CN110407681B - Dehydrogingerol derivative, preparation method and application thereof - Google Patents

Dehydrogingerol derivative, preparation method and application thereof Download PDF

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CN110407681B
CN110407681B CN201910741047.6A CN201910741047A CN110407681B CN 110407681 B CN110407681 B CN 110407681B CN 201910741047 A CN201910741047 A CN 201910741047A CN 110407681 B CN110407681 B CN 110407681B
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孙然锋
宋祥民
朱新月
梁财
张萌
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Abstract

The invention provides a dehydrogingerol derivative, which is shown as follows: wherein R is 1 ～R 5 Each independently selected from hydrogen, halogen, nitro, alkyl, substituted alkyl, alkoxy, or hydroxy; the substituent in the substituted alkyl is selected from one or more of halogen, nitro and hydroxyl; r is R 6 And R is R 7 Each independently selected from hydrogen, halogen, or a nitrogen-containing heterocycle; r is R 8 Selected from alkyl, alkoxy or substituted alkyl; the substituent in the substituted alkyl is selected from one or more of halogen, nitro and hydroxyl; x is selected from a heteroatom or a hydroxylamine group. The dehydrogingerol derivative has broad-spectrum plant pathogenic fungi and bacteria resisting activity and certain nematicidal activity, and is a lead compound with wide biological activity.

Description

Dehydrogingerol derivative, preparation method and application thereof
Technical Field
The invention belongs to the technical field of pesticides, and particularly relates to a dehydrogingerol derivative, a preparation method and application thereof.
Background
In the past few years, the cost of developing pesticides has increased significantly. Searching for active lead compounds from natural products, followed by structural modification or derivatization, has proven to be a successful approach to the discovery of pesticides with novel modes of action, such as pyrethroid insecticides, neonicotinoid insecticides, and strobilurin fungicides. Fresh rhizomes of ginger (zingiber officinale Rosc) are recognized by the health department of the people's republic as a plant resource for pharmaceuticals and foods. Dehydrogingerol (a, fig. 1) is one of the chemical components in ginger, which was first isolated from african soybeans in 1976. Subsequently, its pharmacological activities such as antifungal activity (MIC for Aspergillus oryzae, aspergillus flavus, aspergillus niger, aspergillus ochraceus and Fusarium oxysporum, respectively, is 755-911. Mu.M; anticancer activity (markedly increasing oxidative stress associated with hydrogen peroxide in PC12 cells), antioxidant activity (IC) 50 =57.0±2.5 μm) and anti-alzheimer's disease activity were reported separately.
However, few reports have been made on the use of dehydrozingibrone as an insecticide and/or fungicide. Meanwhile, we noted that its analogue cinnamaldehyde (B, fig. 1), which was isolated from cinnamon (Cinnamomum cassia Presl), was reported to be useful for controlling rhizoctonia solani (Rhizoctonia solani) and sclerotinia sclerotiorum (Sclerotinia homeocarpa Bennett). In 2018, fan Yujiao et al isolated five cinnamamide analogs (C, D, E, F, G, FIG. 1) from seeds of wampee with nematicidal activities of 0%,21.4%,71.5%,20.2% and 16.3% on meloidogyne incognita at 2.5mg mL-1, respectively.
Therefore, we decided to divide the dehydrogingerol molecule into two parts, namely benzene ring and ketone part (figure 1), and studied the structure-activity relationship, and found the lead of pesticide compounds with high biological activity.
Disclosure of Invention
In view of the above, the technical problem to be solved by the invention is to provide a dehydrogingerol derivative, a preparation method and application thereof, wherein the dehydrogingerol derivative has excellent broad-spectrum antifungal and bacterial activities, and particularly has special effects on Rhizoctonia solani and Rhizoctonia solani.
The invention provides a dehydrogingerol derivative, which is shown as follows:
Figure BDA0002163950270000021
wherein R is 1 ～R 5 Each independently selected from hydrogen, halogen, nitro, alkyl, substituted alkyl, alkoxy, or hydroxy; the substituent in the substituted alkyl is selected from one or more of halogen, nitro and hydroxyl;
R 6 and R is R 7 Each independently selected from hydrogen, halogen, a nitrogen-containing heterocycle, or a substituted nitrogen-containing heterocycle; the substituent in the substituted nitrogen-containing heterocycle is selected from one or more of halogen, nitro, hydroxyl, alkyl and alkoxy;
R 8 selected from alkyl, alkoxy or substituted alkyl; the substituent in the substituted alkyl is selected from one or more of halogen, nitro and hydroxyl;
x is selected from a heteroatom or a hydroxylamine group.
Preferably, said R 1 ～R 5 Each independently selected from hydrogen, halogen, nitro, C1-C10 alkyl, C1-C10 substituted alkyl, C1-C10 alkoxy or hydroxy; r is R 8 Selected from C1-C10 alkyl, C1-C10 alkoxy or C1-C10 substituted alkyl.
Preferably, said R 1 ～R 5 Each independently selected from hydrogen, halogen, nitro, C1-C5 alkyl, C1-C5 substituted alkyl, C1-C5 alkoxy or hydroxy; r is R 8 Selected from C1-C5 alkyl, C1-C5 alkoxy or C1-C5 substituted alkyl.
Preferably, said R 1 ～R 5 Each independently selected from hydrogen, halogen, nitro, C1-C3 alkyl, C1-C3 substituted alkyl, C1-C3 alkoxy or hydroxy; r is R 8 Selected from C1-C3 alkyl, C1-C3 alkoxy or C1-C3 substituted alkyl; the R is 6 And R is R 7 Each independently selected from hydrogen, halogenA ternary nitrogen-containing heterocycle, a quaternary nitrogen-containing heterocycle, a pentacyclic nitrogen-containing heterocycle, a six-membered nitrogen-containing heterocycle, a substituted ternary nitrogen-containing heterocycle, a substituted quaternary nitrogen-containing heterocycle, a substituted pentacyclic nitrogen-containing heterocycle, or a substituted six-membered nitrogen-containing heterocycle; the X is selected from N, O or hydroxylamine groups.
Preferably, said R 6 And R is R 7 Each independently selected from hydrogen, halogen or triazolyl; the X is selected from N, O or hydroxylamine groups.
Preferably, as shown in any one of the formulas (I-1) to (I-24), the formulas (II-25) to (II-26), the formula (III-27), and the formulas (IV-28) to (IV-29):
Figure BDA0002163950270000031
Figure BDA0002163950270000041
Figure BDA0002163950270000051
the invention also provides a preparation method of the dehydrogingerol derivative, which comprises the following steps:
reacting the substituted benzaldehyde shown in the formula (1) with the substituted acetone shown in the formula (2) to obtain a dehydrogingerol derivative shown in the formula (I);
or reacting the substituted benzaldehyde shown in the formula (1) with a compound shown in the formula (3) to obtain a dehydrogingerol derivative shown in the formula (II);
or reacting the dehydrogingerol derivative shown in the formula (II) with substituted silane shown in the formula (4) to obtain the dehydrogingerol derivative shown in the formula (III);
or reacting the dehydrogingerol derivative shown in the formula (I) with hydroxylamine hydrochloride to obtain the dehydrogingerol derivative shown in the formula (IV);
Figure BDA0002163950270000052
Figure BDA0002163950270000061
R 1 ～R 5 each independently selected from hydrogen, halogen, nitro, alkyl, substituted alkyl, alkoxy, or hydroxy; the substituent in the substituted alkyl is selected from one or more of halogen, nitro and hydroxyl;
R 8 selected from alkyl, alkoxy or substituted alkyl; the substituent in the substituted alkyl is selected from one or more of halogen, nitro and hydroxyl;
R 9 selected from alkyl or substituted alkyl;
R 10 selected from alkyl or substituted alkyl.
