CN108314696B - Utilization method of 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose crystallization mother liquor - Google Patents
Utilization method of 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose crystallization mother liquor Download PDFInfo
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- C07—ORGANIC CHEMISTRY
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- C—CHEMISTRY; METALLURGY
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
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- C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
- C07H13/08—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals directly attached to carbocyclic rings
Abstract
The invention relates to a utilization method of 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose crystallization mother liquor, which comprises the following steps: reacting with acetic anhydride, preparing 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose and isomer thereof 1-hydroxy-2, 3, 5-tri-O-benzoyl-D-ribofuranose contained in the crystallization mother liquor into 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-D-ribofuranose, adsorbing the obtained crude product in hot ethanol by using silica gel and activated carbon, filtering the silica gel and the activated carbon, crystallizing to obtain the 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-D-ribofuranose with the purity of more than 98.5 percent, and recycling the 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-D-ribofuranose as the initial raw material of the fluoro sugar, thereby greatly improving the comprehensive utilization rate of the 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-D-ribofuranose in the preparation process of the fluorose and being beneficial to reducing the production cost of the fluorose.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and relates to a method for recovering 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-D-ribofuranose from dichloromethane-n-hexane crystallization mother liquor of 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose.
Background
The chemical name of the fluorine sugar is 2-deoxy-2-fluoro-1, 3, 5-tribenzoyl-alpha-D-arabinofuranose, CAS RN:97614-43-2, the structure modification of the furanose group is realized by introducing fluorine atoms at the C-2' position of the furanose group, the structure modification greatly improves the biological activity of the glycosyl compound, changes the metabolic pathway and metabolic rate in organisms and prolongs the action time. The fluoroglyco can be used for synthesizing various antiviral and antitumor drugs, wherein Clofarabine is an antitumor drug which is currently concerned.
The existing synthetic routes of the fluosugar all use 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-D-ribofuranose as the starting material, 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose is obtained through rearrangement reaction, and then C-2，Activation of the hydroxyl group in position, followed by Et3N.3HF is a fluorinating reagent to carry out fluoro reaction to obtain the fluoro sugar. The reaction route is shown as the following formula:
when the rearrangement reaction of 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-D-ribofuranose is carried out to prepare 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose, the generation of 1-hydroxy-2, 3, 5-tri-O-benzoyl-D-ribofuranose as an isomer thereof is inevitable. The isomer has higher solubility in a dichloromethane-n-hexane mixed solvent, is removed in the process of crystallizing 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose by using the dichloromethane-n-hexane mixed solvent, and can obtain a target product with higher purity, but the yield of the target product is only 40-50%. The crystallization mother liquor contains a small amount of 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose and a large amount of isomer 1-hydroxy-2, 3, 5-tri-O-benzoyl-D-ribofuranose and other impurities.
Disclosure of Invention
The technical problem to be solved by the invention is as follows: in view of the above problems, the present invention provides a method for recovering 1-O-acetyl-2, 3, 5-tri-O-benzoyl- β -D-ribofuranose from a mother liquor of methylene chloride-n-hexane crystallization of 2-hydroxy-1, 3, 5-tri-O-benzoyl- α -D-ribofuranose, thereby improving the overall utilization of 1-O-acetyl-2, 3, 5-tri-O-benzoyl- β -D-ribofuranose, which is a starting material for producing fluorose.
The technical scheme adopted by the invention for solving the technical problems is as follows: a utilization method of 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose crystallization mother liquor is characterized in that 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose and an isomer thereof, namely 1-hydroxy-2, 3, 5-tri-O-benzoyl-D-ribofuranose, contained in the crystallization mother liquor are prepared into 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-D-ribofuranose by reacting with acetic anhydride, and comprises the following steps:
(1) concentrating and drying dichloromethane-n-hexane crystallization mother liquor of 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose to obtain a concentrate;
(2) dissolving the concentrate with a solvent, adding acetic anhydride, cooling, adding concentrated sulfuric acid, keeping the temperature, stirring for reaction, adding water after the reaction is finished, stirring for 2-3 hours at room temperature, and filtering to obtain a crude product;
(3) dissolving the crude product with ethanol, adding silica gel and active carbon, stirring under heat preservation, filtering, crystallizing the filtrate, and filtering to obtain 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-D-ribofuranose.
