A method for synthesizing natural products asperones A and B

Abstract

The application relates to the technical field of synthetic chemistry, in particular to a synthetic method of natural products asperones A and B. The key to solving the problem of the application is that: 1. A simple synthesis route of two fragments of the natural product is designed and realized; and 2. Efficient reaction conditions of a key [5+2] cycloaddition reaction for synthesizing the natural product are found, so that synthesis of the natural product and analogs thereof is realized.

Description

Technical Field

[0001] This invention relates to the field of synthetic chemistry, specifically to a method for synthesizing natural products asperones A and B. Background Technology

[0002] Fungal secondary metabolites are among the most attractive natural product sources for the pharmaceutical industry. Their unique structures and potential biological activities inspire chemists and pharmacologists, and stimulate the development of new drugs. Asperone A and B are derived from... Aspergillus A polyketide natural product isolated from sp. has certain antibacterial activity (MIC). 50 = 71.6 μg / mL), which can serve as an important source for further structural modification and activity studies. However, the current method for isolating asperone A and B from plants is inefficient, complex, and difficult to obtain in large quantities for subsequent modification and improvement studies. Therefore, rapid and efficient chemical synthesis for large-scale preparation has become an important means to solve this problem. However, no total synthetic route for asperone A and B has been reported yet, so developing an efficient and concise synthetic route is of great significance. Summary of the Invention

[0003] In view of this, the present invention provides an efficient and economical method for synthesizing polyketide compounds asperones A and B, which has advantages such as low cost, short production cycle, and high production efficiency. To achieve the above objectives, the present invention adopts the following technical solution: A method for synthesizing polyketide compounds asperones A and B, wherein the structural formulas of compounds asperones A and B are as follows: , ; The synthesis path is as follows: Segment 5: Segment 14: Asperones A and B: The specific steps are as follows: (1) Compound 1 was dissolved in anhydrous dichloromethane, and then AlCl(S,S), triphenylphosphine oxide, and tert-butyl triphenylphosphoacetate were added at -30°C. After equilibration for 30 minutes, trimethylcyanosilane was added and stirred at this temperature for 36 hours. The crude product was then concentrated under vacuum to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain compound 2.

[0004] (2) Compound 2 was dissolved in anhydrous diethyl ether, and then diisobutylaluminum hydride was added at -30°C and reacted at this temperature for 30 minutes. The reaction was quenched by adding methanol to the reaction system, followed by adding Roche salt and stirring vigorously until both phases were clear. The mixture was then extracted with ethyl acetate, the organic phases were combined, washed three times with 1 mol / L dilute hydrochloric acid, dried over anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain compound 3.

[0005] (3) Dissolve tert-butyl diazonyl acetate in anhydrous dichloromethane, then add tin dichloride at room temperature. Once the system no longer generates gas and becomes a milky white suspension, add compound 3 and react overnight at room temperature. After the reaction is complete, quench with water, then extract with ethyl acetate. Combine the organic phases, dry with anhydrous sodium sulfate, filter under reduced pressure, and concentrate under reduced pressure to obtain the crude product. The crude product is purified by silica gel column chromatography to obtain compound 4.

[0006] (4) Compound 4 was dissolved in anhydrous tetrahydrofuran, and then sodium hydride was added in an ice bath. After no more bubbles were released, compound 6 was added and reacted at this temperature for one hour. Then tetrabutylammonium fluoride was added and reacted for two hours. Then ammonium chloride solution was added to quench the reaction. Then the mixture was extracted with ethyl acetate, the organic phases were combined, dried with anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under reduced pressure under vacuum to obtain crude product. The crude product was purified by silica gel column chromatography to obtain compound 5.

[0007] (5) Triphenylphosphine was dissolved in anhydrous dichloromethane and carbon tetrabromide was added at 0 degrees Celsius. The reaction system changed from yellow to red. Then, compound 6 was added rapidly at the same temperature. After reacting for 30 minutes, the reaction was quenched with water and then extracted with ethyl acetate. The organic phases were combined, dried with anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under reduced pressure under vacuum to obtain crude product. The crude product was purified by silica gel column chromatography to obtain compound 7.

