Preparation method of glassine

Abstract

The preparation method comprises the following reaction steps: performing deprotection on a compound in a formula II under the conditions of acid and alcohol to obtain a compound in a formula I; pg is a hydroxyl protecting group. The acid comprises one or combination of heteropolyacid, acidic cation exchange resin, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, hydrogen chloride, hydrobromic acid and sulfuric acid. Furthermore, the acid is one or a combination of acidic cation exchange resin, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, hydrogen chloride, hydrobromic acid and sulfuric acid. Preferably, the acid is one or a composition of acidic cation exchange resin, p-toluenesulfonic acid and hydrogen chloride. According to the method, complex processes such as desalination and water concentration are avoided, the salt content is controlled, the generation of wastewater is reduced, the reaction condition is mild, the operation is simple, and amplification and commercial production are facilitated.

Description

Technical Field

[0001] The present invention relates to the field of chemical synthesis, and in particular to a method for preparing bosine. Background Art

[0002] Bosin, a xylose derivative discovered by L'Oréal, possesses anti-aging properties. It activates the synthesis of mucopolysaccharides and stimulates the production of aminoglycosides in the skin, thereby promoting collagen synthesis. This strengthens and enhances skin elasticity, improves fine lines, and prevents aging. Bosin is reportedly green, safe, biodegradable, mild, non-toxic, and highly effective.

[0003] Pro-Xylane is known in English as Pro-Xylane, and its international cosmetic designation is "Hydroxypropyltetrahydropyrantriol." Its chemical structure is C-β-D-xylopyranoside-2-hydroxypropane (see Formula I). ​​In 2002, L'Oréal disclosed its chemical structure, preparation route, and cosmetic applications in patent WO2002051828.

[0004]

[0005] Currently, the preparation methods of boson are basically concentrated in the above-mentioned roadmap, but these preparation methods all have the following problems:

[0006] 1. Desalination problem. Because the solubility of phosphene intermediates and phosphene in water is very high, and these preparation processes all involve the use and production of highly water-soluble salts, the salt content in the product is very high, and the pressure of desalination is very high, especially in the reducing agent step and the deprotection step. Regardless of whether metal reducing agents, enzyme catalysis, or alkaline hydrolysis conditions are used, desalination problems exist. Currently, ion exchange resin exchange and membrane separation technology are used for the desalination of phosphene.

[0007] 2. Complicated post-processing. As mentioned above, ion exchange resin and membrane separation technologies have a long cycle time, and it is difficult to completely remove salt in one go. At the same time, the product requires a large amount of water to be concentrated. The long cycle time and small batch size are the biggest problems, making it difficult to achieve industrial production.

[0008] 3. Impurity issues. All preparation methods in the literature produce and retain acetic acid, which can introduce a sour taste to the bosin product. If a boron-containing reducing agent is used, boric acid and borates are produced. These are listed in the list of prohibited additions and residues in the cosmetics industry standards. Therefore, borate residues pose a fatal risk to the quality of the bosin product. Summary of the Invention

[0009] In order to solve the above problems, the present invention discloses a method for preparing bosine, which avoids complex processes such as desalination and water concentration, controls the salt content, reduces the generation of wastewater, and has mild reaction conditions and simple operation, which is conducive to scale-up and commercial production.

[0010] The present invention aims to disclose a method for preparing boson, comprising the following reaction steps:

[0011]

[0012] The compound of formula II is deprotected under acid and alcohol conditions to obtain the compound of formula I;

[0013] Pg is a hydroxyl protecting group.

[0014] Furthermore, the acid includes one or a combination of heteropoly acid, acidic cation exchange resin, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, hydrogen chloride, hydrobromic acid, and sulfuric acid.

[0015] Furthermore, the molar ratio of the compound of formula II to the acid is 1:0.1-20.

[0016] Furthermore, the alcohol includes one or a combination of methanol, ethanol, n-propanol or n-butanol;

[0017] Furthermore, the molar amount of the alcohol is at least 4 times the molar amount of the compound of formula II.

[0018] Furthermore, the protecting group is a C-C6 fatty acyl group or an aromatic acyl group.

