A method for the artificial synthesis of natural product Vestitain A and its analogues

Abstract

The application discloses an artificial synthesis method of natural product Vestitain A and analogs thereof, and belongs to the technical field of organic synthesis. In view of the technical defects that the existing Vestitain A can only be extracted from natural plants, is difficult to obtain, has extremely low yield and cannot be prepared on a large scale, a brand-new chemical synthesis route is provided, in which commercial and easily available chemical raw materials are used as starting materials, and through a plurality of organic synthesis reactions, the artificial synthesis of the natural product Vestitain A is realized for the first time; the structure of the synthetic product is completely consistent with that of the natural Vestitain A compound. The application also provides an artificial synthesis method of 4-CF3 and 3-F substituted analogs of Vestitain A. The synthesis route is reasonable in design, mild in reaction condition and simple and controllable in operation, provides a brand-new technical path for obtaining a large amount of Vestitain A and analogs thereof, and lays a material foundation for subsequent pharmacological research, structure modification and drug development of the compound.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for the artificial synthesis of Vestitain A and its analogues, a natural product with hypoglycemic activity. Background Technology

[0002] Vesitain A, a natural product, is a small molecule compound with significant hypoglycemic biological activity isolated from natural plants. Previous studies have confirmed that this compound has potential effects on blood glucose regulation and is an important lead compound for the development of antidiabetic drugs, possessing extremely high scientific research value and drug development prospects.

[0003] Currently, the acquisition of Vestitain A relies entirely on extraction and separation from natural plants. This method has several insurmountable drawbacks: First, Vestitain A is present in extremely low concentrations in natural plants, and the extraction and separation process is complex, costly, and difficult to obtain sufficient quantities of the compound. Second, natural plants have long growth cycles and limited resources, and large-scale extraction can damage the ecological environment. Third, naturally extracted products are easily affected by factors such as plant origin, growth cycle, and extraction process, making it difficult to control the purity and quality stability of the product. To date, there are no publicly reported methods for the artificial synthesis of Vestitain A globally, and the challenge of large-scale acquisition of this compound continues to hinder its subsequent pharmacological mechanism research, structural optimization, and drug development.

[0004] Therefore, developing a simple, mild, and stable method for the artificial synthesis of Vestitain A and its analogues, overcoming the technical limitations of natural extraction, is of great significance for promoting the in-depth research and development of this hypoglycemic active natural product. Summary of the Invention

[0005] In view of the shortcomings of the existing technology, the purpose of this invention is to provide a method for the artificial synthesis of natural product Vesitain A and its analogues, to solve the technical problems of scarce natural sources and difficulty in large-scale preparation, and to provide a stable and sufficient source of raw materials for the subsequent research of this compound.

[0006] To achieve the above objectives, the present invention employs the following synthetic route and method:

[0007] A method for the artificial synthesis of the natural product Vestitain A and its analogues includes the following steps: (1) Synthesis of compound 2: Compound 1 was used as the starting material. The solvent was added and stirred to dissolve the compound. Alkaline solution and phase transfer catalyst were added in sequence. The reaction was stirred at 0 ℃~60 ℃ for 4~24 h. The reaction process was monitored by thin layer chromatography. After the reaction was completed, compound 2 was obtained by extraction, concentration, drying and rapid silica gel column chromatography. (2) Synthesis of compound 3: Compound 2 was dissolved in a solvent, an alkaline solution was added, the temperature was raised to 25 ℃~45 ℃, and the reaction was stirred for 6~18 h. The reaction was monitored by thin-layer chromatography until the raw materials were completely consumed. After the reaction was completed, the mixture was cooled to room temperature, acidified, filtered, concentrated, and purified by rapid silica gel column chromatography to obtain compound 3. (3) Synthesis of compound 4: Compound 3 was dissolved in a solvent, and cis-vicinal diol chelating directing agent, acid-binding agent and acyl chloride were added. The stirring temperature was controlled at 0 ℃~40 ℃ and the reaction was stirred for 2~18 h. After the reaction was completed, a quenching agent was added to quench the reaction. The mixture was extracted, dried, concentrated and purified by rapid silica gel column chromatography to obtain compound 4. (4) Synthesis of natural product Vestitain A: Compound 4 was dissolved in a solvent, a catalyst and a nucleophilic scavenger were added, and the temperature was raised to 20 ℃~40 ℃ for 2~18 h to complete the deprotection. After the reaction was completed, the compound was extracted, dried, concentrated and purified by rapid silica gel column chromatography to obtain pure Vestitain A compound. (5) Synthesis of 4-CF3 substituted analogs of Vestitain A: Compound 3 was dissolved in a solvent, and cis-vicinal diol chelating directing agent, acid-binding agent and acyl chloride were added. The stirring temperature was controlled at 0 ℃~40 ℃, and the reaction was stirred for 2~18 h. After the reaction was completed, a quencher was added to quench the reaction. The mixture was extracted, dried, concentrated and purified by rapid silica gel column chromatography to obtain compound 6. (6) Synthesis of 3-F substituted analogues of Vestitain A: Compound 3 was dissolved in a solvent, and cis-vicinal diol chelating directing agent, acid-binding agent and acyl chloride were added. The stirring temperature was controlled at 0 ℃~40 ℃, and the reaction was stirred for 2~18 h. After the reaction was completed, a quencher was added to quench the reaction. The mixture was extracted, dried, concentrated and purified by rapid silica gel column chromatography to obtain compound 7. Further, the solvent in step (1) is one or more mixed solvents selected from tetrahydrofuran, dichloromethane, and chloroform, preferably dichloromethane; the alkaline solution is one of 1.0 M sodium hydroxide, 0.5 M potassium carbonate, and 0.25 M potassium carbonate, preferably 1.0 M sodium hydroxide solution; the phase transfer catalyst is one or more of tetrabutylammonium iodide (TBAI), tetrabutylammonium chloride (TBAC), and tetrabutylammonium bromide (TBAB), preferably TBAB; the molar ratio of 2,3,4,6-tetraacetoxy-alpha-D-glucopyranose bromide to glycosyl acceptor (i.e., compound 1) is (1.0~3.0):1.0.

[0008] Further, in step (2), the second solvent is one or more mixed solvents of tetrahydrofuran, methanol, ethanol, and water, preferably a mixed solvent of tetrahydrofuran, methanol, and water; the base is one or more of potassium carbonate, sodium carbonate, potassium hydroxide, and lithium hydroxide, preferably potassium carbonate; the molar ratio of compound 2 to the base is 1.0:(4.0~8.0).

[0009] Further, the solvent in step (3) is one or more of dichloromethane, chloroform, and tetrahydrofuran, preferably tetrahydrofuran; the cis-vicinal diol chelating directive is one or more of dibutyltin oxide, dibutyltin dichloride, and dimethyltin dichloride, preferably dimethyltin dichloride; the acid-binding agent is one or more of N,N-diisopropylethylamine (DIPEA), triethylamine (Et3N), and pyridine, preferably DIPEA; the molar ratio of compound 3, the cis-vicinal diol chelating directive, and the acid-binding agent is 1.0:(0.1~0.5):(1.0~3.0):(1.0~3.0).

[0010] Further, the solvent in step (4) is one or more of dichloromethane, chloroform, and tetrahydrofuran, preferably methanol; the catalyst is one of tetratriphenylphosphine palladium, palladium acetate, and bis(triphenylphosphine palladium), preferably tetratriphenylphosphine palladium; and the nucleophilic scavenger is morpholine.

