Anthracene-9,10-dione compounds and their preparation methods and applications, applications of sulfonamide compounds, and a pharmaceutical

Abstract

The present invention relates to the field of pesticides and discloses an anthracene-9,10-dione compound, its preparation method and application, the application of a sulfonamide compound, and a pharmaceutical agent. The anthracene-9,10-dione compound has the structure represented by formula (I), and the sulfonamide compound has the structure represented by formula (II). The anthracene-9,10-dione compound and the sulfonamide compound provided by the present invention can be used to effectively enhance the ability of plant seedlings to emerge from the soil and delay the flowering period of plants, and have high application value. #imgabs0#

Description

Technical Field

[0001] The present invention relates to the field of pesticides, and in particular to an anthracene-9,10-dione compound, a preparation method and application thereof, an agent for enhancing the ability of plant seedlings to emerge from the soil and / or delaying the flowering period of plants, and applications of a sulfonamide compound in enhancing the ability of plant seedlings to emerge from the soil and / or delaying the flowering period of plants, and an agent for enhancing the ability of plant seedlings to emerge from the soil and / or delaying the flowering period of plants. Background Art

[0002] The time of seed emergence affects the emergence rate and uniformity, especially when the soil is compacted or under adverse growth conditions. Seeds that emerge early can carry out photosynthesis earlier, thereby improving their adaptability to the environment. Seed emergence mainly depends on the elongation of the hypocotyl / coleoptile, which is mainly related to the plant's sensitivity to external light quality. Plants sense changes in the external photoperiod through light receptor proteins, regulate photomorphogenesis, and control plant growth and development. Cryptochrome (CRY) is a highly conserved blue light receptor that can sense external blue light signals and then regulate plant photomorphogenesis, photoperiodic flowering, circadian rhythms, and stomatal opening and closing. By regulating the activity of CRY proteins, plant photomorphogenesis, photoperiodic flowering, vegetative growth and reproductive growth can be effectively regulated, which plays an important role in regulating the growth, development, and quality of crops. Inhibiting the activity of CRY can relieve the inhibition of CRY on the elongation of hypocotyl / coleoptile under blue light and promote the emergence of seedlings; it can inhibit stomatal guard cells, promote stomatal closure, and inhibit transpiration; it can also inhibit the photoperiod flowering process, delay the flowering process, and regulate the flowering period.

[0003] Cryptochromes have a wide range of biological activities, and plant growth regulators targeting cryptochromes have important potential applications. In recent years, a research group has obtained the cryptochrome inhibitor 3-bromo-7-nitroindazole (3B7N) through high-throughput screening technology, which can relieve the inhibition of blue light on hypocotyl elongation (WO2018074554A1). However, the activity of this compound is still unsatisfactory and its stability is poor, which limits its application in agriculture.

[0004] Therefore, the design and synthesis of compounds that modulate cryptochrome activity, and thereby regulate plant photomorphogenesis and growth, is a hot area of chemical research. Research and development of compounds that regulate photomorphogenesis could improve the uniformity of seedlings and enhance their adaptability to the external environment by promoting earlier emergence. Research and development of compounds that modulate cryptochrome activity could also regulate the flowering period of plants. Summary of the Invention

[0005] The purpose of the present invention is to provide a compound to enhance the emergence ability of plant seedlings and delay the flowering period of plants.

[0006] To achieve the above objectives, the first aspect of the present invention provides an anthracene-9,10-dione compound or its stereoisomers, geometric isomers, tautomers, or agrochemically acceptable salts, prodrugs, hydrates, solvates, or metabolites, wherein the compound has a structure represented by formula (I):

[0007]

[0008] Wherein, in formula (I),

[0009] One of R1 and R2 is -L1-L2-R 1 -X, the other is H; or, R1 is a group represented by formula (I-1), and R2 is H;

[0010] One of L1 and L2 is -NH-, and the other is

[0011] R 1 Selected from C 1-5 Alkylene, -NHCH2CH2-;

[0012] X is selected from -OH, halogen, -COOCH3; and when X is -COOCH3 or halogen, L1 is -NH-;

[0013] One of R3 and R4 is the same as R1, and the other is H; or, both R3 and R4 are H;

[0014] And when R1 is -L1-L2-CH2CH2OH or -L1-L2-(CH2)4OH, R3 or R4 is the same as R1.

[0015] A second aspect of the present invention provides a method for preparing anthracene-9,10-dione compounds having a structure represented by formula (I) or stereoisomers, geometric isomers, tautomers thereof, or agrochemically acceptable salts, prodrugs, hydrates, solvates, and metabolites thereof, the method comprising: contacting a compound represented by formula (A) with a compound represented by formula (B) or a compound represented by formula (C) in the presence of a solvent;

[0016] H2N-R 1 -X type (B) or

[0017] Wherein, L4 is selected from H, L3, L5, L6 are each independently selected from H,

[0018]

[0019] Wherein, in formula (B), R 1 The definition of X is the same as that described in the first aspect.

[0020] The third aspect of the present invention provides the use of the anthracene-9,10-dione compound described in the first aspect or its stereoisomers, geometric isomers, tautomers, or agrochemically acceptable salts, prodrugs, hydrates, solvates, and metabolites in enhancing the ability of plant seedlings to emerge from the soil and / or delaying the flowering period of plants.