[0019] Furthermore, the S configuration of the compound of formula II is,

[0020]

[0021] The reaction formula is

[0022]

[0023] Furthermore, the compound of formula II is prepared using D-xylose as a raw material to obtain:

[0024] D-xylose and acetylacetone are subjected to a condensation reaction under inorganic base conditions to generate a compound of formula A, which is then reduced to obtain a crude product of boseidolin, and a protective group is added to the crude product of boseidolin to obtain a compound of formula II;

[0025] The compound of formula A is reacted under the conditions of a metal reducing agent or reductase to obtain a crude product of bosine.

[0026] Furthermore, the crude bosine reacts with one compound under alkaline conditions to prepare the compound of formula II.

[0027] Furthermore, the method for preparing the compound of formula II is a "one-pot method".

[0028] Compared with the prior art, the present application has the following advantages: the present invention uses alcohol and acid reaction conditions, which are mild and simple to operate, and are conducive to scale-up and commercial production. The materials of the present invention are simple and easy to obtain, highly safe, and meet the development requirements of green environmental protection. The present process route circumvents the complex processes such as desalination and water concentration that must be used in the prior art, avoids the generation of large amounts of wastewater, and meets the development requirements of green environmental protection. The products prepared by the present invention are superior to the products obtained by the process routes reported in the literature in terms of color, odor, purity and isomer purity control, boric acid and borate, and salt content. The present process route can also obtain highly selective S-bosine. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 Example 1-1-2 Boseiin 1 H NMR spectrum;

[0030] Figure 2 Example 2-2-2S-Bosone purity spectrum;

[0031] Figure 3 Example 2-3-1 Purity spectrum of the compound of formula II-1;

[0032] Figure 4 MS spectrum of the compound of formula II-1 of Example 2-3-1;

[0033] Figure 5 Example 2-3-1 Compound of Formula II-1 1 H NMR spectrum;

[0034] Figure 6 Example 2-3-2S-Bosone purity spectrum;

[0035] Figure 7 Example 2-3-2 MS spectrum of S-Bosine;

[0036] Figure 8 Example 2-3-2S-Bosone 1 H NMR spectrum. Example

[0037] It should be noted that, in the absence of conflict, the embodiments and features of the embodiments in this application can be combined with each other. The present invention will be described in detail below with reference to the accompanying drawings and in combination with the embodiments.

[0038] The present invention discloses a method for preparing boson, comprising the following reaction steps:

[0039]

[0040] The compound of formula II is deprotected under acid and alcohol conditions to obtain the compound of formula I;

[0041] Pg is a hydroxyl protecting group.

[0042] The acid includes one or a combination of heteropolyacid, acidic cation exchange resin, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, hydrogen chloride, hydrobromic acid, and sulfuric acid. Further, the acid is one or a combination of acidic cation exchange resin, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, hydrogen chloride, hydrobromic acid, and sulfuric acid. Preferably, the acid is one or a combination of acidic cation exchange resin, p-toluenesulfonic acid, and hydrogen chloride.

[0043] Hydrates, polymers, acid radicals and the like of the acids listed in the present invention all fall within the scope of protection of the present invention.

[0044] The commercial form of hydrogen chloride is hydrochloric acid solution, including gas dissolved in aqueous solution or organic solvent solution, or low concentration solution prepared from high concentration solution, etc. In fact, it is hydrogen chloride that participates in the reaction, and no matter what form is used, it belongs to hydrogen chloride in the present invention.

[0045] The molar ratio of the compound of formula II to the acid is 1:0.1 to 20. Further, the molar ratio of the compound of formula II to the acid is 1:0.1 to 10.

[0046] The commercially available acid is in the form of a solution, and the molar ratio of the compound of formula II to the acid is calculated according to the molar ratio of the solute.

[0047] The alcohol includes one or a combination of methanol, ethanol, n-propanol or n-butanol; further, the alcohol is methanol or ethanol.

[0048] The molar amount of the alcohol is at least 4 times the molar amount of the compound of formula II.

[0049] The protecting group is a C-C6 fatty acyl group or an aromatic acyl group, further comprising an acetyl group or a benzoyl group.

