Preparation method of 3-hydroxytanshinone IIA

Abstract

The invention discloses a preparation method of 3-hydroxytanshinone IIA, and particularly discloses a preparation method of a compound as shown in a formula II. The preparation method comprises the following steps: in a solvent, in the presence of an acid, carrying out a reaction as shown in the specification on a tanshinone IIA sodium sulfonate derivative as shown in a formula I to obtain a compound as shown in a formula II, wherein the *-labeled carbon atom is of an R configuration, an S configuration or a mixture of the R configuration and the S configuration; the molar ratio of the acid to the tanshinone IIA sodium sulfonate derivative as shown in the formula I is (12-25): 1. The method has the advantages of high yield and high purity. # imgabs0 #

Description

Technical Field

[0001] The invention relates to a method for preparing 3-hydroxytanshinone IIA. Background Art

[0002] 3alpha-Hydroxytanshinone IIA is mainly extracted from Danshen medicinal materials, and its content is very low. Studies have found that 3alpha-Hydroxytanshinone IIA also has multiple pharmacological activities, such as protective effects on cardiovascular and cerebrovascular diseases, dilation of blood vessels, lowering blood pressure, and inhibiting platelet aggregation. The literature (Development and structure–activity relationships of tanshinones as selective 11β-hydroxysteroid dehydrogenase 1inhibitors, Xu Deng et al., Natural Products and Bioprospecting (2022)) also reported that 3alpha-Hydroxytanshinone IIA and its derivatives prepared as intermediates have inhibitory effects on 11β-HSD1 in 3T3-L1 adipocytes and ob / ob mouse livers, and can be further studied as anti-diabetic drugs. CN109824753A also discloses that a compound prepared using 3alpha-hydroxytanshinone IIA as an intermediate has a significant inhibitory effect on indoleamine 2,3-dioxygenase IDO and tryptophan 2,3-dioxygenase, and can be used to prepare drugs for IDO or TOO-mediated diseases. CN 110859845B also discloses the use of 3alpha-hydroxytanshinone IIA as an intermediate in the preparation of anti-Helicobacter pylori drugs.

[0003] However, in the prior art, 3alpha-hydroxytanshinone IIA is mainly extracted from natural products, and there are fewer artificial synthesis methods. CN109824753A discloses that tanshinone IIA uses carbon tetrachloride as a solvent and prepares dehydrotanshinone IIA in the presence of NBS and AIBN, with a yield of 27%. Subsequently, CN102603861A uses dehydrotanshinone IIA to obtain 3alpha-hydroxytanshinone IIA through a two-step reaction, with a yield of 34%. The total yield of the above three-step reaction is 9%. This method is cumbersome to operate, uses dangerous reagents such as hydrogen, and has a low yield. Therefore, it is of great significance to develop a new preparation method for 3alpha-hydroxytanshinone IIA. Summary of the invention

[0004] The technical problem to be solved by the present invention is to overcome the low yield, complicated operation and high risk of the method for preparing 3-hydroxytanshinone IIA in the prior art. To this end, the present invention provides a method for preparing 3-hydroxytanshinone IIA. The method has the advantages of high yield, convenient and safe operation.

[0005] The present invention provides a method for preparing a compound as shown in formula II, comprising the following steps: in a solvent, in the presence of an acid, subjecting a sodium tanshinone IIA sulfonate derivative as shown in formula I to a reaction as shown below to obtain a compound as shown in formula II;

[0006] ;

[0007] Among them, the carbon atoms marked with * are R configuration, S configuration, or a mixture of R configuration and S configuration;

[0008] The molar ratio of the acid to the sodium tanshinone IIA sulfonate derivative shown in formula I is (12-25):1.

[0009] In some embodiments, the sodium tanshinone IIA sulfonate derivative as shown in formula I is

[0010] , the compound shown in formula II is .

[0011] In some embodiments, the solvent is a nitrile and / or ether solvent, preferably, the solvent is acetonitrile or 1,4-dioxane.

