CN116375702A - 1,2,3, 4-tetrahydro-beta-carboline compound containing alkyl or aryl, composition, preparation method and application - Google Patents

Abstract

The invention provides a 1,2,3, 4-tetrahydro-beta-carboline compound containing alkyl or aryl, a composition, a preparation method and application, and belongs to the technical field of pharmaceutical chemistry. Based on tryptamine, various aldehyde or ketone fragments are introduced into the system to synthesize a series of 1,2,3, 4-tetrahydro-beta-carboline compounds containing alkyl or aryl structures, and the compounds have excellent inhibition effects on plant pathogenic bacteria such as bacterial blight bacteria, citrus canker bacteria, kiwi fruit canker bacteria and the like; the series of compounds have excellent control effects on plant pathogenic fungi such as grape vine cavity germ, rice sheath blight germ, pepper fusarium, eggplant verticillium wilt germ, wheat gibberella, and the like, and provide an important scientific basis for developing and creating new pesticides.

Description

A 1,2,3,4-tetrahydro-β-carboline compound containing an alkyl or aromatic group, a composition, a preparation method and an application

Technical Field

The present invention relates to the technical field of pharmaceutical chemistry, and in particular to a 1,2,3,4-tetrahydro-β-carboline compound containing an alkyl group or an aromatic group, a combination, a preparation method and an application thereof.

Background Art

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 great economic losses, but also threatening human health. For example, rice bacterial blight, citrus canker, kiwi 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 thiophanate-methyl, chlorothalonil, streptomycin sulfate, etc., not only increases the drug resistance of plant pathogens, but also has a harmful impact on the ecological environment and plant safety.

Plant fungal diseases are caused by plant pathogenic fungi, accounting for about 70-80% of plant diseases. Several or even dozens of fungal diseases can be found on a crop, causing necrosis, rot, and wilt of the crop. Specific symptoms may also occur, that is, the special manifestations of pathogens on the diseased tissue, such as small black particles, ring-shaped mold layers, flocculent matter, etc. At present, commonly used fungicides include sulfur-containing fungicides (such as methyl thiophanate), copper-containing fungicides (such as Bordeaux mixture), and organic fungicides (such as neem oil). These fungicides are either ineffective or not highly selective.

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

Summary of the invention

In view of this, the object of the present invention is to provide a 1,2,3,4-tetrahydro-β-carboline compound containing an alkyl or aromatic group, a composition containing the compound, and a preparation method and 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.

In order to achieve the above object, the present invention provides the following technical solution: a 1,2,3,4-tetrahydro-β-carboline compound containing an alkyl group or an aromatic group, the structural formula of which is shown below:

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;

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

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, optionally substituted or unsubstituted α-methyl-benzyl;

Preferably, R1 and R2 are each independently selected from hydrogen, optionally substituted or unsubstituted _C1-8 alkyl, optionally substituted or unsubstituted _C2-6 alkenyl, optionally substituted or unsubstituted _C5-10 cycloalkyl, optionally substituted or unsubstituted _C5-10 aryl, optionally substituted or unsubstituted _C5-10 heteroaryl, and optionally substituted or unsubstituted benzyl;

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

R3 is selected from hydrogen, optionally substituted or unsubstituted _C1-8 alkyl, optionally substituted or unsubstituted _C2-6 alkenyl, optionally substituted or unsubstituted _C5-10 cycloalkyl, optionally substituted or unsubstituted _C5-10 aryl, optionally substituted or unsubstituted _C5-10 heteroaryl, optionally substituted or unsubstituted benzyl;

Preferably, R1, R2 and R3 are each 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-nitro ... -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, furanyl, thephenylmethyl, α-methylbenzyl, fluoro-α-methylbenzyl, methoxy-α-methylbenzyl;

The present invention also provides a method for preparing the alkyl or aromatic 1,2,3,4-tetrahydro-β-carboline compounds, which uses tryptamine or a tryptamine derivative as a starting material, trifluoroacetic acid as a catalyst, and reacts with ketone or aldehyde in a solvent at 60°C under stirring for 6 to 8 hours.

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.

Preferably, the solvent is dichloromethane.

The present invention also provides a composition containing the compound.

Preferably, the composition is in the form of emulsifiable concentrate, wettable powder, granules, aqueous solution, suspension, ultra-low volume spray, soluble powder, microcapsule, smoke concentrate, aqueous emulsion or water-dispersible granules.

