A method for synthesizing xylulose-5-phosphate

Abstract

The application discloses a synthesis method of xylulose-5-phosphate. The method takes a commercially available compound 1 as a starting material, and obtains the target product xylulose-5-phosphate through seven independent step-by-step reactions. The intermediates are compound 2 to compound 7 in turn. The synthesis method provided by the application is a step-by-step reaction, each reaction is an independent unit, the process parameters are accurately controllable and suitable for industrial operation errors, the side reactions are few, and the product selectivity is high. The method innovatively uses tetrabenzyl pyrophosphate as a phosphorylation reagent, replaces expensive reagents, and reduces the synthesis cost. The reaction condition of the method is mild, the operation is convenient, the crude compound 2 and the crude compound 4 can be directly used in the next step reaction, the post-treatment process is simple, and the route is simple and easy to be industrialized. The synthesis method of xylulose-5-phosphate has stable yield and accurate product structure, is suitable for large-scale industrialized preparation of xylulose-5-phosphate, and can effectively meet the market demand in the field of biological medicines.

Description

Technical Field

[0001] This invention relates to the field of biopharmaceutical synthesis technology, and in particular to a method for synthesizing xylulose-5-phosphate. Background Technology

[0002] Xylanose-5-phosphate (CAS: 4212-65-1) is a core pentose phosphate intermediate in the pentose phosphate pathway, playing an irreplaceable role in the regulation of cellular metabolism. Xylanose-5-phosphate can regulate immune metabolic reprogramming, maintain the stemness and directional differentiation ability of T cells, significantly enhance the anti-tumor killing activity of T cells, and inhibit the epithelial-mesenchymal transition process of tumor cells, effectively reducing the risk of tumor metastasis. It has extremely high application value in core biomedical fields such as tumor immunotherapy and research on cell metabolic mechanisms. Furthermore, xylanose-5-phosphate can also serve as a key synthetic precursor in the preparation of novel sugar derivatives, pharmaceutical intermediates, and bioactive molecules, with market demand for its large-scale, high-purity products continuing to grow.

[0003] Currently, the preparation methods of xylulose-5-phosphate are mainly divided into two categories: bio-enzyme catalysis and chemical synthesis. Bio-enzyme catalysis relies on the catalytic action of microorganisms or specific enzyme preparations to achieve synthesis, but it has problems such as high enzyme preparation costs, sensitivity of the reaction system to environmental conditions such as temperature and pH, difficulty in separating and purifying the product from the enzyme preparation, low efficiency in large-scale production, and unstable product yield, making it difficult to meet the actual needs of industrial-scale mass production. Chemical synthesis has become the mainstream research direction for the preparation of xylulose-5-phosphate due to its advantages such as strong controllability of product structure, easy guarantee of purity, and good process scalability. However, there are very few reports on related technologies, and the few published chemical synthesis methods have many technical defects, such as: 1. The starting materials are mostly non-commercial rare sugar derivatives, which limit the availability of raw materials and are costly, thus restricting the industrial scale-up of the process from the source; 2. The synthetic route design is unreasonable, the reaction steps are lengthy and the reaction conditions of each step are harsh, and some steps require special reaction environments such as ultra-low temperature and high pressure, which places strict requirements on production equipment and increases the cost of industrial production; 3. The key phosphorylation steps often use expensive phosphorylating reagents, which not only greatly increases the synthesis cost, but also has problems such as poor reaction selectivity and many by-products, resulting in increased difficulty in product separation and low yield; 4. The process parameters of each reaction step lack systematic optimization, the reaction reproducibility is poor, and there is no mature industrial process control scheme, so a chemical synthesis process of xylulose-5-phosphate suitable for large-scale industrial production has not yet been formed.

[0004] Therefore, there is an urgent need in this field to develop a chemical synthesis method for xylulose-5-phosphate that is readily available, easy to operate, has mild reaction conditions, a simple and controllable route, high yield, and can be scaled up industrially. Summary of the Invention

