Novel curcumenol derivative as well as synthesis method and application thereof

Abstract

The invention provides a novel curcumenol derivative as well as a synthesis method and application thereof, the structural general formula of the novel curcumenol derivative is as follows: # imgabs0 #, and R1 is selected from naphthyl, dimethylamino, substituted phenyl, aryl and substituted aryl. The curcumenol derivative with anti-influenza virus activity is obtained by introducing a sulfonyl compound at the hydroxyl of curcumenol, the synthesis method is green and environment-friendly, the reaction conditions are mild, the efficiency is high, the yield is high, and the drug effect is superior to that of a parent compound curcumenol.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine and relates to a new curcuminol derivative and a synthesis method and application thereof. Background Art

[0002] The Chinese medicine Curcuma phaeocaulis Valeton is the dried rhizome of a perennial herbaceous plant of the genus Curcuma in the ginger family. It is pungent and bitter in taste, warm in nature, and enters the liver and spleen meridians. It has the effects of breaking blood and promoting qi, eliminating accumulation and relieving pain. It is used to treat blood stasis, amenorrhea, food accumulation, swelling and pain, and lumps. According to the Compendium of Materia Medica, "Curcuma phaeocaulis Valeton and stewed costus root can treat all cold and heart-wrenching pains, and the pain will cause death. It can be caused by long-term heart and stomach pains."

[0003] Curcuma is rich in volatile oils, and its composition is quite complex, mainly sesquiterpenes and sesquiterpenes. Studies have found that the extract of Curcuma, Curcuma volatile oil, has good anti-tumor, anti-inflammatory and antiviral effects. The anti-tumor active ingredients in Curcuma volatile oil are mainly β-elemene, curcumol, curcumone, curdione and isocurcumol. Among them, curcumol is a guaiacyl sesquiterpenoid. As one of the main active ingredients in Curcuma volatile oil, it has a high content and is used as an important indicator component for the quality evaluation of Curcuma oil and its preparations. In the preliminary research work of the research group, it was first discovered that guaiacyl components represented by curcumol in Curcuma have antiviral activity. However, curcumol has poor water solubility and low bioavailability, and there are still certain difficulties in its application as a clinical preparation.

[0004] To date, there is still a lack of effective treatment measures for most viral pneumonias, and antiviral chemical drugs are still the main means of treating viral pneumonia. However, the antiviral spectrum of existing antiviral drugs is relatively narrow, and it is very easy to develop drug resistance. In addition, treatment is often accompanied by toxic side effects such as bone marrow suppression and existing gastrointestinal reactions, which seriously limits the scope of application of such drugs. Summary of the invention

[0005] Based on the above, the purpose of the present invention is to provide a new curcuminol derivative and its synthesis method and application, and introduce a sulfonyl compound at the hydroxyl group of curcuminol to obtain a curcuminol derivative with anti-influenza virus activity. The synthesis method is green and environmentally friendly, the reaction conditions are mild, the efficiency is high and the yield is high, and the efficacy is better than the parent compound curcuminol.

[0006] To achieve the above object, the present invention provides the following technical solutions:

[0007] A new curcuminol derivative has the following general structural formula:

[0008]

[0009] Wherein, R1 is selected from naphthyl, dimethylamino, substituted phenyl, aromatic group, substituted aromatic group and the like.

[0010] The present invention also provides a novel synthesis method of curcuminol derivatives, comprising: weighing curcuminol I and 2 times the amount of sulfonyl chloride compounds, mixing them, dissolving them with DMF, stirring at room temperature, adding 6 times the amount of NaH, heating to 70° C. and stirring, monitoring the reaction by TLC, and after the reaction is complete, separating and purifying to obtain curcuminol derivative II. The synthesis route is as follows:

[0011]

[0012] R1 is selected from naphthyl, dimethylamino, substituted phenyl, aromatic group, substituted aromatic group and the like.

[0013] Preferably, thin layer chromatography is used for separation and purification, with cyclohexane:ethyl acetate=20:1.

[0014] Preferably, the structural formula of the curcuminol derivative II is as follows:

[0015]

[0016]

[0017] The present invention further provides the use of the curcuminol derivatives in preparing drugs for resisting influenza viruses.

[0018] Preferably, the medicament inhibits the replication of influenza virus by means of curcuminol derivatives.

[0019] Preferably, the medicament alleviates weight loss caused by influenza virus infection through curcumin derivatives.

[0020] More preferably, the structural formula of the curcumol derivative is:

[0021]

[0022] The beneficial effects of the present invention are:

[0023] The present invention develops a curcuminol derivative with anti-influenza virus activity, the synthesis method is green and safe, the reaction is rapid, and the yield is high. In the in vitro antiviral activity experiment, the firefly Luciferase driven by the influenza virus promoter was inserted into the 293T-IAV-Luc cell genome, and the degree of virus replication was characterized by detecting the Luciferase activity. The results show that the curcuminol derivatives 1 and 2 prepared by the present invention both have the ability to inhibit influenza virus replication, among which derivative 1 has the strongest activity, which is better than the parent compound curcuminol. In the in vivo experiment, derivative 1 can also effectively inhibit influenza virus replication in vivo. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 Display derivative 1 1 H-NMR spectrum.

[0025] Figure 2 Display derivative 1 13 C-NMR spectrum.

[0026] Figure 3 The HRMS spectrum of derivative 1 is shown.

[0027] Figure 4 Display derivative 2 1 H-NMR spectrum.

[0028] Figure 5 Display derivative 2 13 C-NMR spectrum.

[0029] Figure 6 The HRMS spectrum of derivative 2 is shown.

[0030] Figure 7 Shows the luciferase activity test results of different compounds.

[0031] Figure 8 The in vivo pharmacodynamics test results of the antiviral activity of the derivative 1 of the present invention are shown, A. body weight, B. survival rate, C. virus titer. DETAILED DESCRIPTION

[0032] In order to explain the present invention more clearly, the present invention is further described in detail below in conjunction with embodiments and with reference to the accompanying drawings. It should be understood by those skilled in the art that the content described below is illustrative rather than restrictive, and should not be used to limit the scope of protection of the present invention.

[0033] The synthetic route of the curcuminol derivatives of the present application is as follows:

[0034]

[0035] Preferably, R1 is selected from naphthyl, dimethylamino, substituted phenyl, aromatic group, substituted aromatic group and the like.

[0036] In the following embodiments, "room temperature" may be 20°C to 30°C.

[0037] Example 1: Synthesis of Curcuma alcohol sulfonyl ester derivative 1

[0038] Preparation method: Weigh curcumol I (0.21 mmol) and 2 times the amount of 2-naphthalenesulfonyl chloride (0.42 mmol), mix, dissolve in DMF (2 mL), stir at room temperature, then add 6 times the amount of NaH (1.2 mmol), heat to 70 ° C and stir, and monitor the reaction by TLC. After the reaction is complete, separate and purify by preparative thin layer chromatography (cyclohexane: ethyl acetate = 20: 1) to obtain derivative 1 with a yield of 80%.

