Preparation method of L-mannose

Abstract

The invention belongs to the technical field of sugar synthesis chemistry, and particularly relates to a preparation method of L-mannose. According to the method, 1, 2, 3, 4, 6-penta-O-acetyl-beta-L-glucopyranose is used as a raw material, L-mannose is obtained by modifying and overturning L-glucose 2-OH, the raw material is easy to obtain, and the method is simple in process, low in cost, high in yield and suitable for large-scale production.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of sugar synthesis chemistry, and particularly relates to a preparation method of L-mannose. BACKGROUND

[0002] The information disclosed in this background section is intended to provide an overview of the general background of the application and is not necessarily a complete description of the prior art. It is not intended to be used as an aid in determining the prior art.

[0003] L-mannose (CAS: 10030-80-5) is a mirror image isomer of natural D-mannose (CAS: 3458-28-4) and has a very small content in nature. L-mannose and its derivatives have important application value in studying mirror biology and developing active drugs. Due to the difficulty in obtaining L-mannose, especially the high price of commercial L-mannose, the development and research of its application are limited.

[0004] In the existing chemical synthesis technology, L-mannose can be synthesized from bispropyl-D-glucose as a raw material in 7 steps (Hung S C, Wang C C, Thopate S R. Efficient synthesis of L-altrose and L-mannose. Tetrahedron Letters [J]. 2000, 41(17): 3119-3122. DOI: 10.1016 / S0040-4039(00)00363-4), and the total yield is less than 30%, and it is difficult to scale up the preparation. In addition, there are other total synthesis methods (Draskovits, Markus, Stanetty, Christian, Baxendale, Ian R. Indium- and Zinc-Mediated Acyloxyallylation of Protected and Unprotected Aldotetroses-Revealing a Pronounced Diastereodivergence and a Fundamental Difference in the Performance of the Mediating Metal. Journal of Organic Chemistry, 2018, 83(5), 2647-2659, DOI: 10.1021 / acs.joc.7b03063), and it is also difficult to synthesize L-mannose in large quantities due to the complicated steps. SUMMARY

[0005] To address the problems in the existing technology, this invention provides a method for preparing L-mannose that is safe, simple to operate, easy to purify, low in cost, and suitable for large-scale production.

[0006] To achieve the above objectives, the present invention adopts the following technical solution.

[0007] A method for preparing L-mannose includes the following steps: (1) 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose and PCl5 were mixed in an organic solvent at -10℃ to 0℃ and reacted at room temperature. After the reaction was completed, the temperature was lowered to -10℃ to 0℃ and intermediate 1 was obtained by separation. (2) Intermediate 1, N,N-dimethylformamide (DMF), and water were reacted in an organic solvent at room temperature. After the reaction was completed, intermediate 2 was obtained by separation. (3) Intermediate 2 and trifluoromethanesulfonic anhydride (Tf2O) were reacted in an organic solvent in the presence of pyridine at -10℃ to 0℃. After the reaction was completed, intermediate 3 was obtained by separation. (4) Intermediate 3 and sodium nitrite react in an organic solvent at room temperature, and intermediate 4 is obtained after the reaction is completed; (5) Intermediate 4 and sodium methoxide react in methanol at room temperature. After the reaction is complete, the product is separated and purified.

[0008] In step (1), the molar ratio of 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose to PCl5 is 1:(1~2.5); preferably 1:(1.5~2.5); more preferably 1:(2~2.5).

[0009] In steps (1) and (3), the separation step involves adding a saturated sodium bicarbonate solution at a temperature not higher than 0°C to the reaction system until the pH is greater than 7, allowing it to stand to separate the organic phase, and removing the solvent.

[0010] In step (2), the mass ratio of water to 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose is 2:5. The volume ratio of DMF to water is 1:4; the volume ratio of DMF to organic solvent is 1:100.

[0011] In step (2), the separation step is to remove the solvent from the reaction system, add an equal amount of dichloromethane to the original volume, wash with saturated brine, let stand to separate the organic phase, and remove the solvent.

[0012] In step (3), the molar ratio of 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose to trifluoromethanesulfonic anhydride is 1:(1.5~3); preferably 1:(2~2.5). The molar ratio of pyridine to trifluoromethanesulfonic anhydride is (1~4):1; preferably (2.5~4):1; more preferably (3.5~4):1.

