An alkyl- or aryl-containing 1,2,3,4-tetrahydro-β-carboline compound, composition, preparation method and application

Abstract

The present invention provides an alkyl- or aryl-containing 1,2,3,4-tetrahydro-β-carboline compound, composition, preparation method and application, belonging to the technical field of medicinal chemistry. Based on tryptamine, the present invention introduces various aldehyde or ketone fragments into this system to synthesize a series of alkyl- or aryl-containing 1,2,3,4-tetrahydro-β-carboline compounds, which have excellent inhibitory effects on phytopathogenic bacteria such as Xanthomonas oryzae pv. oryzae, Xanthomonas axonopodis pv. citri, Pseudomonas syringae pv. actinidiae, etc.; and this series of compounds have excellent control effects on phytopathogenic fungi such as Botryosphaeria dothidea, Rhizoctonia solani, Fusarium oxysporum f. sp. capsici, Verticillium dahliae, Gibberella zeae, etc., providing an important scientific basis for the research and development of new pesticides.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical chemistry, and particularly relates to a 1,2,3,4-tetrahydro-β-carboline compound containing an alkyl or aryl group, a combination, a preparation method and an application thereof. Background Art

[0002] Plant bacterial diseases are one of the main factors affecting global agricultural production, seriously affecting the yield and quality of agricultural products, not only causing huge economic losses, but also threatening human health. For example, bacterial blight of rice, citrus canker, kiwifruit canker, tobacco bacterial wilt, etc. break out to varying degrees every year, causing huge economic losses to farmers. The long-term use of traditional fungicides, such as thiodiazole copper, bismerthiazol, streptomycin sulfate, etc., not only increases the drug resistance of plant pathogens, but also has harmful effects on the ecological environment and the safety of plants.

[0003] Plant fungal diseases are diseases caused by plant pathogenic fungi, accounting for about 70-80% of plant diseases. Several or even dozens of fungal diseases can be found on one crop, resulting in necrosis, rot, and wilting of crops, and there will also be specific symptoms, that is, the special manifestations of the pathogen on the diseased tissue, such as small black particles, concentric ring-shaped mildew layers, flocs, etc. At present, the commonly used fungicides include sulfur-containing fungicides (such as thiophanate-methyl), copper-containing fungicides (such as Bordeaux mixture), and organic fungicides (such as neem oil), and these fungicides either have poor effects or low selectivity.

[0004] Therefore, it is necessary to develop a compound that is resistant to both bacterial diseases and fungal diseases to provide a scientific basis for the research and development of new pesticides. Summary of the Invention

[0005] In view of this, the purpose of the present invention is to provide a 1,2,3,4-tetrahydro-β-carboline compound containing an alkyl or aryl group, a composition containing this compound, a preparation method and an application thereof. The compound provided by the present invention has a good inhibitory effect on plant pathogenic bacteria and an excellent control effect on plant pathogenic fungi.

[0006] In order to achieve the above purpose, the present invention provides the following technical solutions: A 1,2,3,4-tetrahydro-β-carboline compound containing an alkyl or aryl group, and its structural formula is shown as follows:

[0007]

[0008] In the formula, R1 and R2 are each independently selected from one or more of hydrogen, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted aryl, optionally substituted or unsubstituted heteroaryl, optionally substituted or unsubstituted benzyl, and optionally substituted or unsubstituted α-methyl-benzyl;

[0009] or R1 and R2 are linked to form an optionally substituted 4- to 10-membered ring or a heteroatom-containing ring, where the heteroatom is at least one of N, O, and S;

[0010] R3 is selected from one or more of hydrogen, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted aryl, optionally substituted or unsubstituted heteroaryl, optionally substituted or unsubstituted benzyl, and optionally substituted or unsubstituted α-methyl-benzyl;

[0011] Preferably, each of R1 and R2 is independently selected from hydrogen, optionally substituted or unsubstituted C 1-8 alkyl, optionally substituted or unsubstituted C 2-6 alkenyl, optionally substituted or unsubstituted C 5-10 cycloalkyl, optionally substituted or unsubstituted C 5-10 aryl, optionally substituted or unsubstituted C 5-10 heteroaryl, and optionally substituted or unsubstituted benzyl;

