Preparation method of natural product 5,6-Deoxywithaferin A

Abstract

The present invention discloses a method for preparing the natural product 5,6-Deoxywithaferin A, belonging to the technical field of preparing natural active ingredients from plants. Using the commercially available natural product withaferin A as a raw material, the present invention achieves efficient semi-synthetic conversion of the natural product 5,6-Deoxywithaferin A through only three reaction steps. Compared with existing technologies, the synthetic route is greatly simplified and the yield is significantly improved.

Description

Technical Field

[0001] The present invention relates to the preparation of natural active ingredients in plants, and in particular to a preparation method of the natural product 5,6-Deoxywithaferin A. Background Art

[0002] In 2008, nearly 7.6 million people died of cancer, accounting for about 13% of all deaths worldwide. In addition, the number of people who died of cancer is increasing and is expected to reach 11.5 million by 2030 (Int J Cancer, 2010, 127(12): 2893-917). Therefore, there is a constant demand for lead compounds that can serve as new anticancer drugs. Natural products are an important source of new anticancer drugs because of their diverse structures and good biological activities. Currently, natural products and their synthetic analogs are widely used as antitumor drugs, including paclitaxel, vinblastine and etoposide. Withanolides are a class of naturally occurring C-based ergotane-based compounds. 28 Steroidal compounds contain four rings, A, B, C, and D, within their molecules. Their primary structural characteristic is the ergostane side chain's C-26 carboxyl group interacting with the C-22 hydroxyl group to form a δ-lactone ring (Type A). A less common structure is the C-26 carboxyl group interacting with the C-23 hydroxyl group to form a γ-lactone ring (Type B). These lactone rings often have an α,β-unsaturated lactone structure, as shown in Types A and B below. Furthermore, C-1 is readily oxidized to a 1-keto group. Over 90% of these compounds are 1-oxosteroids. Withanolide compounds not only possess complex structural characteristics but also possess diverse biological activities and potential for drug development. The most widely studied activities are anti-tumor and anti-inflammatory. Other activities include hypoglycemic and hypolipidemic, immunomodulatory, anti-cognitive dysfunction, antioxidant, hepatoprotective, antibacterial / fungal and leishmanial activities (Nat Prod Rep, 2022, 39(4):784-813.; Nat Prod Rep, 2011, 28(4):705-40.).

[0003]

[0004] Withaferin A (WA) is the first withanolide component extracted by Lavie from the Indian medicinal plant Withaniasomnifera in 1965 (Journal of Organic Chemistry, 1965, 30 (6): 490-507), and its structure is shown in Formula 1 below. Both in vivo and in vitro studies have shown that WA has a wide range of pharmacological effects, such as anti-inflammatory, anti-tumor and anti-cancer chemoprevention, immunomodulation, chemotherapy sensitization, anti-herpes, anti-fibrosis, anti-platelet and fibrinolysis, anti-leishmaniasis, anti-adipogenesis, anti-pigmentation, healing, treatment of neurodegenerative diseases, etc. (Molecules, 2021, 26 (24): 7696.). Although a lot of research has been done on the potential anti-cancer properties of WA, there are few reports on its structural modification. In addition, 5,6-Deoxywithaferin A is also one of the natural components of withanolide, and its structure is shown in Formula 4 below. It has been reported that 5,6-Deoxywithaferin A has significant cytotoxic effects on a variety of cancer cell lines, including human pancreatic cancer cell PANC-1 (IC 50 :11.9μM), prostate cancer DU145 (IC 50 :10.6μM) and breast cancer cells MCF7 (IC 50 : 22.6μM), etc., but there are currently few total or semi-synthetic strategies for 5,6-Deoxywithaferin A. Many valuable trace components isolated by phytochemists can only meet the needs of structural identification and simple in vitro activity studies. The low content of natural products is the biggest obstacle restricting its systematic and in-depth research.