[0039] 1 H NMR(600MHz, CDCl3)δ:8.5(s,1H,H-1′),7.95(m,1H,H-4′),7.93(m,1H,H-9′),7.92(m,1H,H-3′),7.89(m,1H,H-7′ ),7.63(m,1H,H-6′),7.54(m,1H,H-8′),4.86(s,2H,H-14),3.11(m,1H,H-9a),2.70(m,1H,H-9b),2.12(m,1H,H-1) ,2.06(m,1H,H-7),1.99(m,1H,H-3a),1.72(m,1H,H-11),1.70(m,1H,H-6a),1.68(m,1H,H-4),1.51(m,1H,H-2a),1 .47(m,1H,H-2b),1.07(m,3H,H-13),1.04(m,1H,H-3b),0.94(m,1H,H-6b),0.85(m,3H,H-12),0.49(m,3H,H-15).See Figure 1 .

[0040] 13 C NMR (150MHz, CDCl3) δ: 143.40 (C-10), 137.13 (C-2′), 134.96 (C-5′), 131.94 (C-10 ， ),129.25(C-4′),129.18(C-1′),128.81(C-9′),128.70(C-6′),127.85(C-7′),127.36(C-8′),123.05(C-3 V ),114.28(C-8),114.87(C-14),91.25(C-5),55.22(C-1),54.13(C-7),39.13(C-4),37.71(C-9),32.79(C-3),30.62(C-6),28.40(C-11),27.73(C-2),22.73(C-12),21.48(C-13),11.66(C-15).See Figure 2 .

[0041] HR-ESI-MS m / z:427.1936[M+H] + (calcd for 427.1943). Figure 3 .

[0042] Example 2: Synthesis of Curcuma alcohol sulfonyl ester derivative 2

[0043] Preparation method: Weigh curcumol I (0.21 mmol) and 2 times the amount of dimethylaminosulfonyl chloride (0.42 mmol), mix, dissolve in DMF (2 mL), stir at room temperature, then add 6 times the amount of NaH (1.2 mmol), heat to 70 ° C and stir, and monitor the reaction by TLC. After the reaction is complete, separate and purify by preparative thin layer chromatography (cyclohexane: ethyl acetate = 20: 1) to obtain derivative 2 with a yield of 70%.

[0044] 1 H NMR(500MHz, CDCl3)δ:4.87(s,2H,H-14),3.05(m,1H,H-9a),2.91(s,6H,H-1′,H-2′),2 .69(m,1H,H-9b),2.11(m,1H,H-7),2.03(m,1H,H-3a),1.86(m,1H,H-6a),1.77(m,1H,H- 4),1.73(m,1H,H-11),1.72(m,1H,H-1),1.60(m,1H,H-2a),1.53(m,1H,H-2b),1.16(m, 1H,H-6b),1.07(m,1H,H-3b),1.05(m,3H,H-13),0.86(m,3H,H-12),0.66(m,3H,H-15). See Figure 4 .

[0045] 13 C NMR(125MHz, CDCl3)δ:143.70(C-10),113.71(C-8),112.53(C-14),90.92(C-5),54.48(C-1),54.36(C-7),39.44(C-4),38.4 1(C-1′,C-2′),37.15(C-9),33.31(C-3),30.98(C-6),28.40(C-11),28.09(C-2),22.80(C-12),21.49(C-13),12.49(C-15). See Figure 5 .

[0046] HR-ESI-MS m / z:344.1869[M+H] +(calcd for 344.1896). Figure 6 .

[0047] Example 3: Synthesis of Curcuma alcohol sulfonyl ester derivative 3

[0048] Preparation method: Weigh curcumol I (0.21 mmol) and 2 times the amount of 3,5-difluorobenzenesulfonyl chloride (0.42 mmol), mix, dissolve in DMF (2 mL), stir at room temperature, then add 6 times the amount of NaH (1.2 mmol), heat to 70 ° C and stir, and monitor the reaction by TLC. After the reaction is complete, separate and purify by preparative thin layer chromatography (cyclohexane: ethyl acetate = 20: 1) to obtain derivative 3 with a yield of 62.3%.

[0049] 1 H NMR(500MHz, CDCl3)δ:7.42(m,2H,H-2′,H-6′),7.03(m,1H,H-4′),4.88(s,2H,H-14),3.09( m,1H,H-9a),2.72(m,1H,H-9b),2.13(m,1H,H-7),2.06(m,1H,H-1),2.02(m,1H,H-3a),1.91 (m,1H,H-6a),1.81(m,1H,H-4),1.72(m,1H,H-11),1.67(m,1H,H-2a),1.54(m,1H,H-2b),1. 22(m,1H,H-6b),1.09(m,1H,H-3b),1.04(m,3H,H-13),0.89(m,3H,H-12),0.65(m,3H,H-15).

[0050] 13 C NMR (125MHz, CDCl3) δ: 163.37 (C-5′), 161.61 (C-3′), 142.84 (C-10), 115.37 ( C-1′),114.36(C-4′),111.69(C-2′,6′),111.50(C-8),108.56(C-14),91.89 (C-5),55.25(C-1),54.08(C-7),39.12(C-4),37.63(C-9),32.62(C-3),30.7 1(C-6),28.47(C-11),27.90(C-2),22.78(C-12),21.56(C-13),11.94(C-15).

[0051] HR-ESI-MS m / z:413.1588[M+H] + (calcd for 413.1598).

[0052] Example 4: Synthesis of Curcuma alcohol sulfonyl ester derivative 4

[0053] Preparation method: Weigh curcumol I (0.21 mmol) and 2 times the amount of 3,5-dichlorobenzenesulfonyl chloride (0.42 mmol), mix, dissolve in DMF (2 mL), stir at room temperature, then add 6 times the amount of NaH (1.2 mmol), heat to 70 ° C and stir, and monitor the reaction by TLC. After the reaction is complete, separate and purify by preparative thin layer chromatography (cyclohexane: ethyl acetate = 20: 1) to obtain derivative 4 with a yield of 53.9%.

[0054] NMR and high-resolution mass spectrometry data of derivative 4: 1 H NMR(600MHz, CDCl3)δ:7.83(m,2H,H-2′,H-6′),7.55(m,1H,H-4′),4.89(s,2H,H-14),3.07( m,1H,H-9a),2.70(m,1H,H-9b),2.14(m,1H,H-7),2.08(m,1H,H-1),2.06(m,1H,H-3a),1.90 (m,1H,H-6a),1.80(m,1H,H-4),1.73(m,1H,H-11),1.65(m,1H,H-2a),1.58(m,1H,H-2b),1. 23(m,1H,H-6b),1.09(m,1H,H-3b),1.06(m,3H,H-13),0.89(m,3H,H-12),0.69(m,3H,H-15).

[0055] 13 C NMR(150MHz, CDCl3)δ:142.79(C-10),135.41(C-1′),132.74(C-4′),126.31(C-2′,6′),115.24(C-8),114.18(C-14),91.87(C-5),55.24(C -1),54.06(C-7),39.11(C-4),37.61(C-9),32.65(C-3),30.69(C-6), 28.28(C-11),27.69(C-2),22.59(C-12),21.37(C-13),11.70(C-15).

