CN116715645A - Synthesis and purification method of hydroxypropyl tetrahydropyran triol - Google Patents
Synthesis and purification method of hydroxypropyl tetrahydropyran triol Download PDFInfo
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- CN116715645A CN116715645A CN202310477905.7A CN202310477905A CN116715645A CN 116715645 A CN116715645 A CN 116715645A CN 202310477905 A CN202310477905 A CN 202310477905A CN 116715645 A CN116715645 A CN 116715645A
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- acetic acid
- hydroxypropyl tetrahydropyran
- tetrahydropyran triol
- hydroxypropyl
- triol
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- KOGFZZYPPGQZFZ-QVAPDBTGSA-N (2s,3r,4s,5r)-2-(2-hydroxypropyl)oxane-3,4,5-triol Chemical compound CC(O)C[C@@H]1OC[C@@H](O)[C@H](O)[C@H]1O KOGFZZYPPGQZFZ-QVAPDBTGSA-N 0.000 title claims abstract description 57
- 238000000034 method Methods 0.000 title claims abstract description 35
- 230000015572 biosynthetic process Effects 0.000 title claims description 12
- 238000003786 synthesis reaction Methods 0.000 title claims description 12
- 238000000746 purification Methods 0.000 title claims description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 25
- 229930182476 C-glycoside Natural products 0.000 claims abstract description 23
- 150000000700 C-glycosides Chemical class 0.000 claims abstract description 23
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 claims abstract description 20
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000000203 mixture Substances 0.000 claims abstract description 15
- 239000007787 solid Substances 0.000 claims abstract description 14
- 238000005406 washing Methods 0.000 claims abstract description 13
- 239000012141 concentrate Substances 0.000 claims abstract description 12
- 238000000199 molecular distillation Methods 0.000 claims abstract description 11
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 claims abstract description 10
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 claims abstract description 10
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 10
- 238000002156 mixing Methods 0.000 claims abstract description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims abstract description 8
- 238000010791 quenching Methods 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 8
- 238000010992 reflux Methods 0.000 claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 7
- 239000007864 aqueous solution Substances 0.000 claims abstract description 6
- 230000008569 process Effects 0.000 claims abstract description 6
- 230000000171 quenching effect Effects 0.000 claims abstract description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims abstract description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 claims abstract description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 81
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 34
- 239000012074 organic phase Substances 0.000 claims description 32
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 30
- 239000012071 phase Substances 0.000 claims description 20
- 239000008346 aqueous phase Substances 0.000 claims description 18
- 239000011259 mixed solution Substances 0.000 claims description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 9
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 8
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 5
- 238000004821 distillation Methods 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 239000005457 ice water Substances 0.000 claims description 5
- 238000007790 scraping Methods 0.000 claims description 5
- 238000000605 extraction Methods 0.000 abstract 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 4
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 4
- 238000009833 condensation Methods 0.000 description 4
- 230000005494 condensation Effects 0.000 description 4
- 210000002744 extracellular matrix Anatomy 0.000 description 4
- 238000002390 rotary evaporation Methods 0.000 description 4
- 108010035532 Collagen Proteins 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 3
- 229920001436 collagen Polymers 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 2
- 229920000045 Dermatan sulfate Polymers 0.000 description 2
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 2
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 2
- AVJBPWGFOQAPRH-FWMKGIEWSA-L dermatan sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@H](OS([O-])(=O)=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](C([O-])=O)O1 AVJBPWGFOQAPRH-FWMKGIEWSA-L 0.000 description 2
- 229940051593 dermatan sulfate Drugs 0.000 description 2
- 230000002500 effect on skin Effects 0.000 description 2
- 229940126864 fibroblast growth factor Drugs 0.000 description 2
- 229920002674 hyaluronan Polymers 0.000 description 2
- 229960003160 hyaluronic acid Drugs 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 101710132601 Capsid protein Proteins 0.000 description 1
- 102000005867 Fibrillin-1 Human genes 0.000 description 1
- 108010030229 Fibrillin-1 Proteins 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 108010050808 Procollagen Proteins 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 238000010612 desalination reaction Methods 0.000 description 1
- 108010028309 kalinin Proteins 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 150000003741 xylose derivatives Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/10—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Saccharide Compounds (AREA)
Abstract
The invention provides a method for synthesizing and purifying hydroxypropyl tetrahydropyran triol, which takes xylose, acetylacetone and sodium bicarbonate as raw materials, and obtains oily concentrate after reflux, water washing, extraction and concentration, and the oily concentrate is refrigerated to obtain viscous solid, and the viscous solid is washed by ethyl acetate and dried to obtain intermediate C-glycoside; intermediate C-glycoside and NaBH 4 Mixing, reacting, performing temperature control reaction to obtain a mixture, quenching the mixture by using an HCl aqueous solution, extracting, and concentrating to obtain a crude hydroxypropyl tetrahydropyran triol; and (3) treating the crude hydroxypropyl tetrahydropyran triol by a molecular distillation system to obtain the refined hydroxypropyl tetrahydropyran triol. The yield of the refined hydroxypropyl tetrahydropyran triol prepared by the method is more than 80 percent; the purity is more than 99 percent, and the method has the advantages of high yield and good product quality; in addition, the method has the advantages of simple and easily controlled process, high consistency of batch product quality and stable yield.