[0021] A fourth aspect of the present invention provides an agent for enhancing the ability of plant seedlings to emerge from the soil and / or delaying the flowering period of plants. The active ingredient of the agent is the anthracene-9,10-dione compound described in the first aspect, or at least one of its stereoisomers, geometric isomers, tautomers, or agrochemically acceptable salts, prodrugs, hydrates, solvates, and metabolites. The content of the active ingredient is 0.1-100% by weight, based on the total weight of the agent.

[0022] The fifth aspect of the present invention provides the use of a sulfonamide compound represented by formula (II) in enhancing the ability of plant seedlings to emerge from the soil and / or delaying the flowering period of plants.

[0023]

[0024] Wherein, in formula (II), one of W and Z is -S(O)2-, and the other is -NH-;

[0025] R b Selected from hydroxy-substituted C 1-6 of alkyl.

[0026] A sixth aspect of the present invention provides an agent for enhancing the ability of plant seedlings to emerge from the soil and / or delaying the flowering period of plants, wherein the active ingredient of the agent is a sulfonamide compound represented by formula (II) or at least one of its stereoisomers, geometric isomers, tautomers, or agrochemically acceptable salts, prodrugs, hydrates, solvates, and metabolites, and the content of the active ingredient is 0.1-100% by weight, based on the total weight of the agent;

[0027]

[0028] Among them, W, Z, R b The definition is the same as that described in the fifth aspect.

[0029] The anthracene-9,10-dione compound of the structure represented by formula (I) provided by the present invention has excellent ability to enhance plant seedling emergence from soil, delay plant flowering period, and has high application value.

[0030] The inventors of the present invention have discovered for the first time that the sulfonamide compound represented by formula (II) can significantly enhance the ability of plant seedlings to emerge from the soil and delay the flowering period of plants, and thus has high application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1a These are phenotypic images of the hypocotyls of Arabidopsis thaliana treated with 5 μM concentrations of compounds N1 and N2, and the control group, after being cultured at room temperature for 5 days under continuous irradiation of blue light at intensities of 400 lux and 100 lux, respectively.

[0032] Figure 1b This is a statistical graph of the length of the hypocotyls of Arabidopsis thaliana treated with 5 μM concentrations of compounds N1 and N2 and the control group after being cultured at room temperature for 5 days under continuous irradiation of blue light with intensities of 400 lux and 100 lux, respectively.

[0033] Figure 1c These are phenotypic images of the hypocotyls of Arabidopsis thaliana treated with 5 μM concentrations of Compound 1, Compound 2, Compound 6, and Compound 8, as well as a control group, after being cultured at room temperature for 5 days under continuous irradiation with 400 lux blue light.

[0034] Figure 1d This is a statistical result graph of the hypocotyl length of Arabidopsis thaliana treated with 5 μM concentration of Compound 1, Compound 2, Compound 6, and Compound 8 and the control group after being cultured at room temperature for 5 days under continuous irradiation of 400 lux intensity blue light.

[0035] Figure 2a 、 Figure 2b The figure shows the results of measuring the specific binding of compound N1 to the receptor protein AtCRY2 using microthermophoresis (MST) and comparing it with ATP;

[0036] Figure 2a This is a schematic diagram of the MST test results of compound ATP and receptor protein AtCRY2;

[0037] Figure 2b This is a schematic diagram of the MST test results of compound N1 and receptor protein AtCRY2.

[0038] Figure 3a This is a comparison chart of the results of compounds N1 and N2 in Test Example 3 accelerating the emergence rate of wheat seedlings.

[0039] Figure 3b This is a statistical chart showing the effects of compounds N1, N2 and the control (CK) on the emergence rate of wheat seedlings in Test Example 3.

[0040] Figure 4a This is a comparison chart of the results of compound N1 in Test Example 4 delaying the flowering period of Arabidopsis thaliana.

[0041] Figure 4b This is a statistical graph showing the results of compound N1 and the control group delaying the flowering period of Arabidopsis thaliana in Test Example 4.

[0042] Figure 4c This is a comparison chart of the results of Compound 1 in Test Example 4 delaying the flowering period of Arabidopsis thaliana.

[0043] Figure 4d This is a statistical graph showing the results of compound 1 and the control group delaying the flowering period of Arabidopsis thaliana in Test Example 4. DETAILED DESCRIPTION

[0044] The endpoints of the ranges and any values disclosed herein are not limited to the precise ranges or values, and these ranges or values should be understood to include values close to these ranges or values. For numerical ranges, the endpoints of each range, the endpoints of each range and individual point values, and the individual point values can be combined with each other to obtain one or more new numerical ranges, which should be considered to be specifically disclosed herein.

[0045] The following terms are explained for the present invention:

[0046] In this article, the wavy lines in the groups Indicates the bonding position.

[0047] "Halogen" includes fluorine, chlorine, bromine and iodine.

[0048] “C 1-5 "Alkylene" means an alkylene group having 1 to 5 carbon atoms, which can be 1, 2, 3, 4 or 5. For example, C 1-5 The alkylene group may be methylene, ethylene, n-propylene, isopropylene, butylene, pentylene, or the like.

[0049] In the present invention, the alkylene group refers to the residue after an alkane loses two hydrogen atoms. The two hydrogen atoms can be two hydrogen atoms on the same carbon atom or two hydrogen atoms on different carbon atoms. The group can be linear or branched. For example, the ethylene group can be -CH2CH2- or -CH(CH3)-.

[0050] "Hydroxy-substituted C 1-6 "Alkyl" means that at least one H in a straight-chain or branched alkyl group with 1 to 6 carbon atoms is replaced by a hydroxy group, and the total number of carbon atoms can be 1, 2, 3, 4, 5, or 6. For example, the group can be -CH2OH, -CH2CH2OH, -CH(CH3)OH, -CH2CH2CH2CH2OH, -(CH2)6OH, etc.