[0012] In some embodiments, the molar volume ratio of the sodium tanshinone IIA sulfonate derivative as shown in formula I to the solvent is (0.005-0.2) mol / L, preferably, the molar volume ratio of the sodium tanshinone IIA sulfonate derivative as shown in formula I to the solvent is (0.01-0.05) mol / L, and more preferably, the molar volume ratio of the sodium tanshinone IIA sulfonate derivative as shown in formula I to the solvent is 0.02 mol / L or 0.04 mol / L.

[0013] In some embodiments, the acid is selected from one or more of organic acids and / or inorganic acids, such as sulfuric acid, hydrochloric acid, and p-toluenesulfonic acid.

[0014] In some embodiments, the sulfuric acid participates in the reaction in the form of a 1-15 mol / L sulfuric acid aqueous solution. Preferably, the sulfuric acid participates in the reaction in the form of a 1.8 mol / L or 9.0 mol / L sulfuric acid aqueous solution.

[0015] In some embodiments, the hydrochloric acid participates in the reaction in the form of a 1-12 mol / L hydrochloric acid aqueous solution. Preferably, the hydrochloric acid participates in the reaction in the form of a 1.8 mol / L or 12.0 mol / L hydrochloric acid aqueous solution.

[0016] In some embodiments, the molar ratio of the acid to the sodium tanshinone IIA sulfonate derivative of formula I is (15-20):1, for example 18:1.

[0017] In some embodiments, the solvent is acetonitrile, the acid is p-toluenesulfonic acid or a 12.0 mol / L aqueous hydrochloric acid solution; and the molar ratio of the acid to the sodium tanshinone IIA sulfonate derivative is 18:1.

[0018] In some embodiments, the solvent is 1,4-dioxane, the acid is a 12.0 mol / L aqueous hydrochloric acid solution or a 9.0 mol / L aqueous sulfuric acid solution; and the molar ratio of the acid to the sodium tanshinone IIA sulfonate derivative is 18:1.

[0019] In some embodiments, the reaction temperature is 60-80°C, preferably, the reaction temperature is 70°C.

[0020] In some embodiments, the progress of the reaction can be monitored by conventional monitoring methods for such reactions in the art (e.g., HPLC, TLC, or LC-MS), with the disappearance or no-reaction of the sodium tanshinone IIA sulfonate derivative as shown in Formula I being taken as the endpoint of the reaction. For example, the reaction time of the reaction is 2-6 hours.

[0021] In some embodiments, the reaction materials of the reaction consist of the solvent, the acid and the sodium tanshinone IIA sulfonate derivative as shown in Formula I.

[0022] In some embodiments, the method for preparing the compound of Formula II comprises the following steps (a) and (b):

[0023] (a) mixing the solvent and the sodium tanshinone IIA sulfonate derivative as shown in formula I to obtain a mixed solution;

[0024] (b) mixing the acid with the mixed solution obtained in step (a), and reacting the mixture to obtain the compound shown in formula II.

[0025] After the reaction is completed, the conventional post-processing steps for such reactions in the art may be further included, for example, the post-processing steps may include concentration, extraction, drying and purification.

[0026] In some embodiments, the concentrating is distillation under reduced pressure.

[0027] In some embodiments, the solvent for the extraction is dichloromethane.

[0028] In some embodiments, the dry desiccant is anhydrous sodium sulfate or anhydrous magnesium sulfate.

[0029] In some embodiments, the purification is performed by silica gel plate or silica gel column purification, and the eluent for the purification may be a mixed solvent of dichloromethane and methanol, and the volume ratio of dichloromethane to methanol may be (10-50):1, for example 30:1.

[0030] Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

[0031] The reagents and raw materials used in the present invention are commercially available.

[0032] The positive and progressive effect of the present invention is that the present invention provides a method for preparing 3-hydroxytanshinone IIA, and the preparation method has a high yield or purity. DETAILED DESCRIPTION

[0033] The present invention is further described below by way of examples, but the present invention is not limited to the scope of the examples. The experimental methods in the following examples without specifying specific conditions are carried out according to conventional methods and conditions, or selected according to the product specifications.