The invention also provides application of the dehydrogingerol derivative in preparing pesticides for resisting one or more of plant pathogenic fungi, bacterial diseases and nematicides.
Preferably, the phytopathogenic fungi are selected from one or more of the group consisting of pyraclostrobin, alternaria, photinia mangiferum, anthrax, gibberella, trichoderma, fusarium, sclerotinia, alternaria, rhizoctonia and phytophthora; the bacterial disease is selected from one or more of xanthomonas, bacterial leaf blight of rice, bacterial soft rot, bacterial wilt and canker.
Preferably, the anthracnose fungus is selected from one or more of banana anthracnose, colletotrichum gloeosporioides and wax gourd anthracnose; the gibberella fungus is selected from gibberella zeae; the trichoderma fungi are selected from the group consisting of trichoderma koningii and/or trichoderma longibrachiatum; the fusarium fungi are selected from one or more of fusarium moniliforme, gibberella wheat and fusarium wilt; the sclerotinia fungus is selected from sclerotinia sclerotiorum; the Alternaria fungus is selected from Alternaria solani; the rhizoctonia fungi is selected from rhizoctonia cerealis and/or Rhizoctonia oryzae; the phytophthora is selected from phytophthora nicotianae; the genus Botrytis is selected from Botrytis cinerea and/or Botrytis cinerea.
The invention provides a dehydrogingerol derivative which has broad-spectrum activity against plant pathogenic fungi and bacteria and certain nematicidal activity, and is a lead compound with wide biological activity.
Experiments show that the series of dehydrogingerol derivatives provided by the invention have excellent broad-spectrum plant pathogenic fungi and bacteria resisting activity and southern root knot nematode killing activity. The target compounds I-13, I-16, I-18, I-19 and III-27 were present in 50. Mu.g mL -1 Exhibits a more excellent broad-spectrum antifungal activity than pyrimethanil and azoxystrobin; at 250 μg mL -1 When the nematicidal composition is used, the nematicidal composition also has certain nematicidal activity on two-instar larvae of the meloidogyne incognita, and the nematicidal activity is 100%, 74.8%, 100%, 68.6% and 64.4% respectively. In particular, the target compound III-27 is superior to azoxystrobin in the living body control effect of rice sheath blight disease and cucumber gray mold, and in addition, the in-vitro and living body control effects of the target compound III-27 on rice bacterial wilt caused by xanthomonas are superior to those of the Zhongshengmycin. In conclusion, the broad-spectrum anti-plant pathogenic fungi and bacterial activities have certain nematicidal activities, and the dehydrogingerol derivative is a lead compound with wide biological activities. The target compounds I-13, I-16, I-18, I-19 and III-27 have antibacterial and nematicidal activities, so that the target compounds are worthy of further optimization and derivatization, and particularly the target compound III-27 has great potential to be developed as pesticides for killing nematodes and resisting plant pathogenic fungi and bacteria for agricultural production.
Drawings
FIG. 1 is a design concept diagram of the dehydrogingerol derivative provided by the invention.
Detailed Description
The technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention, and it is apparent that the described embodiments are only some embodiments of the present invention, not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
The invention provides a dehydrogingerol derivative, which is shown as follows:
Figure BDA0002163950270000071
wherein R is 1 ～R 5 Each independently is hydrogen, halogen, nitro, alkyl, substituted alkyl, alkoxy or hydroxy, preferably hydrogen, halogen, nitro, C1-C10 alkyl, C1-C10 substituted alkyl, C1-C10 alkoxy or hydroxy, more preferably hydrogen, halogen, nitro, C1-C8 alkyl, C1-C8 substituted alkyl, C1-C8 alkoxy or hydroxy, still more preferably hydrogen, halogen, nitro, C1-C5 alkyl, C1-C5 substituted alkyl, C1-C5 alkoxy or hydroxy, still more preferably hydrogen, halogen, nitro, C1-C3 alkyl, C1-C3 substituted alkyl, C1-C3 alkoxy or hydroxy, still more preferably hydrogen, halogen, nitro, C1-C2 alkyl, C1-C2 substituted alkyl, C1-C2 alkoxy or hydroxy, most preferably hydrogen, halogen, nitro, methyl, methoxy or hydroxy; the substituent in the substituted alkyl is selected from one or more of halogen, nitro and hydroxyl; the halogen is preferably fluorine, chlorine or bromine; in the present invention, the R 1 ～R 5 Preferably at least one is other than hydrogen, more preferably 1 to 4 are other than hydrogen, still more preferably 1 to 3 are other than hydrogen, and most preferably 2 are other than hydrogen.
R 6 And R is R 7 Each independently is hydrogen, halogen, a nitrogen-containing heterocycle, or a substituted nitrogen-containing heterocycle, more preferably hydrogen, halogen, a ternary nitrogen-containing heterocycle, a quaternary nitrogen-containing heterocycle, a pentacyclic nitrogen-containing heterocycle, a hexa-membered nitrogen-containing heterocycle, a substituted ternary nitrogen-containing heterocycle, a substituted quaternary nitrogen-containing heterocycle, a substituted pentacyclic nitrogen-containing heterocycle, a substituted hexa-membered nitrogen-containing heterocycle; the number of nitrogen atoms in the nitrogen-containing heterocycle is preferably 1 to 5, more preferably 2 to 4, still more preferably 3; the substituent in the substituted nitrogen-containing heterocycle is one or more of halogen, nitro, hydroxyl, alkyl or alkoxy, preferablyHalogen, nitro, hydroxyl, one or more of C1-C10 alkyl and C1-C10 alkoxy, more preferably halogen, nitro, hydroxyl, one or more of C1-C6 alkyl and C1-C6 alkoxy, still more preferably halogen, nitro, hydroxyl, one or more of C1-C3 alkyl and C1-C3 alkoxy, most preferably halogen, nitro, hydroxyl, one or more of C1-C2 alkyl and C1-C2 alkoxy; in the present invention, the R 6 And R is R 7 Most preferably each independently is hydrogen, halogen or triazolyl; the halogen is preferably fluorine, chlorine or bromine;
R 8 alkyl, alkoxy or substituted alkyl, preferably C1-C10 alkyl, C1-C10 alkoxy or C1-C10 substituted alkyl, more preferably C1-C8 alkyl, C1-C8 alkoxy or C1-C8 substituted alkyl, still more preferably C1-C6 alkyl, C1-C6 alkoxy or C1-C6 substituted alkyl, still more preferably C1-C4 alkyl, C1-C4 alkoxy or C1-C4 substituted alkyl, still more preferably C1-C3 alkyl, C1-C3 alkoxy or C1-C3 substituted alkyl, still more preferably C1-C2 alkyl, C1-C2 alkoxy or C1-C2 substituted alkyl; the substituent in the substituted alkyl is one or more of halogen, nitro and hydroxyl; the halogen is preferably fluorine, chlorine or bromine; in the present invention, the R 8 Most preferably methyl, methoxy or trifluoromethyl;
x is a heteroatom or a hydroxylamine group, preferably N, O or a hydroxylamine group.