[0051] "Hydrate" refers to the compound of formula (I) provided herein, which forms a solid or liquid molecular compound by hydration with water. It can also be said to be an association compound formed when the solvent molecule is water. Solid hydrates contain water in a stoichiometric ratio as so-called water of crystallization, wherein the water molecules are not necessarily equivalent to their bound state. For example, the hydrate may be a monohydrate, a dihydrate, etc.

[0052] "Solvate" refers to an association formed between one or more solvent molecules and the compound of the present invention. Solvents that form solvates include but are not limited to water, isopropanol, ethanol, methanol, dimethyl sulfoxide, ethyl acetate, and the like.

[0053] "Prodrug" refers to the compound of the above general formula (I) provided by the present invention, which itself may be biologically active or inactive, but can be converted into a corresponding biologically active form (eg, by metabolism, solvent or other means).

[0054] "Metabolites" refer to products produced by the metabolism of a specific compound or its salt in a plant. Metabolites of a compound can be identified using techniques known in the art, and their activity can be characterized using assays such as those described herein. Such products can be obtained by oxidation, reduction, hydrolysis, amidation, deamidation, esterification, defatting, enzymatic cleavage, or the like of the administered compound.

[0055] As mentioned above, the first aspect of the present invention provides an anthracene-9,10-dione compound or its stereoisomers, geometric isomers, tautomers, or agrochemically acceptable salts, prodrugs, hydrates, solvates, or metabolites, wherein the compound has a structure shown in formula (I):

[0056]

[0057] Wherein, in formula (I),

[0058] One of R1 and R2 is -L1-L2-R 1 -X, the other is H; or, R1 is a group represented by formula (I-1), and R2 is H;

[0059] One of L1 and L2 is -NH-, and the other is

[0060] R 1 Selected from C 1-5 Alkylene, -NHCH2CH2-;

[0061] X is selected from -OH, halogen, -COOCH3; and when X is -COOCH3 or halogen, L1 is -NH-;

[0062] One of R3 and R4 is the same as R1, and the other is H; or, both R3 and R4 are H;

[0063] And when R1 is -L1-L2-CH2CH2OH or -L1-L2-(CH2)4OH, R3 or R4 is the same as R1.

[0064] Preferably, R 1 Selected from -(CH2)2-, -(CH2)3-, -(CH2)4-, -(CH2)5-, -NHCH2CH2-.

[0065] Preferably, X is selected from -OH, -Br, -COOCH3.

[0066] According to a preferred embodiment, the anthracene-9,10-dione compound of the present invention is selected from at least one of the following compounds:

[0067] Compound 1: Compound 2:

[0068] Compound 3: Compound 4:

[0069] Compound 5: Compound 6:

[0070] Compound 7: Compound 8:

[0071] Compound 9: Compound 10:

[0072] Compound 11:

[0073] As mentioned above, the second aspect of the present invention provides a method for preparing anthracene-9,10-dione compounds of the structure represented by formula (I) or stereoisomers, geometric isomers, tautomers, or agrochemically acceptable salts, prodrugs, hydrates, solvates, and metabolites thereof, the method comprising: contacting a compound represented by formula (A) with a compound represented by formula (B) or a compound represented by formula (C) in the presence of a solvent;

[0074] H2N-R 1 -X type (B) or

[0075] Wherein, L4 is selected from H, L3, L5, L6 are each independently selected from H,

[0076]

[0077] Wherein, in formula (B), R 1 The definitions of X are the same as those described in the first aspect. The present invention will not be described in detail here, and those skilled in the art should not be construed as limiting the present invention.

[0078] Preferably, the contacting conditions include: a reaction temperature of 0-200°C and a reaction time of 0.5-24 hours. The contacting in the present invention is preferably carried out under stirring conditions. The present invention does not particularly limit the stirring speed, and those skilled in the art can use known technical means to carry out the contacting.

[0079] Preferably, the solvent is selected from at least one of tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, dimethyl sulfoxide, ethyl acetate, acetone, ethanol, water, dichloromethane, chloroform, and acetonitrile.

[0080] Preferably, the amount of the solvent used is 1-100 mL relative to 1 mmol of the compound represented by formula (A).

[0081] Preferably, the molar ratio of the compound represented by formula (A) to the compound represented by formula (B) is 1:0.8-2.4.

[0082] The aforementioned preparation method of the present invention may also involve various post-processing operations known in the art, such as extraction, washing, filtration, column chromatography, recrystallization, etc. The present invention has no particular limitation thereto, and those skilled in the art should not interpret this as a limitation of the present invention.

[0083] The raw materials involved in the preparation method of the present invention can be synthesized according to the raw material structural formula in combination with organic synthesis methods in the art, or can be obtained commercially. The preparation methods of a few raw materials are exemplified below, and those skilled in the art should not be construed as limiting the present invention.

[0084] As mentioned above, the third aspect of the present invention provides the use of the anthracene-9,10-dione compound described in the first aspect or its stereoisomers, geometric isomers, tautomers, or agrochemically acceptable salts, prodrugs, hydrates, solvates, and metabolites in enhancing the ability of plant seedlings to emerge from the soil and / or delaying the flowering period of plants.

[0085] Preferably, the plant is selected from at least one of wheat, peanut, corn, cotton, mung bean, rice, soybean, Arabidopsis, sorghum and rapeseed.

