Curcumenol derivative containing triazole structure, synthesis method and application of curcumenol derivative in preparation of anti-inflammatory drugs

Abstract

The invention provides a curcumenol derivative containing a triazole structure, a synthesis method and application of the curcumenol derivative in preparation of anti-inflammatory drugs, and belongs to the technical field of medicinal chemistry. A plurality of curcumenol derivatives containing triazole structures are obtained by modifying 8-site hydroxyl and 10-site double bond structures of curcumenol. The synthesis method of the curcumenol derivative containing the triazole structure, disclosed by the invention, is simple and convenient, mild in reaction condition and easy to operate, raw materials are easy to obtain in the synthesis process, the production cost is relatively low, and the synthesis method is suitable for industrial production and application. An in-vitro cell experiment shows that the curcumenol derivative containing the triazole structure shows good anti-inflammatory biological activity. In-vivo research shows that the compound h1 has a treatment effect on acute lung injury, can improve LPS-induced acute lung injury and relieve lung inflammation under the dosage of 5mg / kg, and provides a thought for research and development of specific acute lung injury resisting drugs.

Description

Technical Field

[0001] The present invention belongs to the technical field of medicinal chemistry, and relates to curcumol derivatives containing a triazole structure, a synthesis method thereof, and an application thereof in the preparation of anti-inflammatory drugs. Background Art

[0002] Acute lung injury (ALI) is an inflammatory disease characterized by damage to alveolar epithelial cells and vascular endothelial cells, often accompanied by non-cardiogenic pulmonary edema and hypoxemia, and can develop into acute respiratory distress syndrome (ARDS) in severe cases, with a mortality rate as high as 40%. Currently, clinical treatment mainly relies on glucocorticoids and mechanical ventilation support. However, glucocorticoids lack specificity and are prone to cause side effects such as immunosuppression and metabolic disorders after long-term use. Existing anti-inflammatory drugs (such as dexamethasone) have limited regulatory effects on key inflammatory targets and also have problems of drug resistance and toxicity. Therefore, the development of new drugs with high efficiency, low toxicity, and targeting key inflammatory pathways is an urgent need for the treatment of ALI. Summary of the Invention

[0003] The purpose of the present invention is to provide curcumol derivatives containing a triazole structure, a synthesis method thereof, and an application thereof in the preparation of anti-inflammatory drugs. The curcumol derivatives containing a triazole structure in the present invention exhibit good anti-inflammatory activity against RAW264.7 cells. In particular, curcumol derivative h1 has a therapeutic effect on acute lung injury at an effective dose, and the mechanism of action and molecular targets of curcumol derivative h1 in the treatment of acute lung injury are revealed.

[0004] To achieve the above purpose, the present invention provides the following technical solutions: Curcumol derivatives containing a triazole structure, having the following formula (a-i):

[0005] In formula (a-i), R is selected from benzyl, p-benzoic acid group, ethanol group, o-benzoic acid group, o-benzyl alcohol group, methyl acetate group, p-anisyl group, ethyl acetate group, ethylene glycol-1-methyl ether-2-ethyl ether group, ethylene glycol monoethyl ether group, propanol group, acetic acid group, propionic acid group.

[0006] Preferably, the curcumol derivatives containing a triazole structure are selected from any one of the compounds represented by formula a1-a10, b1-b6, c1-c3, d1, e1-e5, f1-f7, g1-g9, h1, i1:

[0007] The present invention also provides a method for synthesizing the above curcumol derivatives containing a triazole structure. When the curcumol derivatives are compounds a1-a10, b1-b6, the synthetic route is as follows:

[0008] The synthesis method includes the following steps: Curcumol is mixed with NaH in dimethylformamide and stirred at room temperature for 0.5 h, then 2 equivalents of haloalkyne are added and stirred at room temperature for 3 h. After the reaction is completed, the reaction is quenched with water, extracted with ethyl acetate, the upper layer is recovered, separated and purified to obtain yellow oily intermediate products a and b; in the reaction flask, intermediate products a and b, azide compound, copper sulfate pentahydrate, and sodium ascorbate are added in sequence, dissolved in dichloromethane solvent, and stirred at room temperature to make the reaction occur. After the reaction is completed, the reaction is quenched with water, extracted with dichloromethane, the lower layer is recovered, separated and purified to obtain products a1-a10, b1-b6.

[0009] Furthermore, when the curcumol derivative is compound c1-c3, the synthetic route is as follows:

[0010] The synthesis method includes the following steps: Curcumol derivative G1 is mixed with NaHCO 3 in dimethylformamide and stirred at room temperature for 0.5 h, then 1 equivalent of propargyl bromide is added and stirred at room temperature for 3 h. After the reaction is completed, the reaction is quenched with water, extracted with ethyl acetate, the upper layer is recovered, separated and purified to obtain yellow oily intermediate product c; in the reaction flask, intermediate product c, azide compound, copper sulfate pentahydrate, and sodium ascorbate are added in sequence, dissolved in dichloromethane solvent, and stirred at room temperature to make the reaction occur. After the reaction is completed, the reaction is quenched with water, extracted with dichloromethane, the lower layer is recovered, separated and purified to obtain products c1-c3.

[0011] Furthermore, when the curcumol derivative is compound d1, the synthetic route is as follows:

[0012] The synthesis method includes the following steps: Curcumol derivative G1 was mixed with NaH in dimethylformamide and stirred at room temperature for 0.5 h. Then propargyl bromide was added and the mixture was stirred at room temperature for 3 h. After the reaction was completed, the reaction was quenched with water, extracted with ethyl acetate, the upper layer was recovered, separated and purified to obtain a yellow oily intermediate d; in the reaction flask, intermediate d, 2-azidobenzyl alcohol, copper sulfate pentahydrate, and sodium ascorbate were added successively, dissolved in dichloromethane solvent, and stirred at room temperature to make them react. After the reaction was completed, the reaction was quenched with water, extracted with dichloromethane, the lower layer was recovered, separated and purified to obtain product d1.

[0013] Further, when the curcumol derivative is compound e1-e5, f1-f7, g1-g9, i1, the synthesis route is as follows:

[0014] The synthesis method includes the following steps: Alkynoic acid and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide were dissolved in CH 2 Cl 2 and stirred at room temperature for 0.5 h. Then curcumol derivative G1 and 4-dimethylaminopyridine were added to the reaction system and stirred at room temperature for 3 h. After the reaction was completed, the reaction was quenched with water, extracted with CH 2 Cl 2 The lower layer was recovered, separated and purified to obtain yellow oily intermediates e, f, g, i; in the reaction flask, the intermediate, azide compound, copper sulfate pentahydrate, and sodium ascorbate were added successively, dissolved in dichloromethane solvent, and stirred at room temperature to make them react. After the reaction was completed, the reaction was quenched with water, extracted with dichloromethane, the lower layer was recovered, separated and purified to obtain products e1-e5, f1-f7, g1-g9, i1.

[0015] Further, when the curcumol derivative is compound h1, the synthesis route is as follows:

[0016] The synthesis method includes the following steps: The intermediate g was dissolved in tetrahydrofuran, the air in the reaction device was evacuated, the reaction device was filled with nitrogen, ethylmagnesium bromide was added, and the mixture was refluxed at 55 °C for 30 min. Then succinic anhydride was added and the mixture was refluxed at 75 °C for 4 h. Water was added to stop the reaction, the pH was adjusted to 4 with hydrochloric acid, and after extraction with ethyl acetate, the upper layer was purified by silica gel column chromatography to obtain a yellow oily substance h; in the reaction flask, intermediate h, benzyl azide, copper sulfate pentahydrate, and sodium ascorbate were added successively, dissolved in dichloromethane solvent, and stirred at room temperature to make them react. After the reaction was completed, the reaction was quenched with water, extracted with dichloromethane, the lower layer was recovered, separated and purified to obtain product h1.

[0017] The present invention also provides the application of the above curcumol derivatives containing a triazole structure in the preparation of anti-inflammatory drugs.

[0018] Preferably, the anti-inflammatory drug can inhibit the inflammatory response of M1 macrophages.

[0019] Preferably, the application includes the application of curcumol derivative h1 in the preparation of a drug for improving acute lung injury. The structural formula of curcumol derivative h1 is as follows: .

[0020] More preferably, curcumol derivative h1 can significantly inhibit the expression of inflammatory factors IFN-γ and IL-17A; curcumol derivative h1 exerts an anti-acute lung injury effect by inhibiting the activation of NLRP3 inflammasome.

[0021] Compared with the prior art, the beneficial effects of the present invention are: By modifying the 8-hydroxy and 12-double bond structures of curcumol, the present invention obtains a plurality of curcumol derivatives containing a triazole structure. In vitro cell experiments show that the curcumol derivatives containing a triazole structure exhibit good anti-inflammatory activity against RAW264.7 cells, can be used for the treatment or prevention of inflammatory diseases, and have good application prospects.

[0022] The synthesis method of the curcumol derivatives containing a triazole structure disclosed by the present invention is simple, the reaction conditions are mild, it is easy to operate, the raw materials are easily available during the synthesis process, the production cost is low, and it is suitable for industrial production applications.

[0023] The curcumol derivative h1 obtained by the present invention can improve LPS-induced acute lung injury and reduce lung inflammation at a dose of 5 mg / kg. Through molecular docking, surface plasmon resonance (SPR) and Western blot experiments, it is determined that curcumol derivative h1 mainly exerts an anti-inflammatory effect by inhibiting the activation of NLRP3 inflammasome. NLRP3 is the direct action target of curcumol derivative h1. The present invention demonstrates the potential of curcumol derivative h1 as a lead compound and provides ideas for the development of specific drugs against ALI. Description of the Drawings

[0024] Figure 1 1H NMR spectrum of curcumol derivative h1 obtained in Example VIII; Figure 2 13C NMR spectrum of curcumol derivative h1 obtained in Example VIII; Figure 3 High-resolution mass spectrum of curcumol derivative h1 obtained in Example VIII; Figure 4In A, it is the molecular docking model of curcumol derivative h1 and NLRP3; in B, it is the 2D interaction map of curcumol derivative h1 and NLRP3; Figure 5 It is the experimental result of the Western blot (WB) experiment in Application Example 3; Figure 6 It is the experimental result of surface plasmon resonance (SPR) in Application Example 4. Specific Embodiments

[0025] The present invention will be described in detail below in conjunction with specific embodiments. The following specific examples are helpful for those skilled in the art to further understand the present invention, but do not limit the present invention in any form.

[0026] Example 1: Synthesis of curcumol derivatives a1 - a10 containing a triazole structure

[0027] Curcumol (0.2 mmol) and NaH (0.2 mmol) were mixed in 2 mL of dimethylformamide and stirred at room temperature for 0.5 h. Then 2 equivalents of propargyl bromide were added, and the mixture was stirred at room temperature for 3 h, and the reaction progress was monitored by thin layer chromatography (TCL). After the reaction was completed, the reaction was quenched with 10 mL of water, and extracted with ethyl acetate three times. The upper layer was recovered and separated and purified by silica gel column chromatography or preparative thin layer chromatography to obtain a yellow oily intermediate a with a yield of 70%. In the reaction flask, intermediate a (0.2 mmol), azide compound (0.2 mmol), copper sulfate pentahydrate (0.02 mmol), and sodium ascorbate (0.02 mmol) were successively added and dissolved in 2 mL of solvent (CH 2 CL 2 :H 2 O 3:1), and stirred at room temperature to react, and the reaction progress was monitored by TCL. After the reaction was completed, the reaction was quenched with 10 mL of water, and extracted with dichloromethane three times. The lower layer was recovered and separated and purified by silica gel column chromatography or preparative thin layer chromatography to obtain products a1 - a10 with a yield of 80 - 85%.