The present invention also provides the use of the compound or the composition in preventing and controlling agricultural pests and diseases; the agricultural pests and diseases are plant bacterial diseases or plant fungal diseases.

The present invention also provides a method for preventing and controlling agricultural pests and diseases, wherein the compound or composition acts on the harmful substance or the environment in which it lives, or the composition is directly contacted with the plant.

Beneficial technical effects:

The invention uses tryptamine or tryptamine derivatives as starting materials, uses aldehydes or ketones of different structures as connecting chains, introduces a series of alkyl groups or amino groups into the system, and synthesizes a series of 1,2,3,4-tetrahydro-β-carboline compounds. The compounds have excellent inhibitory effects on plant pathogenic bacteria such as rice bacterial blight, citrus canker, kiwi fruit canker, etc.; and the series of compounds have excellent control effects on plant pathogenic fungi such as grape spores, rice sheath blight, pepper wilt, eggplant verticillium dahliae, wheat fusarium head blight, rapeseed sclerotinia, etc.

DETAILED DESCRIPTION

The following will be described clearly and completely in conjunction with the technical solutions in the embodiments of the present invention. Obviously, the embodiments are for better illustrating the present invention, but the content of the present invention is not limited to the embodiments. Therefore, those skilled in the art can make non-essential improvements and adjustments to the implementation scheme according to the above invention content, which still fall within the protection scope of the present invention.

The terms used herein are only used to describe specific embodiments and are not intended to limit the present disclosure. Unless the context has a significantly different meaning, expressions in the singular include expressions in the plural. As used herein, it should be understood that terms such as "include", "have", "comprise" and the like are intended to indicate the presence 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 that one or more other features, numbers, operations, components, parts, elements, materials or combinations thereof may exist or may be added. As used herein, "/" may be interpreted as "and" or "or", depending on the circumstances.

The term "alkyl" as used in the present invention includes branched and straight chain saturated hydrocarbon groups having a specific number of carbon atoms. For example, "C _1-10 alkyl" (or alkylene) refers to C1, C2, C3, C4, C5, C6, C7, C8, C9 and C10 alkyl. In addition, for example, "C _1-6 alkyl" refers to an alkyl group having 1 to 6 carbon atoms. The alkyl group may be unsubstituted or substituted so 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.

The term "alkenyl" as used in the present invention is a hydrocarbon that includes both straight or branched structures and has one or more carbon-carbon double bonds that appear at any stable point in the chain. For example, " _C2-6 alkenyl" (or alkenylene) is intended to include C2, C3, C4, C5 and C6 alkenyl. Examples of alkenyl 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.

The term "substituted" as used herein refers to the replacement of any one or more hydrogen atoms on a designated atom or group with a selected designated group, provided that the general valence of the designated atom is not exceeded. If not otherwise specified, the 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 portion. 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 referring to substitution, especially polysubstitution, it means that multiple substituents are substituted at various positions on the designated group, such as dichlorobenzyl refers to 2,3-dichlorobenzyl, 2,4-dichlorobenzyl, 2,5-dichlorobenzyl, 2,6-dichlorobenzyl, 3,4-dichlorobenzyl and 3,5-dichlorobenzyl.

Combinations of substituents and variables are permissible only if such 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 in a useful degree of purity from a reaction mixture, and then formulated into an efficacious therapeutic agent.

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, the heteroatom-containing ring preferably having 1, 2 or 3 heteroatoms selected from O, S and N. Each ring of the heteroatom-containing heteroaryl group 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. The nitrogen may be optionally oxidized and quaternized. The bicyclic or tricyclic heteroaryl group must include at least one fully aromatic ring, and the nitrogen other fused rings may be aromatic or non-aromatic. The heteroaryl group may be attached at any available nitrogen or carbon atom of any ring. If the other ring is a cycloalkyl or heterocycle, it is additionally optionally substituted with =0 (oxygen) when valence permits.

Exemplary monocyclic heteroaryl groups include pyrrolyl, pyrazolyl, pyrazolinyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, furanyl, thienyl, oxadiazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, and the like.