[0086] As described above, the fourth aspect of the present invention provides an agent for enhancing the ability of plant seedlings to emerge from the soil and / or delaying the flowering period of plants, wherein the active ingredient of the agent is the anthracene-9,10-dione compound described in the first aspect or at least one of its stereoisomers, geometric isomers, tautomers, or agrochemically acceptable salts, prodrugs, hydrates, solvates, and metabolites, and the content of the active ingredient is 0.1-100 weight % based on the total weight of the agent.

[0087] Preferably, the content of the active ingredient is 5-90% by weight. Exemplarily, the content of the active ingredient is 10% by weight, 15% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, 50% by weight, 55% by weight, 60% by weight, 65% by weight, 70% by weight, 75% by weight, 80% by weight, 85% by weight, etc.

[0088] The agent for enhancing the emergence ability of plant seedlings and / or delaying the flowering period of plants of the present invention may further contain various additives, auxiliary materials, solvents, etc. commonly used in the art, and the present invention has no particular limitation thereto.

[0089] Preferably, the dosage form of the medicament is at least one selected from hydrate, powder, granule, suspension and emulsion.

[0090] As mentioned above, the fifth aspect of the present invention provides the use of a sulfonamide compound represented by formula (II) in enhancing the emergence ability of plant seedlings and / or delaying the flowering period of plants.

[0091]

[0092] Wherein, in formula (II), one of W and Z is -S(O)2-, and the other is -NH-;

[0093] R b Selected from hydroxy-substituted C 1-6 of alkyl.

[0094] Preferably, R b Selected from hydroxy-substituted C 1-6 of a straight chain alkyl group.

[0095] According to a preferred embodiment, the sulfonamide compound of the present invention is selected from at least one of the following compounds:

[0096] Compound N1: Compound N2:

[0097] Compound N3: Compound N4:

[0098] The plant in the present invention is preferably at least one of wheat, peanut, corn, cotton, mung bean, rice, soybean, Arabidopsis, sorghum, and rapeseed.

[0099] As mentioned above, the sixth aspect of the present invention provides an agent for enhancing the ability of plant seedlings to emerge from the soil and / or delaying the flowering period of plants, wherein the active ingredient of the agent is a sulfonamide compound represented by formula (II) or at least one of its stereoisomers, geometric isomers, tautomers, or agrochemically acceptable salts, prodrugs, hydrates, solvates, and metabolites, and the content of the active ingredient is 0.1-100% by weight based on the total weight of the agent;

[0100]

[0101] Among them, W, Z, R b The definition of is the same as that described in the fifth aspect. The present invention will not be described in detail here, and those skilled in the art should not be understood as limiting the present invention.

[0102] Preferably, the content of the active ingredient is 5-90% by weight. Exemplarily, the content of the active ingredient is 10% by weight, 15% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, 50% by weight, 55% by weight, 60% by weight, 65% by weight, 70% by weight, 75% by weight, 80% by weight, 85% by weight, etc.

[0103] The agent for enhancing the emergence ability of plant seedlings and / or delaying the flowering period of plants of the present invention may further contain various additives, auxiliary materials, solvents, etc. commonly used in the art, and the present invention has no particular limitation thereto.

[0104] Preferably, the dosage form of the medicament containing sulfonamide compounds of the present invention is at least one selected from hydrates, powders, granules, suspensions and emulsions.

[0105] The plant in the present invention is preferably at least one of wheat, peanut, corn, cotton, mung bean, rice, soybean, Arabidopsis, sorghum, and rapeseed.

[0106] The sulfonamide compounds represented by the aforementioned formula (II) of the present invention can be prepared by existing methods or can be commercially available; the present invention is not particularly limited thereto. The present invention hereinafter provides several exemplary methods for preparing the compounds, which should not be construed by those skilled in the art as limiting the present invention.

[0107] The present invention will be described in detail below through preparation examples and test examples. In the following preparation examples and tests, all raw materials used are commercially available unless otherwise specified. Unless otherwise specified, room temperature refers to 25±3°C.

[0108] Preparation Example 1: Preparation of Compound 1

[0109]

[0110] Step 1: In a 100-mL single-necked round-bottom flask at room temperature, add 40 mL of thionyl chloride, 0.2 mL of N,N-dimethylformamide, and 4.96 g of sodium anthraquinone-1-sulfonate. The reaction system is then heated to 80°C and refluxed for 5 hours. After completion of the reaction, the remaining thionyl chloride is removed using a rotary evaporator, and the remaining mixture is slowly added to ice water. A large amount of solid material precipitates, which is then filtered under reduced pressure and dried to yield 9,10-anthracenedione-1-sulfonyl chloride as a yellow solid in a 90% yield.

[0111] Step 2: In a 100 mL single-necked round-bottom flask, add 20 mL of 1,4-dioxane, 9,10-anthracenedione-1-sulfonyl chloride (2.0 mmol), 5-amino-1-pentanol (2.0 mmol), and triethylamine (1 mL) in that order. Stir the reaction at room temperature for 6 hours. After the reaction, remove all solvents using a rotary evaporator. Add 20 mL of saturated brine to the mixture, and extract the desired product with ethyl acetate (20 mL x 3). The organic layer is collected and dried over anhydrous sodium sulfate. Purify by column chromatography using a 1:2 volume ratio of petroleum ether to ethyl acetate as the eluent to obtain a light yellow solid in a 62% yield.