[0013] In step (4), the molar amount of sodium nitrite added is 2 to 3 times that of 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose.

[0014] In step (4), the separation step involves pouring the reaction system into a 1N hydrochloric acid solution at 0℃~4℃, and then extracting it with ethyl acetate. The extraction can be performed 1-3 times. The ratio of hydrochloric acid solution to 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose is 2mL:1g, and the ratio of ethyl acetate to 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose is 5mL:1g. The ethyl acetate phase obtained by separation is dried to remove the solvent.

[0015] In step (5), the molar ratio of 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose to sodium methoxide is (25~30):1.

[0016] In step (5), the separation and purification steps are as follows: after neutralizing the reaction system, the solvent is removed, and methanol and methyl ether with a volume ratio of 1:2 are added to the residue to 0.5 to 1 volume times the reaction system. The product is then obtained by filtration and drying.

[0017] In the above steps, the concentration of 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose and each intermediate in the organic solvent is not higher than 0.5 mol / L; preferably 0.1 mol / L to 0.5 mol / L; more preferably 0.2 mol / L to 0.3 mol / L. The organic solvent is selected from at least one of dichloromethane, acetone, and N,N-dimethylformamide (DMF).

[0018] The present invention has the following advantages: This invention uses readily available 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose as raw material, and obtains L-mannose by modifying and inverting L-glucose 2-OH. The method is simple, low-cost, and has a high yield, making it suitable for large-scale production. Attached Figure Description

[0019] Figure 1 It is L-mannose. 1 H NMR spectrum; Figure 2 It is L-mannose.13 C NMR spectrum; Figure 3 This is a high-resolution mass spectrum (HRMS) image of L-mannose; Figure 4 This is the HPLC chromatogram of L-mannose. Detailed Implementation

[0020] This invention provides a method for preparing L-mannose, the reaction route of which is as follows: .

[0021] Specifically, the above preparation method includes the following steps: (1) 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose and PCl5 were mixed in dichloromethane at a molar ratio of 1:(1~2.5) at -10℃~0℃. The mixture was heated to room temperature and the reaction was stopped after the starting material disappeared. The reaction system was cooled to -10℃~0℃ and intermediate 1 was obtained. The intermediate was directly added to the next reaction. Specifically, the separation steps are as follows: saturated sodium bicarbonate ice water solution is added to the reaction system until it is weakly alkaline (pH>7), the organic phase is separated by standing, and the solvent is evaporated from the organic phase under reduced pressure to obtain oily intermediate 1.

[0022] (2) Intermediate 1 is dissolved in acetone, and DMF and water are added in a volume ratio of 1:4. The volume ratio of DMF to acetone is 1:100. The reaction is carried out at room temperature. After the raw material disappears, intermediate 2 is separated and directly added to the next reaction. Specifically, the separation steps are as follows: the solvent is removed from the reaction system under reduced pressure to obtain an oily substance, which is then dissolved in an equal volume of dichloromethane, washed with saturated brine, allowed to stand to separate the organic phase, and the washing is repeated once. The solvent is evaporated from the organic phase under reduced pressure to obtain oily intermediate 2.

[0023] (3) Intermediate 2 is dissolved in dichloromethane and pyridine, and trifluoromethanesulfonic anhydride is added dropwise at -10℃ to 0℃. The molar amount of trifluoromethanesulfonic anhydride added is 1 to 1.5 times that of 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose; the molar ratio of trifluoromethanesulfonic anhydride to pyridine is 1:3.8. After monitoring the disappearance of the raw material, intermediate 3 is separated and directly added to the next reaction. Specifically, the separation steps are as follows: a saturated sodium bicarbonate solution at a temperature not higher than 0°C is added to the reaction system until the pH is greater than 7, the organic phase is separated by standing, and the solvent is evaporated from the organic phase under reduced pressure to obtain oily intermediate 3.