[0011] Further, the solvent in step (5) is one or more of dichloromethane, chloroform, and tetrahydrofuran, preferably tetrahydrofuran; the cis-vicinal diol chelating directive is one or more of dibutyltin oxide, dibutyltin dichloride, and dimethyltin dichloride, preferably dimethyltin dichloride; the acid-binding agent is one or more of N,N-diisopropylethylamine (DIPEA), triethylamine (Et3N), and pyridine, preferably DIPEA; the molar ratio of compound 3, the cis-vicinal diol chelating directive, and the acid-binding agent is 1.0:(0.1~0.5):(1.0~3.0):(1.0~3.0).

[0012] Further, the solvent in step (6) is one or more of dichloromethane, chloroform, and tetrahydrofuran, preferably tetrahydrofuran; the cis-vicinal diol chelating directive is one or more of dibutyltin oxide, dibutyltin dichloride, and dimethyltin dichloride, preferably dimethyltin dichloride; the acid-binding agent is one or more of N,N-diisopropylethylamine (DIPEA), triethylamine (Et3N), and pyridine, preferably DIPEA; the molar ratio of compound 3, the cis-vicinal diol chelating directive, and the acid-binding agent is 1.0:(0.1~0.5):(1.0~3.0):(1.0~3.0).

[0013] The chemical structural formula of the acyl halide described in this invention is as follows:

[0014] Wherein, X is selected from Cl, Br, I, preferably Cl. When X is Cl, it is abbreviated as acyl chloride. Substituents on the benzene ring are defined as follows: Y is selected from H, F; Z is selected from H, allyloxy, trifluoromethyl (CF3); and simultaneously satisfy: (1) when Y=H, Z is allyloxy or CF3; (2) when Y=F, Z is H.

[0015] The beneficial effects of this invention are as follows:

[0016] (1) This invention is the first to realize the artificial synthesis of the natural product Vesitain A and its analogues, which completely breaks the limitation that the compound can only be extracted from nature, and has pioneering technical significance.

[0017] (2) The synthetic route of this invention is scientifically and simply designed. It adopts conventional organic synthesis reaction throughout the process. The reaction conditions are mild, the operation is simple and controllable, and no special precision equipment is required. All raw materials used are commercially available chemical raw materials, which are widely available and inexpensive. They are suitable for small-batch preparation in the laboratory and subsequent scale-up production. High-purity Vesitain A and its analogues can be obtained stably.

[0018] (3) The structure of the artificially synthesized Vestitain A compound of this invention is completely consistent with that of the naturally derived compound. It has high purity and stable quality and can be directly used as a standard and tool reagent for blood sugar-related scientific research. This provides a solid material basis for the subsequent exploration of the pharmacological mechanism, structural modification and transformation and anti-diabetic drug development of this compound. Detailed Implementation

[0019] The present invention will be further described in detail below with reference to specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0020] Synthesis of compound 2:

[0021] p-Hydroxybenzaldehyde (3.0 g, 24.57 mmol) was dissolved in 82 mL of dichloromethane solution. 2,3,4,6-Tetraacetoxy-alpha-D-glucopyranose bromide (15.2 g, 36.85 mmol) and TBAB (4.0 g, 12.28 mmol) were added sequentially with stirring at room temperature. The reaction was allowed to proceed for 15 min. Then, 82 mL of 1 M sodium hydroxide solution was slowly added dropwise at 0 °C, and the temperature was raised to 45 °C for 12 h. The reaction was quenched by adding 20 mL of H₂O at 0 °C. The mixture was extracted with dichloromethane solution, washed with saturated NaCl solution, dried over anhydrous Na₂SO₄, filtered, concentrated, and purified by rapid silica gel column chromatography to obtain compound 2 (5.29 g, 48%). 1 H NMR (400MHz, CDCl3) δ 9.92 (s, 1H), 7.88-7.83 (m, 2H), 7.09 (d, J = 8.0 Hz, 2H),5.32-5.30 (m, 2H), 5.22-5.15 (m, 2H), 4.28 (dd, J = 12.0, 4.0 Hz, 1H), 4.17(dd, J = 12.0, 4.0 Hz, 1H), 3.92 (ddd, J = 8.0, 5.6, 2.4 Hz, 1H), 2.06 (s,3H), 2.051 (s, 3H),2.05 (s, 3H), 2.04 (s, 3H); 13 C NMR (100 MHz, CDCl3) δ190.84, 170.62, 170.32, 169.51, 169.36, 161.34, 131.94, 116.88, 98.14, 72.64,72.41, 71.11, 68.22, 61.98, 20.78, 20.72; HRMS (ESI) calculated for C 21 H 24 NaO 11 [M + Na] + 475.1211 found 475.1214

