Andrographolide derivative containing thiazolidinone heterocycle, preparation method and application thereof

Abstract

The present invention discloses an andrographolide derivative containing a thiazolidinone heterocycle, a preparation method and an application thereof. The chemical structural formula of the andrographolide derivative containing a thiazolidinone heterocycle is shown in Formula VII, wherein: R 1 Select TBS or TIPS; R 2 Selected from benzyl, substituted benzyl, (2-chloropyridin-5-yl)methylene, and alkyl groups. Studies have shown that some andrographolide derivatives containing thiazolidinone heterocycles exhibit significantly improved 48-hour insecticidal activity compared to andrographolide, with some derivatives exhibiting 48-hour insecticidal activity exceeding 60%. These derivatives are expected to be used in the preparation of highly effective, environmentally friendly, and low-toxic botanical insecticides.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis and relates to andrographolide derivatives, in particular to an andrographolide derivative containing a thiazolidinone heterocycle, a preparation method and an application thereof. Background Art

[0002] Andrographolide is a diterpene lactone compound extracted from the plant Andrographis paniculata (Acanthaceae). It contains an α,β-unsaturated γ-butyrolactone moiety, a trans-decalin ring with a terminal olefin bond, and three hydroxyl groups at the C-3, C-14, and C-19 positions. Andrographolide exhibits antibacterial, antiviral, anticancer, anti-inflammatory, antidepressant, and cardiovascular protective activities. 4-Thiazolidinone is a five-membered heterocyclic ring containing nitrogen and sulfur atoms and exhibits antibacterial, anticancer, anti-inflammatory, antidiabetic, insecticidal, and bactericidal activities. Summary of the Invention

[0003] Based on the inventors' research findings, the present invention provides an andrographolide derivative containing a thiazolidinone heterocycle. The provided andrographolide derivative containing a thiazolidinone heterocycle has a chemical structural formula as shown in Formula VII:

[0004]

[0005] Where:

[0006] R 1 TBS or TIPS;

[0007] R 2 is selected from benzyl, substituted benzyl, (2-chloropyridin-5-yl)methylene or alkyl.

[0008] Further optionally, the R 2 is selected from benzyl, p-chlorobenzyl, m-chlorobenzyl, o-chlorobenzyl, p-bromobenzyl, m-bromobenzyl, o-bromobenzyl, p-methylbenzyl, m-methylbenzyl, o-methylbenzyl, p-nitrobenzyl, p-cyanobenzyl, p-isopropylbenzyl, p-tert-butylbenzyl, (2-chloropyridin-5-yl)methylene, methyl, ethyl, n-propyl, n-butyl or n-pentyl.

[0009] The present invention also provides a method for preparing the above-mentioned andrographolide derivatives containing thiazolidinone heterocycles, which comprises:

[0010] Step 1, in the presence of aluminum oxide, using andrographolide of formula I as a raw material to prepare intermediate II of formula II;

[0011] Step 2, reacting intermediate II with tert-butyldimethylsilyl chloride or reacting intermediate II with triisopropylsilyl chloride to prepare intermediate III of formula III;

[0012] Step 3, in the presence of pyridinium chlorochromate, using intermediate III as a raw material to prepare intermediate IV of formula IV;

[0013] Step 4, intermediate IV is reacted with thiosemicarbazide to prepare intermediate V shown in formula V;

[0014] Step 5, intermediate V is reacted with methyl bromoacetate to prepare intermediate VI shown in formula VI;

[0015] Step 6, reacting intermediate VI with a halogenated hydrocarbon to prepare an andrographolide derivative containing a thiazolidinone heterocycle;

[0016]

[0017] An optional solution is that the reaction in step 1 is carried out in a first organic solvent under heating under reflux; after the reaction in step 1 is completed, intermediate II is obtained by cooling, filtering, concentrating and separating by column chromatography.

[0018] The reaction in step 2 is carried out in a second organic solvent at room temperature; after the reaction in step 2 is completed, intermediate III is obtained by extraction, concentration and column chromatography separation.

[0019] The reaction in step 3 is carried out in a third organic solvent at room temperature; after the reaction in step 3 is completed, intermediate IV is obtained by extraction, concentration and column chromatography separation.

[0020] The step 4 is carried out in a fourth organic solvent under reflux conditions; after the reaction in step 4 is completed, V is obtained by concentration and column chromatography purification.

[0021] The step 5 is carried out in a fifth organic solvent under reflux reaction conditions; after the reaction in step 5 is completed, V is obtained by extraction, concentration and column chromatography purification.

[0022] The step 6 is carried out in the presence of a catalyst in a sixth organic solvent at room temperature; after the reaction in step 6 is completed, the mixture is purified by filtration, extraction, concentration and thin layer chromatography to obtain compound VII.

[0023] Preferably and specifically, in step 1, the molar ratio of andrographolide to aluminum oxide is 1:0.6.

[0024] Preferably and specifically, in step 2, the molar ratio of the intermediate II to tert-butyldimethylsilyl chloride (or triisopropylsilyl chloride) is 1:2.

[0025] Preferably and specifically, in step 3, the molar ratio of the intermediate III to pyridinium chlorochromate is 1:4.

[0026] Preferably and specifically, in step 4, the molar ratio of the intermediate IV to thiosemicarbazide is 1:1.2.

[0027] Preferably and specifically, in step 5, the molar ratio of the intermediate V to methyl bromoacetate is 1:1.

[0028] Preferably and specifically, in step 6, the molar ratio of the intermediate VI to the halogenated hydrocarbon is 1:1.1.

[0029] Compared to the parent andrographolide, the present invention's thiazolidinone heterocycle-containing andrographolide derivatives exhibit significantly enhanced insecticidal activity and can be used to prepare highly effective, environmentally friendly, and low-toxic botanical insecticides. The present invention also protects the use of the aforementioned thiazolidinone heterocycle-containing andrographolide derivatives in the preparation of insecticides. These insecticides target common agricultural lepidopteran pests, such as common armyworms and diamondback moths.

[0030] The present invention proposes for the first time a technical idea of ​​introducing a 4-thiazolidinone heterocycle into the chemical structure of andrographolide, and the synthesis method has simple steps. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 is the H NMR spectrum of compound VII-1.

[0032] Figure 2 This is the H NMR spectrum of compound VII-2.

[0033] Figure 3 This is the hydrogen nuclear magnetic resonance spectrum of compound VII-21.

[0034] Figure 4 This is the hydrogen nuclear magnetic resonance spectrum of compound VII-23.

[0035] The specific contents of the present invention are further explained in detail below with reference to the embodiments. DETAILED DESCRIPTION

[0036] Unless otherwise specified, the scientific and technical terms used herein are understood according to the knowledge of ordinary technicians in the relevant fields.

[0037] The synthetic routes of the compounds of the present invention are exemplified as follows:

[0038]

[0039] In the specific scheme, based on the above reaction scheme and the disclosure of the present invention, those skilled in the art can optimize the reaction conditions, organic solvents, catalysts, etc. of each step to obtain the compounds of the present invention. It should be noted that all raw materials used in the present invention, unless otherwise specified, are conventional raw materials known in the art.

[0040] In the above synthetic route, compound I-1 is andrographolide, compounds II-a, II-b, III-a, III-b, IV-a, IV-b, Va, Vb, VI-a and VI-b can be selected from the intermediates of the following Examples 1 to 40, and compounds VII-1 to VII-40 can be selected from the target products of the following Examples 1 to 40; corresponding to the following examples, R 1 TBS or TIPS; R 2 For PhCH2, 4-ClPhCH2, 3-ClPhCH2, 2-ClPhCH2, 4-BrPhCH2, 3-BrPhCH2, 2-BrPhCH2, 4-MePhCH2, 3-MePhCH2, 2-MePhCH2, 4 -NO2PhCH2, 4-CNPhCH2, 4-i-PrPhCH2, 4-t-BuPhCH2, (2-chloropyridin-5-yl)methylene, CH3, C2H5, C3H7, C4H9 or C5H 11 .

[0041] Specific embodiments of the present invention are given below. It should be noted that the present invention is not limited to the following specific embodiments, and all equivalent modifications made on the basis of the technical solution of this application fall within the protection scope of the present invention.

[0042] Example 1:

[0043] This embodiment provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle, which specifically comprises the following steps:

[0044] Step 1: Dissolve 10 mmol of compound I and 6 mmol of aluminum oxide in anhydrous pyridine and reflux in an oil bath at 110°C for 15 hours. After the reaction, filter out the aluminum oxide, wash the filter cake with dichloromethane, and then wash the filtrate with 1M hydrochloric acid. Combine the organic phases, dry them over anhydrous Na2SO4, filter and concentrate them, and purify them by column chromatography to obtain intermediate II in a yield of 45%.

[0045] Step 2: Dissolve 1 mmol of intermediate II and 2 mmol of TBSCl in anhydrous dichloromethane, add 5 mmol of triethylamine, and stir at room temperature for 1 hour; after the reaction, add dichloromethane to the above system, wash with saturated NaHCO3 solution, dry over anhydrous sodium sulfate, concentrate under reduced pressure, and purify by silica gel column chromatography to obtain intermediate III-a;

[0046] The physicochemical properties of intermediate III-a are as follows:

[0047] Physical and chemical properties: Pale yellow solid, melting point 136-137°C, yield 76%.

