Preparation method of plant growth regulator and agricultural application of plant growth regulator

Abstract

The invention discloses a preparation method of a plant growth regulator and an agricultural application of the plant growth regulator, and particularly relates to a synthesis method of a novel sulfanilamide-containing dehydroabietic acid derivative plant growth regulator, a preparation method of a composition of the plant growth regulator and an application of the composition in resisting xanthomonas oryzae pv. Oryzae. The general formula of the derivative is as follows: # imgabs0 #, 2, 6-dimethoxypyrimidine-4-yl) benzenesulfonamide, N-(4, 6-dimethyl pyrimidine-2-yl) benzenesulfonamide, 3-amino-N-phenyl benzenesulfonamide, 4-amino-N-(2, 6-dimethoxypyrimidine-4-yl) benzenesulfonamide, 4-amino-N-(2, 6-dimethoxypyrimidine-4-yl) benzenesulfonamide, 4-amino-N, N-dimethyl benzenesulfonamide, 4-amino-N-methyl benzenesulfonamide and the like or disubstitution of any combination of the substituent groups. The derivative disclosed by the invention has a relatively good inhibition effect on rice bacterial leaf streak, tobacco bacterial wilt, potato late blight and tobacco mosaic disease. The compound I-19 and ethylicin show a synergistic effect in the process of preventing and treating Xanthomonas oryzae pv. Oryzae, and the purposes of pesticide reduction and synergism can be achieved. The plant growth regulator activity of part of the compounds is tested, and the compound I-5 is found to have good auxin activity and cytokinin activity.

Description

Technical Field

[0001] The present invention relates to the field of chemical technology, in particular to a sulfonamide-containing dehydroabietic acid compound plant growth regulator, a preparation method of the compound and a composition thereof having an inhibitory effect on rice bacterial blight pathogen, tobacco bacterial wilt pathogen, potato late blight pathogen and tobacco mosaic virus. Background Art

[0002] Plant diseases caused by bacteria and viruses have led to a significant decrease in the grain yield of crops. Diseases caused by bacteria or viruses such as tobacco wilt, potato late blight, and tobacco mosaic virus have caused huge economic losses to agriculture. At present, the commonly used antibacterial agents on the market not only have poor field protection effects and are not conducive to environmental sustainable development, but also increase the drug resistance of bacteria. Therefore, it is urgent to develop an efficient, low-toxic, and environmentally friendly antiviral and antibacterial agent.

[0003] Plant growth regulators are substances that have similar physiological and biological effects to natural plant hormones, which are studied and produced by humans through microbial fermentation or chemical synthesis. Together with natural plant hormones, they are collectively called plant growth substances. At present, the research and wide application of new plant growth regulators are reflected in the fact that the sales of plant growth hormones have increased from US$260 million in 1974 to US$700 million in 2007, which is a greater increase than any other type of pesticides. They are also used to cultivate short and strong rice and rapeseed seedlings, prevent rice and wheat from lodging, regulate cotton plant type, regulate hybrid rice flowering period, increase rubber yield, promote rooting, fruit setting and improve crop quality. Therefore, the development and research of plant growth regulators are of certain importance to the development of the national economy.

[0004] Ethylalicin is the ethyl homologue of allicin. It is a highly effective, pollution-free, broad-spectrum bionic fungicide that has a good control effect on a variety of diseases and also has a plant growth regulating effect. Ethylalicin reacts with substances containing -SH groups in bacterial molecules through the (SS=O=O) group in its molecular structure, thereby inhibiting the normal metabolism of the bacteria and achieving the effect of preventing and controlling diseases.

[0005] In 2018, Zhang et al. (Zhang, WM; Yao, Y.; Yang, T.; Wang, XY; Zhu, ZY; Xu, WT; Lin, HX; Gao, ZB; Zhou, H.; Yang, CG; Cui, YM The synthesis and antistaphylococcal activity of N-sulfonaminoethyloxime derivatives of dehydroabietic acid. Bioorg. Med. Chem. Lett. 2018, 28, 1943-1948.) designed and synthesized a series of sulfonamide-containing dehydroabietic acid derivatives. Through biological activity tests, dehydroabietic acid compounds have good antibacterial activity against Staphylococcus aureus, with the highest MIC activity of 0.39-0.78 mg / L. Several analogs showed similar effective antibacterial activity against five multidrug-resistant Staphylococcus aureus, with MIC values ​​between 0.78-1.56 mg / L.

[0006] In 2023, Qi et al. (Qi, PY; Wang, N.; Zhang, YH; Feng, YM; Zhou, X.; Zeng, D.; Meng, J.; Liu, LW; Jin, LH; Yang, S. Anti-virulence strategy of novel dehydroabietic acid derivatives: Design, synthesis, and antibacterial evaluation. Int. J. Mol. Sci. 2023, 24, 2897-2903.) designed and synthesized a series of dehydroabietic acid derivatives, using thiophanate-methyl as a positive control. The biological activity test showed that such derivatives had good anti-Xoo and Xac activity. Among them, EC with the best antibacterial activity against Xoo 50 The concentration of thiophanate-methyl (EC 50 =61.2mg / L), and preliminary mechanism studies were conducted. It was found that the most active compound could interfere with bacterial flagella assembly, inhibit bacterial motility, interfere with EPS secretion and prevent bacterial biofilm formation.

[0007] In summary, the dehydroabietic acid derivatives exhibited certain bactericidal activity, providing a reference for the creation of new and efficient antiviral agents and bactericides. Based on the previous work, the present invention designed and synthesized a series of dehydroabietic acid compounds containing sulfonamide, and studied their plant growth regulator activity, hoping to screen out highly active antiviral and antibacterial plant growth regulators. Summary of the invention

[0008] The present invention aims to provide a method for preparing a sulfonamide-containing dehydroabietic acid derivative plant growth regulator having bactericidal and antiviral activity and a composition thereof.

[0009] Another object of the present invention is to use the compound to inhibit rice streak disease, tobacco bacterial wilt, potato late blight and tobacco mosaic disease.

[0010] The technical solution of the present invention is: a dehydroabietic acid compound containing sulfonamide, wherein the derivative has the general formula of the following formula (I):

[0011]

[0012] Wherein: R is N-(5,6-dimethoxypyrimidin-4-yl)benzenesulfonamide, N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide, 3-amino-N-phenylbenzenesulfonamide, 4-amino-N-(2,6-dimethoxypyrimidin-4-yl)benzenesulfonamide, 4-amino-N,N-dimethylbenzenesulfonamide, 4-amino-N-methylbenzenesulfonamide, 4-amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide, 4-amino-N-(pyrimidin-2-yl)benzenesulfonamide, 4-amino-N-(thiazol-2-yl)benzenesulfonamide, 4-amino-N-(6-chloropyridazin-3-yl)benzenesulfonamide, 4-amino-N-(3,4-dimethylisoxazine-2-yl)benzenesulfonamide, benzenesulfonamide, 4-amino-N-(3-methoxypyrazin-2-yl)benzenesulfonamide, 4-amino-N-(5-methoxypyrimidin-2-yl)benzenesulfonamide, 4-(morpholinesulfonyl)aniline, 6-amino-N-methylnaphthalene-2-sulfonamide, 4-amino-N-(6-methoxypyridazin-3-yl)benzenesulfonamide, N-(4-aminophenyl)-4-methylbenzenesulfonamide, 4-amino-N-cyclopropylbenzenesulfonamide, or a disubstituted form of any combination of the above substituents.