Further, the concentration temperature of the dichloromethane-n-hexane crystallization mother liquor of the 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose in the step (1) is below 35 ℃, and the concentration time is not more than 3 hours.
Further, in the step (2), the solvent is acetone, acetonitrile or 1, 4-dioxane, and the dosage of the solvent is 2-3 times of the total weight of the 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose and the isomer thereof, namely 1-hydroxy-2, 3, 5-tri-O-benzoyl-D-ribofuranose, contained in the crystallization mother liquor.
Further, in the step (2), the molar ratio of acetic anhydride to 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose is 2-3: 1, the dosage of the concentrated sulfuric acid is a catalytic amount.
Further, in the step (2), the temperature of the heat preservation stirring reaction is 0-5 ℃, and the reaction time is 6-8 hours.
Further, the amount of water used in the step (2) is 1.5-2.5 times of the volume of the solvent.
Further, in the step (3), the using amount of ethanol is 4-8 times of the weight of the crude product, and the dissolving temperature is 65-80 ℃; the dosage of the silica gel is 5-10% of the weight of the ethanol, and the dosage of the active carbon is 1-3% of the weight of the ethanol; the heat preservation stirring temperature is 65-80 ℃, and the heat preservation stirring time is 30-60 minutes.
Further, the crystallization temperature in the step (3) is 0-10 ℃, the crystallization time is 1-2 hours, and the HPLC purity of the obtained 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-D-ribofuranose is more than 98.5%.
The concentration temperature in the step (1) of the invention needs to be controlled below 35 ℃, the total concentration time is not longer than 3 hours, otherwise, the content of 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose and the isomer 1-hydroxy-2, 3, 5-tri-O-benzoyl-D-ribofuranose in the mother liquor can be reduced, and the content of impurities can be obviously increased; the 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-D-ribofuranose crude product obtained in the step (2) is yellow to light yellow, the HPLC purity is between 90 and 94 percent, the crude product is directly recrystallized for 2 times by using ethanol, the obtained product is light yellow to off-white, the product purity is between 96 and 98 percent, and the obtained product is recrystallized by using ethanol, so that the purity is basically unchanged; and (4) after recrystallization treatment is carried out according to the mode in the step (3), the obtained solid is off-white to white, the HPLC purity can be improved to more than 98.5 percent, and the solid can be recycled as a starting material for preparing the fluosugar.
It should be noted that the yield difference of recovering 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-D-ribofuranose from the crystallization mother liquor of different batches of 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose is large; the longer the same batch of 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose crystallization mother liquor is stored, the lower the yield of the recovered 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-D-ribofuranose is, and the poorer the purity is, namely, the 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose crystallization mother liquor is not suitable for long-time storage at room temperature, and needs to be recovered as soon as possible.
The invention has the beneficial effects that: the utilization method of the crystallization mother liquor of the 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose has simple operation and lower cost; the quality purity of the recovered 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-D-ribofuranose reaches more than 98.5 percent, and the recovered 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-D-ribofuranose can be recycled as the initial raw material of the fluorose, so that the comprehensive utilization rate of the 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-D-ribofuranose can be greatly improved, and the production cost of the fluorose can be reduced.
Detailed Description
The invention will now be further illustrated by reference to specific examples, which are intended to be illustrative of the invention and are not intended to be a further limitation of the invention.
Example 1
Taking 200ml of mother liquor containing 20g of 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose and 1-hydroxy-2, 3, 5-tri-O-benzoyl-D-ribofuranose isomer thereof, concentrating the mother liquor under reduced pressure below 35 ℃, adding 40ml of acetone and 17ml of acetic anhydride to dissolve the concentrate, cooling to below 0 ℃, slowly adding 2ml of concentrated sulfuric acid, stirring and preserving heat at 0-5 ℃ for reaction for 6 hours.