[0005] To solve the above-mentioned technical problems, the present invention provides a method for synthesizing xylulose-5-phosphate, comprising the following steps: S1. At 0℃, compound 1 is dissolved in methanol, and acetyl chloride is added dropwise. The temperature is raised to 25℃~30℃ and reacted for 4-6 hours. After quenching and concentration under reduced pressure, crude compound 2 is obtained. The crude product is directly used in the next step. Preferably, the reaction conditions are to raise the temperature to 25℃ and react for 4 hours. S2, 0℃ feeding, compound 2 and benzyl bromide are dissolved in N,N-dimethylformamide, sodium hydride is added in batches, reaction is carried out at 25℃~30℃ for 12~16h, and compound 3 is obtained by extraction, drying, vacuum concentration and column chromatography purification; preferably, the reaction condition is 25℃ for 12h. S3, feed at 25℃, dissolve compound 3 in acetic acid, add 3M sulfuric acid aqueous solution, heat at 90℃~110℃ for 0.5h~1h, extract, dry, concentrate under reduced pressure to obtain crude compound 4, which is directly used in the next step; preferably, the reaction conditions are heating at 100℃ for 0.5h. S4. At 0℃, compound 4 is dissolved in ethanol, and sodium borohydride is added in batches. The reaction is carried out at 25℃~30℃ for 12~16h. After quenching, acidification, extraction, drying, vacuum concentration, and column chromatography purification, compound 5 is obtained. Preferably, the reaction conditions are 25℃ for 12h. S5. At 0℃, compound 5 is dissolved in dichloromethane, and tetrabenzyl pyrophosphate, tetraisopropyl titanate and diisopropylethylamine are added. The reaction is carried out at 25℃-30℃ for 12-16h. After quenching, acidification, extraction, drying, vacuum concentration and column chromatography purification, compound 6 is obtained. Preferably, the reaction conditions are 25℃ for 12h. S6. At 25°C, compound 6 is dissolved in dichloromethane, and Dys-Martin oxidant is added. The reaction is carried out at 25°C to 30°C for 2 to 3 hours. After washing with water, extraction, drying, concentration under reduced pressure, and purification by column chromatography, compound 7 is obtained. Preferably, the reaction conditions are 25°C for 2 hours. S7, 25℃, compound 7 was dissolved in ethanol, 10% wet palladium on carbon catalyst was added, after three hydrogen replacements, the reaction was carried out at 25℃ and 15psi hydrogen pressure for 2-3 hours, and the target product compound 8 was obtained by filtration and vacuum concentration. The structural formulas of compounds 1 to 8 are as follows: Compound 1 ; Compound 2 ; Compound 3 ; Compound 4 ; Compound 5 ; Compound 6 ; Compound 7 ; Compound 8 .

[0006] Specifically, in S1, the molar ratio of compound 1 to acetyl chloride is 1:(0.7~0.9), preferably 1:0.8, the amount of methanol used is 8~12 mL of methanol per 1g of compound 1, preferably 10 mL, and the quenching agent is ammonium bicarbonate.

[0007] Specifically, in S2, the sodium hydride is 60% pure industrial grade sodium hydride, the molar ratio of compound 2, benzyl bromide and sodium hydride is 1:(4~5):(4~5), preferably 1:4.3:4.3, the amount of N,N-dimethylformamide used is 8~12 mL of N,N-dimethylformamide per 1g of compound 2, preferably 10 mL, the column chromatography uses silica gel as packing material and petroleum ether-ethyl acetate mixture as eluent.

[0008] Specifically, in step S3, the molar ratio of compound 3 to sulfuric acid is 1:(1.8~2.2), preferably 1:2, and the amount of acetic acid used is 4~6 mL of acetic acid per 1 g of compound 3, preferably 5.4 mL.

[0009] Specifically, in step S4, the molar ratio of compound 4 to sodium borohydride is 1:(1.4~1.6), preferably 1:1.52, the amount of ethanol used is 8~12mL of ethanol per 1g of compound 4, preferably 10mL, the quenching reagent is acetone, the acidification reagent is 1M dilute hydrochloric acid aqueous solution, the column chromatography uses silica gel as packing material, and the eluent is a mixture of petroleum ether and ethyl acetate.

[0010] Specifically, in step S5, the molar ratio of compound 5 to tetrabenzyl pyrophosphate is 1:(1.1~1.3), preferably 1:1.2; the amount of tetraisopropyl titanate and diisopropylethylamine added is 3.0~3.5 times the molar amount of compound 5, preferably 3.2 times; the amount of dichloromethane used is 8~12mL of dichloromethane per 1g of compound 5, preferably 10mL; the column chromatography uses silica gel as packing material and a petroleum ether-ethyl acetate mixture as eluent.