[0112] 1 H NMR(600MHz,DMSO-d6)δ8.50(d,1H),8.47(d,1H),8.22–8.13(m,2H),8.09(t,1H),8.01–7.90(m, 2H),7.28(s,1H),4.23(t,1H),3.27(s,2H),2.95(t,2H),1.41(m,2H),1.29(m,2H),1.20(m,2H). 13 C NMR(151MHz,DMSO-d6)δ183.07,182.07,141.42,136.19,135.65,135.39,135.13,134.7 3,134.40,132.42,132.01,131.47,127.52,126.98,60.90,43.64,32.39,29.61,23.00.

[0113] Preparation Example 2: Preparation of Compound 2

[0114]

[0115] To a 100 mL single-necked round-bottom flask, 20 mL of 1,4-dioxane, 9,10-anthracenedione-1-sulfonyl chloride (2.0 mmol), L-proline methyl ester hydrochloride (2.0 mmol), and triethylamine (1 mL) were added sequentially and stirred at room temperature for 6 hours. After the reaction, all solvents were removed using a rotary evaporator. 20 mL of saturated brine was added to the mixture, and the desired product was extracted with ethyl acetate (20 mL x 3). The organic layer was collected, dried over anhydrous sodium sulfate, and purified by column chromatography to obtain a light yellow solid in a 65% yield.

[0116] 1 H NMR(400MHz,DMSO-d6)δ8.50(dd,1H),8.40(dd,1H),8.20-8.13(m,2H),8.08(t,1H), 7.99-7.91(m,2H),4.74(dd,1H),3.58(s,3H),3.49(m,1H),2.37(m,1H),2.00(m,3H). 13 C NMR(101MHz,DMSO-d6)δ182.02,181.92,173.06,140.35,136.17,135.48,135.40,134.82,1 34.55,134.51,133.01,132.31,131.43,127.30,126.88,61.21,52.50,49.16,30.93,24.82.

[0117] Preparation Example 3: Preparation of Compound 5

[0118]

[0119] In a 100mL three-necked round-bottom flask, 20mL of tetrahydrofuran and 2mmol of sulfonyl chloride were added in sequence. A constant pressure dropping funnel was used to dropwise add a tetrahydrofuran solution (20mL) of 1-aminoanthraquinone (2mmol) and react at 45°C for 6 hours. Subsequently, a tetrahydrofuran solution of ethanolamine (2.2mmol) was added dropwise and the reaction was continued at 45°C for 6 hours. After the reaction was completed, the solvent was removed using a rotary evaporator. 20mL of saturated brine was added to the mixture, and the product was extracted with ethyl acetate (20mL×3 times). The organic layer was collected and dried over anhydrous sodium sulfate and purified by column chromatography to obtain the target product with a yield of 45%.

[0120] 1H NMR (400MHz, CDCl3) δ10.52(s,1H),8.27–8.16(m,2H),7.76(m,2H),7.66–7.45(m,2H),7.34(s,1H),7.08(dd,1H),3.47(t,2H),2.98(q,2H). 13 C NMR (101MHz, CDCl3) δ185.67,182.43,148.36,135.64,134.45,133.39,126.83,126.76,119.86,116.46,59.81,43.37.

[0121] Preparation Example 4: Preparation of Compound 6

[0122]

[0123] Step 1: In a 100-mL single-necked round-bottom flask at room temperature, add 40 mL of thionyl chloride, 0.2 mL of N,N-dimethylformamide, and 3.55 g of dipotassium anthraquinone-1,8-disulfonate. The mixture was then heated to 80°C and refluxed for 5 hours. After the reaction was complete, the remaining thionyl chloride was removed using a rotary evaporator, and the remaining mixture was slowly added to ice water. A large amount of solid material precipitated, which was filtered under reduced pressure and dried to obtain a yellow solid compound, anthraquinone-1,8-disulfonyl chloride, in an 85% yield.

[0124] Step 2: In a 100 mL single-necked round-bottom flask, add 20 mL of 1,4-dioxane, anthraquinone-1,8-disulfonyl chloride (2.0 mmol), ethanolamine (4.4 mmol), and triethylamine (1 mL) in sequence. Stir and react at room temperature for 6 hours. After the reaction, remove all solvents using a rotary evaporator. Add 20 mL of saturated brine to the mixture, and extract the desired product with ethyl acetate (20 mL x 3). Collect the organic layer and dry it over anhydrous sodium sulfate. The filtrate is then drained under reduced pressure and purified by column chromatography to obtain a reddish-brown solid in a 65% yield.

[0125] 1 H NMR (600MHz, DMSO-d6) δ8.45(ddd,4H),8.07(t,2H),7.15(t,2H),4.65(s,2H),3.37(d,4H),2.98(d,4H). 13 C NMR (151MHz, DMSO-d6) δ184.27,180.70,140.41,135.25,134.35,133.93,132.71,130.44,59.58,45.42.

[0126] Compounds 3 to 4, and compounds 7 to 11 of the present invention were prepared using a method similar to the above preparation examples, and the NMR data were:

[0127] Compound 3:

[0128] 1 H NMR (400MHz, CDCl3) δ9.88(s,1H),8.27–8.16(m,2H),7.72(m,2H),7.66–7.50(m,2H),7.02(dd,1H),4.37(q,2H),3.47(t,2H). 13 C NMR (101MHz, CDCl3) δ185.37,183.43,150.36,135.64,134.05,133.29,126.83,126.76,116.86,116.56,66.61,37.37.