[0012] or R1 and R2 are linked to form an optionally substituted 5- to 10-membered ring or a heteroatom-containing ring, where the heteroatom is at least one of N, O, and S;

[0013] R3 is selected from hydrogen, optionally substituted or unsubstituted C 1-8 alkyl, optionally substituted or unsubstituted C 2-6 alkenyl, optionally substituted or unsubstituted C 5-10 cycloalkyl, optionally substituted or unsubstituted C 5-10 aryl, optionally substituted or unsubstituted C 5-10 heteroaryl, and optionally substituted or unsubstituted benzyl;

[0014] Preferably, each of R1, R2 and R3 is independently selected from hydrogen, deuterium, methyl, ethyl, n-propyl, isopropyl, phenyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, 1,1-dimethyl, 1,5-dimethylhexyl, 1,1-diethanol, propenyl, allyl, methoxy, ethoxy, propoxy, butoxy, phenyl, 4-nitrophenyl, 4-ethoxyphenyl, 4-aminophenyl, 2,4-difluorophenyl, 2-chloro-4-fluorophenyl, 2-methyl-4-fluorophenyl, 2,5-dichlorophenyl, 2,4-dichlorophenyl, 2-chloro-4-bromophenyl, 2-methyl-4-chlorophenyl, 4-methyl-3-chlorophenyl, benzyl, 2-fluorobenzyl, 4-fluorobenzyl, 4-trifluoromethylbenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 4-methylbenzyl, 4-methoxybenzyl, phenethyl, cyclopropyl, cyclopentyl, furfuryl, thiophenemethyl, α-methylbenzyl, fluoro-α-methylbenzyl, methoxy-α-methylbenzyl;

[0015] The present invention also provides a method for preparing the 1,2,3,4-tetrahydro-β-carboline compound containing an alkyl or aryl group. Using tryptamine or a tryptamine derivative as a starting material, trifluoroacetic acid as a catalyst, reacting with a ketone or an aldehyde in a solvent at 60 °C with heating and stirring for 6 h to 8 h.

[0016] Preferably, the molar ratio of the ketone to tryptamine or a tryptamine derivative is 1.2:1; the molar ratio of the aldehyde to tryptamine or a tryptamine derivative is 1.2:1.

[0017] Preferably, the solvent is dichloromethane.

[0018] The present invention also provides a composition containing the compound.

[0019] Preferably, the dosage form of the composition is an emulsifiable concentrate, wettable powder, granule, aqueous solution, suspension, ultra-low volume spray, soluble powder, microcapsule, smoke agent, emulsion in water or water dispersible granule.

[0020] The present invention also provides the application of the compound or the composition in controlling agricultural pests and diseases; the agricultural pests and diseases are plant bacterial diseases or plant fungal diseases.

[0021] The present invention also provides a method for controlling agricultural pests and diseases, applying the compound or composition to the harmful substances or their living environment, or directly contacting the composition with plants.

[0022] Beneficial technical effects:

[0023] The present invention uses tryptamine or tryptamine derivatives as starting materials, aldehydes or ketones with different structures as linking chains, introduces a series of alkyl groups or amino groups into this system, and synthesizes a series of 1,2,3,4-tetrahydro-β-carboline compounds. Such compounds have excellent inhibitory effects on phytopathogenic bacteria such as Xanthomonas oryzae pv. oryzae, Xanthomonas axonopodis pv. citri, and Pseudomonas syringae pv. actinidiae; and this series of compounds have excellent control effects on phytopathogenic fungi such as Botryosphaeria dothidea, Rhizoctonia solani, Fusarium oxysporum f. sp. capsici, Verticillium dahliae, Gibberella zeae, and Sclerotinia sclerotiorum. Detailed implementation manners

[0024] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the illustrated embodiments are for better explaining the present invention, but the content of the present invention is not limited only to the illustrated embodiments. Therefore, those skilled in the art who make non-essential improvements and adjustments to the implementation manners according to the above invention content still fall within the protection scope of the present invention.