[0056] HR-ESI-MS m / z:445.1012[M+H] + (calcd for 445.1007).

[0057] Example 5: Synthesis of Curcuma alcohol sulfonyl ester derivative 5

[0058] Preparation method: Weigh curcumol I (0.21 mmol) and 2 times the amount of 2,4,6-trichlorobenzenesulfonyl chloride (0.42 mmol), mix, dissolve in DMF (2 mL), stir at room temperature, then add 6 times the amount of NaH (1.2 mmol), heat to 70 ° C and stir, and monitor the reaction by TLC. After the reaction is complete, separate and purify by preparative thin layer chromatography (cyclohexane: ethyl acetate = 20: 1) to obtain derivative 5 with a yield of 59.4%.

[0059] 1 H NMR(500MHz, CDCl3)δ:7.47(s,2H,H-3′,H-5′),4.91(s,2H,H-14),3.37(m,1H,H-9 a),2.69(m,1H,H-9b),2.11(m,1H,H-7),1.99(m,1H,H-1),1.98(m,1H,H-3a),1.84 (m,1H,H-6a),1.74(m,1H,H-11),1.73(m,1H,H-4),1.63(m,2H,H-2),1.15(m,1H,H -6b),1.07(m,1H,H-3b),1.06(m,3H,H-13),0.68(m,3H,H-12),0.41(m,3H,H-15).

[0060] 13 C NMR (125MHz, CDCl3) δ: 143.01 (C-10), 138.10 (C-4′), 136.14 (C-2′, 6′), 135.41 (C-1′), 115.79 (C-8), 113.96 (C-14), 92.16 (C-5), 55.23 (C -1),54.31(C-7),38.94(C-4),37.16(C-9),32.67(C-3),30.76(C-6), 28.30(C-11),27.67(C-2),22.62(C-12),21.45(C-13),11.27(C-15).

[0061] HR-ESI-MS m / z:479.0612[M+H] + (calcd for 479.0617).

[0062] Example 6: Synthesis of Curcuma alcohol sulfonyl ester derivative 6

[0063] Preparation method: Weigh curcumol I (0.21 mmol) and 2 times the amount of 4-trifluoromethylbenzenesulfonyl chloride (0.42 mmol), mix, dissolve in DMF (2 mL), stir at room temperature, then add 6 times the amount of NaH (1.2 mmol), heat to 70 ° C and stir, and monitor the reaction by TLC. After the reaction is complete, separate and purify by preparative thin layer chromatography (cyclohexane: ethyl acetate = 20: 1) to obtain derivative 6 with a yield of 60.4%.

[0064] 1 H NMR(500MHz, CDCl3)δ:8.06(m,2H,H-3′,H-5′),7.76(m,2H,H-2′,H-6′),4.88(s,2H,H-14),3 .09(m,1H,H-9a),2.64(m,1H,H-9b),2.11(m,1H,H-7),2.08(m,1H,H-1),2.01(m,1H,H-3a),1. 89(m,1H,H-6a),1.74(m,1H,H-4),1.73(m,1H,H-11),1.60(m,1H,H-2a),1.51(m,1H,H-2b),1 .07(m,1H,H-6b),1.06(m,1H,H-3b),1.08(m,3H,H-13),0.86(m,3H,H-12),0.53(m,3H,H-15).

[0065] 13 C NMR(125MHz, CDCl3)δ:142.92(C-10),128.26(C-5′,C-3′),125.69(C-2′,6′),114.92(C-8),114.16(C-14),91.38(C-5),55.19(C-1), 54.12(C-7),39.16(C-4),37.66(C-9),32.76(C-3),30.81(C-6),28.36(C-11),27.76(C-2),22.69(C-12),21.93(C-13),11.90(C-15).

[0066] HR-ESI-MS m / z:445.1653[M+H] + (calcd for 445.1660).

[0067] Example 7: Synthesis of Curcuma alcohol sulfonyl ester derivative 7

[0068] Preparation method: Weigh curcumol I (0.21 mmol) and 2 times the amount of 4-fluorobenzenesulfonyl chloride (0.42 mmol), mix, dissolve in DMF (2 mL), stir at room temperature, then add 6 times the amount of NaH (1.2 mmol), heat to 70 ° C and stir, and monitor the reaction by TLC. After the reaction is complete, separate and purify by preparative thin layer chromatography (cyclohexane: ethyl acetate = 20: 1) to obtain derivative 7 with a yield of 63.3%.

[0069] 1 H NMR(600MHz, CDCl3)δ:7.96(m,2H,H-3′,H-5′),7.16(m,2H,H-2′,H-6′),4.87(s,2H,H-14),3 .05(m,1H,H-9a),2.69(m,1H,H-9b),2.11(m,1H,H-7),2.03(m,1H,H-3a),1.86(m,1H,H-6a),1 .77(m,1H,H-4),1.73(m,1H,H-11),1.72(m,1H,H-1),1.60(m,1H,H-2a),1.53(m,1H,H-2b),1 .16(m,1H,H-6b),1.07(m,1H,H-3b),1.05(m,3H,H-13),0.86(m,3H,H-12),0.66(m,3H,H-15).

[0070] 13 C NMR (150MHz, CDCl3) δ: 166.04 (C-4′), 143.16 (C-10), 136.35 (C-1′), 130.5 0(C-5′,C-3′),115.83(C-2′,6′),114.44(C-8),113.97(C-14),91.38(C-5 ),55.19(C-1),54.12(C-7),39.16(C-4),37.66(C-9),32.76(C-3),30.81( C-6),28.36(C-11),27.76(C-2),22.69(C-12),21.93(C-13),11.90(C-15).

[0071] HR-ESI-MS m / z:395.1685[M+H] + (calcd for 395.1692).

[0072] Example 8: Synthesis of Curcuma alcohol sulfonyl ester derivative 8

[0073] Preparation method: Weigh curcumol I (0.21 mmol) and 2 times the amount of 4-nitro-3-chlorosulfonyl chloride (0.42 mmol), mix, dissolve in DMF (2 mL), stir at room temperature, then add 6 times the amount of NaH (1.2 mmol), heat to 70 ° C and stir, and monitor the reaction by TLC. After the reaction is complete, separate and purify by preparative thin layer chromatography (cyclohexane: ethyl acetate = 20: 1) to obtain derivative 8 with a yield of 65.7%.

[0074] 1 H NMR (600MHz, CDCl3) δ: 8.45 (s, 1H, H-2′), 8.06 (d, J=10.6Hz, 1H, H-5′), 7.71 (d, J=10.4Hz, 1H, H-6′), 4.91 (s, 2H, H-14), 3.8 6(s,3H,H-7′),3.07(d,J=14.8Hz,1H,H-9a),2.69(dd,J=14.8,2.8Hz,1H,H-9b),2.16(m,1H,H-1),2.14(m,1H,H-7),2.14(m ,2H,H-6a),2.06(m,1H,H-3a),1.88(m,1H,H-3a),1.80(m,1H,H-4),1.73(m,1H,H-11),1.62(m,2H,H-2),1.27(m,1H,H-3b), 1.16(m,2H,H-6b),1.08(m,1H,H-3b),1.05(d,J=6.6Hz,3H,H-13),0.85(d,J=6.6Hz,3H,H-12),0.71(d,J=6.6Hz,3H,H-15).