[0050] The S configuration of the compound of formula II is,

[0051]

[0052] The reaction formula is

[0053]

[0054] The compound of formula II is prepared using D-xylose as raw material to obtain:

[0055] D-xylose and acetylacetone are subjected to a condensation reaction under inorganic base conditions to generate a compound of formula A, which is then reduced to obtain a crude product of boseidolin, and a protective group is added to the crude product of boseidolin to obtain a compound of formula II;

[0056] The compound of formula A is reacted under the conditions of a metal reducing agent or reductase to obtain a crude product of bosine.

[0057] The crude bosine reacts with one of the compounds under alkaline conditions to prepare the compound of formula II.

[0058] The method for preparing the compound of formula II is a "one-pot process".

[0059] The molar ratio of D-xylose to acetylacetone is 1:1 to 3, and further 1:1.5.

[0060] The inorganic base is one of sodium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, and potassium hydroxide, and further the inorganic base is one of sodium hydroxide, sodium carbonate, and sodium bicarbonate. The molar ratio of D-xylose to the inorganic base is 1:1-3, and further 1:1.5.

[0061] The reaction temperature of D-xylose and acetylacetone is 35 to 100°C, further 40 to 95°C, further 50 to 90°C.

[0062] The pH of the reaction between D-xylitol and acetylacetone is 6-7.

[0063] The compound of formula A reacts with a metal reducing agent and an enzyme reducing agent to obtain bosine. The metal reducing agent is sodium triacetoxyborohydride or sodium borohydride. The enzyme reducing agent includes dehydrogenase and ketoreductase.

[0064] Under alkaline conditions, a protecting group is added to bosine, wherein the protecting group is a C-C6 fatty acyl group or an aromatic acyl group, further comprising an acetyl group or a benzoyl group. The base is triethylamine.

[0065] In some embodiments, the preparation process of the compound of formula II is as follows:

[0066]

[0067] In some embodiments, the process for preparing S-bosine from the S-configuration of the compound of formula II is as follows:

[0068]

[0069] The technical solution of the present invention also includes, after preparing the compound of formula I, refluxing the mixed solution, concentrating the solution collected after reflux under reduced pressure, and recrystallizing it in isopropanol to obtain the final product.

[0070] It should be noted that the present invention primarily protects a process for preparing bosonine or S-bosonine, which primarily involves protecting crude bosonine prepared in the prior art and then deprotecting it under alcohol or acid conditions to produce high-purity bosonine or S-bosonine. This method avoids the drawbacks of the prior art.

[0071] Example 1

[0072]

[0073] Example 1-1-1

[0074] Pg: Acetyl

[0075] Add D-xylose (20.0 g, 1.0 eq) and purified water (120.0 g) to a 250 mL three-necked flask. Stir and dissolve the solid until it dissolves. Add acetylacetone (16.0 g, 1.2 eq) and stir until uniform. Add sodium bicarbonate (16.8 g, 1.5 eq). After the addition is complete, control the temperature at 90°C and react for 18-24 hours. The reaction is complete. Directly evaporate the water under reduced pressure to obtain the concentrate, which is the crude product of Compound A.

[0076] Add methanol (100 mL) to the crude compound A, then add sodium borohydride (7.6 g) in portions while stirring at room temperature. After the addition is complete, allow to react at room temperature for 2-4 hours. The reaction is complete. Filter, collect the filtrate, and concentrate under reduced pressure to dryness to obtain the crude boron sulfoxide.

[0077] Tetrahydrofuran (100 mL) was added to the crude bosaicin product, and after stirring, triethylamine (40.0 g) was added, and finally acetic anhydride (70.0 g) was added dropwise. After the addition of the ingredients, the reaction was allowed to proceed at room temperature for 2-4 hours, and the reaction was completed. Purified water (200 mL) was added dropwise to quench the reaction, and then the product was extracted three times with ethyl acetate (100 mL). The organic phases were combined and washed with purified water (100 mL). The organic phases were concentrated to dryness under reduced pressure to obtain the crude product of Formula II (43.6 g, yield: 90.8%).

