A synthetic method of Alstoschlarinoid B

Abstract

The present invention discloses a synthesis method of Alstoschlarinoid B. The synthesis method uses oleanolic acid as a raw material, protects the carboxyl group and hydroxyl group of oleanolic acid through a protecting group, then obtains an olefin isomerization product through oxidation rearrangement, reduction, elimination and removal of the protecting group. The olefin isomerization product is subjected to an oxidation reaction to break the carbon-carbon double bond to obtain a dialdehyde intermediate, and the dialdehyde intermediate is directly obtained as the natural product Alstoschlarinoid B through an aldol condensation reaction; or the dialdehyde intermediate reacts under the action of a strong base to obtain an aldol condensation product, and then the natural product Alstoschlarinoid B is obtained through transesterification. The present invention provides another acquisition way for subsequent drug research and industrial production of the natural product Alstoschlarinoid B.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis and relates to a method for synthesizing Alstoschlarinoid B. Background Art

[0002] Alstoschlarinoid B is a triterpenoid natural product isolated from the leaves of Alstonia scholaris, with a complex polycyclic structure of 6 / 6 / 5 / 6 / 6 / 6. Studies have shown that Alstoschlarinoid B has good bioactivity against hyperuricemia. Uric acid is the final product of purine metabolism in the human body. An imbalance between the production and excretion of uric acid in the body will lead to an increase in blood uric acid and cause diseases, which is the main cause of gout.

[0003] Currently, the main drugs for treating gout on the market are febuxostat and probenecid, etc. These drugs mainly achieve the treatment of hyperuricemia by inhibiting uric acid production and accelerating uric acid excretion. However, these drugs are generally prone to cause adverse reactions such as gastrointestinal diseases and allergies in the human body. As a natural product, Alstoschlarinoid B has good inhibitory activity against hyperuricemia and relatively high safety.

[0004] As a natural product, Alstoschlarinoid B is currently mainly isolated and extracted from the leaves of Alstonia scholaris. The separation and extraction method is relatively complex and costly. Therefore, it is of great significance to develop a method for synthesizing Alstoschlarinoid B with low price, simple synthesis method and easy industrial production. Summary of the Invention

[0005] In order to solve the problem that the existing separation and extraction method of the natural product Alstoschlarinoid B is complex and costly, the present invention provides a method for synthesizing Alstoschlarinoid B, using oleanolic acid as a raw material and converting it into Alstoschlarinoid B through chemical reactions. This synthesis method is simple and the purity of the obtained product is 99%. The raw materials are rich in source and low in price. There is no relevant report on the artificial synthesis of the natural product Alstoschlarinoid B at present. The present invention creates conditions for the subsequent drug research and industrial production of Alstoschlarinoid B and provides another acquisition way.

[0006] To achieve the technical purpose of the present invention, on the one hand, the present invention provides a method for synthesizing Alstoschlarinoid B, which prepares Alstoschlarinoid B through nine-step chemical reactions using oleanolic acid as a raw material.

[0007] Furthermore, in the synthetic method of the present invention, using oleanolic acid as a raw material, the carboxyl group and hydroxyl group of oleanolic acid are protected through substitution reactions, and then a hydroxyl compound is obtained through oxidation and reduction reactions. The hydroxyl compound is converted into an olefin isomerization product through esterification, thermal elimination, and substitution reactions (removing the protecting group), or the hydroxyl compound is converted into an olefin isomerization product through dehydration and substitution reactions; the olefin isomerization product is oxidized by an oxidizing reagent to cleave the carbon-carbon double bond to obtain a dialdehyde intermediate, which directly reacts with a metal salt and a base through an aldol condensation reaction (Aldol reaction) to obtain the natural product Alstoschlarinoid B.

[0008] Exemplarily, the present invention provides another synthetic method of Alstoschlarinoid B. The dialdehyde intermediate is reacted with a strong base to obtain an aldol condensation product, which is then subjected to transesterification to obtain the natural product Alstoschlarinoid B.

[0009] On the other hand, the present invention provides a synthetic method of Alstoschlarinoid B, specifically including the following steps:

[0010] S1: Using oleanolic acid (compound a) as a raw material, under the action of a first base, a first reaction solvent, and an alkylating reagent, the carboxyl group is protected through a substitution reaction to obtain compound b; the mass ratio of compound a to the first base, the alkylating reagent, and the first reaction solvent is 1.0:0.5 - 1.0:0.2 - 0.5:10.0 - 20.0; the reaction temperature is 20 - 30 °C, and the reaction time is 10 - 24 h.

[0011] S2: Using compound b as a raw material, under the action of a base, a protecting reagent, a small molecule catalyst, and a second reaction solvent, the hydroxyl group is protected through a substitution reaction to obtain compound c; the mass ratio of compound b to the protecting reagent, the small molecule catalyst, and the base is 1.0:0.3 - 0.5:0.02 - 0.05:0.2 - 0.5; the mass ratio of compound b to the second reaction solvent is 1.0:10.0 - 20.0; the reaction temperature is 20 - 30 °C, and the reaction time is 10 - 24 h.

[0012] S3: Using compound c as a raw material, mixing it with a third reaction solvent, and performing an oxidation reaction with an oxidizing reagent while undergoing rearrangement to obtain compound d (a carbonyl compound); the mass ratio of compound c to the oxidizing reagent is 1.0:0.6 - 1.1; the mass ratio of compound c to the third reaction solvent is 1.0:20.0 - 40.0; the reaction temperature is 30 - 40 °C, and the reaction time is 24 - 48 h.

[0013] S4: Using compound d as a raw material, mixing it with a fourth reaction solvent, and performing a reduction reaction with a reducing agent to obtain compound e (a hydroxyl compound); the mass ratio of compound d to the reducing agent is 1.0:0.1 - 0.5; the mass ratio of compound d to the fourth reaction solvent is 1.0:20.0 - 40.0; the reaction temperature is 20 - 30 °C, and the reaction time is 5 - 10 h.

[0014] S5: Using compound e as a raw material, after performing an esterification reaction with a second base, a fifth reaction solvent, carbon disulfide, and an alkylating agent, mixing the reaction product (compound f) with a sixth reaction solvent, and performing a thermal elimination reaction under continuous high-temperature stirring to obtain compound g (an elimination product); the reaction temperature of the esterification reaction is 20 - 80 °C, and the reaction time is 24 - 36 h; the reaction temperature of the thermal elimination reaction is 160 - 180 °C, and the reaction time is 6 - 10 h; the mass ratio of compound e to carbon disulfide, the second base, and the alkylating agent is 1.0:0.1 - 0.4:0.1 - 0.2:0.4 - 0.6; the mass ratio of compound e to the fifth reaction solvent is 1.0:20.0 - 40.0; the mass ratio of compound f to the sixth reaction solvent is 1.0:5.0 - 10.0.

[0015] Or using compound e as a raw material, adding a dehydrating agent to perform a dehydration reaction to obtain compound g; the reaction temperature of the dehydration reaction is 60 - 120 °C, and the reaction time is 1 - 3 h; the mass ratio of compound e to the dehydrating agent is 1.0:0.60 - 1.20.