[0024] (4) Intermediate 3 and sodium nitrite react in DMF at room temperature. The molar amount of sodium nitrite added is 2-3 times that of 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose. After monitoring the disappearance of the raw material, the reaction system is separated to obtain intermediate 4, which is then directly added to the next reaction. Specifically, the separation steps are as follows: the reaction system is poured into a 1N hydrochloric acid solution at 0℃~4℃, and then extracted three times with ethyl acetate. The ethyl acetate phases obtained by separation are combined and dried with anhydrous sodium sulfate. The solvent is evaporated under reduced pressure to obtain an oily intermediate 4. The ratio of hydrochloric acid solution to 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose is 2mL:1g, and the ratio of ethyl acetate to 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose is 5mL:1g.

[0025] (5) Intermediate 4 and sodium methoxide reacted in methanol at room temperature. The amount of sodium methoxide added was 1:(25~30) of the molar amount of 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose. After monitoring the reaction, the product L-mannose was separated and purified. Specifically, the separation and purification steps are as follows: acidic resin is added to the reaction system to neutralize the system, the acidic resin is removed by filtration, and the mixture is concentrated under reduced pressure until no fraction is distilled. Then, methanol and methyl ether in a volume ratio of 1:2 are added to the residue to 0.5 to 1 times the volume of the reaction system. After stirring, the mixture is cooled to 0°C and stirred again before filtration. After drying the filtrate, a white powdery product is obtained.

[0026] In the above steps, the concentration of 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose and each intermediate in the organic solvent is not higher than 0.5 mol / L.

[0027] The present invention will be further described below with reference to embodiments and accompanying drawings, but the present invention is not limited to the embodiments described below. Unless otherwise specified, room temperature refers to 10℃~30℃; low temperature refers to no higher than 5℃, especially -10℃~5℃; ice water is 0℃~4℃; weakly alkaline pH is 7.1~8.5.

[0028] Example 1: Synthesis of L-mannose (1) Add 10.0 g (25.6 mmol) of 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose (CAS: 66966-07-2) to 100 mL of dichloromethane with stirring. Stir the system until homogeneous and cool it to below -5 °C. Then add 11.7 g (56.4 mmol) of PCl5 in batches, keeping the system temperature below -5 °C during the addition process. After the addition is complete, raise the system temperature to 25 °C and continue stirring for 6 hours. After the raw material disappears as detected by TLC, cool the system to below -5 °C and slowly pour it into a saturated sodium bicarbonate ice solution with vigorous stirring. Stir for 30 minutes. The system is weakly alkaline. Then allow it to stand and separate the organic phase. The oily substance (intermediate 1) obtained by vacuum concentration of the organic phase is added to the next step.

[0029] (2) At room temperature, intermediate 1 was dissolved in 100 mL of acetone. 4 mL of water and 1 mL of DMF were added to the system. The mixture was stirred at room temperature and reacted. After about 6 hours, the TLC showed that the raw material had disappeared. The system was concentrated under reduced pressure. The resulting oil was dissolved in 100 mL of dichloromethane. After washing twice with saturated brine, the organic phase was separated. The oil was concentrated under reduced pressure and added to the next step.

[0030] (3) Dissolve the oily substance from step (2) in 100 mL of dichloromethane and 20 mL (19.6 g, 247 mmol) of pyridine, cool to below -5 °C, and then slowly add 16.6 g (64.7 mmol) of trifluoromethanesulfonic anhydride dropwise under controlled temperature. After the addition is complete, the system is stirred and reacted at below -5 °C for about 2 hours. The starting material disappears as detected by TLC. Pour the system into a saturated sodium bicarbonate ice water solution and stir to neutralize until it becomes weakly alkaline. Allow it to stand to separate the dichloromethane phase, concentrate under reduced pressure to obtain the oily substance, and add it to the next step.

[0031] (4) Dissolve the oily substance from step (3) in 100 mL of DMF, add 5.30 g (76.8 mmol) of sodium nitrite under stirring at room temperature, and then stir for about 6 hours until the raw material disappears as detected by TLC. Pour the system into 20 mL of 1N hydrochloric acid ice water solution, stir thoroughly for 30 minutes, and then extract the aqueous phase three times with ethyl acetate, each time using 50 mL of ethyl acetate. Combine the three ethyl acetate phases, dry with anhydrous sodium sulfate, and concentrate under reduced pressure to obtain the oily substance for the next step.