[0034] The sodium tanshinone IIA sulfonate derivative (Compound 1) used in the following examples can be extracted from the reaction solution obtained in the preparation process of sodium tanshinone IIA sulfonate described in Example 20 described in patent document CN 113861263 A published by Shanghai No. 1 Biochemical Pharmaceutical Co., Ltd.

[0035] Proton spectrum data of compound 1: 1 H NMR (600 MHz, Methanol-d4) δ 7.82 (d, J = 7.8 Hz, 1H), 7.75 (d, J = 7.8 Hz, 1H), 4.43 (dd, J = 7.8, 2.4 Hz, 1H), 3.45 (dt, J =19.2, 6.6 Hz, 1H), 3.25 (dt, J = 19.2, 6.6 Hz, 1H), 2.47 (s, 3H), 2.33 – 2.23(m, 2H), 1.42 (s, 3H), 1.40 (s, 3H).

[0036] The following examples use Shimadzu LC-2030C Plus high performance liquid phase for purity detection and analysis. Chromatographic conditions: ZORBAX SB-C18 column (4.6×150 mm, 5-micton), mobile phase A: 20 mM KH2PO4+0.5% triethylamine (pH4.0)-methanol (60:40), mobile phase B: 20 ​​mM KH2PO4+0.5% triethylamine (pH 4.0)-methanol (20:80). Gradient elution program: flow rate 1.0 mL / min, column temperature 25°C, detection wavelength 271 nm, injection volume 10 μL.

[0037]

[0038] Example 1

[0039] Weigh 51.4 mg (0.1 mmol, 1.0 equiv) of the sodium tanshinone IIA sulfonate derivative shown in formula 1 into a 10 mL single-necked flask, add 5 mL of acetonitrile, stir, then add 150 μL (1.8 mmol, 18.0 equiv) of 12.0 mol / L hydrochloric acid, heat to 70 ° C, stir for 2 h, cool to room temperature and remove the solvent under reduced pressure, add 40 mL of dichloromethane to dissolve, and then extract and wash with water twice (50 mL * 2). Dry with anhydrous sodium sulfate, filter, remove the solvent from the filtrate under reduced pressure, separate using a preparation plate (dichloromethane: methanol = 30:1), scrape off the silica gel with the target product, soak with dichloromethane and filter after ultrasonication, combine and concentrate the filtrates to obtain 28.8 mg of red solid, with a yield of 92.9% and a purity of 98.0%.

[0040] The high-resolution mass spectrum of the product 3alpha-hydroxytanshinone IIA shown in Formula 2 obtained in this example is C 19 H 18 NaO4(M+Na) + = 333.1099, 1 H NMR and 13 C NMR is as follows:

[0041] 1H NMR (600 MHz, Chloroform-d) δ 7.65 (d, J = 7.8 Hz, 1H), 7.59 (d, J= 8.4 Hz, 1H), 7.23 (d, J = 1.8 Hz, 1H), 3.78 (dd, J = 8.4, 2.4 Hz, 1H), 3.42(dt, J = 19.8, 6.6, Hz, 1H), 3.26 (dt, J = 19.8, 6.6, Hz, 1H), 2.27 (d, J =1.2 Hz, 3H), 2.08 – 2.00 (m, 1H), 1.97 – 1.91 (m, 1H), 1.36 (s, 3H), 1.34 (s, 3H), 1.71 – 1.64 (m, 1H).

[0042] 13 C NMR (151 MHz, Chloroform-d) δ 183.4, 175.5, 161.5, 148.7, 142.8,141.4, 133.8, 127.8, 126.0, 121.2, 120.8, 120.0, 74.0, 39.8, 29.7, 26.3,26.2, 25.2, 8.8.