[0075] 13 C NMR (150MHz, CDCl3) δ: 159.51 (C-4′), 157.51 (C-3′), 142.90 (C-10), 132.34 (C- 6′),133.85(C-2′),125.29(C-2′),116.34(C-6′),115.71(C-8),114.48(C-14), 92.11(C-5),55.23(C-1),54.06(C-7),39.08(C-4),37.73(C-9),32.69(C-3),30 .75(C-6),28.30(C-11),27.75(C-2),22.61(C-12),21.42(C-13),11.79(C-15).

[0076] HR-ESI-MS m / z:456.1261[M+H] +(calcd for 456.1248).

[0077] Example 9: Synthesis of Curcumol Sulfonyl Ester Derivative 9

[0078] Preparation method: Weigh curcumol I (0.21 mmol) and 2 times the amount of 2-pyridinesulfonyl chloride (0.42 mmol), mix, dissolve in DMF (2 mL), stir at room temperature, then add 6 times the amount of NaH (1.2 mmol), heat to 70 ° C and stir, and monitor the reaction by TLC. After the reaction is complete, separate and purify by preparative thin layer chromatography (cyclohexane: ethyl acetate = 20: 1) to obtain derivative 9 with a yield of 59.4%.

[0079] 1 H NMR (600MHz, CDCl3) δ: 9.11 (s, 1H, H-2′), 8.76 (d, J=4.50Hz, 1H, H-6′), 8.17 (d, 1H, J=8.04Hz, H-4′), 7.43 (dd ,1H,J=4.50,8.04Hz,H-4′),4.84(s,2H,H-14),3.06(m,1H,H-9a),2.68(m,1H,H-9b),2.08(m,1H,H-7),2.00( m,1H,H-3a),1.81(m,1H,H-6a),1.73(m,1H,H-4),1.70(m,1H,H-11),1.58(m,1H,H-2a),1.50(m,1H,H-2b),1. 46(m,1H,H-1),1.10(m,1H,H-6b),1.06(m,1H,H-3b),1.05(m,3H,H-13),0.83(m,3H,H-12),0.52(m,3H,H-15).

[0080] 13 C NMR (150MHz, CDCl3) δ: 153.27 (C-6′), 148.68 (C-2′), 142.91 (C-10), 137.19 (C-3′),135.41(C-4′),123.32(C-5′),115.15(C-8),114.28(C-14),91.86(C -5),55.11(C-1),54.15(C-7),39.20(C-4),37.88(C-9),32.71(C-3),30.82 (C-6),28.41(C-11),27.79(C-2),22.73(C-12),21.52(C-13),11.97(C-15).

[0081] HR-ESI-MS m / z:378.1736[M+H] + (calcd for 378.1739).

[0082] Example 10: Synthesis of Curcuma alcohol sulfonyl ester derivative 10

[0083] Preparation method: Weigh curcumol I (0.21 mmol) and 2 times the amount of 8-quinolinesulfonyl chloride (0.42 mmol), mix, dissolve in DMF (2 mL), stir at room temperature, then add 6 times the amount of NaH (1.2 mmol), heat to 70 ° C and stir, and monitor the reaction by TLC. After the reaction is complete, separate and purify by preparative thin layer chromatography (cyclohexane: ethyl acetate = 20: 1) to obtain derivative 10 with a yield of 57.4%.

[0084] 1 H NMR (600MHz, CDCl3) δ: 9.16 (dd, J=4.2, 1.6Hz, 1H, H-2′), 8.47 (dd, J=4.2, 1.6Hz, 1 H,H-4′),8.21(dd,J=8.3,1.5Hz,1H,H-7′),8.03(dd,J=8.2,1.1Hz,1H,H-5′),7.5 9(t,J=7.8Hz,1H,H-6′),7.50(dd,J=8.3,4.2Hz,1H,H-3′),4.83(dt,J=10.6,2.2H z,2H,H-14),2.97(dq,J=14.6,2.5Hz,1H,H-9a),2.71(d,J=14.7Hz,1H,H-9b),2.16 (m,1H,H-7),2.14(m,1H,H-1),2.08(t,J=12.3Hz,1H,H-3a),1.92(m,2H,H-6a),1. 87(m,1H,H-3a),1.80(m,1H,H-4),1.62(m,2H,H-2),1.73(m,1H,H-11),1.45(m,1H, H-7),1.26(m,1H,H-3b),1.08(dd,J=33.3,6.5Hz,1H,H-3b),1.05(d,J=6.6Hz,3H, H-13),0.98(m,2H,H-6b),0.87(d,J=6.6Hz,3H,H-12),0.79(d,J=6.6Hz,3H,H-15).

[0085] 13C NMR (150MHz, CDCl3) δ: 171.14 (C-2′), 151.61 (C-8′), 144.06 (C-10), 143.44 (C-9′), 137.77 (C-10′),136.20(C-7′),133.79(C-5′),132.05(C-4′),125.09(C-6′),121.98(C-3′),114.3 4(C-8),113.65(C-14),90.93(C-5),54.20(C-1),53.94(C-7),38.93(C-4),37.54(C-9),32. 62(C-3),30.51(C-6),28.45(C-11),27.46(C-2),22.74(C-12),21.51(C-13),11.56(C-15).

[0086] HR-ESI-MS m / z:428.1885[M+H] + (calcd for 428.1896).

[0087] Example 11: Synthesis of Curcuma alcohol sulfonyl ester derivative 11

[0088] Preparation method: Weigh curcumol I (0.21 mmol) and 2 times the amount of 5-bromothiophenesulfonyl chloride (0.42 mmol), mix, dissolve in DMF (2 mL), stir at room temperature, then add 6 times the amount of NaH (1.2 mmol), heat to 70 ° C and stir, and monitor the reaction by TLC. After the reaction is complete, separate and purify by preparative thin layer chromatography (cyclohexane: ethyl acetate = 20: 1) to obtain derivative 11 with a yield of 57.4%.

[0089] 1H NMR (600MHz, CDCl3) δ: 7.46 (s, 1H, H-4′), 7.03 (s, 2H, H-3′), 4.88 (s, 2H, H-14), 3.08 (dq, J=14.4, 2.5Hz, 1H, H-9a), 2.69(d,J=14.5Hz,1H,H-9b),2.16(m,1H,H-1),2.14(m,1H,H-7),2.12(m,2H,H-6a),2.06(t,J=12.3Hz,1H,H-3a),1 .84(m,1H,H-3a),1.77(m,1H,H-4),1.74(m,1H,H-11),1.65(m,2H,H-2),1.27(m,1H,H-3b),1.18(m,2H,H-6b),1.08 (dd,J=33.3,6.5Hz,1H,H-3b),1.03(d,J=6.6Hz,3H,H-13),0.88(d,J=6.6Hz,3H,H-12),0.76(d,J=6.6Hz,3H,H-15).