After the reaction is finished, 80ml of ice water is slowly added, the temperature is controlled below 5 ℃, and white solid is generated. Stirring for 2 hours at 15-25 ℃, and then performing suction filtration to obtain 22.6g of crude product with the HPLC purity of 93.1%; heating and dissolving the obtained solid by using 100ml of ethanol, adding 5g of silica gel and 1g of activated carbon after complete dissolution, stirring at 70-80 ℃, and keeping the temperature for 30 minutes; filtering while the solution is hot, washing a filter cake by a small amount of hot ethanol, cooling the washing filtrate to room temperature, and then cooling and stirring the solution in an ice-water bath for 2 hours.
And (3) carrying out suction filtration, washing a filter cake twice by using a proper amount of ethanol, and drying at about 60 ℃ to obtain 14.2g of white crystalline solid with the HPLC purity of 98.9%.
Example 2
Taking 200ml of mother liquor containing 20g of 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose and 1-hydroxy-2, 3, 5-tri-O-benzoyl-D-ribofuranose isomer thereof, concentrating the mother liquor under reduced pressure below 35 ℃, adding 40ml of acetonitrile and 17ml of acetic anhydride to dissolve the concentrate, cooling to below 0 ℃, slowly adding 2ml of concentrated sulfuric acid, stirring and preserving heat at 0-5 ℃ for reacting for 6 hours.
After the reaction is finished, 80ml of ice water is slowly added, the temperature is controlled below 5 ℃, and white solid is generated. Stirring for 2 hours at 15-25 ℃, and then performing suction filtration to obtain 21.4g of crude product with the HPLC purity of 93.7%; heating and dissolving the obtained solid by using 100ml of ethanol, adding 5g of silica gel and 1g of activated carbon after complete dissolution, stirring at 70-80 ℃, and keeping the temperature for 30 minutes; filtering while the solution is hot, washing a filter cake by a small amount of hot ethanol, cooling the washing filtrate to room temperature, and then cooling and stirring the solution in an ice-water bath for 2 hours.
And (3) carrying out suction filtration, washing a filter cake twice by using a proper amount of ethanol, and drying at about 60 ℃ to obtain 13.4g of white crystalline solid with the HPLC purity of 98.6%.
Example 3
Taking 200ml of mother liquor containing 20g of 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose and 1-hydroxy-2, 3, 5-tri-O-benzoyl-D-ribofuranose isomer thereof, concentrating the mother liquor under reduced pressure below 35 ℃ to dry, adding 40ml of 1, 4-dioxane and 17ml of acetic anhydride to dissolve the concentrate, cooling to below 0 ℃, slowly adding 2ml of concentrated sulfuric acid, stirring and preserving heat at 0-5 ℃ for reaction for 6 hours.
After the reaction is finished, 80ml of ice water is slowly added, the temperature is controlled below 5 ℃, and white solid is generated. Stirring for 2 hours at 15-25 ℃, and then performing suction filtration to obtain 21.2g of crude product with the HPLC purity of 91.7%; heating and dissolving the obtained solid by using 100ml of ethanol, adding 5g of silica gel and 1g of activated carbon after complete dissolution, stirring at 70-80 ℃, and keeping the temperature for 30 minutes; filtering while the solution is hot, washing a filter cake by a small amount of hot ethanol, cooling the washing filtrate to room temperature, and then cooling and stirring the solution in an ice-water bath for 2 hours.
And (3) carrying out suction filtration, washing a filter cake twice by using a proper amount of ethanol, and drying at about 60 ℃ to obtain 12.9g of white crystalline solid with the melting point of 129-131 ℃, the specific rotation degree of 42.8 degrees (c is 1, chloroform) and the HPLC purity of 98.5%.
Example 4
Taking 200ml of mother liquor containing 20g of 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose and 1-hydroxy-2, 3, 5-tri-O-benzoyl-D-ribofuranose isomer thereof, concentrating the mother liquor under reduced pressure below 35 ℃, adding 40ml of acetone and 17ml of acetic anhydride to dissolve the concentrate, cooling to below 0 ℃, slowly adding 2ml of concentrated sulfuric acid, stirring and preserving heat at 0-5 ℃ for reaction for 6 hours.
