A method for preparing a natural product embeloside A

Abstract

The application belongs to the technical field of pharmaceutical chemistry, and relates to a preparation method of a natural product embeloside A. The application takes 2,3,4,6-tetra-benzoyl-alpha-bromoglucose as raw material, and linear 4-step reaction is used to prepare the embeloside A. The application has the advantages of short reaction steps, high yield, mild reaction conditions, easy operation and good application development prospect.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of pharmaceutical chemistry, and relates to a preparation method of a natural product embeloside A. BACKGROUND

[0002] The information disclosed in this Background section is only for the purpose of increasing the understanding of the general background of the application and does not necessarily constitute an admission or a recognition that the information forms part of the prior art that is already known in any country in the world.

[0003] In recent years, on the one hand, with the continuous progress of separation technology and structural research means, people have isolated a large number of novel glycoside compounds from plants, and have elucidated their structures and biological activities; on the other hand, with the development of sugar chemistry, more and more new glycosylation methods and reagents have appeared, making it possible to synthesize complex glycosides. According to the research and understanding of the inventors, the mature and dried Embelia yunnanensis fruit contains a glycoside embeloside A in which the 6-position hydroxyl group of the sugar chain is acylated, and the glycoside has significant hypoglycemic effect.

[0004] However, up to now, embeloside A is mainly obtained from the extraction and separation of natural plants, and the amount of the target compound obtained by the extraction and separation is small, which is difficult to meet the needs. SUMMARY

[0005] In order to solve the problems of the prior art, the present application aims to provide a preparation method of a natural product embeloside A, which uses 2,3,4,6-tetra-benzoyl-alpha-bromoglucose as a starting material to prepare embeloside A, and has short synthesis steps, high yield and high product purity.

[0006] In order to achieve the above-mentioned purpose, the technical scheme of the present application is as follows:

[0007] A preparation method of a natural product embeloside A, comprising using 2,3,4,6-tetra-benzoyl-alpha-bromoglucose (raw material A) and a glycosylation acceptor (raw material B) as starting materials to obtain embeloside A according to the following reaction route:

[0008]

[0009] The present application first uses a hydroxyl-protected glucose derivative to perform glycosylation reaction with a glycosylation acceptor, then removes the protecting group, then performs selective esterification reaction of the 6-position hydroxyl group of the sugar ring with an acyl halide, and then removes the protecting group, so as to obtain embeloside A.

[0010] In the glycosylation reaction, generally, the full acetyl-β-glucose is selected as the raw material A for the glycosylation reaction, but the intermediate obtained from the raw material has a low yield, which is not conducive to the large-scale production of embeloside A. However, through further research, it is accidentally found that when the 2, 3, 4, 6-tetra-benzoyl-α-bromoglucose is selected as the raw material A, the yield of the intermediate can be greatly improved, thereby being conducive to improving the yield of embeloside A in the reaction route.

[0011] Meanwhile, after the selective esterification reaction, generally, the protecting groups need to be removed step by step due to the existence of two protecting groups; however, through experiments, it is found that when the silyl ether (TBDPS, tert-butyl diphenyl silyl) and naphthalene methylene (Nap) are used as the protecting groups, not only can the protecting groups be removed at the same time, but also the yield of embeloside A obtained after the simultaneous removal is higher, and the reaction route can be shortened, thereby further reducing the synthesis steps.

[0012] In some embodiments, the molar ratio of the 2, 3, 4, 6-tetra-benzoyl-α-bromoglucose to the glycosylation acceptor is 1-3:1.

[0013] In some embodiments, in the process of preparing the intermediate 1, a phase transfer catalyst is added in the two-phase solution of the organic solvent and the alkaline aqueous solution.

[0014] In one or more embodiments, in the process of preparing the intermediate 1, the organic solvent includes one or more of dichloromethane, trichloromethane or 1, 2-dichloroethane.

[0015] In one or more embodiments, in the process of preparing the intermediate 1, the alkaline aqueous solution is one or more of a potassium carbonate solution, a sodium carbonate solution, a potassium hydroxide solution and a sodium hydroxide solution. Specifically, the potassium carbonate solution is preferably a saturated potassium carbonate solution. Specifically, the sodium carbonate solution is preferably a saturated sodium carbonate solution. Specifically, the potassium hydroxide solution is preferably a potassium hydroxide solution with a concentration of 1.8-2.2 M (mol / L). Specifically, the sodium hydroxide solution is preferably a sodium hydroxide solution with a concentration of 1.8-2.2 M.