[0090] 13 C NMR (150MHz, CDCl3) δ: 166.04 (C-4′), 143.08 (C-10), 141.03 (C-5′), 136.35 (C- 1′),133.45(C-4′),129.58(C-3′),120.71(C-2′),115.23(C-8),114.10(C-14), 91.63(C-5),55.21(C-1),54.22(C-7),39.34(C-4),37.70(C-9),32.77(C-3),30 .86(C-6),28.34(C-11),27.89(C-2),22.66(C-12),21.41(C-13),11.94(C-15).

[0091] HR-ESI-MS m / z:461.0480[M+H] + (calcd for 461.0456).

[0092] Example 12: Synthesis of Curcuma alcohol sulfonyl ester derivative 12

[0093] Preparation method: Weigh curcumol I (0.21 mmol) and 2 times the amount of thiophenesulfonyl chloride (0.42 mmol), mix, dissolve in DMF (2 mL), stir at room temperature, then add 6 times the amount of NaH (1.2 mmol), heat to 70 ° C and stir, and monitor the reaction by TLC. After the reaction is complete, separate and purify by preparative thin layer chromatography (cyclohexane: ethyl acetate = 20: 1) to obtain derivative 12 with a yield of 60.6%.

[0094] 1 H NMR (600MHz, CDCl3) δ: 7.72 (dd, J=3.8, 1.4Hz, 1H, H-3′), 7.61 (dd, J=5.0, 1.4Hz, 1H, H-5′), 7.05 (dd, J=5.0, 3.8Hz, 1H, H-4′), 4.88 (dt, J=10.6,2.2Hz,2H,H-14),3.07(dq,J=14.6,2.5Hz,1H,H-9a),2.69(d,J=14.7Hz,1H,H-9b),2.16(m,1H,H-1),2.14(m,1H,H-7),2.14(m,2 H,H-6a),2.06(t,J=12.3Hz,1H,H-3a),1.88(m,1H,H-3a),1.80(m,1H,H-4),1.73(m,1H,H-11),1.62(m,2H,H-2),1.27(m,1H,H-3b),1.1 6(m,2H,H-6b),1.08(dd,J=33.3,6.5Hz,1H,H-3b),1.05(d,J=6.6Hz,3H,H-13),0.87(d,J=6.6Hz,3H,H-12),0.79(d,J=6.6Hz,3H,H-15).

[0095] 13 C NMR (150MHz, CDCl3) δ: 166.04 (C-4′), 143.08 (C-10), 141.03 (C-5′), 136.35 (C-1′) ,133.45(C-4′),129.58(C-3′),120.71(C-2′),115.23(C-8),114.10(C-14),91.63 (C-5),55.21(C-1),54.22(C-7),39.34(C-4),37.70(C-9),32.77(C-3),30.86(C-6 ),28.34(C-11),27.89(C-2),22.66(C-12),21.41(C-13),11.94(C-15).HR-ESI-MS m / z:383.1317[M+H] +(calcd for 383.1357).

[0096] Example 13: Synthesis of Curcuma alcohol sulfonyl ester derivative 13

[0097] Preparation method: Weigh curcumol I (0.21 mmol) and 2 times the amount of 4-chlorobenzenesulfonyl chloride (0.42 mmol), mix, dissolve in DMF (2 mL), stir at room temperature, then add 6 times the amount of NaH (1.2 mmol), heat to 70 ° C and stir, and monitor the reaction by TLC. After the reaction is complete, separate and purify by preparative thin layer chromatography (cyclohexane: ethyl acetate = 20: 1) to obtain derivative 13 with a yield of 57.7%.

[0098] 1 H NMR(500MHz, CDCl3)δ:7.87(m,2H,H-3′,H-5′),7.46(m,2H,H-2′,H-6′),4.87(s,2H,H-14),3 .09(m,1H,H-9a),2.69(m,1H,H-9b),2.12(m,1H,H-7),2.08(m,1H,H-3a),2.03(m,1H,H-1),1. 86(m,1H,H-6a),1.77(m,1H,H-4),1.74(m,1H,H-11),1.60(m,1H,H-2a),1.54(m,1H,H-2b),1 .16(m,1H,H-6b),1.07(m,1H,H-3b),1.04(m,3H,H-13),0.87(m,3H,H-12),0.66(m,3H,H-15).

[0099] 13 C NMR (125MHz, CDCl3) δ: 143.12 (C-10), 139.34 (C-1′), 138.82 (C-4′), 129.2 3(C-5′,C-3′),128.81(C-2′,6′),114.55(C-8),114.00(C-14),91.43(C-5 ),55.22(C-1),54.12(C-7),39.20(C-4),37.67(C-9),32.76(C-3),30.81( C-6),28.35(C-11),27.78(C-2),22.68(C-12),21.43(C-13),11.84(C-15).

[0100] HR-ESI-MS m / z:411.1382[M+H] + (calcd for 411.1397).

[0101] Example 14: Synthesis of Curcuma alcohol sulfonyl ester derivative 14

[0102] Preparation method: Weigh curcumol I (0.21 mmol) and 2 times the amount of 4-methylbenzenesulfonyl chloride (0.42 mmol), mix, dissolve in DMF (2 mL), stir at room temperature, then add 6 times the amount of NaH (1.2 mmol), heat to 70 ° C and stir, and monitor the reaction by TLC. After the reaction is complete, separate and purify by preparative thin layer chromatography (cyclohexane: ethyl acetate = 20: 1) to obtain derivative 14 with a yield of 64.1%.

[0103] 1 H NMR (500MHz, CDCl3) δ: 7.81 (d, J=8.22Hz, 2H, H-3′, H-5′), 7.28 (d, J=8.16Hz, 2H, H-2′, H-6′) ,4.86(s,2H,H-14),3.06(m,1H,H-9a),2.66(m,1H,H-9b),2.10(m,1H,H-7),2.08(m,1H,H-1), 1.99(m,1H,H-3a),1.81(m,1H,H-6a),1.77(m,1H,H-11),1.75(m,1H,H-4),1.56(m,2H,H-2),1 .15(m,1H,H-6b),1.06(m,1H,H-3b),1.04(m,3H,H-13),0.85(m,3H,H-12),0.66(m,3H,H-15).

[0104] 13 C NMR (125MHz, CDCl3) δ: 166.04 (C-4′), 143.16 (C-10), 136.35 (C-1′), 130.5 0(C-5′,C-3′),115.83(C-2′,6′),114.44(C-8),113.97(C-14),91.38(C-5 ),55.19(C-1),54.12(C-7),39.16(C-4),37.66(C-9),32.76(C-3),30.81( C-6),28.36(C-11),27.76(C-2),22.69(C-12),21.93(C-13),11.90(C-15).

[0105] HR-ESI-MS m / z:391.1934[M+H] + (calcd for 391.1943).