[0013] Preferably, R is N-(5,6-dimethoxypyrimidin-4-yl)benzenesulfonamide, N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide, 3-amino-N-phenylbenzenesulfonamide, 4-amino-N-(2,6-dimethoxypyrimidin-4-yl)benzenesulfonamide, 4-amino-N,N-dimethylbenzenesulfonamide, 4-amino-N-methylbenzenesulfonamide, 4-amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide, 4-amino-N-(pyrimidin-2-yl)benzenesulfonamide, 4-amino-N-(thiazol-2-yl)benzenesulfonamide, 4-amino-N-(6-chloropyridazin-3-yl)benzenesulfonamide, 4-amino-N-(3 , 4-dimethylisoxazol-5-yl)benzenesulfonamide, N-((4-aminophenyl)sulfonyl)benzenesulfonamide, 4-amino-N-(4-methylpyrimidin-2-yl)benzenesulfonamide, 4-amino-N-(pyridin-2-yl)benzenesulfonamide, 4-amino-N-(3-methoxypyrazin-2-yl)benzenesulfonamide, 4-amino-N-(5-methoxypyrimidin-2-yl)benzenesulfonamide, 4-(morpholinesulfonyl)aniline, 6-amino-N-methylnaphthalene-2-sulfonamide, 4-amino-N-(6-methoxypyridazin-3-yl)benzenesulfonamide, N-(4-aminophenyl)-4-methylbenzenesulfonamide, 4-amino-N-cyclopropylbenzenesulfonamide.

[0014] Dehydroabietic acid derivatives containing sulfonamide, the specific compounds are as follows:

[0015] Compound II-1: (1R, 4S, 10R)-N-(4-(N-(5,6-dimethoxypyrimidin-4-yl)aminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide;

[0016] Compound II-2: (1R, 4S, 10R)-N-(4-(N-(4,6-dimethylpyrimidin-2-yl)aminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide;

[0017] Compound II-3: (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(3-(N-phenylaminosulfonyl)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide;

[0018] Compound II-4: (1R, 4S, 10R)-N-(4-(N-(2,6-dimethoxypyrimidin-4-yl)aminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide;

[0019] Compound II-5: (1R, 4S, 10R)-N-(4-(N,N-dimethylaminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide;

[0020] Compound II-6: (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(4-(N-methylaminosulfonyl)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide;

[0021] Compound II-7: (1R, 4S, 10R)-7-isopropyl-N-(4-(N-(6-methoxypyrimidin-4-yl)aminosulfonyl)phenyl)-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide;

[0022] Compound II-8: (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(4-(N-(pyrimidin-2-yl)aminosulfonyl)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide;

[0023] Compound II-9: (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(4-(N-(thiazol-2-yl)aminosulfonyl)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide;

[0024] Compound II-10: (1R, 4S, 10R)-N-(4-(N-(6-chloropyridazin-3-yl)aminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide;

[0025] Compound II-11: (1R, 4S, 10R)-N-(4-(N-(3,4-dimethylisoxazol-5-yl)aminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide;

[0026] Compound II-12: (1R, 4S, 10R)-N-(4-(N-benzoylaminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide;

[0027] Compound II-13: (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(4-(N-(4-methylpyrimidin-2-yl)aminosulfonyl)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide;

[0028] Compound II-14: (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(4-(N-(pyridin-2-yl)aminosulfonyl)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide;

[0029] Compound II-15: (1R, 4S, 10R)-7-isopropyl-N-(4-(N-(3-methoxypyrazin-2-yl)aminosulfonyl)phenyl)-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide;

[0030] Compound II-16: (1R, 4S, 10R)-7-isopropyl-N-(4-(N-(5-methoxypyrimidin-2-yl)aminosulfonyl)phenyl)-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide;

[0031] Compound II-17: (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(4-(morpholinesulfonyl)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide;

[0032] Compound II-18: (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(6-(N-methylaminosulfonyl)naphthalen-2-yl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide;

[0033] Compound II-19: (1R, 4S, 10R)-7-isopropyl-N-(4-(N-(6-methoxypyridazin-3-yl)aminosulfonyl)phenyl)-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide;

[0034] Compound II-20: (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(4-((4-methylphenyl)sulfonamido)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide;

[0035] Compound II-21: (1R, 4S, 10R)-N-(4-(N-cyclopropylaminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide.

[0036] A method for preparing a dehydroabietic acid derivative containing sulfonamide comprises the following steps:

[0037] (1) Dehydroabietic acid: thionyl chloride was added in a ratio of 1:3, heated under reflux for 1-3 h, and after the reaction was completed and the temperature dropped to room temperature, evaporated under reduced pressure to obtain 1-formyl chloride dehydroabietic acid;

[0038]

[0039] (2) 1-Chloroformyl dehydroabietic acid: substituted amine: triethylamine = 1:1 to 1.2:0.5 was added, and 5 mL of dichloromethane was added. The mixture was stirred in an ice bath for 20 min. After the reaction was completed, the reaction system was poured into saturated brine and extracted with dichloromethane. The organic layer was collected and separated and purified by column chromatography (petroleum ether: ethyl acetate = 3:1 to 1:1) to obtain the target compound.

[0040]

[0041] The derivatives are used in preparing medicines and medicaments for preventing and treating rice bacterial blight, tobacco bacterial wilt, potato late blight and tobacco mosaic disease.

[0042] A compound pesticide composition, characterized in that: the composition comprises the derivative and ethionine. The mass ratio of the derivative to ethionine is 1:2-2:1. The derivative is (1R, 4S, 10R)-7-isopropyl-N-(4-(N-(6-methoxypyridazin-3-yl)aminosulfonyl)phenyl)-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide.

[0043] The composition is used in the preparation of a drug for preventing and treating plant bacterial diseases. The plant bacterial disease is rice bacterial blight pathogen.