[0016] In one or more embodiments, in the process of preparing the intermediate 1, the phase transfer catalyst includes one or more of tetrabutylammonium bromide, polyethylene glycol or Tween 80.

[0017] In some embodiments, in the process of preparing the intermediate 2 from the intermediate 1, the process is performed under the condition of an alkaline catalyst.

[0018] In one or more embodiments, in the process of preparing the intermediate 2 from the intermediate 1, the alkaline catalyst includes one or more of potassium carbonate, sodium carbonate, sodium methoxide, sodium ethoxide, sodium hydroxide and potassium hydroxide.

[0019] In one or more embodiments, the molar ratio of intermediate 1 to the basic catalyst in the process of preparing intermediate 2 from intermediate 1 is 0.5-1:1.

[0020] In some embodiments, the solvent used in the process of preparing intermediate 2 from intermediate 1 is one or more of methanol, ethanol, tetrahydrofuran, acetonitrile, acetone, and water.

[0021] In some embodiments, the reaction time in the process of preparing intermediate 2 from intermediate 1 is 0.5-1.5 h.

[0022] In some embodiments, in the process of preparing intermediate 3 from intermediate 2, dimethyltin dichloride is used as the catalyst, and an acid-binding agent is added to selectively esterify the hydroxyl group at the 6-position of the sugar ring of the acyl halide with intermediate 2.

[0023] The chemical structural formula of the acyl halide is as follows:

[0024]

[0025] wherein X is selected from Cl, Br, and I, and is preferably Cl. When X is Cl, the acyl halide is referred to as acyl chloride.

[0026] In one or more embodiments, the molar ratio of intermediate 2 to the acid-binding agent in the process of preparing intermediate 3 from intermediate 2 is 1:1.0-5.0, and is further preferably 1:3.0.

[0027] In one or more embodiments, the acid-binding agent used in the process of preparing intermediate 3 from intermediate 2 is one or more of N,N-diisopropylethylamine, triethylamine, pyridine, and 1,8-diazabicyclo[5.4.0]undec-7-ene, and is preferably N,N-diisopropylethylamine.

[0028] In some embodiments, the solvent used in the process of preparing intermediate 3 from intermediate 2 is one or more of tetrahydrofuran, dichloromethane, and acetonitrile, and is preferably tetrahydrofuran.

[0029] In some embodiments, the catalyst used in the process of preparing embeloside A from intermediate 3 is trifluoroacetic acid and / or concentrated sulfuric acid. The concentrated sulfuric acid used in the present application is a sulfuric acid solution with a mass percentage of 70% or more, and is preferably a sulfuric acid solution with a mass percentage of 97.5-98.5%.

[0030] In some embodiments, the solvent used in the process of preparing embeloside A from intermediate 3 is one or more of toluene, tetrahydrofuran, and acetonitrile, and is preferably toluene. Research shows that toluene has higher reaction selectivity and higher embeloside A yield.

[0031] In some embodiments, the reaction time in the process of preparing the intermediate 3 for embeloside A is 2.5-5.0 h.

[0032] In some embodiments, the steps are:

[0033] a) dissolving 2,3,4,6-tetra-benzoyl-α-bromoglucose and glycosylated acceptor in an organic solvent, adding an alkaline aqueous solution and a phase transfer catalyst at room temperature, and reacting completely to prepare the intermediate 1;

[0034] b) dissolving the intermediate 1 in a solvent, adding an alkaline catalyst, and stirring to react at room temperature to prepare the intermediate 2;

[0035] c) performing selective esterification of the hydroxyl group at the 6-position of the sugar ring of the generated intermediate 2 with an acyl halide in the presence of a catalyst to obtain the intermediate 3;

[0036] d) removing the naphthalene methylene and silyl ether protective groups of the generated intermediate 3 simultaneously in the presence of a catalyst to obtain the natural product embeloside A.

