A preparation method of a glycoside derivative containing a quinazoline structure and a composition thereof and application thereof in preventing and treating kiwifruit canker

Abstract

The present invention discloses a preparation method of a glycoside derivative containing a quinazoline structure and a composition thereof and an application thereof in preventing and treating kiwifruit canker. The general formula of the derivative is as follows: wherein: R1 is a halogen, a methyl group, a methoxy group or a disubstituted or trisubstituted group in any combination of the above-mentioned substituent groups. The derivative of the present invention is applied in the preparation of drugs and medicaments for preventing and treating kiwifruit canker, cucumber mosaic virus disease and tobacco mosaic virus disease. In the present invention, compound A23 and copper rosinate show a synergistic effect in the process of preventing and treating kiwifruit canker pathogens, and can achieve the purpose of reducing the amount of pesticides and increasing their effectiveness.

Description

Technical Field

[0001] The invention relates to the field of chemical technology, and in particular to a preparation method of glycoside derivatives containing a quinazoline structure and use of a composition thereof having an inhibitory effect on kiwifruit canker, cucumber mosaic virus disease and tobacco mosaic virus disease. Background Art

[0002] The kiwifruit planting industry has a good development prospect. In terms of economic benefits, it is an important measure to increase farmers' income and enrich themselves and drive the development of rural industries. However, due to the presence of Pseudomonas syringae pv. Actinidiae (PSA) that can cause kiwifruit canker, kiwifruit cannot grow healthily, which hinders the development of the kiwifruit industry in my country and even the world. Since the kiwifruit canker caused by PSA has the characteristics of rapid spread, multiple transmission routes, and the transmission process is not easy to be discovered, the plants generally do not show symptoms in the early stage of infection. When canker symptoms appear in the planting area, the disease may have reached a level that is difficult to control. With the continued development of protected areas and the continuous cultivation of high-value-added crops, the disease is becoming increasingly difficult to control. In addition, plant diseases caused by bacteria and viruses have led to a significant decrease in the grain yield of crops. Diseases caused by viruses or pathogens such as cucumber mosaic virus 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 prevention 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, environmentally friendly antiviral and antibacterial agent.

[0003] Copper rosinate is a highly efficient broad-spectrum fungicide. When using copper rosinate, after spraying it on plants, a drug film will be formed on the surface of the plants, which can effectively kill the pathogens that fall on the drug film. In addition, the drug film formed by copper rosinate has very similar adhesion, spreadability and permeability, and the drug effect is long-lasting. It has a good preventive and control effect on bacterial and fungal diseases on plants.

[0004] Among heterocyclic compounds, nitrogen-containing heterocyclic compounds occupy an important position. Due to their unique biological activity, they are favored by many chemists. Due to the good biological activity and environmental compatibility of quinazoline heterocyclic compounds, they have become a hot topic of research at home and abroad. In recent years, it has been found that compounds containing quinazoline heterocyclic compounds have good anti-plant bacterial activity.

[0005] In 2007, Xu Guangfang (Xu Guangfang. Screening of antibacterial activity of novel quinazoline compounds and preliminary study on their mechanism of action [D]. Guizhou University, 2007.) used the indoor growth rate method to conduct a preliminary screening of the antibacterial activity of dozens of synthesized quinazoline compounds. Through screening, it was found that compounds containing quinazoline parent ring structure have good antifungal activity. The compound 6-fluoro-4-ethylthioquinazoline has the best antibacterial effect, against wheat fusarium zeae (G.zeae), pepper wilt pathogen (F.oxysporum), apple rot Nine plant pathogenic fungi, including C. mandshurica, R. solani, T. cucumeris, P. infestans, S. sclerotiorum, B. cinerea, and C. gloeosporioides, all have good biological activity, which even exceeds that of the commercial agent carbendazim.

[0006] In 2020, Zhang Guiqiang et al. (Zhang Guiqiang, Guo Qingqing, Yi Junming, et al. Synthesis and antibacterial activity of new 1,2,4-triazole quinazoline derivatives containing 2,4-dichlorophenyl [J]. Synthetic Chemistry, 2020 (6): 491-499.) synthesized 1,2,4-triazole 1,3,4-thiadiazine quinazoline compounds containing 2,4-dichlorophenyl, and used the turbidity method to test the inhibitory activity of the target compounds against citrus canker pathogen (Xac), tobacco wilt pathogen (Rs), and rice leaf blight pathogen (Xoo). The results showed that some compounds had good antibacterial activity, and the inhibition rate was comparable to that of the control agents thiophanate-methyl and chlorothalonil.

[0007] In summary, quinazolinone derivatives have shown certain bactericidal activity. In order to create new and efficient antiviral agents and bactericides, the present invention, based on previous work, designed and synthesized a series of glycoside derivative compounds containing quinazoline structure, hoping to screen out highly active antiviral drugs and antibacterial drugs. Summary of the invention

[0008] The object of the present invention is to provide a method for preparing a glycoside derivative containing a quinazoline structure and having bactericidal and antiviral activities and a composition thereof.

[0009] Another object of the present invention is to use the invention to inhibit kiwifruit canker, cucumber mosaic virus disease and tobacco mosaic virus disease.

[0010] The technical solution of the present invention is: a glycoside derivative containing a quinazoline structure, the general formula of which is the following formula (I):

[0011]

[0012] Wherein: R1 is halogen, methyl, methoxy or disubstituted or trisubstituted by any combination of the above substituent groups.

[0013] Preferably, R1 is 6-chloro, 3-chloro, 5-bromo, 5-methyl, 5-fluoro, 4-chloro, 3-methoxy, 3-methyl, 3,4-dimethyl, 6-fluoro, 3-fluoro, 6-methoxy, 3-methyl-5-chloro, 5-iodo, 4-fluoro, 4-methyl, 5-methoxy, 4-bromo or 6-methyl.