[0043] Example 2

[0044] Weigh 51.4 mg (0.1 mmol, 1.0 equiv) of the sodium tanshinone IIA sulfonate derivative shown in formula 1 into a 10 mL single-necked flask, add 5 mL 1,4-dioxane, stir, then add 150 μL (1.8 mmol, 18.0 equiv) of 12.0 mol / L hydrochloric acid, heat to 70 ° C, stir for 2 h, cool to room temperature and remove the solvent under reduced pressure, add 40 mL of dichloromethane to dissolve, and then extract and wash with water twice (50 mL*2). Dry with anhydrous sodium sulfate, filter, remove the solvent from the filtrate under reduced pressure, separate using a preparation plate (dichloromethane: methanol = 30:1), scrape off the silica gel with the target product, soak with dichloromethane and filter after ultrasonication, combine and concentrate the filtrates to obtain 29.2 mg of red solid, with a yield of 94.2% and a purity of 97.5%. The structural characterization data of the red solid are the same as in Example 1.

[0045] Example 3

[0046] Weigh 51.4 mg (0.1 mmol, 1.0 equiv) of the sodium tanshinone IIA sulfonate derivative shown in formula 1 into a 10 mL single-necked flask, add 5 mL of 1,4-dioxane, stir, then add 200 μL (1.8 mmol, 18.0 equiv) of 9.0 mol / L sulfuric acid, heat to 70 ° C, stir for 2 h, cool to room temperature and remove the solvent under reduced pressure, add 40 mL of dichloromethane to dissolve, and then extract and wash with water twice (50 mL*2). Dry with anhydrous sodium sulfate, filter, remove the solvent from the filtrate under reduced pressure, separate using a preparation plate (dichloromethane: methanol = 30:1), scrape off the silica gel with the target product, soak with dichloromethane and filter after ultrasonication, combine and concentrate the filtrates to obtain 27.9 mg of a red solid with a yield of 90.0% and a purity of 97.1%. The structural characterization data of the red solid are the same as in Example 1.

[0047] Example 4

[0048] Weigh 51.4 mg (0.1 mmol, 1.0 equiv) of the sodium tanshinone IIA sulfonate derivative shown in formula 1 into a 10 mL single-necked flask, add 5 mL acetonitrile, stir, then add 310 mg (1.8 mmol, 18.0 equiv) of p-toluenesulfonic acid, heat to 70 ° C, stir for 6 hours, cool to room temperature and remove the solvent under reduced pressure, add 40 mL of dichloromethane to dissolve, and then extract and wash with water twice (50 mL * 2). Dry with anhydrous magnesium sulfate, filter, remove the solvent from the filtrate under reduced pressure, separate using a preparation plate (dichloromethane: methanol = 30:1), scrape off the silica gel with the target product, soak with dichloromethane and filter after ultrasonication, combine and concentrate the filtrates to obtain 22.6 mg of red solid, with a yield of 72.9% and a purity of 95.4%. The structural characterization data of the red solid are the same as those in Example 1.

[0049] Example 5

[0050] Weigh 514 mg (1.0 mmol, 1.0 equiv) of the sodium tanshinone IIA sulfonate derivative shown in formula 1 into a 100 mL single-necked flask, add 50 mL 1,4-dioxane, stir, then add 1.5 mL (1.8 mmol, 18.0 equiv) of 12.0 mol / L hydrochloric acid, heat to 70°C, stir for 6 h, cool to room temperature, remove the solvent under reduced pressure, add 300 mL of dichloromethane to dissolve, and then extract and wash with water 3 times (200 mL*3). The organic phase is dried over anhydrous sodium sulfate, filtered, the filtrate is decompressed to remove the solvent, mixed with silica gel and loaded onto a column, and the sample is separated using a dichloromethane / methanol system (dichloromethane: methanol = (5-40): 1), and the eluent is combined and concentrated to obtain 277.8 mg of a red solid with a yield of 89.6%. The structural characterization data of the red solid are the same as in Example 1.

[0051] Comparative Example 1

[0052] Weigh 51.4 mg (0.1 mmol, 1.0 equiv) of the sodium tanshinone IIA sulfonate derivative shown in formula 1 into a 10 mL single-necked flask, add 5 mL of methanol, stir, then add 200 μL (0.36 mmol, 3.6 equiv) of 1.8 mol / L sulfuric acid, heat to 60 ° C, stir for 6 h, and take the reaction solution for HPLC detection, which basically shows 3-hydroxytanshinone IIA product without subsequent treatment.