[0078] Example 1-1-2

[0079] Take crude bosonine (43.6 g), add anhydrous methanol (320.0 g), stir evenly, then add acidic cation exchange resin (10.0 g), and reflux for 36-48 hours to complete the reaction. After cooling the reaction solution to room temperature, filter out the resin and collect the filtrate. Add activated carbon (2.0 g) to the filtrate, heat to 50°C, stir for half an hour, filter, and collect the filtrate. The filtrate is then concentrated under reduced pressure to dryness to obtain a colorless viscous substance, bosonine (9.7 g, yield: 41.6%, NMR identification S / R: 0.47:0.53). 1H NMR (400MHz, CD3OD): δ3.99-3.94(m, 1H), δ3.87-3.82(m, 1H), δ3.48-3.42(m, 1H) , δ3.31-2.99 (m, 4H), δ1.94-1.88 (m, 1H), δ1.65-1.39 (m, 1H), δ1.18-1.16 (m, 3H).

[0080] Example 1-2-1

[0081] Pg:Benzoyl

[0082] Add D-xylose (20.0 g, 1.0 eq) and purified water (120.0 g) to a 250 mL three-necked flask. Stir and dissolve the solid until it dissolves. Add acetylacetone (16.0 g, 1.2 eq) and stir until uniform. Add sodium bicarbonate (16.8 g, 1.5 eq). After the addition is complete, control the temperature at 90°C and react for 18-24 hours. The reaction is complete. Directly evaporate the water under reduced pressure to obtain the concentrate, which is the crude product of Compound A.

[0083] Add methanol (100 mL) to the crude compound A, then add sodium borohydride (7.6 g) in portions while stirring at room temperature. After the addition is complete, allow to react at room temperature for 2-4 hours. The reaction is complete. Filter, collect the filtrate, and concentrate under reduced pressure to dryness to obtain the crude boron sulfoxide.

[0084] Tetrahydrofuran (100 mL) was added to the crude bosaicin product, and after stirring, triethylamine (40.0 g) was added, and finally benzoic anhydride (151.4 g) was added dropwise. After the addition of the ingredients, the reaction was allowed to proceed at room temperature for 2-4 hours, and the reaction was completed. Purified water (200 mL) was added dropwise to quench the reaction, and then the product was extracted three times with ethyl acetate (100 mL). The organic phases were combined and washed with purified water (100 mL). The organic phases were concentrated to dryness under reduced pressure to obtain the crude product of Formula II (43.5 g, yield: 90.6%).

[0085] Example 1-2-2

[0086] Take crude bosonine (43.5g), add anhydrous methanol (320.0g), stir evenly, then add acidic cation exchange resin (10.0g), and reflux for 36-48 hours to complete the reaction. After cooling the reaction solution to room temperature, filter out the resin and collect the filtrate. Add activated carbon (2.0g) to the filtrate, heat to 50°C, stir for half an hour, filter, and collect the filtrate. The filtrate is then concentrated under reduced pressure to dryness to obtain a colorless viscous substance, bosonine (9.7g, yield: 41.7%, NMR identification S / R: 0.47:0.53). 1H NMR (400MHz, CD3OD): δ3.99-3.94(m, 1H), δ3.87-3.82(m, 1H), δ3.48-3.42(m, 1H) , δ3.31-2.99 (m, 4H), δ1.94-1.88 (m, 1H), δ1.65-1.39 (m, 1H), δ1.18-1.16 (m, 3H).

[0087] Example 1-3-1

[0088] Pg: Acetyl

[0089] Add D-xylose (10.0 g, 1.0 eq) and purified water (80.0 g) to a 250 mL three-necked flask. Stir and dissolve the solid until it is almost dissolved. Add acetylacetone (8.0 g, 1.2 eq) and stir until evenly mixed. Add sodium bicarbonate (8.4 g, 1.5 eq). After the addition is complete, control the temperature at 90°C and react for 18-24 hours. The reaction is complete. Directly evaporate the water under reduced pressure to obtain the concentrate, which is the crude product of Compound A.

[0090] Add methanol (100 mL) to the crude compound A, then add sodium borohydride (3.9 g) in portions while stirring at room temperature. After the addition is complete, allow to react at room temperature for 2-4 hours. The reaction is complete. Filter, collect the filtrate, and concentrate under reduced pressure to dryness to obtain the crude boron sulfoxide.