[0028] Compound a1: 1 H NMR (500 MHz, CDCl 3) δ 7.45 (s, 1H, H-18), 7.36 (s, 3H),7.26 (d, J = 2.8 Hz, 2H), 5.51 (d, J = 3.2 Hz, 2H), 4.85 (d, J = 9.8 Hz, 3H),4.79 (d, J = 12.4 Hz, 1H), 2.50 (q, J = 14.8 Hz, 2H), 2.16 (t, J = 10.3 Hz,1H), 2.07 (t, J = 12.3 Hz, 1H), 1.88 (tq, J = 17.2, 9.9 Hz, 3H), 1.73 – 1.60(m, 3H), 1.44 – 1.36 (m, 1H), 1.18 – 1.12 (m, 1H), 0.94 – 0.91 (m, 3H), 0.91– 0.86 (m, 3H), 0.84 (t, J = 4.3 Hz, 3H). 13 C NMR (125 MHz, CDCl 3 ) δ 145.12, 129.08, 128.70, 128.14, 122.37,112.78, 107.42, 87.57, 55.78, 54.72, 54.19, 48.98, 39.48, 38.22, 34.33,31.05, 28.70, 28.33, 23.05, 21.08, 12.31. HRMS (ESI): Calcd forC 25 H 34 N 3 O 2 (M + H): 408.2651; found: 408.2690. Compound a2: 1 H NMR (600 MHz, CDCl 3) δ 8.25 (d, J = 8.3 Hz, 2H), 8.05 (s,1H), 7.87 (d, J = 8.3 Hz, 2H,), 5.02 (d, J = 12.6 Hz, 1H), 4.93 – 4.85 (m,3H), 2.65 (d, J = 14.9 Hz, 1H), 2.56 (d, J = 14.8 Hz, 1H), 2.25 – 2.18 (m,1H), 2.14 (t, J = 12.4 Hz, 1H), 1.98-1.89 (m, 3H), 1.78-1.69 (m, 3H), 1.48(d, J = 11.0 Hz, 1H), 1.24 – 1.18 (m, 1H), 1.00 (dd, J = 11.9, 6.5 Hz, 6H),0.89 (d, J = 6.5 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 169.25, 148.00, 144.89, 140.78, 131.95,129.13, 120.34, 119.88, 113.04, 107.60, 87.85, 55.76, 54.75, 49.05, 39.51,38.23, 34.33, 31.10, 28.73, 28.34, 23.07, 21.15, 12.38. HRMS (ESI): Calcd for C 25 H 32 N 3 O 4 (M + H): 438.2393; found: 438.2394. Compound a3: 1 H NMR (600 MHz, CDCl 3) δ 7.65 (s, 1H), 4.92 – 4.85 (m, 3H), 4.79 (d, J = 12.2 Hz, 1H), 4.47 (s, 2H), 4.07 (s, 2H), 2.61 – 2.46 (m, 2H), 2.19 (t, J = 10.0 Hz, 1H), 2.09 (t, J = 12.2 Hz, 1H), 1.98 – 1.84 (m, 3H,), 1.77 – 1.63 (m, 3H), 1.51 – 1.42 (m, 1H), 1.19 (dd, J = 11.9, 6.1 Hz, 1H), 0.96 (dd, J = 21.3, 5.8 Hz, 6H), 0.86 (d, J = 5.7 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 145.08, 123.57, 112.86, 107.42, 87.63, 61.28, 55.66, 54.74, 52.56, 49.04, 39.51, 38.19, 34.34, 31.10, 28.72, 28.35, 23.07, 21.13, 12.35. HRMS (ESI): Calcd for C 20 H 32 N 3 O 3 (M + H): 362.2444; found: 362.2463. Compound a4: 1 H NMR (600 MHz, CDCl 3) δ 8.06 (d, J = 7.7 Hz, 1H), 7.85 (s,1H), 7.67 (t, J = 7.7 Hz, 1H), 7.59 (t, J = 7.6 Hz), 7.48 (d, J = 7.8 Hz),4.98 (d, J = 12.3 Hz, 1H), 4.93 – 4.83 (m, 3H), 2.60 (d, J = 14.8 Hz, 1H),2.53 (d, J = 14.7 Hz, 1H), 2.22 – 2.16 (m, 1H), 2.11 (t, J = 12.3 Hz, 1H),1.98 – 1.84 (m, 3H), 1.78 – 1.62 (m, 3H), 1.51 – 1.41 (m, 1H), 1.20 (dd, J =12.4, 6.4 Hz, 1H), 0.98 (dd, J = 17.7, 6.5 Hz, 6H), 0.87 (d, J = 6.5 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 168.61, 145.05, 132.79, 131.68, 129.82,126.71, 112.90, 107.56, 87.76, 55.59, 54.75, 49.04, 39.52, 38.18, 34.35,31.07, 28.74, 28.34, 23.07, 21.15, 12.36. HRMS (ESI): Calcd for C 25 H 32 N 3 O 4 (M + H): 438.2393; found: 438.1973. Compound a5: 1 H NMR (600 MHz, CDCl 3) δ 7.92 (s, 1H), 7.63 (dd, J = 7.3,1.8 Hz, 1H), 7.49 (dtd, J = 17.5, 7.5, 1.6 Hz, 2H), 7.38 (dd, J = 7.6, 1.6Hz, 1H), 5.01 (d, J = 12.4 Hz, 1H), 4.94 – 4.85 (m, 3H), 4.48 (s, 2H), 2.65 –2.51 (m, 2H), 2.21 (dd, J = 11.3, 8.8 Hz, 1H), 2.13 (t, J = 12.4 Hz, 1H),1.99 – 1.88 (m, 3H), 1.72 (m, J = 25.3, 12.6, 7.4, 2.9 Hz, 3H), 1.48 (dtd, J= 11.6, 8.4, 4.3 Hz, 1H), 1.22 (dd, J = 12.4, 6.5 Hz, 1H), 0.99 (dd, J =15.3, 6.5 Hz, 6H), 0.89 (d, J = 6.4 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 147.14, 144.98, 136.16, 135.74, 131.59,129.84, 129.05, 124.28, 123.76, 112.96, 107.52, 87.75, 61.92, 55.70, 54.75,49.19, 39.52, 38.21, 34.36, 31.12, 28.73, 28.37, 23.07, 21.18, 12.38. HRMS (ESI): Calcd for C 25 H 34 N 3 O 3 (M + H): 424.2600; found: 424.2618. Compound a6: 1 H NMR (600 MHz, CDCl 3) δ 7.67 (s, 1H), 5.16 (d, J = 2.0 Hz,2H), 4.95 – 4.79 (m, 4H), 3.81 (s, 3H), 2.61 – 2.47 (m, 2H), 2.19 (dd, J =11.4, 8.8 Hz, 1H), 2.10 (t, J = 12.4 Hz, 1H), 1.99 – 1.85 (m, 3H), 1.76 –1.64 (m, 3H), 1.47 (tdd, J = 11.4, 8.2, 3.5 Hz, 1H), 1.20 (dd, J = 12.5, 6.4Hz, 1H), 0.99 (d, J = 6.6 Hz, 3H), 0.94 (d, J = 6.4 Hz, 3H), 0.87 (d, J = 6.5Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 166.72, 147.23, 145.15, 123.67, 112.80,107.41, 87.63, 55.74, 54.75, 52.96, 50.72, 49.14, 39.53, 38.17, 34.36,31.09, 28.72, 28.36, 23.06, 21.13, 12.32. HRMS (ESI): Calcd for C 21 H 32 N 3 O 4 (M + H): 390.2393; found: 390.2396. Compound a7: 1 H NMR (600 MHz, CDCl 3) δ 7.41 (s, 1H), 7.23 (d, J = 8.5 Hz,2H), 6.91 – 6.87 (m, 2H), 5.44 (d, J = 2.4 Hz, 2H), 4.88 – 4.81 (m, 3H), 4.77(d, J = 12.4 Hz, 1H), 3.81 (d, J = 0.9 Hz, 3H), 2.50 (q, J = 14.8 Hz, 2H),2.16 (dd, J = 11.3, 8.9 Hz, 1H), 2.07 (t, J = 12.3 Hz, 1H), 1.95 – 1.81 (m,3H), 1.73 – 1.60 (m, 3H), 1.44 – 1.36 (m, 1H), 1.17 (dd, J = 12.4, 6.4 Hz,1H), 0.93 (d, J = 6.5 Hz, 3H), 0.89 (d, J = 6.4 Hz, 3H), 0.84 (d, J = 6.5 Hz,3H). 13 C NMR (150 MHz, CDCl 3 ) δ 159.91, 146.91, 145.13, 129.71, 126.69,122.14, 114.45, 112.78, 107.41, 87.5, 55.77, 55.34, 54.72, 53.71, 48.93,39.48, 38.24, 34.32, 31.05, 28.70, 28.33, 23.06, 21.08, 12.31. HRMS (ESI): Calcd for C 26 H 36 N 3 O 3 (M + H): 438.2757; found: 438.2876. Compound a8: 1 H NMR (600 MHz, CDCl 3) δ 7.67 (s, 1H), 5.14 (d, J = 2.3 Hz,2H), 4.93 (d, J = 12.4 Hz, 1H), 4.87 (d, J = 2.7 Hz, 2H), 4.82 (d, J = 12.4Hz, 1H), 4.27 (q, J = 7.2 Hz, 2H), 2.60 – 2.48 (m, 2H), 2.22 – 2.16 (m, 1H),2.12 – 2.04 (m, 1H), 1.97 – 1.84 (m, 3H), 1.77 – 1.63 (m, 3H), 1.48 (dt, J =11.8, 8.3 Hz, 1H), 1.30 (t, J = 7.1 Hz, 3H), 1.20 (dd, J = 12.4, 6.5 Hz, 1H),0.99 (d, J = 6.6 Hz, 3H), 0.93 (d, J = 6.4 Hz, 3H), 0.86 (d, J = 6.5 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 166.29, 145.17, 123.07, 112.81, 107.41,87.05, 62.36, 55.74, 54.75, 50.89, 49.07, 39.53, 38.19, 34.36, 31.08, 28.73,28.36, 23.08, 21.14, 14.07, 12.34. HRMS (ESI): Calcd for C 22 H 34 N 3 O 4 (M + H): 404.2549; found: 404.2549. Compound a9: 1 H NMR (600 MHz, CDCl 3) δ 7.70 (s, 1H), 4.95 – 4.84 (m, 3H),4.80 (d, J = 12.2 Hz, 1H), 4.54 (t, J = 5.2 Hz, 2H), 3.87 (t, J = 5.2 Hz,2H), 3.63 – 3.56 (m, 2H), 3.56 – 3.47 (m, 2H), 3.37 (s, 3H), 2.58 (dp, J =14.9, 2.1 Hz, 1H), 2.50 (d, J = 14.7 Hz, 1H), 2.19 (dd, J = 11.3, 8.8 Hz,1H), 2.10 (t, J = 12.3 Hz, 1H), 1.99 – 1.86 (m, 3H), 1.77 – 1.64 (m, 3H),1.48 (tdd, J = 11.3, 8.2, 3.5 Hz, 1H), 1.19 (dd, J = 12.4, 6.4 Hz, 1H), 0.99(d, J = 6.6 Hz, 3H), 0.93 (d, J = 6.4 Hz, 3H), 0.86 (d, J = 6.4 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 146.38, 145.20, 123.57, 112.77, 107.39,87.56, 71.77, 70.58, 69.60, 59.05, 55.73, 54.75, 50.20, 49.02, 40.05, 38.21,34.36, 31.09, 28.73, 28.35, 23.09, 21.13, 12.35. HRMS (ESI): Calcd for C 23 H 38 N 3 O 4 (M + H): 420.2862; found: 420.2866. Compound a10: 1 H NMR (600 MHz, CDCl 3) δ 7.69 (s, 1H), 4.94 – 4.85 (m, 3H), 4.80 (d, J = 12.2 Hz, 1H), 4.54 (t, J = 5.1 Hz, 2H), 3.89 (t, J = 5.1 Hz, 2H), 3.70 (dd, J = 5.3, 3.7 Hz, 2H), 3.56 (dd, J = 5.2, 3.8 Hz, 2H), 2.61 – 2.46 (m, 2H), 2.19 (dd, J = 11.3, 8.8 Hz, 1H), 2.14 – 2.01 (m, 1H), 2.00 – 1.84 (m, 3H), 1.71 (dtdd, J = 25.0, 12.8, 6.9, 2.5 Hz, 3H), 1.47 (tdd, J = 11.5, 8.3, 3.5 Hz, 1H), 1.20 (dd, J = 12.4, 6.4 Hz, 1H), 0.99 (d, J = 6.6 Hz, 3H), 0.93 (d, J = 6.4 Hz, 3H), 0.87 (d, J = 6.5 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 146.40, 145.06, 123.50, 112.86, 107.43, 87.62, 72.56, 69.39, 61.61, 55.67, 54.72, 50.22, 49.06, 39.50, 38.21, 34.33, 31.08, 28.70, 28.33, 23.07, 21.11, 12.35. HRMS (ESI): Calcd for C 22 H 36 N 3 O 4 (M + H): 406.2706; found: 406.2724. Example 2: Synthesis of Curcumol Derivatives b1 - b6 Containing Triazole Structure