[0016] S6: Using compound g as a raw material, mixing it with a seventh reaction solvent, and under the action of a third base, removing the hydroxyl protecting group through a substitution reaction to obtain compound h; the mass ratio of compound g to the third base is 1.0:0.8 - 1.5; the mass ratio of compound g to the seventh reaction solvent is 1.0:20.0 - 40.0; the reaction temperature is 40 - 60 °C, and the reaction time is 5 - 10 h.

[0017] S7: Using compound h as a raw material, mixing it with an eighth reaction solvent, and performing an ozonolysis reaction to break the carbon-carbon double bond to obtain compound i (a dialdehyde compound); the mass ratio of compound h to the eighth reaction solvent is 1.0:500 - 800; the reaction temperature is -78 - 40 °C, and the reaction time is 12 - 24 h.

[0018] S8: Using compound i as a raw material, mixing it with a ninth reaction solvent, and performing an aldol condensation reaction under the action of a metal salt to obtain compound Alstoschlarinoid B; the mass ratio of compound i to the metal salt is 1.0:0.3 - 0.6; the mass ratio of compound i to the ninth reaction solvent is 1.0:8.0 - 20.0; the reaction temperature is 130 - 180 °C, and the reaction time is 4 - 8 h.

[0019] Alternatively, using compound i as a raw material, mixing it with the tenth reaction solvent, and subjecting it to a rearrangement reaction under the action of the fourth base. The reaction product (compound j) is then mixed with the eleventh reaction solvent and stirred at room temperature, and is gradually converted into compound Alstoschlarinoid B through transesterification; the molar ratio of compound i to the fourth base is 1.0:4.0 - 8.0; the mass ratio of compound i to the tenth reaction solvent is 1.0:20.0 - 40.0; the mass ratio of compound j to the eleventh reaction solvent is 1.0:160.0 - 200.0; the reaction temperature of the rearrangement reaction is -60 to -78 °C, and the reaction time is 2 - 3 h; the reaction temperature of the transesterification is 20 - 30 °C, and the reaction time is 10 - 24 h.

[0020] Furthermore, in the method for synthesizing Alstoschlarinoid B provided by the present invention, any one of the first reaction solvent, the second reaction solvent, the third reaction solvent, the fourth reaction solvent, the fifth reaction solvent, the sixth reaction solvent, the seventh reaction solvent, the eighth reaction solvent, the ninth reaction solvent, the tenth reaction solvent, and the eleventh reaction solvent is selected from one of tetrahydrofuran, dichloromethane, methanol, N,N-dimethylformamide, water, methylnaphthalene, 2,6-dimethylpyridine, and 2,4,6-trimethylpyridine.

[0021] Furthermore, in the method for synthesizing Alstoschlarinoid B provided by the present invention, any one of the first base, the second base, the third base, and the fourth base is selected from one of potassium carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, sodium ethoxide, potassium tert-butoxide, lithium hexamethyldisilazide, potassium hexamethyldisilazide, sodium hexamethyldisilazide, and lithium diisopropylamide.

[0022] Furthermore, in the method for synthesizing Alstoschlarinoid B provided by the present invention, the alkylating agent is selected from one of methyl iodide, ethyl iodide, vinyl iodide, benzyl bromide, and benzyl chloride; the protecting agent is selected from one of acetic anhydride, acetyl chloride, methyl iodide, benzyl bromide, benzyl chloride, tert-butyldimethylchlorosilane, trimethylchlorosilane, tert-butyldimethylsilyl trifluoromethanesulfonate, and trimethyltrifluoromethanesulfonate. The oxidizing agent is selected from one of m-chloroperbenzoic acid, ozone, osmium tetroxide, potassium osmate, hydrogen peroxide, and tert-butyl hydroperoxide. The metal salt is selected from one of lithium iodide, potassium iodide, lithium bromide, and copper(I) iodide.

[0023] The method for synthesizing Alstoschlarinoid B provided by the present invention has a synthetic route as Figure 1 shown. In the synthetic route, R1 is a functional group for protecting the carboxyl group, and R1 is one of methyl, ethyl, and benzyl; in the synthetic route, R2 is a functional group for protecting the hydroxyl group, and R2 is one of acetic anhydride, tert-butyldimethylsilyl, trimethylsilyl, and methyl.

[0024] Compared with the prior art, the technical solution provided by the present invention has at least the following beneficial effects or advantages:

[0025] The present invention uses oleanolic acid as a raw material and prepares the natural product Alstoschlarinoid B through nine steps. The natural product Alstoschlarinoid B is prepared by an artificial synthesis method. The synthesis method provided by the present invention provides another way for the source of the natural product Alstoschlarinoid B, thereby protecting natural resources and the ecological environment. The compound source is sufficient and not restricted by the shortage of natural resources.

[0026] The raw materials involved in the method of the present invention are simple, easy to obtain, and low in price. The reaction yield is high, and the product purity is as high as 99%, which can effectively reduce the production cost. At the same time, the synthesis method of the present invention has a simple reaction route, mild reaction conditions, convenient operation, high safety, and is easy to industrialize. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for the description of the embodiments or the prior art. Obviously, the drawings in the following description are only some embodiments of the present invention.

[0028] Figure 1 It is a synthetic route diagram of Alstoschlarinoid B.

[0029] Figure 2 For the 1 1H NMR spectrum of Alstoschlarinoid B.

[0030] Figure 3 It is a crystal structure characterization diagram of Alstoschlarinoid B. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0031] Next, the technical solutions of the present invention will be described in conjunction with the embodiments. However, the present invention is not limited to the following embodiments. The experimental methods and detection methods described in each embodiment are all conventional methods unless otherwise specified; the reagents and materials described are all commercially available unless otherwise specified.

[0032] Example 1

[0033] This example provides a synthesis method of Alstoschlarinoid B, which specifically includes the following steps:

[0034] S1: Add 15 g of oleanolic acid, 11.34 g of potassium carbonate, 4.56 mL of methyl iodide, and 150 mL of N,N-dimethylformamide into a 1 L three-necked flask equipped with mechanical stirring in sequence. Stir at room temperature for 12 h. Stop the reaction after detecting by thin-layer chromatography (TLC) that the raw material oleanolic acid has completely disappeared. Pour the reaction solution into 2 L of water, stir for 30 min, directly filter to obtain a white solid, dissolve it with dichloromethane, separate the layers, dry, and evaporate to dryness to obtain 15 g of a white solid (Compound b).