[0022] Synthesis of compound 3:

[0023] Compound 2 (4.99 g, 10.83 mmol) was dissolved in a mixed solution of THF (49 mL), methanol (49 mL), and H2O (10 mL). Potassium carbonate (9.0 g, 64.98 mmol) was added at 0 °C, and the mixture was heated to 40 °C and reacted for 12 h. The reaction was quenched and acidified (pH 5-6) with 1 M dilute hydrochloric acid at 0 °C. The solution was concentrated and purified by rapid silica gel column chromatography to obtain compound 3 (2.69 g, 86%). 1 H NMR (400 MHz, DMSO-d6) δ 9.89 (s, 1H), 7.87 (d, J = 8.0 Hz, 2H), 7.20(d, J = 8.0 Hz, 2H), 5.41 (brs, 1H), 5.05 (d, J = 8.0 Hz, 1H), 4.58 (brs,1H), 3.69 (d, J = 12.0 Hz, 1H), 3.49-3.45 (m, 1H), 3.43-3.38 (m, 1H), 3.36(brs, 1H), 3.33-3.25 (m, 1H), 3.18 (t, J = 8.0 Hz, 1H); 13 HRMS (ESI) calculated for C 13 H 16 NaO7 [M + Na] + 307.0788 found 307.0790

[0024] Synthesis of compound 4:

[0025] Compound 3 (600 mg, 2.11 mmol) was dissolved in anhydrous THF (35 mL), and dimethyltin dichloride (49 mg, 0.21 mmol) was added at room temperature. The mixture was stirred at room temperature for 10 min, and then 10 mL of THF solutions of DIPEA (0.74 mL, 4.22 mmol) and acyl chloride (704 mg, 3.16 mmol) were added sequentially at 0 °C. The reaction was carried out at 25 °C for 12 h. The reaction was quenched with methanol at 0 °C, washed with 1 M HCl, concentrated, and purified by rapid silica gel column chromatography to obtain compound 4 (0.39 g, 31%). 1 H NMR (400MHz, DMSO-d6) δ 9.77 (s, 1H), 7.81 (d, J = 8.0 Hz, 2H), 7.65 (d, J = 8.0 Hz, 2H), 7.57 (d, J = 16.0 Hz, 1H), 7.20 (d, J = 8.0 Hz, 2H), 6.99 (d, J = 8.0Hz, 1H), 6.48 (d, J = 16.0 Hz, 1H), 6.09-6.00 (m, 1H), 5.52 (d, J = 4.0 Hz,1H), 5.43-5.40 (m, 1H), 5.38-5.36 (m, 1H), 5.30-5.26 (m, 2H), 5.14 (d, J =8.0 Hz, 1H), 4.63-4.60 (m, 2H), 4.44 (dd, J = 12.0, 4.0 Hz, 1H), 4.21 (dd, J = 12.0, 8.0 Hz, 1H), 3.80-3.75 (m, 1H), 3.35-3.31 (m, 2H), 3.31-3.24 (m, 1H); 13C NMR (100 MHz, DMSO-d6) δ 191.27, 166.30, 161.84, 160.12, 144.44, 133.37,131.58, 130.51, 130.17, 126.70, 117.75, 116.42, 115.27, 115.12, 99.42, 76.31,73.91, 73.07, 69.90, 68.33, 63.34; HRMS (ESI) calculated for C 25 H 26 NaO9 [M + Na] + 493.1469 found 493.1475