[0029] Curcumol (0.2 mmol) was mixed with NaH (0.2 mmol) in 2 mL of dimethylformamide and stirred at room temperature for 0.5 h. Then, 2 equivalents of iodopent-1-yne were added and the mixture was stirred at room temperature for 3 h, and the reaction progress was monitored by TLC. After the reaction was completed, the reaction was quenched with 10 mL of water, and the mixture was extracted with ethyl acetate three times. The upper layer was recovered and separated and purified by silica gel column chromatography or preparative thin-layer chromatography to obtain a yellow oily intermediate b with a yield of 70%. In a reaction flask, intermediate b (0.2 mmol), azide compound (0.2 mmol), copper(II) sulfate pentahydrate (0.02 mmol), and sodium ascorbate (0.02 mmol) were successively added and dissolved in 2 mL of solvent (CH 2 CL 2 :H 2 O3:1), and the mixture was stirred at room temperature to react, and the reaction progress was monitored by TLC. After the reaction was completed, the reaction was quenched with 10 mL of water, and the mixture was extracted with dichloromethane three times. The lower layer was recovered and separated and purified by silica gel column chromatography or preparative thin-layer chromatography to obtain products b1 - b6 with a yield of 80 - 85%.

[0030] Compound b1: 1 H NMR (600 MHz, CDCl 3 ) δ 7.76 (s, 1H), 7.62 (dd, J = 7.5, 1.7 Hz, 1H), 7.56 – 7.40 (m, 2H), 7.36 (d, J = 7.6 Hz, 1H), 4.85 (d, J = 2.6 Hz, 2H), 4.46 (s, 2H), 3.76 (dt, J = 9.4, 6.3 Hz, 1H), 3.63 (dt, J = 9.3, 6.0 Hz, 1H), 2.94 (td, J = 7.4, 3.6 Hz, 2H), 2.58 – 2.40 (m, 2H), 2.16 (dd, J = 11.4, 8.7 Hz, 1H), 2.06 – 1.97 (m, 3H), 1.94 – 1.79 (m, 3H ), 1.75 – 1.61 (m, 3H), 1.38 (dtd, J = 11.6, 8.4, 4.3 Hz, 1H), 1.16 (dd, J = 12.4, 6.4 Hz, 1H), 0.96 (d, J = 6.4 Hz, 3H), 0.90 (d, J = 6.5 Hz, 3H), 0.85 (d, J = 6.4 Hz, 3H). 13 C NMR (150 MHz, CDCl3 ) δ 148.22, 145.41, 136.24, 135.71, 131.51, 129.70, 128.97, 124.26, 122.61, 112.58, 107.12, 87.20, 61.88, 59.74, 54.76, 48.88, 39.46, 38.11, 34.37, 31.03, 29.55, 28.74, 28.35, 23.12, 22.27, 21.12, 12.29. HRMS (ESI): Calcd for C 27 H 38 N 3 O 3 (M + H): 452.2913; found: 452.2981. Compound b2: 1 H NMR (600 MHz, CDCl 3 ) δ 7.46 (s, 1H), 4.85 (d, J = 2.5 Hz, 2H), 4.47 – 4.39 (m, 2H), 4.05 (t, J = 5.0 Hz, 2H), 3.71 (dt, J = 9.3, 6.3 Hz, 1H), 3.57 (dt, J = 9.3, 6.1 Hz, 1H), 2.78 (td, J = 7.4, 5.1 Hz, 2H), 2.56 – 2.40 (m, 2H,), 2.16 (dd, J = 11.3, 8.8 Hz, 1H), 2.03 (t, J = 12.3 Hz, 1H), 1.97 – 1.84 (m, 3H), 1.84 – 1.76 (m, 2H), 1.75 – 1.61 (m, 3H), 1.45 (tdd, J = 11.7, 8.5, 3.5 Hz, 1H), 1.15 (dd, J = 12.4, 6.4 Hz, 1H), 0.95 (t, J = 6.2 Hz, 6H), 0.85 (d, J = 6.4 Hz, 3H). 13 C NMR (150 MHz, CDCl 3) δ 147.7, 145.45, 122.24, 112.54, 107.10, 87.18, 61.13, 59.94, 54.77, 52.52, 48.87, 39.50, 38.08, 34.37, 31.11, 29.71, 28.73, 28.35, 23.11, 22.30, 21.10, 12.33. HRMS (ESI): Calcd for C 22 H 36 N 3 O 3 (M + H): 390.2757; found: 390.2797. Compound b3: 1 H NMR (600 MHz, CDCl 3 ) δ 7.49 (s, 1H), 5.12 (d, J = 2.5 Hz, 2H), 4.85 (d, J = 2.6 Hz, 2H), 4.26 (q, J = 7.1 Hz, 2H), 3.73 (dt, J = 9.2, 6.3 Hz, 1H), 3.59 (dt, J = 9.2, 6.0 Hz, 1H), 2.85 (td, J = 7.4, 2.4 Hz, 2H), 2.60 – 2.40 (m, 2H), 2.16 (dd, J = 11.4, 8.8 Hz, 1H), 2.03 (t, J = 12.3 Hz, 1H), 1.95 (q, J = 6.9 Hz, 3H), 1.92 – 1.76 (m, 3H), 1.74 – 1.60 (m, 3H), 1.45 (tdd, J = 11.9, 8.5, 3.6 Hz, 1H), 1.30 (t, J = 7.1 Hz, 3H), 1.15 (dd, J = 12.4, 6.4 Hz, 1H), 0.95 (dd, J = 6.6, 4.2 Hz, 6H), 0.85 (d, J = 6.4 Hz, 3H). 13 C NMR (150 MHz, CDCl 3) δ 166.41, 148.41, 145.53, 122.35, 112.49, 107.09, 87.16, 61.97, 59.89, 54.78, 50.81, 48.97, 39.50, 38.04, 34.38, 31.13, 29.68, 28.74, 28.34, 23.11, 22.37, 21.10, 14.06, 12.34. HRMS (ESI): Calcd for C 24 H 38 N 3 O 4 (M + H): 432.2862; found: 432.2398. Compound b4: 1 H NMR (600 MHz, CDCl 3 ) δ 7.49 (s, 1H), 5.14 (d, J = 2.2 Hz, 2H), 4.85 (d, J = 2.5 Hz, 2H), 3.80 (s, 3H), 3.73 (dt, J = 9.4, 6.3 Hz, 1H), 3.59 (dt, J = 9.4, 6.1 Hz, 1H), 2.85 (td, J = 7.3, 2.3 Hz, 2H), 2.58 – 2.40 (m, 2H), 2.16 (dd, J = 11.4, 8.7 Hz, 1H), 2.08 – 1.96 (m, 2H), 1.96 – 1.86 (m, 3H), 1.86 – 1.75 (m, 2H), 1.68 (dddd, J = 25.4, 16.9, 12.0, 7.6 Hz, 3H), 1.44 (tdd, J = 11.8, 8.5, 3.5 Hz, 1H), 1.16 (dd, J = 12.4, 6.4 Hz, 1H), 0.95 (dd, J = 6.5, 3.9 Hz, 6H), 0.85 (d, J = 6.4 Hz, 3H). 13 C NMR (150 MHz, CDCl 3) δ 166.87, 148.46, 145.51, 122.34, 112.48, 107.08, 87.15, 59.88, 54.77, 52.91, 50.63, 48.98, 39.50, 38.03, 34.38, 31.13, 29.65, 28.73, 28.34, 23.10, 22.36, 21.09, 12.33. HRMS (ESI): Calcd for C 23 H 36 N 3 O 4 (M + H): 418.2706; found: 418.2746. Compound b5: 1 H NMR (600 MHz, CDCl 3 ) δ 7.36 (d, J = 7.1 Hz, 3H), 7.26 (s, 3H), 5.54 – 5.43 (m, 2H), 4.83 (d, J = 2.6 Hz, 2H), 3.69 (dt, J = 9.4, 6.3 Hz, 1H), 3.55 (dt, J = 9.4, 6.2 Hz, 1H), 2.80 (dd, J = 8.6, 6.6 Hz, 2H), 2.53 – 2.35 (m, 2H), 2.14 (dd, J = 11.3, 8.8 Hz, 1H), 2.01 (t, J = 12.3 Hz, 1H), 1.90 (dq, J = 15.2, 7.9, 7.3 Hz, 3H), 1.86 – 1.72 (m, 2H), 1.72 – 1.59 (m, 3H), 1.42 (tdd, J = 11.6, 8.5, 3.6 Hz, 1H), 1.13 (dd, J = 12.4, 6.4 Hz, 1H), 0.92 (dd, J = 13.9, 6.5 Hz, 6H), 0.83 (d, J = 6.4 Hz, 3H). 13 C NMR (150 MHz, CDCl 3) δ 148.42, 145.53, 134.94, 129.06, 128.6, 127.95), 120.93, 112.49, 107.05, 87.12, 59.95, 54.77, 48.83, 39.50, 38.06, 34.38, 31.11, 29.71, 28.72, 28.34, 23.12, 22.42, 21.09, 12.35. HRMS (ESI): Calcd for C 27 H 36 N 3 O 2 (M - H): 434.2964; found: 434.2398. Compound b6: 1 H NMR (600 MHz, CDCl 3 ) δ 7.69 (s, 1H), 4.94 – 4.85 (m, 3H), 4.80 (d, J = 12.2 Hz, 1H), 4.54 (t, J = 5.1 Hz, 2H), 3.89 (t, J = 5.1 Hz, 2H), 3.70 (dd, J = 5.3, 3.7 Hz, 2H), 3.56 (dd, J = 5.2, 3.8 Hz, 2H), 2.61 – 2.46 (m, 2H), 2.19 (dd, J = 11.3, 8.8 Hz, 1H), 2.14 – 2.01 (m, 1H), 2.00 – 1.84 (m, 3H), 1.71 (dtdd, J = 25.0, 12.8, 6.9, 2.5 Hz, 3H), 1.47 (tdd, J = 11.5, 8.3, 3.5 Hz, 1H), 1.20 (dd, J = 12.4, 6.4 Hz, 1H), 0.99 (d, J = 6.6 Hz, 3H), 0.93 (d, J = 6.4 Hz, 3H), 0.87 (d, J = 6.5 Hz, 3H). 13 C NMR (150 MHz, CDCl 3) δ 148.43, 145.53, 134.94, 129.07, 128.63, 127.96, 120.94, 112.51, 107.05, 87.13, 59.95, 54.77, 54.05, 48.80, 39.50, 38.08, 34.38, 31.11, 29.71, 28.73, 28.34, 23.13, 22.43, 21.09, 12.36. HRMS (ESI): Calcd for C 28 H40N 3 O 4 (M + H): 466.6406; found: 466.6424. Example 3: Synthesis of curcumol derivatives c1 - c3 containing 1,2,3 - triazole structure

[0031] Curcumol derivative G1 (0.2 mmol) and NaHCO 3 (0.2 mmol) were mixed in 2 mL of dimethylformamide and stirred at room temperature for 0.5 h. Then 1 equivalent of propargyl bromide was added and stirred at room temperature for 3 h, and the reaction progress was monitored by TLC. After the reaction was completed, the reaction was quenched with 10 mL of water, extracted with ethyl acetate three times, the upper layer was recovered, and separated and purified by silica gel column chromatography or preparative thin - layer chromatography to obtain a yellow oily intermediate c with a yield of 60%. In the reaction flask, intermediate c (0.2 mmol), azide compound (0.2 mmol), copper sulfate pentahydrate (0.02 mmol), and sodium ascorbate (0.02 mmol) were added successively and dissolved in 2 mL of solvent (CH 2 CL 2 :H 2 O 3:1), stirred at room temperature to react, and the reaction progress was monitored by TLC. After the reaction was completed, the reaction was quenched with 10 mL of water, extracted with dichloromethane three times, the lower layer was recovered, and separated and purified by silica gel column chromatography or preparative thin - layer chromatography to obtain products c1 - c3 with a yield of 80 - 85%.