[0048] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2946,2863,1752,1645,1352,1057; 1 H NMR(400MHz, CDCl3)δ:7.15-7.16(m,1H),6.88-6.94(m,1H),6.14(d,J=15.6Hz,1H),4.811-4.813(m,2H),4.76-4 .77(m,1H),4.53-4.54(m,1H),4.33(d,J=6.8Hz,1H),4.23(d,J=10.0Hz,1H),3.41(d,J=10.0Hz,1H),3.28-3.34(m ,1H),2.41-2.46(m,1H),2.33(d,J=10.0Hz,1H),2.00-2.08(m,1H),1.76-1.84(m,2H),1.60-1.70(m,1H),1.47-1. 52(m,1H),1.25-1.38(m,2H),1.23(s,3H),1.13-1.20(m,1H),0.89(s,9H),0.82(s,3H),0.07(s,3H),0.06(s,3H).

[0049] Its chemical structure is shown in Formula III-a:

[0050] Step 3: Dissolve 1 mmol of intermediate III-a, 4 mmol of pyridinium chlorochromate, and 4 mmol of sodium acetate in dry dichloromethane and stir at room temperature for 24 hours; then add dichloromethane to the above system, wash with saturated NaHSO3 solution and saturated NaCl solution, dry over anhydrous Na2SO4, concentrate under reduced pressure, and purify by silica gel column chromatography to obtain intermediate IV-a.

[0051] In this example, the target compound IV-a obtained in step 3 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0052] Physical and chemical properties: white solid, melting point 131-133°C, yield 25%.

[0053] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2953,2877,1754,1646,1351,1088; 1H NMR(400MHz, CDCl3)δ:7.16-7.17(m,1H),6.93-7.00(m,1H),6.15(d,J=16.0Hz,1H),4.82-4.84 (m,3H),4.605-4.608(m,1H),3.86(d,J=10.0Hz,1H),3.54(d,J=9.6Hz,1H),2.55-2.64(m,1H),2 .47-2.51(m,1H),2.41(d,J=10.4Hz,1H),2.26-2.32(m,1H),2.03-2.10(m,1H),1.72-1.83(m,2 H),1.59-1.67(m,2H),1.42-1.50(m,1H),1.14(s,3H),1.10(s,3H),0.84(s,9H),-0.007(s,6H).

[0054] Its chemical structure is shown in Formula IV-a:

[0055] Step 4: 1 mmol of intermediate IV-a and 1.2 mmol of thiosemicarbazide were dissolved in ethanol, 0.2 mL of acetic acid was added dropwise to the mixture, and the mixture was refluxed and stirred for 19 h, then concentrated under reduced pressure and purified by silica gel column chromatography to obtain intermediate Va.

[0056] In this example, the target compound Va obtained in step 4 was subjected to physical and chemical properties and characterization analysis, and the results are as follows:

[0057] Physical and chemical properties: white solid, melting point 188-190°C, yield 69%.

[0058] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2942,1755,1585,1257,1084,842; 1H NMR(600MHz, CDCl3)δ:8.62(s,1H),7.21-7.22(m,1H),7.17-7.18(m,1H),6.92-6.97(m,1H),6.22(s,1H),6.13 (d,J=16.2Hz,1H),4.83(s,3H),4.59(s,1H),3.78(d,J=10.2Hz,1H),3.52(d,J=10.2Hz,1H),2.47-2.54(m,2H) ,2.34-2.36(m,1H),2.10-2.15(m,1H),2.03-2.08(m,1H),1.81-1.84(m,1H),1.70-1.74(m,1H),1.55-1.60(m, 1H),1.46-1.48(m,1H),1.21-1.24(m,1H),1.20(s,3H),1.03(s,3H),0.82(s,9H),-0.03(s,3H),-0.04(s,3H).

[0059] Its chemical structure is shown in Formula Va:

[0060] Step 5: Dissolve 1 mmol of intermediate Va, 4 mmol of sodium acetate and 1 mmol of methyl bromoacetate in ethanol and reflux with stirring for 3 hours; after the reaction is completed, concentrate under reduced pressure, add aqueous solution, extract with dichloromethane, dry over anhydrous sodium sulfate, concentrate under reduced pressure, and purify by silica gel column chromatography to obtain intermediate VI-a.

[0061] In this example, the target compound VI-a obtained in step 5 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0062] Physical and chemical properties: white solid, melting point 118-119°C, yield 56%.

[0063] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2935,1754,1631,1251,1082,842; 1H NMR(400MHz, CDCl3)δ:7.14-7.15(m,1H),6.89-6.95(m,1H),6.11(d,J=16.0Hz,1H),4.81(s,3H) ,4.56(s,1H),3.73-3.78(m,3H),3.60-3.63(m,1H),3.20-3.24(m,1H),2.45-2.50(m,1H),2.33-2 .35(m,1H),2.06-2.13(m,1H),1.99-2.03(m,1H),1.84-1.88(m,1H),1.57-1.67(m,2H),1.46-1. 50(m,1H),1.25(s,3H),1.18-1.22(m,1H),1.04(s,3H),0.84(s,9H),-0.01(s,3H),-0.03(s,3H).

[0064] Its chemical structure is shown in Formula VI-a:

[0065] Step 6: Dissolve 1 mmol of intermediate VI-a, 1.1 mmol of halogenated hydrocarbon, 1 mmol of potassium carbonate and a catalytic amount of potassium iodide in acetone and stir the reaction at room temperature; concentrate under reduced pressure, add saturated NaCl solution, extract with ethyl acetate, dry over anhydrous sodium sulfate, concentrate under reduced pressure, and purify by preparative thin-layer chromatography to obtain the target compound VII.

[0066] In this embodiment, R 1 is TBS and the halogenated hydrocarbon is benzyl chloride.

[0067] In this example, the target compound VII-1 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0068] Physical and chemical properties: yellow solid, melting point 82-84°C, yield 48%.

[0069] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2938,1757,1620,1257,1084,843; 1H NMR(400MHz, CDCl3)δ:7.42-7.43(m,2H),7.27-7.30(m,2H),7.23-7.25(m,1H),7.16(s,1H),6.91-6.97(m,1H),6. 12(d,J=16.0Hz,1H),4.94(s,2H),4.82(s,3H),4.56(s,1H),3.76(d,J=10.0Hz,1H),3.71(s,2H),3.63(d,J=9.6Hz ,1H),3.33-3.39(m,1H),2.46-2.49(m,1H),2.34-2.37(m,1H),2.00-2.11(m,2H),1.84-1.87(m,1H),1.61-1.68(m ,2H),1.47-1.50(m,1H),1.25(s,3H),1.17-1.21(m,1H),1.06(s,3H),0.81(s,9H),-0.050(s,3H),-0.054(s,3H).

[0070] Its chemical structure is shown in Formula VII-1:

[0071] Example 2:

[0072] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 1, except that in step six, the halogenated hydrocarbon is different, specifically 4-chlorobenzyl chloride.

[0073] In this example, the target compound VII-2 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0074] Physical and chemical properties: yellow solid, melting point 94-95°C, yield 70%.

[0075] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2940,1757,1615,1253,1087,842; 1H NMR(400MHz, CDCl3)δ:7.35-7.38(m,2H),7.22-7.24(m,2H),7.17-7.18(m,1H),6.92-6.98(m,1H),6.13(d,J=15.6 Hz,1H),4.85-4.93(m,2H),4.81-4.82(m,3H),4.56-4.57(m,1H),3.78(d,J=10.0Hz,1H),3.72(s,2H),3.62(d,J=10 .0Hz,1H),3.31-3.36(m,1H),2.45-2.50(m,1H),2.34-2.36(m,1H),2.00-2.12(m,2H),1.83-1.87(m,1H),1.60-1.6 9(m,2H),1.46-1.49(m,1H),1.24(s,3H),1.15-1.23(m,1H),1.07(s,3H),0.81(s,9H),-0.04(s,3H),-0.05(s,3H).

[0076] Its chemical structure is shown in Formula VII-2:

[0077] Example 3:

[0078] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 1, except that in step six, the halogenated hydrocarbon is different, specifically 3-chlorobenzyl chloride.

[0079] In this example, the target compound VII-3 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0080] Physical and chemical properties: yellow solid, melting point 147-148°C, yield 58%.

[0081] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2939,1760,1622,1257,1087,848; 1H NMR(400MHz, CDCl3)δ:7.43-7.44(m,1H),7.30-7.32(m,1H),7.21-7.24(m,2H),7.15-7.17(m,1H),6.91-6.98(m,1H),6. 12(d,J=16.0Hz,1H),4.86-4.93(m,2H),4.80-4.82(m,3H),4.571-4.573(m,1H),3.79(d,J=10.0Hz,1H),3.73(s,2H),3. 62(d,J=10.0Hz,1H),3.32-3.38(m,1H),2.45-2.50(m,1H),2.34-2.36(m,1H),2.00-2.13(m,2H),1.83-1.88(m,1H),1.6 0-1.71(m,2H),1.46-1.50(m,1H),1.25(s,3H),1.18-1.23(m,1H),1.06(s,3H),0.81(s,9H),-0.04(s,3H),-0.05(s,3H).

[0082] Its chemical structure is shown in Formula VII-3:

[0083] Example 4:

[0084] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 1, except that in step six, the halogenated hydrocarbon is different, specifically 2-chlorobenzyl chloride.

[0085] In this example, the target compound VII-4 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0086] Physical and chemical properties: yellow solid, melting point 86-88°C, yield 55%.