[0005]

[0006] The only existing method for synthesizing the natural product 5,6-deoxywithaferin A is a 10-step chemical reaction route reported by Ikekawa et al., which starts from a higher intermediate and obtains 5,6-deoxywithaferin A in extremely low total yield (Tetrahedron Letters, 1982. 23(45), 4725-4728). However, the synthetic route reported in this report is complex and the yield is too low. Summary of the Invention

[0007] The technical problem to be solved by the present invention is to provide a method for preparing the natural product 5,6-Deoxywithaferin A with a simple synthesis route and high yield.

[0008] In order to solve the above technical problems, the present invention adopts the following technical solutions:

[0009] The natural product 5,6-Deoxywithaferin A described in the present invention is a compound having a structure shown in the following formula 4, and its preparation method comprises the following steps:

[0010] 1) placing a compound represented by the following formula 1 in an organic solvent, adding an oxidizing agent to react, and obtaining a compound represented by the following formula 2;

[0011] 2) placing the compound of Formula 2 in an organic solvent, adding a first reducing agent to react, and obtaining a compound of Formula 3;

[0012] 3) placing the compound of formula 3 in an organic solvent, adding a second reducing agent to react, and obtaining a crude target compound;

[0013]

[0014]

[0015] In the preparation method of the present invention, the organic solvent can be one or a combination of two or more selected from dichloromethane (DCM), 1,2-dichloroethane (DCE), chloroform, chlorobenzene, acetonitrile, acetic acid, methanol, and ethanol. The amount of the organic solvent can be determined as needed to fully dissolve the raw materials involved in the reaction.

[0016] In step 1) of the preparation method of the present invention, the selection and dosage of the oxidant are the same as those in the prior art. Specifically, the oxidant can be one or a combination of two or more selected from hydrogen peroxide, sodium hypochlorite, hypochlorous acid, chromium trioxide, and manganese dioxide. Manganese dioxide is preferably used. The amount of the oxidant is generally used in excess relative to the compound represented by Formula 1, preferably 10 to 20 times the molar amount of the compound represented by Formula 1. In this step, the reaction is preferably carried out at room temperature, and completion of the reaction is monitored by thin-layer chromatography. When the reaction is carried out at room temperature, the reaction time is generally controlled to be 0.5 to 1 hour.

[0017] The crude product of the compound represented by Formula 2 is obtained in step 1). To improve its purity, it may be subjected to impurity removal and / or purification before being used to prepare the compound represented by Formula 3. Preferably, the resulting reaction material is first adsorbed on diatomaceous earth to remove excess oxidant, and then subjected to silica gel column chromatography to obtain the purified compound represented by Formula 2. The eluent used for elution during column chromatography is preferably a mixed solvent consisting of petroleum ether (PE) and ethyl acetate (EtOAc) (or dichloromethane and ethyl acetate) in a volume ratio of 5:1 to 1:1.

[0018] The first reducing agent and the second reducing agent involved in the preparation method of the present invention both refer to reducing agents, and the "first" and "second" are only used to distinguish the different reducing agents used in steps 2) and 3). In steps 2) and 3), the first reducing agent and the second reducing agent involved can both be conventional reducing agents in the prior art. Specifically, in step 2), the purpose of using the reducing agent is to convert the epoxy group on the compound of the structure shown in Formula 1 into a carbon-carbon double bond. Therefore, the first reducing agent is preferably selected from one or a combination of two or more of iodine, sodium iodide, zinc powder and trimethylsilyl chloride (TMSCl). The amount of the first reducing agent is usually used in excess relative to the compound of the structure shown in Formula 2, preferably 2 to 5 times the molar amount of the compound of the structure shown in Formula 2. When sodium iodide is selected as the first reducing agent, TMSCl is also preferably added, and the amount of TMSCl is preferably 1.5 to 2 times the molar amount of the compound of the structure shown in Formula 2. In step 3), the purpose of using a reducing agent is to reduce the carbonyl group on the compound of Formula 3 to a hydroxyl group. Therefore, the second reducing agent is preferably sodium borohydride, potassium borohydride, or lithium aluminum tetrahydride, preferably sodium borohydride. The amount of the second reducing agent is generally in excess relative to the compound of Formula 3, preferably 1.1 to 1.5 times the molar amount of the compound of Formula 3.