[0129] Compound 4:

[0130] 1 H NMR(400MHz, CDCl3)δ9.88(s,1H),8.29–8.26(m,2H),8.32(m,1H),7.85(m,1 H),7.56–7.40(m,2H),7.31(dd,1H),3.80(q,2H),3.55(s,3H),2.63(t,2H). 13 C NMR (101MHz, CDCl3) δ185.67,182.43,175.66,150.36,137.64,134.15,133.29,126.83,126.76,116.86,116.56,55.22,51.96,22.45.

[0131] Compound 7:

[0132] 1 H NMR (600MHz, DMSO-d6) δ8.45(ddd,4H),8.07(t,2H),7.15(t,2H),4.65(s,2H),3.75(t,4H),3.24(q,4H),1.78(m,4H). 13 C NMR (151MHz, DMSO-d6) δ184.27,180.70,140.41,135.25,134.35,133.93,132.71,130.44,59.86,40.85,32.29.

[0133] Compound 8:

[0134] 1 H NMR (600MHz, DMSO-d6) δ8.45 (m, 4H), 8.07 (t, J = 7.8Hz, 2H), 7.24 (t, 2H), 4. 22(s,2H),3.30(t,4H),2.91(q,4H),1.49-1.43(m,4H),1.38-1.32(m,4H). 13 C NMR (151MHz, DMSO-d6) δ184.00,180.62,140.53,135.37,134.46,133.99,132.67,130.44,60.06,42.92,29.37,25.98.

[0135] Compound 9:

[0136] 1 H NMR (600MHz, DMSO-d6) δ8.55(m,4H),8.17(t,2H),7.24(t,2H),4.22(s,2H),3.30(t,4H),2.91(q,4H),1.49-1.43(m,4H),1.38-1.32(m,4H). 13 C NMR (151MHz, DMSO-d6) δ182.62,140.53,135.37,134.46,133.99,132.67,130.44,60.06,42.92,29.37,25.98.

[0137] Compound 10:

[0138] 1 H NMR(400MHz, CDCl3)δ8.58(dd,2H),8.29–8.18(m,2H),7.94(t,1H),7.86–7. 75(m,2H),6.93(t,1H),3.75(t,2H),3.24(q,2H),2.14(s,1H),1.78(m,2H). 13 C NMR (101MHz, CDCl3) δ184.06,181.86,140.76,136.22,135.93,134.93,134.78, 134.27,133.95,132.10,132.08,131.90,128.01,127.10,59.86,40.85,32.29.

[0139] Compound 11:

[0140] 1 H NMR (400MHz, CDCl3) δ8.80(s,1H),8.54-8.22(m,5H),7.87(s,2H),5.16(s,1H),3.76(t,2H),3.23(t,2H). 13 C NMR (101MHz, CDCl3) δ182.62,181.68,141.50,135.72,135.35,134.91,134. 61,134.20,133.75,131.90,131.45,131.25,127.21,126.51,59.52,45.65.

[0141] Preparation Example 5: Preparation of Compound N1

[0142]

[0143] Step 1: In a 100-mL single-necked round-bottom flask at room temperature, add 40 mL of thionyl chloride, 0.2 mL of N,N-dimethylformamide, and 4.96 g of sodium anthraquinone-1-sulfonate. The temperature was then raised to 80°C and refluxed for 5 hours. After the reaction was complete, the remaining thionyl chloride was removed using a rotary evaporator, and the remaining mixture was slowly added to stirring ice water. A large amount of solid material precipitated, which was filtered under reduced pressure and dried to obtain 9,10-anthracenedione-1-sulfonyl chloride as a yellow solid in a 90% yield.

[0144] Step 2: In a 100-mL single-necked round-bottom flask, add 20 mL of 1,4-dioxane, 613.4 mg of 9,10-anthracenedione-1-sulfonyl chloride, 146.6 mg of ethanolamine, and 1 mL of triethylamine. Stir the reaction at room temperature for 6 hours. After the reaction, remove all solvents using a rotary evaporator. Add 20 mL of saturated brine to the mixture, and extract the desired product with ethyl acetate (20 mL x 3). Collect the organic layer and dry it over anhydrous sodium sulfate. The filtrate is then dried under reduced pressure and subjected to column chromatography using a 1:2 volume ratio of petroleum ether to ethyl acetate as the eluent to obtain a light yellow solid in 90% yield.

[0145] 1H NMR(400MHz,DMSO-d6)δ8.51-8.47(m,2H),8.18-8.13(m,2H),8.11-8.06(t,1H),7.95 -7.91(m,2H),7.29-7.26(t,1H),4.03(br,1H),3.40-3.37(t,2H),3.04-3.00(q,2H). 13 C NMR(101MHz,DMSO-d6)δ182.71,181.58,140.50,135.70,135.34,134.94,134 .71,134.30,133.85,131.90,131.45,131.15,127.15,126.49,59.49,45.62.

[0146] Compounds N2-N4 of the present invention were prepared by a method similar to the above preparation example, and the NMR data were:

[0147] Compound N2: 1 H NMR (400MHz, CDCl3) δ8.60(ddd,2H),8.31–8.22(m,2H),7.95(t,1H),7.90–7.80(m,2H),6.80(t,1H),3.63(t,2H),3.15(q,2H),1.62(m,4H). 13 C NMR (101MHz, CDCl3) δ184.18,181.81,140.93,136.15,135.87,134.87,134.73,134 .24,133.88,132.05,132.03,131.79,127.97,127.06,62.15,43.53,29.55,26.41.