[0025] The terms used herein are only for describing specific embodiments and are not intended to limit the present disclosure. Unless having a significantly different meaning in the context, the singular forms of expressions include the plural forms of expressions. As used herein, it should be understood that terms such as "including", "having", and "containing" are intended to indicate the existence of features, numbers, operations, components, parts, elements, materials, or combinations. The terms of the present invention are disclosed in the specification, and are not intended to exclude the possibility of the existence or addition of one or more other features, numbers, operations, components, parts, elements, materials, or their combinations. As used herein, depending on the circumstances, " / " can be interpreted as "and" or "or".

[0026] The term "alkyl" used in the present invention includes branched-chain and straight-chain saturated hydrocarbon groups having a specific number of carbon atoms. For example, "C 1-10 alkyl" (or alkylene) is intended to be C1, C2, C3, C4, C5, C6, C7, C8, C9, and C10 alkyl. Additionally, for example, "C 1-6 alkyl" represents an alkyl group having 1 to 6 carbon atoms. The alkyl group can be unsubstituted or substituted such that one or more of its hydrogen atoms are replaced by other chemical groups. Examples of alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), propyl (such as n-propyl and isopropyl), butyl (such as n-butyl, isobutyl, tert-butyl), pentyl (such as n-pentyl, isopentyl, neopentyl), and the like.

[0027] The term "alkenyl" used in the present invention includes both straight-chain or branched-chain hydrocarbons and having one or more carbon-carbon double bonds appearing at any stable point in the chain. For example, "C 2-6The term "alkenyl" (or "alkenylene") is intended to include C2, C3, C4, C5 and C6 alkenyls. Examples of alkenyls include, but are not limited to, vinyl, 1-propenyl, 2-propenyl, 2-butenyl, 3-butenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-methyl-2-propenyl, 4-methyl-3-pentenyl and the like.

[0028] As used herein, the term "substituted" means that any one or more hydrogen atoms on a specified atom or group are replaced with a selected specified group, provided that the normal valence of the specified atom is not exceeded. Unless otherwise specified, substituents are named to the central structure. For example, it is understood that when (cycloalkyl)alkyl is a possible substituent, the point of attachment of the substituent to the central structure is in the alkyl moiety. A ring double bond as used herein is a double bond formed between two adjacent ring atoms (such as C═C, C═N or N═N). When substitution is mentioned, especially polysubstitution, it means that multiple substituents replace at each position on the specified group, such as dichlorobenzyl means 2,3-dichlorobenzyl, 2,4-dichlorobenzyl, 2,5-dichlorobenzyl, 2,6-dichlorobenzyl, 3,4-dichlorobenzyl and 3,5-dichlorobenzyl.

[0029] Combinations of substituents and variables are permitted only if these combinations result in stable compounds or useful synthetic intermediates. A stable compound or stable structure implies that the compound is sufficiently stable to be isolated from the reaction mixture in useful purity and subsequently formulated into an effective therapeutic agent.

[0030] The term "heteroaryl" refers to substituted and unsubstituted aromatic 5- or 6-membered monocyclic groups, 9- or 10-membered bicyclic groups, and 11- to 14-membered tricyclic groups having at least one heteroatom (O, S or N) in at least one ring, and the heteroatom-containing ring preferably has 1, 2 or 3 heteroatoms selected from O, S and N. Each ring of the heteroaryl containing heteroatoms may contain one or two oxygen or sulfur atoms and / or from 1 to 4 nitrogen atoms, provided that the total number of heteroatoms in each ring is 4 or less and each ring has at least one carbon atom. The fused rings completing the bicyclic and tricyclic groups may contain only carbon atoms and may be saturated, partially saturated or unsaturated. Nitrogen may optionally be oxidized and quaternized. The bicyclic or tricyclic heteroaryl must include at least one fully aromatic ring, and the other fused rings may be aromatic or non-aromatic. The heteroaryl may be attached at any available nitrogen or carbon atom of any ring. When the valence allows, if the other ring is a cycloalkyl or heterocycle, it is additionally optionally substituted with ═O (oxygen).

[0031] Exemplary monocyclic heteroaryl groups include pyrrolyl, pyrazolyl, pyrazolinyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, furyl, thienyl, oxadiazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl and the like.