In the present invention, the dehydrogingerol derivative is most preferably one of the following formulas:
Figure BDA0002163950270000091
Figure BDA0002163950270000101
Figure BDA0002163950270000111
the invention also provides a preparation method of the dehydrogingerol derivative, which comprises the following steps:
reacting the substituted benzaldehyde shown in the formula (1) with the substituted acetone shown in the formula (2) to obtain the dehydrogingerol derivative shown in the formula (I).
Figure BDA0002163950270000112
Wherein R is 1 ～R 5 Each independently selected from hydrogen, halogen, nitro, alkyl, substituted alkyl, alkoxy, or hydroxy; the substituent in the substituted alkyl is selected from one or more of halogen, nitro and hydroxyl;
R 8 selected from alkyl, alkoxy or substituted alkyl; the substituent in the substituted alkyl is selected from one or more of halogen, nitro and hydroxyl.
In the present invention, the R 1 ～R 5 R is R 8 All are the same as described above, and are not repeated here.
The substituted benzaldehyde shown in the formula (1) and the substituted acetone shown in the formula (2) are preferably performed in the presence of a catalyst; the catalyst is preferably obtained by reacting morpholine and trifluoroacetic acid in an organic solvent; the organic solvent is preferably one or more of dichloromethane, tetrahydrofuran, diethyl ether, methyl tertiary butyl ether, ethanol, DMF (N, N-dimethylformamide) and ethylene glycol diethyl ether; the substituted benzaldehyde shown in the formula (1) and the substituted acetone shown in the formula (2) are preferably performed in an organic solvent; the organic solvent is preferably one or more of dichloromethane, tetrahydrofuran, diethyl ether, methyl tert-butyl ether, ethanol, DMF (N, N-dimethylformamide) and ethylene glycol diethyl ether.
The reaction has the following reaction formula:
Figure BDA0002163950270000113
or reacting the substituted benzaldehyde shown in the formula (1) with a compound shown in the formula (3) to obtain a dehydrogingerol derivative shown in the formula (II);
Figure BDA0002163950270000121
wherein R is 1 ～R 5 Each independently selected from hydrogen, halogen, nitro, alkyl, substituted alkyl, alkoxy, or hydroxy; the substituent in the substituted alkyl is selected from one or more of halogen, nitro and hydroxyl;
R 9 selected from alkyl or substituted alkyl, preferably C1-C10 alkyl or C1-C10 substituted alkyl, more preferably C1-C8 alkyl or C1-C8 substituted alkyl, still more preferably C1-C6 alkyl or C1-C6 substituted alkyl, still more preferably C1-C4 alkyl or C1-C4 substituted alkyl, still more preferably C1-C3 alkyl or C1-C3 substituted alkyl, still more preferably C1-C2 alkyl or C1-C2 substituted alkyl; the substituent in the substituted alkyl is selected from one or more of halogen, nitro and hydroxyl.
In the present invention, the R 1 ～R 5 All are the same as described above, and are not repeated here.
The substituted benzaldehyde shown in the formula (1) and the compound shown in the formula (3) are preferably reacted in an organic solvent containing organic base; the organic base is preferably sodium methoxide; the organic solvent is preferably one or more of dichloromethane, tetrahydrofuran, diethyl ether, methyl tert-butyl ether, ethanol, DMF (N, N-dimethylformamide) and ethylene glycol diethyl ether.
The reaction has the following reaction formula:
Figure BDA0002163950270000122
or reacting the dehydrogingerol derivative shown in the formula (II) with substituted silane shown in the formula (4) to obtain the dehydrogingerol derivative shown in the formula (III);
Figure BDA0002163950270000123
wherein R is 1 ～R 5 Each independently selected from hydrogen, halogen, nitro, alkyl, substituted alkyl, alkoxy, or hydroxy; the substituent in the substituted alkyl is selected from one or more of halogen, nitro and hydroxyl;
R 10 selected from alkyl or substituted alkyl, preferably C1-C10 alkyl or C1-C10 substituted alkyl, more preferably C1-C8 alkyl or C1-C8 substituted alkyl, still more preferably C1-C6 alkyl or C1-C6 substituted alkyl, still more preferably C1-C4 alkyl or C1-C4 substituted alkyl, still more preferably C1-C3 alkyl or C1-C3 substituted alkyl, still more preferably C1-C2 alkyl or C1-C2 substituted alkyl; the substituent in the substituted alkyl is selected from one or more of halogen, nitro and hydroxyl.
In the present invention, the R 1 ～R 5 All are the same as described above, and are not repeated here.
The dehydrogingerol derivative shown in the formula (II) and the substituted silane shown in the formula (4) are preferably reacted in an organic solvent containing organic alkali; the organic base is preferably cesium fluoride; the organic solvent is preferably one or more of dichloromethane, tetrahydrofuran, diethyl ether, methyl tert-butyl ether, ethanol, DMF (N, N-dimethylformamide) and ethylene glycol diethyl ether.
The reaction has the following reaction formula:
Figure BDA0002163950270000131
or reacting the dehydrogingerol derivative shown in the formula (I) with hydroxylamine hydrochloride to obtain the dehydrogingerol derivative shown in the formula (IV).
Figure BDA0002163950270000132
The dehydrogingerol derivative shown in the formula (I) and hydroxylamine hydrochloride are preferably reacted in an organic solvent containing organic alkali; the organic base is preferably pyridine; the organic solvent is preferably one or more of dichloromethane, tetrahydrofuran, diethyl ether, methyl tert-butyl ether, ethanol, DMF (N, N-dimethylformamide) and ethylene glycol diethyl ether.
The reaction has the following reaction formula:
Figure BDA0002163950270000141
the invention also provides application of the dehydrogingerol derivative in preparing pesticides for resisting plant pathogenic fungi and/or bacteria.
The plant pathogenic fungi are preferably one or more of Pitaya ulcer germs, apriona, mango Di-rot germs, anthrax fungi, gibberella fungi, fusarium fungi, sclerotinia fungi, alternaria fungi, rhizoctonia fungi and Phytophthora fungi; the anthracnose fungi are preferably one or more of banana anthracnose germs, colletotrichum gloeosporioides and wax gourd anthracnose germs; the gibberella fungus is preferably gibberella zeae; the fungus of the genus Pediophora is preferably Pediophora tea brown spot and/or Pediophora longifolia; the fusarium fungi are preferably one or more of fusarium moniliforme, gibberella wheat and fusarium wilt; the sclerotinia fungus is preferably sclerotinia sclerotiorum; the alternaria fungus is preferably alternaria solani; the rhizoctonia fungi are preferably rhizoctonia cerealis and/or Rhizoctonia oryzae; the phytophthora is preferably phytophthora nicotianae; the genus Botrytis is preferably Botrytis cinerea and/or Botrytis cinerea.