[0087] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2940,1757,1620,1254,1083,842; 1H NMR(400MHz, CDCl3)δ:7.32-7.35(m,1H),7.11-7.20(m,4H),6.88-6.94(m,1H),6.10(d,J=16.0Hz,1H),5.03-5 .14(m,2H),4.79-4.82(m,3H),4.546-4.549(m,1H),3.81(s,2H),3.73(d,J=9.6Hz,1H),3.59(d,J=10.0Hz,1H) ,3.14-3.19(m,1H),2.44-2.48(m,1H),2.30-2.33(m,1H),1.81-2.06(m,3H),1.61-1.65(m,1H),1.53-1.56(m, 1H),1.43-1.47(m,1H),1.24(s,3H),1.07-1.15(m,1H),1.01(s,3H),0.80(s,9H),-0.07(s,3H),-0.08(s,3H).

[0088] Its chemical structure is shown in Formula VII-4:

[0089] Example 5:

[0090] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 1, except that in step six, the halogenated hydrocarbon is different, specifically 4-bromobenzyl chloride.

[0091] In this example, the target compound VII-5 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0092] Physical and chemical properties: yellow solid, melting point 94-96°C, yield 60%.

[0093] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2938,1758,1619,1253,1083,841; 1H NMR(400MHz, CDCl3)δ:7.37-7.41(m,2H),7.28-7.32(m,2H),7.18-7.19(m,1H),6.92-6.99(m,1H),6.13(d,J=16.0H z,1H),4.84-4.91(m,2H),4.81-4.83(m,3H),4.56-4.57(m,1H),3.77(d,J=10.0Hz,1H),3.72(s,2H),3.62(d,J=10. 0Hz,1H),3.30-3.35(m,1H),2.45-2.50(m,1H),2.34-2.36(m,1H),2.00-2.12(m,2H),1.83-1.87(m,1H),1.64-1.69 (m,2H),1.46-1.49(m,1H),1.24(s,3H),1.15-1.23(m,1H),1.07(s,3H),0.81(s,9H),-0.050(s,3H),-0.056(s,3H).

[0094] Its chemical structure is shown in Formula VII-5:

[0095] Example 6:

[0096] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 1, except that in step six, the halogenated hydrocarbon is different, specifically 3-bromobenzyl chloride.

[0097] In this example, the target compound VII-6 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0098] Physical and chemical properties: yellow solid, melting point 80-82°C, yield 57%.

[0099] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2937,1758,1619,1254,1084,842; 1H NMR(400MHz, CDCl3)δ:7.60-7.61(m,1H),7.35-7.39(m,2H),7.13-7.17(m,2H),6.91-6.98(m,1H),6.12(d,J=15.6 Hz,1H),4.85-4.92(m,2H),4.80-4.82(m,3H),4.56-4.57(m,1H),3.79(d,J=9.6Hz,1H),3.73(s,2H),3.63(d,J=10. 0Hz,1H),3.33-3.38(m,1H),2.45-2.50(m,1H),2.34-2.37(m,1H),2.00-2.13(m,2H),1.84-1.88(m,1H),1.60-1.7 2(m,2H),1.46-1.50(m,1H),1.25(s,3H),1.19-1.24(m,1H),1.06(s,3H),0.81(s,9H),-0.04(s,3H),-0.05(s,3H).

[0100] Its chemical structure is shown in Formula VII-6:

[0101] Example 7:

[0102] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 1, except that in step six, the halogenated hydrocarbon is different, specifically 2-bromobenzyl bromide.

[0103] In this example, the target compound VII-7 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0104] Physical and chemical properties: yellow solid, melting point 89-91°C, yield 36%.

[0105] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2937,1756,1620,1254,1085,842; 1H NMR(400MHz, CDCl3)δ:7.52-7.54(m,1H),7.19-7.23(m,1H),7.14-7.16(m,1H),7.05-7.12(m,2H),6.87-6.94(m,1H),6. 10(d,J=15.6Hz,1H),5.00-5.11(m,2H),4.79-4.82(m,3H),4.545-4.548(m,1H),3.82(s,2H),3.73(d,J=10.0Hz,1H),3. 58(d,J=10.0Hz,1H),3.13-3.19(m,1H),2.43-2.48(m,1H),2.30-2.33(m,1H),1.81-2.03(m,3H),1.61-1.65(m,1H),1.5 2-1.57(m,1H),1.43-1.46(m,1H),1.24(s,3H),1.07-1.15(m,1H),1.01(s,3H),0.81(s,9H),-0.07(s,3H),-0.08(s,3H).

[0106] Its chemical structure is shown in Formula VII-7:

[0107] Example 8:

[0108] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 1, except that in step six, the halogenated hydrocarbon is different, specifically 4-methylbenzyl chloride.

[0109] In this example, the target compound VII-8 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0110] Physical and chemical properties: yellow solid, melting point 87-89°C, yield 42%.

[0111] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2938,1758,1620,1252,1085,842; 1H NMR(400MHz, CDCl3)δ:7.33(d,J=7.2Hz,2H),7.16(s,1H),7.09(d,J=7.2Hz,2H),6.92-6.98(m,1H),6.13(d,J =15.6Hz,1H),4.89(s,2H),4.82(s,3H),4.56(s,1H),3.76(d,J=9.6Hz,1H),3.70(s,2H),3.63(d,J=9.6Hz,1H) ,3.36-3.40(m,1H),2.46-2.49(m,1H),2.35-2.37(m,1H),2.30(s,3H),2.01-2.11(m,2H),1.84-1.87(m,1H), 1.65-1.68(m,2H),1.47-1.50(m,1H),1.25(s,3H),1.17-1.21(m,1H),1.07(s,3H),0.81(s,9H),-0.05(s,6H).

[0112] Its chemical structure is shown in Formula VII-8:

[0113] Example 9:

[0114] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 1, except that in step six, the halogenated hydrocarbon is different, specifically 3-methylbenzyl chloride.

[0115] In this example, the target compound VII-9 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0116] Physical and chemical properties: yellow solid, melting point 82-84°C, yield 57%.

[0117] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2939,1757,1617,1251,1085,842; 1H NMR(400MHz, CDCl3)δ:7.22-7.24(m,2H),7.14-7.18(m,2H),7.05-7.07(m,1H),6.92-6.98(m,1H),6.12(d,J=16.0H z,1H),4.86-4.93(m,2H),4.81-4.82(m,3H),4.56(s,1H),3.77(d,J=9.6Hz,1H),3.71(s,2H),3.63(d,J=9.6Hz,1H), 3.36-3.42(m,1H),2.46-2.49(m,1H),2.34-2.36(m,1H),2.29(s,3H),2.00-2.12(m,2H),1.84-1.88(m,1H),1.62-1. 68(m,2H),1.46-1.50(m,1H),1.25(s,3H),1.17-1.22(m,1H),1.06(s,3H),0.81(s,9H),-0.04(s,3H),-0.05(s,3H).

[0118] Its chemical structure is shown in Formula VII-9:

[0119] Example 10:

[0120] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 1, except that in step six, the halogenated hydrocarbon is different, specifically 2-methylbenzyl chloride.

[0121] In this example, the target compound VII-10 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0122] Physical and chemical properties: yellow solid, melting point 80-82°C, yield 65%.

[0123] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2939,1756,1621,1252,1085,841; 1H NMR(400MHz, CDCl3)δ:7.07-7.19(m,5H),6.89-6.95(m,1H),6.10(d,J=15.6Hz,1H),4.92-5.00(m,2H),4.80-4.8 2(m,3H),4.54-4.55(m,1H),3.77(s,2H),3.74(d,J=9.6Hz,1H),3.60(d,J=10.0Hz,1H),3.15-3.20(m,1H),2.44- 2.49(m,1H),2.40(s,3H),2.31-2.34(m,1H),1.92-2.06(m,2H),1.83-1.87(m,1H),1.62-1.66(m,1H),1.55-1.59 (m,1H),1.44-1.48(m,1H),1.25(s,3H),1.09-1.17(m,1H),1.03(s,3H),0.81(s,9H),-0.05(s,3H),-0.06(s,3H).

[0124] Its chemical structure is shown in Formula VII-10:

[0125] Example 11:

[0126] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 1, except that in step six, the halogenated hydrocarbon is different, specifically 4-nitrobenzyl chloride.

[0127] In this example, the target compound VII-11 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0128] Physical and chemical properties: yellow solid, melting point 81-83°C, yield 49%.

[0129] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2938,1755,1619,1252,1087,843; 1H NMR(400MHz, CDCl3)δ:8.11-8.15(m,2H),7.56-7.58(m,2H),7.20-7.21(m,1H),6.91-6.97(m,1H),6.11(d,J=15.6Hz,1H ),4.96-5.07(m,2H),4.81-4.84(m,3H),4.566-4.569(m,1H),3.77-3.79(m,3H),3.60(d,J=10.0Hz,1H),3.23-3.28(m,1H ),2.44-2.49(m,1H),2.31-2.34(m,1H),2.05-2.10(m,1H),1.99-2.03(m,1H),1.82-1.87(m,1H),1.64-1.67(m,1H),1.5 6-1.60(m,1H),1.44-1.47(m,1H),1.24(s,3H),1.09-1.17(m,1H),1.05(s,3H),0.81(s,9H),-0.05(s,3H),-0.06(s,3H).

[0130] Its chemical structure is shown in Formula VII-11:

[0131] Example 12:

[0132] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 1, except that in step 6, the halogenated hydrocarbon is different, specifically 4-cyanobenzyl chloride.