[0106] Example 15: Synthesis of Curcuma alcohol sulfonyl ester derivative 15

[0107] Preparation method: Weigh curcumol I (0.21 mmol) and 2 times the amount of 4-nitrobenzenesulfonyl chloride (0.42 mmol), mix, dissolve in DMF (2 mL), stir at room temperature, then add 6 times the amount of NaH (1.2 mmol), heat to 70 ° C and stir, and monitor the reaction by TLC. After the reaction is complete, separate and purify by preparative thin layer chromatography (cyclohexane: ethyl acetate = 20: 1) to obtain derivative 15 with a yield of 58.8%.

[0108] 1 H NMR (600MHz, CDCl3) δ: 8.35 (d, J=8.88Hz, 2H, H-3′, H-5′), 8.13 (d, J=8.94Hz2H, H-2′, H-6′), 4.90 (s,2H,H-14),3.08(m,1H,H-9a),2.71(m,1H,H-9b),2.11(m,1H,H-7),2.03(m,1H,H-3a),1.86(m,1 H,H-6a),1.73(m,1H,H-11),1.77(m,1H,H-4),1.63(m,1H,H-2a),1.51(m,1H,H-2b),1.26(m,1H,H- 1),1.11(m,1H,H-3b),1.09(m,1H,H-6b),1.07(m,3H,H-13),0.87(m,3H,H-12),0.57(m,3H,H-15).

[0109] 13 C NMR (150MHz, CDCl3) δ: 150.24 (C-4′), 146.10 (C-10), 142.75 (C-1′), 129.1 6(C-2′,6′),123.94(C-5′,C-3′),115.54(C-8),114.53(C-14),92.01(C-5 ),55.35(C-1),54.17(C-7),39.26(C-4),37.87(C-9),32.82(C-3),30.99( C-6),28.45(C-11),27.86(C-2),22.77(C-12),21.58(C-13),12.05(C-15).

[0110] HR-ESI-MS m / z:422.1643[M+H] + (calcd for 422.1637).

[0111] Example 16: Synthesis of Curcuma alcohol sulfonyl ester derivative 16

[0112] Preparation method: Weigh curcumol I (0.21 mmol) and 2 times the amount of dansyl chloride (0.42 mmol), mix, dissolve in DMF (2 mL), stir at room temperature, then add 6 times the amount of NaH (1.2 mmol), heat to 70 ° C and stir, and monitor the reaction by TLC. After the reaction is complete, separate and purify by preparative thin layer chromatography (cyclohexane: ethyl acetate = 20: 1) to obtain derivative 16 with a yield of 57.2%.

[0113] 1 H NMR (500MHz, CDCl3) δ: 8.53 (d, J=8.3Hz, 1H,, H-8′), 8.33 (dd, J=4.2, 1.6Hz, 1H, H-4′),8.26(dd,J=7.3,1.3Hz,1H,H-2′),7.56(dd,J=8.5,7.3Hz,1H,H-7′),7.50 (dd,J=8.5,7.3Hz,1H,H-3′),7.17(d,J=7.3Hz,1H,H-6′),4.83(dt,J=10.6,2.2H z,2H,H-14),2.97(dq,J=14.6,2.5Hz,1H,H-9a),2.86(s,6H,H-11′,H-12′),2.71 (d,J=14.7Hz,1H,H-9b),2.16(m,1H,H-7),2.14(m,1H,H-1),2.08(t,J=12.3Hz,1 H,H-3a),1.92(m,2H,H-6a),1.80(m,1H,H-4),1.62(m,2H,H-2),1.73(m,1H,H-11 ),1.26(m,1H,H-6b),1.08(dd,J=33.3,6.5Hz,1H,H-3b),1.05(d,J=6.6Hz,3H,H- 13),0.98(m,2H,H-6b),0.87(d,J=6.6Hz,3H,H-12),0.79(d,J=6.6Hz,3H,H-15).

[0114] 13C NMR (125MHz, CDCl3) δ: 171.12 (C-5′), 143.51 (C-10), 136.26 (C-1′), 130.48 (C-8′), 130.04 (C-9′), 1 29.61(C-2′),129.15(C-10′),127.96(C-7′),123.00(C-3′),120.08(C-4′),114.99(C-6′),114.06( C-8),113.59(C-14),91.04(C-5),55.18(C-1),54.07(C-7),45.40(C-11′,12′),38.98(C-4),37.38( C-9),32.58(C-3),30.57(C-6),28.37(C-11),27.53(C-2),22.70(C-12),21.53(C-13),11.40(C-15).

[0115] HR-ESI-MS m / z:470.2365[M+H] + (calcd for 470.2365).

[0116] Example 17: Synthesis of Curcuma alcohol sulfonyl ester derivative 17

[0117] Preparation method: Weigh curcumol I (0.21 mmol) and 2 times the amount of 4-methoxybenzenesulfonyl chloride (0.42 mmol), mix, dissolve in DMF (2 mL), stir at room temperature, then add 6 times the amount of NaH (1.2 mmol), heat to 70 ° C and stir, and monitor the reaction by TLC. After the reaction is complete, separate and purify by preparative thin layer chromatography (cyclohexane: ethyl acetate = 20: 1) to obtain derivative 17 with a yield of 82.1%.

[0118] 1H NMR (600MHz, CDCl3) δ: 7.87 (dd, J=9.2, 3.3Hz, 2H, H-2′, H-6′), 6.94 (dd, J=9.1, 3.2Hz, 2H, H-3′, H-5′), 4.86 (m, 2H, H -14),3.86(s,3H,H-7′),3.06(dq,J=14.6,2.5Hz,1H,H-9a),2.66(d,J=14.7Hz,1H,H-9b),2.16(m,1H,H-1),2.14(m,1 H,H-7),2.14(m,2H,H-3a),2.06(t,J=12.3Hz,1H,H-6a),1.80(m,1H,H-4),1.73(m,1H,H-11),1.62(m,2H,H-2),1.27( m,1H,H-3b),1.16(m,1H,H-6b),1.05(d,J=6.6Hz,3H,H-13),0.85(d,J=6.6Hz,3H,H-12),0.71(d,J=6.6Hz,3H,H-15).

[0119] 13 C NMR (150MHz, CDCl3) δ: 150.24 (C-4′), 146.10 (C-10), 142.75 (C-1′), 129.1 6(C-2′,6′),123.94(C-5′,C-3′),115.54(C-8),114.53(C-14),92.01(C-5 ),55.35(C-1),54.17(C-7),39.26(C-4),37.87(C-9),32.82(C-3),30.99( C-6),28.45(C-11),27.86(C-2),22.77(C-12),21.58(C-13),12.05(C-15).

[0120] HR-ESI-MS m / z:407.1844[M+H] + (calcd for 407.1892).