[0011] Specifically, in step S6, the molar ratio of compound 6 to Dys-Martin oxidant is 1:(1.4~1.6), preferably 1:1.5, and the amount of dichloromethane used is 4~6 mL of dichloromethane per 1 g of compound 6, preferably 5.3 mL. Silica gel is used as the packing material for column chromatography, and a mixture of petroleum ether and ethyl acetate is used as the eluent.

[0012] Specifically, in step S7, the amount of the 10% wet palladium on carbon catalyst added is 70-85% of the mass of compound 7, preferably 78.2%, and the amount of ethanol used is 8-10 mL of ethanol per 1 g of compound 7, preferably 9.1 mL.

[0013] Specifically, in S1 and S3, the vacuum degree of crude product concentration under reduced pressure is -0.08 ~ -0.10 MPa, and the temperature is 40 ~ 50℃.

[0014] Specifically, in S7, the filtration is performed by diatomaceous earth filtration with a mesh size of 200-300 mesh.

[0015] The beneficial effects of this invention include: (1) The present invention adopts a stepwise synthesis method, and the synthesis route is designed with only seven steps. The steps are simple, the reaction conditions are mild, and there is no need for special reaction environments such as ultra-low temperature and ultra-high pressure. The requirements for production equipment are low, the operation is convenient, and it is suitable for industrial production. In addition, each step of the reaction is an independent reaction unit, the process parameters are set in a reasonable range, which is precise and controllable and adaptable to the operation error of industrial production. It avoids the mutual interference of multiple reagents coexisting, has few side reactions, high product selectivity, stable yield of each step of the reaction, good process reproducibility, and facilitates further industrial scale-up production and quality control of the production process.

[0016] (2) The reaction method provided by the present invention uses commercially available and low-cost compound 1 (xylose) as the starting material. The raw material has a wide range of acquisition channels, which solves the problem of limited raw materials and high cost in the existing methods. It significantly reduces the raw material cost of industrial production. In addition, tetrabenzyl pyrophosphate is introduced as a phosphorylation reagent to introduce phosphate groups, replacing the expensive phosphorylation reagents in the existing technology. This not only significantly reduces the synthesis cost, but also improves the selectivity and yield of the phosphorylation reaction, and significantly improves the economic efficiency of phosphoric acid synthesis.

[0017] (3) The preparation method provided by the present invention allows the crude products of compounds 2 and 4 to be used directly in the next reaction without purification, which simplifies the post-processing operation and shortens the production cycle. Other purification steps can be achieved by conventional silica gel column chromatography. The purification process is simple and easy to operate, suitable for industrial development. Moreover, the target product compound 8 has an accurate structure and good purity. The overall yield is suitable for industrial production, which effectively meets the demand of the field for large-scale and high-purity xylulose-5-phosphate products. Attached Figure Description

[0018] Figure 1 This is a synthetic route diagram of xylulose-5-phosphate according to the present invention; In the figure, Bn represents benzyl (—CH2C6H5). Detailed Implementation

[0019] The technical solution of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. 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.

[0020] Example 1

[0021] like Figure 1 The synthetic route shown below has the following specific operational steps: (1) Preparation of compound 2:

[0022] At 0°C, acetyl chloride (83.66 g, 1.07 mol, 75.78 mL) was added dropwise to a methanol (2000.0 mL) solution of compound 1 (200.00 g, 1.33 mol), with a molar ratio of compound 1 to acetyl chloride of 1:0.8 and a methanol volume of 10 mL per 1 g of compound 1. The mixture was naturally heated to 25°C and maintained for 4 hours. Thin-layer chromatography (developing solvent: dichloromethane: methanol = 5:1, Rf = 0.32) showed that compound 1 was completely consumed. The reaction mixture was cooled to 0°C, quenched with ammonium bicarbonate (50 g) under vigorous stirring, and then concentrated under reduced pressure to give crude compound 2 (160.0 g, 974.68 mmol, yield 73.2%), a yellow slurry. The crude product was used directly in the next step without further purification.

[0023] (2) Preparation of compound 3:

[0024] At 0°C, compound 2 (160.0 g, 974.68 mmol) and benzyl bromide (716.83 g, 4.19 mol) were dissolved in N,N-dimethylformamide (1600 mL), with 10 mL of N,N-dimethylformamide per 1 g of compound 2. Sodium hydride (167.63 g, 4.19 mol) of 60% purity was added in portions, resulting in a molar ratio of compound 2, benzyl bromide, and sodium hydride of 1:4.3:4.3 based on the active ingredient. The reaction was carried out at 25°C for 12 hours. Thin-layer chromatography (developing solvent: petroleum ether: ethyl acetate = 10:1, Rf = 0.50) showed that compound 2 was completely consumed. The reaction mixture was poured into ice water (1000 mL) under vigorous stirring, and ethyl acetate (2000 mL) was added for washing and extraction. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude compound. The crude compound was purified by silica gel column chromatography (200-300 mesh) (eluent: petroleum ether / ethyl acetate = 50 / 1 to 10 / 1, atmospheric pressure gradient elution) to give compound 3 (184.00 g, 423.45 mmol, yield 43.5%), a pale yellow oil.