[0019] In step 2) of the preparation method of the present invention, the reaction can be carried out at room temperature, in an ice bath, or under heating conditions, typically at 50-70°C. Completion of the reaction is monitored by thin-layer chromatography. When the reaction is carried out at 0°C or room temperature, the reaction time is preferably controlled to be 2-3 hours.

[0020] The crude product of the structural compound shown in Formula 3 is prepared by the above step 1), which can be purified by existing conventional purification methods to improve the purity of the compound of Formula 3. Specifically, the crude product can be purified by silica gel column chromatography. It is more preferred to extract the material obtained by the reaction and then perform silica gel column chromatography to reduce the burden on the silica gel column. Among them, the eluent used for elution during column chromatography is preferably a mixed solvent consisting of petroleum ether and ethyl acetate (or dichloromethane and ethyl acetate) in a volume ratio of 5:1 to 1:1. If extraction is involved, the extraction agent is the same as the organic solvent used in the reaction, and can also be a conventional extraction agent such as ethyl acetate.

[0021] In step 3) of the preparation method of the present invention, a Lewis acid catalyst is preferably added before the reaction to prevent 1,4-reduction of the enone structure. The selection and dosage of the Lewis acid catalyst are the same as those in the prior art. Specifically, the Lewis acid catalyst may be AlCl3, BF3, SbCl5, FeBr3, FeCl3, SnCl4, TiCl4, ZnCl2, or CeCl3·7H2O, preferably CeCl3·7H2O. The dosage of the Lewis acid catalyst is preferably 1.1 to 2 times the molar amount of the compound represented by the structure of Formula 3. In this step, the reaction is preferably carried out at room temperature or in an ice bath, more preferably in an ice bath. When the reaction is carried out in an ice bath, the reaction time is preferably controlled to 20 to 30 minutes.

[0022] The above method produces a crude target compound. Therefore, the method of the present invention further includes a step of purifying the crude target compound. Specifically, conventional purification methods can be employed to improve the purity of the target compound. Purification is typically performed using silica gel column chromatography, and the eluent used during chromatography can be a mixed solvent of petroleum ether and ethyl acetate, or dichloromethane and ethyl acetate. In the mixed solvent, the volume ratio of petroleum ether to ethyl acetate, or dichloromethane to ethyl acetate, is preferably 5:1 to 1:1.

[0023] On the other hand, the present invention also provides a compound having a structure represented by the following formula 2 or 3 or a pharmaceutically acceptable salt thereof:

[0024]

[0025] In another aspect, the present invention also provides a method for preparing the compound of the structure shown in Formula 2 or 3, wherein:

[0026] The preparation method of the compound of the structure shown in Formula 2 is as follows: taking the compound of the structure shown in Formula 1 below, placing it in an organic solvent, adding an oxidizing agent to react, and obtaining the compound of the structure shown in Formula 2;

[0027] The preparation method of the compound of the structure shown in Formula 3 is as follows: taking the compound of the structure shown in Formula 2, placing it in an organic solvent, adding a first reducing agent to react, and obtaining the compound of the structure shown in Formula 3;

[0028]

[0029] In the preparation method of the structural compound represented by Formula 2 or 3, the selection and dosage of the organic solvent, oxidant, first reducing agent, and reaction parameters are the same as those in the preparation method of the aforementioned natural product 5,6-Deoxywithaferin A and will not be described in detail here.