[0032] (5) Dissolve the oily substance from step (4) in 50 mL of methanol, add 50 mg (0.92 mmol) of sodium methoxide, stir at room temperature for 1 hour, and detect no raw material or intermediate by HPLC. Add acidic resin to neutralize the system to neutral. After filtering to remove the acidic resin, concentrate the system under reduced pressure until no fraction remains. Then add 10 mL of methanol and 20 mL of methyl ether to the concentrated residue and stir for 1 hour until a white insoluble substance is produced. Cool the system to 0 °C and continue stirring for 1 hour. Filter the system, dry the filter with hot air, and weigh to obtain 2.58 g of white powdery product, with a total yield of 56%.

[0033] The above products 1 H NMR, 13 The C NMR and HRMS spectra are as follows: Figures 1-3 As shown: 1 H NMR (400 MHz, D2O) δ: 5.15(d, 0.63 H, J = 0.8 Hz), 4.87(s, 0.38 H), 3.91-3.86(m, 1 H), 3.86-3.85(d, 0.43 H, J = 2 Hz), 3.83-3.82(m, 0.65 H), 3.80-3.76(m, 1.08 H), 3.74-3.67(m, 1 H), 3.64-3.59(m, 1 H), 3.56-3.51(t, 0.38H, J = 9.6 Hz), 3.37-3.32(m, 0.35 H); 13 C NMR (101 MHz, D2O) δ: 94.11, 93.75, 76.24, 73.13, 72.47, 71.30,70.76, 70.71, 70.31, 66.94, 66.69, 61.05.

[0034] The hydrogen and carbon spectra are consistent with the literature Indium- and Zinc-Mediated Acyloxyallylation ofProtected and Unprotected Aldotetroses-Revealing a PronouncedDiastereodivergence and a Fundamental Difference in the Performance of theMediating Metal. Journal of Organic Chemistry, 2018, 83(5), 2647-2659.

[0035] HRMS(ESI, m / z) calculated for C6H 12 ClO6[M+H] + : 215.0322, found215.0327; Molecular formula is C6H 12 O6.

[0036] Specific rotation [α]20 / D = -14.1° (c=1, H2O), commercially available L-mannose products have specific rotation [α]20 / D specifications: -15.5°~-13.5°.

[0037] The L-mannose sample was prepared into a 50 mg / mL solution using acetonitrile / water at a volume ratio of 80:20 for HPLC analysis. The chromatographic conditions were as follows: Column: Durashell NH2, φ4.6×250mm×5μm; Column temperature: 40℃; Mobile phase: Acetonitrile / water = 80:20; Flow rate: 1.0 mL / min; Detector: Evaporative light scattering detector (ELSD).

[0038] The HPLC chromatogram of the L-mannose sample is shown below. Figure 4 As shown, the peak elution time was 5.49 min, and the content was 100% according to the area normalization method.

[0039] Example 2 Synthesis of L-mannose (1) Add 100 g of 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose to 1 L of dichloromethane with stirring. Stir the system until homogeneous and cool it to below -5°C. Then add 110 g of PCl5 in batches, keeping the system temperature below -5°C during the addition process. After the addition is complete, raise the system temperature to 25°C and continue stirring for 6 hours. After the raw material disappears as detected by TLC, cool the system to below -5°C and slowly pour it into a saturated sodium bicarbonate ice solution with vigorous stirring. Stir for 30 minutes and the system is weakly alkaline (pH=8.0). Then let it stand to separate the organic phase. The oily substance (intermediate 1) obtained by vacuum concentration of the organic phase is added to the next step.

[0040] (2) At room temperature, intermediate 1 was dissolved in 1 liter of acetone. 40 ml of water and 10 ml of DMF were added to the system. The mixture was stirred at room temperature and reacted. After about 6 hours, the TLC showed that the raw material had disappeared. The system was concentrated under reduced pressure. The resulting oil was dissolved in 1 liter of dichloromethane. After washing twice with saturated brine, the organic phase was separated. The oil (intermediate 2) was concentrated under reduced pressure and added to the next step.