[0044] A novel plant growth regulator is a compound (1R, 4S, 10R)-7-isopropyl-N-(4-(N-(6-methoxypyridazin-3-yl)aminosulfonyl)phenyl)-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide, which is a compound of the following formula (7):

[0045]

[0046] Beneficial effects of the present invention: The present invention synthesizes sulfonamide-containing dehydroabietic acid derivatives with anti-rice bacterial leaf blight activity. The advantages of the present invention are that the raw materials are easily available, the process is simple, and the reaction conditions are mild. The compound II-19 in the present invention has an inhibition rate of 69.4% on rice bacterial leaf blight at a concentration of 100 mg / L, which exceeds the inhibition rate of 58.2% of the commercial agent thiophanate-methyl. In addition, the composition selected by the present invention, compound II-19 and ethoxylated, show a synergistic effect in the process of preventing and controlling rice bacterial leaf blight, which can further reduce the production cost and the use cost, and achieve the purpose of reducing the drug and increasing the effect. The experimental results show that compound II-19 has good plant growth regulating activity, which provides a basis for the subsequent study of dehydroabietic acid plant growth regulating agents. DETAILED DESCRIPTION

[0047] Example 1: Synthesis of (1R, 4S, 10R)-N-(4-(N-(5,6-dimethoxypyrimidin-4-yl)aminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide (compound number II-1), comprising the following steps:

[0048] (1) Dehydroabietic acid: thionyl chloride = 1:3, heat under reflux for 1-3 hours, wait for the reaction to complete, cool to room temperature, and evaporate under reduced pressure to obtain 1-formyl chloride dehydroabietic acid.

[0049] (2) 1-formyl chloride dehydroabietic acid: 4-amino-N-(5,6-dimethoxypyrimidin-4-yl)benzenesulfonamide: triethylamine = 1:1 to 1.2:0.5 was added, and 5 mL of dichloromethane was added. The mixture was stirred in an ice bath for 20 min. After the reaction was completed, the reaction system was poured into saturated brine, extracted with dichloromethane, and the organic layer was collected. The organic layer was separated and purified by column chromatography (petroleum ether: ethyl acetate = 3:1 to 1:1) to obtain (1R, 4S, 10R)-N-(4-(N-(5,6-dimethoxypyrimidin-4-yl)aminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide in a yield of 67%.

[0050] Example 2: Synthesis of (1R, 4S, 10R)-N-(4-(N-(4,6-dimethylpyrimidin-2-yl)aminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide (compound number II-2), comprising the following steps:

[0051] (1) Dehydroabietic acid: thionyl chloride = 1:3, heat under reflux for 1-3 hours, wait for the reaction to complete, cool to room temperature, and evaporate under reduced pressure to obtain 1-formyl chloride dehydroabietic acid.

[0052] (2) 1-formyl chloride dehydroabietic acid: 4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide: triethylamine = 1:1 to 1.2:0.5 was added, and 5 mL of dichloromethane was added. The mixture was stirred in an ice bath for 20 min. After the reaction was completed, the reaction system was poured into saturated brine, extracted with dichloromethane, and the organic layer was collected. The organic layer was separated and purified by column chromatography (petroleum ether: ethyl acetate = 3:1 to 1:1) to obtain (1R, 4S, 10R)-N-(4-(N-(4,6-dimethylpyrimidin-2-yl)aminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide in a yield of 58%.

[0053] Example 3: Synthesis of (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(3-(N-phenylaminosulfonyl)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide (compound number II-3), comprising the following steps:

[0054] (1) Dehydroabietic acid: thionyl chloride = 1:3, heat under reflux for 1-3 hours, wait for the reaction to complete, cool to room temperature, and evaporate under reduced pressure to obtain 1-formyl chloride dehydroabietic acid.

[0055] (2) 1-formyl chloride dehydroabietic acid: 3-amino-N-phenylbenzenesulfonamide: triethylamine = 1:1 to 1.2:0.5 was added, and 5 mL of dichloromethane was added. The mixture was stirred in an ice bath for 20 min. After the reaction was completed, the reaction system was poured into saturated brine, extracted with dichloromethane, and the organic layer was collected. The organic layer was separated and purified by column chromatography (petroleum ether: ethyl acetate = 3:1 to 1:1) to obtain (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(3-(N-phenylaminosulfonyl)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide in a yield of 46%.

[0056] Example 4: Synthesis of (1R, 4S, 10R)-N-(4-(N-(2,6-dimethoxypyrimidin-4-yl)aminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide (compound number II-4), comprising the following steps:

[0057] (1) Dehydroabietic acid: thionyl chloride = 1:3, heat under reflux for 1-3 hours, wait for the reaction to complete, cool to room temperature, and evaporate under reduced pressure to obtain 1-formyl chloride dehydroabietic acid.

[0058] (2) 1-formyl chloride dehydroabietic acid: 4-amino-N-(2,6-dimethoxypyrimidin-4-yl)benzenesulfonamide: triethylamine = 1:1 to 1.2:0.5 was added, and 5 mL of dichloromethane was added. The mixture was stirred in an ice bath for 20 min. After the reaction was completed, the reaction system was poured into saturated brine, extracted with dichloromethane, and the organic layer was collected. The organic layer was separated and purified by column chromatography (petroleum ether: ethyl acetate = 3:1 to 1:1) to obtain (1R, 4S, 10R)-N-(4-(N-(2,6-dimethoxypyrimidin-4-yl)aminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide, with a yield of 60%.

[0059] Example 5: Synthesis of (1R, 4S, 10R)-N-(4-(N, N-dimethylaminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide (compound number II-5), comprising the following steps:

[0060] (1) Dehydroabietic acid: thionyl chloride = 1:3, heat under reflux for 1-3 hours, wait for the reaction to complete, cool to room temperature, and evaporate under reduced pressure to obtain 1-formyl chloride dehydroabietic acid.

[0061] (2) 1-formyl chloride dehydroabietic acid: 4-amino-N,N-dimethylbenzenesulfonamide: triethylamine = 1:1 to 1.2:0.5 was added, and 5 mL of dichloromethane was added. The mixture was stirred in an ice bath for 20 min. After the reaction was completed, the reaction system was poured into saturated brine, extracted with dichloromethane, and the organic layer was collected. The organic layer was separated and purified by column chromatography (petroleum ether: ethyl acetate = 3:1 to 1:1) to obtain (1R, 4S, 10R)-N-(4-(N,N-dimethylaminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide in a yield of 66%.

[0062] Example 6: Synthesis of (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(4-(N-methylaminosulfonyl)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide (compound number II-6), comprising the following steps:

[0063] (1) Dehydroabietic acid: thionyl chloride = 1:3, heat under reflux for 1-3 hours, wait for the reaction to complete, cool to room temperature, and evaporate under reduced pressure to obtain 1-formyl chloride dehydroabietic acid.