[0014] A method for preparing a glycoside derivative containing a quinazoline structure comprises the following steps:

[0015] (1) Add substituted benzoic acid and triethyl orthoacetate in a molar ratio of 1:20-50, heat under reflux for 4-6 hours, wait for the reaction to complete, cool the temperature to room temperature, filter and collect the solid, and obtain substituted 2-methyl-4H-benzo[d][1,3]oxazin-4-one.

[0016]

[0017] (2) Add substituted 2-methyl-4H-benzo[d][1,3]oxazin-4-one: p-aminophenol or 3-aminophenol: glacial acetic acid in a molar ratio of 1:1.1:20-50, heat under reflux for 4-6 hours, and after the reaction is completed, pour the reaction system into ice water with a magnetic stirrer and stir well. After the temperature drops to room temperature, filter and collect the solid to obtain substituted 2-methyl-3-phenylquinazolin-4(3H)-one.

[0018]

[0019] (3) Substituting 2-methyl-3-phenylquinazoline-4(3H)-one: glycoside: dichloromethane in a molar ratio of 1:3:30, heating to 35° C., and after the reaction is completed, extracting the reaction system with a sodium hydroxide aqueous solution and a saturated sodium chloride solution, and purifying by column chromatography to obtain the target compound containing a glycoside of a 2-methyl-4-oxoquinazoline structure;

[0020]

[0021] The invention discloses an application of a glycoside derivative containing a quinazoline structure in the preparation of drugs and medicaments for preventing and treating kiwifruit canker, cucumber mosaic virus disease and tobacco mosaic virus disease.

[0022] A composite composition comprising a synthesized glycoside derivative containing a quinazoline structure, A23 ((2S, 3S, 4R, 5S, 6S)-2-(acetoxymethyl)-6-(3-(7-chloro-2-methyl-4-oxoquinazoline-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetate) and copper rosinate, wherein the compound A23 has the following formula (2):

[0023]

[0024] The mass ratio of A23 to copper rosinate in the pesticide composition is 1:1; 1:2; 2:1. The composition is used for preventing and treating plant diseases, wherein the plant diseases are plant bacterial diseases. The plant bacterial diseases are kiwifruit canker.

[0025] Beneficial effects of the present invention: The present invention synthesizes glycoside derivatives containing a quinazoline structure having anti-kiwifruit canker activity. The present invention has the advantages of easy availability of raw materials, simple process, and mild reaction conditions. Compound A23 in the present invention has good anti-kiwifruit canker activity. In addition, the selected composition of the present invention, compound A23 and copper rosinate show a synergistic effect in the process of preventing and treating kiwifruit canker, which can further reduce production costs and use costs, and achieve the purpose of reducing the drug and increasing the effect. DETAILED DESCRIPTION

[0026] Example 1: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-(5-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A1), comprising the following steps:

[0027] (1) 2-Amino-6-chlorobenzoic acid (10.0 mmol) and 50 mL of triethyl orthoacetate as solvent were added to a 100 mL three-necked flask and refluxed for 4-5 h. After the reaction was completed, the mixture was cooled to room temperature and the solid was collected by filtration to obtain the intermediate 5-chloro-2-methyl-4H-benzo[d][1,3]oxazin-4-one.

[0028] (2) 5-chloro-2-methyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and p-aminophenol (1.1 mmol) were heated to reflux for 4-6 hours with 30 mL of glacial acetic acid as solvent. The reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. When the temperature reached room temperature, the solid was collected by filtration to obtain 5-chloro-3-(4-hydroxyphenyl)-2-methylquinazolin-4(3H)-one.

[0029] (3) 5-Chloro-3-(4-hydroxyphenyl)-2-methylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S, 3S, 4R, 5S, 6S)-2-(acetoxymethyl)-6-(4-(5-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 66.6% and a melting point of 219.2-220.1° C.

[0030] Example 2: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-(8-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A2), comprising the following steps:

[0031] (1) 2-Amino-3-chlorobenzoic acid (10.0 mmol) and 50 mL of triethyl orthoacetate as solvent were added to a 100 mL three-necked flask and refluxed for 4-5 h. After the reaction was completed, the mixture was cooled to room temperature and the solid was collected by filtration to obtain the intermediate 8-chloro-2-methyl-4H-benzo[d][1,3]oxazin-4-one.

[0032] (2) 8-chloro-2-methyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and p-aminophenol (1.1 mmol) were heated to reflux for 4-6 hours with 30 mL of glacial acetic acid as solvent. The reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. When the temperature reached room temperature, the solid was collected by filtration to obtain 8-chloro-3-(4-hydroxyphenyl)-2-methylquinazolin-4(3H)-one.

[0033] (3) 8-Chloro-3-(4-hydroxyphenyl)-2-methylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S, 3S, 4R, 5S, 6S)-2-(acetoxymethyl)-6-(4-(8-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 52.6% and a melting point of 206.3-207.6° C.

[0034] Example 3: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A3), comprising the following steps:

[0035] (1) 2-Amino-5-bromobenzoic acid (10.0 mmol) and 50 mL of triethyl orthoacetate as solvent were added to a 100 mL three-necked flask and refluxed for 4-5 h. After the reaction was completed, the mixture was cooled to room temperature and the solid was collected by filtration to obtain the intermediate 6-bromo-2-methyl-4H-benzo[d][1,3]oxazin-4-one.

[0036] (2) 6-bromo-2-methyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and p-aminophenol (1.1 mmol) were heated to reflux for 4-6 hours with 30 mL of glacial acetic acid as solvent. The reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. When the temperature reached room temperature, the solid was collected by filtration to obtain 6-bromo-3-(4-hydroxyphenyl)-2-methylquinazolin-4(3H)-one.

[0037] (3) 6-bromo-3-(4-hydroxyphenyl)-2-methylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S, 3S, 4R, 5S, 6S)-2-(acetoxymethyl)-6-(4-(6-bromo-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 40.1% and a melting point of 198.1-199.3° C.