[0035] The nuclear magnetic resonance hydrogen spectrum of Compound b 1 H NMR is as follows: (400 MHz, Chloroform-d) δ 5.29 (t, 1H, J = 3.5 Hz), 3.63 (s, 3H), 3.22 (dd, 1H, J1 = 11.5 Hz, J2 = 4.4 Hz), 2.86 (dd, J = 13.8, 4.2 Hz, 1H), 1.25 - 1.73 (m, 20H), 1.15 - 1.22 (m, 2H), 1.13 (s, 3H), 1.04 - 1.10 (m, 1H), 0.99 (s, 3H), 0.96 - 1.01 (m, 1H), 0.93 (s, 3H), 0.91 (s, 3H), 0.90 (s, 3H), 0.78 (s, 3H), 0.72 (s, 3H).

[0036] The nuclear magnetic resonance carbon spectrum of Compound b 13 C NMR is as follows: (101 MHz, CDCl3) δ 178.32, 143.80, 122.37, 79.03, 55.23, 51.55, 47.64, 46.73, 45.89, 41.65, 41.30, 39.28, 38.77, 38.44, 37.05, 33.87, 33.13, 32.67, 32.39, 30.71, 28.11, 27.71, 27.20, 25.95, 23.65, 23.41, 23.08, 18.34, 16.84, 15.59, 15.31.

[0037] S2: Add 15 g of the white solid (Compound b), 6.64 mL of pyridine, 5.25 mL of acetic anhydride, 0.6 g of 4-dimethylaminopyridine, and 150 mL of tetrahydrofuran into a 1 L three-necked flask equipped with mechanical stirring in sequence. Stir at room temperature for 12 h. Detect by TLC that the raw material Compound b has completely reacted. Pour the reaction solution into 2 L of water, stir for 30 min, directly filter to obtain a white solid, dissolve it with dichloromethane, separate the layers, dry, and evaporate to dryness to obtain 15 g of a white solid (Compound c).

[0038] The nuclear magnetic resonance hydrogen spectrum of Compound c 11H NMR): (500 MHz, Chloroform-d) δ 5.27 (t, J = 3.55 Hz, 1H), 4.55 - 4.41 (m, 1H), 3.61 (s, 3H) 2.94 - 2.74 (m, 1H), 2.03 (s, 3H), 1.98 - 1.93 (m, 1H), 1.90 - 1.87 (m, 2H), 1.71 - 1.64 (m, 1H), 1.62 - 1.59 (m, 6H), 1.57 - 1.50 (m, 3H), 1.47 - 1.26 (m, 4H), 1.19 - 1.16 (m, 2H), 1.12 (s, 3H), 1.05 - 1.02 (m, 2H), 0.92 (s, 6H), 0.89 (s, 3H) 0.85 (s, 3H), 0.84 (s, 3H), 0.81 (s, 1H), 0.71 (s, 3H).

[0039] The carbon nuclear magnetic resonance spectrum of compound c ( 13 13C NMR): (126 MHz, CDCl3) δ 178.30, 171.01, 143.83, 122.30, 80.94, 55.34, 51.53, 47.58, 46.75, 45.87, 41.66, 41.33, 39.32, 38.14, 37.71, 36.96, 33.89, 33.13, 32.63, 32.41, 30.72, 28.06, 27.71, 25.92, 23.67, 23.56, 23.43, 23.09, 21.33, 18.25, 16.86, 16.71, 15.39.

[0040] S3: Add 15 g of white solid (compound c), 9.6 g of m-chloroperoxybenzoic acid, and 300 mL of dichloromethane to a 1 L round-bottom flask equipped with magnetic stirring in sequence. Stir at 30 °C for 48 h. Stop the reaction after TLC detection shows that the raw material compound c has completely disappeared. Rotate to dry the solvent, and obtain 14.76 g of white solid (compound d) by column chromatography. The total yield of the three-step reaction (1) - (3) is 85%.

[0041] The proton nuclear magnetic resonance spectrum of compound d ( 1 1H NMR): (500 MHz, Chloroform-d) δ 4.48 (dd, J = 11.5, 4.9 Hz, 1H), 3.68 (s, 2H), 2.79 (dt,

[0042] J = 13.7, 4.0 Hz, 1H), 2.62 (d, J = 4.3 Hz, 1H), 2.24 (dd, J = 16.8, 5.0 Hz, 1H), 2.14 (dd, J = 16.8, 13.0 Hz, 1H), 2.05 (s, 3H), 1.98–1.84 (m, 2H), 1.80 (td, J = 13.7, 4.6 Hz, 1H), 1.70–1.54 (m, 6H), 1.57–1.42 (m, 5H), 1.37–1.31 (m, 2H), 1.24–1.19 (m, 2H), 1.12–1.05 (m, 1H), 0.98 (s, 3H), 0.97 (s, 3H), 0.94 (s, 3H), 0.91 (s, 3H), 0.88 (s, 3H), 0.87 (s, 3H), 0.86 (s, 3H), 0.84 - 0.83 (s, 2H).

[0043] The carbon-13 nuclear magnetic resonance spectrum of compound d ( 13 C NMR) is as follows: (126 MHz, CDCl3) δ 211.57, 178.36, 170.86, 80.40, 55.16, 51.82, 51.79, 49.62, 47.33, 41.83, 41.23, 38.47, 37.74, 37.62, 36.82, 36.17, 34.47, 33.40, 32.94, 31.96, 31.74, 30.64, 27.90, 27.54, 23.39, 23.16, 22.73, 21.27, 20.56, 18.17, 16.46, 16.11, 15.26.

[0044] S4: Add 5 g of the white solid (compound d) and 50 mL of the mixed solvent (tetrahydrofuran:water = 10:1 by volume) to a 1 L round-bottom flask equipped with magnetic stirring in sequence. Slowly add 716 mg of sodium borohydride to the mixed solution in batches. After 10 h, stop the reaction when TLC detection shows that the starting compound d has completely disappeared. Add water for extraction, dry, evaporate to dryness, and perform column chromatography to obtain 3.1 g of a white solid (compound e), with a yield of 62% based on molar mass.

[0045] The proton nuclear magnetic resonance spectrum of compound e ( 11H NMR): (500 MHz, Chloroform-d) δ 4.50 (dd, J = 11.2, 5.2 Hz, 1H), 3.82–3.74 (m, 1H), 3.73 (s, 3H), 2.74 (dt, J = 11.4, 5.0 Hz, 1H), 2.08 (s, 3H), 1.93–1.77 (m, 3H), 1.77–1.70 (m, 2H), 1.70–1.63 (m, 3H), 1.58–1.47 (m, 4H), 1.44–1.32 (m, 5H), 1.30–1.29 (m, 2H), 1.27–1.23 (m, 2H), 1.04 (m, 2H), 0.99 (s, 3H), 0.95 (s, 3H), 0.94 (s, 3H), 0.89 (s, 3H), 0.88 (s, 6H), 0.87 (s, 3H), 0.83–0.77 (m, 1H).

[0046] The carbon nuclear magnetic resonance spectrum of compound e ( 13 13C NMR) is: (126 MHz, CDCl 3 ) δ 178.90, 171.06, 80.80, 68.16, 55.32, 51.84, 49.04, 47.51, 42.98, 41.52, 40.52, 38.29, 37.79, 36.91, 36.09, 34.48, 33.46, 33.20, 32.50, 31.80, 31.43, 30.54, 28.90, 27.98, 23.64, 23.37, 23.22, 21.34, 18.17, 17.87, 16.50, 16.38, 15.93.