[0026] Synthesis of the natural product Vestitain A:

[0027] Under nitrogen protection, compound 4 (333 mg, 0.71 mmol) was dissolved in anhydrous methanol (7 mL), and morpholine (0.19 mL, 2.12 mmol) was added at room temperature. The mixture was stirred at room temperature for 5 min, and then tetrakis(triphenylphosphine)palladium (85 mg, 0.07 mmol) was added at room temperature. The mixture was heated to 30 °C and stirred for 12 h. The reaction was quenched by adding H₂O (10 mL) at 0 °C, extracted with dichloromethane solution, washed with saturated NaCl solution, dried over anhydrous Na₂SO₄, filtered, concentrated, and purified by rapid silica gel column chromatography to obtain the natural product Vesitain A (206 mg, 68%). 1 The H NMR data simultaneously observed the dominant pyran cyclic configuration signal and a small number of open-chain isomer characteristic signals, which is due to the naturally occurring pyran ring-open-chain tautomerism equilibrium in carbohydrate compounds in deuterated solvents. The coupling constants are averaged due to dynamic equilibrium, showing a reasonable deviation from literature data with a single fixed pyran ring configuration. The main signal is attributed to the target pyran cyclic structure; the weak signals of the few open-chain isomers are not individually assigned and analyzed due to their low content and severe peak overlap. 1 H NMR (600 MHz, DMSO-d6) δ 9.79 (s, 1H), 7.81 (d, J = 6.0 Hz, 2H), 7.50 (t, J = 12.0 Hz, 3H), 7.19 (d, J = 6.0 Hz, 2H), 6.81 (d, J = 12.0,2H), 6.34 (d, J = 12.0 Hz, 1H), 5.10 (d,J = 12.0 Hz, 1H), 4.45 (dd, J =12.0, 6.0 Hz, 1H), 4.20 (dd, J = 12.0, 6.0 Hz, 1H), 3.77-3.74 (m, 1H), 3.39-3.34 (m, 2H), 3.29-3.26 (m, 1H); 13 C NMR (100 MHz, DMSO-d6) δ 191.28, 166.40,161.83, 159.92, 144.88, 131.57, 130.50, 130.35, 125.02, 116.42, 115.83,114.01, 99.38, 76.32, 73.92, 73.06, 69.93, 63.27; HRMS (ESI) calculated forC 22 H 22 NaO9 [M + Na] + 453.1156 found 453.1164

[0028] Synthesis of compound 6:

[0029] Compound 3 (500 mg, 1.76 mmol) was dissolved in anhydrous THF (30 mL), and dimethyltin dichloride (39 mg, 0.18 mmol) was added at room temperature. The mixture was stirred at room temperature for 10 min, and then 10 mL of THF solutions of DIPEA (0.62 mL, 3.52 mmol) and acyl chloride (619 mg, 2.64 mmol) were added sequentially at 0 °C. The reaction was allowed to proceed for 12 h at room temperature. The reaction was quenched with methanol at 0 °C, washed with 1 M HCl, concentrated, and purified by rapid silica gel column chromatography to obtain compound 6 (0.38 g, 35%). 1 H NMR (400MHz, DMSO-d6) δ 9.77 (s, 1H), 7.93 (d, J = 8.0 Hz, 2H), 7.80 (d, J = 12.0 Hz, 2H), 7.77 (d, J = 8.0 Hz, 2H), 7.68 (d, J = 16.0 Hz, 2H), 7.19 (d, J = 12.0Hz, 2H), 6.81 (d, J= 16.0 Hz, 1H), 5.51 (brs, 1H), 5.40 (brs, 1H), 5.29(brs, 1H), 5.15 (d, J = 4.0 Hz, 1H), 4.46 (dd, J = 12.0, 4.0 Hz, 1H), 4.28(dd, J = 12.0, 4.0 Hz, 1H), 3.82-3.77 (m, 1H), 3.36 (t, J = 8.0 Hz, 2H),3.32-3.27 (m, 1H); 13 C NMR (100 MHz, DMSO-d6) δ 191.32, 165.74, 161.88,142.91, 138.05, 131.63, 130.59, 130.32, 130.00, 129.10, 125.85, 125.82,125.45, 122.75, 120.93, 116.48, 99.45, 76.37, 73.88, 73.13, 69.93, 63.76;HRMS (ESI) calculated for C 23 H 21 CF3NaO8 [M + Na] + 505.1081 found 505.1081