[0025] (3) Preparation of compound 4:

[0026] Compound 3 (184.00 g, 423.45 mmol) was dissolved in acetic acid (1000 mL) at 25°C, with 5.4 mL of acetic acid per 1 g of compound 3. 3M sulfuric acid aqueous solution (282.30 mL, 846.90 mmol) was added, with a molar ratio of compound 3 to sulfuric acid of 1:2. The reaction was heated to 100°C and allowed to proceed for 0.5 hours. Thin-layer chromatography (developing solvent: petroleum ether: ethyl acetate = 10:1, Rf = 0.22) showed complete consumption of compound 3. The reaction mixture was poured into ice water (1000 mL), and ethyl acetate (2000 mL) was added for washing and extraction. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain crude compound 4 (130 g, 309.16 mmol, yield 73.0%), a yellow oily substance. The crude product was used directly in the next step without further purification.

[0027] (4) Preparation of compound 5:

[0028] At 0°C, sodium borohydride (17.15 g, 453.32 mmol) was added in portions to an ethanol (1250.0 mL) solution of compound 4 (125.00 g, 297.27 mmol), with a molar ratio of compound 4 to sodium borohydride of 1:1.52 and an ethanol volume of 10 mL per 1 g of compound 4. The mixture was stirred at 25°C for 12 hours, and thin-layer chromatography (developing solvent: petroleum ether: ethyl acetate = 2:1, Rf = 0.35) showed that compound 4 was completely consumed. At 0°C, acetone (20 mL) was added to quench the reaction mixture, and after stirring for 15 minutes, the mixture was acidified with 1M dilute hydrochloric acid aqueous solution (500 mL). The mixture was extracted three times with ethyl acetate (900 mL), and the combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude compound. The crude compound was purified by silica gel column chromatography (200-300 mesh) (eluent: petroleum ether / ethyl acetate = 10 / 1 to 2 / 1, gradient elution at atmospheric pressure) to give compound 5 (100.0 g, 236.68 mmol, yield 79.6%), as an off-white solid. The product was identified as consistent with one-dimensional nuclear magnetic resonance (NMR) hydrogen spectrum. ¹H NMR (400 MHz, Chloroform-d) δ ppm: 7.35 (s, 15 H), 4.67 (s, 2 H), 4.62 (d, J=2.5 Hz, 2 H), 4.57 (d, J=1.4 Hz, 2 H), 4.01 - 4.08 (m, 1 H), 3.73 - 3.84 (m, 4 H), 3.66 - 3.69 (m, 2 H), 2.93 - 3.12 (m, 1 H), 2.22 - 2.40 (m, 1 H).

[0029] (5) Preparation of compound 6:

[0030] At 0°C, tetrabenzyl pyrophosphate (91.76 g, 170.41 mmol), tetraisopropyl titanate (17.15 g, 453.32 mmol), and diisopropylethylamine (17.15 g, 453.32 mmol) were added to a dichloromethane (600.0 mL) solution of compound 5 (60.0 g, 142.01 mmol). The molar ratio of compound 5 to tetrabenzyl pyrophosphate was 1:1.2. The amounts of tetraisopropyl titanate and diisopropylethylamine added were 3.2 times the molar amount of compound 5. The amount of dichloromethane used was 10 mL per 1 g of compound 5. The mixture was stirred at 25°C for 12 hours. Thin-layer chromatography (developing solvent: petroleum ether: ethyl acetate = 2:1, Rf = 0.55) showed that compound 5 was completely consumed. At 0°C, acetone (20 mL) was added to quench the reaction mixture. After stirring for 15 minutes, 1M dilute hydrochloric acid aqueous solution (500 mL) was added for acidification. The mixture was extracted three times with ethyl acetate (900 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude compound. The crude compound was purified by silica gel column chromatography (200-300 mesh) (eluent: petroleum ether / ethyl acetate = 10 / 1 to 2 / 1, gradient elution at atmospheric pressure) to obtain compound 6 (101.0 g, 106.51 mmol, yield 75.0%, purity 72.0%), which was a yellow oil. The product was identified as consistent with one-dimensional nuclear magnetic resonance (1H) spectroscopy (400 MHz, Chloroform-d): δ ppm 7.15 - 7.30 (m, 25 H), 4.98 (s, 2 H), 4.96 (s, 2 H), 4.57 (s, 1 H), 4.40 - 4.50 (m, 5 H), 4.13 (d, J=6.8 Hz, 2 H), 3.84 - 3.94 (m, 2 H), 3.55 (br d, J=3.5 Hz, 3 H).