[0047] S5: Under argon protection, 5 g of white solid (compound e), 755 mg of sodium hydride and 100 mL of anhydrous tetrahydrofuran were successively added to a 500 mL three-necked flask equipped with magnetic stirring. After stirring at room temperature for 30 min, the temperature was raised to the reflux of tetrahydrofuran. 5.66 mL of carbon disulfide was added to the flask in batches and stirred until the starting compound e completely disappeared. The temperature was lowered to 40 °C, 4.69 mL of methyl iodide was added to the three-necked flask, and stirring was continued for 2 h. The reaction was stopped by adding water, and the solvent was evaporated to dryness. Water and dichloromethane were added for extraction, dried, and column chromatography was performed to obtain 5 g of pale yellow solid (compound f) with a yield of 86%. 5 g of pale yellow solid (compound f) and 30 mL of methylnaphthalene were successively added to a 250 mL round-bottomed flask equipped with magnetic stirring, and the temperature was raised to 160 °C and stirring was continued for 8 h. Column chromatography was performed to obtain 3.9 g of pale yellow solid (compound g) with a yield of 95%.

[0048] The proton nuclear magnetic resonance spectrum of compound f ( 11H NMR): (400 MHz, Chloroform-d) δ 5.71 (m, J = 11.0, 7.7 Hz, 1H), 4.46 (dd, J = 11.3, 4.7 Hz, 1H), 3.71 (s, 3H), 2.55 (s, 3H), 2.28 (dd, J = 11.7, 5.0 Hz, 1H), 2.22 - 2.18 (m, 1H), 2.03 (s, 3H), 1.89–1.04 (m, 22H), 1.02 (s, 3H), 0.92 (s, 3H), 0.87 (s, 3H), 0.86–0.83 (m, 6H), 0.83 (s, 3H), 0.80 (s, 3H).

[0049] The 13C NMR spectrum of compound f 13 13C NMR): (101 MHz, CDCl3) δ 214.73, 178.59, 170.91, 82.44, 80.61, 55.33, 51.86, 48.76, 47.31, 41.48, 40.95, 40.49, 38.16, 37.78, 37.08, 36.52, 34.29, 33.28, 33.02, 32.35, 31.65, 30.49, 28.90, 27.97, 26.24, 23.52, 23.01, 21.30, 18.28, 18.10, 17.86, 16.48, 16.35, 15.93.

[0050] The 1H NMR spectrum of compound g 1 1H NMR): (500 MHz, Chloroform-d) δ 5.57 (d, J = 9.6 Hz, 1H), 5.40 (d, J = 10.2 Hz, 1H), 4.48 (dd, J = 11.0, 5.4 Hz, 1H), 3.68 (s, 3H), 2.45 (d, J = 10.6 Hz, 1H), 2.26 (s, 1H), 2.04 (s, 3H), 1.88–1.78 (m, 4H), 1.74–1.54 (m, 5H), 1.42–1.39 (m, 4H), 1.28–1.11 (m, 6H), 1.08–0.97 (m, 2H), 0.90 (s, 3H), 0.89–0.88 (m, 6H), 0.87 (s, 3H), 0.84 (s, 3H), 0.83 (s, 3H), 0.75 (s, 3H).

[0051] The 13C NMR spectrum of compound g 13The \(^{13}\)C NMR data are as follows: (126 MHz, CDCl\(_3\)) δ 179.15, 171.02, 131.93, 126.52, 80.87, 54.91, 53.76, 51.84, 47.93, 40.91, 40.67, 39.62, 37.87, 37.77, 37.50, 36.86, 36.53, 34.65, 33.34, 32.97, 30.61, 30.36, 27.79, 26.63, 23.82, 23.45, 23.27, 21.35, 18.35, 18.15, 17.37, 16.96, 16.14.

[0052] S6: 3 g of pale yellow solid (Compound g), 3.28 g of potassium hydroxide, and 80 mL of mixed solvent (volume ratio: tetrahydrofuran:methanol:water = 10:10:1) were successively added to a 250 mL round-bottom flask equipped with magnetic stirring. The temperature was raised to 60 °C and stirring was continued for 6 h. The reaction was stopped after TLC detection showed that the starting compound g had completely disappeared. The mixture was extracted with water, dried, concentrated by rotary evaporation, and purified by column chromatography to obtain 2.6 g of white solid (Compound h) with a yield of 95%.

[0053] The \(^1\)H NMR spectrum of Compound h 1 is as follows: (500 MHz, Chloroform-d) δ 5.58–5.56 (m, 1H), 5.41–5.39 (m, 1H), 4.50–4.47 (m, 1H), 3.68 (s, 3H), 2.47–2.44 (m, 1H), 2.28 - 2.24 (m, 1H), 2.04 (s, 3H), 1.86 - 1.77 (m, 4H), 1.76 - 1.55 (m, 5H), 1.43–1.38 (m, 4H), 1.31–1.26 (m, 2H), 1.22–1.11 (m, 3H), 1.07–0.98 (m, 2H), 0.90–0.89 (m, 9H), 0.87–0.85 (m, 3H), 0.84–0.80 (m, 6H), 0.75 (s, 3H).

[0054] The \(^{13}\)C NMR spectrum of Compound h 1313C NMR): (126 MHz, CDCl3) δ 179.15, 171.02, 131.93, 126.52, 80.87, 54.91, 53.76, 51.84, 47.93, 40.91, 40.67, 39.62, 37.87, 37.77, 37.50, 36.86, 36.53, 34.65, 33.34, 32.97, 30.61, 30.36, 27.79, 26.63, 23.82, 23.45, 23.27, 21.35, 18.35, 18.15, 17.37, 16.96, 16.14.

[0055] S7: 1 g of white solid (compound h) and 500 mL of dichloromethane were successively added to a 250 mL round-bottom flask equipped with magnetic stirring. The temperature was lowered to -78 °C, and ozone was introduced for 10 min. After TLC detection showed that the starting compound h had completely disappeared, 10 mL of dimethyl sulfide was added, and the mixture was stirred at room temperature for 12 h. The reaction was stopped, and the mixture was extracted with water, dried, concentrated by rotary evaporation, and purified by column chromatography to obtain 830 mg of white solid (compound i) with a yield of 75%.

[0056] The 1H NMR spectrum of compound i 1 1H NMR): (500 MHz, Chloroform-d) δ 10.05 (d, J = 4.9 Hz, 1H), 9.98 (d, J = 6.0 Hz, 1H), 3.82 (s, 3H), 3.22 (dd, J = 11.6, 4.7 Hz, 1H), 2.80–2.72 (m, 1H), 2.69 (t, J = 5.2 Hz, 1H), 1.99–1.89 (m, 2H), 1.80–1.72 (m, 3H), 1.70–1.60 (m, 3H), 1.60–1.54 (m, 2H), 1.53–1.47 (m, 3H), 1.44–1.30 (m, 5H), 1.26 (s, 3H), 1.23 (s, 3H), 1.17 (s, 3H), 0.98 (s, 3H), 0.92 (s, 3H), 0.86 (s, 3H), 0.78 (s, 3H), 0.58 (dd, J = 12.1, 2.5 Hz, 1H).