Description
Technical Field
The invention relates to the technical field of preparation of hydroxypropyl tetrahydropyran triol, in particular to a method for synthesizing and purifying hydroxypropyl tetrahydropyran triol.
Background
Hydroxypropyl tetrahydropyran triol is a xylose derivative, and researches show that the hydroxypropyl tetrahydropyran triol can promote the synthesis of Dermatan Sulfate (DS), fibroblast Growth Factor (FGF) -10 and Hyaluronic Acid (HA); in addition, it is a key component of the dermal extracellular matrix (ECM) and the dermal-epidermal junction (DEJ), and can promote the synthesis of collagen IV, collagen VII and laminin 5, as well as subsurface dermal markers, procollagen I and fibrillin 1.
The mechanical properties of skin are mainly determined by the extracellular matrix of dermis, and the mechanical and biological properties of skin change significantly with age. Proteoglycans are the main components of the extracellular matrix, are molecules composed of core proteins and covalently linked glycosaminoglycans, which can participate in biological processes such as the correct formation of collagen networks, thus affecting the function of dermal cells.
The function of hydroxypropyl tetrahydropyran triol makes it possible to improve the mechanical properties of the skin when applied to cosmetics, and therefore, the studies on hydroxypropyl tetrahydropyran triol are also increasing.
At present, the preparation of hydroxypropyl tetrahydropyran triol is mainly a chemical synthesis method, and the synthesis process comprises the steps of taking xylose as a raw material, reacting with acetylacetone under alkaline conditions to obtain an intermediate C-glycoside, and then reducing the C-glycoside to obtain a target product (figure 1). The following problems are mainly existed in the process: firstly, an intermediate PX (C-glycoside) is directly put into the next step after simple desalination without purification, so that the product quality is affected; secondly, borate generated by the sodium borohydride reduction method is difficult to remove, and the product quality is affected.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides a method for synthesizing and purifying hydroxypropyl tetrahydropyran triol, which takes xylose, acetylacetone and sodium bicarbonate as raw materials to prepare an intermediate C-glycoside; then with NaBH 4 Preparing hydroxypropyl tetrahydropyran triol by mixing reaction; the yield of the refined hydroxypropyl tetrahydropyran triol prepared by the method is more than 80 percent; the purity is more than 99 percent, and the method has the advantages of high yield and good product quality; in addition, the method has simple and easily controlled process and high consistency of the quality of the batch products,the yield is stable.
The technical scheme of the invention is as follows:
the synthesis and purification method of the hydroxypropyl tetrahydropyran triol comprises the following steps:
(1) Mixing xylose, acetylacetone and sodium bicarbonate, refluxing, and collecting water phase A; washing the aqueous phase A with ethyl acetate, and collecting the aqueous phase B; extracting the aqueous phase B with an extractant, and collecting the organic phase A; washing the organic phase A with water, collecting the organic phase B, concentrating the organic phase B to obtain an oily concentrate, refrigerating to obtain a viscous solid, washing with ethyl acetate, and drying the solid to obtain an intermediate C-glycoside;
(2) Dissolving an intermediate C-glycoside in a solvent to obtain a solution A; solution A was reacted with NaBH 4 Mixing and reacting, controlling the temperature in the reaction process to be less than or equal to 20 ℃, and continuously stirring for 4-6 hours to obtain a mixture; quenching the mixture with HCl aqueous solution, collecting water phase C, extracting water phase C with n-butanol, collecting organic phase C, concentrating organic phase C to obtain crude hydroxypropyl tetrahydropyran triol;
(3) Adding the crude hydroxypropyl tetrahydropyran triol into a raw material bottle of a molecular distillation system, starting a vacuum pump, and when the vacuum degree reaches 0.1Pa, carrying out molecular distillation at the set feeding rate of 200mL/h, the film scraping rotating speed of 310r/min and the distillation temperature of 270 ℃, and collecting heavy phase at the condensation temperature (100 ℃) to obtain the refined hydroxypropyl tetrahydropyran triol.