[0037] The present application has the following beneficial effects:

[0038] The present application selects 2,3,4,6-tetra-benzoyl-α-bromoglucose as the glycosylation donor, which can effectively avoid the occurrence of side reactions in the glycosylation process; the present application selects the silyl ether and naphthalene methylene protective groups, which can be removed simultaneously using a catalyst, simplifying the reaction route and improving the yield.

[0039] The present application has the following beneficial effects: BRIEF DESCRIPTION OF DRAWINGS

[0040] The drawings constituting a part of the specification of the present application serve to provide a further understanding of the present application, and the illustrative embodiments of the present application and their descriptions serve to explain the present application, and do not constitute an improper limitation on the present application.

[0041] Figure 1 The figure is the nuclear magnetic resonance hydrogen spectrum (H-NMR) of the intermediate 1 prepared in Example 1; 1

[0042] Figure 2 The figure is the nuclear magnetic resonance carbon spectrum (C-NMR) of the intermediate 1 prepared in Example 1; 13

[0043] Figure 3 The figure is the nuclear magnetic resonance hydrogen spectrum (H-NMR) of the intermediate 2 prepared in Example 1; 1 ​​​

[0044] Figure 4 The carbon NMR spectrum of intermediate 2 prepared in Example 1 ( 13 C-NMR spectrum;

[0045] Figure 5 The proton NMR spectrum of intermediate 3 prepared in Example 1 ( 1 H-NMR spectrum;

[0046] Figure 6 The carbon NMR spectrum of intermediate 3 prepared in Example 1 ( 13 C-NMR spectrum;

[0047] Figure 7 The 1H NMR spectrum of embeloside A prepared in Example 1 ( 1 H-NMR spectrum;

[0048] Figure 8 The carbon NMR spectrum of embeloside A prepared in Example 1 ( 13 C-NMR spectrum. Detailed Implementation

[0049] To enable those skilled in the art to better understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with reference to specific embodiments and comparative examples.

[0050] Example 1

[0051] 1) Preparation of intermediate 1

[0052] In a 500 mL round-bottom flask, 4-((2-tert-butyldiphenylsiloxy)ethyl)phenol (5.64 g, 15.0 mmol) and 2,3,4,6-tetra-benzoyl-α-bromoglucose (18.09 g, 30.0 mmol) were dissolved in 100 mL of chloroform. A saturated potassium carbonate solution (100 mL) and a phase-transfer catalyst, tetrabutylammonium bromide (2.59 g, 7.5 mmol), were added with stirring at room temperature. After the addition was complete, the mixture was stirred at 45 °C for 18.0 h. TLC (V1) was then performed. 乙酸乙酯 :V 正己烷 =1:2) The reaction was checked to ensure completeness. After standing at room temperature, the mixture was separated, washed with saturated saline (150 mL) of organic phase, separated again, dried over anhydrous sodium sulfate, and concentrated by column chromatography to give intermediate 1, a white solid (9.71 g, 72%). The NMR spectrum is shown below. Figures 1-2 As shown: 1H NMR (600 MHz, CDC13) δ 8.01 (d, J = 7.9 Hz, 2H), 7.96 (d, J = 7.9 Hz, 2H), 7.93 (d, J = 7.9 Hz, 2H), 7.86 (d, J = 7.9 Hz, 2H), 7.56 (dd, J = 16.4, 7.5 Hz, 4H), 7.50 (t, J = 7.2 Hz, 3H), 7.44 (t, J = 7.4 Hz, 1H), 7.34 (m, 14H), 6.91 (q, J = 8.6 Hz, 4H), 5.98 (t, J = 9.6 Hz, 1H), 5.80 (m, 1H), 5.71 (t, J = 9.6 Hz, 1H), 5.34 (d, J = 7.8 Hz, 1H), 4.67 (dd, J = 12.0, 2.6 Hz, 1H), 4.53 (dd, J = 12.0, 6.6 Hz, 1H), 4.31 (ddd, J = 9.5, 6.6, 2.8 Hz, 1H), 3.75 (td, J = 10.1, 2.9 Hz, 2H), 2.75 (t, J = 6.9 Hz, 2H), 1.00 (s, 9H); 13 C NMR (150 MHz, CDC13) δ 166.04, 165.78, 165.26, 165.09, 155.49, 135.54, 135.52, 134.12, 133.75, 133.70, 133.55, 133.32, 133.19, 130.17, 129.89, 129.81, 129.76, 129.57, 129.56, 129.54, 129.13, 128.75, 128.67, 128.46, 128.41, 128.37, 128.34, 127.60, 127.59, 117.05, 99.97, 72.84, 72.53, 71.73, 69.69, 65.13, 63.23, 38.44, 26.81, 19.13.