[0038] Example 4: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-(2,6-dimethyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A4), comprising the following steps:

[0039] (1) 2-Amino-5-methylbenzoic acid (10.0 mmol) and 50 mL of triethyl orthoacetate as solvent were added to a 100 mL three-necked flask and refluxed for 4-5 h. After the reaction was completed, the mixture was cooled to room temperature and the solid was collected by filtration to obtain the intermediate 2,6-dimethyl-4H-benzo[d][1,3]oxazin-4-one.

[0040] (2) 2,6-dimethyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and p-aminophenol (1.1 mmol) were heated to reflux for 4-6 hours with 30 mL of glacial acetic acid as solvent, and the reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. After the temperature reached room temperature, the solid was collected by filtration to obtain 3-(4-hydroxyphenyl)-2,6-dimethylquinazolin-4(3H)-one.

[0041] (3) 3-(4-Hydroxyphenyl)-2,6-dimethylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-(2,6-dimethyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 20.8% and a melting point of 213.2-214.8° C.

[0042] Example 5: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-(6-fluoro-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A5), comprising the following steps:

[0043] (1) 2-Amino-5-fluoro-benzoic acid (10.0 mmol) and 50 mL of triethyl orthoacetate as solvent were added to a 100 mL three-necked flask and refluxed for 4-5 h. After the reaction was completed, the mixture was cooled to room temperature and the solid was collected by filtration to obtain the intermediate 6-fluoro-2-methyl-4H-benzo[d][1,3]oxazin-4-one.

[0044] (2) 6-Fluoro-2-methyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and p-aminophenol (1.1 mmol) were heated to reflux for 4-6 h with 30 mL of glacial acetic acid as solvent. The reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. When the temperature reached room temperature, the solid was collected by filtration to obtain 6-fluoro-3-(4-hydroxyphenyl)-2-methylquinazolin-4(3H)-one.

[0045] (3) 6-Fluoro-3-(4-hydroxyphenyl)-2-methylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S, 3S, 4R, 5S, 6S)-2-(acetoxymethyl)-6-(4-(6-fluoro-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 56.3% and a melting point of 204.5-204.9° C.

[0046] Example 6: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-(7-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A6), comprising the following steps:

[0047] (1) 2-Amino-4-chloro-benzoic acid (10.0 mmol) and 50 mL of triethyl orthoacetate as solvent were added to a 100 mL three-necked flask and refluxed for 4-5 h. After the reaction was completed, the mixture was cooled to room temperature and the solid was collected by filtration to obtain the intermediate 7-chloro-2-methyl-4H-benzo[d][1,3]oxazin-4-one.

[0048] (2) 7-chloro-2-methyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and p-aminophenol (1.1 mmol) were heated to reflux for 4-6 h with 30 mL of glacial acetic acid as solvent. The reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. When the temperature reached room temperature, the solid was collected by filtration to obtain 7-chloro-3-(4-hydroxyphenyl)-2-methylquinazolin-4(3H)-one.

[0049] (3) 7-chloro-3-(4-hydroxyphenyl)-2-methylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S, 3S, 4R, 5S, 6S)-2-(acetoxymethyl)-6-(4-(7-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 54.2% and a melting point of 223.1-224.7° C.

[0050] Example 7: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-(8-methoxy-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A7), comprising the following steps:

[0051] (1) 2-Amino-3-methoxy-benzoic acid (10.0 mmol) was added to a 100 mL three-necked flask with 50 mL of triethyl orthoacetate as solvent and refluxed for 4-5 h. After the reaction was completed, the mixture was cooled to room temperature and the solid was collected by filtration to obtain the intermediate 8-methoxy-2-methyl-4H-benzo[d][1,3]oxazin-4-one.

[0052] (2) 8-methoxy-2-methyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and p-aminophenol (1.1 mmol) were heated to reflux for 4-6 hours with 30 mL of glacial acetic acid as solvent. The reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. When the temperature reached room temperature, the solid was collected by filtration to obtain 3-(4-hydroxyphenyl)-8-methoxy-2-methylquinazolin-4(3H)-one.

[0053] (3) 3-(4-Hydroxyphenyl)-8-methoxy-2-methylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S, 3S, 4R, 5S, 6S)-2-(acetoxymethyl)-6-(4-(8-methoxy-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 28.8% and a melting point of 205.1-206.4° C.

[0054] Example 8: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-(2,8-dimethyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A8), comprising the following steps:

[0055] (1) 2-Amino-3-methyl-benzoic acid (10.0 mmol) and 50 mL of triethyl orthoacetate as solvent were added to a 100 mL three-necked flask and refluxed for 4-5 h. After the reaction was completed, the mixture was cooled to room temperature and the solid was collected by filtration to obtain the intermediate 2,8-dimethyl-4H-benzo[d][1,3]oxazin-4-one.

[0056] (2) 2,8-dimethyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and p-aminophenol (1.1 mmol) were heated to reflux for 4-6 hours with 30 mL of glacial acetic acid as solvent, and the reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. When the temperature reached room temperature, the solid was collected by filtration to obtain 3-(4-hydroxyphenyl)-2,8-dimethylquinazolin-4(3H)-one.

[0057] (3) 3-(4-Hydroxyphenyl)-2,8-dimethylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-(2,8-dimethyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 55.1% and a melting point of 193.3-194.8° C.

[0058] Example 9: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-(2,7,8-trimethyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A9), comprising the following steps:

[0059] (1) 2-Amino-3,4-dimethyl-benzoic acid (10.0 mmol) and 50 mL of triethyl orthoacetate as solvent were added to a 100 mL three-necked flask and refluxed for 4-5 h. After the reaction was completed, the mixture was cooled to room temperature and the solid was collected by filtration to obtain the intermediate 2,7,8-trimethyl-4H-benzo[d][1,3]oxazin-4-one.