[0133] In this example, the target compound VII-12 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0134] Physical and chemical properties: yellow solid, melting point 86-88°C, yield 64%.

[0135] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2939,1754,1618,1252,1086,841; 1H NMR(400MHz, CDCl3)δ:7.56-7.58(m,2H),7.50-7.52(m,2H),7.20-7.21(m,1H),6.91-6.97(m,1H),6.13(d,J=1 6.0Hz,1H),4.92-5.02(m,2H),4.81-4.83(m,3H),4.564-4.567(m,1H),3.76-3.79(m,3H),3.60(d,J=10.0Hz,1H ),3.22-3.27(m,1H),2.45-2.50(m,1H),2.32-2.35(m,1H),1.99-2.09(m,2H),1.82-1.87(m,1H),1.62-1.66(m ,2H),1.44-1.48(m,1H),1.24(s,3H),1.10-1.18(m,1H),1.06(s,3H),0.81(s,9H),-0.05(s,3H),-0.06(s,3H).

[0136] Its chemical structure is shown in Formula VII-12:

[0137] Example 13:

[0138] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 1, except that in step six, the halogenated hydrocarbon is different, specifically 4-isopropylbenzyl chloride.

[0139] In this example, the target compound VII-13 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0140] Physical and chemical properties: yellow solid, melting point 90-92°C, yield 44%.

[0141] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2945,1759,1620,1253,1085,842; 1H NMR(400MHz, CDCl3)δ:7.35-7.37(m,2H),7.12-7.16(m,3H),6.92-6.99(m,1H),6.13(d,J=16.0Hz,1H),4.90( s,2H),4.82(s,3H),4.56(s,1H),3.76(d,J=10.0Hz,1H),3.70(s,2H),3.63(d,J=10.0Hz,1H),3.36-3.40(m,1H ),2.82-2.89(m,1H),2.46-2.49(m,1H),2.34-2.37(m,1H),2.01-2.12(m,2H),1.84-1.87(m,1H),1.65-1.68(m ,2H),1.47-1.50(m,1H),1.25-1.29(m,4H),1.21(s,3H),1.19(s,3H),1.07(s,3H),0.81(s,9H),-0.05(s,6H).

[0142] Its chemical structure is shown in Formula VII-13:

[0143] Example 14:

[0144] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 1, except that in step six, the halogenated hydrocarbon is different, specifically 4-tert-butylbenzyl chloride.

[0145] In this example, the target compound VII-14 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0146] Physical and chemical properties: yellow solid, melting point 100-102°C, yield 57%.

[0147] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2949,1760,1619,1255,1085,843; 1H NMR(400MHz, CDCl3)δ:7.35-7.38(m,2H),7.28-7.30(m,2H),7.15-7.16(m,1H),6.93-6.99(m,1H),6.13(d,J=15.6Hz,1H) ,4.90(s,2H),4.81-4.82(m,3H),4.561-4.566(m,1H),3.76(d,J=9.6Hz,1H),3.70(s,2H),3.63(d,J=10.0Hz,1H),3.35-3. 40(m,1H),2.45-2.50(m,1H),2.34-2.37(m,1H),2.07-2.12(m,1H),2.00-2.03(m,1H),1.83-1.88(m,1H),1.65-1.68(m,2 H),1.47-1.50(m,1H),1.27(s,9H),1.25(s,3H),1.17-1.21(m,1H),1.07(s,3H),0.81(s,9H),-0.04(s,3H),-0.05(s,3H).

[0148] Its chemical structure is shown in Formula VII-14:

[0149] Example 15:

[0150] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 1, except that in step six, the halogenated hydrocarbon is different, specifically 2-chloro-5-chloromethylpyridine.

[0151] In this example, the target compound VII-15 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0152] Physical and chemical properties: yellow solid, melting point 91-93°C, yield 45%.

[0153] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2941,1755,1614,1250,1090,842; 1H NMR(400MHz, CDCl3)δ:8.48-8.49(m,1H),7.74-7.77(m,1H),7.24-7.26(m,1H),7.20-7.21(m,1H),6.91-6.97(m,1H),6.15(d,J =16.0Hz,1H),4.91(s,2H),4.81-4.83(m,3H),4.57-4.58(m,1H),3.77(d,J=10.0Hz,1H),3.73(s,2H),3.62(d,J=10.0Hz,1H),3. 28-3.34(m,1H),2.45-2.50(m,1H),2.34-2.36(m,1H),2.06-2.14(m,1H),2.00-2.03(m,1H),1.83-1.88(m,1H),1.68-1.71(m,1 H),1.57-1.64(m,1H),1.46-1.50(m,1H),1.24(s,3H),1.16-1.21(m,1H),1.06(s,3H),0.81(s,9H),-0.04(s,3H),-0.05(s,3H).

[0154] Its chemical structure is shown in Formula VII-15:

[0155] Example 16:

[0156] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is substantially the same as that in Example 1, except that in step six, the halogenated hydrocarbon is different, specifically iodomethane.

[0157] In this example, the target compound VII-16 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0158] Physical and chemical properties: yellow solid, melting point 88-89°C, yield 74%.

[0159] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2939,1758,1620,1253,1086,842; 1H NMR (400MHz, CDCl3) δ: 7.14-7.16 (m, 1H), 6.91-6.97 (m, 1H), 6.12 (d, J = 16.0Hz, 1H), 4.81 (s, 3H), 4.563-4. 567(m,1H),3.77(d,J=10.0Hz,1H),3.71(s,2H),3.66(d,J=10.0Hz,1H),3.38-3.43(m,1H),3.25(s,3H),2.4 5-2.50(m,1H),2.34-2.37(m,1H),2.00-2.11(m,2H),1.85-1.90(m,1H),1.66-1.68(m,1H),1.63-1.65(m,1H ),1.47-1.51(m,1H),1.27(s,3H),1.19-1.24(m,1H),1.06(s,3H),0.84(s,9H),-0.01(s,3H),-0.02(s,3H).

[0160] Its chemical structure is shown in Formula VII-16:

[0161] Example 17:

[0162] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 1, except that in step six, the halogenated hydrocarbon is different, specifically iodoethane.

[0163] In this example, the target compound VII-17 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0164] Physical and chemical properties: yellow solid, melting point 86-88°C, yield 71%.

[0165] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2940,1759,1620,1248,1085,843; 1H NMR (400MHz, CDCl3) δ: 7.15-7.16 (m, 1H), 6.91-6.97 (m, 1H), 6.12 (d, J = 16.0Hz, 1H), 4.81 (s, 3H), 4.56 (s,1H),3.81-3.86(m,2H),3.77(d,J=10.0Hz,1H),3.69(s,2H),3.66(d,J=10.0Hz,1H),3.36-3.42(m, 1H),2.46-2.49(m,1H),2.35-2.37(m,1H),2.00-2.12(m,2H),1.85-1.89(m,1H),1.64-1.69(m,2H),1. 48-1.51(m,1H),1.27(s,3H),1.19-1.25(m,4H),1.07(s,3H),0.84(s,9H),-0.01(s,3H),-0.02(s,3H).

[0166] Its chemical structure is shown in Formula VII-17:

[0167] Example 18:

[0168] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 1, except that in step six, the halogenated hydrocarbon is different, specifically bromopropane.

[0169] In this example, the target compound VII-18 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0170] Physical and chemical properties: yellow solid, melting point 79-80°C, yield 73%.

[0171] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2942,1759,1620,1248,1085,842; 1H NMR(400MHz, CDCl3)δ:7.16-7.17(m,1H),6.91-6.97(m,1H),6.13(d,J=15.6Hz,1H),4.81-4.82(m,3H),4.561- 4.562(m,1H),3.72-3.76(m,3H),3.70(s,2H),3.66(d,J=10.0Hz,1H),3.35-3.40(m,1H),2.45-2.50(m,1H),2.3 5-2.37(m,1H),2.00-2.11(m,2H),1.85-1.89(m,1H),1.69-1.74(m,2H),1.62-1.67(m,2H),1.48-1.51(m,1H), 1.27(s,3H),1.19-1.25(m,1H),1.07(s,3H),0.93(t,J=7.2Hz,3H),0.83(s,9H),-0.023(s,3H),-0.028(s,3H).

[0172] Its chemical structure is shown in Formula VII-18:

[0173] Example 19:

[0174] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 1, except that in step six, the halogenated hydrocarbon is different, specifically bromobutane.

[0175] In this example, the target compound VII-19 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0176] Physical and chemical properties: yellow solid, melting point 69-70°C, yield 50%.

[0177] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2941,1759,1620,1254,1086,842; 1H NMR (400MHz, CDCl3) δ: 7.15 (s, 1H), 6.90-6.96 (m, 1H), 6.12 (d, J = 15.6Hz, 1H), 4.80 (s, 3H), 4.55 (s, 1 H),3.73-3.79(m,3H),3.68(s,2H),3.64(d,J=9.6Hz,1H),3.35-3.39(m,1H),2.45-2.49(m,1H),2.34- 2.37(m,1H),1.99-2.11(m,2H),1.85-1.87(m,1H),1.62-1.66(m,4H),1.47-1.50(m,1H),1.29-1.34( m,2H),1.26(s,3H),1.18-1.23(m,1H),1.06(s,3H),0.93(t,J=7.2Hz,3H),0.83(s,9H),-0.03(s,6H).