[0053] Comparative Example 2

[0054] Weigh 51.4 mg (0.1 mmol, 1.0 equiv) of the sodium tanshinone IIA sulfonate derivative shown in formula 1 into a 10 mL single-necked flask, add 5 mL of ethanol, stir, then add 200 μL (0.36 mmol, 3.6 equiv) of 1.8 mol / L sulfuric acid, heat to 60 ° C, stir for 6 h, and take the reaction solution for HPLC detection. There is basically no 3-hydroxytanshinone IIA product, and no subsequent treatment is performed.

[0055] Comparative Example 3

[0056] 51.4 mg (0.1 mmol, 1.0 equiv) of the sodium tanshinone IIA sulfonate derivative shown in formula 1 was weighed into a 10 mL single-necked flask, 5 mL of 1,4-dioxane was added, and the mixture was stirred. Subsequently, 200 μL (0.36 mmol, 3.6 equiv) of 1.8 mol / L sulfuric acid was added and heated to 60 °C. The mixture was stirred for 6 h, and the reaction solution was taken for HPLC detection, which showed that the content of 3-hydroxytanshinone IIA product was 8.9%, and no subsequent treatment was performed.

[0057] Comparative Example 4

[0058] Weigh 51.4 mg (0.1 mmol, 1.0 equiv) of the sodium tanshinone IIA sulfonate derivative shown in formula 1 into a 10 mL single-necked flask, add 5 mL of tetrahydrofuran, stir, then add 200 μL (0.36 mmol, 3.6 equiv) of 1.8 mol / L sulfuric acid, heat to 60 ° C, stir for 6 h, and take the reaction solution for HPLC detection, which shows that the content of 3-hydroxytanshinone IIA product is 3.2%, and no subsequent treatment is performed.

[0059] Comparative Example 5

[0060] Weigh 51.4 mg (0.1 mmol, 1.0 equiv) of the sodium tanshinone IIA sulfonate derivative shown in formula 1 into a 10 mL single-necked flask, add 5 mL of dichloromethane, stir, then add 200 μL (0.36 mmol, 3.6 equiv) of 1.8 mol / L sulfuric acid, heat to 60 ° C, stir for 6 h, and take the reaction solution for HPLC detection. There is basically no 3-hydroxytanshinone IIA product, and no subsequent treatment is performed.

[0061] Comparative Example 6

[0062] 51.4 mg (0.1 mmol, 1.0 equiv) of the sodium tanshinone IIA sulfonate derivative shown in formula 1 was weighed into a 10 mL single-necked flask, 5 mL of acetonitrile was added, and the mixture was stirred. Subsequently, 200 μL (0.36 mmol, 3.6 equiv) of 1.8 mol / L sulfuric acid was added and heated to 60 °C. The mixture was stirred for 6 h, and the reaction solution was taken for HPLC detection, which showed that the content of 3-hydroxytanshinone IIA product was 5.2%, and no subsequent treatment was performed.

[0063] Comparative Example 7

[0064] Weigh 51.4 mg (0.1 mmol, 1.0 equiv) of the sodium tanshinone IIA sulfonate derivative shown in formula 1 into a 10 mL single-necked flask, add 5 mL of water, stir, then add 200 μL (0.36 mmol, 3.6 equiv) of 1.8 mol / L sulfuric acid, heat to 60 ° C, stir for 6 h, and take the reaction solution for HPLC detection. There is basically no 3-hydroxytanshinone IIA product, and no subsequent treatment is performed.

[0065] Comparative Example 8

[0066] Weigh 51.4 mg (0.1 mmol, 1.0 equiv) of the sodium tanshinone IIA sulfonate derivative shown in formula 1 into a 10 mL single-necked flask, add 5 mL of methanol, stir, then add 200 μL (0.36 mmol, 3.6 equiv) of 1.8 mol / L sulfuric acid, heat to 70 ° C, stir for 6 h, and take the reaction solution for HPLC detection, which basically shows 3-hydroxytanshinone IIA product without subsequent treatment.