[0031] (6) Preparation of compound 7:

[0032] At 25°C, a solution of compound 6 (95.0 g, 100.19 mmol) in dichloromethane (500.0 mL) was treated with Dys-Martin oxidant (63.74 g, 150.28 mmol), with a molar ratio of compound 6 to Dys-Martin oxidant of 1:1.5 and a dichloromethane volume of 5.3 mL per 1 g of compound 6. The mixture was stirred at 25°C for 2 hours. Thin-layer chromatography (developing solvent: petroleum ether: ethyl acetate = 2:1, Rf = 0.68) showed that compound 6 was completely consumed. Water (500 mL) was added to the reaction system, and the mixture was extracted three times with dichloromethane (900 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude compound. The crude compound was purified by silica gel column chromatography (200-300 mesh) (eluent: petroleum ether / ethyl acetate = 10 / 1 to 2 / 1, gradient elution at atmospheric pressure) to give compound 7 (59.6 g, 87.55 mmol, yield 87.4%), which was a colorless oil. The product was identified as consistent with one-dimensional nuclear magnetic resonance (NMR) proton and phosphorus spectra. ¹H NMR (400 MHz, Chloroform-d) δ ppm 7.16 - 7.43 (m, 25 H), 4.97 - 5.07 (m, 4H), 4.34 - 4.55 (m, 6 H), 4.24 (d, J=5.0 Hz, 2 H), 4.08 (d, J=3.2 Hz, 3 H), 3.96 - 4.05 (m, 1 H); ³¹P NMR (162 MHz, Chloroform-d) δ ppm -1.00.

[0033] (7) Preparation of compound 8:

[0034] At 25°C, 42.99 g of 10% wet palladium on carbon was added to a 500.0 mL ethanol solution of compound 7 (55 g, 80.80 mmol). The amount of 10% wet palladium on carbon added was 78.2% of the mass of compound 7. The amount of ethanol added was 9.1 mL per 1 g of compound 7. A hydrogen atmosphere was established by three hydrogen purgings. The mixture was stirred at 25°C and 15 psi hydrogen pressure for 2 hours. LCMS analysis showed that compound 7 was completely consumed. The reaction system was filtered through diatomaceous earth to remove the palladium on carbon catalyst. The filtrate was concentrated under reduced pressure to obtain the target product compound 8 (10.5 g, 44.97 mmol, yield 55.7%), which was a yellow oil. The product was identified as consistent with one-dimensional nuclear magnetic resonance (NMR) proton and phosphorus spectra. 1H NMR (400 MHz, D2O) δ ppm 4.34 - 4.61 (m, 3 H), 4.09 - 4.19 (m, 1 H), 3.82 - 3.93 (m, 2 H); 31P NMR (162MHz, D2O) δ ppm 0.116.