[0178] Its chemical structure is shown in Formula VII-19:

[0179] Example 20:

[0180] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 1, except that in step six, the halogenated hydrocarbon is different, specifically bromopentane.

[0181] In this example, the target compound VII-20 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0182] Physical and chemical properties: yellow solid, melting point 61-62°C, yield 52%.

[0183] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2940,1760,1621,1254,1085,841; 1H NMR(400MHz, CDCl3)δ:7.15-7.16(m,1H),6.91-6.98(m,1H),6.12(d,J=15.6Hz,1H),4.81-4.82(m,3H),4.560- 4.564(m,1H),3.73-3.80(m,3H),3.69(s,2H),3.65(d,J=9.6Hz,1H),3.35-3.41(m,1H),2.46-2.50(m,1H),2.3 5-2.37(m,1H),2.00-2.12(m,2H),1.84-1.89(m,1H),1.63-1.70(m,4H),1.48-1.51(m,1H),1.29-1.36(m,4H), 1.27(s,3H),1.19-1.23(m,1H),1.07(s,3H),0.89(t,J=6.8Hz,3H),0.83(s,9H),-0.024(s,3H),-0.029(s,3H).

[0184] Its chemical structure is shown in Formula VII-20:

[0185] Example 21:

[0186] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is substantially the same as that in Example 1, except that:

[0187] In step 6, the solid product obtained is the target compound VII-21; in this embodiment, R 1 is TIPS, and the halogenated hydrocarbon is benzyl chloride. Specifically:

[0188] Step 1: Dissolve 10 mmol of compound I and 6 mmol of aluminum oxide in anhydrous pyridine and reflux in an oil bath at 110°C for 15 hours. After the reaction, filter out the aluminum oxide, wash the filter cake with dichloromethane, and then wash the filtrate with 1M hydrochloric acid. Combine the organic phases, dry them over anhydrous Na2SO4, filter and concentrate them, and purify them by column chromatography to obtain intermediate II in a yield of 45%.

[0189] Step 2: Dissolve 1 mmol of intermediate II and 2 mmol of TIPSCl in anhydrous dichloromethane, add 5 mmol of triethylamine, and stir at room temperature for 2 hours; after the reaction, add dichloromethane to the above system, wash with saturated NaHCO3 solution, dry over anhydrous sodium sulfate, concentrate under reduced pressure, and purify by silica gel column chromatography to obtain intermediate III-b;

[0190] The physicochemical properties of intermediate III-b are as follows:

[0191] Physical and chemical properties: light yellow liquid, yield 54%.

[0192] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2950,2870,1760,1646,1348,1067; 1 H NMR(400MHz, CDCl3)δ:7.14-7.15(m,1H),6.88-6.94(m,1H),6.14(d,J=15.6Hz,1H),4.80-4.81(m,2H) ,4.76-4.77(m,1H),4.53-4.54(m,1H),4.36(d,J=10.0Hz,1H),3.52(d,J=9.6Hz,1H),3.30-3.34(m,1H ),2.42-2.46(m,1H),2.32(d,J=10.0Hz,1H),2.00-2.08(m,1H),1.78-1.85(m,2H),1.61-1.70(m,1H), 1.47-1.52(m,1H),1.32-1.36(m,1H),1.30(s,3H),1.20-1.26(m,2H),1.05-1.12(m,21H),0.81(s,3H).

[0193] Its chemical structure is shown in Formula III-b:

[0194] Step 3: Dissolve 1 mmol of intermediate III-b, 4 mmol of pyridinium chlorochromate, and 4 mmol of sodium acetate in dry dichloromethane and stir at room temperature for 19 hours; then add dichloromethane to the above system, wash with saturated NaHSO3 solution and saturated NaCl solution, dry over anhydrous Na2SO4, concentrate under reduced pressure, and purify by silica gel column chromatography to obtain intermediate IV-b.

[0195] In this example, the target compound IV-b obtained in step 3 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0196] Physical and chemical properties: light yellow liquid, yield 37%.

[0197] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2950,2870,1764,1708,1381,1093; 1H NMR (500MHz, CDCl3) δ: 7.17 (s, 1H), 6.94-7.00 (m, 1H), 6.15 (d, J = 15.5Hz, 1H), 4.81-4. 83(m,3H),4.60(s,1H),4.10(d,J=9.0Hz,1H),3.62(d,J=9.5Hz,1H),2.64-2.70(m,1H) ,2.50(d,J=13.0Hz,1H),2.39(d,J=9.0Hz,1H),2.30(d,J=14.0Hz,1H),2.03-2.08(m,1 H),1.75-1.82(m,2H),1.55-1.64(m,2H),1.44-1.49(m,1H),1.15(s,6H),1.02(s,21H).

[0198] Its chemical structure is shown in Formula IV-b:

[0199] Step 4: 1 mmol of intermediate IV-b and 1.2 mmol of thiosemicarbazide were dissolved in ethanol, 0.2 mL of acetic acid was added dropwise to the mixture, and the mixture was refluxed and stirred for 12 h, then concentrated under reduced pressure and purified by silica gel column chromatography to obtain intermediate Vb.

[0200] In this example, the target compound Vb obtained in step 4 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0201] Physical and chemical properties: white solid, melting point 195-197°C, yield 58%.

[0202] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2947,1755,1579,1206,1087,821; 1H NMR(400MHz, CDCl3)δ:8.62(s,1H),7.23-7.24(m,1H),7.17-7.18(m,1H),6.92-6.99(m,1H),6.19(s, 1H),6.13(d,J=16.0Hz,1H),4.83(s,3H),4.59-4.60(m,1H),3.99(d,J=9.6Hz,1H),3.58(d,J=9.6Hz, 1H),2.46-2.56(m,2H),2.33-2.35(m,1H),2.02-2.18(m,2H),1.83-1.87(m,1H),1.70-1.75(m,1H),1 .50-1.57(m,1H),1.44-1.48(m,1H),1.25(s,3H),1.17-1.21(m,1H),1.04(s,3H),0.96-1.03(m,21H).

[0203] Its chemical structure is shown in Formula Vb:

[0204] Step 5: Dissolve 1 mmol of intermediate Vb, 4 mmol of sodium acetate and 1 mmol of methyl bromoacetate in ethanol and reflux with stirring for 5 hours. After the reaction is completed, concentrate under reduced pressure, add aqueous solution, extract with dichloromethane, dry over anhydrous sodium sulfate, concentrate under reduced pressure, and purify by silica gel column chromatography to obtain intermediate VI-b.

[0205] In this example, the target compound VI-b obtained in step 5 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0206] Physical and chemical properties: yellow solid, melting point 119-121°C, yield 46%.

[0207] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2940,1756,1632,1239,1083,885; 1H NMR(400MHz, CDCl3)δ:7.14-7.15(m,1H),6.90-6.96(m,1H),6.10(d,J=16.0Hz,1H),4.80-4.8 1(m,3H),4.56-4.57(m,1H),3.99(d,J=9.6Hz,1H),3.72(s,2H),3.68(d,J=9.6Hz,1H),3.23-3. 28(m,1H),2.45-2.50(m,1H),2.33-2.35(m,1H),2.00-2.14(m,2H),1.87-1.91(m,1H),1.54-1. 69(m,2H),1.46-1.49(m,1H),1.30(s,3H),1.18-1.23(m,1H),1.05(s,3H),0.98-1.04(m,21H).

[0208] Its chemical structure is shown in Formula VI-b:

[0209] Step 6: Dissolve 1 mmol of intermediate VI-b, 1.1 mmol of halogenated hydrocarbon, 1 mmol of potassium carbonate and a catalytic amount of potassium iodide in acetone and stir the reaction at room temperature; after completion of both reactions, concentrate under reduced pressure, add saturated NaCl solution, extract with ethyl acetate, dry over anhydrous sodium sulfate, concentrate under reduced pressure, and purify by preparative thin-layer chromatography to obtain the target compound VII.

[0210] In this example, the target compound VII-21 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0211] Physical and chemical properties: yellow solid, melting point 174-175°C, yield 57%.

[0212] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2933,1758,1626,1181,1086,884; 1H NMR(400MHz, CDCl3)δ:7.41-7.43(m,2H),7.27-7.29(m,2H),7.22-7.25(m,1H),7.15-7.17(m,1H),6.91-6.98(m, 1H),6.12(d,J=15.6Hz,1H),4.93(s,2H),4.80-4.82(m,3H),4.562-4.565(m,1H),3.97(d,J=9.6Hz,1H),3.71(s, 2H),3.68(d,J=9.6Hz,1H),3.38-3.43(m,1H),2.45-2.50(m,1H),2.34-2.36(m,1H),2.01-2.12(m,2H),1.86-1.9 1(m,1H),1.59-1.69(m,2H),1.46-1.50(m,1H),1.30(s,3H),1.17-1.24(m,1H),1.07(s,3H),0.96-1.02(m,21H).

[0213] Its chemical structure is shown in Formula VII-21:

[0214] Example 22:

[0215] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as Example 21, except that in step six, the halogenated hydrocarbon is different, specifically 4-chlorobenzyl chloride.

[0216] In this example, the target compound VII-22 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0217] Physical and chemical properties: yellow solid, melting point 83-85°C, yield 73%.