[0030] The results of the applicant's preliminary in vitro activity screening test show that the compound represented by the structure of Formula 2 or 3 has good anti-tumor activity. Therefore, the present invention further includes the use of the compound represented by the structure of Formula 2 or 3 or its pharmaceutically acceptable salt in the preparation of anti-tumor drugs.

[0031] Furthermore, the present invention also includes a pharmaceutical composition comprising a therapeutically effective dose of a compound having a structure represented by the above formula 2 or 3. The dosage form of the drug can be any pharmaceutically acceptable dosage form, such as conventional dosage forms such as granules, tablets, pills, capsules or injections.

[0032] This invention uses the commercially available natural product withaferin A as a starting material and achieves an efficient semi-synthetic conversion of the natural product 5,6-Deoxywithaferin A through only three steps. Compared with existing technologies, the synthetic route is greatly simplified and the yield is significantly improved. Furthermore, the invention provides two novel withaferin A derivatives. The applicant's in vitro activity tests have shown that these derivatives have good anti-tumor activity and are promising for the treatment of cancer, with great potential medicinal value. DETAILED DESCRIPTION

[0033] In order to better explain the technical solution of the present invention, the present invention is further described in detail below with reference to examples, but the embodiments of the present invention are not limited thereto.

[0034] Example 1

[0035]

[0036] Synthesis conditions: (a): MnO2, DCM, rt, 0.5~1h; (b): NaI, TMSCl, Et3N, rt; (c): CeCl3·7H2O, NaBH4, MeOH, 0℃.

[0037] 1) 500.0 mg of the compound represented by Formula 1 (hereinafter referred to as Compound 1) (1.1 mmol, 1.0 equ.) and MnO2 (21.2 mmol, 20.0 equ.) were placed in a container, 25 mL of DCM was added, and the reaction was stirred at room temperature for 0.5 to 1 hour. The reaction was monitored by TLC. After the reaction was complete, the mixture was filtered through Celite to remove the remaining MnO2, concentrated in vacuo, and the resulting residue was purified by silica gel flash chromatography (eluent: PE / EtOAc, 5 / 1 to 1 / 1, volume ratio) to obtain the compound represented by Formula 2 (hereinafter referred to as Compound 2), which was characterized as follows:

[0038] Compound 2 (4-oxowithaferin A): yield 37.0%, light yellow solid; 1H NMR(600MHz,Chloroform-d)δ6.82–6.78(m,2H),4.38–4.26(m,3H),3.36(d,J=2.6Hz,1H),2.44(dd,J=17.8,13.3Hz,1H),2.10(dt,J=15.0,3.3Hz,1H),1. 98(s,3H),1.62–1.50(m,5H),1.42–1.37(m,2H),1.32(s,3H),1.22–1.16(m,4 H),1.13–1.04(m,3H),0.95(d,J=6.7Hz,3H),0.82–0.77(m,1H),0.66(s,3H); 13 CNMR(150MHz, CDCl3)δ201.13,192.86,165.98,151.79,140.59,138.15,124.70,77.67,62.94,62.51,56.45,54.57,51.06 ,48.85,42.64,41.65,38.41,37.74,29.51,28.80,28.61,26.17,23.23,22.44,19.00,18.17,12.32,10.77.HRMS(ESI):m / z calcd for C 28 H 37 O6 + [M+H] + :469.2585; found:469.2613.

[0039] 2) At 0°C, 184.0 mg of compound 2 (0.4 mmol, 1.0 equ.) was dissolved in 10 mL of DCM, and a DCM solution containing NaI (1.2 mmol, 3.0 equ.) and TMSCl (0.6 mmol, 1.5 equ.) was added. The ice bath was removed and the reaction was stirred at room temperature for 20 to 30 min. The reaction was monitored by TLC. After the reaction was complete, the reaction mixture was diluted with 10 mL of DCM and washed three times with saturated sodium thiosulfate solution. The organic phase was washed once with saturated brine, dried over anhydrous Na2SO4, filtered and concentrated. The resulting residue was purified by flash chromatography on silica gel (eluent: PE / EtOAc, 5 / 1 to 1 / 1, volume ratio) and filtered to obtain the compound of formula 3 (hereinafter referred to as compound 3), which was characterized as follows:

[0040] Compound 3 (5,6-deepoxy-5-enoyl withaferin A): yield 84.4%, light yellow solid; 1H NMR(600MHz,Chloroform-d)δ6.83(dd,J=5.8,2.3Hz,1H),6.74–6.66(m,2H),4.47–4.33(m,3H),2.52(dd,J=17.9,13.3Hz,1H),2.28(dt,J=19.8,5.4Hz,1H ),2.20(dd,J=13.4,3.6Hz,1H),2.05(s,3H),1.78–1.59(m,8H),1.39(s,3H), 1.21–1.10(m,4H),1.04(d,J=6.6Hz,3H),0.87(t,J=6.8Hz,2H),0.75(s,3H); 13 C NMR (150MHz, CDCl3) δ202.44,187.97,167.16,153.26,140.32,139.49,139.20,137.80,125.71,78.84,57.45,55.94,52.10 ,51.43,42.89,42.48,39.50,38.87,31.59,31.03,29.90,27.26,24.33,23.77,22.65,20.14,13.45,12.01.HRMS(ESI):m / z calcd for C 28 H 37 O5 + [M+H] + :453.2636; found:453.2642.

[0041] 3) Methanol (10 mL) was placed in a container, compound 3 (0.6 mmol, 1.0 equ.) and CeCl3·7H2O (0.9 mmol, 1.5 equ.) were added, and after stirring for 5 min, the reaction mixture was placed in an ice bath and NaBH4 (0.3 mmol, 1.1 equ.) was added. The reaction was stirred at 0°C for 20-30 min and monitored by TLC. After the reaction was complete, water and ethyl acetate were added and extracted three times (15 mL x 3). The combined organic phases were washed with saturated brine, dried over anhydrous Na2SO4, filtered, and concentrated. The resulting residue was purified by silica gel flash chromatography (eluent: PE / EtOAc, 5 / 1 to 1 / 1, volume ratio) to obtain the target compound (hereinafter referred to as compound 4), which was characterized as follows:

[0042] Compound 4 (5,6-Deoxywithaferin A): yield 79.7%, light yellow solid; 1H NMR(600MHz,Chloroform-d)δ6.76(dd,J=10.2,2.3Hz,1H),6.02(dt,J=6.6,2.0Hz,1H),5.88(dd,J=10.2 ,2.6Hz,1H),5.03(s,1H),4.44(dt,J=13.3,3.5Hz,1H),4.41–4.33(m,2H),2.55–2.48(m,1H),2.16(dd,J =13.6,3.6Hz,1H),2.05–2.03(m,3H),2.01(ddd,J=12.7,5.6,2.4Hz,3H),1.69–1.60(m,5H),1.38–1.33( m,2H),1.26(s,3H),1.25(s,2H),1.15(ddd,J=18.1,10.3,6.0Hz,3H),1.03(d,J=6.6Hz,3H),0.74(s,3H); 13 C NMR (150MHz, CDCl3) δ202.98,166.11,152.00,151.98,146.60,139.55,126.87,124.60,120.35,77.83,66.24,56.47,55.14 ,51.04,49.83,42.38,41.67,38.59,37.81,31.60,29.32,28.78,26.24,23.28,22.13,19.01,12.32,10.84.HRMS(ESI):m / z calcd for C 28 H 39 O5 + [M+

[0043] H] + :455.2792; found:455.2796.

[0044] Example 2

[0045] Repeat Example 1, except that:

[0046] In step 1), DCE is used instead of DCM, and hydrogen peroxide is used instead of manganese dioxide;

[0047] In step 2), chloroform was used instead of DCM, zinc powder was used instead of sodium iodide, and TMSCl was not added;

[0048] In step 3), acetic acid is used instead of methanol, and potassium borohydride is used instead of sodium borohydride.