[0064] (2) 1-formyl chloride dehydroabietic acid: 4-amino-N-methylbenzenesulfonamide: triethylamine = 1:1 to 1.2:0.5 was added, and 5 mL of dichloromethane was added. The mixture was stirred in an ice bath for 20 min. After the reaction was completed, the reaction system was poured into saturated brine, extracted with dichloromethane, and the organic layer was collected. The organic layer was separated and purified by column chromatography (petroleum ether: ethyl acetate = 3:1 to 1:1) to obtain (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(4-(N-methylaminosulfonyl)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide in a yield of 49%.

[0065] Example 7: Synthesis of (1R, 4S, 10R)-7-isopropyl-N-(4-(N-(6-methoxypyrimidin-4-yl)aminosulfonyl)phenyl)-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide (compound number II-7), comprising the following steps:

[0066] (1) Dehydroabietic acid: thionyl chloride = 1:3, heat under reflux for 1-3 hours, wait for the reaction to complete, cool to room temperature, and evaporate under reduced pressure to obtain 1-formyl chloride dehydroabietic acid.

[0067] (2) 1-formyl chloride dehydroabietic acid: 4-amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide: triethylamine = 1:1 to 1.2:0.5 was added, and 5 mL of dichloromethane was added. The mixture was stirred in an ice bath for 20 min. After the reaction was completed, the reaction system was poured into saturated brine, extracted with dichloromethane, and the organic layer was collected. The organic layer was separated and purified by column chromatography (petroleum ether: ethyl acetate = 3:1 to 1:1) to obtain (1R, 4S, 10R)-7-isopropyl-N-(4-(N-(6-methoxypyrimidin-4-yl)aminosulfonyl)phenyl)-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide in a yield of 52%.

[0068] Example 8: Synthesis of (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(4-(N-(pyrimidin-2-yl)aminosulfonyl)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide (compound number II-8), comprising the following steps:

[0069] (1) Dehydroabietic acid: thionyl chloride = 1:3, heat under reflux for 1-3 hours, wait for the reaction to complete, cool to room temperature, and evaporate under reduced pressure to obtain 1-formyl chloride dehydroabietic acid.

[0070] (2) 1-formyl chloride dehydroabietic acid: 4-amino-N-(pyrimidin-2-yl)benzenesulfonamide: triethylamine = 1:1 to 1.2:0.5 was added, and 5 mL of dichloromethane was added. The mixture was stirred in an ice bath for 20 min. After the reaction was completed, the reaction system was poured into saturated brine, extracted with dichloromethane, and the organic layer was collected. The organic layer was separated and purified by column chromatography (petroleum ether: ethyl acetate = 3:1 to 1:1) to obtain (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(4-(N-(pyrimidin-2-yl)aminosulfonyl)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide in a yield of 47%.

[0071] Example 9: Synthesis of (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(4-(N-(thiazol-2-yl)aminosulfonyl)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide (compound number II-9), comprising the following steps:

[0072] (1) Dehydroabietic acid: thionyl chloride = 1:3, heat under reflux for 1-3 hours, wait for the reaction to complete, cool to room temperature, and evaporate under reduced pressure to obtain 1-formyl chloride dehydroabietic acid.

[0073] (2) 1-formyl chloride dehydroabietic acid: 4-amino-N-(thiazol-2-yl)benzenesulfonamide: triethylamine = 1:1 to 1.2:0.5 was added, and 5 mL of dichloromethane was added. The mixture was stirred in an ice bath for 20 min. After the reaction was completed, the reaction system was poured into saturated brine, extracted with dichloromethane, and the organic layer was collected. The organic layer was separated and purified by column chromatography (petroleum ether: ethyl acetate = 3:1 to 1:1) to obtain (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(4-(N-(thiazol-2-yl)aminosulfonyl)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide in a yield of 62%.

[0074] Example 10: Synthesis of (1R, 4S, 10R)-N-(4-(N-(6-chloropyridazin-3-yl)aminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide (compound number II-10), comprising the following steps:

[0075] (1) Dehydroabietic acid: thionyl chloride = 1:3, heat under reflux for 1-3 hours, wait for the reaction to complete, cool to room temperature, and evaporate under reduced pressure to obtain 1-formyl chloride dehydroabietic acid.

[0076] (2) 1-formyl chloride dehydroabietic acid: 4-amino-N-(6-chloropyridazin-3-yl)benzenesulfonamide: triethylamine = 1:1 to 1.2:0.5 was added, and 5 mL of dichloromethane was added. The mixture was stirred in an ice bath for 20 min. After the reaction was completed, the reaction system was poured into saturated brine, extracted with dichloromethane, and the organic layer was collected. The organic layer was separated and purified by column chromatography (petroleum ether: ethyl acetate = 3:1 to 1:1) to obtain (1R, 4S, 10R)-N-(4-(N-(6-chloropyridazin-3-yl)aminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide in a yield of 55%.

[0077] Example 11: Synthesis of (1R, 4S, 10R)-N-(4-(N-(3,4-dimethylisoxazol-5-yl)aminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide (compound number II-11), comprising the following steps:

[0078] (1) Dehydroabietic acid: thionyl chloride = 1:3, heat under reflux for 1-3 hours, wait for the reaction to complete, cool to room temperature, and evaporate under reduced pressure to obtain 1-formyl chloride dehydroabietic acid.

[0079] (2) 1-formyl chloride dehydroabietic acid: 4-amino-N-(3,4-dimethylisoxazol-5-yl)benzenesulfonamide: triethylamine = 1:1 to 1.2:0.5 was added, 5 mL of dichloromethane was added, and the mixture was stirred in an ice bath for 20 min. After the reaction was completed, the reaction system was poured into saturated brine, extracted with dichloromethane, and the organic layer was collected. The organic layer was separated and purified by column chromatography (petroleum ether: ethyl acetate = 3:1 to 1:1) to obtain (1R, 4S, 10R)-N-(4-(N-(3,4-dimethylisoxazol-5-yl)aminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide, with a yield of 47%.

[0080] Example 12: Synthesis of (1R, 4S, 10R)-N-(4-(N-benzoylaminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide (compound number II-12), comprising the following steps:

[0081] (1) Dehydroabietic acid: thionyl chloride = 1:3, heat under reflux for 1-3 hours, wait for the reaction to complete, cool to room temperature, and evaporate under reduced pressure to obtain 1-formyl chloride dehydroabietic acid.

[0082] (2) 1-formyl chloride dehydroabietic acid: N-((4-aminophenyl)sulfonyl)benzamide: triethylamine = 1:1 to 1.2:0.5 was added, and 5 mL of dichloromethane was added. The mixture was stirred in an ice bath for 20 min. After the reaction was completed, the reaction system was poured into saturated brine, extracted with dichloromethane, and the organic layer was collected. The organic layer was separated and purified by column chromatography (petroleum ether: ethyl acetate = 3:1 to 1:1) to obtain (1R, 4S, 10R)-N-(4-(N-benzoylaminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide in a yield of 73%.