[0057] The 13C NMR spectrum of compound i 1313C NMR): (126 MHz, CDCl3) δ 208.11, 177.37, 78.13, 64.49, 53.53, 52.44, 52.36, 46.41, 45.39, 42.99, 38.94, 38.83, 38.31, 37.92, 37.78, 33.87, 33.20, 32.56, 30.69, 27.86, 26.66, 23.24, 23.19, 18.73, 18.01, 15.48.

[0058] S8: 3 g of white solid (Compound i), 1.6 g of lithium iodide and 30 mL of 2,4,6-trimethylpyridine were successively added to a 250 mL round-bottom flask equipped with magnetic stirring. The temperature was raised to 160 °C and stirred continuously for 8 h. After the raw material Compound i completely disappeared by TLC detection, the reaction was stopped, diluted with 150 mL of dichloromethane, and washed with 0.5 M dilute hydrochloric acid until 2,4,6-trimethylpyridine was not contained in the solution. Extracted, dried, rotary evaporated, and column chromatography was used to obtain 1.42 g of white solid (Compound k), which is the natural product Alstoschlarinoid B, with a yield of 52% and a purity of 99%.

[0059] The 1H NMR of Compound k 1 1H NMR): (500 MHz, Chloroform-d) δ 10.01 (s, 1H), 5.12 (d, J = 2.5 Hz, 1H), 3.18 (dd, J = 10.4, 5.8 Hz, 1H), 2.18 (t, J = 8.7 Hz, 1H), 2.04–1.91 (m, 2H), 1.90 - 1.80 (m, 4H), 1.72–1.69 (m, 2H), 1.68–1.59 (m, 4H), 1.55 - 1.53 (m, 2H), 1.40 - 1.32 (m, 4H), 1.24 (s, 3H), 1.21 (s, 3H), 1.19 (s, 3H), 0.95 (s, 3H), 0.93 (s, 3H), 0.88–0.87 (m, 1H), 0.85 (s, 3H), 0.79 (s, 3H), 0.63 (dd, J = 11.5, 3.4 Hz, 1H).

[0060] The 13C NMR of Compound k 13The \(^{13}\)C NMR data are as follows: (126 MHz, CDCl\(_3\)) δ 206.33, 177.47, 84.46, 78.89, 60.69, 57.34, 56.39, 48.69, 46.78, 38.76, 38.37, 38.04, 37.61, 37.45, 37.21, 37.05, 33.56, 33.19, 30.83, 30.25, 29.51, 28.10, 27.54, 27.23, 27.05, 23.99, 20.82, 19.82, 18.25, 15.12.

[0061] Example 2

[0062] This example provides a method for synthesizing Alstoschlarinoid B, which specifically includes the following steps:

[0063] S1: Add 15 g of oleanolic acid, 11.34 g of potassium carbonate, 4.56 mL of iodoethane, and 150 mL of N,N-dimethylformamide to a 1 L three-necked flask equipped with a mechanical stirrer in sequence. Stir at room temperature for 12 h. Stop the reaction after detecting by thin-layer chromatography (TLC) that the raw material oleanolic acid has completely disappeared. Pour the reaction solution into 2 L of water, stir for 30 min, then directly filter to obtain a white solid. After dissolving in dichloromethane, separating, drying, and rotary evaporation, 15 g of a white solid (Compound b) is obtained.

[0064] S2: Add 15 g of the white solid (Compound b), 6.64 mL of pyridine, 4.85 mL of acetyl chloride, and 150 mL of N,N-dimethylformamide to a 1 L three-necked flask equipped with a mechanical stirrer in sequence. Stir at room temperature for 12 h. Detect by TLC that the raw material Compound b has completely reacted. Pour the reaction solution into 2 L of water, stir for 30 min, then directly filter to obtain a white solid. After dissolving in dichloromethane, separating, drying, and rotary evaporation, 15 g of a white solid (Compound c) is obtained.

[0065] S3: Add 15 g of the white solid (Compound c), 9.6 g of m-chloroperbenzoic acid, and 300 mL of dichloromethane to a 1 L round-bottom flask equipped with a magnetic stirrer in sequence. Stir at 30 °C for 48 h. Stop the reaction after detecting by TLC that the raw material Compound c has completely disappeared. Rotary evaporate the solvent, and column chromatography gives 14.76 g of a white solid (Compound d). In terms of molar mass, the total yield of the three-step reactions (1)-(3) is 85%.

[0066] S4: Add 5 g of white solid (Compound d) and 50 mL of a mixed solvent (tetrahydrofuran:water = 10:1 by volume) to a 1 L round-bottom flask equipped with magnetic stirring. Slowly add 716 mg of sodium borohydride to the mixed solution in batches. After 10 h, stop the reaction when TLC detection shows that the starting compound d has completely disappeared. Add water for extraction, dry, rotary evaporate, and perform column chromatography to obtain 3.1 g of white solid (Compound e), with a yield of 62% based on molar mass.

[0067] S5: Under argon protection, add 1 g of white solid (Compound e), 0.5 g of Burgess reagent, and 20 mL of toluene to a round-bottom flask. Heat to 120 °C and reflux with toluene for 2 h. After the starting materials have completely disappeared, rotary evaporate the solvent and perform column chromatography to obtain 0.6 g of solid (Compound g), with a yield of 62%.

[0068] S6: Add 3 g of pale yellow solid (Compound g), 3.28 g of potassium hydroxide, and 80 mL of a mixed solvent (tetrahydrofuran:methanol:water = 10:10:1 by volume) to a 250 mL round-bottom flask equipped with magnetic stirring. Heat to 60 °C and stir continuously for 6 h. Stop the reaction when TLC detection shows that the starting compound g has completely disappeared. Add water for extraction, dry, rotary evaporate, and perform column chromatography to obtain 2.6 g of white solid (Compound h), with a yield of 95%.

[0069] S7: Add 1 g of white solid (Compound h) and 500 mL of dichloromethane to a 250 mL round-bottom flask equipped with magnetic stirring. Cool to -78 °C and introduce ozone for 10 min. After TLC detection shows that the starting compound h has completely disappeared, add 10 mL of dimethyl sulfide and stir at room temperature for 12 h. Stop the reaction, add water for extraction, dry, rotary evaporate, and perform column chromatography to obtain 830 mg of white solid (Compound i), with a yield of 75%.