[0032] Compound c1: 1 H NMR (600 MHz, CDCl 3) δ 7.47 (s, 1H), 7.36 (d, J = 6.7 Hz,3H), 7.28 (d, J = 6.6 Hz, 2H), 5.85 (s, 1H), 5.49 (s, 2H), 4.81 (q, J = 12.8Hz, 2H), 4.12 – 4.03 (m, 2H), 2.14 (t, J = 11.8 Hz, 2H), 1.99 (t, J = 8.5Hz), 1.90 – 1.81 (m, 3H), 1.55 – 1.39 (m, 3H), 1.24 – 1.19 (m, 1H), 0.93 (d,J = 6.5 Hz, 3H), 0.89 (d, J = 6.5 Hz, 3H), 0.84 (d, J = 6.5 Hz, 3H). 13 C NMR (150 MHz, CDCl3) δ 146.90, 145.05, 134.64, 129.08, 128.69,128.14, 122.78), 122.57, 106.92, 86.88, 64.44, 58.23, 55.99, 54.14, 49.48,40.16, 36.11, 31.34, 30.78, 27.77, 22.59, 21.15, 11.76. HRMS (ESI): Calcd for C 25 H 34 N 3 O 3 (M + H): 424.2600; found: 424.2592. Compound c2: 1 H NMR (600 MHz, CDCl 3) δ 7.93 (s, 1H), 7.62 (dd, J = 7.4,1.7 Hz, 1H), 7.48 (dtd, J = 20.0, 7.5, 1.6 Hz, 2H), 7.36 (dd, J = 7.7, 1.5Hz, 1H), 5.91 (q, J = 1.6 Hz, 1H), 4.99 – 4.86 (m, 2H), 4.47 (s, 2H), 4.16 –4.04 (m, 2H), 2.19 (dd, J = 12.6, 10.9 Hz, 1H), 2.06 – 1.96 (m, 1H), 1.94 –1.81 (m, 4H), 1.58 – 1.45 (m, 3H), 1.31 – 1.21 (m, 1H), 0.98 (dd, J = 18.5,6.5 Hz, 6H), 0.87 (d, J = 6.5 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 146.94, 145.26, 136.07, 135.71, 131.51,129.89, 129.05, 124.34, 124.05, 122.62, 107.02, 87.05, 64.44, 61.79, 58.11,56.14, 49.54, 40.19, 36.16, 31.41, 30.81, 27.83, 22.59, 21.24, 11.82. HRMS (ESI): Calcd for C 25 H 34 N 3 O 4 (M + H): 440.2549; found: 440.2563. Compound c3: 1 H NMR (600 MHz, CDCl 3) δ 7.42 (s, 1H), 7.25 – 7.17 (m, 2H), 6.91 – 6.82 (m, 2H,), 5.84 (q, J = 1.5 Hz, 1H), 5.42 (s, 2H), 4.85 – 4.74 (m, 2H), 4.13 – 4.01 (m, 2H), 3.80 (s, 3H), 2.14 (dd, J = 12.7, 11.0 Hz, 1H), 1.98 (d, J = 9.0 Hz, 1H), 1.84 (tddd, J = 24.8, 15.2, 10.0, 2.5 Hz, 4H), 1.54 – 1.39 (m, 3H), 1.22 (dt, J = 12.6, 6.7 Hz, 1H), 0.90 (dd, J = 13.5, 6.5 Hz, 6H), 0.84 (d, J = 6.5 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 159.91, 146.76, 144.96, 129.75, 126.60, 122.93, 122.35, 114.46, 106.88, 86.84, 64.51, 58.21, 55.91 55.35, 53.72, 49.47, 40.16, 36.11, 31.34), 30.80, 27.76, 22.58, 21.14, 11.75. HRMS (ESI): Calcd for C 26 H 36 N 3 O 4 (M + H): 454.2706; found: 454.2717. Example 4: Synthesis of Zedoaryturmerol Derivative d1 Containing 1,2,4-Triazole Structure

[0033] Curcumol derivative G1 (0.2 mmol) was mixed with NaH (0.2 mmol) in 2 mL of dimethylformamide and stirred at room temperature for 0.5 h. Then 2 equivalents of propargyl bromide (0.3 mmol) were added and the mixture was stirred at room temperature for 3 h, and the reaction progress was monitored by TLC. After the reaction was completed, the reaction was quenched with 10 mL of water, and the mixture was extracted with ethyl acetate three times. The upper layer was recovered and separated and purified by silica gel column chromatography or preparative thin layer chromatography to obtain a yellow oily intermediate d with a yield of 70%. In a reaction flask, intermediate d (0.2 mmol), 2-azidobenzyl alcohol (0.2 mmol), copper(II) sulfate pentahydrate (0.02 mmol), and sodium ascorbate (0.02 mmol) were added successively and dissolved in 2 mL of a solvent (CH 2 CL 2 :H 2 O 3:1), and the reaction was carried out by stirring at room temperature, and the reaction progress was monitored by TLC. After the reaction was completed, the reaction was quenched with 10 mL of water, and the mixture was extracted with dichloromethane three times. The lower layer was recovered and separated and purified by silica gel column chromatography or preparative thin layer chromatography to obtain product d1 with a yield of 80 - 85%.

[0034] Compound d1: 1 H NMR (600 MHz, CDCl 3) δ 8.03 (s, 1H), 7.95 (s, 1H), 7.68 –7.58 (m, 2H), δ 7.53 – 7.47 (m, 2H), δ 7.48 – 7.44 (m, 2H), δ 7.42 (d, J =7.7 Hz, 1H), 7.37 (d, J = 7.7 Hz, 1H), 6.01 (s, 1H), 4.95 (q, J = 12.8 Hz,2H), 4.74 (q, J = 12.3 Hz, 2H), 4.49 (s, 2H), 4.46 (s, 2H, ), δ 4.17 – 4.03(m, 2H), 2.23 (t, J = 11.8 Hz, 1H), 2.08 (t, J = 7.4 Hz, 1H), 1.96 (dd, J =10.7, 7.2 Hz, 1H), 1.93 (d, J = 3.0 Hz, 1H), 1.92 – 1.89 (m, 1H), 1.86 (t, J= 6.8 Hz, 1H), 1.59 (s, 1H), 1.56 (t, J = 4.1 Hz, 1H), 1.53 (t, J = 5.5 Hz,1H), δ 1.31 (dd, J = 12.7, 7.4 Hz, 1H), 1.02 (d, J = 6.2 Hz, 3H), 0.99 (d, J= 6.5 Hz, 3H), 0.89 (d, J = 6.6 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 146.84, 145.43, 141.99, 136.06, 135.97,135.69, 135.53, 131.45, 131.41, 129.99, 129.87, 129.07, 129.03, 125.33,124.57, 124.36, 124.16, 124.03, 106.91, 87.04, 72.11, 63.62, 61.76, 61.64,58.18, 56.23, 49.74, 40.23, 36.25, 31.38, 30.97, 27.74, 22.67, 21.28, 11.83. HRMS (ESI): Calcd for C 35 H 43 N6 O 5 (M + H): 627.3295; found: 627.3309. Example 5: Synthesis of curcumol derivatives e1 - e5 containing 1,2,4 - triazole structure

[0035] Hexynoic acid (0.3 mmol) and 1-(3 - dimethylaminopropyl)-3 - ethylcarbodiimide (EDCI) (0.3 mmol) were dissolved in 2 mL of CH 2 Cl 2 and stirred at room temperature for 0.5 h. Then curcumol derivative G1 (0.2 mmol) and 4 - dimethylaminopyridine (DMAP) (0.2 mmol) were added to the reaction system and stirred at room temperature for 3 h. The reaction progress was monitored by TLC. After the reaction was completed, the reaction was quenched with 10 mL of water, and extracted with CH 2 Cl 2 three times. The lower layer was recovered and separated and purified by silica gel column chromatography or preparative thin - layer chromatography to obtain a yellow oily intermediate e with a yield of 60%. In a reaction flask, the intermediate, azide compound (0.2 mmol), copper(II) sulfate pentahydrate (0.02 mmol), and sodium ascorbate (0.02 mmol) were successively added and dissolved in 2 mL of solvent (CH 2 CL 2 :H 2 O 3:1), and stirred at room temperature to react. The reaction progress was monitored by TLC. After the reaction was completed, the reaction was quenched with 10 mL of water, extracted with dichloromethane three times, the lower layer was recovered, and separated and purified by silica gel column chromatography or preparative thin - layer chromatography to obtain products e1 - e5 with a yield of 80 - 85%.