[0032] Exemplary bicyclic heteroaryl groups include indolyl, benzothiazolyl, benzodioxolyl, benzoxazolyl, benzothienyl, quinolinyl, tetrahydroisoquinolinyl, isoquinolinyl, benzimidazolyl, benzofuranyl, indolizinyl, benzofuranyl, chromonyl, coumarinyl, benzofuranyl, cinnolinyl, quinoxalinyl, indazolyl, pyrrolopyridyl, fluoropyridyl, dihydroisoindolyl, tetrahydroquinolinyl and the like.

[0033] In the present invention, the term "compound", unless otherwise specified, is understood to include the free form and its salts. "Salt" refers to acid addition and / or base salts formed with inorganic and / or organic acids and bases; in addition, salts may include zwitterions (inner salts), such as when the compound of Formula I contains a basic moiety such as an amine or a pyridine or imidazole ring, and an acidic moiety such as a carboxylic acid. Pharmaceutically acceptable (i.e., non-toxic, physiologically acceptable) salts are preferred, such as acceptable metal and amine salts, where the cation does not significantly contribute to the toxicity or biological activity of the salt. However, other salts may be useful, such as in the separation or purification steps during preparation, and are thus also included within the scope of the present invention.

[0034] In the present invention, C1-C8 alkyl refers to methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl and their isomers; C2-C6 alkenyl refers to vinyl, propenyl, allyl, butenyl, pentenyl, hexenyl and their isomers.

[0035] When a substituent is an alkenyl, alkyl, aryl, benzyl, cycloalkyl group, or when these substituents are specifically a particular alkenyl, alkyl, aryl, benzyl, cycloalkyl group, it refers to one to three of the above substituents. For example, chlorobenzyl refers to benzyl substituted with one to three chlorine atoms.

[0036] In this application, tryptamine or a tryptamine derivative is used as the starting material to synthesize a series of 1,2,3,4-tetrahydro-β-carboline compounds with different substituents, and their structural formulas are shown as follows:

[0037]

[0038] In the formula, R1 and R2 are each independently selected from one or more of hydrogen, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted aryl, optionally substituted or unsubstituted heteroaryl, optionally substituted or unsubstituted benzyl, and optionally substituted or unsubstituted α-methyl-benzyl;

[0039] Alternatively, R1 and R2 are linked to form an optionally substituted 4- to 10-membered ring or a heteroatom-containing ring, where the heteroatom is at least one of N, O, and S;

[0040] R3 is selected from one or more of hydrogen, an optionally substituted or unsubstituted alkyl group, an optionally substituted or unsubstituted alkenyl group, an optionally substituted or unsubstituted cycloalkyl group, an optionally substituted or unsubstituted aryl group, an optionally substituted or unsubstituted heteroaryl group, an optionally substituted or unsubstituted benzyl group, and an optionally substituted or unsubstituted α-methyl-benzyl group;

[0041] In some embodiments, each of R1 and R2 is independently selected from hydrogen, an optionally substituted or unsubstituted C 1-8 alkyl group, an optionally substituted or unsubstituted C 2-6 alkenyl group, an optionally substituted or unsubstituted C 5-10 cycloalkyl group, an optionally substituted or unsubstituted C 5-10 aryl group, an optionally substituted or unsubstituted C 5-10 heteroaryl group, and an optionally substituted or unsubstituted benzyl group;

[0042] Alternatively, R1 and R2 are linked to form an optionally substituted 5- to 10-membered ring or a heteroatom-containing ring, where the heteroatom is at least one of N, O, and S;

[0043] R3 is selected from hydrogen, an optionally substituted or unsubstituted C 1-8 alkyl group, an optionally substituted or unsubstituted C 2-6 alkenyl group, an optionally substituted or unsubstituted C 5-10 cycloalkyl group, an optionally substituted or unsubstituted C 5-10 aryl group, an optionally substituted or unsubstituted C 5-10 heteroaryl group, and an optionally substituted or unsubstituted benzyl group;