[0091] Tetrahydrofuran (50 mL) was added to the crude bosaicin product, and after stirring, triethylamine (20.0 g) was added, and finally acetic anhydride (35.2 g) was added dropwise. After the addition of the ingredients, the reaction was allowed to proceed at room temperature for 2-4 hours, and the reaction was completed. Purified water (200 mL) was added dropwise to quench the reaction, and then the product was extracted three times with ethyl acetate (100 mL). The organic phases were combined and washed with purified water (100 mL). The organic phases were concentrated to dryness under reduced pressure to obtain the crude product of Formula II (21.9 g, yield: 91.2%).

[0092] Example 1-3-2

[0093] Take crude bosonine (21.9 g), add anhydrous methanol (165.0 g), stir evenly, then add hydrochloric acid (5.0 g of hydrogen chloride), reflux reaction, and the reaction is complete. After the reaction solution is cooled to room temperature, filter out the resin and collect the filtrate. Add activated carbon (2.0 g) to the filtrate, heat to 50°C, stir for half an hour, filter, and collect the filtrate. The filtrate is then concentrated under reduced pressure to dryness to obtain a colorless viscous substance, i.e., bosonine (4.9 g, yield: 41.7%, NMR identification S / R: 0.47:0.53). 1H NMR (400MHz, CD3OD): δ3.99-3.94(m, 1H), δ3.87-3.82(m, 1H), δ3.48-3.42(m, 1H) , δ3.31-2.99 (m, 4H), δ1.94-1.88 (m, 1H), δ1.65-1.39 (m, 1H), δ1.18-1.16 (m, 3H).

[0094] Example 2

[0095]

[0096] Example 2-1-1

[0097] Pg: Acetyl

[0098] Add D-xylose (10.0 g, 1.0 eq) and purified water (30.0 g) to a 100 mL three-necked flask and stir until the solid is substantially dissolved. Add acetylacetone (8.0 g, 1.2 eq) and stir evenly. Prepare a mixed solution of sodium hydroxide (4.0 g, 1.5 eq) and purified water (20.0 g) and slowly add it dropwise to the reaction flask. After the addition is complete, control the temperature at 50°C and react for 1-3 hours to complete the reaction. Then, adjust the pH to 6-7 with acetic acid, and evaporate the water under reduced pressure to obtain a concentrate, which is the crude product of Compound A.

[0099] Isopropanol (50 mL) was added to the crude compound A. Sodium triacetoxyborohydride (30.0 g) was then added portionwise with stirring at room temperature. The reaction was allowed to proceed at room temperature for 5-8 hours. The reaction was complete. The filtrate was collected and concentrated to dryness under reduced pressure to obtain the crude S-bosonine product.

[0100] Tetrahydrofuran (60 mL) was added to the crude S-bosine product, and after stirring, triethylamine (20.0 g) was added, followed by the dropwise addition of acetic anhydride (35.0 g). After the addition of the ingredients, the reaction was allowed to proceed at room temperature for 2-4 hours, and the reaction was completed. Purified water (100 mL) was added dropwise to quench the reaction, and the product was then extracted three times with ethyl acetate (50 mL). The organic phases were combined, washed once with purified water (80 mL), and then concentrated under reduced pressure to dryness to obtain a concentrate of the crude compound of formula II-1. The crude compound of formula II-1 was recrystallized from isopropanol to obtain the compound of formula II-1 (17.6 g, yield: 73.3%, purity: 98.9%). MS (ESI): m / z: 378.3 [M+NH4]+. 1H NMR (400MHz, CD3OD): δ5.17-5.13 (t, 1H), δ5.08-5.00 (m, 1H), δ4.94-4.88 (m, 1H), δ4.79-4.75 (t, 1H), δ4.05-4.0 0 (dd, 1H), δ3.57-3.52 (m, 1H), δ3.34-3.28 (m, 1H), δ2.02-1.98 (m, 12H), δ1.81-1.66 (m, 2H), δ1.22-1.21 (d, 3H).