[0070] S8: Under argon protection, add 502 mg of white solid (Compound i) and 15 mL of anhydrous tetrahydrofuran to a 50 mL round-bottom flask equipped with magnetic stirring. Cool to -78 °C and slowly add 5 mL of 1 M LiHMDS dropwise. Continuously stir at low temperature for 2 h, add saturated ammonium chloride to quench the reaction, add water for extraction, dry, rotary evaporate, and perform column chromatography to obtain 260 mg of white solid (Compound j), with a yield of 51%. Add 50 mg of white solid (Compound j), 5 mL of methanol, and 5 mL of chloroform to a 50 mL round-bottom flask equipped with magnetic stirring. Continuously stir at room temperature for 24 h, rotary evaporate, and perform column chromatography to obtain 47 mg of white solid (Compound k), which is the natural product Alstoschlarinoid B, with a yield of 95% and a purity of 99%.

[0071] 1H NMR spectrum of Compound j 11H NMR): (500 MHz, DMSO-d6) δ 9.92 (d, J = 5.3 Hz, 1H), 6.75 (d, J = 6.2 Hz, 1H), 5.03 (d, J = 6.5 Hz, 1H), 3.67 (s, 3H), 3.58 - 3.56 (m, 1H), 3.03–2.95 (m, 2H), 2.88 (dd, J = 10.5, 5.4 Hz, 1H), 2.49 - 2.46 (m, 3H), 2.34–2.24 (m, 2H), 1.91–1.79 (m, 2H), 1.60–1.53 (m, 3H), 1.50 - 1.40 (m, 5H), 1.25 - 1.22 (m, 4H), 1.15 (s, 6H), 1.09 (s, 3H), 0.86 (s, 3H), 0.85 (s, 3H), 0.75 (s, 3H), 0.66 (s, 3H).

[0072] The carbon nuclear magnetic resonance spectrum of compound j ( 13 13C NMR): (126 MHz, DMSO) δ 208.52, 177.43, 105.93, 84.08, 77.24, 62.34, 53.17, 52.19, 47.25, 44.33, 43.56, 42.48, 39.33, 39.14, 38.33, 37.58, 36.81, 34.32, 34.08, 33.94, 33.75, 33.40, 30.95, 28.73, 26.90, 23.64, 23.49, 19.14, 18.78, 17.64, 17.22, 15.98.

[0073] Example 3

[0074] This example provides a method for synthesizing Alstoschlarinoid B, which specifically includes the following steps:

[0075] S1: Add 15 g of oleanolic acid, 7.5 g of potassium carbonate, 3 g of benzyl bromide and 150 mL of N,N-dimethylformamide to a 1 L three-necked flask equipped with mechanical stirring in sequence. Stir at room temperature for 10 h. Stop the reaction after detecting by thin layer chromatography (TLC) that the raw material oleanolic acid has completely disappeared. Pour the reaction solution into 2 L of water, stir for 30 min, then directly filter to obtain a white solid. After dissolving with dichloromethane, separating, drying and rotary evaporation, 15 g of white solid (compound b) is obtained.

[0076] S2: Add 15 g of white solid (Compound b), 4.5 mL of pyridine, 3 mL of acetic anhydride, 0.3 g of 4-dimethylaminopyridine, and 150 mL of tetrahydrofuran into a 1-L three-necked flask equipped with mechanical stirring in sequence. Stir at room temperature for 10 h. Detect by TLC that the raw material Compound b has completely reacted. Pour the reaction solution into 2 L of water, stir for 30 min, then directly filter to obtain a white solid. Add dichloromethane to dissolve it, separate the layers, dry, and evaporate to dryness to obtain 15 g of white solid (Compound c).

[0077] S3: Add 15 g of white solid (Compound c), 9 g of m-chloroperoxybenzoic acid, and 300 mL of dichloromethane into a 1-L round-bottomed flask equipped with magnetic stirring in sequence. Stir at 30 °C for 24 h. Stop the reaction after detecting by TLC that the raw material Compound c has completely disappeared. Evaporate the solvent, and perform column chromatography to obtain 14.76 g of white solid (Compound d). The total yield of the three-step reactions (1)-(3) is 72%.

[0078] S4: Add 5 g of white solid (Compound d) and 100 mL of mixed solvent (tetrahydrofuran:water = 10:1 by volume ratio) into a 1-L round-bottomed flask equipped with magnetic stirring in sequence. Slowly add 500 mg of sodium borohydride to the mixed solution in batches. Stop the reaction after detecting by TLC that the raw material Compound d has completely disappeared after 5 h. Add water for extraction, dry, evaporate to dryness, and perform column chromatography to obtain 2.75 g of white solid (Compound e), with a yield of 55% based on molar mass.

[0079] S5: Under argon protection, add 5 g of white solid (Compound e), 500 mg of sodium hydride, and 100 mL of anhydrous tetrahydrofuran into a 500-mL three-necked flask equipped with magnetic stirring in sequence. Stir at room temperature for 30 min, then heat up to reflux of tetrahydrofuran. Add 0.5 mL of carbon disulfide to the flask in batches, and stir until the raw material Compound e has completely disappeared. Cool down to 40 °C, add 2 mL of iodomethane to the three-necked flask, continuously stir for 24 h, add water to stop the reaction, and evaporate the solvent. Add water and dichloromethane for extraction, dry, and perform column chromatography to obtain 3.26 g of pale yellow solid (Compound f), with a yield of 56%. Add 3.26 g of pale yellow solid (Compound f) and 16.3 mL of methylnaphthalene into a 250-mL round-bottomed flask equipped with magnetic stirring in sequence. Heat up to 160 °C and continuously stir for 6 h. Perform column chromatography to obtain 2.5 g of pale yellow solid (Compound g), with a yield of 90%.

[0080] S6: Add 3 g of pale yellow solid (Compound g), 2.4 g of potassium hydroxide, and 60 mL of a mixed solvent (by volume: tetrahydrofuran:methanol:water = 10:10:1) to a 250 mL round-bottom flask equipped with magnetic stirring in sequence. Heat the temperature to 40 °C and continuously stir for 5 h. Stop the reaction after detecting the complete disappearance of the raw material Compound g by TLC. Add water for extraction, dry, rotary evaporate, and perform column chromatography to obtain 2.5 g of white solid (Compound h) with a yield of 93%.

[0081] S7: Add 1 g of white solid (Compound h) and 500 mL of dichloromethane to a 250 mL round-bottom flask equipped with magnetic stirring in sequence. Cool the temperature to -78 °C, introduce ozone for 6 min. After detecting the complete disappearance of the raw material Compound h by TLC, add 1 mL of dimethyl sulfide and stir at room temperature for 12 h. Stop the reaction, add water for extraction, dry, rotary evaporate, and perform column chromatography to obtain 720 mg of white solid (Compound i) with a yield of 65%.