[0008] (6) Compound 7 was dissolved in anhydrous tetrahydrofuran, and n-butyllithium was added at -78°C. After reacting for 30 minutes, the temperature was raised to room temperature and the reaction was continued for 30 minutes. The temperature was then lowered to -78°C again, and n-butyllithium was added. After equilibration for 15 minutes, methyl chloroformate was slowly added. The temperature was then raised to 0°C and the reaction was carried out for 1 hour. The reaction was quenched with water and then extracted with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain compound 8.

[0009] (7) Compound 8 was dissolved in anhydrous tetrahydrofuran, and tetrabutylammonium fluoride was added at room temperature. After reacting for 30 minutes, the reaction was quenched with saturated ammonium chloride solution, and then extracted with ethyl acetate. The organic phases were combined, dried with anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under reduced pressure under vacuum to obtain crude product. The crude product was purified by silica gel column chromatography to obtain compound 9.

[0010] (8) Compound 9 was dissolved in anhydrous dichloromethane, and diisopropylethylamine was added at room temperature, followed by chloromethyl methyl ether. The reaction was carried out overnight at room temperature, and the reaction was quenched with saturated ammonium chloride solution. The mixture was then extracted with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under reduced pressure to obtain crude product. The crude product was purified by silica gel column chromatography to obtain compound 10.

[0011] (9) Compound 10 and cyclodiene were directly mixed and heated at 180 degrees for two days. The product was then stirred and mixed with silica gel. After standing for two hours, compound 11 was purified by silica gel column chromatography.

[0012] (10) Compound 11 was dissolved in anhydrous dichloromethane, and triethylamine was added at 0 degrees Celsius, followed by tert-butyldimethylsilyltrifluoromethanesulfonate. After reacting for 30 minutes, the reaction was quenched with saturated ammonium chloride solution, and then extracted with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under reduced pressure under vacuum to obtain crude product. The crude product was purified by silica gel column chromatography to obtain compound 12.

[0013] (11) Compound 12 was dissolved in anhydrous dichloromethane, and diisobutylaluminum hydride was added at 0 degrees Celsius. The reaction was carried out for one hour, and then the reaction was quenched with 1 mol / L hydrochloric acid aqueous solution. The mixture was then extracted with ethyl acetate, the organic phases were combined, dried with anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under vacuum to obtain crude product. The crude product was purified by silica gel column chromatography to obtain compound 13.

[0014] (12) Compound 13 was dissolved in anhydrous dichloromethane, and triethylsilane was added at 0 degrees Celsius, followed by boron trifluoride diethyl ether. After reacting for one hour, the reaction was quenched with water, and then extracted with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under reduced pressure to obtain crude product. The crude product was purified by silica gel column chromatography to obtain compound 14.

[0015] (13) Compound 14 was dissolved in anhydrous tetrahydrofuran, and tetrabutylammonium fluoride was added at 0 degrees Celsius. After reacting for one hour, the reaction was quenched with 1 mol / L hydrochloric acid aqueous solution, and then extracted with ethyl acetate. The organic phases were combined, dried with anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under reduced pressure under vacuum to obtain crude product. The crude product was purified by silica gel column chromatography to obtain compound 15.

[0016] (14) Compound 15 was dissolved in a mixed solution of acetone and water in a ratio of 1:1. Disodium hydrogen phosphate was added at room temperature, followed by Fermi salt. The reaction was carried out at room temperature for three hours. The reaction was quenched with 1 mol / L hydrochloric acid aqueous solution, and then extracted with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under reduced pressure to obtain crude product. The crude product was purified by silica gel column chromatography to obtain compound 16.

[0017] (15) Compound 16 and compound 5 were dissolved in dimethyl sulfoxide, compound 17 was added at room temperature, and the reaction was carried out at 30 degrees for two hours. The reaction was quenched with 1 mol / L hydrochloric acid aqueous solution, and then extracted with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under reduced pressure to obtain crude product. The crude product was purified by silica gel column chromatography to obtain compounds 18 and 19.

[0018] (16) Compound 18 was dissolved in acetonitrile, and hydrofluoric acid aqueous solution was added at room temperature. After reacting for ten minutes, the reaction was quenched with 1 mol / L hydrochloric acid aqueous solution, and then extracted with ethyl acetate. The organic phases were combined, dried with anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under reduced pressure under vacuum to obtain crude product. The crude product was purified by silica gel column chromatography to obtain asperone A.