Exemplary bicyclic heteroaryl groups include indolyl, benzothiazolyl, benzodioxolyl, benzoxazolyl, benzothiophenyl, quinolinyl, tetrahydroisoquinolinyl, isoquinolinyl, benzimidazolyl, benzofuranyl, indolizinyl, benzofuranyl, chromonyl, coumarinyl, benzofuranyl, cinnolinyl, quinoxalinyl, indazolyl, pyrrolopyridinyl, fluoropyridinyl, dihydroisoindolyl, tetrahydroquinolinyl, and the like.

The term "compound" used in the present invention is understood to include the free state and its salts if there is no other explanation. "Salt" means acidic and/or basic 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 basic fragments such as amines or pyridine or imidazole rings, and acidic fragments such as carboxylic acids. Pharmaceutically acceptable (i.e., non-toxic, physiologically acceptable) salts are preferred, such as acceptable metal and amine salts, in which the cation does not significantly contribute to the toxicity or biological activity of the salt. However, other salts may be useful, such as separation or purification steps used in the preparation process, and are therefore also included in the scope of the present invention.

In the present invention, C ₁ -C ₈ alkyl refers to methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl and isomers thereof; C ₂ -C ₆ alkenyl refers to vinyl, propenyl, allyl, butenyl, pentenyl, hexenyl and isomers thereof.

When a substituent is referred to as alkenyl, alkyl, aryl, benzyl, or cycloalkyl, or when these substituents are specifically alkenyl, alkyl, aryl, benzyl, or cycloalkyl, it refers to one to three of the above substituents. For example, chlorobenzyl refers to one to three chlorine-substituted benzyls.

The present invention uses tryptamine or tryptamine derivatives as starting materials to synthesize a series of 1,2,3,4-tetrahydro-β-carboline compounds containing different substituents, and the structural formula thereof is shown below:

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;

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

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, optionally substituted or unsubstituted α-methyl-benzyl;

In some embodiments, R1 and R2 are each independently selected from hydrogen, optionally substituted or unsubstituted _C1-8 alkyl, optionally substituted or unsubstituted _C2-6 alkenyl, optionally substituted or unsubstituted _C5-10 cycloalkyl, optionally substituted or unsubstituted _C5-10 aryl, optionally substituted or unsubstituted _C5-10 heteroaryl, and optionally substituted or unsubstituted benzyl;

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

R3 is selected from hydrogen, optionally substituted or unsubstituted _C1-8 alkyl, optionally substituted or unsubstituted _C2-6 alkenyl, optionally substituted or unsubstituted _C5-10 cycloalkyl, optionally substituted or unsubstituted _C5-10 aryl, optionally substituted or unsubstituted _C5-10 heteroaryl, optionally substituted or unsubstituted benzyl;

In some embodiments, R1, R2 and R3 are each 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-chlorophenyl, -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, furanyl, thephenylmethyl, α-methylbenzyl, fluoro-α-methylbenzyl, methoxy-α-methylbenzyl;

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

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

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.

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

In the present invention, the specific operation of the reaction is: adding tryptamine or a tryptamine derivative and different types of aldehydes or ketones to dichloromethane, then slowly adding trifluoroacetic acid, reacting at 60°C, quenching the reaction system with water after the reaction, extracting organic matter with ethyl acetate, washing with 10% potassium carbonate solution, drying with anhydrous sodium sulfate, removing the solvent, and purifying and separating to obtain the target compound.

The present invention also provides a composition containing the compound.

In some embodiments, the composition is in the form of emulsifiable concentrate, wettable powder, granules, aqueous solution, suspension, ultra-low volume spray, soluble powder, microcapsule, smoke agent, aqueous emulsion or water-dispersible granules; the composition can be a fungicide, insecticide or herbicide prepared by combining the above-mentioned compounds with agricultural adjuvants.

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

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.

Furthermore, the bacterial diseases are rice bacterial leaf blight, cucumber bacterial leaf blight, konjac bacterial leaf blight, citrus canker, tobacco bacterial wilt, grape canker, tomato canker, kiwi fruit canker, and apple canker.

Furthermore, the fungal diseases are cucumber gray mold, pepper wilt, rapeseed sclerotinia, wheat fusarium wilt, potato late blight, blueberry root rot, grape syringa, pitaya anthracnose, rice sheath blight, and eggplant verticillium wilt.

The present invention also provides a method for preventing and controlling agricultural pests and diseases: the compound or the composition is applied to harmful substances or their living environment, or the composition is directly contacted with plants.