The bacterial disease is selected from one or more of xanthomonas, bacterial leaf blight of rice, bacterial soft rot, bacterial wilt and canker.
The invention also provides application of the dehydrozingibnone derivative in preparing nematicides.
In order to further illustrate the present invention, the following examples are provided to describe in detail a dehydrozingibnone derivative, a preparation method and an application thereof.
The reagents used in the examples below are all commercially available.
Example 1: preparation of target Compounds I-1 to I-24
The morpholine (1 mmol) is dissolved in diethyl ether (10 mL), the temperature is reduced to 0 ℃ by ice bath, trifluoroacetic acid (1 mmol) is sucked and mixed in 5mL of diethyl ether solution, then the diethyl ether solution of the trifluoroacetic acid is slowly added dropwise into the morpholine diethyl ether solution, the reaction is kept for 1h, the temperature is restored to room temperature, the solvent is rapidly filtered off by a Buchner funnel under reduced pressure, the obtained white solid is washed by diethyl ether (20 mL) and is repeatedly used for 3 times, and the obtained white solid is used as a catalyst for the next reaction after being dried. The catalyst (1 mmol) prepared was dissolved in 10mL of acetone solution, 3, 4-dimethoxybenzaldehyde (5 mmol), and after 48h of reflux reaction, cooled to room temperature, diluted with 20mL of ethyl acetate, and taken up in saturated NaHCO respectively 3 The solution was washed with brine (20 ml×3), the solution was separated, and the organic phase was dried over anhydrous magnesium sulfate, the solvent was removed by rotary evaporator under reduced pressure to give a crude product, which was separated by column chromatography (petroleum ether: ethyl acetate=10:1) to give 0.55g (2.65 mmol) of a white solid, yield 53%, m.p 85-86 ℃.
Analysis by nuclear magnetic resonance gave the result: 1 H NMR(500MHz,Chloroform-d)δ7.45(d,J＝16.2Hz,1H),7.11(dd,J＝8.3,1.9Hz,1H),7.06(d,J＝1.9Hz,1H),6.87(d,J＝8.3Hz,1H),6.59(d,J＝16.2Hz,1H),3.91(s,6H),2.36(s,3H)。 13 C NMR(125MHz,Chloroform-d)δ198.3,151.4,149.3,143.5,127.3,125.3,123.0,111.1,109.6,56.0,55.9,27.4。
analysis by Mass Spectrometry gives results HRMS (ESI): m/z calcd for C 12 H 14 O 3 [M+H] + :207.1016，found 207.1018。
A method for synthesizing a reference target compound I-1 from I-2 to I-24 of the target compound.
Target compound I-2: yellow solid, yield 85%, m.p. 81-82 ℃. 1 H NMR(500MHz,Chloroform-d)δ7.64(d,J＝16.6Hz,1H),7.54(td,J＝7.6,1.7Hz,1H),7.37–7.32(m,1H),7.17–7.13(m,1H),7.08(ddd,J＝10.7,8.3,1.2Hz,1H),6.75(d,J＝16.4Hz,1H),2.37(s,3H). 13 C NMR(125MHz,Chloroform-d)δ198.3,160.3,135.6,132.0,131.9,129.2,129.2,128.7,128.7,124.6,124.5,122.5,122.4,116.3,116.1,27.5.HRMS(ESI):m/z calcd for C 10 H 9 FO[M+H] + :165.0710,found 165.0714。
Target compound I-3: brown liquid, 83% yield. 1 H NMR(500MHz,Chloroform-d)δ7.93(d,J＝16.4Hz,1H),7.63(dd,J＝7.5,1.9Hz,1H),7.42(dd,J＝7.8,1.4Hz,1H),7.33(dd,J＝7.4,1.9Hz,1H),7.31–7.29(m,1H),6.66(d,J＝16.4Hz,1H),2.42(s,3H).HRMS(ESI):m/z calcd for C 10 H 9 ClO[M+H] + :181.0415,found 181.0413。
Target compound I-4: yellow liquid, 69% yield. 1 H NMR(500MHz,Chloroform-d)δ7.88(d,J＝16.3Hz,1H),7.61(d,J＝8.0Hz,2H),7.33(t,J＝7.4Hz,1H),7.24(td,J＝7.7,1.6Hz,1H),6.61(d,J＝16.3Hz,1H),2.42(s,3H). 13 C NMR(125MHz,Chloroform-d)δ198.3,141.9,134.4,133.5,131.4,129.8,127.8,127.8,125.6,27.2.HRMS(ESI):m/z calcd for C 10 H 9 BrO[M+H] + :224.9910,found 224.9915。
Target compound I-5: brown liquid, 53% yield. 1 H NMR(500MHz,Chloroform-d)δ8.07(d,J＝8.4Hz,1H),7.98(d,J＝16.2Hz,1H),7.68–7.63(m,2H),7.56(ddd,J＝8.6,7.0,2.0Hz,1H),6.57(d,J＝16.2Hz,1H),2.43(s,3H).HRMS(ESI):m/z calcd for C 10 H 9 NO 3 [M+H] + :192.0655,found 192.0651。
Target compound I-6: brown liquid, 75% yield. 1 H NMR(500MHz,Chloroform-d)δ7.88(d,J＝16.2Hz,1H),7.72(d,J＝7.9Hz,2H),7.58(t,J＝7.6Hz,1H),7.49(t,J＝7.5Hz,1H),6.64(d,J＝16.1Hz,1H),2.41(s,3H). 13 C NMR(125MHz,Chloroform-d)δ198.2,139.0,138.9,132.2,131.2,129.8,127.8,126.3,126.2,77.2,27.1.HRMS(ESI):m/z calcd for C 11 H 9 F 3 O[M+H] + :215.0678,found 216.0675。
Target compound I-7: pale yellow liquid, 82% yield. 1 H NMR(500MHz,Chloroform-d)δ7.82(d,J＝16.1Hz,1H),7.57(d,J＝7.6Hz,1H),7.29(t,J＝7.3Hz,1H),7.22(t,J＝7.4Hz,2H),6.65(d,J＝16.1Hz,1H),2.45(s,3H),2.39(s,3H). 13 C NMR(125MHz,Chloroform-d)δ198.4,140.9,137.9,133.4,130.9,130.2,128.1,126.4,126.4,27.8,19.8.HRMS(ESI):m/z calcd for C 11 H 12 O[M+H] + :161.0961,found 161.0959。
Target compound I-8: pale yellow solid, yield 76%, m.p. 48-50 ℃. 1 H NMR(500MHz,Chloroform-d)δ7.91–7.85(m,1H),7.53(dd,J＝7.7,1.6Hz,1H),7.39–7.33(m,1H),6.96(t,J＝7.5Hz,1H),6.91(d,J＝8.3Hz,1H),6.74(d,J＝16.5Hz,1H),3.89(s,3H),2.38(s,3H). 13 C NMR(125MHz,Chloroform-d)δ199.1,158.3,138.7,131.8,128.3,127.8,123.3,120.8,111.1,55.5,27.2.HRMS(ESI):m/z calcd for C 11 H 12 O 2 [M+H]+:177.0910,found 177.0913。
Target compound I-9: pale yellow solid, yield 92%, m.p. 136-138 ℃. 1 H NMR(500MHz,Chloroform-d)δ7.85(d,J＝16.4Hz,1H),7.47(dd,J＝8.0,1.4Hz,1H),7.28–7.24(m,1H),7.04(d,J＝16.4Hz,1H),6.97–6.90(m,2H),2.43(s,3H). 13 C NMR(125MHz,Chloroform-d)δ201.1,156.0,140.7,131.9,129.7,127.8,121.5,120.7,116.6,26.9.HRMS(ESI):m/z calcd for C 10 H 10 O 2 [M+H] + :163.0754,found 163.0752。