[0060] (2) 2,7,8-trimethyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and p-aminophenol (1.1 mmol) were heated to reflux for 4-6 hours with 30 mL of glacial acetic acid as solvent, and the reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. After the temperature reached room temperature, the solid was collected by filtration to obtain 3-(4-hydroxyphenyl)-2,7,8-trimethylquinazolin-4(3H)-one.

[0061] (3) 3-(4-Hydroxyphenyl)-2,7,8-trimethylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-(2,7,8-trimethyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 56.6% and a melting point of 210.3-211.6° C.

[0062] Example 10: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-(5-fluoro-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetate triester (compound number A10), comprising the following steps:

[0063] (1) 2-Amino-6-fluoro-benzoic acid (10.0 mmol) was added to a 100 mL three-necked flask with 50 mL of triethyl orthoacetate as solvent and refluxed for 4-5 h. After the reaction was completed, the mixture was cooled to room temperature and the solid was collected by filtration to obtain the intermediate 6-fluoro-2-methyl-4H-benzo[d][1,3]oxazin-4-one.

[0064] (2) 6-Fluoro-2-methyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and p-aminophenol (1.1 mmol) were heated to reflux for 4-6 h with 30 mL of glacial acetic acid as solvent. The reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. When the temperature reached room temperature, the solid was collected by filtration to obtain 6-fluoro-3-(4-hydroxyphenyl)-2-methylquinazolin-4(3H)-one.

[0065] (3) 6-Fluoro-3-(4-hydroxyphenyl)-2-methylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S, 3S, 4R, 5S, 6S)-2-(acetoxymethyl)-6-(4-(5-fluoro-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 48.0% and a melting point of 219.8-220.5° C.

[0066] Example 11: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-(8-fluoro-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A11), comprising the following steps:

[0067] (1) 2-Amino-3-fluoro-benzoic acid (10.0 mmol) and 50 mL of triethyl orthoacetate as solvent were added to a 100 mL three-necked flask and refluxed for 4-5 h. After the reaction was completed, the mixture was cooled to room temperature and the solid was collected by filtration to obtain the intermediate 8-fluoro-2-methyl-4H-benzo[d][1,3]oxazin-4-one.

[0068] (2) 8-Fluoro-2-methyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and p-aminophenol (1.1 mmol) were heated to reflux for 4-6 h with 30 mL of glacial acetic acid as solvent. The reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. After the temperature reached room temperature, the solid was collected by filtration to obtain 8-fluoro-3-(4-hydroxyphenyl)-2-methylquinazolin-4(3H)-one.

[0069] (3) 8-Fluoro-3-(4-hydroxyphenyl)-2-methylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S, 3S, 4R, 5S, 6S)-2-(acetoxymethyl)-6-(4-(8-fluoro-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 54.0% and a melting point of 171.3-172.9° C.

[0070] Example 12: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-(5-methoxy-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A12), comprising the following steps:

[0071] (1) 2-Amino-6-methoxy-benzoic acid (10.0 mmol) and 50 mL of triethyl orthoacetate as solvent were added to a 100 mL three-necked flask and refluxed for 4-5 h. After the reaction was completed, the mixture was cooled to room temperature and the solid was collected by filtration to obtain the intermediate 5-methoxy-2-methyl-4H-benzo[d][1,3]oxazin-4-one.

[0072] (2) 5-methoxy-2-methyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and p-aminophenol (1.1 mmol) were heated to reflux for 4-6 hours with 30 mL of glacial acetic acid as solvent. The reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. When the temperature reached room temperature, the solid was collected by filtration to obtain 3-(4-hydroxyphenyl)-5-methoxy-2-methylquinazolin-4(3H)-one.

[0073] (3) 3-(4-Hydroxyphenyl)-5-methoxy-2-methylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S, 3S, 4R, 5S, 6S)-2-(acetoxymethyl)-6-(4-(5-methoxy-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 39.9% and a melting point of 241.2-242.8° C.

[0074] Example 13: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-(6-chloro-2,8-dimethyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A13), comprising the following steps:

[0075] (1) 2-Amino-3-methyl-5-chloro-benzoic acid (10.0 mmol) was added to a 100 mL three-necked flask with 50 mL of triethyl orthoacetate as solvent and refluxed for 4-5 h. After the reaction was completed, the mixture was cooled to room temperature and the solid was collected by filtration to obtain the intermediate 6-chloro-2,8-dimethyl-4H-benzo[d][1,3]oxazin-4-one.

[0076] (2) 6-chloro-2,8-dimethyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and p-aminophenol (1.1 mmol) were heated to reflux for 4-6 hours with 30 mL of glacial acetic acid as solvent, and the reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. When the temperature reached room temperature, the solid was collected by filtration to obtain 6-chloro-3-(4-hydroxyphenyl)-2,8-dimethylquinazolin-4(3H)-one.

[0077] (3) 6-chloro-3-(4-hydroxyphenyl)-2,8-dimethylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S, 3S, 4R, 5S, 6S)-2-(acetoxymethyl)-6-(4-(6-chloro-2,8-dimethyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 21.2% and a melting point of 195.8-196.3° C.

[0078] Example 14: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-(6-iodo-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A14), comprising the following steps:

[0079] (1) 2-Amino-5-iodo-benzoic acid (10.0 mmol) and 50 mL of triethyl orthoacetate as solvent were added to a 100 mL three-necked flask and refluxed for 4-5 h. After the reaction was completed, the mixture was cooled to room temperature and the solid was collected by filtration to obtain the intermediate 6-iodo-2-methyl-4H-benzo[d][1,3]oxazin-4-one.