[0083] Example 13: Synthesis of (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(4-(N-(4-methylpyrimidin-2-yl)aminosulfonyl)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide (compound number II-13), comprising the following steps:

[0084] (1) Dehydroabietic acid: thionyl chloride = 1:3, heat under reflux for 1-3 hours, wait for the reaction to complete, cool to room temperature, and evaporate under reduced pressure to obtain 1-formyl chloride dehydroabietic acid.

[0085] (2) 1-formyl chloride dehydroabietic acid: 4-amino-N-(4-methylpyrimidin-2-yl)benzenesulfonamide: triethylamine = 1:1 to 1.2:0.5 was added, and 5 mL of dichloromethane was added. The mixture was stirred in an ice bath for 20 min. After the reaction was completed, the reaction system was poured into saturated brine, extracted with dichloromethane, and the organic layer was collected. The organic layer was separated and purified by column chromatography (petroleum ether: ethyl acetate = 3:1 to 1:1) to obtain (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(4-(N-(4-methylpyrimidin-2-yl)aminosulfonyl)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide in a yield of 63%.

[0086] Example 14: Synthesis of (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(4-(N-(pyridin-2-yl)aminosulfonyl)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide (compound number II-15), comprising the following steps:

[0087] (1) Dehydroabietic acid: thionyl chloride = 1:3, heat under reflux for 1-3 hours, wait for the reaction to complete, cool to room temperature, and evaporate under reduced pressure to obtain 1-formyl chloride dehydroabietic acid.

[0088] (2) 1-formyl chloride dehydroabietic acid: 4-amino-N-(pyridin-2-yl)benzenesulfonamide: triethylamine = 1:1 to 1.2:0.5 was added, and 5 mL of dichloromethane was added. The mixture was stirred in an ice bath for 20 min. After the reaction was completed, the reaction system was poured into saturated brine, extracted with dichloromethane, and the organic layer was collected. The organic layer was separated and purified by column chromatography (petroleum ether: ethyl acetate = 3:1 to 1:1) to obtain (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(4-(N-(pyridin-2-yl)aminosulfonyl)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide in a yield of 55%.

[0089] Example 15: Synthesis of (1R, 4S, 10R)-7-isopropyl-N-(4-(N-(3-methoxypyrazin-2-yl)aminosulfonyl)phenyl)-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide (compound number II-16), comprising the following steps:

[0090] (1) Dehydroabietic acid: thionyl chloride = 1:3, heat under reflux for 1-3 hours, wait for the reaction to complete, cool to room temperature, and evaporate under reduced pressure to obtain 1-formyl chloride dehydroabietic acid.

[0091] (2) 1-formyl chloride dehydroabietic acid: 4-amino-N-(3-methoxypyrazin-2-yl)benzenesulfonamide: triethylamine = 1:1 to 1.2:0.5 was added, and 5 mL of dichloromethane was added. The mixture was stirred in an ice bath for 20 min. After the reaction was completed, the reaction system was poured into saturated brine, extracted with dichloromethane, and the organic layer was collected. The organic layer was separated and purified by column chromatography (petroleum ether: ethyl acetate = 3:1 to 1:1) to obtain (1R, 4S, 10R)-7-isopropyl-N-(4-(N-(3-methoxypyrazin-2-yl)aminosulfonyl)phenyl)-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide in a yield of 53%.

[0092] Example 16: Synthesis of (1R, 4S, 10R)-7-isopropyl-N-(4-(N-(5-methoxypyrimidin-2-yl)aminosulfonyl)phenyl)-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide ketone (compound number II-17), comprising the following steps:

[0093] (1) Dehydroabietic acid: thionyl chloride = 1:3, heat under reflux for 1-3 hours, wait for the reaction to complete, cool to room temperature, and evaporate under reduced pressure to obtain 1-formyl chloride dehydroabietic acid.

[0094] (2) 1-formyl chloride dehydroabietic acid: 4-amino-N-(5-methoxypyrimidin-2-yl)benzenesulfonamide: triethylamine = 1:1 to 1.2:0.5 was added, and 5 mL of dichloromethane was added. The mixture was stirred in an ice bath for 20 min. After the reaction was completed, the reaction system was poured into saturated brine, extracted with dichloromethane, and the organic layer was collected. The organic layer was separated and purified by column chromatography (petroleum ether: ethyl acetate = 3:1 to 1:1) to obtain (1R, 4S, 10R)-7-isopropyl-N-(4-(N-(5-methoxypyrimidin-2-yl)aminosulfonyl)phenyl)-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide in a yield of 58%.

[0095] Example 17: Synthesis of (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(4-(morpholinesulfonyl)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide (compound number II-18), comprising the following steps:

[0096] (1) Dehydroabietic acid: thionyl chloride = 1:3, heat under reflux for 1-3 hours, wait for the reaction to complete, cool to room temperature, and evaporate under reduced pressure to obtain 1-formyl chloride dehydroabietic acid.

[0097] (2) 1-formyl chloride dehydroabietic acid: 4-(morpholinesulfonyl)aniline: triethylamine = 1:1 to 1.2:0.5 was added, and 5 mL of dichloromethane was added. The mixture was stirred in an ice bath for 20 min. After the reaction was completed, the reaction system was poured into saturated brine, extracted with dichloromethane, and the organic layer was collected. The organic layer was separated and purified by column chromatography (petroleum ether: ethyl acetate = 3:1 to 1:1) to obtain (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(4-(morpholinesulfonyl)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide in a yield of 58%.

[0098] Example 18: Synthesis of (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(6-(N-methylaminosulfonyl)naphthalen-2-yl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide (compound number II-19), comprising the following steps:

[0099] (1) Dehydroabietic acid: thionyl chloride = 1:3, heat under reflux for 1-3 hours, wait for the reaction to complete, cool to room temperature, and evaporate under reduced pressure to obtain 1-formyl chloride dehydroabietic acid.

[0100] (2) 1-formyl chloride dehydroabietic acid: 6-amino-N-methylnaphthalene-2-sulfonamide: triethylamine = 1:1 to 1.2:0.5 was added, and 5 mL of dichloromethane was added. The mixture was stirred in an ice bath for 20 min. After the reaction was completed, the reaction system was poured into saturated brine, extracted with dichloromethane, and the organic layer was collected. The organic layer was separated and purified by column chromatography (petroleum ether: ethyl acetate = 3:1 to 1:1) to obtain (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(6-(N-methylaminosulfonyl)naphthalene-2-yl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide in a yield of 46%.

[0101] Example 19: Synthesis of (1R, 4S, 10R)-7-isopropyl-N-(4-(N-(6-methoxypyridazin-3-yl)aminosulfonyl)phenyl)-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide (compound number II-20), comprising the following steps:

[0102] (1) Dehydroabietic acid: thionyl chloride = 1:3, heat under reflux for 1-3 hours, wait for the reaction to complete, cool to room temperature, and evaporate under reduced pressure to obtain 1-formyl chloride dehydroabietic acid.