[0030] Synthesis of compound 7:

[0031] Compound 3 (500 mg, 1.76 mmol) was dissolved in anhydrous THF (30 mL), and dimethyltin dichloride (41 mg, 0.18 mmol) was added at room temperature. The mixture was stirred at room temperature for 10 min, and then 10 mL of THF solutions of DIPEA (0.62 mL, 3.52 mmol) and acyl chloride (487 mg, 2.64 mmol) were added sequentially at 0 °C. The reaction was allowed to proceed for 12 h at room temperature. The reaction was quenched with methanol at 0 °C, washed with 1 M HCl, concentrated, and purified by rapid silica gel column chromatography to obtain compound 7 (0.41 g, 53%). 1 H NMR (400MHz, DMSO-d6) δ 9.76 (s, 1H), 7.81 (d, J = 8.0 Hz, 2H), 7.64-7.59 (m, 2H),7.53 (d, J= 8.0 Hz, 1H), 7.49-7.43 (m, 1H), 7.26 (td, J = 8.0, 1.6 Hz, 1H), 7.19 (d, J = 8.0 Hz, 2H), 6.73 (d, J = 16.0 Hz, 1H), 5.44 (brs, 3H), 5.14 (d, J = 8.0 Hz, 1H), 4.45 (dd, J = 12.0, 4.0 Hz, 1H), 4.27 (dd, J = 12.0, 8.0 Hz,1H), 3.81-3.77 (m, 1H), 3.36 (t, J = 8.0 Hz, 2H), 3.32-3.26 (m, 1H); 13 C NMR(100 MHz, DMSO-d6) δ 191.29, 165.95, 163.79, 161.92, 161.36, 143.43, 136.65,136.57, 131.68, 131.06, 130.98, 130.61, HRMS(ESI) calculated for C 22 H 21 FNaO8 [M + Na] + 455.1113 found 455.1113

[0032] Finally, it should be noted that those skilled in the art can reasonably adjust the reaction conditions and reagent dosages during the actual preparation process according to the technical solution of this invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this invention should be included within the protection scope of this invention.

Claims

1. A method for the artificial synthesis of the natural product Vesitain A and its analogues, characterized in that, The compound has the structure of formula (I): The substituents on the benzene ring are defined as follows: R1 is selected from hydrogen (H) and fluorine (F); R2 is selected from H, hydroxyl (OH) and trifluoromethyl (CF3); and simultaneously satisfy the following: (1) when R1=H, R2 is OH or CF3; (2) when R1=F, R2 is H.

2. The method for artificially synthesizing the natural product Vesitain A and its analogues according to claim 1, characterized in that: R1=H, R2=OH, this compound is the natural product Vesitain A.

3. The method for artificially synthesizing the natural product Vesitain A and its analogues according to claim 1, characterized in that: R1=H, R2=CF3, this compound is a 4-CF3 substituted analog of Vesitain A.

4. The method for artificially synthesizing the natural product Vesitain A and its analogues according to claim 1, characterized in that: R1=F, R2=H, this compound is a 3-F substituted analog of Vesitain A.