[0019] (17) Compound 19 was dissolved in acetonitrile, and hydrofluoric acid aqueous solution was added at room temperature. After reacting for ten minutes, the reaction was quenched with 1 mol / L hydrochloric acid aqueous solution, and then extracted with ethyl acetate. The organic phases were combined, dried with anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under reduced pressure under vacuum to obtain crude product. The crude product was purified by silica gel column chromatography to obtain asperone B.

[0020] The advantages of this invention are: 1. Most of the reagents used in this invention are commercially available. The chiral ligands to be synthesized are widely available, inexpensive, and stable at room temperature and pressure. They are easy to handle and require no special treatment.

[0021] 2. The present invention can obtain optically pure products, and the post-processing is simple and convenient, avoiding the previous method that required chiral separation to obtain chiral products, and greatly reducing the product separation cost.

[0022] 3. The catalyst used in this invention is inexpensive and requires low amounts of metals and ligands. While maintaining good catalytic effect and reducing costs, it also facilitates post-processing and reduces environmental pollution.

[0023] 4. The reaction of this invention is completely atom-economical, meets the requirements of green chemistry, and will not produce other by-products in large-scale production, thus achieving the requirements of simplifying the process, reducing costs, and reducing environmental pollution. Attached Figure Description

[0024] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the provided drawings without creative effort.

[0025] Figure 1 The attached figure shows the hydrogen spectrum of compound 4 prepared in this invention; Figure 2 The attached figure shows the carbon spectrum of compound 4 prepared in this invention; Figure 3 The attached figure shows the hydrogen spectrum of compound 5 prepared in this invention; Figure 4 The attached figure shows the carbon spectrum of the compound prepared in this invention (carbon 5); Figure 5 The attached figure is the proton NMR spectrum of compound 11 prepared in this invention; Figure 6 The attached figure shows the carbon spectrum of compound 11 prepared in this invention; Figure 7 The attached figure shows the hydrogen spectrum of compound 18 prepared in this invention; Figure 8 The attached figure shows the 18-carbon spectrum of the compound prepared in this invention; Figure 9 The attached figure is the proton NMR spectrum of compound 19 prepared in this invention; Figure 10 The attached figure shows the carbon spectrum of compound 19 prepared in this invention. Detailed Implementation

[0026] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0027] Example 1 Example 1 of this invention provides a method for synthesizing compound 4 used in this invention, as detailed below: At 0°C, tin dichloride (203.5 mg, 1.1 mmol) was added to a stirred solution of tert-butyl diazonate (3.1 g, 21.5 mmol) in dichloromethane (10.0 mL). After the mixture no longer produced gas, a solution of compound 3 (2.4 g, 10.7 mmol) in dichloromethane (10.0 mL) was added at 0°C, and the mixture was stirred at room temperature for 12 hours. The mixture was then quenched with water (10.0 mL) and extracted with ethyl acetate (100.0 mL × 3). The combined organic phases were washed with brine (300.0 mL) and dried over anhydrous sodium sulfate. The solvent was evaporated under vacuum (150 mbar), and the crude product was purified by rapid column chromatography (silica gel, petroleum ether: ethyl acetate = 20:1) to give compound 4 (2.9 g, 79% yield) as a colorless oil.