[0053] 2) Preparation of intermediate 2

[0054] In a 250 mL round-bottom flask, intermediate 1 (8.99 g, 10.0 mmol) was dissolved in a solvent system of methanol (40 mL), tetrahydrofuran (40 mL), and purified water (8 mL), and anhydrous potassium carbonate (2.76 g, 20.0 mmol) was added under stirring at room temperature. After stirring at room temperature for 0.5 h, TLC (V 乙酸乙酯 ) detection showed that the reaction was complete. The reaction was terminated by slowly adding 3M HC1 (15 mL) dropwise, and extracted twice with ethyl acetate (100 mL), and the organic phase was washed with saturated brine (150 mL), separated, dried over anhydrous sodium sulfate, and concentrated for column chromatography to obtain intermediate 2 as a white solid (4.90 g, 91%); the nuclear magnetic resonance spectrum is as follows:Figures 3-4 As shown: 1 H NMR(600MHz,DMSO-d6)δ7.54(ddd,J=9.4,8.0,1.3Hz,4H),7.49-7.35(m,6H),7.08(d,J=8.6Hz,2H ),6.94(d,J=8.6Hz,2H),5.30(d,J=5.0Hz,1H),5.08(d,J=4.8Hz,1H),5.01(d,J=5.3Hz,1H),4.81( d,J=7.6Hz,1H),4.54(t,J=5.8Hz,1H),3.82-3.74(m,2H),3.70(ddd,J=11.7,5.2,1.9Hz,1H),3.48 (dt,J=11.9,6.0Hz,1H),3.34-3.21(m,3H),3.20-3.14(m,1H),2.77(t,J=6.7Hz,2H),0.97(s,9H); 13 C NMR(150MHz,DMSO-d6)δ155.99,135.03,133.13,133.11,132.02,129.88,129.79,127 .86,116.06,100.62,76.99,76.65,73.27,69.73,65.01,60.73,37.73,26.64,18.73.

[0055] 3) Preparation of intermediate 3

[0056] Intermediate 2 (1.62 g, 3.0 mmol) and dimethyltin dichloride (66.0 mg, 0.3 mmol) were dissolved in anhydrous tetrahydrofuran (40 mL) under nitrogen protection at room temperature. After stirring at room temperature for 10 min, N,N-diisopropylethylamine (1.2 mL, 6.0 mmol) was added at 0 °C, followed by the slow dropwise addition of anhydrous tetrahydrofuran (20 mL) solution of acyl chloride (1.92 g, 4.0 mmol). After the addition was complete, the ice bath was removed, and the mixture was stirred at room temperature for 1.5 h. The mixture was then analyzed by TLC (V0). 乙酸乙酯 The reaction was checked to ensure it was complete. The reaction was terminated by adding methanol (2 mL), and the reaction system was concentrated. Ethyl acetate (100 mL) was added to the residue, followed by washing with 3M HCl (50 mL) and saturated brine (50 mL) successively. The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure by column chromatography to give intermediate 3, a white solid (2.32 g, 79%). The NMR spectrum is shown below. Figures 5-6 As shown: 1H NMR (600 MHz, CDC13) δ 7.88 (s, 1H), 7.85 (s, 1H), 7.82-7.77 (m, 4H), 7.74-7.69 (m, 2H), 7.61 (d, J = 15.9 Hz, 1H), 7.58-7.55 (m, 2H), 7.54 (dd, J = 6.7, 1.1 Hz, 3H), 7.50 (d, J = 8.4 Hz, 1H), 7.48-7.41 (m, 4H), 7.37 (ddd, J = 7.2, 2.9, 1.2 Hz, 2H), 7.31 (td, J = 7.2, 3.3 Hz, 4H), 7.16 (d, J = 1.5 Hz, 1H), 7.01 (dd, J = 13.2, 4.9 Hz, 3H), 6.94 (d, J = 8.5 Hz, 2H), 6.90 (d, J = 8.4 Hz, 1H), 6.29 (d, J = 15.9 Hz, 1H), 5.27 (s, 4H), 4.92-4.81 (m, 1H), 4.71 (dd, J = 12.3, 4.0 Hz, 1H), 4.35 (d, J = 10.7 Hz, 1H), 3.84 (s, 1H), 3.75 (td, J = 9.9, 3.3 Hz, 2H), 3.72-3.68 (m, 2H), 3.60 (dd, J = 9.7, 2.4 Hz, 2H), 3.52 (d, J = 6.5 Hz, 1H), 3.07 (s, 1H), 2.73 (t, J = 6.7 Hz, 2H), 1.70 (s, 1H), 1.00 (d, J = 5.8 Hz, 9H); 13 C NMR (150 MHz, CDC13) δ 168.17, 155.51, 151.38, 149.01, 146.09, 135.54, 134.26, 134.12, 133.88, 133.75, 133.71, 133.27, 133.24, 133.07, 133.06, 130.27, 129.55, 128.38, 128.35, 128.02, 127.98, 127.72, 127.70, 127.61, 126.25, 126.22, 126.16, 126.10, 126.08, 126.02, 125.16, 124.95, 123.29, 116.74, 114.96, 114.19, 113.78, 101.12, 75.72, 74.47, 73.43, 71.40, 71.05, 69.57, 65.12, 62.92, 38.43, 26.81, 19.13.