Target compound I-10: yellow liquid, 82% yield. 1 H NMR(500MHz,Chloroform-d)δ7.51(s,1H),7.42(d,J＝16.3Hz,1H),7.40–7.26(m,3H),6.69(d,J＝16.3Hz,1H),2.37(s,3H).HRMS(ESI):m/z calcd for C 10 H 9 ClO[M+H] + :181.0415,found 181.0417。
Target compound I-11: white solid, yield 82%, m.p. 49-51 ℃. 1 H NMR(500MHz,Chloroform-d)δ7.49–7.46(m,2H),7.43(s,1H),7.39–7.34(m,2H),6.68(d,J＝16.3Hz,1H),2.37(s,3H).HRMS(ESI):m/z calcd for C 10 H 9 ClO[M+H] + :181.0415,found 181.0421。
Target compound I-12: brown liquid, 83% yield. 1 H NMR(500MHz,Chloroform-d)δ7.54(dd,J＝6.6,3.2Hz,2H),7.50(s,1H),7.41–7.37(m,3H),6.72(d,J＝16.3Hz,1H),2.38(s,3H).HRMS(ESI):m/z calcd for C 10 H 10 O[M+H] + :147.0804,found 147.0801。
Target compound I-13: yellow solid, yield 79%, m.p. 78-79 ℃. 1 H NMR(500MHz,Chloroform-d)δ7.90(d,J＝16.3Hz,1H),7.50(ddd,J＝18.1,7.9,1.3Hz,2H),7.23(t,J＝7.9Hz,1H),6.63(d,J＝16.3Hz,1H),2.41(s,3H). 13 C NMR(125MHz,Chloroform-d)δ198.0,139.1,135.1,134.0,133.1,131.7,130.6,127.5,125.7,27.4.HRMS(ESI):m/z calcd for C 10 H 8 Cl 2 O[M+H] + :215.0025,found 215.0027。
Target compound I-14: yellow solid, yield 89%, m.p. 80-81 ℃. 1 H NMR(500MHz,Chloroform-d)δ7.84(d,J＝16.3Hz,1H),7.56(d,J＝8.5Hz,1H),7.44(d,J＝2.0Hz,1H),7.29–7.26(m,1H),6.64(d,J＝16.3Hz,1H),2.40(s,3H). 13 C NMR(125MHz,Chloroform-d)δ198.0,137.9,136.6,135.6,131.3,130.0,129.8,128.3,127.7,27.4.HRMS(ESI):m/z calcd for C 10 H 8 Cl 2 O[M+Na] + :236.9844,found 236.9848。
Target compound I-15: white solid, yield 99%, m.p 83-84 ℃. 1 H NMR(500MHz,Chloroform-d)δ7.81(d,J＝16.3Hz,1H),7.59(d,J＝2.4Hz,1H),7.35(d,J＝8.6Hz,1H),7.28(dd,J＝8.6,2.5Hz,1H),6.65(d,J＝16.3Hz,1H),2.41(s,3H). 13 C NMR(125MHz,Chloroform-d)δ197.7,137.7,137.7,134.2,133.2,131.2,131.0,130.3,127.4,27.6.HRMS(ESI):m/z calcd for C 10 H 8 Cl 2 O[M+H] + :215.0025,found 215.0022。
Target compound I-16: yellow liquid, 79% yield. 1 H NMR(500MHz,Chloroform-d)δ7.59(d,J＝16.7Hz,1H),7.36(d,J＝8.1Hz,2H),7.19(t,J＝8.1Hz,1H),6.80(d,J＝16.7Hz,1H),2.41(s,3H). 13 C NMR(125MHz,Chloroform-d)δ198.1,136.8,135.0,134.9,132.1,129.9,128.8,27.6.HRMS(ESI):m/z calcd for C 10 H 8 Cl 2 O[M+Na] + :236.9844,found 236.9847。
Target compound I-17: yellow solid, yield 92%, m.p. 77-79 ℃. 1 H NMR(500MHz,Chloroform-d)δ7.85(d,J＝16.3Hz,1H),7.63(dd,J＝8.8,6.0Hz,1H),7.17(dd,J＝8.3,2.6Hz,1H),7.02(td,J＝8.3,2.6Hz,1H),6.61(d,J＝16.3Hz,1H),2.40(s,3H). 13 C NMR(125MHz,Chloroform-d)δ198.0,164.4,138.0,129.3,129.3,129.1,128.9,128.9,117.6,117.4,115.0,114.8,27.3.HRMS(ESI):m/z calcd for C 10 H 8 ClFO[M+H] + :199.0320,found 199.0321。
Target compound I-18: brown liquid, yield 90%. 1 H NMR(500MHz,Chloroform-d)δ7.71(d,J＝16.6Hz,1H),7.25(dd,J＝3.8,1.6Hz,2H),7.06–7.01(m,1H),6.95(d,J＝16.6Hz,1H),2.39(s,3H). 13 C NMR(125MHz,Chloroform-d)δ198.5,160.9,136.1,133.4,133.3,133.3,130.9,130.8,126.0,126.0,121.7,121.6,115.1,114.9,77.3,27.8.HRMS(ESI):m/z calcd for C 10 H 8 ClFO[M+Na] + :221.0140,found 221.0137。
Target compound I-19: yellow liquid, 75% yield. 1 H NMR(500MHz,Chloroform-d)δ7.52(d,J＝16.6Hz,1H),7.38(d,J＝8.7Hz,1H),7.31(d,J＝8.7Hz,1H),6.72(d,J＝16.6Hz,1H),2.42(s,3H). 13 C NMR(125MHz,Chloroform-d)δ197.7,136.7,135.5,134.2,133.2,132.7,132.5,130.5,129.0,27.8.HRMS(ESI):m/z calcd for C 10 H 7 Cl 3 O[M+H] + :248.9635,found 248.9639。
Target compound I-20: pale yellow solid, yield 72%, m.p. 101-103 ℃. 1 H NMR(500MHz,Chloroform-d)δ7.52(d,J＝16.6Hz,1H),7.39(s,2H),6.80(d,J＝16.6Hz,1H),2.41(s,3H). 13 C NMR(125MHz,Chloroform-d)δ197.8,135.7,135.5,135.1,135.0,130.7,128.9,27.8.HRMS(ESI):m/z calcd for C 10 H 7 Cl 3 O[M+Na] + :270.9455,found 270.9457。
Target compound I-21: yellow liquid, 79% yield. 1 H NMR(500MHz,Chloroform-d)δ7.46(d,J＝16.6Hz,1H),7.00(d,J＝16.6Hz,1H),2.39(s,3H). 13 C NMR(125MHz,Chloroform-d)δ197.4,146.7,144.6,138.8,133.6,133.6,133.5,133.5,133.5,133.4,126.4,126.4,126.4,110.0,110.0,28.4.HRMS(ESI):m/z calcd for C 10 H 5 F 5 O[M+Na] + :259.0153,found 259.0159。
Target compound I-22: pale yellow solid, yield 78%, m.p. 92-94 ℃. 1 H NMR(500MHz,Chloroform-d)δ7.87(d,J＝16.3Hz,1H),7.56(d,J＝8.5Hz,1H),7.44(d,J＝2.1Hz,1H),7.29–7.25(m,1H),6.67(d,J＝16.3Hz,1H),2.73(q,J＝7.3Hz,2H),1.17(t,J＝7.3Hz,3H). 13 C NMR(125MHz,Chloroform-d)δ200.5,136.7,136.4,135.7,131.5,130.0,128.8,128.3,127.6,33.9,8.1.HRMS(ESI):m/z calcd for C 11 H 10 Cl 2 O[M+H]+:229.0181,found 229.0186。
Target compound I-23: pale yellow solid, yield 68%, m.p. 96-97 ℃. 1 H NMR(500MHz,Chloroform-d)δ7.86(d,J＝16.3Hz,1H),7.56(d,J＝8.5Hz,1H),7.43(d,J＝2.1Hz,1H),7.26(dd,J＝8.5,2.1Hz,1H),6.66(d,J＝16.3Hz,1H),2.67(t,J＝7.3Hz,2H),1.71(h,J＝7.4Hz,2H),0.98(t,J＝7.4Hz,3H). 13 C NMR(125MHz,Chloroform-d)δ200.1,136.8,136.4,135.7,131.5,130.0,129.1,128.3,127.6,42.6,17.7,13.8.HRMS(ESI):m/z calcd for C 12 H 12 Cl 2 O[M+H] + :243.0338,found 243.0333。
Target compound I-24: pale yellow solid, yield 92%, m.p. 103-104 ℃. 1 H NMR(500MHz,Chloroform-d)δ7.98(d,J＝15.6Hz,1H),7.58(d,J＝8.5Hz,1H),7.43(d,J＝2.1Hz,1H),7.28–7.23(m,1H),7.08(d,J＝15.6Hz,1H),1.23(s,9H). 13 C NMR(125MHz,Chloroform-d)δ204.0,137.9,136.5,136.4,132.3,130.5,128.8,127.8,124.0,43.7,26.6.HRMS(ESI):m/z calcd for C 13 H 14 Cl 2 O[M+H] + :257.0494,found 257.0488。