In order to better understand the present invention, the content of the present invention is further explained in conjunction with the following examples, but the content of the present invention is not limited to the following examples. All raw materials and solvents used in the examples are commercially available products.

Example 1

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

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, and the organic phase was collected by extraction with ethyl acetate, washed with 10% _{K2CO3 solution} , dried over anhydrous sodium sulfate, desolventized, and subjected to column chromatography ( _CH2Cl2 : _CH3OH =10:1, v/v) to obtain a yellow solid with a yield of 92.8 _% .

Its NMR data are: ¹ H NMR (500MHz, CDCl ₃ )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,CH ₂ ),3.09(s,1H,CH ₂ ),2.84(d,J＝1.4Hz,2H,CH ₂ ),1.97(s,1H,NH). ¹³ C NMR (126MHz,CDCl ₃ )δ149.08,140.71,136.09,133.71,130.14,127.34,122.04,121.38,119.60,118.45,111.05,110.55,57.22,42.45,22.49.

Example 2

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

5-Methoxytryptamine (0.15 g, 0.8 mmol) and p-trifluoromethoxybenzaldehyde (139 μL, 0.96 mmol) were added to a 15 mL pressure tube containing 6 mL of dichloromethane, and trifluoroacetic acid (94 μL, 1.2 mmol) was added. The mixture was heated and stirred at 60°C. The reaction was detected by TLC until the reaction was complete. The reaction was quenched with water, and the organic phase was collected by extraction with ethyl acetate and washed with 10% K ₂ CO ₃ solution, dried over anhydrous sodium sulfate, and the solvent was removed under vacuum. The product was purified by using dichloromethane: methanol = 10: 1 as the eluent to obtain a yellow solid with a yield of 56.3%.

Its nuclear magnetic data are: ¹ H NMR (400MHz, CDCl ₃ ) δ7.85 (s, 1H, NH), 7.31 (d, J = 8.6Hz, 2H, Ar-H), 7.20 (d, J = 8.1Hz, 2H, Ar-H), 7.08 (s, 1H, Ar-H), 7.04 (d, J＝2.4Hz, 1H, Ar-H), 6.83 (d, J＝2.4Hz, 1H, Ar-H), 5.13(s,1H,CH),3.89(s,3H,CH ₃ ),3.30(s,1H,CH2),3.13(s,1H,CH ₂ ),2.82(d,J＝0.9Hz,2H,CH ₂ ),1.91(s,1H,NH). ¹³ C NMR(101MHz, CDCl ₃ )δ154.05,148.97,148.95(q, ³ J _CF =2.4Hz),140.68,134.64,131.03,129.99,127.64,121.30(q, ¹ J _CF =258.3Hz),111.75,111.64,110.29,100.4 7,57.29,55.95 ,42.52,22.51.

The following compounds were prepared by similar steps to the above examples except that the corresponding raw materials were replaced. The structures and H NMR and C NMR data of the compounds are shown in Table 1, and the physicochemical properties are shown in Table 2.

Table 1 H NMR and C NMR data of compounds

Table 2 Physicochemical properties of target compounds

Test Example 1

EC ₅₀ (median effective concentration) is an important indicator for evaluating the sensitivity of plant pathogens to compounds. It is also an important parameter for setting compound concentration when studying the mechanism of action of target compounds. In the concentration gradient experiment, the two-fold dilution method was used to set 5 appropriate concentrations. Finally, the inhibition rate of the agent on plant pathogens and the concentration of the agent were converted into logarithmic values. The toxicity curve was obtained through regression analysis with SPSS software, and EC ₅₀ was calculated.