[0057] 4) Preparation of embeloside A

[0058] Intermediate 3 (1.96 g, 2.0 mmol) was dissolved in trifluoroacetic acid (18.0 mL) and toluene (2.0 mL) in a 100 mL round bottom flask. After stirring at room temperature for 3.0 h, TLC (V 乙酸乙酯 ) indicated the reaction was complete. Column chromatography gave embeloside A (0.72 g, 78%) after concentration. The NMR spectra are shown in Figures 7-8 1 H NMR (600 MHz, DMSO-d6) δ 7.47 (d, J = 15.9 Hz, 1H), 7.06 (m, 3H), 6.99 (dd, J = 8.1, 1.5 Hz, 1H), 6.92 (d, J = 8.6 Hz, 2H), 6.77 (d, J = 8.1 Hz, 1H), 6.25 (d, J = 15.9 Hz, 1H), 4.84 (d, J = 7.3 Hz, 1H), 4.43 (m, 1H), 4.16 (dd, J = 119, 7.0 Hz, 1H), 3.64 (m, 1H), 3.50 (t, J = 7.1 Hz, 2H), 3.28 (m, 1H), 3.25 (m, 1H), 3.22 (m, 1H), 2.59 (t, J = 7.1 Hz, 2H); 13 C NMR (150 MHz, DMSO-d6) δ 166.30, 155.52, 148.63, 145.66, 145.21, 132.85, 129.58, 125.29, 121.33, 116.00, 115.74, 114.72, 113.67, 100.44, 76.39, 73.72, 73.15, 70.00, 63.33, 62.23, 38.11.

[0059] Example 2

[0060] In Example 1, Step 1), the feeding ratio of glycosyl donor 2,3,4,6-tetra- benzoyl-a-bromoglucose to glycosyl acceptor 4-((2-tert-butyldiphenylsiloxy)ethyl)phenol was changed to 1.5:1, and the organic solvent chloroform was replaced by dichloromethane. Other operations were the same as in Example 1. The yield of the corresponding product in this step was 68%.

[0061] Example 3

[0062] In Example 1, Step 1), the feeding ratio of glycosyl donor 2,3,4,6-tetra- benzoyl-a-bromoglucose to glycosyl acceptor 4-((2-tert-butyldiphenylsiloxy)ethyl)phenol was changed to 2.5:1, and saturated potassium carbonate solution was replaced by 2M hydroxide solution. Other operations were the same as in Example 1. The yield of the corresponding product in this step was 63%.