[0218] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2940,1758,1621,1186,1087,883; 1H NMR(400MHz, CDCl3)δ:7.37(d,J=8.0Hz,2H),7.24(d,J=8.4Hz,2H),7.18(s,1H),6.92-6.99(m,1H),6.13(d,J=1 6.0Hz,1H),4.85-4.93(m,2H),4.81-4.82(m,3H),4.56(s,1H),3.99(d,J=9.6Hz,1H),3.71(s,2H),3.67(d,J=9.6 Hz,1H),3.35-3.41(m,1H),2.46-2.49(m,1H),2.34-2.36(m,1H),2.02-2.13(m,2H),1.87-1.90(m,1H),1.65-1.6 9(m,1H),1.55-1.59(m,1H),1.46-1.49(m,1H),1.29(s,3H),1.16-1.23(m,1H),1.07(s,3H),0.98-1.04(m,21H).

[0219] Its chemical structure is shown in Formula VII-22:

[0220] Example 23:

[0221] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as Example 21, except that in step six, the halogenated hydrocarbon is different, specifically 3-chlorobenzyl chloride.

[0222] In this example, the target compound VII-23 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0223] Physical and chemical properties: yellow solid, melting point 79-81°C, yield 73%.

[0224] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2939,1758,1621,1196,1082,884; 1H NMR(400MHz, CDCl3)δ:7.43(s,1H),7.29-7.32(m,1H),7.18-7.24(m,2H),7.15-7.16(m,1H),6.92-6.98(m,1H) ,6.12(d,J=15.6Hz,1H),4.85-4.93(m,2H),4.81-4.82(m,3H),4.57(s,1H),4.00(d,J=9.6Hz,1H),3.73(s,2H) ,3.67(d,J=9.6Hz,1H),3.37-3.42(m,1H),2.45-2.49(m,1H),2.34-2.36(m,1H),2.00-2.14(m,2H),1.87-1.91 (m,1H),1.61-1.72(m,2H),1.46-1.50(m,1H),1.30(s,3H),1.19-1.25(m,1H),1.07(s,3H),0.96-1.02(m,21H).

[0225] Its chemical structure is shown in Formula VII-23:

[0226] Example 24:

[0227] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 21, except that in step six, the halogenated hydrocarbon is different, specifically 2-chlorobenzyl chloride.

[0228] In this example, the target compound VII-24 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0229] Physical and chemical properties: yellow solid, melting point 83-84°C, yield 69%.

[0230] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2939,1757,1622,1201,1081,883; 1H NMR(400MHz, CDCl3)δ:7.32-7.34(m,1H),7.10-7.19(m,4H),6.88-6.95(m,1H),6.10(d,J=15.6Hz,1H) ,5.03-5.13(m,2H),4.79-4.81(m,3H),4.54(s,1H),3.94(d,J=9.6Hz,1H),3.80(s,2H),3.64(d,J=9.6H z,1H),3.17-3.23(m,1H),2.44-2.49(m,1H),2.30-2.33(m,1H),1.99-2.07(m,1H),1.84-1.96(m,2H), 1.52-1.60(m,2H),1.43-1.47(m,1H),1.29(s,3H),1.09-1.15(m,1H),1.02(s,3H),0.93-1.01(m,21H).

[0231] Its chemical structure is shown in Formula VII-24:

[0232] Example 25:

[0233] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as Example 21, except that in step six, the halogenated hydrocarbon is different, specifically 4-bromobenzyl chloride.

[0234] In this example, the target compound VII-25 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0235] Physical and chemical properties: yellow solid, melting point 84-85°C, yield 58%.

[0236] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2939,1758,1622,1186,1079,883; 1H NMR(400MHz, CDCl3)δ:7.37-7.40(m,2H),7.29-7.31(m,2H),7.17-7.18(m,1H),6.93-6.99(m,1H),6.13(d, J=15.6Hz,1H),4.84-4.92(m,2H),4.80-4.82(m,3H),4.56(s,1H),3.99(d,J=9.6Hz,1H),3.72(s,2H),3.67( d,J=9.6Hz,1H),3.34-3.39(m,1H),2.45-2.50(m,1H),2.34-2.36(m,1H),2.00-2.13(m,2H),1.87-1.90(m, 1H),1.55-1.64(m,2H),1.46-1.49(m,1H),1.30(s,3H),1.17-1.24(m,1H),1.07(s,3H),0.96-1.02(m,21H).

[0237] Its chemical structure is shown in Formula VII-25:

[0238] Example 26:

[0239] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 21, except that in step six, the halogenated hydrocarbon is different, specifically 3-bromobenzyl chloride.

[0240] In this example, the target compound VII-26 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0241] Physical and chemical properties: yellow solid, melting point 169-171°C, yield 49%.

[0242] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2938,1757,1620,1193,1081,885; 1H NMR(400MHz, CDCl3)δ:7.60-7.61(m,1H),7.34-7.39(m,2H),7.13-7.17(m,2H),6.92-6.98(m,1H),6.12(d,J=16 .0Hz,1H),4.84-4.92(m,2H),4.81-4.82(m,3H),4.57(s,1H),4.00(d,J=9.6Hz,1H),3.73(s,2H),3.68(d,J=9.6H z,1H),3.37-3.42(m,1H),2.45-2.50(m,1H),2.34-2.36(m,1H),2.00-2.14(m,2H),1.86-1.91(m,1H),1.67-1.7 2(m,1H),1.61-1.65(m,1H),1.46-1.50(m,1H),1.30(s,3H),1.20-1.25(m,1H),1.07(s,3H),0.96-1.03(m,21H).

[0243] Its chemical structure is shown in Formula VII-26:

[0244] Example 27:

[0245] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as Example 21, except that in step six, the halogenated hydrocarbon is different, specifically 2-bromobenzyl bromide.

[0246] In this example, the target compound VII-27 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0247] Physical and chemical properties: yellow solid, melting point 83-84°C, yield 64%.

[0248] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2939,1756,1621,1201,1081,883; 1H NMR(400MHz, CDCl3)δ:7.51-7.54(m,1H),7.18-7.22(m,1H),7.14-7.15(m,1H),7.05-7.11(m,2H),6.88-6.94(m,1 H),6.10(d,J=16.0Hz,1H),5.00-5.11(m,2H),4.79-4.82(m,3H),4.544-4.548(m,1H),3.94(d,J=9.6Hz,1H),3.82 (s,2H),3.64(d,J=9.6Hz,1H),3.17-3.22(m,1H),2.43-2.48(m,1H),2.30-2.33(m,1H),1.99-2.07(m,1H),1.84-1 .95(m,2H),1.54-1.63(m,2H),1.43-1.47(m,1H),1.29(s,3H),1.09-1.16(m,1H),1.01(s,3H),0.96-1.00(m,21H).

[0249] Its chemical structure is shown in Formula VII-27:

[0250] Example 28:

[0251] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as Example 21, except that in step six, the halogenated hydrocarbon is different, specifically 4-methylbenzyl chloride.

[0252] In this example, the target compound VII-28 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0253] Physical and chemical properties: yellow solid, melting point 88-90°C, yield 56%.

[0254] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2939,1759,1622,1184,1082,883; 1H NMR (400MHz, CDCl3) δ: 7.33 (d, J = 8.0 Hz, 2H), 7.15-7.16 (m, 1H), 7.08 (d, J = 7.6 Hz, 2H), 6.92-6.98 (m, 1H), 6. 13(d,J=15.6Hz,1H),4.86-4.93(m,2H),4.80-4.81(m,3H),4.56(s,1H),3.97(d,J=9.6Hz,1H),3.66-3.69(m ,3H),3.40-3.45(m,1H),2.45-2.50(m,1H),2.34-2.37(m,1H),2.30(s,3H),2.01-2.13(m,2H),1.86-1.91(m ,1H),1.62-1.69(m,2H),1.46-1.50(m,1H),1.30(s,3H),1.18-1.23(m,1H),1.07(s,3H),0.96-1.01(m,21H).

[0255] Its chemical structure is shown in Formula VII-28:

[0256] Example 29:

[0257] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 21, except that in step six, the halogenated hydrocarbon is different, specifically 3-methylbenzyl chloride.

[0258] In this example, the target compound VII-28 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0259] Physical and chemical properties: yellow solid, melting point 79-81°C, yield 63%.

[0260] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2943,1758,1618,1184,1081,884; 1H NMR(400MHz, CDCl3)δ:7.21-7.24(m,2H),7.13-7.17(m,2H),7.04-7.06(m,1H),6.92-6.98(m,1H),6.12(d,J=16. 0Hz,1H),4.86-4.94(m,2H),4.80-4.82(m,3H),4.564-4.566(m,1H),3.98(d,J=9.6Hz,1H),3.71(s,2H),3.69(d, J=9.6Hz,1H),3.40-3.45(m,1H),2.45-2.50(m,1H),2.34-2.36(m,1H),2.28(s,3H),2.00-2.13(m,2H),1.87-1.9 1(m,1H),1.55-1.69(m,2H),1.46-1.50(m,1H),1.31(s,3H),1.18-1.23(m,1H),1.07(s,3H),0.96-1.04(m,21H).

[0261] Its chemical structure is shown in Formula VII-29:

[0262] Example 30:

[0263] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as Example 21, except that in step six, the halogenated hydrocarbon is different, specifically 2-methylbenzyl chloride.

[0264] In this example, the target compound VII-30 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0265] Physical and chemical properties: yellow solid, melting point 77-78°C, yield 71%.