5. The method for artificially synthesizing the natural product Vesitain A and its analogues according to claim 1, characterized in that, The synthetic route is as follows:

6. The method for artificially synthesizing the natural product Vesitain A and its analogues according to claim 1, characterized in that, Includes the following steps: (1) Starting from compound 1, compound 2 was obtained by glycosylation in the presence of solvent, alkaline solution and phase transfer catalyst. (2) Compound 2 was obtained by deprotection in the presence of solvent and base. (3) Compound 3 was obtained by highly selective esterification in the presence of solvent, cis-vicial diol chelating agent and acid trapping agent. (4) Compound 4 was obtained by deallylation in the presence of solvent, catalyst and nucleophilic trapping agent to obtain the natural product Vesitain A. (5) Compound 3 was obtained by highly selective esterification in the presence of solvent, cis-vicial diol chelating agent and acid trapping agent to obtain 4-CF3 substituted analog 6 of Vesitain A. (6) Compound 3 was obtained by highly selective esterification in the presence of solvent, cis-vicial diol chelating agent and acid trapping agent to obtain 3-F substituted analog 7 of Vesitain A.

7. The method for artificially synthesizing the natural product Vesitain A and its analogues according to claim 6, characterized in that, The solvent in step (1) is one or more of tetrahydrofuran, dichloromethane, and chloroform; the alkaline solution is one or more of 1.0 M sodium hydroxide, 0.5 M potassium carbonate, and 0.25 M potassium carbonate; the phase transfer catalyst is one or more of tetrabutylammonium iodide (TBAI), tetrabutylammonium chloride (TBAC), and tetrabutylammonium bromide (TBAB); the reaction temperature is 0 ℃~60 ℃, and the reaction time is 4~24 h.

8. A method for the artificial synthesis of the natural product Vesitain A and its analogues according to claim 6, characterized in that, The solvent in step (2) is one or more of tetrahydrofuran, methanol, ethanol, and water; the base is one or more of potassium carbonate, sodium carbonate, lithium hydroxide, and potassium hydroxide; the reaction temperature is 0 ℃~45 ℃, and the reaction time is 6~18 h.

9. A method for the artificial synthesis of the natural product Vesitain A and its analogues according to claim 6, characterized in that, The solvent in step (3) is one or more of dichloromethane, chloroform, and tetrahydrofuran; the cis-o-diol chelating directing agent is one or more of dibutyltin oxide, dibutyltin dichloride, and dimethyltin dichloride; the acid-binding agent is one or more of N,N-diisopropylethylamine (DIPEA), triethylamine (Et3N), and pyridine; the reaction temperature is 0 ℃~40℃, and the reaction time is 2~18 h.

10. A method for the artificial synthesis of the natural product Vestitain A and its analogues according to claim 6, characterized in that, The solvent in step (4) is one or more of methanol, ethanol, and tetrahydrofuran; the catalyst is one or more of tetratriphenylphosphine palladium, palladium acetate, and bistriphenylphosphine palladium dichloride; the reaction temperature is 0 ℃~40 ℃, and the reaction time is 2~18 h.

11. A method for the artificial synthesis of the natural product Vesitain A and its analogues according to claim 6, characterized in that, The solvent in step (5) is one or more of dichloromethane, chloroform, and tetrahydrofuran; the cis-o-diol chelating directing agent is one or more of dibutyltin oxide, dibutyltin dichloride, and dimethyltin dichloride; the acid-binding agent is one or more of N,N-diisopropylethylamine (DIPEA), triethylamine (Et3N), and pyridine; the reaction temperature is 0 ℃~40 ℃, and the reaction time is 2~18 h.

12. The method for artificially synthesizing the natural product Vesitain A and its analogues according to claim 6, characterized in that, The solvent in step (6) is one or more of dichloromethane, chloroform, and tetrahydrofuran; the cis-o-diol chelating directing agent is one or more of dibutyltin oxide, dibutyltin dichloride, and dimethyltin dichloride; the acid-binding agent is one or more of N,N-diisopropylethylamine (DIPEA), triethylamine (Et3N), and pyridine; the reaction temperature is 0 ℃~40 ℃, and the reaction time is 2~18 h.

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