[0036] Compound e1: 1 H NMR (600 MHz, CDCl 3) δ 7.36 (d, J = 6.9 Hz, 3H), 7.28 –7.21 (m, 3H), 5.83 (s, 1H), 5.49 (s, 2H), 4.54 – 4.45 (m, 2H), 2.74 (t, J =7.6 Hz, 2H), 2.40 (t, J = 7.3 Hz, 2H), 2.22 – 2.16 (m, 1H), 2.04 – 1.94 (m,3H), 1.85 (dq, J = 21.5, 7.7, 7.0 Hz, 3H), 1.66 – 1.50 (m, 3H), 1.45 (dt, J =10.9, 6.5 Hz, 1H), 1.26 – 1.19 (m, 1H), 0.99 (dd, J = 12.9, 6.5 Hz, 6H), 0.86(d, J = 6.5 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 172.84, 147.50, 139.02, 134.78, 129.10,128.70, 128.04, 126.40, 120.87, 103.22, 86.96, 65.27, 59.67, 54.10, 49.79,40.22, 36.39, 33.48, 31.17, 30.72, 27.51, 24.93, 24.62, 22.63, 21.41, 11.66. HRMS (ESI): Calcd for C 28 H 38 N 3 O 4 (M + H): 480.2862; found: 480.2398. Compound e2: 1 H NMR (600 MHz, CDCl 3) δ 7.24 – 7.18 (m, 3H), 6.89 (d, J =8.2 Hz, 2H), 5.83 (s, 1H), 5.42 (s, 2H), 4.55 – 4.45 (m, 2H), 3.81 (s, 3H),2.73 (t, J = 7.6 Hz, 2H), 2.40 (t, J = 7.3 Hz, 2H), 2.20 (dd, J = 12.8, 10.8Hz, 1H), 1.98 (q, J = 7.5 Hz, 3H), 1.91 – 1.79 (m, 3H), 1.67 – 1.52 (m, 3H),1.48 – 1.41 (m, 1H), 1.26 – 1.20 (m, 1H), 1.00 (dd, J = 12.8, 6.5 Hz, 6H),0.87 (d, J = 6.6 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 172.86, 159.89, 147.67, 139.01, 129.62,126.78, 126.42, 120.60, 114.47, 103.21, 86.96, 65.26, 59.65, 55.33, 53.63, 49.79, 40.22, 36.39, 33.49, 31.18, 30.71, 27.51, 24.95, 24.64, 22.63,21.41, 11.66. HRMS (ESI): Calcd for C 29 H 40 N 3 O 5 (M + H): 510.2968; found: 510.2975. Compound e3: 1 H NMR (600 MHz, CDCl 3) δ 7.75 (s, 1H), 7.62 (dd, J = 7.3,1.8 Hz, 1H), 7.49 (dtd, J = 18.0, 7.5, 1.6 Hz, 2H), 7.38 (dd, J = 7.6, 1.6Hz, 1H), 5.86 (d, J = 1.8 Hz, 1H), 4.54 (q, J = 13.5 Hz, 2H), 4.48 (s, 2H),2.89 (t, J = 7.5 Hz, 2H), 2.50 (t, J = 7.2 Hz, 2H), 2.21 (dd, J = 12.8, 10.8Hz, 1H), 2.12 (p, J = 7.4 Hz, 2H, H-1), 1.99 (t, J = 8.3 Hz, 1H), 1.94 – 1.80(m, 3H), 1.69 – 1.54 (m, 3H), 1.46 (ddt, J = 17.2, 13.3, 6.7 Hz, 1H), 1.26 –1.22 (m, 1H), 1.00 (dd, J = 10.8, 6.5 Hz, 6H), 0.87 (d, J = 6.5 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 172.82, 147.36, 138.99, 136.11, 135.57,131.58, 129.85, 129.08, 126.35, 124.35, 122.59, 103.25, 87.00, 65.36, 61.84,59.67, 49.86, 40.22, 36.39, 33.42, 31.18, 30.73, 27.54, 24.78, 24.49, 22.63,21.41, 11.65. HRMS (ESI): Calcd for C 28 H 38 N 3 O 5 (M + H): 496.2811; found: 496.2803. Compound e4: 1 H NMR (600 MHz, CDCl 3) δ 7.46 (s, 1H), 5.83 (t, J = 1.4 Hz,1H), 5.12 (s, 2H), 4.51 (qd, J = 13.5, 1.5 Hz, 2H), 4.25 (q, J = 7.2 Hz, 2H),2.80 (t, J = 7.5 Hz, 2H), 2.42 (t, J = 7.4 Hz, 2H), 2.19 (dd, J = 12.7, 10.9Hz, 1H), 2.05 – 2.01 (m, 2H), 2.01 – 1.94 (m, 1H), 1.82 (ddd, J = 19.7, 10.4,4.0 Hz, 3H), 1.67 – 1.52 (m, 3H), 1.44 (dq, J = 10.9, 6.5 Hz, 1H), 1.29 (t, J= 7.2 Hz, 3H), 1.24 – 1.19 (m, 1H), 0.99 (dd, J = 9.9, 6.5 Hz, 6H), 0.86 (d,J = 6.6 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 172.85, 166.42, 147.49, 139.01, 126.44,122.36, 103.22, 86.98, 65.28, 62.36, 59.62, 50.80, 49.78, 40.21, 36.38,33.37, 31.18, 30.71, 27.50, 24.83, 24.53, 22.63, 21.40, 14.06, 11.65. HRMS (ESI): Calcd for C 25 H 38 N 3 O 6 (M + H): 476.2761; found: 476.2771. Compound e5: 1 H NMR (600 MHz, CDCl 3) δ 7.48 (s, 1H), 5.82 (d, J = 1.7 Hz,1H), 4.52 – 4.40 (m, 4H), 4.09 – 3.94 (m, 2H), 2.78 – 2.71 (m, 2H), 2.47 –2.38 (m, 2H), 2.20 (dd, J = 12.8, 10.9 Hz, 1H), 2.05 – 1.93 (m, 3H), 1.93 –1.76 (m, 3H), 1.69 – 1.51 (m, 3H), 1.44 (ddt, J = 17.1, 13.0, 6.5 Hz, 1H),1.22 (dd, J = 12.9, 7.5 Hz, 1H), 0.99 (t, J = 6.1 Hz, 6H), 0.87 (d, J = 6.6Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 172.93, 138.83, 126.51, 122.58, 103.25,87.00, 65.13, 61.11, 59.40, 52.61, 49.83, 40.24, 36.36, 33.33, 31.23,30.74, 27.49, 24.80, 24.46, 22.63, 21.43, 11.65. HRMS (ESI): Calcd for C 23 H 35 N 3 O 5 (M + H): 434.2655; found: 434.2660. Example 6: Synthesis of Curcumol Derivatives f1 - f7 Containing Triazole Structure

[0037] Pentynoic acid (0.3 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (0.3 mmol) were dissolved in 2 mL of CH 2 Cl 2 The mixture was stirred at room temperature for 0.5 h. Then curcumol derivative G1 (0.2 mmol) and 4-dimethylaminopyridine (0.2 mmol) were added to the reaction system, and the mixture was continuously stirred at room temperature for 3 h. The reaction progress was monitored by TLC. After the reaction was completed, the reaction was quenched with 10 mL of water, and CH 2 Cl 2Extract three times, recover the lower layer, and separate and purify by silica gel column chromatography or preparative thin-layer chromatography to obtain the yellow oily intermediate f with a yield of 60%. In a reaction flask, successively add the intermediate, azide compound (0.2 mmol), copper sulfate pentahydrate (0.02 mmol), and sodium ascorbate (0.02 mmol), dissolve in 2 mL of solvent (CH 2 CL 2 :H 2 O 3:1), stir at room temperature to allow the reaction to proceed, and monitor the reaction progress by TLC. After the reaction is completed, quench the reaction with 10 mL of water, extract three times with dichloromethane, recover the lower layer, and separate and purify by silica gel column chromatography or preparative thin-layer chromatography to obtain products f1 - f7 with a yield of 80 - 85%.

[0038] Compound f1: 1 H NMR (600 MHz, CDCl 3 ) δ 172.30, 138.78, 136.01, 135.59, 131.41, 129.88, 129.01, 126.68, 124.44, 103.23, 87.06, 65.64, 59.55, 49.82, 40.19, 36.35, 33.41, 31.15, 30.72, 27.55, 22.62, 21.40, 20.90, 11.65. 13 C NMR (150 MHz, CDCl 3 ) δ 172.30, 138.78, 136.01, 135.59, 131.41, 129.88, 129.01, 126.68, 124.44, 103.23, 87.06, 65.64, 59.55, 49.82, 40.19, 36.35, 33.41, 31.15, 30.72, 27.55, 22.62, 21.40, 20.90, 11.65. HRMS (ESI): Calcd for C 27 H 36 N 3 O 5 (M + H): 482.2655; found: 482.2683. Compound f2: 1 H NMR (600 MHz, CDCl 3) δ 7.25 – 7.17 (m, 3H), 6.89 (d, J =8.2 Hz, 2H), 5.81 (s, 1H), 5.42 (s, 2H), 4.57 – 4.41 (m, 2H), 3.80 (s, 3H),3.01 (t, J = 7.3 Hz, 2H), 2.76 (t, J = 7.4 Hz, 2H), 2.20 (t, J = 11.8 Hz,1H), 1.95 (t, J = 9.2 Hz, 1H), 1.92 – 1.76 (m, 4H), 1.68 – 1.50 (m, 3H), 1.44(dq, J = 12.7, 6.5 Hz, 1H), 1.27 – 1.18 (m, 1H), 1.00 (dd, J = 9.0, 6.6 Hz,6H), 0.88 (d, J = 6.5 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 172.33, 159.89, 146.53, 138.90, 129.63,126.75, 126.58, 120.94, 114.45, 103.20, 86.96, 65.48, 59.70, 55.34, 53.64,49.72, 40.21, 36.37, 33.55, 31.17, 30.71, 27.47, 22.65, 21.42, 21.02, 11.67. HRMS (ESI): Calcd for C 28 H 38 N 3 O 5 (M + H): 496.2811; found: 496.2815. Compound f3: 1 H NMR (600 MHz, CDCl 3) δ 7.41 – 7.32 (m, 3H), 7.27 – 7.24(m, 2H,), 5.81 (d, J = 1.8 Hz, 1H), 5.49 (s, 2H), 4.59 – 4.41 (m, 2H), 3.03(t, J = 7.3 Hz, 2H), 2.77 (t, J = 7.4 Hz, 2H), 2.20 (dd, J = 12.8, 10.8 Hz,1H), 1.96 (t, J = 9.2 Hz, 1H), 1.93 – 1.78 (m, 4H), 1.68 – 1.48 (m, 3H), 1.44(dq, J = 10.7, 6.6 Hz, 1H), 1.22 (dd, J = 12.8, 7.4 Hz, 1H), 1.00 (dd, J =9.0, 6.5 Hz, 6H), 0.88 (d, J = 6.5 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 172.31, 146.62, 138.89, 134.75, 129.10,128.71, 128.04, 126.61, 121.22, 103.19, 86.96, 65.49, 59.70, 54.11, 49.72,40.21, 36.37, 33.53, 31.17, 30.70, 27.46, 22.64, 21.42, 21.00, 11.67. HRMS (ESI): Calcd for C 27 H 36 N 3 O 4 (M + H): 466.2706; found: 466.2718. Compound f4: 1 H NMR (600 MHz, CDCl 3) δ 7.50 (s, 1H), 5.80 (d, J = 1.5 Hz,1H), 5.12 (s, 2H), 4.61 – 4.42 (m, 2H), 4.25 (q, J = 7.2 Hz, 2H), 3.08 (t, J= 7.3 Hz, 2H), 2.80 (t, J = 7.2 Hz, 2H), 2.19 (dd, J = 12.8, 10.9 Hz, 1H),1.96 (t, J = 9.1 Hz, 1H), 1.94 – 1.78 (m, 4H), 1.65 – 1.48 (m, 3H), 1.45(tdd, J = 13.0, 8.4, 5.4 Hz, 1H), 1.29 (t, J = 7.1 Hz, 3H), 1.24 – 1.18 (m,1H), 0.99 (dd, J = 9.8, 6.5 Hz, 6H), 0.87 (d, J = 6.6 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 172.29, 166.41, 138.89, 126.62, 122.57,103.20, 86.97, 65.50, 62.39, 59.67, 50.82, 49.92, 40.20, 36.37, 33.51, 31.18,30.69, 27.48, 22.64, 21.40, 21.13, 14.06, 11.66. HRMS (ESI): Calcd for C 24 H 36 N 3 O 6 (M + H): 462.2604; found: 462.2653. Compound f5: 1 H NMR (600 MHz, CDCl 3) δ 7.51 (s, 1H), 5.81 (d, J = 1.5 Hz,1H), 5.15 (s, 2H), 4.59 – 4.44 (m, 2H), 3.81 (s, 3H), 3.08 (t, J = 7.3 Hz,2H), 2.81 (t, J = 7.2 Hz, 2H), 2.20 (dd, J = 12.8, 10.8 Hz, 1H), 1.97 (t, J =9.0 Hz, 1H), 1.92 – 1.77 (m, 3H), 1.68 – 1.49 (m, 3H), 1.45 (ddd, J = 13.0,10.8, 6.6 Hz, 1H), 1.26 – 1.20 (m, 1H), 1.00 (dd, J = 9.5, 6.6 Hz, 6H), 0.88(d, J = 6.6 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 172.29, 166.88, 138.82, 126.70, 122.74,103.2, 86.99, 65.51, 59.60, 53.02, 50.66, 49.78, 40.20, 36.36, 33.48, 31.18,30.70, 27.46, 22.64, 21.40, 20.98, 11.67. HRMS (ESI): Calcd forC 23 H 34 N 3 O 6 (M + H): 448.2448; found: 448.2460. Compound f6: 1 H NMR (600 MHz, CDCl 3) δ 7.44 (s, 1H), 5.85 (s, 1H), 4.56 –4.42 (m, 4H), 3.61-3.52 (m, 2H), 3.05 (dt, J = 8.6, 4.7 Hz, 2H), 2.92 – 2.68(m, 2H), 2.20 (dd, J = 12.8, 10.9 Hz, 1H), 2.09 (tt, J = 11.5, 5.8 Hz, 1H),1.97 – 1.76 (m, 4H), 1.68 (td, J = 10.7, 7.3 Hz, 1H), 1.60 – 1.45 (m, 3H),1.46 – 1.41 (m, 1H), 1.22 (dd, J = 12.8, 7.4 Hz, 1H), 1.00 (dd, J = 6.6, 4.1Hz, 6H), 0.88 (d, J = 6.5 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 172.31, 138.69, 126.42, 121.98, 103.29,87.07, 65.18, 59.24, 58.32, 49.81, 46.77, 40.20, 36.30, 33.47, 32.47,31.16, 30.74, 27.49, 22.64, 21.43, 20.96, 11.66. HRMS (ESI): Calcd for C 23 H 36 N 3 O 5 (M + H): 434.2655; found: 434.2675. Compound f7: 1 H NMR (600 MHz, CDCl 3) δ 7.51 (s, 1H), 5.80 (d, J = 1.5 Hz,1H), 4.51 (qd, J = 13.5, 1.5 Hz, 2H), 4.44 (t, J = 4.9 Hz, 2H), 4.10 – 3.96(m, 2H), 3.04 (t, J = 7.1 Hz, 2H), 2.78 (tq, J = 16.5, 8.4, 7.1 Hz, 2H), 2.20(dd, J = 12.8, 10.8 Hz, 1H), 1.98 – 1.76 (m, 4H), 1.66 (td, J = 10.8, 7.4 Hz,1H), 1.58 – 1.40 (m, 3H), 1.22 (dd, J = 12.8, 7.4 Hz, 1H), 0.99 (dd, J = 6.6,4.2 Hz, 6H), 0.88 (d, J = 6.5 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 172.34, 138.79, 126.58, 122.85, 103.26,87.13, 65.33, 60.93, 59.32, 52.50, 49.94, 40.18, 36.34, 33.50, 31.16, 30.73,27.54, 22.64, 21.41, 20.94, 11.67. HRMS (ESI): Calcd for C 22 H 34 N 3 O 5 (M + H): 420.2498; found: 420.2499. Example 7: Synthesis of Curcumol Derivatives g1-g9 Containing Triazole Structure