[0266] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2941,1757,1622,1206,1081,883; 1H NMR (400MHz, CDCl3) δ: 7.06-7.19 (m, 5H), 6.89-6.95 (m, 1H), 6.10 (d, J = 15.6Hz, 1H), 4.96 (s, 2H), 4.7 9-4.81(m,3H),4.54-4.55(m,1H),3.95(d,J=9.6Hz,1H),3.76(s,2H),3.66(d,J=9.6Hz,1H),3.19-3. 24(m,1H),2.44-2.49(m,1H),2.40(s,3H),2.31-2.34(m,1H),1.93-2.07(m,2H),1.85-1.90(m,1H),1 .54-1.58(m,2H),1.44-1.47(m,1H),1.29(s,3H),1.10-1.18(m,1H),1.03(s,3H),0.95-1.02(m,21H).

[0267] Its chemical structure is shown in Formula VII-30:

[0268] Example 31:

[0269] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 21, except that in step six, the halogenated hydrocarbon is different, specifically 4-nitrobenzyl chloride.

[0270] In this example, the target compound VII-31 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0271] Physical and chemical properties: yellow solid, melting point 90-92°C, yield 68%.

[0272] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2940,1757,1620,1187,1084,882; 1H NMR(400MHz, CDCl3)δ:8.11-8.14(m,2H),7.55-7.58(m,2H),7.20-7.21(m,1H),6.91-6.98(m,1H),6.11(d,J=16.0Hz,1 H),4.95-5.07(m,2H),4.80-4.84(m,3H),4.564-4.569(m,1H),4.00(d,J=9.6Hz,1H),3.76(s,2H),3.65(d,J=9.6Hz,1H ),3.27-3.32(m,1H),2.45-2.50(m,1H),2.31-2.34(m,1H),2.06-2.11(m,1H),1.99-2.04(m,1H),1.85-1.89(m,1H),1. 64-1.67(m,1H),1.53-1.60(m,1H),1.44-1.47(m,1H),1.29(s,3H),1.10-1.18(m,1H),1.06(s,3H),0.95-1.00(m,21H).

[0273] Its chemical structure is shown in Formula VII-31:

[0274] Example 32:

[0275] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 21, except that in step six, the halogenated hydrocarbon is different, specifically 4-cyanobenzyl chloride.

[0276] In this example, the target compound VII-32 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0277] Physical and chemical properties: yellow solid, melting point 93-95°C, yield 67%.

[0278] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2945,1756,1587,1186,1081,884; 1H NMR(400MHz, CDCl3)δ:7.55-7.58(m,2H),7.49-7.51(m,2H),7.20-7.21(m,1H),6.91-6.98(m,1H),6.13(d,J=16.0 Hz,1H),4.91-5.02(m,2H),4.80-4.83(m,3H),4.564-4.566(m,1H),3.99(d,J=9.6Hz,1H),3.75(s,2H),3.65(d,J= 9.6Hz,1H),3.27-3.32(m,1H),2.45-2.50(m,1H),2.32-2.35(m,1H),2.00-2.10(m,2H),1.85-1.89(m,1H),1.63-1 .68(m,1H),1.53-1.61(m,1H),1.44-1.48(m,1H),1.29(s,3H),1.14-1.19(m,1H),1.06(s,3H),0.95-1.02(m,21H).

[0279] Its chemical structure is shown in Formula VII-32:

[0280] Example 33:

[0281] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as Example 21, except that in step six, the halogenated hydrocarbon is different, specifically 4-isopropylbenzyl chloride.

[0282] In this example, the target compound VII-33 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0283] Physical and chemical properties: yellow solid, melting point 89-90°C, yield 67%.

[0284] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2947,1759,1617,1187,1082,883; 1H NMR(400MHz, CDCl3)δ:7.34-7.37(m,2H),7.15-7.16(m,1H),7.11-7.13(m,2H),6.93-6.99(m,1H),6.13(d,J=16.0Hz ,1H),4.86-4.94(m,2H),4.80-4.82(m,3H),4.562-4.565(m,1H),3.97(d,J=9.6Hz,1H),3.66-3.69(m,3H),3.39-3.4 5(m,1H),2.80-2.91(m,1H),2.45-2.50(m,1H),2.34-2.37(m,1H),2.01-2.13(m,2H),1.87-1.91(m,1H),1.62-1.69( m,2H),1.47-1.50(m,1H),1.30(s,3H),1.23-1.26(m,1H),1.21(s,3H),1.19(s,3H),1.07(s,3H),0.96-1.03(m,21H).

[0285] Its chemical structure is shown in Formula VII-33:

[0286] Example 34:

[0287] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as Example 21, except that in step six, the halogenated hydrocarbon is different, specifically 4-tert-butylbenzyl chloride.

[0288] In this example, the target compound VII-34 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0289] Physical and chemical properties: yellow solid, melting point 100-102°C, yield 62%.

[0290] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2950,1760,1617,1189,1082,883; 1H NMR(400MHz, CDCl3)δ:7.35-7.38(m,2H),7.27-7.30(m,2H),7.14-7.15(m,1H),6.93-6.99(m,1H),6.12(d,J=15.6Hz, 1H),4.86-4.94(m,2H),4.80-4.82(m,3H),4.562-4.565(m,1H),3.97(d,J=9.6Hz,1H),3.66-3.70(m,3H),3.40-3.45(m ,1H),2.45-2.50(m,1H),2.34-2.37(m,1H),2.07-2.13(m,1H),2.01-2.06(m,1H),1.86-1.91(m,1H),1.64-1.69(m,1H) ),1.59-1.63(m,1H),1.47-1.50(m,1H),1.30(s,3H),1.27(s,9H),1.18-1.22(m,1H),1.07(s,3H),0.96-1.03(m,21H).

[0291] Its chemical structure is shown in Formula VII-34:

[0292] Example 35:

[0293] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as Example 21, except that in step six, the halogenated hydrocarbon is different, specifically 2-chloro-5-chloromethylpyridine.

[0294] In this example, the target compound VII-35 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0295] Physical and chemical properties: yellow solid, melting point 88-89°C, yield 67%.

[0296] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2938,1758,1623,1186,1097,882; 1H NMR(400MHz, CDCl3)δ:8.483-8.488(m,1H),7.73-7.76(m,1H),7.24-7.25(m,1H),7.20-7.21(m,1H),6.91-6.98(m, 1H),6.15(d,J=16.0Hz,1H),4.91(s,2H),4.81-4.83(m,3H),4.58(s,1H),3.98(d,J=9.6Hz,1H),3.73(s,2H),3.67(d ,J=9.6Hz,1H),3.33-3.38(m,1H),2.45-2.50(m,1H),2.34-2.36(m,1H),2.01-2.15(m,2H),1.86-1.90(m,1H),1.66- 1.71(m,1H),1.55-1.64(m,1H),1.46-1.49(m,1H),1.29(s,3H),1.17-1.24(m,1H),1.06(s,3H),0.96-1.03(m,21H).

[0297] Its chemical structure is shown in Formula VII-35:

[0298] Example 36:

[0299] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 21, except that in step six, the halogenated hydrocarbon is different, specifically iodomethane.

[0300] In this example, the target compound VII-36 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0301] Physical and chemical properties: yellow solid, melting point 85-87°C, yield 70%.

[0302] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2942,1759,1619,1180,1083,886; 1H NMR(400MHz, CDCl3)δ:7.14-7.15(m,1H),6.91-6.97(m,1H),6.12(d,J=16.0Hz,1H),4.811-4.8 17(m,3H),4.563-4.565(m,1H),3.97(d,J=10.0Hz,1H),3.70-3.72(m,3H),3.41-3.46(m,1H),3 .24(s,3H),2.45-2.50(m,1H),2.34-2.36(m,1H),2.01-2.12(m,2H),1.88-1.93(m,1H),1.61-1 .69(m,2H),1.47-1.51(m,1H),1.32(s,3H),1.20-1.25(m,1H),1.07(s,3H),0.98-1.04(m,21H).

[0303] Its chemical structure is shown in Formula VII-36:

[0304] Example 37:

[0305] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 21, except that in step six, the halogenated hydrocarbon is different, specifically iodoethane.

[0306] In this example, the target compound VII-37 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0307] Physical and chemical properties: yellow solid, melting point 80-81°C, yield 71%.

[0308] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2944,1759,1615,1179,1082,887; 1H NMR(400MHz, CDCl3)δ:7.15-7.16(m,1H),6.91-6.98(m,1H),6.12(d,J=16.0Hz,1H),4.813-4.818(m, 3H),4.560-4.565(m,1H),3.97(d,J=9.6Hz,1H),3.79-3.88(m,2H),3.69-3.72(m,3H),3.40-3.46(m, 1H),2.45-2.50(m,1H),2.34-2.37(m,1H),2.01-2.12(m,2H),1.88-1.92(m,1H),1.66-1.69(m,1H),1 .57-1.64(m,1H),1.48-1.52(m,1H),1.32(s,3H),1.21-1.24(m,4H),1.07(s,3H),0.98-1.05(m,21H).

[0309] Its chemical structure is shown in Formula VII-37:

[0310] Example 38:

[0311] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 21, except that in step six, the halogenated hydrocarbon is different, specifically bromopropane.

[0312] In this example, the target compound VII-38 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0313] Physical and chemical properties: yellow solid, melting point 70-72°C, yield 62%.