[0035] In summary, the above embodiments are merely preferred embodiments of the present invention and are not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for synthesizing xylulose-5-phosphate, characterized in that, Includes the following steps: S1. Feeding at 0℃: Dissolve compound 1 in methanol, add acetyl chloride dropwise, heat to 25℃~30℃ and react for 4-6 hours. After quenching and concentration under reduced pressure, crude compound 2 is obtained. The crude product is directly used in the next step. S2, 0℃ feeding, compound 2 and benzyl bromide are dissolved in N,N-dimethylformamide, sodium hydride is added in batches, reaction is carried out at 25℃~30℃ for 12~16h, and compound 3 is obtained by extraction, drying, vacuum concentration and column chromatography purification. S3, feed at 25℃, dissolve compound 3 in acetic acid, add 3M sulfuric acid aqueous solution, heat at 90℃~110℃ for 0.5h~1h, extract, dry, concentrate under reduced pressure to obtain crude compound 4, which is directly used in the next step; S4, 0℃ feeding, compound 4 is dissolved in ethanol, sodium borohydride is added in batches, react at 25℃~30℃ for 12~16h, and compound 5 is obtained by quenching, acidification, extraction, drying, vacuum concentration and column chromatography purification. S5, 0℃ feeding, compound 5 is dissolved in dichloromethane, tetrabenzyl pyrophosphate, tetraisopropyl titanate and diisopropylethylamine are added, react at 25℃-30℃ for 12~16h, and compound 6 is obtained by quenching, acidification, extraction, drying, vacuum concentration and column chromatography purification. S6, 25℃, compound 6 was dissolved in dichloromethane, Dys-Martin oxidant was added, and the reaction was carried out at 25℃~30℃ for 2~3h. After washing with water, extraction, drying, vacuum concentration and column chromatography purification, compound 7 was obtained. S7, 25℃, compound 7 was dissolved in ethanol, 10% wet palladium on carbon catalyst was added, after three hydrogen replacements, the reaction was carried out at 25℃ and 15psi hydrogen pressure for 2-3 hours, and the target product compound 8 was obtained by filtration and vacuum concentration. The structural formulas of compounds 1 to 8 are as follows: Compound 1 ； Compound 2 ； Compound 3 ； Compound 4 ； Compound 5 ； Compound 6 ； Compound 7 ； Compound 8 。 2. The method for synthesizing xylulose-5-phosphate according to claim 1, characterized in that, In step S1, the molar ratio of compound 1 to acetyl chloride is 1: (0.7~0.9), the amount of methanol used is 8~12 mL of methanol per 1g of compound 1, and the quenching agent is ammonium bicarbonate.

3. The method for synthesizing xylulose-5-phosphate according to claim 1, characterized in that, In S2, the sodium hydride is 60% pure industrial grade sodium hydride, the molar ratio of compound 2, benzyl bromide and sodium hydride is 1:(4~5):(4~5), the amount of N,N-dimethylformamide used is 8~12 mL of N,N-dimethylformamide per 1g of compound 2, the column chromatography uses silica gel as packing material and the eluent is a mixture of petroleum ether and ethyl acetate.

4. The method for synthesizing xylulose-5-phosphate according to claim 1, characterized in that, In S3, the molar ratio of compound 3 to sulfuric acid is 1:(1.8~2.2), and the amount of acetic acid used is 4~6 mL of acetic acid per 1 g of compound 3.

5. The method for synthesizing xylulose-5-phosphate according to claim 1, characterized in that, In step S4, the molar ratio of compound 4 to sodium borohydride is 1:(1.4~1.6), the amount of ethanol used is 8~12mL of ethanol per 1g of compound 4, the quenching reagent is acetone, the acidification reagent is 1M dilute hydrochloric acid aqueous solution, the column chromatography uses silica gel as packing material, and the eluent is a mixture of petroleum ether and ethyl acetate.

6. The method for synthesizing xylulose-5-phosphate according to claim 1, characterized in that, In step S5, the molar ratio of compound 5 to tetrabenzyl pyrophosphate is 1:(1.1~1.3), the amount of tetraisopropyl titanate and diisopropylethylamine added is 3.0~3.5 times the molar amount of compound 5, the amount of dichloromethane used is 8~12mL of dichloromethane per 1g of compound 5, the column chromatography uses silica gel as packing material, and the eluent is a mixture of petroleum ether and ethyl acetate.

7. The method for synthesizing xylulose-5-phosphate according to claim 1, characterized in that, In step S6, the molar ratio of compound 6 to Dysmart oxidant is 1:(1.4~1.6), the amount of dichloromethane used is 4~6 mL of dichloromethane per 1 g of compound 6, the column chromatography uses silica gel as packing material, and the eluent is a mixture of petroleum ether and ethyl acetate.

8. The method for synthesizing xylulose-5-phosphate according to claim 1, characterized in that, In step S7, the amount of the 10% wet palladium on carbon catalyst added is 70-85% of the mass of compound 7, and the amount of ethanol used is 8-10 mL of ethanol per 1 g of compound 7.

9. The method for synthesizing xylulose-5-phosphate according to claim 1, characterized in that, In S1 and S3, the vacuum degree of crude product concentration is -0.08 ~ -0.10 MPa, and the temperature is 40~50℃.

10. The method for synthesizing xylulose-5-phosphate according to claim 1, characterized in that, In step S7, the filtration is performed by diatomaceous earth filtration with a mesh size of 200-300 mesh.

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