[0082] S8: Under argon protection, add 50 mg of white solid (Compound i) and 1 mL of anhydrous tetrahydrofuran to a 50 mL round-bottom flask equipped with magnetic stirring in sequence. Cool the temperature to -78 °C, slowly dropwise add 0.4 mL of 1 M LiHMDS, continuously stir at low temperature for 2 h, quench the reaction with saturated ammonium chloride, add water for extraction, dry, rotary evaporate, and perform column chromatography to obtain 24 mg of white solid (Compound j) with a yield of 48%. Add 24 mg of white solid (Compound j), 1.9 mL of methanol, and 1.9 mL of chloroform to a 50 mL round-bottom flask equipped with magnetic stirring in sequence. Continuously stir at room temperature for 10 h, rotary evaporate, and perform column chromatography to obtain 16 mg of white solid (Compound k), namely the natural product Alstoschlarinoid B, with a yield of 70% and a purity of 99%.

[0083] Example 4

[0084] This example provides a method for synthesizing Alstoschlarinoid B, which specifically includes the following steps:

[0085] S1: Add 15 g of oleanolic acid, 15 g of potassium carbonate, 7.5 g of benzyl bromide, and 300 mL of N,N-dimethylformamide to a 1 L three-necked flask equipped with mechanical stirring in sequence. Stir at room temperature for 24 h. Stop the reaction after detecting the complete disappearance of the raw material oleanolic acid by thin-layer chromatography (TLC detection). Pour the reaction solution into 2 L of water, stir for 30 min, directly filter to obtain a white solid, dissolve it with dichloromethane, separate the liquid, dry, and rotary evaporate to obtain 15 g of white solid (Compound b).

[0086] S2: Add 15 g of a white solid (Compound b), 7.5 g of pyridine, 7.5 g of acetic anhydride, 0.75 g of 4-dimethylaminopyridine, and 150 mL of tetrahydrofuran into a 1-L three-necked flask equipped with mechanical stirring in sequence. Stir at room temperature for 24 h. Detect by TLC that the raw material Compound b has completely reacted. Pour the reaction solution into 2 L of water, stir for 30 min, directly filter to obtain a white solid, add dichloromethane to dissolve, separate the liquid, dry, and rotary evaporate to obtain 15 g of a white solid (Compound c).

[0087] S3: Add 15 g of a white solid (Compound c), 16.5 g of m-chloroperoxybenzoic acid, and 600 mL of dichloromethane into a 1-L round-bottomed flask equipped with magnetic stirring in sequence. Stir at 40 °C for 48 h. Stop the reaction after detecting by TLC that the raw material Compound c has completely disappeared. Rotary evaporate the solvent, and perform column chromatography to obtain 15.28 g of a white solid (Compound d). The total yield of the three-step reactions (1)-(3) is 88%.

[0088] S4: Add 5 g of a white solid (Compound d) and 200 mL of a mixed solvent (tetrahydrofuran:water = 10:1 by volume ratio) into a 1-L round-bottomed flask equipped with magnetic stirring in sequence. Slowly add 2.5 g of sodium borohydride to the mixed solution in batches. After 10 h, stop the reaction after detecting by TLC that the raw material Compound d has completely disappeared, add water for extraction, dry, rotary evaporate, and perform column chromatography to obtain 3.0 g of a white solid (Compound e), with a yield of 60% in terms of molar mass.

[0089] S5: Under argon protection, add 5 g of a white solid (Compound e), 1 g of sodium hydride, and 100 mL of anhydrous tetrahydrofuran into a 500-mL three-necked flask equipped with magnetic stirring in sequence. Stir at room temperature for 30 min, then heat up to the reflux of tetrahydrofuran. Add 2 g of carbon disulfide to the flask in batches, and stir until the raw material Compound e has completely disappeared. Cool down to 40 °C, add 3 g of methyl iodide to the three-necked flask, continuously stir for 3 h, add water to stop the reaction, and rotary evaporate the solvent. Add water and dichloromethane for extraction, dry, and perform column chromatography to obtain 5.1 g of a pale yellow solid (Compound f), with a yield of 88%. Add 5 g of the pale yellow solid (Compound f) and 30 mL of methylnaphthalene into a 250-mL round-bottomed flask equipped with magnetic stirring in sequence. Heat up to 180 °C and continuously stir for 10 h. Perform column chromatography to obtain 3.8 g of a pale yellow solid (Compound g), with a yield of 93%.

[0090] S6: Add 3 g of a pale yellow solid (Compound g), 4.5 g of potassium hydroxide, and 120 mL of a mixed solvent (tetrahydrofuran:methanol:water = 10:10:1 by volume ratio) into a 250-mL round-bottomed flask equipped with magnetic stirring in sequence. Heat up to 60 °C and continuously stir for 10 h. Stop the reaction after detecting by TLC that the raw material Compound g has completely disappeared, add water for extraction, dry, rotary evaporate, and perform column chromatography to obtain 2.6 g of a white solid (Compound h), with a yield of 95%.

[0091] S7: Add 1 g of white solid (Compound h) and 800 mL of dichloromethane into a 250 mL round-bottom flask equipped with magnetic stirring in sequence. Cool down to -60 °C, introduce ozone for 10 min. After detecting that the raw material Compound h has completely disappeared by TLC, add 10 mL of dimethyl sulfide, stir at room temperature for 12 h, stop the reaction, extract with water, dry, evaporate to dryness, and obtain 698 mg of white solid (Compound i) by column chromatography with a yield of 68%.

[0092] S8: Under argon protection, add 502 mg of white solid (Compound i) and 20 mL of anhydrous tetrahydrofuran into a 50 mL round-bottom flask equipped with magnetic stirring in sequence. Cool down to -60 °C, slowly dropwise add 8 mL of 1 M LiHMDS, continuously stir at low temperature for 3 h, quench the reaction with saturated ammonium chloride, extract with water, dry, evaporate to dryness, and obtain 181 mg of white solid (Compound j) by column chromatography with a yield of 36%. Add 40 mg of white solid (Compound j), 8 mL of methanol and 8 mL of chloroform into a 50 mL round-bottom flask equipped with magnetic stirring in sequence. Continuously stir at room temperature for 24 h, evaporate to dryness, and 37 mg of white solid (Compound k), namely natural product Alstoschlarinoid B, can be obtained by column chromatography with a yield of 94% and a purity of 99%.

[0093] Example 5

[0094] This example provides the crystal structure characterization of natural product Alstoschlarinoid B.

[0095] The crystal structure of natural product Alstoschlarinoid B is as Figure 2 shown, belonging to the orthorhombic system, space group P2(1)2(1)2(1), unit cell parameters: Z = 2, D c = 1.234 Mg / m 3 .

[0096] As described above, the basic principle, main features and advantages of the present invention are preferably described. The above examples and descriptions are only for describing the preferred embodiments of the present invention. The present invention is not limited by the above examples. Without departing from the spirit and scope of the present invention, various changes and improvements made by those of ordinary skill in the art to the technical solutions of the present invention shall fall within the protection scope determined by the present invention.