[0063] Example 4 ​

[0064] In step 2 of Example 1, the catalyst anhydrous potassium carbonate was replaced by sodium methoxide, the reaction solvent was selected as methanol, and other operations were the same as in Example 1. The yield of the corresponding product obtained in this step was 87%.

[0065] Example 5

[0066] In step 3 of Example 1, the solvent tetrahydrofuran was replaced by dichloromethane, and the acid-binding agent N,N-diisopropylethylamine was replaced by triethylamine. The yield of the corresponding product obtained in this step was 77%.

[0067] Example 6

[0068] In step 4 of Example 1, toluene was replaced by tetrahydrofuran, and other operations were the same as in Example 1. The yield of the corresponding product obtained in this step was 58%.

[0069] Comparative Example 1

[0070]

[0071] In a 500 mL round-bottom flask, 4-((2-tert-butyldiphenylsiloxy)ethyl)phenol (9.05 g, 24.07 mmol) and peracetyl-β-glucopyranose (14.05 g, 36.03 mmol) were dissolved in anhydrous dichloromethane (250 mL), and a solution of boron trifluoride etherate (5.90 mL, 48.08 mmol) was slowly added dropwise under ice bath. After the addition was completed, the ice bath was removed, and the mixture was stirred at room temperature for 9.0 h. TLC (V 乙酸乙酯 :V 正己烷 = 1:2) detection showed that the reaction was complete. Saturated sodium bicarbonate solution (250 mL) was slowly added dropwise to the reaction system, and the mixture was stirred at room temperature for 0.5 h. The organic phase was washed with saturated brine (250 mL), separated, dried over anhydrous sodium sulfate, concentrated, and column chromatography to obtain intermediate C white solid (7.98 g, 47%) and intermediate D white solid (2.15 g, 19%).

[0072] Comparative Example 2

[0073]

[0074] In a 250 mL round-bottom flask, intermediate 3 (1.96 g, 2.0 mmol) was dissolved in tetrahydrofuran (40 mL), and 1M tetrabutylammonium fluoride (4.0 mL, 4.0 mmol) was added under stirring at room temperature. After stirring at room temperature for 1.0 h, TLC (V 乙酸乙酯 ) detection showed that the reaction was complete. Column chromatography to obtain intermediate E white solid (1.20 g, 81%).

[0075] Intermediate E (1.11 g, 1.5 mmol) was dissolved in a mixture of dichloromethane (18 mL) and purified water (2 mL), and DDQ (0.68 g, 3.0 mmol) was added at room temperature. After the temperature of the reaction solution returned to room temperature, the reaction was continued for 6.0 hours. After the reaction was completed, the reaction solution was diluted with dichloromethane, and washed sequentially with 10% sodium thiosulfate solution and saturated sodium bicarbonate solution. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel column chromatography to obtain embeloside A (0.49 g, 71%).

[0076] The preferred embodiments of the present application have been described above with the purpose of not limiting the present application, and the present application can be variously changed and modified by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application should be included in the scope of the present application.

Claims

1. A method for preparing a natural product embeloside A, characterized by, comprising obtaining embeloside A from 2,3,4,6-tetra-benzoyl-alpha-bromoglucose and glycosyl acceptor as starting materials according to the following reaction route; 。 2. The method for preparing the natural product embeloside A as described in claim 1, characterized in that, The molar ratio of 2,3,4,6-tetra-benzoyl-alpha-bromoglucose to the glycosyl acceptor is 1-3:

1.

3. The method for preparing the natural product embeloside A as described in claim 1, characterized in that, In the process of preparing intermediate 1, a phase transfer catalyst is added in a two-phase solution of an organic solvent and an alkaline aqueous solution.

4. The method for preparing the natural product embeloside A as described in claim 3, characterized in that, In the process of preparing intermediate 1, the organic solvent is one or more of dichloromethane, chloroform or 1,2-dichloroethane.

5. The method for preparing the natural product embeloside A as described in claim 3, characterized in that, In the process of preparing intermediate 1, the alkaline aqueous solution is one or more of potassium carbonate solution, sodium carbonate solution, potassium hydroxide solution and sodium hydroxide solution.

6. The method for preparing the natural product embeloside A as described in claim 5, characterized in that, The potassium carbonate solution is a saturated potassium carbonate solution.