[0067] Comparative Example 9

[0068] Weigh 51.4 mg (0.1 mmol, 1.0 equiv) of the sodium tanshinone IIA sulfonate derivative shown in formula 1 into a 10 mL single-necked flask, add 5 mL of methanol, stir, then add 200 μL (0.36 mmol, 3.6 equiv) of 1.8 mol / L hydrochloric acid, heat to 70 ° C, stir for 6 h, and take the reaction solution for HPLC detection, which basically shows 3-hydroxytanshinone IIA product without subsequent treatment.

[0069] Comparative Example 10

[0070] Weigh 51.4 mg (0.1 mmol, 1.0 equiv) of the sodium tanshinone IIA sulfonate derivative shown in formula 1 into a 10 mL single-necked flask, add 5 mL of acetonitrile and stir, then add 200 μL (0.36 mmol, 3.6 equiv) of 1.8 mol / L acetic acid and heat to 70 °C. Stir for 6 h, and take the reaction solution for HPLC detection. The product is basically 3-hydroxytanshinone IIA, and no subsequent treatment is performed.

[0071] Comparative Example 11

[0072] Weigh 51.4 mg (0.1 mmol, 1.0 equiv) of the sodium tanshinone IIA sulfonate derivative shown in formula 1 into a 10 mL single-necked flask, add 5 mL of acetonitrile and stir, then add 200 μL (0.36 mmol, 3.6 equiv) of 1.8 mol / L phosphoric acid and heat to 70 °C, stir for 6 h, and take the reaction solution for HPLC detection, which shows that the product is basically 3-hydroxytanshinone IIA, and no subsequent treatment is performed.

[0073] Comparative Example 12

[0074] 51.4 mg (0.1 mmol, 1.0 equiv) of the sodium tanshinone IIA sulfonate derivative shown in formula 1 was weighed into a 10 mL single-necked flask, 5 mL of acetonitrile was added, and the mixture was stirred. Subsequently, 62 mg (0.36 mmol, 3.6 equiv) of toluenesulfonic acid was added, and the mixture was heated to 70 °C and stirred for 6 h. The reaction solution was taken for HPLC detection, which showed that the content of 3-hydroxytanshinone IIA product was 12.5%, and no subsequent treatment was performed.

[0075] Comparative Example 13

[0076] Weigh 51.4 mg (0.1 mmol, 1.0 equiv) of sodium tanshinone IIA sulfonate derivative shown in formula 1 into a 10 mL single-necked flask, add 5 mL of water, stir, then add 40 μL (0.36 mmol, 3.6 equiv) of 9.0 mol / L sulfuric acid, heat to 70 ° C, stir for 6 h, and take the reaction solution for HPLC detection, which shows that the content of 3-hydroxytanshinone IIA product is 18.5%. After the reaction solution is cooled to room temperature, the solvent is removed under reduced pressure, 40 mL of dichloromethane is added to dissolve, and then extracted and washed with water twice (50 mL*2). Dry with anhydrous magnesium sulfate, filter, remove the solvent from the filtrate under reduced pressure, separate using a preparation plate (dichloromethane: methanol = 30:1), scrape the silica gel with the target product, soak it in dichloromethane, filter it by ultrasound, and combine the filtrates to obtain 4.9 mg of red solid, with a yield of 15.8% and a purity of 94.8%.

Claims

1. A method for preparing a compound as shown in formula II, characterized in that: It includes the following steps: In a solvent, in the presence of an acid, the sodium tanshinone IIA sulfonate derivative shown in formula I is subjected to the following reaction to obtain a compound shown in formula II; ； Among them, the carbon atoms marked with * are R configuration, S configuration, or a mixture of R configuration and S configuration; The molar ratio of the acid to the sodium tanshinone IIA sulfonate derivative shown in formula I is (12-25):

1.