[0121] Example 18: Synthesis of Curcuma alcohol sulfonyl ester derivative 18

[0122] Preparation method: Weigh curcumol I (0.21 mmol) and 2 times the amount of 4-iodobenzenesulfonyl chloride (0.42 mmol), mix, dissolve in DMF (2 mL), stir at room temperature, then add 6 times the amount of NaH (1.2 mmol), heat to 70 ° C and stir, and monitor the reaction by TLC. After the reaction is complete, separate and purify by preparative thin layer chromatography (cyclohexane: ethyl acetate = 20: 1) to obtain derivative 18 with a yield of 85.2%.

[0123] 1 H NMR (500MHz, CDCl3) δ: 7.85 (dt, J=8.6, 2.0Hz, 2H, H-2′, 6′), 7.65 (dt, J=8.5, 2.0Hz, 2H, H-5′, H-3′), 4.88 (dt, J=11.1,2.2Hz,2H,H-14),3.07(d,J=14.7Hz,1H,H-9a),2.68(dd,J=14.9,2.3Hz,1H,H-9b),2.11(m,1H,H-7),2. 03(m,1H,H-3a),1.86(m,1H,H-6a),1.77(m,1H,H-4),1.73(m,1H,H-11),1.72(m,1H,H-1),1.60(m,1H,H-2a),1. 53(m,1H,H-2b),1.16(m,1H,H-6b),1.07(m,1H,H-3b),1.05(m,3H,H-13),0.86(m,3H,H-12),0.66(m,3H,H-15).

[0124] 13 C NMR (125MHz, CDCl3) δ: 151.55 (C-4′), 143.12 (C-10), 142.75 (C-1′), 137.7 8(C-2′,6′),129.13(C-5′,C-3′),114.55(C-8),113.97(C-14),91.41(C-5 ),55.31(C-1),54.13(C-7),39.17(C-4),37.63(C-9),32.75(C-3),30.80( C-6),28.35(C-11),27.77(C-2),22.67(C-12),21.42(C-13),11.79(C-15).

[0125] HR-ESI-MS m / z:503.0732[M+H] + (calcd for 503.0753).

[0126] Example 19: Synthesis of Curcuma alcohol sulfonyl ester derivative 19

[0127] Preparation method: Weigh curcumol I (0.21 mmol) and 2 times the amount of 3-fluoro-4-bromobenzenesulfonyl chloride (0.42 mmol), mix, dissolve in DMF (2 mL), stir at room temperature, then add 6 times the amount of NaH (1.2 mmol), heat to 70 ° C and stir, and monitor the reaction by TLC. After the reaction is complete, separate and purify by preparative thin layer chromatography (cyclohexane: ethyl acetate = 20: 1) to obtain derivative 19 with a yield of 45.8%.

[0128] 1 H NMR (500MHz, CDCl3) δ: 7.70 (dt, J=6.4, 3.2Hz, 2H, H-2′, H-6′), 6.94 (m, 1H, H-5′), 4.86 (m, 2H, H-14), 3.86 (s, 3H, H-7′), 3.07 (d,J=14.8Hz,1H,H-9a),2.69(dd,J=14.8,2.8Hz,1H,H-9b),2.16(m,1H,H-1),2.14(m,1H,H-7),2.14(m,2H,H-6a),2.06(t,J= 12.3Hz,1H,H-3a),1.88(m,1H,H-3a),1.80(m,1H,H-4),1.73(m,1H,H-11),1.62(m,2H,H-2),1.27(m,1H,H-3b),1.16(m,2H,H- 6b), 1.08 (dd, J=33.3, 6.5Hz, 1H, H-3b), 1.05 (d, J=6.6Hz, 3H, H-13), 0.85 (d, J=6.6Hz, 3H, H-12), 0.71 (d, J=6.6Hz, 3H, H-15).

[0129] 13 C NMR (125MHz, CDCl3) δ: 159.51 (C-4′), 157.51 (C-3′), 142.90 (C-10), 141.17 (C- 1′),133.85(C-2′),124.41(C-5′),116.34(C-6′),115.01(C-8),114.15(C-14), 91.69(C-5),55.27(C-1),54.11(C-7),39.17(C-4),37.67(C-9),32.75(C-3),30 .82(C-6),28.33(C-11),27.78(C-2),22.64(C-12),21.42(C-13),11.76(C-15).

[0130] HR-ESI-MS m / z:473.0801[M+H] + (calcd for 473.0797).

[0131] Example 20: Synthesis of Curcuma alcohol sulfonyl ester derivative 20

[0132] Preparation method: Weigh curcumol I (0.21 mmol) and 2 times the amount of 3,4,5-trifluorobenzenesulfonyl chloride (0.42 mmol), mix, dissolve in DMF (2 mL), stir at room temperature, then add 6 times the amount of NaH (1.2 mmol), heat to 70 ° C and stir, and monitor the reaction by TLC. After the reaction is complete, separate and purify by preparative thin layer chromatography (cyclohexane: ethyl acetate = 20: 1) to obtain derivative 20 with a yield of 57.2%.

[0133] 1 H NMR (500MHz, CDCl3) δ: 7.63 (m, 2H, H-2′, H-6′), 4.90 (m, 2H, H-14), 3.07 (d, J=14.2Hz, 1H, H-9a) ,2.70(dd,J=14.1,2.8Hz,1H,H-9b),2.16(m,1H,H-1),2.07(m,1H,H-7),2.07(m,1H,H-3a),1.94 (m,1H,H-6a),1.84(m,1H,H-4),1.74(m,1H,H-11),1.67(m,2H,H-2),1.24(m,1H,H-6b),1.10(m, 1H, H-3b), 1.10 (d, J=6.6Hz, 3H, H-13), 0.86 (d, J=6.6Hz, 3H, H-12), 0.71 (d, J=6.6Hz, 3H, H-15).

[0134] 13 C NMR(125MHz, CDCl3)δ:142.67(C-10),115.42(C-8),114.33(C-14),113.2 8(C-4′),113.23(C-3′,5′),113.14(C-2′,6′),113.09(C-1′),91.92(C-5) ,55.25(C-1),54.09(C-7),39.16(C-4),37.69(C-9),32.73(C-3),30.88(C -6),28.31(C-11),27.77(C-2),22.61(C-12),21.40(C-13),11.86(C-15).

[0135] HR-ESI-MS m / z:431.1500[M+H]+ (calcd for 431.1504).

[0136] Example 21: Synthesis of Curcuma alcohol sulfonyl ester derivative 21

[0137] Preparation method: Weigh curcumol I (0.21 mmol) and 2 times the amount of 3-fluorobenzenesulfonyl chloride (0.42 mmol), mix, dissolve in DMF (2 mL), stir at room temperature, then add 6 times the amount of NaH (1.2 mmol), heat to 70 ° C and stir, and monitor the reaction by TLC. After the reaction is complete, separate and purify by preparative thin layer chromatography (cyclohexane: ethyl acetate = 20: 1) to obtain derivative 21 with a yield of 57.5%.