[0103] (2) 1-formyl chloride dehydroabietic acid: 4-amino-N-(6-methoxypyridazin-3-yl)benzenesulfonamide: triethylamine = 1:1 to 1.2:0.5 was added, and 5 mL of dichloromethane was added. The mixture was stirred in an ice bath for 20 min. After the reaction was completed, the reaction system was poured into saturated brine, extracted with dichloromethane, and the organic layer was collected. The organic layer was separated and purified by column chromatography (petroleum ether: ethyl acetate = 3:1 to 1:1) to obtain (1R, 4S, 10R)-7-isopropyl-N-(4-(N-(6-methoxypyridazin-3-yl)aminosulfonyl)phenyl)-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide in a yield of 60%.

[0104] Example 20: Synthesis of (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(4-((4-methylphenyl)sulfonamido)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide (compound number II-21), comprising the following steps:

[0105] (1) Dehydroabietic acid: thionyl chloride = 1:3, heat under reflux for 1-3 hours, wait for the reaction to complete, cool to room temperature, and evaporate under reduced pressure to obtain 1-formyl chloride dehydroabietic acid.

[0106] (2) 1-formyl chloride dehydroabietic acid: N-(4-aminophenyl)-4-methylbenzenesulfonamide: triethylamine = 1:1 to 1.2:0.5 was added, and 5 mL of dichloromethane was added. The mixture was stirred in an ice bath for 20 min. After the reaction was completed, the reaction system was poured into saturated brine, extracted with dichloromethane, and the organic layer was collected. The organic layer was separated and purified by column chromatography (petroleum ether: ethyl acetate = 3:1 to 1:1) to obtain (1R, 4S, 10R)-7-isopropyl-1,4-dimethyl-N-(4-((4-methylphenyl)sulfonamido)phenyl)-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide in a yield of 62%.

[0107] Example 21: Synthesis of (1R, 4S, 10R)-N-(4-(N-cyclopropylaminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide (compound number II-22), comprising the following steps:

[0108] (1) Dehydroabietic acid: thionyl chloride = 1:3, heat under reflux for 1-3 hours, wait for the reaction to complete, cool to room temperature, and evaporate under reduced pressure to obtain 1-formyl chloride dehydroabietic acid.

[0109] (2) 1-formyl chloride dehydroabietic acid: 4-amino-N-cyclopropylbenzenesulfonamide: triethylamine = 1:1 to 1.2:0.5 was added, and 5 mL of dichloromethane was added. The mixture was stirred in an ice bath for 20 min. After the reaction was completed, the reaction system was poured into saturated brine, extracted with dichloromethane, and the organic layer was collected. The organic layer was separated and purified by column chromatography (petroleum ether: ethyl acetate = 3:1 to 1:1) to obtain (1R, 4S, 10R)-N-(4-(N-cyclopropylaminosulfonyl)phenyl)-7-isopropyl-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide in a yield of 47%.

[0110] The nuclear magnetic resonance 1H spectra of the dehydroabietic acid derivatives of sulfonamide synthesized in Examples II-1 to II-22 above ( 1 HNMR), carbon spectrum ( 13 C NMR) and high resolution mass spectrometry (HRMS) data are shown in Table 1.

[0111] Table 1. Spectral data of compounds II-1 to II-21

[0112]

[0113]

[0114]

[0115]

[0116]

[0117]

[0118]

[0119]

[0120]

[0121]

[0122]

[0123] Example 22: Inhibitory activity of target compounds against Xanthomonas oryzae, Psoralea corylifolia, and Psoralea corylifolia

[0124] (1) Test method

[0125] The bactericidal activity of the compound was determined by turbidity method (Yang L.; et al., 2017). The test compound was prepared at a concentration of 100 mg / L. NB medium (3.0 g beef extract, 5.0 g peptone, 1.0 g yeast powder, 10.0 g glucose, 1000 mL distilled water, pH 7.0-7.2) was prepared. A small piece of culture medium containing rice bacterial blight, tobacco bacterial wilt, and potato late blight was cut into two NB culture media with a bacterial loop, plugged, and cultured at 28°C, 180 rpm constant temperature shaker until the logarithmic growth phase (OD 595 =0.6-0.8) for later use. Take 40 μL of bacterial solution, 4 mL of water-Tween (1% Tween-20), and 1 mL of the prepared compound solution, incubate the test tube at 28±1°C, and shake continuously at 180 rpm for 1-3 days. Measure the OD at 595 nm. 595 ) to monitor bacterial growth, but with the same concentration of solvent and 0.1% Tween 20 as a blank control, chlorothiazol as a control agent, and each treatment was repeated three times. The inhibition rate of the agent on bacteria was calculated by the following formula:

[0126] I=(Ctur-Ttur) / Ctur×100%

[0127] Where I is the inhibition rate, Ctur represents the corrected turbidity value of bacterial growth in the test tube without drug treatment (blank control), and Ttur represents the corrected turbidity value of bacterial growth in the test tube treated with the compound.

[0128] (2) Biological test results

[0129] Table 2 Inhibitory activity of target compounds against Xanthomonas oryzae, Psoralea corylifolia, and Psoralea corylifolia

[0130]

[0131] The antibacterial activity of the target compounds was tested by turbidity method at a concentration of 100 mg / L with thiophanate-methyl and thiophanate-zinc as control agents. From the biological activity test results in Table 2, it can be seen that the sulfonamide-containing dehydroabietic acid compounds have moderate to excellent inhibitory activity against kiwifruit canker pathogens, among which II-19 has the best activity, with an inhibitory activity of 69.4% against rice bacterial blight pathogens, which is higher than the control agents thiophanate-methyl and thiophanate-zinc.

[0132] Example 23: Therapeutic, inactivating and protective activities of target compounds against tobacco mosaic virus

[0133] (1) Test method

[0134] A. Virus purification

[0135] The Gooding method (Gooding et al. 1967) was used to select the upper leaves of the host Nicotiana glutinosa L. plants that had been inoculated for more than 3 weeks and infected with TMV system. The leaves were homogenized in phosphate buffer, filtered through double gauze, centrifuged at 1000 rpm, treated with polyethylene glycol twice, and centrifuged again. The precipitate was suspended in phosphate buffer to obtain a crude extract of TMV. The entire experiment was carried out at 4°C. The absorbance value at a wavelength of 260 nm was measured using an ultraviolet spectrophotometer, and the virus concentration was calculated according to the formula.

[0136] Virus concentration (mg / mL) = (A260 × dilution factor) / E0.1% 1cm 260nm

[0137] Where E represents the extinction coefficient, i.e. the light absorption (optical density) value of a suspension with a concentration of 0.1% (1 mg / mL) at a wavelength of 260 nm when the optical path is 1 cm. The E0.1%1cm260nm of TMV is 3.1.