Example 2: preparation of target Compounds II-25, II-26
At 0deg.C, trimethyl phosphonoacetate (2 mmol) and 2, 4-dichlorobenzaldehyde (2.1 mmol) were dissolved in 10mL DMF (N, N-dimethylformamide), followed by slow dropwise addition of 28% sodium methoxide methanol solution (2 mmol), reaction was carried out for 2h at a constant temperature, diluted with 20mL distilled water, extraction with ethyl acetate (20 m)L×3), the organic phase was purified over anhydrous Na 2 SO 4 After drying, the solvent was removed by spin-drying under reduced pressure to give a crude product, which was separated by column chromatography (petroleum ether: ethyl acetate=20:1) to give the desired compound II-25 as a white solid in an amount of 0.45g (1.93 mmol) in a yield of 92%, m.p 113-115 ℃. 1 H NMR(500MHz,Chloroform-d)δ8.01(d,J＝16.0Hz,1H),7.55(d,J＝8.5Hz,1H),7.44(d,J＝2.1Hz,1H),7.28–7.25(m,1H),6.41(d,J＝16.0Hz,1H),3.82(s,3H). 13 C NMR(125MHz,Chloroform-d)δ166.7,139.4,136.4,135.5,131.3,130.0,128.3,127.6,120.9,51.9.HRMS(ESI):m/z calcd for C 10 H 8 Cl 2 O 2 [M+H] + :230.9974,found 230.9976。
The synthesis method of the target product II-26 is the same as that of the compound II-25: white solid, yield 95%, m.p 122-125 ℃. 1 H NMR(500MHz,Chloroform-d)δ7.72(d,J＝16.4Hz,1H),7.38(d,J＝8.7Hz,1H),7.31(d,J＝8.7Hz,1H),6.51(d,J＝16.4Hz,1H),3.84(s,3H). 13 C NMR(125MHz,Chloroform-d)δ166.3,138.3,134.0,133.2,132.7,132.5,130.4,129.0,127.3,52.1.HRMS(ESI):m/z calcd for C 10 H 7 Cl 3 O 2 [M+H] + :264.9584,found 264.9589。
Example 3: preparation of target Compound III-27
Compound II-25 (1 mmol) and 1.25mmol TMS-CF 3 (trifluoromethyl trimethylsilane) was dissolved in 20mL of ethylene glycol diethyl ether, csF (0.01 mmol) was added, and after 5 hours of reaction at room temperature, 4M HCl solution (4 mL) was added dropwise, the reaction was continued at room temperature for 3 hours, 20mL of distilled water was diluted, ethyl acetate was extracted (20 mL. Times.3), the organic phase was dried over anhydrous magnesium sulfate, the solvent was removed by rotary evaporator under reduced pressure to give a crude product, which was separated by column chromatography (petroleum ether: ethyl acetate=10:1) to give 0.22g (0.82 mmol) of a white solid, yield 82%, m.p 76-78 ℃. 1 H NMR(500MHz,Chloroform-d)δ8.32(d,J＝15.9Hz,1H),7.68(d,J＝8.5Hz,1H),7.51(d,J＝2.1Hz,1H),7.33(dd,J＝8.5,2.0Hz,1H),6.99(d,J＝16.0Hz,1H). 13 C NMR(125MHz,Chloroform-d)δ179.8,179.5,144.3,138.5,137.1,130.5,130.1,128.7,127.9,119.1.HRMS(ESI):m/z calcd for C 10 H 5 Cl 2 F 3 O[M+Na] + :290.9562,found 290.9564。
Example 4: preparation of target Compounds IV-28, IV-29
Synthesis of the target Compound IV-28 1mmol of Compound I-14 and 2.5mmol of pyridine were dissolved in 10mL of ethanol, 1.5mmol of hydroxylamine hydrochloride was added, after reacting at 60℃for 1 hour, 5mL of distilled water was added for quenching, extraction with ethyl acetate, washing with saturated brine, drying the organic phase over anhydrous magnesium sulfate, and spin-drying the solvent under reduced pressure with a rotary evaporator to give a crude product, which was separated by column chromatography (Petroleum ether: ethyl acetate=20:1) to give 0.20g (0.85 mmol) of a white solid with a yield of 85%, m.p 157-158 ℃. 1 H NMR(500MHz,Chloroform-d)δ7.55(d,J＝8.5Hz,1H),7.41(d,J＝2.1Hz,1H),7.26–7.22(m,2H),6.81(d,J＝16.5Hz,1H),2.21(s,1H),2.18(s,3H). 13 C NMR(125MHz,Chloroform-d)δ156.8,134.6,134.2,132.9,129.7,128.6,128.2,127.5,127.5,9.8.HRMS(ESI):m/z calcd for C 10 H 9 Cl 2 NO[M+H] + :230.0134,found 230.0137。
The synthesis method of the target product IV-29 is the same as that of the compound IV-28: white solid, yield 88%, m.p177-179 ℃. 1 H NMR(500MHz,Chloroform-d)δ7.75(d,J＝16.9Hz,1H),7.57(d,J＝8.5Hz,1H),7.41(d,J＝2.1Hz,1H),7.27–7.23(m,1H),6.72(d,J＝16.9Hz,1H),1.28(s,9H),1.26(s,1H). 13 C NMR(125MHz,Chloroform-d)δ160.9,134.6,134.5,133.9,133.7,129.6,127.5,127.4,119.4,37.5,28.8.HRMS(ESI):m/z calcd for C 13 H 15 Cl 2 NO[M+H] + :272.0603,found 272.0604。
Example 5: preparation of target Compound A
Vanillin (2 mmol) and 2mL acetone are dissolved in 5mL ethanol, 5mL of 5% aqueous naoh solution is added, after reaction for 1.5h at room temperature, 20mL distilled water is added for dilution, ice bath cooling to 0 ℃, ph=7 is adjusted with 2M HCl, ethyl acetate is extracted, the organic phase is washed with saturated brine, dried over anhydrous magnesium sulfate, the solvent is removed under reduced pressure to obtain the crude product, which is separated by column chromatography (petroleum ether: ethyl acetate=8:1) to obtain 0.25g (1.28 mmol) of pale yellow solid with a yield of 64%, m.p 129-130 ℃. 1 H NMR(500MHz,Chloroform-d)δ7.45(d,J＝16.2Hz,1H),7.09(dd,J＝8.2,1.9Hz,1H),7.06(d,J＝1.9Hz,1H),6.93(d,J＝8.2Hz,1H),6.59(d,J＝16.2Hz,1H),5.90(s,1H),3.94(s,3H),2.37(s,3H). 13 C NMR(125MHz,Chloroform-d)δ198.5,148.3,146.9,143.8,126.9,124.9,123.5,114.9,109.4,56.0,27.3.HRMS(ESI):m/z calcd for C 11 H 12 O 3 [M+H] + :193.0859,found 193.0855。