[0138] 1 H NMR(500MHz, CDCl3)δ:7.74(dt,J=6.5,3.5Hz,1H,H-4′),7.66(m,1H,H-6′),7.48(m,1H,H-2′),7.28(m,1H,H-5 ′),4.88(m,2H,H-14),3.08(d,J=14.6Hz,1H,H-9a),2.70(dd,J=14.8,1H,H-9b),2.12(m,1H,H-1),2.09(m,1H, H-7),2.03(m,2H,H-3a),1.85(m,1H,H-6a),1.77(m,1H,H-4),1.73(m,1H,H-11),1.60(m,2H,H-2),1.16(m,2H, H-6b),1.08(m,1H,H-3b),1.05(d,J=6.6Hz,3H,H-13),0.85(d,J=6.6Hz,3H,H-12),0.63(d,J=6.6Hz,3H,H-15).

[0139] 13 C NMR (125MHz, CDCl3) δ: 143.09 (C-10), 130.26 (C-2′), 123.44 (C-4′), 120.10 (C- 3′),119.93(C-5′),115.37(C-1′),115.17(C-6′),114.71(C-8),114.01(C-14), 91.53(C-5),55.20(C-1),54.12(C-7),39.18(C-4),37.66(C-9),32.75(C-3),30 .76(C-6),28.34(C-11),27.75(C-2),22.66(C-12),21.42(C-13),11.80(C-15).

[0140] HR-ESI-MS m / z:395.1691[M+H]+(calcd for 395.1692).

[0141] Example 22: Synthesis of Curcuma alcohol sulfonyl ester derivative 22

[0142] Preparation method: Weigh curcumol I (0.21 mmol) and 2 times the amount of 3-chloro-4-fluorobenzenesulfonyl chloride (0.42 mmol), mix, dissolve in DMF (2 mL), stir at room temperature, then add 6 times the amount of NaH (1.2 mmol), heat to 70 ° C and stir, and monitor the reaction by TLC. After the reaction is complete, separate and purify by preparative thin layer chromatography (cyclohexane: ethyl acetate = 20: 1) to obtain derivative 22 with a yield of 50.1%.

[0143] 1 H NMR (500MHz, CDCl3) δ: 8.05 (dd, J=6.4, 3.2Hz, 1H, H-2′), 7.85 (m, 1H, H-6′), 7.27 (m, 1H, H-5′), 4.89 (m, 2H, H -14),3.07(d,J=14.8Hz,1H,H-9a),2.68(m,1H,H-9b),2.14(m,1H,H-1),2.07(m,1H,H-7),2.06(m,2H,H-3a) ,1.90(m,1H,H-6a),1.80(m,1H,H-4),1.73(m,1H,H-11),1.64(m,1H,H-2b),1.57(m,1H,H-2a)1.21(m,1H,H- 6b),1.09(m,1H,H-3b),1.07(d,J=6.6Hz,3H,H-13),0.86(d,J=6.6Hz,3H,H-12),0.70(d,J=6.6Hz,3H,H-15).

[0144] 13C NMR(125MHz, CDCl3)δ:142.92(C-10),137.20(C-3′),131.07(C-2′),128.20(C- 6′),121.86(C-4′),116.89(C-1′),116.71(C-5′),114.91(C-8),114.15(C-14), 91.69(C-5),55.24(C-1),54.11(C-7),39.17(C-4),37.67(C-9),32.73(C-3),30 .79(C-6),28.34(C-11),27.77(C-2),22.65(C-12),21.42(C-13),11.82(C-15).

[0145] HR-ESI-MS m / z:429.1294[M+H] + (calcd for 429.1303).

[0146] Test Example 1: Evaluation of the in vitro antiviral activity of curcumol derivatives

[0147] Firefly Luciferase driven by influenza virus promoter is inserted into the genome of 293T-IAV-Luc cells. Luciferase can be transcribed and expressed in the presence of influenza virus polymerase. Detection of Luciferase activity can reflect the activity and content of viral polymerase, thus characterizing the replication of the virus. Laboratory-constructed 293T-IAV-Luc cells (Mingge Wang. et al. Microorganisms. 2024; DOI: 10.3390 / microorganisms12040654) were infected with influenza virus, and DMSO (control), curcumin, derivative 1 (1#), derivative 2 (2#) and hydroxyoseltamivir were added at the same time. The drug concentration was 1 micromolar. After 24 hours, the cell Luciferase activity was detected to indicate the effect of the compound on influenza virus replication.

[0148] Results Figure 7 , showing that derivatives 1 and 2 both have good anti-influenza virus effects and are stronger than curcumin, among which derivative 1 has the best inhibitory effect on influenza virus.

[0149] Test Example 2: Antiviral Pharmacodynamics Experiment of Derivative 1

[0150] Adult C57 / BL6 mice weighing 18.5-20g were infected with influenza virus PR8 and divided into 4 groups, 16 mice in each group, with PBS infection as the uninfected control group. Derivative 1 (50 mg / kg), oseltamivir (50 mg / kg) or no medication (only saline) were administered 2 hours after infection for 5 consecutive days, once a day. After that, the mice were weighed every day, the survival of the mice was counted, and the lung tissues of some mice were taken for lung tissue virus titration 3 days after infection.

[0151] Results Figure 8 , showing that derivative 1 can alleviate the weight loss of mice caused by influenza virus infection (A), improve the death of mice caused by influenza virus infection (B), and that derivative 1 treatment can inhibit influenza virus replication in mouse lung tissue (C).

[0152] Obviously, the above embodiments of the present invention are merely examples to more clearly illustrate the present invention, and are not limitations on the implementation methods of the present invention. For ordinary technicians in the relevant field, other different forms of changes or modifications can be made on the basis of the above description. It is impossible to list all the implementation methods here. All obvious changes or modifications derived from the technical solution of the present invention are still within the protection scope of the present invention.

Claims

1. A new curcuminol derivative, the general structural formula of which is as follows: in, R1 is selected from naphthyl, dimethylamino, substituted phenyl, aromatic group, substituted aromatic group.

2. A new method for synthesizing a curcuminol derivative, comprising: Weigh curcumin I and 2 times the amount of sulfonyl chloride compound, mix them, dissolve them in DMF, stir at room temperature, then add 6 times the amount of NaH, heat to 70°C and stir, monitor the reaction by TLC, and after the reaction is complete, separate and purify to obtain curcumin derivative II. The synthetic route is as follows: R1 is selected from naphthyl, dimethylamino, substituted phenyl, aromatic group, substituted aromatic group.

3. The synthesis method according to claim 2, characterized in that Thin layer chromatography was used for separation and purification: cyclohexane: ethyl acetate = 20:

1.

4. The synthesis method according to claim 2, characterized in that The structural formula of the curcuminol derivative II is as follows:

5. Use of the curcuminol derivative according to claim 1 or the curcuminol derivative prepared by the synthesis method according to any one of claims 2 to 4 in the preparation of anti-influenza virus drugs.

6. The use according to claim 5, characterized in that: The drug inhibits the replication of influenza virus through curcuminol derivatives.

7. The use according to claim 5, characterized in that: The drug alleviates weight loss caused by influenza virus infection through curcumin derivatives.

8. The use according to claim 6 or 7, characterized in that: The structural formula of the curcumol derivative is:

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