[0041] (3) Dissolve intermediate 2 in 1 L of dichloromethane and 200 mL of pyridine, cool to below -5 °C, and then slowly add 166 g of trifluoromethanesulfonic anhydride dropwise under controlled temperature. After the addition is complete, stir the reaction at below -5 °C until the starting material disappears as detected by TLC. Pour the system into a saturated sodium bicarbonate ice solution and stir to neutralize until it is weakly alkaline (pH=8.0). Allow it to stand to separate the dichloromethane phase, concentrate under reduced pressure to obtain an oily substance (intermediate 3), and add it to the next step.

[0042] (4) Dissolve intermediate 3 in 1 L of DMF, add 53.0 g of sodium nitrite under stirring at room temperature, and then stir for about 6 hours. When the starting material disappears as detected by TLC, pour the system into 200 mL of 1 N hydrochloric acid ice water solution, stir thoroughly for 30 minutes, and then extract the aqueous phase three times with 500 mL of ethyl acetate each time. Combine the three ethyl acetate phases, dry with anhydrous sodium sulfate, and concentrate under reduced pressure to obtain an oily substance, which is then added to the next step.

[0043] (5) Dissolve the oily substance from step (4) in 500 mL of methanol, add 500 mg of sodium methoxide, stir at room temperature for 1 hour, and monitor with HPLC until no raw material or intermediate is detected. Add acidic resin to neutralize the system. After filtering to remove the acidic resin, concentrate the system under reduced pressure until no fraction is distilled. Then, add 100 mL of methanol and 200 mL of methyl ether to the concentrated residue and stir until insoluble matter is produced. Cool the system to 0 °C and continue stirring for 1 hour, then filter. After hot air drying, 26.7 g of white powdered L-mannose is obtained, with a total yield of 58% and a purity of 100% (HPLC method).

[0044] Example 3 Synthesis of L-mannose (1) Add 1000g of 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose to 10.0L of dichloromethane with stirring. Stir the system until it is uniform and cool it to about -10℃. Then add 1000g of PCl5 in batches, controlling the system temperature from -10℃ to -5℃ during the addition process. After the addition is complete, the system temperature rises to room temperature of 25℃. Then continue stirring the reaction. After the raw material disappears as detected by TLC, cool the system to below -5℃ and then slowly pour it into a saturated sodium bicarbonate ice water solution that is stirred vigorously until the system is weakly alkaline (pH=7.5). Then let it stand to separate the organic phase. The oily substance (intermediate 1) obtained by vacuum concentration of the organic phase is added to the next step.

[0045] (2) At room temperature, intermediate 1 was dissolved in 10.0 liters of acetone. 400 ml of water and 100 ml of DMF were added to the system. The mixture was stirred at room temperature until the starting material disappeared as detected by TLC. The system was concentrated under reduced pressure. The resulting oil was dissolved in 10.0 liters of dichloromethane. After washing twice with saturated brine, the organic phase was distilled off to remove the dichloromethane. The oil (intermediate 2) was concentrated and added to the next step.

[0046] (3) Dissolve intermediate 2 in 10.0 L of dichloromethane and 2.00 L of pyridine, cool to below -5°C, and then slowly add 1.66 kg (6.47 mol) of trifluoromethanesulfonic anhydride dropwise under controlled temperature. After the addition is complete, stir the reaction at below -5°C until the starting material disappears as detected by TLC. Pour the system into a saturated sodium bicarbonate ice solution and stir to neutralize until the system is weakly alkaline (pH=7.5). Allow to stand to separate the dichloromethane phase, concentrate under reduced pressure to obtain an oily substance (intermediate 3), and add it to the next step.

[0047] (4) Dissolve intermediate 3 in 10.0 L of DMF, add 530 g of sodium nitrite while stirring at room temperature, and then stir until the starting material disappears as detected by TLC. Pour the system into 2 L of 1N hydrochloric acid ice water solution, stir the reaction thoroughly, and then extract the aqueous phase three times with ethyl acetate, using 5 L of ethyl acetate each time. Combine the three ethyl acetate phases, dry with anhydrous sodium sulfate, and concentrate under reduced pressure to obtain an oily substance (intermediate 4), which is then added to the next step.