Example 6: the activity against plant pathogenic fungi was determined as follows:
test strain: pitaya canker (Neoscytalidium dimidiatum), rhizoctonia cerealis (Botryosphaeria dothidea), banana anthracnose (Colletotrichum musae), corn Gibberella zeae (Gibberella zeae), mucor pulmonale (Pestalotipsis guepinii), fusarium moniliformis (Fusarium moniliforme), sclerotinia sclerotiorum (Sclerotinia sclerotiorum), alternaria solani (Alternaria solani), puccinia mangostana (Botryodiip-lodia theobromae), fusarium banana (Fusarium oxysporum), rhizoctonia cerealis (Rhizoctonia cerealis), colletotrichum glomerrill (Colletotrichum gloeosporioides), white gourd anthracnose (Colletotrichum orbiculare), phytophthora nicotianae (Phytophthora nicotianae), mucor longifolius (Pestalotiopsis longiseta), rhizoctonia solani (Rhizoctonia solani), wheat red mould (Fusarium graminearum), and Botrytis cinerea (Botrytis cinerea)
The hypha growth rate method is adopted. Dissolving a sample to be tested with a proper amount of acetone, diluting the solution to a required concentration with an aqueous solution containing 200 mug/mL of emulsifier, adding 9mL of culture medium and 1mL of diluted sample to be tested into a culture dish, shaking the culture dish uniformly to prepare a 50 mug/mL drug-containing flat plate, taking a blank control as a flat plate added with 1mL of sterilized water, cutting a bacterial disc along the outer edge of hypha by using a puncher with the diameter of 4mm, and moving the bacterial disc onto the drug-containing flat plate. Each treatment was repeated three times. The dishes were placed in a constant temperature incubator at 24.+ -. 1 ℃. And 3d, measuring the expansion diameter of the bacterial disc by a cross method, averaging, and comparing with a blank control to calculate the relative antibacterial rate. The computing company is as follows:
Figure BDA0002163950270000221
tables 1, 2 and 3 show the test results of the compounds.
Example 7: the protective effect of the compound on the gray mold of the tomato is measured by the following procedure:
the desired amount of compound III-27 was dissolved in sterile aqueous Tween 80 (0.1%, v/v) to give 200. Mu.g/mL of the test solution. Fresh tomato leaves were sprayed with these solutions (10 mL each) until the liquid flowed over the leaf surfaces 24 hours prior to inoculation. Filtering with 4 layers of gauze to give a concentration of 5×10 6 cfu mL -1 The spore suspension Botrytis cinereal of (iii) was then sprayed onto tomato leaves. Inoculated leaves were placed at 20 ℃,85% relative humidity for disease progression, all treatments replicated 3 plants, azoxystrobin was a positive control. After 5 days, the disease was observed and scored. The scoring criteria are as follows:
level 0: no disease spots;
stage 1: 3 diseased spots in 1 leaf;
3 stages: 4-6 lesions are arranged in one blade;
grade 5; 7-10 lesions are arranged in one blade;
7 stages: 11-20 lesions are arranged in one blade, and the part of the lesions are dense;
stage 9: the area of the single leaf spot dense leaf exceeds one quarter.
Figure BDA0002163950270000222
Figure BDA0002163950270000223
Table 4 shows the results of the measurement of the compounds.
Example 8: the protective effect of the compound on rice sheath blight disease is measured by the following procedure:
the rice variety 'IR24' was cultured for evaluation of the protective activity against rice sheath blight disease, with azoxystrobin as a positive control. Rice plants were treated with the compound of interest by spraying with the compound at a concentration of 200, 100, 50, 25 μg/mL, and then inoculated with r.solani after 24 hours. All treatments replicated 20 plants. After 5 days of inoculation, the control effect was calculated as follows:
Figure BDA0002163950270000231
a0 is the diameter of the lesions of the placebo group; a1 is the diameter of the treatment group lesions.
Table 4 shows the results of the measurement of the compounds.
Example 9: the antibacterial activity of the compound on xanthomonas is measured by the following procedures:
to a 15mL tube was added 4mL Nutrient Broth (NB) medium, 1mL test compound (final concentration 100 and 50. Mu.g mL -1 ) And 40. Mu.L of Xoo bacterial solution, the positive control of the colistin in the commercial bactericide. The tubes were then incubated in a thermostatted shaker at 180rpm and 28.+ -. 1 ℃ for 24-48 hours. The Optical Density (OD) of NB medium in each tube was measured on a microplate reader (model 680, BIO-RAD, hercules, calif.) 600 ) Until the bacteria in the untreated NB medium are in logarithmic growth. The in vitro inhibition I (%) was calculated by the following formula, wherein C represents the corrected absorbance value (OD 600 ) T represents the corrected absorbance value (OD of the treated NB medium 600 )。
Inhibition ratio I (%) = (C-T)/c×100
Table 5 shows the results of the measurement of the compounds.