The effective medium concentration EC ₅₀ of the target compound against plant pathogens was tested by turbidity method. The test objects were Xanthoceras oryzae (Xoo), Xanthoceras citri citri (Xac) and Xanthoceras kiwifruit (Psa). DMSO was dissolved in NB medium as a blank control. Xanthoceras oryzae (on M210 solid medium) was placed in NB medium and cultured in a constant temperature shaker at 28℃ and 180rpm until the logarithmic growth phase for use; Xanthoceras citri citri (on M210 solid medium) was placed in NB medium; Xanthoceras oryzae (on M210 solid medium) was placed in NB medium and cultured in a constant temperature shaker at 28℃ and 180rpm until the logarithmic growth phase for use. 5 mL of toxic NB liquid culture medium containing different concentrations (e.g., 100, 50, 25, 12.5, 6.25 μg/mL) of the agent (compound) was added to a test tube, and 40 μL of NB liquid culture medium containing plant pathogenic bacteria was added respectively, and the mixture was shaken in a constant temperature shaker at 28-30°C and 180 rpm, wherein the rice bacterial leaf blight pathogen was cultured for 48 hours, the citrus canker pathogen was cultured for 48 hours, and the rice bacterial leaf streak pathogen was cultured for 36 hours. The OD ₅₉₅ value of the bacterial solution of each concentration was measured on an ELISA instrument, and the OD ₅₉₅ value of the toxic sterile NB liquid culture medium of the corresponding concentration was also measured.

Among them, NB medium: water: 1L, glucose: 10g, protein: 5g, beef extract: 3g, yeast powder: 1g, M210 solid medium: water: 1L, glucose: 10g, protein: 5g, beef extract: 3g, yeast powder: 1g, agar: 15g.

Corrected OD value = OD value of bacterial culture medium - OD value of sterile culture medium

Inhibition rate % = [(corrected control culture medium bacterial solution OD value - corrected toxic culture medium OD value) / corrected control culture medium bacterial solution OD value] × 100

The examples of the present invention are used to illustrate the technical solutions of the present invention, but the contents of the examples are not limited thereto. The experimental results of the target compounds are shown in Table 3.

Table 3 EC ₅₀ of 1,2,3,4-tetrahydro-β-carboline compounds containing alkyl or aryl substitution against plant pathogenic bacteria

As can be seen from Table 3, in the in vitro test, some target compounds showed good inhibitory activity against plant pathogenic bacteria (such as Xanthoceras oryzae, Xanthoceras citri citrifolia and Xanthoceras kiwifruit). Compound 17 had excellent inhibitory activity against Xanthoceras oryzae and Xanthoceras citrifolia, with EC ₅₀ values of 7.27 and 4.89 g mL ^-1 , respectively; Compound 8 had excellent inhibitory activity against Xanthoceras citrifolia, with EC ₅₀ value of 4.87 g mL ^-1 , and can be used to prepare pesticides against plant pathogenic bacteria.

Test Example 2:

The growth rate method was used to test the inhibition rate of the target compound (50 μg/mL) on plant pathogens, and the test objects were Botrytis cinerea (B. dothidea), Rice Sheath Blight (R. solani Kühn), Pepper Wilt (F. oxysporum), Eggplant Verticillium dahlia (V. dahlia), and Wheat Gibberellic Acid (G. zeae). Dimethyl sulfoxide (DMSO) was dissolved in the culture medium as a blank control. Weigh the compound to be tested with a 1/10,000 balance, add 1 mL DMSO to dissolve the compound, then transfer it to a 15 mL sterilized centrifuge tube on a sterile operating table, add 9 mL Tween-20 to make it 10 mL, pour it into the melted culture medium, mix it evenly and evenly distribute it into 9 culture dishes for cooling and standby use; in a sterile operating table, burn and sterilize the puncher (5 mm), make the colony into a bacterial cake, use a bacterial ring to connect the bacterial cake to the center of the culture medium, and culture it at 25-28°C for about 5 days. When the blank control colony grows to about 6 cm, use a ruler to measure it twice by the cross method, and take the average value as the diameter of the colony. Calculate the mycelium growth inhibition rate of each concentration according to the calculation formula.

Among them, DMSO is dissolved in PDA medium, and PDA medium is: potato, agar powder, glucose, magnesium sulfate, potassium dihydrogen phosphate, vitamin B1, natural pH, 121℃, and sterilization for 30 minutes. The specific process is: 1000mL potato boiled juice: peel the potato, wash and cut into strips, weigh 200g, and boil it in 1L secondary water until the potato strips can be gently crushed with fingers, and filter with gauze; weigh 20g agar powder in a beaker, add a small amount of cold water to disperse it, and then pour it into the boiling potato solution, and boil until the agar powder melts. During this period, it is necessary to stir quickly and continuously. Weigh 20g glucose, 1.5g magnesium sulfate, 3.0g potassium dihydrogen phosphate, and 10mg vitamin B1, add them to the filtrate, stir to dissolve, add secondary water to make up to 1L, natural pH, take 90mL while it is hot and divide it into 200mL conical flasks, seal it with a semi-permeable filter membrane, and sterilize it in a high-pressure sterilizer at 121℃ for 30 minutes for use.