[0080] (2) 6-iodo-2-methyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and p-aminophenol (1.1 mmol) were heated to reflux for 4-6 hours with 30 mL of glacial acetic acid as solvent. The reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. When the temperature reached room temperature, the solid was collected by filtration to obtain 3-(4-hydroxyphenyl)-6-iodo-2-methylquinazolin-4(3H)-one.

[0081] (3) 3-(4-Hydroxyphenyl)-6-iodo-2-methylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S, 3S, 4R, 5S, 6S)-2-(acetoxymethyl)-6-(4-(6-iodo-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 35.6% and a melting point of 123.4-124.2° C.

[0082] Example 15: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-(7-fluoro-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetate triester (compound number A15), comprising the following steps:

[0083] (1) 2-Amino-4-fluoro-benzoic acid (10.0 mmol) was added to a 100 mL three-necked flask with 50 mL of triethyl orthoacetate as solvent and refluxed for 4-5 h. After the reaction was completed, the mixture was cooled to room temperature and the solid was collected by filtration to obtain the intermediate 7-fluoro-2-methyl-4H-benzo[d][1,3]oxazin-4-one.

[0084] (2) 7-fluoro-2-methyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and p-aminophenol (1.1 mmol) were heated to reflux for 4-6 hours with 30 mL of glacial acetic acid as solvent. The reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. After the temperature reached room temperature, the solid was collected by filtration to obtain 7-fluoro-3-(4-hydroxyphenyl)-2-methylquinazolin-4(3H)-one.

[0085] (3) 7-Fluoro-3-(4-hydroxyphenyl)-2-methylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S, 3S, 4R, 5S, 6S)-2-(acetoxymethyl)-6-(4-(7-fluoro-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 33.0% and a melting point of 209.1-210.3° C.

[0086] Example 16: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-(2,7-dimethyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A16), comprising the following steps:

[0087] (1) 2-Amino-4-methyl-benzoic acid (10.0 mmol) and 50 mL of triethyl orthoacetate as solvent were added to a 100 mL three-necked flask and refluxed for 4-5 h. After the reaction was completed, the mixture was cooled to room temperature and the solid was collected by filtration to obtain the intermediate 2,7-dimethyl-4H-benzo[d][1,3]oxazin-4-one.

[0088] (2) 2,7-dimethyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and p-aminophenol (1.1 mmol) were heated to reflux for 4-6 hours with 30 mL of glacial acetic acid as solvent. The reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. When the temperature reached room temperature, the solid was collected by filtration to obtain 3-(4-hydroxyphenyl)-2,7-dimethylquinazolin-4(3H)-one.

[0089] (3) 3-(4-Hydroxyphenyl)-2,7-dimethylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-(2,7-dimethyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 26.7% and a melting point of 211.5-212.2° C.

[0090] Example 17: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-(6-methoxy-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A17), comprising the following steps:

[0091] (1) 2-Amino-5-methoxy-benzoic acid (10.0 mmol) and 50 mL of triethyl orthoacetate as solvent were added to a 100 mL three-necked flask and refluxed for 4-5 h. After the reaction was completed, the mixture was cooled to room temperature and the solid was collected by filtration to obtain the intermediate 6-methoxy-2-methyl-4H-benzo[d][1,3]oxazin-4-one.

[0092] (2) 6-methoxy-2-methyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and p-aminophenol (1.1 mmol) were heated to reflux for 4-6 hours with 30 mL of glacial acetic acid as solvent. The reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. When the temperature reached room temperature, the solid was collected by filtration to obtain 3-(3-hydroxyphenyl)-6-methoxy-2-methylquinazolin-4(3H)-one.

[0093] (3) 3-(4-Hydroxyphenyl)-6-methoxy-2-methylquinazolin-4(3H)-one (1.0 mmol), acetyl bromide-α-D-glucose (3.0 mmol), and 30 mL of dichloromethane as solvent were heated to 35° C. The reaction process was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S, 3S, 4R, 5S, 6S)-2-(acetoxymethyl)-6-(4-(6-methoxy-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 34.2% and a melting point of 116.0-117.6° C.

[0094] Example 18: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-(6-methoxy-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A18), comprising the following steps:

[0095] (1) 2-Amino-5-methoxy-benzoic acid (10.0 mmol) and 50 mL of triethyl orthoacetate as solvent were added to a 100 mL three-necked flask and refluxed for 4-5 h. After the reaction was completed, the mixture was cooled to room temperature and the solid was collected by filtration to obtain the intermediate 6-methoxy-2-methyl-4H-benzo[d][1,3]oxazin-4-one.

[0096] (2) 6-methoxy-2-methyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and p-aminophenol (1.1 mmol) were heated to reflux for 4-6 hours with 30 mL of glacial acetic acid as solvent. The reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. When the temperature reached room temperature, the solid was collected by filtration to obtain 3-(4-hydroxyphenyl)-6-methoxy-2-methylquinazolin-4(3H)-one.

[0097] (3) 3-(4-Hydroxyphenyl)-6-methoxy-2-methylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S, 3S, 4R, 5S, 6S)-2-(acetoxymethyl)-6-(4-(6-methoxy-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 56.8% and a melting point of 196.6-197.3° C.

[0098] Example 19: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-(7-bromo-2-methyl-4-oxoquinazoline)-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A19), comprising the following steps:

[0099] (1) 2-Amino-4-bromo-benzoic acid (10.0 mmol) and 50 mL of triethyl orthoacetate as solvent were added to a 100 mL three-necked flask and refluxed for 4-5 h. After the reaction was completed, the mixture was cooled to room temperature and the solid was collected by filtration to obtain the intermediate 7-bromo-2-methyl-4H-benzo[d][1,3]oxazin-4-one.

[0100] (2) 7-bromo-2-methyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and p-aminophenol (1.1 mmol) were heated to reflux for 4-6 h with 30 mL of glacial acetic acid as solvent. The reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. When the temperature reached room temperature, the solid was collected by filtration to obtain 7-bromo-3-(4-hydroxyphenyl)-2-methylquinazolin-4(3H)-one.