[0028] The detection data for compound 4 are as follows: 4: R f = 0.7 (silica, PE: EtOAc = 20:1); [α]20 D = + 40.14 ( c = 0.4 inCHCl3); IR (film): ν max = 3438, 2978, 2936, 1733, 1323, 1042, 977; 1 H NMR (400MHz, CDCl3): δ 6.3 (dd, J = 15.2, 10.4 Hz, 1H), 6.0 (m, 1H), 5.8 (d, J = 15.2 Hz, 1H), 5.5 (d, J = 15.2 Hz, 1H), 3.6 (d, J = 15.9 Hz, 1H), 3.5 (d, J = 15.9 Hz, 1H), 2.1 (t, J = 7.3 Hz, 2H), 1.5 (s, 3H), 1.4 (s, 9H), 1.0 (t, J = 7.5 Hz, 3H), 0.2(s, 9H). 13C NMR (101 MHz, CDCl3): δ 205.5, 167.2, 138.3, 132.1, 131.5, 128.3,82.6, 81.5, 45.1, 28.2, 25.8, 24.4, 13.5, 2.3; HRMS (m / z): [M+Na] + calcd forC 18 H 32 SiO4Na + 363.1962 found 363.1965. Example 2 Example 2 of this invention provides a method for synthesizing compound 5 used in this invention, as detailed below: Sodium hydride (30.7 mg, 1.3 mmol) was added to a stirred solution of compound 4 (290.0 mg, 0.9 mmol) in tetrahydrofuran (4.2 mL) at 0°C. After the mixture no longer produced gas, a solution of compound 6 (220.0 mg, 1.3 mmol) in tetrahydrofuran (0.5 mL) was added at 0°C, and the mixture was stirred at room temperature for 2 hours. Then, tetrabutylammonium fluoride (670.0 mg, 2.6 mmol, 1 mol / L tetrahydrofuran solution) was added at 0°C, and the mixture was stirred at room temperature for 1 hour. Before quenching with 1N HCl (10.0 mL), tetrabutylammonium fluoride (670.0 mg, 2.6 mmol, 1 N tetrahydrofuran solution) was added to the mixture again at 0°C, and the mixture was extracted with ethyl acetate (10.0 mL × 3). The combined organic phases were washed with brine (30.0 mL) and dried over anhydrous sodium sulfate. The solvent was evaporated under vacuum (150 mbar), and the crude product was purified by rapid column chromatography (silica gel, petroleum ether: ethyl acetate = 5:1) to give compound 5 (160.0 mg, 60%) as a colorless oil.

[0029] The detection data for compound 5 are as follows: 5: R f = 0.6 (silica, PE: EtOAc = 5:1); [α]20 D =-153.16 (c = 0.5 inCHCl3); IR (film): ν max = 3424, 2975, 2874, 1718, 1323, 1049, 990; 1 H NMR (400MHz, CDCl3): δ 7.39 – 7.22(m, 1H), 7.14 (dq, J= 15.8, 6.8 Hz, 1H), 6.25 (dd, J =15.4, 10.3 Hz, 1H), 5.96 (dd, J = 15.3, 10.3 Hz, 1H), 5.79 (dt, J = 15.1, 6.5 Hz, 1H), 5.55 (d, J = 15.4 Hz, 1H), 2.09 (d, J = 7.3 Hz, 1H), 2.07 – 1.98 (m, 2H), 1.54 (s, 9H), 1.51 (s, 3H), 0.98 (t, J = 7.4 Hz, 3H). 13 C NMR (101 MHz, CDCl3): δ 198.8, 184.4, 162.3, 143.8, 139.1, 131.2, 128.0, 126.8, 121.2, 105.1, 90.0,81.5, 28.4, 25.8, 22.6, 19.5, 13.5; HRMS (m / z): [M+Na] + calcd for C 19 H 26 O4Na + 341.1723 found 341.1730 Example 3 This embodiment provides a method for synthesizing compound 11 used in this invention, as detailed below: Compound 10 (360.0 mg, 1.8 mmol) was directly mixed with cyclopentadiene (2.1 g, 7.2 mmol) and heated at 180 °C for two days. The resulting mixture was mixed with silica gel (5.0 g) and allowed to stand for 1 hour. The crude product was then purified by rapid column chromatography (silica gel, petroleum ether: ethyl acetate = 5:1) to give compound 11 (485.0 mg, 95%) as a yellow oil.