[0039] 3-ethynylbenzoic acid (0.3 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (0.3 mmol) were dissolved in 2 mL of CH 2 Cl 2 The mixture was stirred at room temperature for 0.5 h. Then curcumol derivative G1 (0.2 mmol) and 4-dimethylaminopyridine (0.2 mmol) were added to the reaction system, and the mixture was continuously stirred at room temperature for 3 h. The reaction progress was monitored by TLC. After the reaction was completed, the reaction was quenched with 10 mL of water, and CH2 Cl 2 Extract 3 times, recover the lower layer, and perform separation and purification by silica gel column chromatography or preparative thin-layer chromatography to obtain the yellow oily intermediate g with a yield of 60%. In the reaction flask, successively add the intermediate, azide compound (0.2 mmol), copper sulfate pentahydrate (0.02 mmol), and sodium ascorbate (0.02 mmol), and dissolve them in 2 mL of solvent (CH 2 CL 2 :H 2 O 3:1), stir at room temperature to allow the reaction, and monitor the reaction progress by TLC. After the reaction is completed, quench the reaction with 10 mL of water, extract 3 times with dichloromethane, recover the lower layer, and perform separation and purification by silica gel column chromatography or preparative thin-layer chromatography to obtain products g1 - g9 with a yield of 80 - 85%.

[0040] Compound g1: 1 H NMR (600 MHz, CDCl 3 ) δ 8.43 (d, J = 2.2 Hz, 1H), 8.15 (d,J = 7.8 Hz, 1H), 8.03 (s, 1H), 8.00 (d, J = 7.8 Hz, 1H), 7.53 (td, J = 7.8,2.2 Hz, 1H), 5.97 (s, 1H), 5.24 (s, 2H), 4.88 – 4.64 (m, 2H), 4.29 (qd, J =7.1, 2.1 Hz, 2H), 2.23 (dd, J = 13.3, 11.0 Hz, 1H), 2.09 (t, J = 8.9 Hz, 1H),1.95 (d, J = 10.9 Hz, 1H), 1.92 (d, J = 9.5 Hz, 1H), 1.86 (dt, J = 15.4, 7.9Hz, 1H), 1.70 (dd, J = 10.7, 7.5 Hz, 1H), 1.65 (dd, J = 11.1, 2.6 Hz, 1H),1.60 (d, J = 15.2 Hz, 1H), 1.55 – 1.49 (m, 1H), 1.32 (td, J = 7.2, 2.0 Hz,3H), 1.30 – 1.27 (m, 1H), 1.01 (t, J = 6.3 Hz, 6H), 0.89 (d, J = 6.4 Hz, 3H). 13 C NMR (150 MHz, CDCl 3) δ 166.24, 165.90, 147.24, 138.90, 130.88, 130.65, 130.30, 129.24, 129.10, 127.16, 126.94, 121.52, 103.28, 87.18, 66.20, 62.54, 59.58, 51.00, 49.97, 40.20, 36.40, 31.21, 30.74, 27.67, 22.66, 21.42, 14.08, 11.68. HRMS (ESI): Calcd for C 31 H 36 N 3 O 4 (M + H): 514.2704; found: 514.2706. Compound g2: 1 H NMR (600 MHz, CDCl 3 ) δ 8.33 (d, J = 2.1 Hz, 1H), 8.13 (d, J = 7.8 Hz, 1H), 7.97 (d, J = 7.7 Hz, 1H), 7.71 (s, 1H), 7.50 (t, J = 7.7 Hz, 1H), 7.29 (s, 2H), 6.92 (d, J = 8.2 Hz, 2H), 5.95 (s, 1H), 5.52 (s, 2H), 4.86–4.69 (m, 2H), 3.82 (s, 3H), 2.22 (t, J = 11.8 Hz), 2.06 (d, J = 9.6 Hz, 1H), 1.96 – 1.92 (m, 1H), 1.90 (d, J = 9.2 Hz, 1H), 1.86 – 1.80 (m, 1H, 1H), 1.68 (dd, J = 10.8, 7.4 Hz, 1H), 1.63 (d, J = 6.5 Hz, 1H), 1.60 (d, J = 14.7 Hz, 1H), 1.50 (dt, J = 11.5, 6.3 Hz, 1H), 1.28 (d, J = 7.7 Hz, 1H), 1.02 (d, J = 6.4 Hz, 3H, 3H), 0.99 (d, J = 6.4 Hz, 3H), 0.88 (d, J = 6.5 Hz, 3H). 1313C NMR (150 MHz, CDCl 3 ) δ 165.95, 160.05, 147.14, 139.00, 131.12,130.52, 130.22, 129.79, 129.09, 129.08, 126.95, 126.81, 126.39, 119.73,114.61, 103.26, 87.15, 66.17, 59.72, 55.36, 53.93, 49.97, 40.21, 36.42,31.21, 30.74, 27.68, 22.6, 21.42, 11.68. HRMS (ESI): Calcd for C 32 H 38 N 3 O 5 (M + H): 544.2811; found: 544.2822. Compound g3: 1 1H NMR (600 MHz, CDCl 3 ) δ 8.43 (s, 1H), 8.14 (s, 1H), 8.03(s, 1H),8.00 (d, 1H), 7.53 (t, 1H), 5.97 (s, 1H), 5.26 (s, 2H), 4.93 – 4.66(m, 2H), 4.12 (q, 1H), 3.83 (s, 3H), 2.23 (dd, 1H), 2.07 (m, 1H), 2.00 – 1.94(m, 1H), 1.92 (m, 1H), 1.89 – 1.81 (m, 1H), 1.72 – 1.67 (m, 1H), 1.67 – 1.63(m, 1H), 1.63 – 1.57 (m, 1H), 1.51 (m, 1H), 1.31 – 1.26 (m, 1H), 1.02 (d, J =5.4 Hz, 3H), 1.01 (d, J = 5.2 Hz, 3H), 0.89 (d, J = 6.5 Hz, 3H). 13 13C NMR (150 MHz, CDCl 3) δ 166.69, 165.90, 147.29, 138.89, 130.84, 130.65, 130.31, 129.26, 129.11, 127.14, 126.94, 121.53, 103.29, 87.19, 66.20, 59.58, 53.14, 50.85, 49.97, 40.20, 36.40, 31.21, 30.74, 27.67, 22.66, 21.42, 11.68. HRMS (ESI): Calcd for C 27 H 34 N 3 O 6 (M + H): 496.2448; found: 496.2462. Compound g4: 1 H NMR (600 MHz, CDCl 3 ) δ 8.49 (t, J = 1.8 Hz, 1H, H-18), 8.29 (s, 1H), 8.21 (dt, J = 7.7, 1.5 Hz, 1H), 8.04 (dt, J = 7.8, 1.4 Hz, 1H), 7.66 (dd, J = 7.4, 1.7 Hz, 1H), 7.60 – 7.45 (m, 4H), 5.98 (d, J = 1.6 Hz, 1H), 4.91 – 4.71 (m, 2H), 4.56 (s, 2H), 4.12 (q, J = 7.1 Hz, 2H), 2.23 (dd, J = 12.8, 10.8 Hz, 1H), 2.08 (t, J = 8.9 Hz, 1H), 2.05 (s, 1H), 2.00 – 1.81 (m, 3H), 1.73 – 1.58 (m, 3H), 1.57 – 1.45 (m, 1H), 1.31 – 1.26 (m, 1H), 1.01 (t, J = 6.2 Hz, 6H), 0.89 (d, J = 6.6 Hz, 3H). 13 C NMR (150 MHz, CDCl 3) δ 171.22, 165.85, 147.06, 138.90, 135.85, 135.52, 131.56, 130.78, 130.50, 130.33, 130.16, 129.53, 129.29, 129.19, 127.02, 126.96, 124.49, 121.55, 103.30, 87.17, 66.23, 61.74, 59.68, 50.01, 40.21, 36.42, 31.22, 30.76, 27.71, 22.66, 21.43, 21.06, 14.20, 11.68. HRMS (ESI): Calcd for C 32 H 38 N 3 O 5 (M + H): 544.281; found: FOUND: 544.2801. Compound g5: 1 H NMR (600 MHz, CDCl 3 ) δ 8.39 (s, 1H), 8.09 (d, J = 7.9 Hz, 1H), 7.97 (d, J = 7.7 Hz, 2H), 7.50 (t, J = 7.8 Hz, 1H), 5.99 (s, 1H), 4.88 – 4.67 (m, 2H), 4.59 (t, J = 6.7 Hz, 2H), 3.69 (t, J = 5.8 Hz, 2H), 2.27 – 2.15 (m, 3H), 2.06 (d, J = 7.3 Hz, 1H), 1.98 – 1.92 (m, 1H), 1.89 (dd, J = 14.9, 6.1 Hz, 1H), 1.86 – 1.80 (m, 1H), 1.70 (td, J = 10.8, 7.4 Hz, 1H), 1.63 (d, J = 11.5 Hz, 1H), 1.61 – 1.55 (m, 1H), 1.51 (dt, J = 10.8, 6.3 Hz, 1H1), 1.31 – 1.27 (m, 1H), 1.04 – 0.98 (m, 6H), 0.88 (d, J = 6.5 Hz, 3H). 13 C NMR (150 MHz, CDCl 3) δ 165.94, 146.65, 138.79, 131.04, 130.60, 130.19, 129.13, 126.98, 126.78, 120.86, 103.32, 87.16, 66.12, 59.44, 58.55, 50.01, 47.15, 40.20, 36.38, 32.57, 31.23, 30.76, 27.71, 22.66, 21.43, 11.67. HRMS (ESI): Calcd for C 27 H 36 N 3 O 5 (M + H): 482.2655; found: 482.2663. Compound g6: 1 H NMR (600 MHz, CDCl 3 ) δ 8.43 (d, J = 2.2 Hz, 1H), 8.15 (d, J = 7.8 Hz, 1H, H-22), 8.03 (s, 1H, H-20), 8.00 (d, J = 7.8 Hz, 1H, H-21), 7.53 (td, J = 7.8, 2.2 Hz, 1H4), 5.97 (s, 1H), 5.24 (s, 2H), 4.88 – 4.64 (m, 2H), 4.29 (qd, J = 7.1, 2.1 Hz, 2H), 2.23 (dd, J = 13.3, 11.0 Hz, 1H), 2.09 (t, J = 8.9 Hz, 1H), 1.95 (d, J = 10.9 Hz, 1H), 1.92 (d, J = 9.5 Hz, 1H), 1.86 (dt, J = 15.4, 7.9 Hz, 1H), 1.70 (dd, J = 10.7, 7.5 Hz, 1H), 1.65 (dd, J = 11.1, 2.6 Hz, 1H), 1.60 (d, J = 15.2 Hz, 1H), 1.55 – 1.49 (m, 1H), 1.32 (td, J = 7.2, 2.0 Hz, 3H), 1.30 – 1.27 (m, 1H), 1.01 (t, J = 6.3 Hz, 6H), 0.89 (d, J = 6.4 Hz, 3H). 1313C NMR (150 MHz, CDCl 3 ) δ 166.24, 165.90, 147.24, 138.90, 130.88,130.65, 130.30, 129.24, 129.10, 127.16, 126.94, 121.52, 103.28, 87.18, 66.20,62.54, 59.58, 51.00, 49.97, 40.20, 36.40, 31.21, 30.74, 27.67, 22.66, 21.42,14.08, 11.68. HRMS (ESI): Calcd forC 28 H 36 N 3 O 6 (M + H): 510.2604; found: 510.2617. Compound g7: 1 1H NMR (600 MHz, CDCl 3 ) δ 8.45 (d, J = 1.8 Hz, 1H), 8.17 (dt,J = 7.8, 1.5 Hz, 1H), 8.02 (q, J = 3.5, 2.5 Hz, 2H), 7.55 (t, J = 7.8 Hz,1H), 5.98 (d, J = 1.5 Hz, 1H), 5.25 (d, J = 11.3 Hz, 2H), 4.88 – 4.71 (m,2H), 4.36 – 4.22 (m, 1H), 2.24 (dd, J = 12.8, 10.8 Hz, 1H), 2.10 (t, J = 8.8Hz, 1H), 1.96 (ddd, J = 14.5, 6.1, 3.7 Hz, 1H), 1.94 – 1.89 (m, 1H), 1.89 –1.83 (m, 1H), 1.68 (d, J = 3.9 Hz, 1H), 1.66 – 1.63 (m, 1H), 1.63 – 1.59 (m,1H), 1.55 – 1.50 (m, 1H), 1.29 (d, J = 5.9 Hz, 1H), 1.03 – 0.99 (m, 6H), 0.90(d, J = 6.5 Hz, 3H). 13 13C NMR (150 MHz, CDCl 3) δ 166.22, 165.95, 147.32, 139.05, 130.84, 130.65, 130.35, 129.32, 129.16, 126.97, 126.89, 121.48, 103.30, 87.17, 66.21, 62.62, 59.72, 50.88, 49.97, 40.2, 36.42, 31.20, 30.77, 29.72, 27.68, 22.69, 21.44, 11.70. HRMS (ESI): Calcd for C 26 H 32 N 3 O 6 (M + H): 482.2291; found: 482.2291. Compound g8: 1 H NMR (600 MHz, CDCl 3 ) δ 8.38 (s, 1H, H-18), 8.15 – 8.06 (m, 1H), 8.02 (s, 1H), 7.97 (d, J = 7.7 Hz, 1H), 7.50 (t, J = 7.7 Hz, 1H), 5.97 (d, J = 1.7 Hz, 1H), δ 4.87 – 4.76 (m, 2H), 4.73 (q, J = 6.1, 4.9 Hz, 2H), 3.07 (d, J = 6.2 Hz, 2H), 2.24 (dd, J = 12.8, 10.8 Hz, 1H), 2.12 – 2.06 (m, 1H), 1.95 (d, J = 12.4 Hz, 1H), 1.92 – 1.88 (m, 1H), 1.85 (td, J = 8.8, 8.3, 6.3 Hz, 1H), 1.75 – 1.69 (m, 1H), 1.69 – 1.62 (m, 1H), 1.62 – 1.56 (m, 1H), 1.56 – 1.48 (m, 1H), 1.32 – 1.27 (m, 1H), 1.00 (t, J = 6.8 Hz, 6H), 0.88 (d, J = 6.5 Hz, 3H). 13 C NMR (150 MHz, CDCl 3) δ 165.92, 138.96, 130.86, 130.60, 130.28, 129.20, 129.16, 127.00, 126.89, 121.38, 103.63, 87.71, 66.07, 59.30, 50.15, 45.69, 40.18, 36.37, 31.16, 30.73, 29.69, 27.70, 22.59, 21.39, 11.64. HRMS (ESI): Calcd for C 27 H 34 N 3 O 6 (M + H): 496.2448; found: 496.2492. Compound g9: 1 H NMR (600 MHz, CDCl 3 ) δ 8.39 (d, J = 1.9 Hz, 1H), 8.15 (d, J = 7.7 Hz, 1H), 8.10 (s, 1H), 7.98 (d, J = 7.7 Hz, 1H), 7.51 (t, J = 7.7 Hz, 1H), 5.98 (d, J = 1.4 Hz, 1H), 4.88 – 4.71 (m, 2H), 4.62 (t, J = 4.9 Hz, 2H), 3.93 (t, J = 4.9 Hz, 2H), 3.77 (t, J = 4.4 Hz, 2H), 3.61 (t, J = 4.4 Hz, 2H), 2.23 (dd, J = 12.8, 10.8 Hz, 1H), 2.07 (t, J = 8.9 Hz, 1H), 2.00 – 1.94 (m, 1H), 1.94 – 1.89 (m, 1H), 1.89 – 1.81 (m, 1H), 1.73 – 1.67 (m, 1H), 1.67 – 1.62 (m, 1H), 1.62 – 1.56 (m, 1H), 1.55 – 1.47 (m, 1H), 1.32 – 1.27 (m, 1H), 1.02 (d, J = 6.5 Hz, 3H), 1.00 (d, J = 6.4 Hz, 3H), 0.89 (d, J = 6.6 Hz, 3H). 13 C NMR (150 MHz, CDCl3 ) δ 165.96, 138.96, 131.15, 130.60, 130.22, 129.10, 126.99, 126.83, 121.34, 103.30, 87.17, 72.52, 69.29, 66.13, 61.60, 59.61, 50.40, 50.1, 40.20, 36.41, 31.24, 30.73, 27.77, 22.64, 21.42, 11.67. HRMS (ESI): Calcd for C 28 H 38 N 3 O 6 (M + H): 512.2761; found: 512.2764. Example 8: Synthesis of Curcumol Derivative h1 Containing 1,2,3-Triazole Structure