[0044] In some embodiments, each of R1, R2, and R3 is independently selected from hydrogen, deuterium, methyl, ethyl, n-propyl, isopropyl, phenyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, 1,1-dimethyl, 1,5-dimethylhexyl, 1,1-diethanolyl, propenyl, allyl, methoxy, ethoxy, propoxy, butoxy, phenyl, 4-nitrophenyl, 4-ethoxyphenyl, 4-aminophenyl, 2,4-difluorophenyl, 2-chloro-4-fluorophenyl, 2-methyl-4-fluorophenyl, 2,5-dichlorophenyl, 2,4-dichlorophenyl, 2-chloro-4-bromophenyl, 2-methyl-4-chlorophenyl, 4-methyl-3-chlorophenyl, benzyl, 2-fluorobenzyl, 4-fluorobenzyl, 4-trifluoromethylbenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 4-methylbenzyl, 4-methoxybenzyl, phenethyl, cyclopropyl, cyclopentyl, furanmethyl, thiophenemethyl, α-methylbenzyl, fluoro-α-methylbenzyl, and methoxy-α-methylbenzyl;

[0045] In some embodiments, the alkyl- or aryl-containing 1,2,3,4-tetrahydro-β-carboline compounds provided by the present invention are selected from any one of the following structures:

[0046]

[0047] The present invention also provides a method for preparing the alkyl- or aryl-containing 1,2,3,4-tetrahydro-β-carboline compounds described in the above technical solution. Using tryptamine or a tryptamine derivative as a starting material, trifluoroacetic acid (TFA) as a catalyst, reacting with a ketone or an aldehyde in a solvent at 60 °C with heating and stirring for 6 h to 8 h. The reaction general formula is:

[0048]

[0049] In some embodiments, the molar ratio of the ketone to tryptamine or a tryptamine derivative is 1.2:1; the molar ratio of the aldehyde to tryptamine or a tryptamine derivative is 1.2:1.

[0050] In some embodiments, the solvent is dichloromethane (DCM).

[0051] In the present invention, the specific operation of the reaction is as follows: Add tryptamine or a tryptamine derivative and different kinds of aldehydes or ketones to dichloromethane, then slowly dropwise add trifluoroacetic acid, carry out the reaction at 60 °C. After the reaction is completed, quench the reaction system with water, extract the organic matter with ethyl acetate, wash with a 10% potassium carbonate solution, dry with anhydrous sodium sulfate, remove the solvent, and obtain the target compound after purification and separation.

[0052] The present invention also provides a composition containing the compound.

[0053] In some embodiments, the dosage form of the composition is an emulsifiable concentrate, a wettable powder, a granule, an aqueous solution, a suspension concentrate, an ultra-low volume spray, a soluble powder, a microcapsule, a smoke agent, an emulsion in water or a water dispersible granule; the composition can be a bactericide, an insecticide or a herbicide made from the above compound and an agricultural adjuvant.

[0054] The present invention also provides the application of the compound or the composition in preventing and controlling agricultural pests and diseases.

[0055] In some embodiments, the agricultural pests and diseases are plant bacterial diseases or plant fungal diseases. Specifically, the agricultural pests and diseases are plant leaf blight or plant canker.

[0056] Furthermore, the bacterial diseases are rice bacterial blight, cucumber bacterial blight, konjac bacterial blight, citrus canker, tobacco bacterial wilt, grape canker, tomato canker, kiwifruit canker, apple canker.

[0057] Furthermore, the fungal diseases are cucumber gray mold, pepper fusarium wilt, rape sclerotinia, wheat scab, potato late blight, blueberry root rot, Botryosphaeria dothidea, pitaya anthracnose, rice sheath blight, and eggplant verticillium wilt.

[0058] The present invention also provides a method for controlling agricultural pests and diseases: applying the compound or the composition to the harmful organisms or their living environment, or directly contacting the composition with plants.

[0059] To better understand the present invention, the content of the present invention will be further clarified below in conjunction with embodiments. However, the content of the present invention is not limited to the following embodiments. All raw materials and solvents used in the embodiments are commercially available products.