[0148] Compound N3: 1 H NMR(600MHz,DMSO-d6)δ8.51(d,1H),8.48(d,1H),8.18(s,2H),8.10(t,1H),7.96(t,2H),7 .29(s,1H),4.23(t,1H),3.29(t,2H),2.96(d,2H),1.41(m,2H),1.29(m,2H),1.17(m,4H). 13C NMR(151MHz,DMSO-d6)δ182.51,181.51,140.89,135.62,135.12,134.85,134.58,134.19,1 33.83,131.86,131.45,130.91,126.97,126.43,60.44,43.03,32.24,29.24,25.81,24.92.

[0149] Compound N4: 1 H NMR (400MHz, CDCl3) δ10.58(m,1H),8.31–8.22(m,3H),7.95(t,1H),7.90–7.80(m,2H),4.24(s,1H),4.09(t,2H),3.60(q,2H).

[0150] Test Example 1

[0151] This test example is used to illustrate the activity of anthracene-9,10-dione compounds with a structure represented by formula (I) and sulfonamide compounds with a structure represented by formula (II) in relieving the inhibition of hypocotyl elongation by blue light.

[0152] Initial screening test (MS culture medium method):

[0153] The plants under investigation were wild-type (Columbia type, Col-0) Arabidopsis thaliana;

[0154] The sterilized and vernalized Arabidopsis seeds were cultured in a light incubator at 23°C, 16 hours of light, and 8 hours of darkness. When the Arabidopsis seeds germinated and turned white, they could be transplanted for use.

[0155] Compounds 1 to 11 and compounds N1 to N4 were added to MS medium at a final concentration of 5 μM. All compounds were dissolved in DMSO and tested with 0.5% (volume fraction) DMSO added to the medium. A blank control was used: MS medium containing 0.5% (volume fraction) DMSO. Arabidopsis seedlings of uniform growth were selected for transplantation. After transplantation, they were placed vertically in an incubator and cultured at 23°C with continuous blue light of 400 lux and 100 lux, respectively. Images were taken after 5 days of growth.

[0156] For example, in Figure 1a The following pictures show the hypocotyl length of Arabidopsis thaliana seedlings treated with compound N1 and compound N2 and the blank control under blue light intensity of 400 lux and 100 lux respectively; Figure 1bThe hypocotyl length statistics of Arabidopsis thaliana seedlings treated with compound N1 and compound N2 and the blank control under blue light intensity of 400 lux and 100 lux respectively are given in the table. Figure 1a 、 Figure 1b It can be seen that compared with the control group, compounds N1 and N2 can promote the elongation of hypocotyls and enhance the ability of plant seedlings to emerge from the soil.

[0157] For example, in Figure 1c The hypocotyl length phenotypes of Arabidopsis seedlings cultured under 400 lux blue light intensity for compound 1, compound 2, compound 6, compound 8 and blank control are given in FIG; Figure 1d The hypocotyl length statistics of Arabidopsis thaliana seedlings treated with Compound 1, Compound 2, Compound 6, and Compound 8 and the blank control under blue light (400 lux) are given in FIG. Figure 1c 、 Figure 1d It can be seen that compared with the control group, compound 1, compound 2, compound 6, and compound 8 can promote hypocotyl elongation and enhance the ability of plant seedlings to emerge from the soil.

[0158] The hypocotyl length of each Arabidopsis seedling was measured using ImageJ-2x software, the average hypocotyl length of the total number of seeds on the culture dish was calculated, and the ratio of the hypocotyl length of the experimental group (treated with the compound represented by the structure of formula (I) or the compound represented by the structure of formula (II)) to the control group was calculated. The results are shown in Table 1.

[0159] Calculation method of hypocotyl length ratio:

[0160]

[0161] Table 1. Experimental results of Compounds N1 to N4, Compounds 1 to 11 relieving the inhibition of hypocotyl elongation by blue light (Arabidopsis hypocotyl length ratio)

[0162]

[0163]

[0164] From the results in Table 1, it can be seen that the anthracene-9,10-dione compounds of the structure shown in formula (I) provided by the present invention can effectively relieve the inhibitory activity of cryptochrome on hypocotyl elongation under blue light; the sulfonamide compounds of the structure shown in formula (II) can effectively relieve the inhibitory activity of cryptochrome on hypocotyl elongation under blue light.

[0165] Test Example 2

[0166] Microthermophoresis (MST): The MST (microthermophoresis) test method was used to determine the specific binding of compound N1 to the receptor protein AtCRY2, and ATP was used as a control. The results are as follows: Figure 2a 、 Figure 2b The dissociation constant K between compound N1 and receptor protein AtCRY2 is shown. d The value was 0.513 μM ( Figure 2b ), which is significantly better than the binding of ATP to the receptor protein AtCRY2 ( Figure 2a As shown, K d is 2.69 μM).

[0167] Test Case 3

[0168] Wheat seedling emergence experiment: Take the same culture pots (large pot + small pot), fill the small pot with the same mass of nutrient soil, move in the same amount (150 grains) of wheat (variety: Shannong No. 46), and cover with the same thickness (5cm) of 20-mesh river sand. Add 2L of a 10μM solution of compound N1 and compound N2 (0.4% by volume of DMSO aqueous solution) to the large pot; add 2L of a 0.4% by volume DMSO aqueous solution to the blank control group. Then put the small pot into the large pot, and after the aqueous solution in the large pot is saturated with the sand in the small pot, place all the culture pots at 23°C for culture, and take pictures every day to record the number of wheat seedlings. The results are as follows Figure 3a 、 3b As shown, in Figure 3a Compared with the control group (CK), compounds N1 and N2 accelerated the emergence rate of wheat seedlings. Figure 3b It can be seen that after treatment with compounds N1 and N2 of the present invention, the emergence time of wheat seedlings was significantly advanced. In particular, after treatment with compound N2, the emergence rate of wheat seedlings reached 50% 21 hours earlier than that of the control group (CK).