[0138] B. Active therapeutic effect of the agent on TMV infection: Select heart-leaf tobacco with consistent growth, first dip the virus juice with a brush, inoculate the whole leaf with the virus, and rinse with clean water after inoculation. After the leaves are dry, apply the agent to the right half of the leaf, and apply the corresponding dose of solvent to the left half of the leaf as a control. Then moisturize and cultivate in a light incubator, control the temperature at 23±1℃, and light at 10000Lux. After 3-4 days, observe and record the number of dead spots. Set up 3 plants for each agent treatment, each with 3 to 4 leaves. Repeat 3 times for each agent according to the above method, and calculate the inhibition rate according to the following formula.

[0139] C. The protective effect of the agent on TMV infection

[0140] The living protective effect of the agent on TMV infection: Select heart-leaf tobacco with consistent growth, first apply the agent on the right half of the leaf with a brush, and apply the corresponding dose of solvent on the left half of the leaf as a control. After the leaves are dry, dip the brush in the virus juice, inoculate the whole leaf with the virus, and rinse with clean water after inoculation. Then moisturize and cultivate in a light incubator, control the temperature at 23±1℃, and light at 10000Lux. After 3-4 days, observe and record the number of dead spots. Set up 3 plants for each agent treatment, with 3 to 4 leaves per plant. Repeat 3 times for each agent according to the above method, and calculate the inhibition rate according to the following formula.

[0141] D. The inactivation effect of the agent on TMV infection in vivo

[0142] The in vivo passivation effect of the agent on TMV infection: select heart-leaf tobacco with consistent growth, sprinkle corundum evenly on the whole leaf, mix the compound with an equal volume of virus juice for passivation for 30 minutes, use a brush to rub and inoculate on the right half leaf of the appropriate-age stalked tobacco sprinkled with corundum, mix the corresponding dose of solvent and virus juice and inoculate on the left half leaf of the appropriate-age stalked tobacco sprinkled with corundum, and observe and record the number of dead spots after 3-4 days. Set up 3 plants for each agent treatment, each with 3-4 leaves. Repeat 3 times for each agent according to the above method, and calculate the inhibition rate according to the following formula.

[0143] Y=(CA) / C×100%

[0144] Wherein: Y is the inhibition rate of the compound on tobacco mosaic virus; C is the number of necrotic spots in the control group (left half leaf); A is the number of necrotic spots in the control group (right half leaf).

[0145] (2) Biological test results

[0146] Table 3 The therapeutic, protective and inactivating activities of target compounds against tobacco mosaic virus

[0147]

[0148]

[0149] The anti-TMV activity of the target compounds was tested using the half-leaf spot method at a concentration of 500 μg / mL and ningnanmycin as the control agent. From the biological activity assay results in Table 3, it can be seen that the rosin acid compounds containing sulfonamide structure have moderate to excellent inhibitory activity against TMV, among which II-15 is superior to the control agent ningnanmycin in both treatment and protection.

[0150] Example 24: Preparation of target compound II-19 composition

[0151] Some of the preparations used below were prepared by adjusting the concentration of commercially available preparations. The following examples are further explanations of the present invention, but the present invention is not limited to the ratios, preparation types and uses in the present examples. In the following examples, wettable powders of target compound II-19 and ethionin were used to prepare composite compositions, and in each composition, the ratio of target compound II-19 to ethionin was calculated according to the mass ratio. The following preparations of target compound II-19 and ethionin were prepared as needed.

[0152] Composition 1: II-19: Ethylhexylglycerol wettable powder = 1:1

[0153] Composition 2: II-19: Ethylhexylglycerol wettable powder = 1:2

[0154] Composition 3: II-19: Ethylhexylglycerol wettable powder = 2:1

[0155] Example 25: Anti-rice streak disease activity of the composition of target compound II-19

[0156] According to the antibacterial activity test method mentioned in Example 22, the antibacterial activity of the composition of the target compound II-19 and ethionyl acetate was tested against rice bacterial blight pathogen.

[0157] Table 4 Inhibitory activity of drugs against Xanthomonas oryzae

[0158]

[0159] The in vitro growth rate method was used to test the anti-kiwifruit canker pathogen activity of the composition at a concentration of 100 μg / mL. From the biological activity assay results in Table 4, it can be seen that the anti-kiwifruit canker pathogen activity of the composite composition is improved compared with the compounds before compounding. The inhibitory activity of composition 3 (II-19: ethyl allicin wettable powder = 2:1) against kiwifruit canker pathogen reached 82.5%. Therefore, the composite composition of II-19 and ethyl allicin has a synergistic effect on kiwifruit canker.

[0160] Example 26: Determination of plant growth regulating activity of some target compounds

[0161] (1) Test method

[0162] The wheat bud sheath cutting test and radish cotyledon expansion method (Song Yangyang. Synthesis and biological activity of new plant growth regulators containing ferrocenyl groups [D]. Northwest University, 2011.) were used to determine the plant growth regulating activity of the target compound. Prepare the required solution: weigh 1.019g of citric acid, 2.350g of potassium hydrogen phosphate trihydrate, and 20g of sugar, mix and dilute to 1L, and then obtain a citric acid-phosphate buffer solution with a pH of -5. In the wheat bud sheath test, indoleacetic acid (IAA) is used as the standard control, and radish cotyledon expansion method uses kinetin (KT) as the standard control. Weigh an appropriate amount of the target compound and the control sample, add a few drops of DMF to dissolve, and then add a drop of emulsifier (Tween-80), and use the buffer solution to prepare sample solutions with a concentration of 100μg / mL, and then dilute to 50, 10, and 1μg / mL in sequence. Weigh 2.4g of agar, heat 400mL of water until dissolved, pour into a porcelain plate and cool to form a germination bed.

[0163] Wheat bud sheath cutting test method: Take about 50g of wheat seeds, soak for 4h, rinse with water several times, drain the water, evenly place them in the germination bed, seal with a film, and place them in an artificial climate box at 25±1℃ for dark culture. When the wheat sheath grows to 2.5-3cm, select the sensitive sections with consistent growth and use a blade to take a section from each bud, shade it, and rinse it in distilled water for one hour. Take 8mL of the sample solution and put it in a culture with a diameter of 9cm. Add two filter papers to each treatment and evenly place 10 cut sheath sections in each treatment, and then place it in an artificial climate box at 25±1℃ for dark culture. After 48h, measure the total length of the 10 sections, compare it with the blank buffer solution control, and at the same time compare it with the standard solution of the same concentration, calculate the inhibition or promotion effect, and use it as an evaluation index for the drug auxin function. The calculation method is:

[0164] Effect = (treatment - blank) / blank * 100%

[0165] If the calculated result is positive, it means there is a promoting effect; if it is negative, it means there is an inhibitory effect. Then the efficacy evaluation is carried out. The evaluation criteria are:

[0166] 40% ≤ Effect Grade A

[0167] 25% ≤ Effect < 40% Grade B

[0168] 10% ≤ effect < 25% Grade C

[0169] Effect <10% D

[0170] Radish cotyledon expansion method: Take about 30g of radish seeds, soak them in warm water until the seeds turn white, wash them with clean water, drain the water, seal them with a film on the germination bed, and place them in an artificial climate box at 25±1℃ for dark culture for about 72h for use. Take 8mL of each sample solution and add two pieces of paper to each culture medium with a diameter of 9cm. Select radish seedlings with uniform growth and uniform cotyledon size, then cut off the cotyledons without petioles, put 10 pieces in each treatment, and weigh the fresh weight of the cotyledons before treatment in each group, record the data, cover the culture dish lid, and culture in the dark in an artificial climate box. After 72h, take out the cotyledons of each group, absorb the water attached to the surface of the cotyledons with absorbent paper, weigh the fresh weight of the cotyledons after treatment in each group, record the data, and calculate the percentage of fresh weight gain of the cotyledons after culture as an evaluation index for the function of the drug sample cytokinin. The calculation method and evaluation criteria are the same as those of the wheat bud sheath cutting test method.

[0171] (2) Biological test results

[0172] Table 5 Plant growth regulator activity of some target compounds

[0173]

[0174] The plant growth activity test results of this series of target compounds are shown in Table 5. The preliminary biological activity test results show that the target compounds have certain plant growth activity, among which compound I-5 has good auxin activity, but is worse than kinetin activity. Within a certain range, the activity of high concentration is better than that of low concentration, such as compound I-19. The activity of compound I-5 is slightly higher than that of indoleacetic acid, which can be further studied.

[0175] The embodiments of the present invention are used to illustrate the technical solution of the present invention. The present invention has the advantages of simple synthesis route, high yield, and a new and highly effective new plant growth regulator for preventing and controlling rice bacterial blight.

Claims

1. A dehydroabietic acid derivative containing sulfonamide, characterized in that: The general formula of the derivative is as follows: Wherein: R is N-(5,6-dimethoxypyrimidin-4-yl)benzenesulfonamide, N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide, 3-amino-N-phenylbenzenesulfonamide, 4-amino-N-(2,6-dimethoxypyrimidin-4-yl)benzenesulfonamide, 4-amino-N,N-dimethylbenzenesulfonamide, 4-amino-N-methylbenzenesulfonamide, 4-amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide, 4-amino-N-(pyrimidin-2-yl)benzenesulfonamide, 4-amino-N-(thiazol-2-yl)benzenesulfonamide, 4-amino-N-(6-chloropyridazin-3-yl)benzenesulfonamide, 4-amino-N-(3,4-dimethylisoxazine-2-yl)benzenesulfonamide, benzenesulfonamide, 4-amino-N-(3-methoxypyrazin-2-yl)benzenesulfonamide, 4-amino-N-(5-methoxypyrimidin-2-yl)benzenesulfonamide, 4-(morpholinesulfonyl)aniline, 6-amino-N-methylnaphthalene-2-sulfonamide, 4-amino-N-(6-methoxypyridazin-3-yl)benzenesulfonamide, N-(4-aminophenyl)-4-methylbenzenesulfonamide, 4-amino-N-cyclopropylbenzenesulfonamide, or a disubstituted form of any combination of the above substituents.

2. A dehydroabietic acid derivative containing sulfonamide according to claim 1, characterized in that: R is N-(5,6-dimethoxypyrimidin-4-yl)benzenesulfonamide, N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide, 3-amino-N-phenylbenzenesulfonamide, 4-amino-N-(2,6-dimethoxypyrimidin-4-yl)benzenesulfonamide, 4-amino-N,N-dimethylbenzenesulfonamide, 4-amino-N-methylbenzenesulfonamide, 4-amino-N-(6-methoxypyrimidin-4-yl)benzenesulfonamide, 4-amino-N-(pyrimidin-2-yl)benzenesulfonamide, 4-amino-N-(thiazol-2-yl)benzenesulfonamide, 4-amino-N-(6-chloropyridazin-3-yl)benzenesulfonamide, 4-amino-N-(3,4-dimethylisoxazol- 4-amino-N-(3-methoxypyrazin-2-yl)benzenesulfonamide, 4-amino-N-(5-methoxypyrimidin-2-yl)benzenesulfonamide, 4-(morpholinesulfonyl)aniline, 6-amino-N-methylnaphthalene-2-sulfonamide, 4-amino-N-(6-methoxypyridazin-3-yl)benzenesulfonamide, N-(4-aminophenyl)-4-methylbenzenesulfonamide, 4-amino-N-cyclopropylbenzenesulfonamide or disubstituted with any combination of the above substituents.

3. The method for preparing a dehydroabietic acid derivative containing sulfonamide according to claim 1, characterized in that: The following steps are involved:

4. The method for preparing a dehydroabietic acid derivative containing sulfonamide according to claim 3, characterized in that: The synthesis steps and process conditions are as follows: add dehydroabietic acid and thionyl chloride in a molar ratio of 1:3, heat under reflux for 1-3 hours, wait for the reaction to be completed, reduce the temperature to room temperature, evaporate under reduced pressure to obtain 1-formyl chloride dehydroabietic acid; add 1-formyl chloride dehydroabietic acid: substituted sulfonamide: triethylamine in a ratio of 1:1 to 1.2:0.5, add dichloromethane, stir in an ice bath, wait for the reaction to be completed, pour the reaction system into saturated brine, extract with dichloromethane, collect the organic layer, separate and purify by column chromatography (petroleum ether: ethyl acetate = 3:1 to 1:1), and obtain the target compound.

5. Use of a sulfonamide-containing dehydroabietic acid derivative as claimed in claim 1 or 2 in the preparation of drugs and medicaments for preventing and controlling rice bacterial blight, tobacco bacterial wilt, potato late blight and tobacco mosaic.

6. A compound pesticide composition, characterized in that: The composition comprises the derivative according to claim 1 and ethionine.

7. The composition according to claim 6, characterized in that: The mass ratio of the derivative to ethionine is 1:2-2:

1.

8. Use of the composition as claimed in claim 6 in the preparation of drugs for preventing and treating plant bacterial diseases.

9. The composition according to claim 6, characterized in that: The derivative is (1R, 4S, 10R)-7-isopropyl-N-(4-(N-(6-methoxypyridazin-3-yl)aminosulfonyl)phenyl)-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide.

10. A novel plant growth regulator, characterized in that: The regulator is (1R, 4S, 10R)-7-isopropyl-N-(4-(N-(6-methoxypyridazin-3-yl)aminosulfonyl)phenyl)-1,4-dimethyl-1,2,3,4,9,10-octahydrophenanthrene-1-carboxamide.

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