Preferably, in step (1), the equivalent ratio of xylose, acetylacetone and sodium bicarbonate is 1:1.2:1.5, and the reflux time is 1-10 hours.
Preferably, in the step (1), the extractant consists of dichloromethane and isopropanol, and the volume ratio of the dichloromethane to the isopropanol is 1:0.1-1.
Preferably, in step (1), the organic phase B is concentrated at a temperature of 40℃or less and the oily concentrate is refrigerated at a temperature of 2-8℃for 48 hours to give a white to yellow powdery viscous solid.
Preferably, in the step (2), the solvent is one of ethanol, methanol, a mixed solution of ethanol and acetic acid, a mixed solution of isopropanol and acetic acid, and a mixed solution of propanol and acetic acid.
Preferably, in the ethanol and acetic acid mixed solution, the volume ratio of the ethanol to the acetic acid is 10:1; in the mixed solution of the isopropanol and the acetic acid, the volume ratio of the isopropanol to the acetic acid is 10:1; in the mixed solution of the propanol and the acetic acid, the volume ratio of the propanol to the acetic acid is 10:1.
Preferably, in step (2), the intermediate C-glycoside is reacted with NaBH 4 The equivalent ratio of (2) is 1:1.2.
Preferably, in step (2), the temperature during the reaction is controlled by using an ice-water bath; in the aqueous HCl quench, the equivalent concentration of HCl was 1N.
Compared with the prior art, the invention has the beneficial effects that:
1. the method provided by the invention is used for preparing refined hydroxypropyl tetrahydropyran triol, and the yield is more than 80%; the purity is more than 99 percent, and the method has the advantages of high yield and good product quality.
2. The method has the advantages of simple process, easy control and high consistency of the quality of the batch products.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are required to be used in the description of the embodiments or the prior art will be briefly described below, and it will be obvious to those skilled in the art that other drawings can be obtained from these drawings without inventive effort.
FIG. 1 is a scheme showing the synthesis of hydroxypropyl tetrahydropyran triol.
Detailed Description
In order to better understand the technical solutions of the present invention, the following description will clearly and completely describe the technical solutions of the embodiments of the present invention in conjunction with the embodiments of the present invention, and it is obvious that the described embodiments are only some embodiments of the present invention, not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the present invention without making any inventive effort, shall fall within the scope of the present invention.
Example 1
The synthesis and purification method of the hydroxypropyl tetrahydropyran triol comprises the following steps:
(1) After mixing 1.5kg of xylose, 1.2kg of acetylacetone and 1.25kg of sodium bicarbonate, refluxing in water for 8 hours, and collecting aqueous phase A; the aqueous phase A is cooled to room temperature, washed with ethyl acetate and the aqueous phase B is collected; extracting the aqueous phase B with an extractant, and collecting the organic phase A; extracting for 3 times, wherein the volume ratio of the extractant to the water phase B is 1:1;
the extractant consists of dichloromethane and isopropanol, and the volume ratio of the dichloromethane to the isopropanol is 1:0.5;
washing the organic phase A with water, collecting the organic phase B, and concentrating the organic phase B at 40 ℃ to obtain an oily concentrate; refrigerating the oily concentrate at 5deg.C for 48 hr to obtain white to yellow powdery viscous solid; washing the viscous solid with ethyl acetate, and then drying to obtain an intermediate C-glycoside; the intermediate C-glycoside is white powder, 1.37kg is added, and the yield is 72%;
(2) 1.14kg of the intermediate C-glycoside was dissolved in 12 liters of ethanol to obtain a solution A; placing the solution A in a reactor; the reactor was placed in an ice-water bath, the reaction temperature was controlled to not exceed 10℃and 272g (1.2 eq.) of NaBH was added 4 Stirring was continued for 4 hours to obtain a mixture; quenching the mixture with 1N HCl aqueous solution, removing the organic solvent by rotary evaporation, collecting a water phase C, extracting the water phase C with N-butanol, collecting the organic phase C, and removing the solvent in the organic phase C by rotary evaporation to obtain crude hydroxypropyl tetrahydropyran triol;
in the crude hydroxypropyl tetrahydropyran triol, configuration beta, S is configuration beta, S=7:3;
(3) Adding 1kg of crude hydroxypropyl tetrahydropyran triol into a raw material bottle of a molecular distillation system, starting a vacuum pump, and when the vacuum degree reaches 0.1Pa, carrying out molecular distillation at the set feeding rate of 200mL/h, the film scraping rotating speed of 310r/min and the distillation temperature of 270 ℃, and collecting a heavy phase at a condensation temperature (100 ℃) to obtain refined hydroxypropyl tetrahydropyran triol, wherein the weight is 784.2g, and the yield is 78.4%.