[0060] Example 1

[0061] Preparation of 1-(4-(trifluoromethoxy)phenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole

[0062] Tryptamine (0.5 g, 0.2 mmol), TFA (227 L, 3 mmol) and 6 mL of dichloromethane were added to a 25 mL round-bottom flask, stirred at room temperature for 20 min, then 4-trifluoromethoxybenzaldehyde (0.4 g, 2.4 mmol) was added, and the reaction was terminated after heating and stirring at 60 °C for 8 h. The reaction was quenched with water, the organic phase was collected by extraction with ethyl acetate, washed with 10% K2CO3 solution, dried over anhydrous sodium sulfate, concentrated by evaporation, and purified by column chromatography (CH2Cl2:CH3OH = 10:1, v / v) to obtain a yellow solid with a yield of 92.8%.

[0063] Its NMR data are as follows: 1 H NMR(500MHz,CDCl3)δ8.09(s,1H,NH),7.60–7.55(m,1H,ph-H),7.26(d,J=8.6Hz,2H,ph-H),7.19(s,1H,ph-H),7.17(s,1H,ph-H),7.15(s,1H,ph-H),7.14(d,J=2.3Hz,2H,ph-H),5.08(s,1H,CH),3.26(d,J=12.5Hz,1H,CH2),3.09(s,1H,CH2),2.84(d,J=1.4Hz,2H,CH2),1.97(s,1H,NH). 1313C NMR (126 MHz, CDCl3) δ 149.08, 140.71, 136.09, 133.71, 130.14, 127.34, 122.04, 121.38, 119.60, 118.45, 111.05, 110.55, 57.22, 42.45, 22.49.

[0064] Example 2

[0065] Preparation of 6-Methoxy-1-(4-(trifluoromethoxy)phenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole

[0066] 5-Methoxytryptamine (0.15 g, 0.8 mmol) and 4-(trifluoromethoxy)benzaldehyde (139 μL, 0.96 mmol) were added to a 15 mL pressure-resistant tube containing 6 mL of dichloromethane. Trifluoroacetic acid (94 μL, 1.2 mmol) was added, and the mixture was heated and stirred at 60 °C. The reaction was monitored by TLC until completion. The reaction was quenched with water, and the organic phase was collected by extraction with ethyl acetate, washed with 10% K2CO3 solution, dried over anhydrous sodium sulfate, and the solvent was removed under vacuum. The product was purified using dichloromethane:methanol = 10:1 as the eluent to obtain a yellow solid with a yield of 56.3%.

[0067] Its NMR data are as follows: 1 1H NMR (400 MHz, CDCl3) δ 7.85 (s, 1H, NH), 7.31 (d, J = 8.6 Hz, 2H, Ar-H), 7.20 (d, J = 8.1 Hz, 2H, Ar-H), 7.08 (s, 1H, Ar-H), 7.04 (d, J = 2.4 Hz, 1H, Ar-H), 6.83 (d, J = 2.4 Hz, 1H, Ar-H), 5.13 (s, 1H, CH), 3.89 (s, 3H, CH3), 3.30 (s, 1H, CH2), 3.13 (s, 1H, CH2), 2.82 (d, J = 0.9 Hz, 2H, CH2), 1.91 (s, 1H, NH). 13 13C NMR (101 MHz, CDCl3) δ 154.05, 148.97, 148.95 (q, 3 J C-F = 2.4 Hz), 140.68, 134.64, 131.03, 129.99, 127.64, 121.30 (q, 1 J C-F = 258.3 Hz), 111.75, 111.64, 110.29, 100.47, 57.29, 55.95, 42.52, 22.51.

[0068] Using steps similar to those in the above embodiments, the following compounds were prepared by only replacing the corresponding raw materials. The structures, proton nuclear magnetic resonance spectra, and carbon nuclear magnetic resonance spectra data of the compounds are shown in Table 1, and the physical and chemical properties are shown in Table 2.

[0069] Table 1 Proton nuclear magnetic resonance spectra and carbon nuclear magnetic resonance spectra data of the compounds

[0070]

[0071]

[0072]

[0073]

[0074]

[0075]

[0076]

[0077]

[0078]

[0079]

[0080]

[0081]

[0082]

[0083]

[0084] Table 2 Physical and chemical properties of the target compounds

[0085]

[0086]

[0087] Test Example 1

[0088] EC 50(Median Effective Concentration) is an important indicator for evaluating the sensitivity of plant pathogens to compounds and is also an important parameter for setting the compound concentration when studying the mechanism of action of target compounds. In the concentration gradient experiment, five appropriate concentrations are set using the two-fold dilution method. Finally, the inhibition rate of the medicament against plant pathogens and the logarithm of the medicament concentration are converted, and the toxicity curve is obtained through regression analysis using SPSS software, and the EC 50 .