[0030] The detection data for compound 11 are as follows: 11: R f = 0.3 (silica, PE: EtOAc = 5:1); [α]20 D = + 101.16 (c = 0.5 inCHCl3); IR (film): ν max = 3383, 2967, 2881, 1682, 1312, 1103; 1H NMR (400 MHz, CDCl3): δ 11.43 (s, 1H), 7.73 (s, 1H), 6.46 (d, J = 2.5 Hz, 1H), 6.27 (d, J = 2.5Hz, 1H), 4.60 (d, J = 7.0 Hz, 1H), 4.47 (d, J = 7.0 Hz, 1H), 3.96 (q, J = 7.0 Hz,1H), 3.90 (s, 3H), 3.79 (p, J = 6.4 Hz, 1H), 3.14 (s, 3H), 1.17 (d, J = 6.9 Hz, 3H), 1.10 (d, J = 6.2 Hz, 3H). 13 C NMR (101 MHz, CDCl3): δ 171.9, 163.9, 161.2,150.0, 108.3,106.2, 101.5, 94.4, 55.2, 52.2, 40.7, 17.3, 16.9; HRMS (m / z): [M+Na] + calcd for C 14 H 20 O6Na + 307.1152 found 307.1153. Example 4 This embodiment provides a method for synthesizing compounds 18 and 19 used in this invention, as detailed below: Compound 17 (16.0 mg, 0.05 mmol) was added to a solution of compound 16 (25.0 mg, 0.1 mmol) and compound 5 (31 mg, 0.1 mmol) in dimethyl sulfoxide (0.5 mL) at room temperature. The mixture was stirred at room temperature for 60 min, then quenched with 1N dilute hydrochloric acid (5.0 mL), and extracted with ethyl acetate (10.0 mL × 3). The combined organic phases were washed with brine (30.0 mL) and dried over anhydrous sodium sulfate. The solvent was evaporated under vacuum (150 mbar), and the crude product was purified by rapid column chromatography (silica gel, PE:EtOAc = 5:1) to give a colorless oil 18:19 = 5:1 (49.0 mg, 87%). The detection data for compounds 18 and 19 are as follows: 18: [α]20 D= -41.77 (c = 0.5 in CHCl3); IR (film): ν max = 3407, 2974,2851, 1697, 1723, 1385, 1035, 812. 1 H NMR (400 MHz, CDCl3): δ 6.61 (s, 1H),6.19 (dd, J = 15.5, 10.2 Hz, 1H), 5.96 (dd, J = 15.3, 10.2 Hz, 1H), 5.90 – 5.73(m, 1H), 5.47 (d, J = 15.5 Hz, 1H), 4.53 (d, J = 6.9 Hz, 1H), 4.39 (d, J = 6.9Hz, 1H), 4.20 (dd, J = 9.3, 6.0 Hz, 1H), 4.11 (d, J = 5.9 Hz, 1H), 3.77 (d, J = 7.3Hz, 1H), 3.17 (s, 3H), 2.97 (dt, J = 13.5, 6.7 Hz, 1H), 2.75 – 2.60 (m, 1H),2.12 (dp, J = 14.3, 6.9 Hz, 2H), 1.53 (s, 9H), 1.49 (s, 3H), 1.41 (d, J = 7.1 Hz,3H), 1.29 (s, 3H), 1.20 (d, J = 6.0 Hz, 3H), 1.07 (s, 3H), 0.99 (t, J = 7.4 Hz,3H). 13C NMR (101 MHz, CDCl3): δ 200.8, 197.8, 192.8, 191.4, 162.0,146.9,144.2, 140.0, 132.2, 127.7, 125.5, 111.0, 95.3, 91.4, 82.1, 75.0, 65.6, 57.1,55.5, 52.9, 50.6, 41.1, 32.7, 28.3, 25.8, 22.3, 19.1, 18.3, 15.3, 13.5,13.4;HRMS (m / z): [M+Na] + calcd for C 32 H 44 O9Na + 595.2878 found 595.2883. 19: [α]20 D= -34.57 (c = 0.5 in CHCl3); IR (film): ν max = 3427, 2933,1766, 1380, 1122, 1036, 668. 1 H NMR (400 MHz, CDCl3): δ 6.68 (s, 1H), 6.25 (dd, J = 15.5, 9.7 Hz, 1H), 6.03 – 5.83 (m, 2H), 5.48 (d, J = 15.5 Hz, 1H), 4.73 (d, J = 6.8 Hz, 1H), 4.66 (d, J = 6.8 Hz, 1H), 4.27 (d, J = 4.4 Hz, 1H), 4.24 – 4.16(m, 1H), 3.76 (d, J = 7.7 Hz, 1H), 3.36 (s, 3H), 2.98 – 2.80 (m, 1H), 2.61 (d, J = 8.4 Hz, 1H), 2.10 (q, J = 6.9 Hz, 2H), 1.53 (s, 9H), 1.47 (s, 3H), 1.32 (d, J =5.9 Hz, 3H), 1.24 (s, 3H), 1.18 (d, J = 7.2 Hz, 3H), 1.04 (d,J = 7.3 Hz, 3H), 1.00 (t, J = 7.4 Hz, 3H). 13 C NMR (101 MHz, CDCl3): δ 201.8, 197.9,193.1, 191.7,161.7,146.9, 139.9, 132.7, 127.7, 125.0, 111.3, 96.1, 91.5, 81.8, 75.8, 65.3,57.6, 55.7, 41.7, 33.6, 28.3, 25.8, 23.3, 19.6, 18.0, 15.2, 13.3, 12.7; HRMS(m / z):[M+Na] + calcd for C 32 H 44 O9Na + 595.2878 found 595.2885. The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on its differences from other embodiments. Similar or identical parts between embodiments can be referred to interchangeably. For the apparatus disclosed in the embodiments, since they correspond to the methods disclosed in the embodiments, the description is relatively simple; relevant parts can be referred to the method section.