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

0.5—is the diameter of the mother fungus cake/cm;

N1—control colony diameter, i.e., the colony diameter of the control group/cm;

N2—treated colony diameter, i.e., colony diameter treated with target compound/cm:

The examples of the present invention are used to illustrate the technical solutions of the present invention, but the contents of the examples are not limited thereto. The experimental results of the target compounds are shown in Table 4.

Table 4 Inhibitory activity of 1,2,3,4-tetrahydro-β-carboline compounds containing alkyl or aryl substitutions against plant pathogenic fungi

As can be seen from Table 4, 5 pathogenic fungi were selected as test objects, and the biological activity of some compounds was tested by the growth rate method. The test results showed that the series of compounds had general antifungal activity, among which compound 8 showed excellent inhibitory activity against rice sheath blight (R. solani Kühn); compound 18 also showed excellent inhibitory activity against eggplant Verticillium wilt (V. dahlia). It can be seen that the compounds of the present invention can be used to prepare pesticides against plant pathogenic fungi.

The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims (10)

1. A 1,2,3,4-tetrahydro-beta-carboline compound containing an alkyl group or an aryl group is characterized in that its structural formula is as follows:

In the formula, R1 and R2 are each independently selected from hydrogen, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted aryl, One or more of optionally substituted or unsubstituted heteroaryl, optionally substituted or unsubstituted benzyl, optionally substituted or unsubstituted α-methyl-benzyl; Or R1 and R2 are connected to form an optionally substituted 4-10 membered ring or a heteroatom-containing ring, and the heteroatom is at least one of N, O and S; R3 is selected from 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 One or more of the radicals, optionally substituted or unsubstituted benzyl, optionally substituted or unsubstituted α-methyl-benzyl. 2. The compound according to claim 1, wherein said R1 and R2 are each independently selected from hydrogen, optionally substituted or unsubstituted _C1-8 alkyl, optionally substituted or unsubstituted _C2-6 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, optionally substituted or unsubstituted Benzyl; Or R1 and R2 are connected to form an optionally substituted 5-10 membered ring or a heteroatom-containing ring, and the heteroatom is at least one of N, O and S; 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, optionally substituted or unsubstituted benzyl. 3. The compound according to claim 1 or 2, characterized in that, said R1, R2 and R3 independently select 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-dimethyl Hexyl, 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-di Chlorophenyl, 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, cyclo Pentyl, furylmethyl, thienylmethyl, α-methylbenzyl, fluoro-α-methylbenzyl, methoxy-α-methylbenzyl. 4. The preparation method of the alkyl or aryl-containing 1,2,3,4-tetrahydro-β-carboline compound according to any one of claims 1 to 3, characterized in that, tryptamine or tryptamine Derivatives are used as starting materials, trifluoroacetic acid is used as a catalyst, and ketones or aldehydes are heated and stirred in a solvent at 60°C for 6h to 8h. 5. preparation method according to claim 4 is characterized in that, the mol ratio of described ketone and tryptamine or tryptamine derivative is 1.2:1; The mol ratio of described aldehyde and tryptamine or tryptamine derivative is 1.2:1. 6. preparation method according to claim 4 is characterized in that, described solvent is dichloromethane. 7. A composition comprising a compound according to any one of claims 1 to 3. 8. according to the described composition of claim 7, it is characterized in that, the dosage form of described composition is emulsifiable concentrate, wettable powder, granule, aqueous preparation, suspending agent, ultra-low volume spray, soluble powder, microcapsule, Smoke agent, water emulsion or water dispersible granule. 9. The application of the compound according to any one of claims 1 to 3 or the composition according to any one of claims 7 to 8 in the prevention and control of agricultural diseases and insect pests; the agricultural diseases and insect pests are plant bacterial diseases or plant fungal diseases. 10. A method for preventing and controlling agricultural diseases and insect pests, characterized in that the compound according to any one of claims 1 to 3 or the composition according to any one of claims 7 to 8 acts on harmful substances or their living environment, or The composition is applied directly to the plant.