[0089] The turbidimetric method is used to test the median effective concentration (EC 50 ) of the target compound against plant pathogens. The test objects are Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas citri subsp. citri (Xac), and Pseudomonas syringae pv. actinidiae (Psa). DMSO is dissolved in NB medium as a blank control. Xanthomonas oryzae pv. oryzae (on M210 solid medium) is placed in NB medium and cultured in a constant temperature shaker at 28 °C and 180 rpm until the logarithmic growth phase for standby; Xanthomonas citri subsp. citri (on M210 solid medium) is placed in NB medium; Xanthomonas oryzae pv. oryzicola (on M210 solid medium) is placed in NB medium and cultured in a constant temperature shaker at 28 °C and 180 rpm until the logarithmic growth phase for standby. 5 mL of toxic NB liquid medium containing the medicament (compound) at different concentrations (e.g., 100, 50, 25, 12.5, 6.25 μg / mL) is added to test tubes, and 40 μL of NB liquid medium containing phytopathogenic bacteria is added respectively. It is shaken in a constant temperature shaker at 28-30 °C and 180 rpm. Among them, Xanthomonas oryzae pv. oryzae is cultured for 48 h, Xanthomonas citri subsp. citri is cultured for 48 h, and Xanthomonas oryzae pv. oryzicola is cultured for 36 h. The OD 595 value of the bacterial liquid at each concentration is measured on an enzyme-linked immunosorbent assay (ELISA) reader, and the OD 595 value of the toxic sterile NB liquid medium at the corresponding concentration is measured separately.

[0090] Among them, NB medium: water: 1 L, glucose: 10 g, peptone: 5 g, beef extract: 3 g, yeast powder: 1 g; M210 solid medium: water: 1 L, glucose: 10 g, peptone: 5 g, beef extract: 3 g, yeast powder: 1 g, agar: 15 g.

[0091] Corrected OD value = OD value of the medium containing bacteria - OD value of the sterile medium

[0092] Inhibition rate % = [(OD value of the bacterial liquid in the control medium after correction - OD value of the toxic medium after correction) / OD value of the bacterial liquid in the control medium after correction] × 100

[0093] The examples of the present invention are used to illustrate the technical solutions of the present invention, but the content of the examples is not limited thereto. The experimental results of the target compound are shown in Table 3.

[0094] Table 3 EC of 1,2,3,4-tetrahydro-β-carboline compounds substituted with alkyl or aryl groups against phytopathogenic bacteria 50

[0095]

[0096]

[0097]

[0098] As can be seen from Table 3, in in vitro tests, some of the target compounds showed good inhibitory activity against phytopathogenic bacteria (such as Xanthomonas oryzae pv. oryzae, Xanthomonas citri subsp. citri, and Pseudomonas syringae pv. actinidiae). Compound 17 had excellent inhibitory activity against Xanthomonas oryzae pv. oryzae and Xanthomonas citri subsp. citri, and its EC 50 was 7.27 and 4.89 g / mL -1 respectively; Compound 8 had excellent inhibitory activity against Pseudomonas syringae pv. actinidiae, and its EC 50 was 4.87 g / mL -1 and could be used to prepare pesticides against phytopathogenic bacteria.

[0099] Test Example 2:

[0100] The growth rate method was used to test the inhibition rate of the target compounds (50 μg / mL) against phytopathogenic bacteria. The test objects were Botryosphaeria dothidea, Rhizoctonia solani Kühn, Fusarium oxysporum, Verticillium dahliae, and Gibberella zeae. Dimethyl sulfoxide (DMSO) was dissolved in the medium as a blank control. The test compound was weighed with a ten-thousandth balance, 1 mL of DMSO was added to dissolve the compound, and then it was transferred to a 15 mL sterilized centrifuge tube in a sterile operating table. 9 mL of Tween-20 was added to make the volume up to 10 mL, and it was poured into the melted medium, mixed well, and evenly distributed into 9 petri dishes for standby after cooling; in the sterile operating table, a puncher (5 mm) was sterilized by burning, the colony was made into a bacterial cake, and the bacterial cake was inoculated in the center of the medium with an inoculation loop. It was cultured at 25-28 °C for about 5 days. When the colony of the blank control grew to about 6 cm, it was measured twice with a ruler by the cross method, and the average value was taken as the diameter of the colony. The mycelial growth inhibition rate of each concentration was calculated according to the calculation formula.