Claims

1. A synthetic method of Alstoschlarinoid B, and the synthetic route adopted is as follows: The compound k is Alstoschlarinoid B; In the synthetic route, R1 is a functional group for protecting the carboxyl group, and R1 is one of methyl, ethyl, and benzyl; In the synthetic route, R2 is a functional group for protecting the hydroxyl group, and R2 is one of acetic anhydride, tert-butyldimethylsilyl, trimethylsilyl, and methyl; Using oleanolic acid as a raw material, under the action of a first base, a first reaction solvent, and an alkylating agent, the carboxyl group is protected through a first substitution reaction to obtain compound b; the oleanolic acid is compound a; the mass ratio of compound a to the first base, the alkylating agent, and the first reaction solvent is 1.0:0.5 - 1.0:0.2 - 0.5:10.0 - 20.0; The reaction temperature of the first substitution reaction is 20 - 30 °C, and the reaction time is 10 - 24 h; Using compound b as a raw material, under the action of a base, a protecting reagent, a small molecule catalyst, and a second reaction solvent, the hydroxyl group is protected through a second substitution reaction to obtain compound c; The mass ratio of compound b to the protecting reagent, the small molecule catalyst, and the base is 1.0:0.3 - 0.5:0.02 - 0.05:0.2 - 0.5; The mass ratio of compound b to the second reaction solvent is 1.0:10.0 - 20.0; The reaction temperature of the second substitution reaction is 20 - 30 °C, and the reaction time is 10 - 24 h; Using compound c as a raw material, mixing it with a third reaction solvent, and undergoing an oxidation reaction through an oxidizing agent, while rearrangement occurs to obtain compound d; compound d is a carbonyl compound; the mass ratio of compound c to the oxidizing agent is 1.0:0.6 - 1.1; The mass ratio of compound c to the third reaction solvent is 1.0:20.0 - 40.0; The reaction temperature of the oxidation reaction is 30 - 40 °C, and the reaction time is 24 - 48 h; Using compound d as a raw material, mixing it with a fourth reaction solvent, and undergoing a reduction reaction through a reducing agent to obtain compound e; compound e is a hydroxyl compound; The mass ratio of compound d to the reducing agent is 1.0:0.1 - 0.5; The mass ratio of compound d to the fourth reaction solvent is 1.0:20.0 - 40.0; The reaction temperature of the reduction reaction is 20 - 30 °C, and the reaction time is 5 - 10 h; Using compound e as a raw material, after esterification reaction with a second base, a fifth reaction solvent, carbon disulfide, and an alkylating agent, the reaction product is mixed with a sixth reaction solvent, and an elimination product g is obtained through a thermal elimination reaction under continuous high-temperature stirring; The product of the esterification reaction is compound f, the reaction temperature is 20 - 80 °C, and the reaction time is 24 - 36 h; The reaction temperature of the thermal elimination reaction is 160 - 180 °C, and the reaction time is 6 - 10 h; The mass ratio of compound e to carbon disulfide, the second base, and the alkylating agent is 1.0:0.1 - 0.4:0.1 - 0.2:0.4 - 0.6; The mass ratio of the compound e to the fifth reaction solvent is 1.0:20.0 - 40.0; The mass ratio of the compound f to the sixth reaction solvent is 1.0:5.0 - 10.0; Or using the compound e as a raw material, adding a dehydrating reagent to obtain compound g through a dehydration reaction; the reaction temperature of the dehydration reaction is 60 - 120 °C, and the reaction time is 1 - 3 h; The mass ratio of the compound e to the dehydrating reagent is 1.0:0.60 - 1.20; Using the compound g as a raw material, mixing it with a seventh reaction solvent, and under the action of a third base, removing the hydroxyl protecting group through a third substitution reaction to obtain compound h; The mass ratio of the compound g to the third base is 1.0:0.8 - 1.5; The mass ratio of the compound g to the seventh reaction solvent is 1.0:20.0 - 40.0; The reaction temperature of the third substitution reaction is 40 - 60 °C, and the reaction time is 5 - 10 h; Using the compound h as a raw material, mixing it with an eighth reaction solvent, and through an ozonolysis reaction, cleaving the carbon-carbon double bond to obtain compound i; The compound i is a dialdehyde compound; The mass ratio of the compound h to the eighth reaction solvent is 1.0:500 - 800; The reaction temperature of the ozonolysis reaction is -60 - -78 °C, and the reaction time is 0.1 - 0.5 h; Using the compound i as a raw material, mixing it with a ninth reaction solvent, and under the action of a metal salt, obtaining compound Alstoschlarinoid B through a condensation cyclization reaction; The mass ratio of the compound i to the metal salt is 1.0:0.3 - 0.6; The mass ratio of the compound i to the ninth reaction solvent is 1.0:8.0 - 20.0; The reaction temperature of the condensation cyclization reaction is 130 - 180 °C, and the reaction time is 4 - 8 h; Or using the compound i as a raw material, mixing it with a tenth reaction solvent, after a rearrangement reaction under the action of a fourth base, mixing the reaction product with an eleventh reaction solvent, stirring at room temperature, and gradually converting it into compound Alstoschlarinoid B through transesterification; The reaction product of the rearrangement reaction is compound j, the reaction temperature is -60 - -78 °C, and the reaction time is 2 - 3 h; The molar ratio of the compound i to the fourth base is 1.0:4.0 - 8.0; The mass ratio of the compound i to the tenth reaction solvent is 1.0:20.0 - 40.0; The mass ratio of the compound j to the eleventh reaction solvent is 1.0:160.0 - 200.0; The reaction temperature of the transesterification is 20 - 30 °C, and the reaction time is 10 - 24 h.

2. The synthesis method of Alstoschlarinoid B according to claim 1, characterized in that, Any one of the first reaction solvent, the second reaction solvent, the third reaction solvent, the fourth reaction solvent, the fifth reaction solvent, the sixth reaction solvent, the seventh reaction solvent, the eighth reaction solvent, the ninth reaction solvent, the tenth reaction solvent, and the eleventh reaction solvent is selected from one of tetrahydrofuran, dichloromethane, methanol, N,N-dimethylformamide, water, methylnaphthalene, 2,6-dimethylpyridine, and 2,4,6-trimethylpyridine; Any one of the first base, the second base, the third base and the fourth base is selected from the group consisting of potassium carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, sodium ethoxide, potassium tert-butoxide, lithium hexamethyldisilazide, potassium hexamethyldisilazide, sodium hexamethyldisilazide and lithium diisopropylamide.

3. The synthetic method of Alstoschlarinoid B according to claim 1, characterized in that, The alkylating agent is selected from the group consisting of methyl iodide, ethyl iodide, vinyl iodide, benzyl bromide and benzyl chloride. The protecting agent is selected from the group consisting of acetic anhydride, acetyl chloride, methyl iodide, benzyl bromide, benzyl chloride, tert-butyldimethylsilyl chloride, trimethylsilyl chloride, tert-butyldimethylsilyl trifluoromethanesulfonate and trimethyl trifluoromethanesulfonate. The oxidizing agent is selected from the group consisting of m-chloroperbenzoic acid, ozone, osmium tetroxide, potassium osmate, hydrogen peroxide and tert-butyl hydroperoxide. The metal salt is selected from the group consisting of lithium iodide, potassium iodide, lithium bromide and cuprous iodide.

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