[0031] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A method for synthesizing natural products asperones A and B, characterized in that, The reaction process and steps are as follows: ， (1) Compound 4 was dissolved in anhydrous THF, and then sodium hydride was added in an ice bath. After no more bubbles were released, compound 6 was added and reacted at this temperature for one hour. Then tetrabutylammonium fluoride was added and reacted for two hours. Then ammonium chloride solution was added to quench the reaction. Then the mixture was extracted with ethyl acetate. The organic phases were combined, dried with anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under reduced pressure under vacuum to obtain crude product. The crude product was purified by silica gel column chromatography to obtain compound 5. (2) Compound 16 and compound 5 were dissolved in dimethyl sulfoxide, compound 17 was added at room temperature, and the reaction was carried out at 30°C for two hours. The reaction was quenched with 1 mol / L hydrochloric acid aqueous solution, and then extracted with ethyl acetate. The organic phases were combined, dried with anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under reduced pressure under vacuum to obtain crude product. The crude product was purified by silica gel column chromatography to obtain compounds 18 and 19. (3) Compound 18 was dissolved in acetonitrile, and HF aqueous solution was added at room temperature. After reacting for ten minutes, the reaction was quenched with 1 mol / L hydrochloric acid aqueous solution, and then extracted with ethyl acetate. The organic phases were combined, dried with anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under reduced pressure under vacuum to obtain crude product. The crude product was purified by silica gel column chromatography to obtain asperone A. (4) Compound 19 was dissolved in acetonitrile, and HF aqueous solution was added at room temperature. After reacting for ten minutes, the reaction was quenched with 1 mol / L hydrochloric acid aqueous solution, and then extracted with ethyl acetate. The organic phases were combined, dried with anhydrous sodium sulfate, filtered under reduced pressure, and concentrated under reduced pressure under vacuum to obtain crude product. The crude product was purified by silica gel column chromatography to obtain asperone B. The structural formula of compound 6 is as follows: The structural formula of compound 17 is as follows: 。 2. The method for synthesizing natural products asperones A and B according to claim 1, characterized in that, In step (1), the ratio of the amount of compound 4, sodium hydride, tetrahydrofuran, tetrabutylammonium fluoride and ammonium chloride solution is 0.9 mmol : 1.3 mmol : 4.2 ml : 2.6 mmol : 10 ml.

3. The method for synthesizing natural products asperones A and B according to claim 1, characterized in that, In step (1), the pressure of the reduced pressure filtration is 500 mbar; the eluent used in the silica gel column chromatography purification is petroleum ether and ethyl acetate, with a volume ratio of petroleum ether to ethyl acetate of 5:

1.

4. The method for synthesizing natural products asperones A and B according to claim 1, characterized in that, In step (2), the ratio of compound 16, compound 5, compound 17, dimethyl sulfoxide, and hydrochloric acid aqueous solution is 0.1 mmol : 0.1 mmol : 0.05 mmol : 0.5 ml : 5 ml.

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