After the reaction is finished, 100ml of ice water is slowly added, the temperature is controlled below 5 ℃, and white solid is generated. Stirring for 2 hours at 15-25 ℃, and then performing suction filtration to obtain 23.5g of crude product with HPLC purity of 92.4%; heating and dissolving the obtained solid by using 100ml of ethanol, adding 10g of silica gel and 1g of activated carbon after complete dissolution, stirring at 70-80 ℃, and keeping the temperature for 30 minutes; filtering while the solution is hot, washing a filter cake by a small amount of hot ethanol, cooling the washing filtrate to room temperature, and then cooling and stirring the solution in an ice-water bath for 2 hours.
Filtering, washing the filter cake twice with appropriate amount of ethanol, drying at about 60 deg.C to obtain white crystalline solid 13.8g with HPLC purity of 98.8%.
Example 5
Taking 200ml of mother liquor containing 20g of 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose and 1-hydroxy-2, 3, 5-tri-O-benzoyl-D-ribofuranose isomer thereof, concentrating the mother liquor under reduced pressure below 35 ℃, adding 40ml of acetone and 17ml of acetic anhydride to dissolve the concentrate, cooling to below 0 ℃, slowly adding 2ml of concentrated sulfuric acid, stirring and preserving heat at 0-5 ℃ for reacting for 8 hours.
After the reaction is finished, 80ml of ice water is slowly added, the temperature is controlled below 5 ℃, and white solid is generated. Stirring for 2 hours at 15-25 ℃, and then performing suction filtration to obtain 22.4g of crude product with the HPLC purity of 93.4%; heating and dissolving the obtained solid by using 100ml of ethanol, adding 5g of silica gel and 1g of activated carbon after complete dissolution, stirring at 70-80 ℃, and keeping the temperature for 30 minutes; filtering while the solution is hot, washing a filter cake by a small amount of hot ethanol, cooling the washing filtrate to room temperature, and then cooling and stirring the solution in an ice-water bath for 2 hours.
Filtering, washing the filter cake twice with appropriate amount of ethanol, drying at about 60 deg.C to obtain white crystalline solid 14.0g with HPLC purity of 98.7%.
Example 6
Taking 200ml of mother liquor containing 20g of 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose and 1-hydroxy-2, 3, 5-tri-O-benzoyl-D-ribofuranose isomer thereof, concentrating the mother liquor under reduced pressure below 35 ℃, adding 60ml of acetone and 20ml of acetic anhydride to dissolve the concentrate, cooling to below 0 ℃, slowly adding 2ml of concentrated sulfuric acid, stirring and preserving heat at 0-5 ℃ for reacting for 8 hours.
After the reaction is finished, 150ml of ice water is slowly added, the temperature is controlled below 5 ℃, and white solid is generated. Stirring for 2 hours at 15-25 ℃, and then performing suction filtration to obtain 22.0g of crude product with the HPLC purity of 93.8%; heating and dissolving the obtained solid by using 100ml of ethanol, adding 5g of silica gel and 1g of activated carbon after complete dissolution, stirring at 70-80 ℃, and keeping the temperature for 30 minutes; filtering while the solution is hot, washing a filter cake by a small amount of hot ethanol, cooling the washing filtrate to room temperature, and then cooling and stirring the solution in an ice-water bath for 2 hours.
And (3) carrying out suction filtration, washing a filter cake twice by using a proper amount of ethanol, and drying at about 60 ℃ to obtain 13.6g of white crystalline solid with the HPLC purity of 98.8%.
Example 7
Taking 200ml of mother liquor containing 20g of 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose and 1-hydroxy-2, 3, 5-tri-O-benzoyl-D-ribofuranose isomer thereof, concentrating the mother liquor under reduced pressure below 35 ℃, adding 40ml of acetone and 17ml of acetic anhydride to dissolve the concentrate, cooling to below 0 ℃, slowly adding 2ml of concentrated sulfuric acid, stirring and preserving heat at 0-5 ℃ for reaction for 6 hours.