7. The method for preparing the natural product embeloside A as described in claim 5, characterized in that, The sodium carbonate solution is a saturated sodium carbonate solution.

8. The method for preparing the natural product embeloside A as described in claim 5, characterized in that, The potassium hydroxide solution has a concentration of 1.8-2.2 M.

9. The method for preparing the natural product embeloside A as described in claim 5, characterized in that, The sodium hydroxide solution has a concentration of 1.8-2.2 M.

10. The method for preparing the natural product embeloside A as described in claim 3, characterized in that, In the process of preparing intermediate 1, the phase transfer catalyst includes one or more of tetrabutylammonium bromide, polyethylene glycol or Tween 80.

11. The method for preparing the natural product embeloside A as described in claim 1, characterized in that, In the process of preparing intermediate 2 from intermediate 1, the reaction is carried out under the condition of an alkaline catalyst.

12. The method for preparing the natural product embeloside A as described in claim 11, characterized in that the intermediate... In the process of preparing intermediate 2, the alkaline catalyst includes one or more of potassium carbonate, sodium carbonate, sodium methoxide, sodium ethoxide, sodium hydroxide and potassium hydroxide.

13. The method for preparing the natural product embeloside A as described in claim 11, characterized in that, In the process of preparing intermediate 2 from intermediate 1, the molar ratio of intermediate 1 to the alkaline catalyst is 0.5-1:

1.

14. The method for preparing the natural product embeloside A as described in claim 1, characterized in that the intermediate... In the process of preparing intermediate 2, the solvent used is one or more of methanol, ethanol, tetrahydrofuran, acetonitrile, acetone and water. Alternatively, in the process of preparing intermediate 2, the reaction time is 0.5-1.5 h.

15. The method for preparing the natural product embeloside A as described in claim 1, characterized in that, In the process of preparing intermediate 3 from intermediate 2, dimethyltin dichloride is used as a catalyst, and an acid-binding agent is added to selectively esterify the acyl halide with the 6-position hydroxyl group of the sugar ring of intermediate 2.

16. The method for preparing the natural product embeloside A as described in claim 1, characterized in that, In the process of preparing intermediate 3 from intermediate 2, the molar ratio of intermediate 2 to the acid-binding agent is 1:1.0-5.

0.

17. The method for preparing the natural product embeloside A as described in claim 16, characterized in that, The molar ratio of intermediate 2 to the acid-binding agent is 1:3.

0.

18. The method for preparing the natural product embeloside A as described in claim 16, characterized in that the intermediate... In the process of preparing intermediate 3, the acid-binding agent is one or more of N,N-diisopropylethylamine, triethylamine, pyridine and 1,8-diazabicyclo[5.4.0]undec-7-ene.

19. The method for preparing the natural product embeloside A as described in claim 1, characterized in that, In the process of preparing intermediate 3 from intermediate 2, the solvent used is one or more of tetrahydrofuran, dichloromethane and acetonitrile.

20. The method for preparing the natural product embeloside A as described in claim 1, characterized in that, In the process of preparing embeloside A from intermediate 3, the catalyst used is trifluoroacetic acid and / or concentrated sulfuric acid.

21. The method for preparing the natural product embeloside A as described in claim 1, characterized in that, In the process of preparing embeloside A from intermediate 3, the solvent used is one or more of toluene, tetrahydrofuran and acetonitrile. Alternatively, in the process of preparing embeloside A from intermediate 3, the reaction time is 2.5-5.0 h.

22. The method of claim 1, wherein the step of To ： a) 2,3,4,6-tetra-benzoyl-alpha-bromoglucose and a glycosyl acceptor are dissolved in an organic solvent, an alkaline aqueous solution and a phase transfer catalyst are added at room temperature, and intermediate 1 is prepared after the reaction is completed; b) dissolving the intermediate 1 in a solvent, adding a basic catalyst, stirring the reaction at room temperature to produce the intermediate 2; c) subjecting the generated intermediate 2 to a selective esterification reaction of the 6-position hydroxyl group of the sugar ring in the presence of a catalyst to produce the intermediate 3; d) removing the naphthalene methylene and the silyl ether protecting groups from the generated intermediate 3 at the same time in the presence of a catalyst to produce the natural product embeloside A.

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