[0101] Among them, DMSO is dissolved in PDA medium. The PDA medium consists of: potatoes, agar powder, glucose, magnesium sulfate, potassium dihydrogen phosphate, vitamin B1, natural pH, sterilized at 121°C for 30 min. The specific process is as follows: 1000 mL of potato juice: Peel and wash the potatoes, cut them into shreds, weigh 200 g, boil them in 1 L of secondary water until the potato shreds can be gently crushed with fingers, and filter with gauze; Weigh 20 g of agar powder into a beaker, add a small amount of cold water to disperse it, then pour it into the boiling potato solution, and boil until the agar powder melts. During this period, continuous rapid stirring is required. Weigh 20 g of glucose, 1.5 g of magnesium sulfate, 3.0 g of potassium dihydrogen phosphate, and 10 mg of vitamin B1, add them to the filtrate, stir to dissolve, add secondary water to make up to 1 L, natural pH. While it is hot, take 90 mL and dispense it into 200 mL conical flasks, seal them with semi-permeable membranes, and sterilize them in a high-pressure sterilizer at 121°C for 30 min for standby.

[0102] Inhibition rate (%) = (N1 - N2) / (N1 - 0.5)×100

[0103] 0.5 — is the diameter of the mother yeast cake / cm;

[0104] N1 — is the control colony diameter, that is, the colony diameter of the control group / cm;

[0105] N2 — is the treated colony diameter, that is, the colony diameter of the colony treated with the target compound / cm:

[0106] The embodiments of the present invention are used to illustrate the technical solutions of the present invention, but the content of the embodiments is not limited thereto. The experimental results of the target compounds are shown in Table 4.

[0107] Table 4 Inhibitory activities of 1,2,3,4 - tetrahydro - β - carboline compounds substituted with alkyl or aryl groups against phytopathogenic fungi

[0108]

[0109]

[0110] As can be seen from Table 4, five pathogenic phytopathogenic fungi were selected as test objects, and the biological activities of some compounds were tested by the growth rate method. The test results showed that this series of compounds had general antifungal activities. Among them, compound 8 showed excellent inhibitory activity against Rhizoctonia solani Kühn; compound 18 also showed excellent inhibitory activity against Verticillium dahliae. It can be seen that the compounds of the present invention can be used to prepare pesticides against phytopathogenic fungi.

[0111] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. Use of an alkyl- or aryl-containing 1,2,3,4-tetrahydro-β-carboline compound in controlling agricultural pests and diseases, characterized in that, The structural formula of the alkyl- or aryl-containing 1,2,3,4-tetrahydro-β-carboline compounds is as follows: The agricultural pests and diseases are Xanthomonas citri subsp. citri or Pseudomonas syringae pv. actinidiae.

2. Use of the alkyl- or aryl-containing 1,2,3,4-tetrahydro-β-carboline compound according to claim 1 in controlling agricultural pests and diseases, characterized in that, The preparation method of the alkyl- or aryl-containing 1,2,3,4-tetrahydro-β-carboline compounds is as follows: Using tryptamine as the starting material, trifluoroacetic acid as the catalyst, reacting with aldehyde in a solvent at 60 °C with heating and stirring for 6 h to 8 h.

3. Use of the alkyl- or aryl-containing 1,2,3,4-tetrahydro-β-carboline compound according to claim 2 in controlling agricultural pests and diseases, characterized in that, The molar ratio of the aldehyde to tryptamine is 1.2:

1.

4. Use of the alkyl- or aryl-containing 1,2,3,4-tetrahydro-β-carboline compound according to claim 2 in controlling agricultural pests and diseases, characterized in that, The solvent is dichloromethane.

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