2. The method for preparing the compound of formula II as claimed in claim 1, characterized in that: It meets one or more of the following conditions: (1) The sodium tanshinone IIA sulfonate derivative as shown in formula I is , the compound as shown in formula II is ; (2) The solvent is a nitrile and / or ether solvent; (3) The molar volume ratio of the sodium tanshinone IIA sulfonate derivative shown in formula I to the solvent is (0.005-0.2) mol / L; (4) The acid is an inorganic acid and / or an organic acid; (5) The molar ratio of the acid to the sodium tanshinone IIA sulfonate derivative of formula I is (15-20):1; (6) The reaction temperature is 60-80°C; (7) The reaction time of the reaction is 2-6 hours; The reaction materials of the reaction described in (8) are composed of the solvent, the acid and the sodium tanshinone IIA sulfonate derivative shown in formula I.

3. The method for preparing the compound of formula II as claimed in claim 2, characterized in that: It meets one or more of the following conditions: (1) The solvent is acetonitrile or 1,4-dioxane; (2) The molar volume ratio of the sodium tanshinone IIA sulfonate derivative shown in formula I to the solvent is (0.01-0.05) mol / L; (3) The acid is selected from one or more of sulfuric acid, hydrochloric acid and p-toluenesulfonic acid; (4) The molar ratio of the acid to the sodium tanshinone IIA sulfonate derivative of formula I is 18:1; The reaction temperature of (5) is 70°C.

4. The method for preparing the compound of formula II as claimed in claim 3, characterized in that: (1) The molar volume ratio of the sodium tanshinone IIA sulfonate derivative represented by formula I to the solvent is 0.02 mol / L or 0.04 mol / L; (2) the sulfuric acid participates in the reaction in the form of a 1-15 mol / L sulfuric acid aqueous solution; and (3) the hydrochloric acid participates in the reaction in the form of a 1-12 mol / L hydrochloric acid aqueous solution.

5. The method for preparing the compound of formula II as claimed in claim 1, characterized in that: It meets one or both of the following conditions: (1) The solvent is acetonitrile, the acid is p-toluenesulfonic acid or a 12.0 mol / L hydrochloric acid aqueous solution; the molar ratio of the acid to the sodium tanshinone IIA sulfonate derivative is 18:1; and (2) the solvent is 1,4-dioxane, the acid is a 12.0 mol / L aqueous hydrochloric acid solution or a 9.0 mol / L aqueous sulfuric acid solution; and the molar ratio of the acid to the sodium tanshinone IIA sulfonate derivative is 18:

1.

6. The method for preparing the compound of formula II as claimed in claim 1, characterized in that: The method for preparing the compound shown in Formula II comprises the following steps (a) and (b): (a) mixing the solvent and the sodium tanshinone IIA sulfonate derivative as shown in formula I to obtain a mixed solution; (b) mixing the acid with the mixed solution obtained in step (a), and reacting the mixture to obtain the compound shown in formula II.

7. A method for preparing a compound as shown in formula II as described in any one of claims 1 to 6, characterized in that: The reaction further comprises a post-treatment step, which comprises concentration, extraction, drying and purification.

8. The method for preparing the compound of formula II as claimed in claim 7, characterized in that: It meets one or more of the following conditions: (1) The concentration is vacuum distillation; (2) The extraction solvent is dichloromethane; (3) The drying agent is anhydrous sodium sulfate or anhydrous magnesium sulfate; and (4) the purification is performed by silica gel plate or silica gel column purification, and the eluent for the purification is a mixed solvent of dichloromethane and methanol.

9. The method for preparing the compound of formula II as claimed in claim 8, characterized in that: The purified eluent is a mixed solvent of dichloromethane and methanol, and the volume ratio of dichloromethane to methanol is (10-50):

1.

10. The method for preparing the compound of formula II as claimed in claim 9, characterized in that: The purified eluent is a mixed solvent of dichloromethane and methanol, and the volume ratio of dichloromethane to methanol is 30:1.

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