[0048] (5) Dissolve intermediate 4 in 5 liters of methanol, add 5.00 g of sodium methoxide, stir at room temperature until no raw material or intermediate is detected by HPLC, add acidic resin to neutralize the system to neutral. After filtering to remove the acidic resin, concentrate the system under reduced pressure until no fraction is distilled, then add 1 liter of methanol and 2 liters of methyl ether to the concentrated residue and stir for about 1 hour. Then cool the system to 0°C and continue stirring until a large amount of insoluble matter is produced. Filter the insoluble matter and dry it with hot air to obtain 272 g of white powdered L-mannose, with a total yield of 59% and a purity of 100% (HPLC method).

Claims

1. A method for preparing L-mannose, characterized in that, Includes the following steps: (1) 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose and PCl5 were mixed in an organic solvent at -10℃ to 0℃ and reacted at room temperature. After the reaction was completed, the temperature was lowered to -10℃ to 0℃ and intermediate 1 was obtained by separation. (2) Intermediate 1 reacts with DMF and water in an organic solvent at room temperature, and intermediate 2 is obtained after the reaction is completed; (3) Intermediate 2 and trifluoromethanesulfonic anhydride were reacted in an organic solvent in the presence of pyridine at -10℃ to 0℃. After the reaction was completed, intermediate 3 was obtained by separation. (4) Intermediate 3 and sodium nitrite react in an organic solvent at room temperature, and intermediate 4 is obtained after the reaction is completed; (5) Intermediate 4 and sodium methoxide react in methanol at room temperature. After the reaction is complete, the product is separated and purified.

2. The preparation method according to claim 1, characterized in that, In step (1), the molar ratio of 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose to PCl5 is 1:(1~2.5); In step (2), the mass ratio of water to 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose is 2:5; the volume ratio of DMF to water is 1:4; and the volume ratio of DMF to organic solvent is 1:

100. In step (3), the molar ratio of 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose to trifluoromethanesulfonic anhydride is 1:(1.5~3); the molar ratio of pyridine to trifluoromethanesulfonic anhydride is (1~4):

1. In step (4), the molar amount of sodium nitrite added is 2-3 times that of 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose. In step (5), the molar ratio of 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose to sodium methoxide is (25~30):1; The concentration of 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose and its intermediates in organic solvents shall not exceed 0.5 mol / L; The organic solvent is selected from at least one of dichloromethane, acetone, and DMF.

3. The preparation method according to claim 1, characterized in that, In step (1), the molar ratio of 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose to PCl5 is 1:(1.5~2.5); In step (3), the molar ratio of 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose to trifluoromethanesulfonic anhydride is 1:(2~2.5); the molar ratio of pyridine to trifluoromethanesulfonic anhydride is (2.5~4):1; The concentrations of 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose and its intermediates in organic solvents range from 0.1 mol / L to 0.5 mol / L. In step (1), the organic solvent is dichloromethane; in step (2), the organic solvent is acetone; in step (3), the organic solvent is dichloromethane; and in step (4), the organic solvent is DMF.

4. The preparation method according to claim 1, characterized in that, In step (1), the molar ratio of 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose to PCl5 is 1:(2~2.5); In step (3), the molar ratio of pyridine to trifluoromethanesulfonic anhydride is (3.5~4):1; The concentrations of 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose and its intermediates in organic solvents range from 0.2 mol / L to 0.3 mol / L.

5. The preparation method according to claim 1, characterized in that, In steps (1) and (3), the separation step is to add a saturated sodium bicarbonate solution at a temperature not higher than 0°C to the reaction system until the pH is greater than 7, let it stand to separate the organic phase, and remove the solvent; In step (2), the separation step is to remove the solvent from the reaction system, add an equal amount of dichloromethane to the original volume, wash with saturated brine, let stand to separate the organic phase, and remove the solvent; In step (4), the separation step involves pouring the reaction system into a 1N hydrochloric acid solution at 0℃~4℃, and then extracting it with ethyl acetate. The extraction is performed 1-3 times. The ratio of hydrochloric acid solution to 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose is 2mL:1g, and the ratio of ethyl acetate to 1,2,3,4,6-penta-O-acetyl-beta-L-pyranose is 5mL:1g. The ethyl acetate phase obtained by separation is dried to remove the solvent. In step (5), the separation and purification steps are as follows: after neutralizing the reaction system, the solvent is removed, and methanol and methyl ether with a volume ratio of 1:2 are added to the residue to 0.5 to 1 volume times the reaction system. The product is then obtained by filtration and drying.

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