[0101] (3) 7-bromo-3-(4-hydroxyphenyl)-2-methylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S, 3S, 4R, 5S, 6S)-2-(acetoxymethyl)-6-(4-(7-bromo-2-methyl-4-oxoquinazolin)-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 45.1% and a melting point of 221.4-222.6° C.

[0102] Example 20: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(3-(2,7,8-trimethyl-4-oxoquinazoline)-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A20), comprising the following steps:

[0103] (1) Same as step (1) of Example 9

[0104] (2) 2,7,8-trimethyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and 3-aminophenol (1.1 mmol) were heated to reflux for 4-6 hours with 30 mL of glacial acetic acid as solvent, and the reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. After the temperature reached room temperature, the solid was collected by filtration to obtain 3-(3-hydroxyphenyl)-2,7,8-trimethylquinazolin-4(3H)-one.

[0105] (3) 3-(3-Hydroxyphenyl)-2,7,8-trimethylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(3-(2,7,8-trimethyl-4-oxoquinazolin)-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 73.5% and a melting point of 238.2-239.5° C.

[0106] Example 21: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(3-(6-fluoro-2-methyl-4-oxoquinazoline)-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A21), comprising the following steps:

[0107] (1) Same as step (1) of Example 5

[0108] (2) 6-Fluoro-2-methyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and 3-aminophenol (1.1 mmol) were heated to reflux for 4-6 h with 30 mL of glacial acetic acid as solvent. The reaction progress was monitored by TLC. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. When the temperature reached room temperature, the solid was collected by filtration to obtain 6-fluoro-3-(3-hydroxyphenyl)-2-methylquinazolin-4(3H)-one.

[0109] (3) 6-Fluoro-3-(3-hydroxyphenyl)-2-methylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S, 3S, 4R, 5S, 6S)-2-(acetoxymethyl)-6-(3-(6-fluoro-2-methyl-4-oxoquinazolin)-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 69.8% and a melting point of 117.5-118.8° C.

[0110] Example 22: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(3-(6-iodo-2-methyl-4-oxoquinazoline)-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A22), comprising the following steps:

[0111] (1) Same as step (1) of Example 14

[0112] (2) 6-iodo-2-methyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and 3-aminophenol (1.1 mmol) were heated to reflux for 4-6 h with 30 mL of glacial acetic acid as solvent. The reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. When the temperature reached room temperature, the solid was collected by filtration to obtain 3-(3-hydroxyphenyl)-6-iodo-2-methylquinazolin-4(3H)-one with a yield of 42.4%.

[0113] (3) 3-(3-Hydroxyphenyl)-6-iodo-2-methylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S, 3S, 4R, 5S, 6S)-2-(acetoxymethyl)-6-(3-(6-iodo-2-methyl-4-oxoquinazolin)-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 56.9% and a melting point of 110.9-111.6° C.

[0114] Example 23: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(3-(7-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A23), comprising the following steps:

[0115] (1) Same as step (1) of Example 6

[0116] (2) 7-chloro-2-methyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and 3-aminophenol (1.1 mmol) were heated to reflux for 4-6 hours with 30 mL of glacial acetic acid as solvent. The reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. After the temperature reached room temperature, the solid was collected by filtration to obtain 7-chloro-3-(3-hydroxyphenyl)-2-methylquinazolin-4(3H)-one.

[0117] (3) 7-Chloro-3-(3-hydroxyphenyl)-2-methylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S, 3S, 4R, 5S, 6S)-2-(acetoxymethyl)-6-(3-(7-chloro-2-methyl-4-oxoquinazolin-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 74.4% and a melting point of 105.3-106.7° C.

[0118] Example 24: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(3-(8-fluoro-2-methyl-4-oxoquinazoline)-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A24), comprising the following steps:

[0119] (1) Same as step (1) of Example 11

[0120] (2) 8-Fluoro-2-methyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and 3-aminophenol (1.1 mmol) were heated to reflux for 4-6 h with 30 mL of glacial acetic acid as solvent. The reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. When the temperature reached room temperature, the solid was collected by filtration to obtain 8-fluoro-3-(3-hydroxyphenyl)-2-methylquinazolin-4(3H)-one.

[0121] (3) 8-Fluoro-3-(3-hydroxyphenyl)-2-methylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S, 3S, 4R, 5S, 6S)-2-(acetoxymethyl)-6-(3-(8-fluoro-2-methyl-4-oxoquinazolin)-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 45.0% and a melting point of 125.9-126.7° C.

[0122] Example 25: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(3-(5-fluoro-2-methyl-4-oxoquinazoline)-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A25), comprising the following steps:

[0123] (1) Same as step (1) of Example 10

[0124] (2) 5-Fluoro-2-methyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and 3-aminophenol (1.1 mmol) were heated to reflux for 4-6 h with 30 mL of glacial acetic acid as solvent. The reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. When the temperature reached room temperature, the solid was collected by filtration to obtain 5-fluoro-3-(3-hydroxyphenyl)-2-methylquinazolin-4(3H)-one.

[0125] (3) 5-Fluoro-3-(3-hydroxyphenyl)-2-methylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S, 3S, 4R, 5S, 6S)-2-(acetoxymethyl)-6-(3-(5-fluoro-2-methyl-4-oxoquinazolin)-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 30.0% and a melting point of 112.9-113.5° C.

[0126] Example 26: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(3-(2,8-dimethyl-4-oxoquinazoline)-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A26), comprising the following steps:

[0127] (1) Same as step (1) of Example 8

[0128] (2) 2,8-dimethyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and 3-aminophenol (1.1 mmol) were heated to reflux for 4-6 hours with 30 mL of glacial acetic acid as solvent, and the reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. When the temperature reached room temperature, the solid was collected by filtration to obtain 3-(3-hydroxyphenyl)-2,8-dimethylquinazolin-4(3H)-one.