[0314] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2943,1760,1621,1180,1082,885; 1H NMR(400MHz, CDCl3)δ:7.15-7.16(m,1H),6.91-6.98(m,1H),6.13(d,J=15.6Hz,1H),4.814-4.81 9(m,3H),4.55-4.56(m,1H),3.97(d,J=9.6Hz,1H),3.69-3.78(m,5H),3.39-3.44(m,1H),2.45-2. 50(m,1H),2.35-2.37(m,1H),2.01-2.12(m,2H),1.88-1.92(m,1H),1.60-1.72(m,4H),1.48-1.5 2(m,1H),1.32(s,3H),1.20-1.25(m,1H),1.07(s,3H),0.98-1.05(m,21H),0.92(t,J=7.2Hz,3H).

[0315] Its chemical structure is shown in Formula VII-38:

[0316] Example 39:

[0317] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 21, except that in step six, the halogenated hydrocarbon is different, specifically bromobutane.

[0318] In this example, the target compound VII-39 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0319] Physical and chemical properties: yellow solid, melting point 71-73°C, yield 60%.

[0320] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2948,1758,1585,1206,1081,888; 1H NMR (400MHz, CDCl3) δ: 7.15 (s, 1H), 6.91-6.98 (m, 1H), 6.12 (d, J = 16.0Hz, 1H), 4.81 (s, 3H), 4.56 ( s,1H),3.97(d,J=9.6Hz,1H),3.74-3.83(m,2H),3.69-3.70(m,3H),3.39-3.45(m,1H),2.46-2.50( m,1H),2.35-2.37(m,1H),2.01-2.12(m,2H),1.89-1.91(m,1H),1.62-1.68(m,4H),1.48-1.51(m, 1H),1.29-1.35(m,5H),1.20-1.25(m,1H),1.07(s,3H),1.00-1.01(m,21H),0.93(t,J=7.2Hz,3H).

[0321] Its chemical structure is shown in Formula VII-39:

[0322] Example 40:

[0323] This example provides a method for preparing an andrographolide derivative containing a thiazolidinone heterocycle. The method is basically the same as that in Example 21, except that in step six, the halogenated hydrocarbon is different, specifically bromopentane.

[0324] In this example, the target compound VII-40 obtained in step 6 was subjected to physicochemical properties and characterization analysis, and the results are as follows:

[0325] Physical and chemical properties: yellow solid, melting point 60-62°C, yield 62%.

[0326] The infrared spectrum and nuclear magnetic resonance spectrum characteristics of the compound are: IR cm -1 (KBr):2942,1760,1623,1194,1082,885; 1H NMR (400MHz, CDCl3) δ: 7.14-7.16 (m, 1H), 6.92-6.98 (m, 1H), 6.12 (d, J = 16.0Hz, 1H), 4.81 (s, 3H),4.56(s,1H),3.97(d,J=9.6Hz,1H),3.69-3.82(m,5H),3.39-3.45(m,1H),2.46-2.50(m,1 H),2.34-2.37(m,1H),2.01-2.12(m,2H),1.87-1.92(m,1H),1.64-1.69(m,4H),1.48-1.51(m ,1H),1.32(s,3H),1.19-1.30(m,5H),1.07(s,3H),0.98-1.05(m,21H),0.89(t,J=6.8Hz,3H).

[0327] Its chemical structure is shown in Formula VII-40:

[0328] Example 41:

[0329] This example illustrates the use of andrographolide derivatives containing thiazolidinone heterocycles as insecticides. Specifically, the diamondback moth (Plutella xylostella) was used as the test insect (subcultured at the Plant Protection Laboratory of Northwest Agriculture and Forestry University). The andrographolide derivatives containing thiazolidinone heterocycles prepared in Examples 1 to 40, andrographolide, Intermediate II, Intermediate III-a, Intermediate III-b, Intermediate IV-a, Intermediate IV-b, Intermediate Va, Intermediate Vb, Intermediate VI-a, and Intermediate VI-b were used as experimental groups, respectively. High-efficiency cypermethrin technical was used as a positive control group.

[0330] This application uses the leaf disc method, and the specific process is as follows:

[0331] Uniform and robust third-instar larvae of the diamondback moth were placed in culture dishes, with 15 test larvae in each dish, and starved for 4 hours. An acetone solution was used as a blank control, and a highly effective cypermethrin was used as a positive control. The starved test larvae were randomly divided into a control group and a treatment group. Fresh cabbage leaves were made into 0.5 cm × 0.5 cm leaf discs, immersed in the prepared solution for 3 seconds, and the treated leaves were placed in culture dishes. Three replicates were set up for each treatment group, and 15 test larvae were treated in each replicate. The larvae were covered with gauze to retain moisture and raised in an artificial climate chamber at a temperature of 25±2°C, a humidity of 65-80%, and a light / dark cycle of 16 h / 8 h. The number of test larvae that died was checked 24 h and 48 h after treatment, and the mortality rate (%) and the adjusted mortality rate (%) were calculated.

[0332] The mortality rate (%) and the adjusted mortality rate (%) of the test insects at 24 hours and 48 hours were calculated according to the following formula: The final experimental results are shown in Table 1.

[0333] Table 1 Insecticidal activity of andrographolide derivatives containing thiazolidinone heterocycles, andrographolide, intermediate II, intermediate II III-a, intermediate III-b, intermediate IV-a, intermediate IV-b, intermediate Va, intermediate Vb, intermediate VI-a and intermediate VI-b

[0334]

[0335]

[0336] As can be seen from Table 1, the 48-hour insecticidal activity of some of the above-mentioned andrographolide derivatives containing thiazolidinone heterocycles is significantly improved compared with andrographolide; the 48-hour corrected mortality rate of compound VII-26 reaches 72.7%, which is close to the insecticidal effect of highly effective chlorpyrifos (48-hour corrected mortality rate: 90.7%), and is expected to be used to prepare highly effective, environmentally friendly, and low-toxic botanical insecticides.

Claims

1. An andrographolide derivative containing a thiazolidinone heterocycle, characterized in that: Its chemical structure is shown in Formula VII: Formula VII; Where: R 1 When TBS is used, R 2 is selected from benzyl, p-chlorobenzyl, m-chlorobenzyl, o-chlorobenzyl, m-bromobenzyl, o-bromobenzyl, p-methylbenzyl, m-methylbenzyl, o-methylbenzyl, p-nitrobenzyl, p-cyanobenzyl, p-tert-butylbenzyl, methyl, ethyl, n-propyl, n-butyl or n-pentyl; R 1 When TIPS is used, R 2 is selected from benzyl, p-chlorobenzyl, m-chlorobenzyl, o-chlorobenzyl, p-bromobenzyl, m-bromobenzyl, o-bromobenzyl, p-methylbenzyl, m-methylbenzyl, o-methylbenzyl, p-cyanobenzyl, p-isopropylbenzyl, p-tert-butylbenzyl, ethyl, n-propyl, n-butyl or n-pentyl.

2. The method for preparing the andrographolide derivative containing a thiazolidinone heterocycle according to claim 1, characterized in that: The method includes: Step 1, in the presence of aluminum oxide, using andrographolide of formula I as a raw material to prepare intermediate II of formula II; Step 2, reacting intermediate II with tert-butyldimethylsilyl chloride or reacting intermediate II with triisopropylsilyl chloride to prepare intermediate III of formula III; Step 3, in the presence of pyridinium chlorochromate, using intermediate III as a raw material to prepare intermediate IV of formula IV; Step 4, intermediate IV is reacted with thiosemicarbazide to prepare intermediate V shown in formula V; Step 5, intermediate V is reacted with methyl bromoacetate to prepare intermediate VI shown in formula VI; Step 6, reacting intermediate VI with a halogenated hydrocarbon to prepare an andrographolide derivative containing a thiazolidinone heterocycle; Formula I Formula II Formula III Formula IV Formula V Formula VI; The halogenated hydrocarbon is selected from benzyl chloride, 4-chlorobenzyl chloride, 3-chlorobenzyl chloride, 2-chlorobenzyl chloride, 4-bromobenzyl chloride, 3-bromobenzyl chloride, 2-bromobenzyl bromide, 4-methylbenzyl chloride, 3-methylbenzyl chloride, 2-methylbenzyl chloride, 4-nitrobenzyl chloride, 4-cyanobenzyl chloride, 4-isopropylbenzyl chloride, 4-tert-butylbenzyl chloride, methyl iodide, ethyl iodide, propyl bromide, butyl bromide or pentane bromide.

3. The method for preparing the andrographolide derivative containing a thiazolidinone heterocycle according to claim 2, wherein: The reaction in step 1 is carried out in a first organic solvent under heating and reflux conditions; after the reaction in step 1 is completed, intermediate II is obtained by cooling, filtering, concentrating and column chromatography separation; The reaction in step 2 is carried out in a second organic solvent at room temperature; after the reaction in step 2 is completed, intermediate III is obtained by extraction, concentration and column chromatography separation; The reaction in step 3 is carried out in a third organic solvent at room temperature; after the reaction in step 3 is completed, intermediate IV is obtained by extraction, concentration and column chromatography separation; The step 4 is carried out in a fourth organic solvent under reflux conditions; after the reaction in step 4 is completed, V is obtained by concentration and column chromatography purification; Step 5 is carried out in a fifth organic solvent under reflux reaction conditions; after the reaction in step 5 is completed, VI is obtained by extraction, concentration and column chromatography purification; The step 6 is carried out in the presence of a catalyst in a sixth organic solvent at room temperature; after the reaction in step 6 is completed, compound VII is obtained by extraction, concentration and thin layer chromatography purification.

4. Use of the andrographolide derivative containing a thiazolidinone heterocycle as claimed in claim 1 in preparing an insecticide for lepidopteran pests.

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