[0101] Example 2-1-2

[0102] Compound II-1 (10.0 g, 1.0 eq) was added to anhydrous ethanol (100.0 g), followed by the addition of p-toluenesulfonic acid monohydrate (0.53 g, 0.1 eq) with stirring. The mixture was refluxed for 36-48 hours to complete the reaction. After concentration under reduced pressure, the mixture was recrystallized from isopropanol to obtain S-Bosylamine (4.6 g, yield: 86.2%, purity: 99.5%, R-Bosylamine: 0.40%, borate: not detected, acetic acid: not detected, residue on ignition: not detected). MS (ESI): m / z: 215.0888 [M+Na]+. 1H NMR (400MHz, CD3OD): δ4.01-3.93 (m, 1H), δ3.86-3.82 (dd, 1H), δ3.45-3.40 (m, 1H), δ3.25-3.21 (t, 1H) , δ3.19-3.08 (m, 2H), δ3.05-3.00 (t, 1H), δ1.92-1.87 (m, 1H), δ1.64-1.56 (m, 1H), δ1.16-1.15 (d, 3H).

[0103] Example 2-2-1

[0104] Pg:Benzoyl

[0105] Add D-xylose (20.0 g, 1.0 eq) and purified water (120.0 g) into a 250 mL three-necked flask and stir until the solid is substantially dissolved. Continue to add acetylacetone (16.0 g, 1.2 eq) and stir evenly. Finally, add sodium carbonate (14.1 g, 1.0 eq). After the addition is completed, control the temperature at 90°C and react for 6 to 10 hours to complete the reaction. Then adjust the pH to 6 to 7 with acetic acid, and then evaporate the water under reduced pressure. Then add isopropanol (100.0 g) to slurry and filter to obtain an isopropanol solution of compound A.

[0106] To an isopropanol solution of Compound A, add purified water (100.0 g), then add ketoreductase at 30±5°C. Stir the mixture for 24–48 hours. The reaction is complete. The reaction mixture is concentrated to dryness under reduced pressure, followed by the addition of dichloromethane (200.0 g) and stirring at room temperature for 30–60 minutes. Filter and collect the filtrate to obtain a dichloromethane solution of crude S-bosine.

[0107] Triethylamine (40.0 g) was added to a dichloromethane solution of crude S-bosine, and finally benzoic anhydride (150.7 g) was added dropwise. After the addition was completed, the reaction was allowed to proceed at room temperature for 2 to 4 hours, and the reaction was completed. Purified water (100 mL) was added dropwise to quench the reaction, and then the liquids were separated, and the aqueous phase was extracted once with dichloromethane (100 mL). The organic phases were combined and washed once with purified water (100 mL), and then the organic phase was concentrated under reduced pressure to dryness to obtain a concentrate as a crude compound II-1. The crude product of formula II-1 was recrystallized from isopropanol to obtain a compound of formula II-1 (55.2 g, yield: 68.1%, purity: 98.4%).

[0108] Example 2-2-2

[0109] Compound II-1 (25.0 g, 1.0 eq) was added to anhydrous methanol (250.0 g). Hydrochloric acid (41.6 g, 10.0 eq, calculated as hydrogen chloride) was then added with stirring. The reaction was refluxed for 36-48 hours. After concentration under reduced pressure, the mixture was recrystallized from isopropanol to obtain S-Bosylamine (5.5 g, yield: 69.7%, purity: 99.5%, R-Bosylamine: 0.37%).

[0110] Example 2-3-1

[0111] Pg: Acetyl

[0112] Add D-xylose (20.0 g, 1.0 eq) and purified water (70.0 g) to a 100 mL three-necked flask and stir until the solid is substantially dissolved. Add acetylacetone (16.0 g, 1.2 eq) and stir evenly. Prepare a mixed solution of sodium hydroxide (8.0 g, 1.5 eq) and purified water (50.0 g) and slowly add it dropwise to the reaction flask. After the addition is complete, control the temperature at 50°C and react for 1-3 hours to complete the reaction. Then, adjust the pH to 6-7 with acetic acid, and evaporate the water under reduced pressure to obtain a concentrate, which is the crude product of Compound A.