After the reaction is finished, 80ml of ice water is slowly added, the temperature is controlled below 5 ℃, and white solid is generated. Stirring for 2 hours at 15-25 ℃, and then performing suction filtration to obtain a crude product, 21.7g, and the HPLC purity is 93.3%; heating and dissolving the obtained solid by using 100ml of ethanol, cooling to room temperature after complete dissolution, and then cooling and stirring for 2 hours in an ice-water bath; performing suction filtration, washing a filter cake twice by using a proper amount of ethanol to obtain light yellow solid 19.1g, wherein the HPLC purity is 96.6%;
heating and dissolving the obtained solid by using 100ml of ethanol, cooling to room temperature after complete dissolution, and then cooling and stirring for 2 hours in an ice-water bath; performing suction filtration, washing a filter cake twice by using a proper amount of ethanol to obtain light yellow solid 17.4g, wherein the HPLC purity is 97.4%;
the obtained solid was recrystallized once more from 100ml of ethanol to give 15.7g of pale yellow solid, which was then dried at about 60 ℃ to give 12.6g of white crystalline solid with an HPLC purity of 97.6%.
In light of the foregoing description of the preferred embodiment of the present invention, many modifications and variations will be apparent to those skilled in the art without departing from the spirit and scope of the invention. The technical scope of the present invention is not limited to the content of the specification, and must be determined according to the scope of the claims.
Claims (7)
1. A method for utilizing 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose crystallization mother liquor is characterized by comprising the following steps: preparing 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-D-ribofuranose from 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose and its isomer 1-hydroxy-2, 3, 5-tri-O-benzoyl-D-ribofuranose contained in the crystallization mother liquor by reacting with acetic anhydride, comprising the following steps:
(1) concentrating and drying dichloromethane-n-hexane crystallization mother liquor of 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose to obtain a concentrate;
(2) dissolving the concentrate with a solvent, adding acetic anhydride, cooling, adding concentrated sulfuric acid, keeping the temperature, stirring for reaction, adding water after the reaction is finished, stirring for 2-3 hours at room temperature, and filtering to obtain a crude product;
(3) dissolving the crude product with ethanol, adding silica gel and active carbon, stirring under heat preservation, filtering, crystallizing the filtrate, and vacuum filtering to obtain 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-D-ribofuranose;
in the step (2), the solvent is acetone, acetonitrile or 1, 4-dioxane, and the dosage of the solvent is 2-3 times of the total weight of 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose and 1-hydroxy-2, 3, 5-tri-O-benzoyl-D-ribofuranose isomers thereof contained in the crystallization mother liquor.
2. The method for utilizing a mother liquid for crystallization of 2-hydroxy-1, 3, 5-tri-O-benzoyl- α -D-ribofuranose according to claim 1, wherein: the concentration temperature of the dichloromethane-n-hexane crystallization mother liquor of the 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose in the step (1) is below 35 ℃, and the concentration time is not more than 3 hours.
3. The method for utilizing a mother liquid for crystallization of 2-hydroxy-1, 3, 5-tri-O-benzoyl- α -D-ribofuranose according to claim 1, wherein: in the step (2), the molar ratio of acetic anhydride to 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose is 2-3: 1, the dosage of the concentrated sulfuric acid is a catalytic amount.
4. The method for utilizing a mother liquid for crystallization of 2-hydroxy-1, 3, 5-tri-O-benzoyl- α -D-ribofuranose according to claim 1, wherein: in the step (2), the temperature of the heat preservation stirring reaction is 0-5 ℃, and the reaction time is 6-8 hours.
5. The method for utilizing a mother liquid for crystallization of 2-hydroxy-1, 3, 5-tri-O-benzoyl- α -D-ribofuranose according to claim 1, wherein: the amount of water used in the step (2) is 1.5-2.5 times of the volume of the solvent.
6. The method for utilizing a mother liquid for crystallization of 2-hydroxy-1, 3, 5-tri-O-benzoyl- α -D-ribofuranose according to claim 1, wherein: in the step (3), the using amount of ethanol is 4-8 times of the weight of the crude product, and the dissolving temperature is 65-80 ℃; the dosage of the silica gel is 5-10% of the weight of the ethanol, and the dosage of the active carbon is 1-3% of the weight of the ethanol; the heat preservation stirring temperature is 65-80 ℃, and the heat preservation stirring time is 30-60 minutes.
7. The method for utilizing a mother liquid for crystallization of 2-hydroxy-1, 3, 5-tri-O-benzoyl- α -D-ribofuranose according to claim 1, wherein: the crystallization temperature in the step (3) is 0-10 ℃, the crystallization time is 1-2 hours, and the HPLC purity of the obtained 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-D-ribofuranose is more than 98.5%.
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