3. a method for preparing the 1-methyl-5-bromoarundoin derivative according to claim 1, wherein: the specific steps are shown in the following chemical reaction equation,
Figure FDA0002383880230000013
1-methyl-5-bromoindole shown in a chemical structural formula 1 is used as a raw material to react with formaldehyde aqueous solution and dimethylamine aqueous solution to generate a 1-methyl-5-bromoarundoin intermediate product shown in a chemical structural formula 2, the intermediate product is dissolved in methanol, and inorganic acid or organic acid HX is added to react to prepare the 1-methyl-5-bromoarundoin derivative shown in a chemical structural formula I.
4. Use of the 1-methyl-5-bromoarundoin derivatives according to claim 1, characterized in that: the 1-methyl-5-bromine arundoin derivative is used as an anti-plant virus agent and is a compound shown in the following chemical structural formulas I-1-I-10:
Figure FDA0002383880230000021
the plant virus is tobacco mosaic virus.
5. Use of the 1-methyl-5-bromoarundoin derivatives according to claim 1, characterized in that: the 1-methyl-5-bromoarundoin derivative is used as a plant pathogenic fungicide and is a compound shown in the following chemical structural formulas I-1 to I-10:
Figure FDA0002383880230000022
the plant pathogenic fungi include cucumber fusarium wilt, peanut brown spot, apple ring spot, tomato early blight, rice bakanae fungus, rape sclerotinia, phytophthora capsici, corn microsporum, watermelon anthracnose, potato late blight, rice sheath blight and cucumber gray mold.
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