[0113] Isopropanol (50 mL) was added to the crude compound A. Sodium triacetoxyborohydride (60.0 g) was then added portionwise with stirring at room temperature. The reaction was allowed to proceed at room temperature for 5-8 hours. The reaction was complete. The filtrate was collected and concentrated to dryness under reduced pressure to obtain the crude S-bosonine product.

[0114] Tetrahydrofuran (60 mL) was added to the crude S-bosine product, and after stirring, triethylamine (40.0 g) was added, followed by the dropwise addition of acetic anhydride (70.0 g). After the addition of the ingredients, the reaction was allowed to proceed at room temperature for 2-4 hours, and the reaction was complete. Purified water (200 mL) was added dropwise to quench the reaction, and the product was then extracted three times with ethyl acetate (100 mL). The organic phases were combined, washed once with purified water (160 mL), and then concentrated under reduced pressure to dryness to obtain a crude product of the compound of formula II-1. The crude compound of formula II-1 was recrystallized from isopropanol to obtain the compound of formula II-1 (35.5 g, yield: 73.4%, purity: 99.4%). MS (ESI): m / z: 378.3 [M+NH4]+. 1H NMR (400MHz, CD3OD): δ5.17-5.13 (t, 1H), δ5.08-5.00 (m, 1H), δ4.94-4.88 (m, 1H), δ4.79-4.75 (t, 1H), δ4.05-4.0 0 (dd, 1H), δ3.57-3.52 (m, 1H), δ3.34-3.28 (m, 1H), δ2.02-1.98 (m, 12H), δ1.81-1.66 (m, 2H), δ1.22-1.21 (d, 3H).

[0115] Example 2-3-2

[0116] Compound II-1 (35.5 g, 1.0 eq) was added to anhydrous methanol (440.0 g). Hydrochloric acid (85.0 g, 10.0 eq, calculated as hydrogen chloride) was then added with stirring. The reaction was refluxed for 36-48 hours. After concentration under reduced pressure, the mixture was recrystallized from isopropanol to obtain S-Bosylamine (11.1 g, yield: 73.3%, purity: 99.5%, R-Bosylamine: 0.37%).

[0117] The foregoing description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Those skilled in the art will readily appreciate that various modifications and variations of the present invention are possible. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present invention are intended to be within the scope of protection of the present invention.

Claims

1. A method for preparing boson, characterized in that: The following reaction steps are included: The compound of formula II is deprotected under acid and alcohol conditions to obtain the compound of formula I; Pg is a hydroxyl protecting group.

2. The method for preparing boson according to claim 1, wherein: The acid includes one or a combination of heteropolyacid, acidic cation exchange resin, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, hydrogen chloride, hydrobromic acid, and sulfuric acid.

3. The method for preparing boson according to claim 2, wherein: The molar ratio of the compound of formula II to the acid is 1:0.1-20.

4. The method for preparing boson according to claim 2, wherein: The alcohol includes one or a combination of methanol, ethanol, n-propanol or n-butanol; 5. The method for preparing boson according to claim 4, wherein: The molar amount of the alcohol is at least 4 times the molar amount of the compound of formula II.

6. The method for preparing boson according to claim 5, characterized in that: The protecting group is a C-C6 fatty acyl group or an aromatic acyl group.

7. The method for preparing boson according to claim 6, wherein: The S configuration of the compound of formula II is, The reaction formula is Pg is a C-C6 fatty acyl group or an aromatic acyl group.

8. The method for preparing boson according to any one of claims 1 to 7, characterized in that: The compound of formula II is prepared using D-xylose as raw material to obtain: D-xylose and acetylacetone are subjected to a condensation reaction under inorganic base conditions to generate a compound of formula A, which is then reduced to obtain a crude product of boseidolin, and a protective group is added to the crude product of boseidolin to obtain a compound of formula II; The compound of formula A is reacted under the conditions of a metal reducing agent or reductase to obtain a crude product of bosine.

9. The method for preparing boson according to claim 8, wherein: The crude bosine reacts with one of the compounds under alkaline conditions to prepare the compound of formula II.

10. The method for preparing boson according to claim 9, characterized in that: The method for preparing the compound of formula II is a "one-pot process".

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