[0049] Finally, a light yellow solid was obtained with a yield of 76%. Characterization confirmed that the obtained light yellow solid was the target compound 5,6-Deoxywithaferin A.

[0050] Example 3

[0051] Repeat Example 1, except that:

[0052] In step 1), methanol is used instead of DCM, and sodium hypochlorite is used instead of manganese dioxide;

[0053] In step 2), ethanol was used instead of DCM, periodine was used instead of sodium iodide, and TMSCl was not added;

[0054] In step 3), chlorobenzene is used instead of methanol.

[0055] Finally, a light yellow solid was obtained with a yield of 70%. Characterization confirmed that the obtained light yellow solid was the target compound 5,6-Deoxywithaferin A.

[0056] Example 4

[0057] Repeat Example 1, except that:

[0058] In steps 1) to 3), the organic solvent used is acetonitrile; in step 1), chromium trioxide is used instead of manganese dioxide; in step 2), the reaction is carried out at 70° C. and the reaction time is changed to 30 min.

[0059] Finally, a light yellow solid was obtained with a yield of 21%. Characterization confirmed that the obtained light yellow solid was the target compound 5,6-Deoxywithaferin A.

[0060] Example 5

[0061] Example 1 was repeated, except that CeCl 3 ·7H 2 O was not added in step 3).

[0062] Finally, a light yellow solid was obtained with a yield of 62%. Characterization confirmed that the obtained light yellow solid was the target compound 5,6-Deoxywithaferin A.

[0063] Example 6

[0064] Example 1 was repeated, except that TMSCl was not added in step 2).

[0065] Finally, a light yellow solid was obtained with a yield of 33%. Characterization confirmed that the obtained light yellow solid was the target compound 5,6-Deoxywithaferin A.

[0066] Experimental Example 1: Anti-cancer Activity Test of Compounds 2 to 4

[0067] The anti-tumor activity of compounds 2 to 4 was tested using the MTT colorimetric method, and cisplatin (DDP) was selected as a positive control drug.

[0068] Instruments: clean bench (SW-CJ-1FD, AIRTECH, Sujing Antai), constant temperature CO2 incubator (3111, Thermo, USA), inverted biological microscope (IX71, OLYMPUS, Japan), enzyme-linked immunosorbent assay (Mode1680, BIO-RAD, USA), plate shaker (Kylin-bell lab Instruments), high pressure sterilizer (YX0.SG41.280, Shanghai Huaxian), centrifuge (SIGMA).

[0069] Reagents: DMEM (GIBCO), fetal bovine serum (GIBCO), trypsin (SIGMA), DMSO (SIGMA).

[0070] Cell lines: Human colon cancer HCT-116 cells, human large cell lung cancer H460 cells, human osteosarcoma HOS cells, nasopharyngeal carcinoma 5-8F cells, breast cancer MCF-7 cells, and triple-negative breast cancer M231 cells were purchased from the Stem Cell Bank of the Chinese Academy of Sciences.

[0071] Cell culture: Resuscitate the frozen cell lines and culture them in a constant temperature 37℃ CO2 incubator. Change the medium once a day. When the cells are in the exponential growth phase and in good condition, plate them. Add 1ml of 0.25% trypsin digestion solution and digest for 1-2 minutes. Observe the cell state under a microscope. When the adherent cells become round and shrink, remove the digestion solution and add 1-2ml of DMEM medium containing 10% fetal bovine serum to make a cell suspension. Count the cells and use 5×10 cells per well. 4 The amount of cell suspension required was calculated based on the number of cells and the total number of wells, and the cell suspension was inoculated into a 96-well plate at 100 μl / well, sealed with PBS, and cultured in a constant temperature 37°C CO2 incubator for 24 h.