[0169] Test Example 4

[0170] Arabidopsis delayed flowering experiment: Wild-type Arabidopsis seedlings with the same growth (cultivated for 20 days, with strong growth and differentiated flower buds) were taken and treated with 5 μM concentrations of compound N1 and compound 1 (V DMSO :V 水 =1:10000) soaked in soil and planted, watered once every 20 days, 500 mL per time; the blank control group was added with an equal amount of DMSO aqueous solution (V DMSO :V 水 =1:10000). The flowering period is from seed germination to the appearance of the first flower of the Arabidopsis plant; the flowering period of each Arabidopsis plant is recorded. Figure 4a 、 4b , 4c, 4d, by Figure 4a and Figure 4c It can be seen that after applying compound N1 and compound 1, the flowering period of Arabidopsis thaliana was significantly later than that of the control group; Figure 4b It can be seen that the flowering period of Arabidopsis thaliana treated with compound N1 (35 days) was delayed by two days compared with the control group (33 days). Figure 4d It can be seen that the flowering period of Arabidopsis thaliana treated with compound 1 (33.6 days) was delayed by three days compared with the control group (30.7 days).

[0171] In summary, from the results of the above test examples, it can be seen that the anthracene-9,10-dione compounds with the structure shown in formula (I) provided by the present invention can effectively eliminate the inhibitory activity of cryptochrome on hypocotyl elongation under blue light; can significantly promote the emergence of plant seedlings and delay the flowering period of plants.

[0172] At the same time, the sulfonamide compound represented by formula (II) can effectively eliminate the inhibitory activity of cryptochrome on hypocotyl elongation under blue light; it can significantly promote the emergence of plant seedlings and delay the flowering period of plants.

[0173] The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, various simple variations of the technical solution of the present invention may be made, including combining the various technical features in any other appropriate manner. These simple variations and combinations should also be regarded as disclosed in the present invention and fall within the scope of protection of the present invention.

Claims

1. An anthracene-9,10-dione compound, characterized in that: The compound has the structure shown in formula (I): Formula (I), Formula (I-1), Wherein, in formula (I), One of R1 and R2 is -L1-L2-R 1 -X, the other is H; or, R1 is a group represented by formula (I-1), and R2 is H; L1 is -NH-, L2 is ; R 1 Selected from C 1-5 Alkylene, -NHCH2CH2-; X is selected from -OH, -COOCH3; One of R3 and R4 is the same as R1, and the other is H; or, both R3 and R4 are H; And when R1 is -L1-L2-CH2CH2OH or -L1-L2-(CH2)4OH, R3 or R4 is the same as R1.

2. The anthracene-9,10-dione compound according to claim 1, wherein The compound is selected from at least one of the following compounds: Compound 2: Compound 4: Compound 5: .

3. A method for preparing anthracene-9,10-dione compounds of the structure represented by formula (I) in claim 1 or 2, characterized in that: The method comprises: contacting a compound represented by formula (A) with a compound represented by formula (B) or a compound represented by formula (C) in the presence of a solvent; Formula (A), H2N-R 1 -X type (B) or Formula (C), Wherein, L4 is selected from H, 、 ; L3, L5, L6 are each independently selected from H, ; and L3 and L4 are not H at the same time; In formula (B), R 1 , the definition of X corresponds to the same as that in claim 1 or 2.

4. Use of the anthracene-9,10-dione compound according to claim 1 or 2 for enhancing the emergence ability of plant seedlings and / or delaying the flowering period of plants.

5. A pharmaceutical agent for enhancing the emergence ability of plant seedlings and / or delaying the flowering period of plants, characterized in that: The active ingredient of the medicament is at least one of the anthracene-9,10-dione compounds according to claim 1 or 2, and the content of the active ingredient is 0.1-100% by weight based on the total weight of the medicament.

6. The medicament according to claim 5, characterized in that Based on the total weight of the medicament, the content of the active ingredient is 5-90 weight %.

7. Use of the sulfonamide compound represented by formula (II) in enhancing the emergence ability of plant seedlings and / or delaying the flowering period of plants, Formula (II), in, In formula (II), one of W and Z is -S(O)2-, and the other is -NH-; R b Selected from hydroxy-substituted C 1-6 of alkyl.

8. The use according to claim 7, wherein: The compound is selected from at least one of the following compounds: Compound N1: Compound N2: Compound N3: Compound N4: .

9. A pharmaceutical agent for enhancing the emergence ability of plant seedlings and / or delaying the flowering period of plants, characterized in that: The active ingredient of the medicament is at least one of the sulfonamide compounds represented by formula (II), and the content of the active ingredient is 0.1-100% by weight based on the total weight of the medicament; Formula (II), Among them, W, Z, R b The definition is the same as that in claim 7 or 8.

10. The pharmaceutical agent according to claim 9, wherein The content of the active ingredient is 5-90% by weight.

11. The pharmaceutical agent according to claim 10, wherein The dosage form of the medicament is selected from at least one of hydrate, powder, granule, suspension and emulsion.

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