[0129] (3) 3-(3-Hydroxyphenyl)-2,8-dimethylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(3-(2,8-dimethyl-4-oxoquinazolin)-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 52.1% and a melting point of 116.1-117.8° C.

[0130] Example 27: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(3-(7-fluoro-2-methyl-4-oxoquinazoline)-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetate (compound number A27), comprising the following steps:

[0131] (1) Same as step (1) of Example 15

[0132] (2) 7-Fluoro-2-methyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and 3-aminophenol (1.1 mmol) were heated to reflux for 4-6 h with 30 mL of glacial acetic acid as solvent. The reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. After the temperature reached room temperature, the solid was collected by filtration to obtain 7-fluoro-3-(3-hydroxyphenyl)-2-methylquinazolin-4(3H)-one.

[0133] (3) 7-Fluoro-3-(3-hydroxyphenyl)-2-methylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S, 3S, 4R, 5S, 6S)-2-(acetoxymethyl)-6-(3-(7-fluoro-2-methyl-4-oxoquinazolin)-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 58.5% and a melting point of 133.2-134.9° C.

[0134] Example 28: Synthesis of (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(3-(2,5-dimethyl-4-oxoquinazoline)-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester (compound number A28), comprising the following steps:

[0135] (1) 2-Amino-6-methyl-benzoic acid (10.0 mmol) and 50 mL of triethyl orthoacetate as solvent were added to a 100 mL three-necked flask and refluxed for 4-5 h. After the reaction was completed, the mixture was cooled to room temperature and the solid was collected by filtration to obtain the intermediate 2,5-dimethyl-4H-benzo[d][1,3]oxazin-4-one.

[0136] (2) 2,5-dimethyl-4H-benzo[d][1,3]oxazin-4-one (1.0 mmol) and 3-aminophenol (1.1 mmol) were heated to reflux for 4-6 hours with 30 mL of glacial acetic acid as solvent, and the reaction progress was monitored by TLC tracking. After the reaction was completed, the system was poured into ice water with a magnetic stirrer and stirred thoroughly. When the temperature reached room temperature, the solid was collected by filtration to obtain 3-(3-hydroxyphenyl)-2,5-dimethylquinazolin-4(3H)-one.

[0137] (3) 3-(3-Hydroxyphenyl)-2,5-dimethylquinazolin-4(3H)-one (1.0 mmol) and acetyl bromide-α-D-glucose (3.0 mmol) were heated to 35° C. with 30 mL of dichloromethane as solvent, and the reaction progress was monitored by TLC tracking until the reaction was completed. The reaction system was extracted with 20 mL of sodium hydroxide solution and 20 mL of saturated sodium chloride solution, and purified by column chromatography to obtain solid (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(3-(2,5-dimethyl-4-oxoquinazolin)-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester with a yield of 25.3% and a melting point of 142.1-143.8° C.

[0138] The nuclear magnetic resonance hydrogen spectra of the glycoside derivatives containing quinazoline structure synthesized in the above Examples A1-A28 ( 1 HNMR), carbon spectrum ( 13 The C NMR and high resolution mass spectrometry (HRMS) data are shown in Table 1.

[0139] Table 1. Spectral data of compounds of Examples A1-A28

[0140]

[0141]

[0142]

[0143]

[0144]

[0145]

[0146]

[0147]

[0148]

[0149]

[0150] Example 29: Inhibitory activity of target compounds against kiwifruit canker pathogens

[0151] (1) Test method

[0152] 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 μg / mL. 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 medium containing tobacco bacterial wilt pathogen and konjac soft rot pathogen was cut into two NB mediums with a bacterial loop, plugged, and cultured at 28°C, 180 rpm constant temperature shaker to the logarithmic growth phase (OD = 0.6-0.8) for use. Take 40 μL of bacterial solution, 4 mL of water-Tween (1% Tween 20), and 1 mL of the prepared compound solution, culture the test tube at 28 ± 1°C, and shake continuously at 180 rpm for 1-3 days. The growth of bacteria was monitored by measuring the optical density at 600nm (OD600), but the same concentration of solvent and 0.1% Tween20 were used as blank controls, and chlorothiazide was used as a control agent. Each treatment was repeated three times. The inhibition rate of the agent on bacteria was calculated by the following formula:

[0153] I=(Ctur-Ttur) / Ctur×100%

[0154] 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.

[0155] (2) Biological test results

[0156] Table 2 Inhibitory activity of target compounds against kiwifruit canker pathogen at 100 μg / mL

[0157]

[0158]

[0159] The in vitro growth rate method was used to test the antibacterial activity of the target compound at a concentration of 100 μg / mL, with chloroquine as the control agent. From the biological activity test results in Table 2, it can be seen that the glycoside derivatives containing quinazoline structure have good inhibitory activity against kiwifruit canker bacteria, among which A23 has the best activity, with an inhibition rate of 90.8%, which is better than the control agent chloroquine. Example 30: Therapeutic, inactivating and protective activities of the target compound against cucumber mosaic virus

[0160] (1) Test method

[0161] A. Virus purification

[0162] The Gooding method (Gooding et al. 1967) was used to select the upper leaves of Nicotiana glutinosa L. plants that had been inoculated for more than 3 weeks and infected by CMV 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 CMV. 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.

[0163] Virus concentration (mg / mL) = (A260 × dilution factor) / E0.1% 1cm260nm

[0164] 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.

[0165] B. Active therapeutic effect of the agent on CMV 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, 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.

[0166] C. The protective effect of the drug on CMV infection in vivo

[0167] The living protective effect of the agent on CMV 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 into 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.

[0168] D. The inactivation effect of the drug on CMV infection in vivo

[0169] The in vivo passivation effect of the agent on CMV 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 of the cinnamon sprinkled with corundum, mix the corresponding dose of solvent and virus juice and inoculate on the left half leaf of the appropriate age of the cinnamon 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.