[0072] The anti-tumor activity was analyzed using the MTT method: the test drug, positive control DDP, and blank control DMSO were prepared with DMEM culture medium to a final concentration of 5 μM / well, with 3 replicates for each drug, and cultured for 48 hours. The MTT reagent was added to a 96-well plate at 10 μl / well and incubated for another 4 hours. The culture medium in the plate was aspirated, 100 μl DMSO was added to each well, and the plate was shaken on a shaker for 10 minutes to dissolve the crystals. The absorbance of each well was detected at a wavelength of 570 nm using an enzyme-linked immunosorbent assay (ELISA), and the cell inhibition rate was calculated according to the following formula. The average value of the three initial screening results was the final inhibition rate. Compounds with an initial screening inhibition rate greater than 60% were subjected to concentration gradient screening (5-fold dilution) to prepare for the calculation of the IC of the test drug.50 The results of three repeated experiments were the final IC values of the tested compounds. 50 value.

[0073] Statistical analysis: IC50 was performed using GraphPad Prism version 9.0 (GraphPad Software, San Diego, CA). Data are expressed as mean ± SD, and P < 0.05 was considered to indicate a significant difference.

[0074] Cell inhibition rate % = [(blank control OD value - drug group OD value) / blank control group OD value] × 100%

[0075] Results: The inhibition rates of the tested compounds were all greater than 50%, so IC 50 The test results are shown in Table 1 below.

[0076] Table 1. Inhibitory effects of target compounds 2, 3, and 4 on various cancer cell lines

[0077]

[0078] Note: a Each experiment was repeated three times, and the results were expressed as (mean ± SD).

[0079] b Data is expressed as IC 50 , that is, the concentration of compound that inhibits 50% of free radicals (mean±SD).

[0080] As can be seen from Table 1, the inhibitory activities of compounds 2 to 4 of the present invention against various cancer cell lines, with cisplatin (DDP) as the positive control drug, showed moderate to strong anti-cancer activities.

Claims

1. A method for preparing the natural product 5,6-Deoxywithaferin A having the structure shown in Formula 4, comprising the following steps: 1) placing a compound represented by the following formula 1 in an organic solvent, adding an oxidant to react, and obtaining a compound represented by the following formula 2; the oxidant is one or a combination of two or more selected from hydrogen peroxide, sodium hypochlorite, hypochlorous acid, chromium trioxide, and manganese dioxide; 2) placing the compound of Formula 2 in an organic solvent, adding a first reducing agent to react, and obtaining a compound of Formula 3; wherein the first reducing agent is a combination of sodium iodide and trimethylsilyl chloride; 3) placing the compound of Formula 3 in an organic solvent, adding a second reducing agent to react, and obtaining a crude target compound; the second reducing agent is sodium borohydride, potassium borohydride, or lithium aluminum tetrahydride; 、 、 、 。 2. The preparation method according to claim 1, wherein The organic solvent is one or a combination of two or more selected from the group consisting of dichloromethane, 1,2-dichloroethane, chloroform, chlorobenzene, acetonitrile, acetic acid, methanol and ethanol.

3. The preparation method according to claim 1 or 2, characterized in that: In step 3), a Lewis acid catalyst is added before the reaction.

4. The preparation method according to claim 1 or 2, characterized in that: The method also includes the step of purifying the obtained crude target compound.

5. A method for preparing a compound having a structure represented by the following formula 3, characterized in that: The compound represented by the following formula 1 is placed in an organic solvent, and an oxidant is added to react to obtain a compound represented by the following formula 2; The compound of formula 2 is placed in an organic solvent, and a first reducing agent is added to react to obtain a compound of formula 3; 、 、 ； The oxidant is one or a combination of two or more selected from hydrogen peroxide, sodium hypochlorite, hypochlorous acid, chromium trioxide and manganese dioxide; The first reducing agent is a combination of sodium iodide and trimethylchlorosilane.

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