[0041] Dissolve the intermediate g (0.4 mmol) in 2.5 mL of tetrahydrofuran, evacuate the air in the reaction apparatus, and fill the reaction apparatus with nitrogen. Add ethylmagnesium bromide (0.4 mmol), and reflux at 55 °C for 30 min. Then add succinic anhydride (1.2 mmol), and reflux at 75 °C for 4 h. Add water to stop the reaction, and adjust the pH to 4 with hydrochloric acid. After extraction with ethyl acetate, take the upper layer and purify it by silica gel column chromatography to obtain a yellow oil h with a yield of 82%. In the reaction flask, successively add intermediate h, benzyl azide (0.2 mmol), copper(II) sulfate pentahydrate (0.02 mmol), and sodium ascorbate (0.02 mmol), dissolve in 2 mL of solvent (CH 2 CL 2 :H 2 O3:1), stir at room temperature to make the reaction proceed, and monitor the reaction progress by TLC. After the reaction is completed, quench the reaction with 10 mL of water, extract 3 times with dichloromethane, recover the lower layer, and separate and purify it by silica gel column chromatography or preparative thin layer chromatography to obtain product h1 with a yield of 80 - 85%.

[0042] Compound h1: 1 H NMR (500 MHz, CDCl 3) δ 8.39 (t, J = 1.8 Hz, 1H), 8.00 (dt,J = 7.8, 1.5 Hz, 1H, H-18), 7.95 (dt, J = 7.9, 1.5 Hz, 1H, H-24), 7.75 (s,1H, H-20), 7.48 (t, J = 7.8 Hz, 1H), 7.43 – 7.37 (m, 3H), 7.32 (dd, J = 7.5,2.1 Hz, 2H), 6.04 (d, J = 1.6 Hz, 1H), 5.59 (s, 2H), 4.87 – 4.67 (m, 2H),2.82 – 2.66 (m, 2H), 2.66 – 2.55 (m, 2H), 2.19 (t, J = 11.7 Hz, 1H), 2.09 (s,1H), 2.02 (t, J = 8.9 Hz, 1H), 1.97 – 1.92 (m, 1H), 1.92 – 1.89 (m, 1H), 1.89– 1.83 (m, 1H), 1.75 (qd, J = 9.7, 8.1, 3.1 Hz, 1H), 1.69 – 1.61 (m, 1H),1.54 (dt, J = 10.7, 6.5 Hz, 1H), 1.27 – 1.24 (m, 1H), 1.01 (d, J = 6.3 Hz,3H), 0.94 (d, J = 6.5 Hz, 3H), 0.88 (d, J = 6.6 Hz, 3H). As Figure 1 shown.

[0043] 13 C NMR (125 MHz, CDCl 3 ) δ 175.97, 169.91, 165.92, 147.18 135.94,134.26, 130.84, 130.35, 129.62, 129.26, 129.03, 128.99, 128.21, 126.68,124.59, 120.28, 105.55, 88.99, 65.91, 57.86, 54.52, 49.72, 40.13, 34.97,31.05, 30.42, 29.90, 29.03, 27.67, 22.54, 21.19, 11.57. As Figure 2 shown.

[0044] HRMS (ESI): Calcd for C 35 H 40 N 3 O 7 (M + H): 614.2866; found: 614.2898. As Figure 3 shown

[0045] Example 9: Synthesis of Curcumol Derivative i1 Containing 1,2,4-Triazole Structure

[0046] p-Ethynylbenzoic acid (0.3 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (0.3 mmol) were dissolved in 2 mL of CH 2 Cl 2 and stirred at room temperature for 0.5 h. Then, curcumol derivative G1 (0.2 mmol) and 4-dimethylaminopyridine (0.2 mmol) were added to the reaction system, and the mixture was continuously stirred at room temperature for 3 h. The reaction progress was monitored by TLC. After the reaction was completed, the reaction was quenched with 10 mL of water, and the mixture was extracted with CH 2 Cl 2 three times. The lower layer was recovered and separated and purified by silica gel column chromatography or preparative thin-layer chromatography to obtain a yellow oily intermediate i with a yield of 60%. In a reaction flask, intermediate i, methyl azidoacetate (0.2 mmol), copper sulfate pentahydrate (0.02 mmol), and sodium ascorbate (0.02 mmol) were successively added and dissolved in 2 mL of a solvent (CH 2 CL 2 :H 2 O 3:1), and the reaction was carried out by stirring at room temperature. The reaction progress was monitored by TLC. After the reaction was completed, the reaction was quenched with 10 mL of water, and the mixture was extracted with dichloromethane three times. The lower layer was recovered and separated and purified by silica gel column chromatography or preparative thin-layer chromatography to obtain product i1 with a yield of 80 - 85%.

[0047] Compound i1: 1 H NMR (500 MHz, CDCl 3) δ 8.11 – 8.06 (m, 2H), 8.05 (s, 1H), 7.96 – 7.87 (m, 2H), 5.97 (d, J = 1.6 Hz, 1H), 5.26 (s, 2H), 4.92 – 4.55 (m, 2H), 3.83 (s, 3H), 2.23 (dd, J = 12.8, 10.8 Hz, 1H), 2.09 (t, J = 8.7 Hz, 1H), 2.00 – 1.80 (m, 3H), 1.74 – 1.57 (m, 3H), 1.51 (dq, J = 10.7, 6.4 Hz, 1H), 1.32 – 1.27 (m, 1H), 1.02 (t, J = 6.7 Hz, 6H), 0.89 (d, J = 6.6 Hz, 3H). 13 C NMR (125 MHz, CDCl 3 ) δ 166.67, 165.82, 147.13, 138.86, 134.81, 130.24, 129.59, 127.14, 125.65, 122.04, 103.30, 87.19, 66.10, 59.51, 53.12, 50.83, 50.01, 40.21, 36.41, 31.23, 30.74, 27.67, 22.62, 21.39, 11.66. HRMS (ESI): Calcd for C 27 H 34 N 3 O 6 (M + H): 496.2448; found: 496.2454. Application Example 1: In vitro anti-inflammatory experiment The anti-inflammatory activity of the present invention was evaluated using a lipopolysaccharide (LPS)-induced RAW 264.7 macrophage model: The cells were seeded at 8×10 5Inoculate at a density of cells / mL into a 48-well plate, add LPS (final concentration 1 μg / mL) to establish an inflammatory model. The experimental groups were respectively given curcumol derivatives, parent compound or the positive control drug dexamethasone at concentrations of 25 - 100 nM, with concentration gradients of 100 nM, 50 μM, and 25 μM. Four replicate wells were set for each concentration gradient, and they were incubated for 48 hours in total. After the cells were stimulated with a mixture of phorbol 12-myristate 13-acetate (PMA) (50 μg / mL) and ionomycin (1 mg / mL), the expression level of TNF-α was detected by flow cytometry after staining with a fluorescently labeled anti-TNF-α antibody. The data were analyzed using FlowJo software. The experiment was independently repeated 3 times, and one-way ANOVA was used for statistical analysis (P < 0.05 was the significance threshold).