[0170] Y=(CA) / C×100%

[0171] 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).

[0172] (2) Biological test results

[0173] Table 3 The therapeutic, protective and inactivating activities of target compounds against cucumber mosaic virus

[0174]

[0175]

[0176] The anti-TMV activity of the target compound 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 glycoside derivatives containing quinazoline structure have moderate to excellent inhibitory activity against CMV, among which A23 is superior to the control agent Ningnanmycin in terms of treatment, protection and passivation.

[0177] Example 31: Therapeutic, inactivating and protective activities of target compounds against tobacco mosaic virus

[0178] (1) Test method

[0179] A. Virus purification

[0180] 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.

[0181] Virus concentration (mg / mL) = (A260 × dilution factor) / E0.1% 1cm260nm

[0182] 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.

[0183] 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.

[0184] C. The protective effect of the agent on TMV infection

[0185] 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.

[0186] D. The inactivation effect of the agent on TMV infection in vivo

[0187] 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, and use a brush to rub and inoculate it on the right half leaf of the appropriate-age sedum sprinkled with corundum. The corresponding dose of solvent and virus juice are mixed and inoculated on the left half leaf of the appropriate-age sedum sprinkled with corundum. After 3-4 days, observe and record the number of dead spots. 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.

[0188] Y=(CA) / C×100%

[0189] 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).

[0190] (2) Biological test results

[0191] Table 4 The therapeutic, protective and inactivating activities of target compounds against tobacco mosaic virus

[0192]

[0193]

[0194] The anti-TMV activity of the target compound 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 4, it can be seen that the glycoside derivatives containing quinazoline structure have moderate to excellent inhibitory activity against TMV, among which A23 is superior to the control agent Ningnanmycin in terms of treatment, protection and passivation.

[0195] Example 32: Preparation of target compound A23 composition

[0196] Some of the preparations used below were prepared by adjusting the concentration of commercially purchased 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, the wettable powder of the target compound A23 and copper rosinate was used to prepare a composite composition, and in each composition, the ratio of the target compound A23 to copper rosinate was calculated according to the mass ratio. The following preparations of the target compound A23 and copper rosinate were prepared as needed.

[0197] Composition 1: A23: copper rosinate wettable powder = 1:1

[0198] Composition 2: A23: copper rosinate wettable powder = 1:2

[0199] Composition 3: A23: copper rosinate wettable powder = 2:1

[0200] Example 33: Anti-kiwifruit canker activity of the composition of target compound A23

[0201] According to the antibacterial activity test method mentioned in Example 29, the antibacterial activity of the composition of the target compound A23 and copper rosinate was tested for its antibacterial activity against kiwifruit canker bacteria.

[0202] Table 5 Inhibitory activity of drugs against kiwifruit canker pathogens

[0203]

[0204] 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 test results in Table 5, it can be seen that the anti-kiwifruit canker pathogen activity of the composite composition is improved compared with the compound before the composite. The inhibitory activity of composition 3 (A23: copper rosinate wettable powder = 2:1) on kiwifruit canker pathogens reached 100.0%. Therefore, the composite composition of A23 and copper rosinate has a synergistic effect on kiwifruit canker.

Claims

1. A glycoside derivative containing a quinazoline structure, characterized in that: The general formula of the derivative is as follows: Wherein: R1 is halogen, methyl, methoxy or disubstituted or trisubstituted by any combination of the above substituents, and the glycoside substituent is located at the meta or para position of the benzene ring.

2. The method for preparing a glycoside derivative containing a quinazoline structure according to claim 1, characterized in that: The following steps are involved: (1) (2) (3) 3. The method for preparing a glycoside derivative containing a quinazoline structure according to claim 2, characterized in that: The synthesis steps and process conditions are as follows: add substituted benzoic acid and triethyl orthoacetate in a molar ratio of 1:20-50, heat under reflux for 4-6 hours, wait for the reaction to be completed, and after the temperature drops to room temperature, filter and collect the solid to obtain substituted 2-methyl-4H-benzo[d][1,3]oxazine-4-one; add substituted 2-methyl-4H-benzo[d][1,3]oxazine-4-one and p-aminophenol or 3-aminophenol and glacial acetic acid in a molar ratio of 1:1-1.2:20-50, heat under reflux for 4-6 hours, wait for the reaction to be completed. After the reaction is completed, the reaction system is poured into ice water with a magnetic stirrer and stirred thoroughly; after the temperature drops to room temperature, the solid is collected by filtration to obtain substituted 2-methyl-3-phenylquinazoline-4(3H)-one; the substituted 2-methyl-3-phenylquinazoline-4(3H)-one: glycoside: dichloromethane are added in a molar ratio of 1:3:30, and the mixture is heated to 35°C. After the reaction is completed, the reaction system is extracted with a sodium hydroxide aqueous solution and a saturated sodium chloride solution, and purified by column chromatography to obtain a target glycoside compound containing a quinazoline structure.

4. Use of a glycoside derivative containing a quinazoline structure as claimed in claim 1 in the preparation of drugs and medicaments for preventing and treating kiwifruit canker, cucumber mosaic virus disease and tobacco mosaic virus disease.

5. A compound pesticide composition, characterized in that: The composition comprises the derivative according to claim 1 and copper rosinate.

6. The composition according to claim 5, characterized in that: The mass ratio of the derivative to copper rosinate is 1:2-2:

1.

7. Use of the composition according to claim 5 in the preparation of a drug for preventing and treating plant bacterial diseases, wherein the plant bacterial disease is kiwifruit canker.

8. The composition according to claim 5, characterized in that: The derivative is: (2S, 3S, 4R, 5S, 6S)-2-(acetoxymethyl)-6-(3-(7-chloro-2-methyl-4-oxoquinazoline-3(4H)-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetic acid triester.

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