Example 10: the compound is used for measuring the activity of living bodies of bacterial leaf blight of rice, and the measurement procedure is as follows:
the pathogenicity of the Xoo strain was studied by the leaf cutting method. Rice line IR24 (susceptible) was used as a host for virulence testing. By immersing fresh diluted bacterial suspension (OD 600 =0.8, about 4×10 9 cfu mL -1 ) The tips were sheared to seed the fully deployed leaves. Control inoculation was performed simultaneously by immersing the leaves in sterilized M210 liquid medium. At least 25 tablets were inoculated for each Xoo strain testedLeaves were scored. Symptoms were scored by measuring lesion length 14 days after inoculation and the values were expressed as mean lesion length ± SD. The whole experiment was repeated three times independently. The control efficiency I (%) of the treatment and protection activities is calculated by the following equation. In this equation, C is the disease index of the negative control and T is the disease index of the treatment group.
Inhibition ratio I (%) = (C-T)/c×100
Table 6 shows the results of the measurement of the compounds.
Example 11: the insecticidal activity of the compound on the meloidogyne incognita is measured by the following procedures:
1mL of 200 nematode solutions per mL of the prepared compound mother solution to be tested is added into a sample hole of a 12-hole plate by adopting a liquid medicine soaking method, 1mL of the prepared compound mother solution to be tested is added into the sample hole, diluted to a required test concentration, the liquid medicine is mixed uniformly by slight shaking, the mixture is placed into a 25 ℃ incubator for culture, each treatment is repeated for 3 times, the death and survival conditions of nematodes in each liquid to be tested are checked at 24, 48 and 72 hours after the treatment, and the death rate and the correction death rate of the nematodes are calculated respectively.
Mortality (%) = (number of dead insects/total number of insects tested) ×100
Corrected mortality (%) = [ (treatment mortality-control mortality)/(1-control mortality) ]x100
Table 7 shows the results of the measurement of the compounds.
Determination of the Activity of the compounds of Table 1 against phytopathogenic fungi
Figure BDA0002163950270000241
Figure BDA0002163950270000251
Determination of the Activity of the compounds of Table 2 against phytopathogenic fungi
Figure BDA0002163950270000252
Figure BDA0002163950270000261
N.D, dragon fruit canker pathogen; B.D apple ring rot germ; F.O banana vascular wilt bacteria; R.C is rhizoctonia cerealis; C.M banana anthracnose germ; C.G colletotrichum gloeosporioides; G.Z gibberella zeae; P.G Phanerochaete chrysosporium; C.O, white gourd anthracnose pathogen; F.M Fusarium moniliforme; P.N. Phytophthora nicotianae; A.S Alternaria solani; P.L Long-bristle Pelargonium Graveolense; S.S. sclerotium of rape; B.T mango pedicle rot;
determination of the Activity of the compounds of Table 3 against phytopathogenic fungi
Figure BDA0002163950270000262
Figure BDA0002163950270000271
Results of measuring protective effects of the compounds of Table 4 on Botrytis cinerea and Rhizoctonia solani
Figure BDA0002163950270000272
a Not tested. b 'A' indicates that the difference is significant at the level of 0.01; 'a' indicates that the difference is significant at the level of 0.05.
Results of determination of antibacterial Activity of the Compounds of Table 5 against Xanthomonas
Figure BDA0002163950270000273
a Not tested. b 'A' indicates that the difference is significant at the level of 0.01; 'a' indicates that the difference is significant at a level of 0.05
Measurement results of in vivo Activity of Table 6 Compounds against bacterial leaf blight of Rice
Figure BDA0002163950270000281
a The values are the average of 5 replicates. b 'A' indicates that the difference is significant at the level of 0.01; 'a' indicates that the difference is significant at the level of 0.05.
Table 7 results of measurement of insecticidal Activity of Compounds against Meloidogyne incognita
Figure BDA0002163950270000282
a Not measured.
Evaluation of results
A series of dehydrogingerol derivatives show excellent and broad-spectrum activity against plant pathogenic fungi and bacteria and activity against meloidogyne incognita. The target compounds I-13, I-16, I-18, I-19 and III-27 were present in 50. Mu.g mL -1 Exhibits a more excellent broad-spectrum antifungal activity than pyrimethanil and azoxystrobin; at 250 μg mL -1 When the nematicidal composition is used, the nematicidal composition also has certain nematicidal activity on two-instar larvae of the meloidogyne incognita, and the nematicidal activity is 100%, 74.8%, 100%, 68.6% and 64.4% respectively. In particular, the target compound III-27 is superior to azoxystrobin in the living body control effect of rice sheath blight disease and cucumber gray mold, and in addition, the in-vitro and living body control effects of the target compound III-27 on rice bacterial blight caused by xanthomonas are superior to those of the mesogenic fungi. In conclusion, the broad-spectrum anti-plant pathogenic fungi and bacterial activities have certain nematicidal activities, and the dehydrogingerol derivative is a lead compound with wide biological activities. The target compounds I-13, I-16, I-18, I-19 and III-27 have antibacterial and nematicidal activities, so that the target compounds are worthy of further optimization and derivatization, and particularly the target compound III-27 has great potential to be developed as pesticides for killing nematodes and resisting plant pathogenic fungi and bacteria for agricultural production.

Claims (1)

1. Application of dehydrozingibnone derivative in preparing pesticide for resisting plant pathogenic fungi, bacterial diseases and killing nematodes;
the plant pathogenic fungi are selected from one or more of Pitaya ulcer germs, apple ring rot germs, mango stalk rot germs, anthracnose fungi, gibberella fungi, mucor pseudodiscus fungi, fusarium fungi, sclerotinia fungi, alternaria fungi, rhizoctonia fungi, phytophthora fungi and Botrytis;
the bacterial diseases are selected from one or more of xanthomonas, bacterial leaf blight of rice, bacterial soft rot, bacterial wilt and canker;
the anthracnose fungi are selected from one or more of banana anthracnose germs, colletotrichum gloeosporioides and wax gourd anthracnose germs; the gibberella fungus is selected from gibberella zeae; the trichoderma fungi are selected from the group consisting of trichoderma koningii and/or trichoderma longibrachiatum; the fusarium fungi are selected from one or more of fusarium moniliforme, gibberella wheat and fusarium wilt; the sclerotinia fungus is selected from sclerotinia sclerotiorum; the Alternaria fungus is selected from Alternaria solani; the rhizoctonia fungi is selected from rhizoctonia cerealis and/or Rhizoctonia oryzae; the phytophthora is selected from phytophthora nicotianae; the genus Botrytis is selected from Botrytis cinerea and/or Botrytis cinerea;
the dehydrogingerol derivative is shown as a formula (I-13), a formula (I-16), a formula (I-18), a formula (I-19) or a formula (III-27):
Figure FDA0004090705910000011
Figure FDA0004090705910000021
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