[0048] Table 1

[0049] Evaluated by the LPS-induced RAW 264.7 macrophage inflammatory model, the curcumol derivatives showed dose-dependent anti-inflammatory activity in the concentration range of 25 - 100 nM: at a concentration of 100 nM, 29 derivatives significantly inhibited TNF-α expression (inhibition rate ≥ 50%, P < 0.05), and their effects were comparable to those of the parent compound curcumol and the positive control drug dexamethasone; when the concentration decreased to 50 nM, 28 derivatives still had significant inhibitory activity, and the TNF-α inhibition rate of compound h1 was better than that of curcumol and dexamethasone; when the concentration was further reduced to 25 nM, 22 derivatives maintained significant activity, and the inhibition rate of h1 was still significantly higher than that of the parent and control drugs (P < 0.05). The above data indicate that the triazole curcumol derivatives (especially h1) have the characteristic of highly inhibiting the inflammatory response of M1 macrophages at low doses, and their activity improvement is due to the structural optimization of the synergistic modification at positions C-8 / C-10.

[0050] Application Example 2: Curcumol derivative h1 with a triazole ring improves LPS-induced acute lung injury Dissolve curcumol derivative h1 in 5% sodium bicarbonate injection to prepare the corresponding administration concentration.

[0051] Thirty-six C57BL / 6 mice were selected for the experiment. After one week of environmental adaptation, they were randomly divided into 6 groups (n = 6): blank control group (Control), model group (Model), high-dose group of curcumol derivative h1 with a triazole ring (h1-H, 25 mg / kg), medium-dose group (h1-M, 10 mg / kg), low-dose group (h1-L, 5 mg / kg), and dexamethasone positive control group (DEX, 5 mg / kg).

[0052] The modeling method is as follows: First, mice were anesthetized by intraperitoneal injection of tribromoethanol (1 μL / g), and then an acute lung injury model in mice was established by tracheal perfusion of 50 μL of LPS solution (15 mg / kg). The blank control group was perfused with an equal volume of normal saline. 24 hours after modeling, the mice were sacrificed and lung tissues were collected, and bronchoalveolar lavage fluid was collected for standby.

[0053] Table 2

[0054] The results showed that the curcumol derivative h1 with a triazole ring could inhibit the expression of inflammatory factors in the bronchoalveolar lavage fluid of LPS-induced acute lung injury mice. At a dose of 5 mg / kg, it could significantly inhibit the expression of IFN-γ and IL-17A, which was superior to the positive drug dexamethasone (DEX).

[0055] Application Example 3: Molecular docking and Western blot experiments to determine the mechanism of action of the curcumol derivative h1 with a triazole ring in the treatment of acute lung injury Based on the Discovery Studio 2020 molecular simulation platform (Dassault Systèmes, v19.1.0), this study performed molecular docking analysis on the interaction between the target compound curcumol derivative h1 and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3, PDB ID: 8ETR). First, the crystal structure of NLRP3 was obtained from the RCSB Protein Data Bank. The receptor protein was pretreated by removing water molecules, non-standard residues, and heterologous ligands, and the protein was optimized by adding hydrogen atoms and energy minimization using the CHARMM force field. At the same time, the "Prepare Ligands" module was used to perform charge assignment, protonation state adjustment, and conformational optimization on the ligand molecule. Subsequently, based on the CDOCKER molecular docking operation, the binding mode between the ligand and the receptor was evaluated. Finally, the lowest binding energy and the best binding site between the two were obtained, and 2D / 3D binding mode diagrams were generated.

[0056] The molecular docking results showed (see Figure 4 A and B in), the curcumol derivative h1 with a triazole ring showed strong binding affinity with the NLRP3 protein, and its binding free energy was -30.4976 kcal / mol. Further analysis of the binding mode found that the terminal hydroxyl group of the curcumol derivative h1 with a triazole ring formed stable hydrogen bond interactions with the key amino acid residues of the NLRP3 protein.

[0057] To further explore the regulatory effect of the curcumol derivative h1 with a triazole ring on the NLRP3 inflammasome pathway, Western blot analysis showed (see Figure 5), the expression of NLRP3 inflammasome-related proteins (NLRP3, caspase-1 and IL-1β) in the lung tissues of mice in the LPS-induced acute lung injury (ALI) model group was significantly up-regulated compared with that in the blank control group, indicating that the NLRP3 inflammasome pathway was activated; after intervention with the curcumol derivative h1 with a triazole ring, the expression levels of the above proteins were significantly decreased, suggesting that this derivative could play an anti-ALI role by inhibiting the activation of the NLRP3 inflammasome.

[0058] Application Example 4: Surface plasmon resonance (SPR) verified that NLRP3 was the direct action target of the curcumol derivative h1.

[0059] SPR measurements were performed on a Berthold bScreen LB 991 (V4 device) to determine the binding affinity of the curcumol derivative h1 for NLRP 3. The results are shown in Figure 6 , and the experimental results showed that there was a significant direct interaction between the curcumol derivative h1 and the NLRP3 protein, and its binding constant (KD value) was 35.30 nM. This result indicated that the curcumol derivative h1 had a high binding affinity for NLRP3.

[0060] Obviously, the above embodiments of the present invention are merely examples for more clearly explaining the present invention, rather than limiting the implementation manners of the present invention. For those of ordinary skill in the art, other different forms of changes or variations can be made on the basis of the above description. It is impossible to list all the implementation methods here. Any obvious changes or variations derived from the technical solutions of the present invention still fall within the protection scope of the present invention.

Claims

1. A curcuminol derivative containing a triazole structure, characterized in that: The structure is shown in the following formula (ai): In formula (ai), R is selected from benzyl, p-benzoyl, ethanol, o-benzoyl, o-benzyl alcohol, methyl acetate, p-anisole, ethyl acetate, ethylene glycol-1-methyl ether-2-ethyl ether, ethylene glycol monoethyl ether, propanol, acetate, and propionate.

2. The curcumol derivative containing a triazole structure according to claim 1, characterized in that: The curcumol derivative is selected from any one of the compounds represented by formula a1-a10, b1-b6, c1-c3, d1, e1-e5, f1-f7, g1-g9, h1, i1: 。 3. The method for synthesizing the curcumol derivative containing a triazole structure according to claim 2, characterized in that: When the curcumol derivative is compound a1-a10, b1-b6, the synthetic route is: The synthesis method comprises the following steps: Curcumol and NaH were mixed in dimethylformamide, stirred at room temperature for 0.5 h, and then 2 equivalents of halogenated alkyne were added and stirred at room temperature for 3 h. After the reaction was completed, the reaction was quenched with water, extracted with ethyl acetate, and the upper layer was recovered. After separation and purification, yellow oily intermediates a and b were obtained. In a reaction flask, intermediates a and b, azide, copper sulfate pentahydrate, and sodium ascorbate were added in sequence, dissolved in dichloromethane solvent, stirred at room temperature to react, and after the reaction was completed, the reaction was quenched with water, extracted with dichloromethane, and the lower layer was recovered. After separation and purification, products a1-a10 and b1-b6 were obtained.

4. The method for synthesizing the curcumol derivative containing a triazole structure according to claim 2, characterized in that: When the curcuminol derivative is compound c1-c3, the synthesis route is: The synthesis method comprises the following steps: Curcumol derivative G1 was mixed with NaHCO3 in dimethylformamide, stirred at room temperature for 0.5 h, and then 1 equivalent of propargyl bromide was added and stirred at room temperature for 3 h. After the reaction was completed, the reaction was quenched with water, extracted with ethyl acetate, the upper layer was recovered, and separated and purified to obtain a yellow oily intermediate c. In a reaction flask, intermediate c, azide compound, copper sulfate pentahydrate, and sodium ascorbate were added in sequence, dissolved in dichloromethane solvent, stirred at room temperature to react, and after the reaction was completed, the reaction was quenched with water, extracted with dichloromethane, the lower layer was recovered, and separated and purified to obtain products c1-c3. When the curcuminol derivative is compound d1, the synthesis route is: The synthesis method comprises the following steps: Curcumol derivative G1 was mixed with NaH in dimethylformamide, stirred at room temperature for 0.5 h, and then propargyl bromide was added and stirred at room temperature for 3 h. After the reaction was completed, the reaction was quenched with water, extracted with ethyl acetate, and the upper layer was recovered. After separation and purification, a yellow oily intermediate product d was obtained. In a reaction flask, intermediate d, 2-azidobenzyl alcohol, copper sulfate pentahydrate, and sodium ascorbate were added in sequence, dissolved in dichloromethane solvent, stirred at room temperature to react, and after the reaction was completed, the reaction was quenched with water, extracted with dichloromethane, and the lower layer was recovered. After separation and purification, the product d1 was obtained.

5. The method for synthesizing the curcumol derivative containing a triazole structure according to claim 2, characterized in that: When the curcumol derivative is compound e1-e5, f1-f7, g1-g9, i1, the synthesis route is: The synthesis method comprises the following steps: Alkynyl acid and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide were dissolved in CH2Cl2 and stirred at room temperature for 0.5 h. Then, curcuminol derivative G1 and 4-dimethylaminopyridine were added to the reaction system and stirred at room temperature for 3 h. After the reaction, the reaction was quenched with water, extracted with CH2Cl2, and the lower layer was recovered. After separation and purification, yellow oily intermediates e, f, g, and i were obtained. In the reaction bottle, the intermediate, azide compound, copper sulfate pentahydrate, and sodium ascorbate were added in sequence and dissolved in dichloromethane solvent. The mixture was stirred at room temperature to react. After the reaction, the reaction was quenched with water, extracted with dichloromethane, and the lower layer was recovered. After separation and purification, products e1-e5, f1-f7, g1-g9, and i1 were obtained.

6. The method for synthesizing the curcumol derivative containing a triazole structure according to claim 5, characterized in that: When the curcuminol derivative is compound h1, the synthetic route is: The synthesis method comprises the following steps: The intermediate product g was dissolved in tetrahydrofuran, the air in the reaction apparatus was evacuated, the reaction apparatus was filled with nitrogen, ethylmagnesium bromide was added, refluxed at 55°C for 30 min, succinic anhydride was added, refluxed at 75°C for 4 h, water was added to stop the reaction, the pH was adjusted to 4 with hydrochloric acid, and after extraction with ethyl acetate, the upper layer was purified by silica gel column chromatography to obtain a yellow oily substance h; the intermediate h, benzyl azide, copper sulfate pentahydrate, and sodium ascorbate were added to the reaction bottle in sequence, dissolved in dichloromethane solvent, stirred at room temperature to react, and after the reaction was completed, the reaction was quenched with water, extracted with dichloromethane, the lower layer was recovered, separated and purified to obtain the product h1.

7. Use of the curcumol derivative containing a triazole structure according to claim 1 or 2 in the preparation of anti-inflammatory drugs.

8. The use according to claim 7, characterized in that: The anti-inflammatory drug can inhibit the inflammatory response of M1 macrophages.

9. The use according to claim 7, characterized in that: The application includes the application of the curcuminol derivative h1 in the preparation of a drug for improving acute lung injury. The structural formula of the curcuminol derivative h1 is as follows: 。 10. The use according to claim 9, characterized in that: The curcuminol derivative h1 can significantly inhibit the expression of inflammatory factors IFN-γ and IL-17A; the curcuminol derivative h1 exerts an anti-acute lung injury effect by inhibiting the activation of NLRP3 inflammasome.

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