Example 2
The difference from example 1 is that in step (2), methanol is used instead of ethanol;
the weight of the C-glycoside obtained in the step (1) is 1.2kg, and the yield is 80%;
in the crude hydroxypropyl tetrahydropyran triol obtained in the step (2), the configuration beta and the S=7:3 are adopted;
the weight of the refined hydroxypropyl tetrahydropyran triol obtained in the step (3) is 813.2g, and the yield is 81.3 percent
Example 3
The synthesis and purification method of the hydroxypropyl tetrahydropyran triol comprises the following steps:
(1) After mixing 1.5kg of xylose, 1.2kg of acetylacetone and 1.25kg of sodium bicarbonate, refluxing in water for 3 hours, and collecting aqueous phase A; the aqueous phase A is cooled to room temperature, washed with ethyl acetate and the aqueous phase B is collected; extracting the aqueous phase B with an extractant, and collecting the organic phase A; extracting for 3 times, wherein the volume ratio of the extractant to the water phase B is 1:1;
the extractant consists of dichloromethane and isopropanol, and the volume ratio of the dichloromethane to the isopropanol is 1:0.2;
washing the organic phase A with water, collecting the organic phase B, and concentrating the organic phase B at 35 ℃ to obtain an oily concentrate; refrigerating the oily concentrate at 2deg.C for 48 hr to obtain white to yellow powdery viscous solid; washing the viscous solid with ethyl acetate, and then drying to obtain an intermediate C-glycoside;
(2) 272g (1.2 eq.) NaBH was added to the reactor by controlling the temperature in the reactor to not exceed 10℃using an ice-water bath 4 Stirring for 30 minutes; 1.14kg of an intermediate C-glycoside is dissolved in ethanol, then is dripped into a reactor, and is continuously stirred for 4 hours after dripping is finished, so as to obtain a mixture; quenching the mixture with 1N HCl aqueous solution, collecting a water phase C, extracting the water phase C with N-butanol, collecting an organic phase C, and removing a solvent in the organic phase C by a rotary evaporation method to obtain a crude hydroxypropyl tetrahydropyran triol;
in the crude hydroxypropyl tetrahydropyran triol, configuration beta, S is configuration beta, S=1:1;
(3) Adding 1kg of crude hydroxypropyl tetrahydropyran triol into a raw material bottle of a molecular distillation system, starting a vacuum pump, and when the vacuum degree reaches 0.1Pa, carrying out molecular distillation at the set feeding rate of 200mL/h, the film scraping rotating speed of 310r/min and the distillation temperature of 270 ℃, and collecting a heavy phase at a condensation temperature (100 ℃) to obtain the refined hydroxypropyl tetrahydropyran triol, wherein the weight is 873.6g, and the yield is 87.3%.
Example 4
The difference from example 3 is that in step (2), methanol is used instead of ethanol;
the weight of the C-glycoside obtained in the step (1) is 1.04kg, and the yield is 69.5%;
in the crude hydroxypropyl tetrahydropyran triol obtained in the step (2), the configuration beta and the S=1:1 are adopted
The weight of the refined hydroxypropyl tetrahydropyran triol obtained in the step (3) is 873.6g, and the yield is 87.3 percent
Example 5
The synthesis and purification method of the hydroxypropyl tetrahydropyran triol comprises the following steps:
(1) After mixing 1.5kg of xylose, 1.2kg of acetylacetone and 1.25kg of sodium bicarbonate, refluxing in water for 10 hours, and collecting aqueous phase A; the aqueous phase A is cooled to room temperature, washed with ethyl acetate and the aqueous phase B is collected; extracting the aqueous phase B with an extractant, and collecting the organic phase A; extracting for 3 times, wherein the volume ratio of the extractant to the water phase B is 1:1;
the extractant consists of dichloromethane and isopropanol, and the volume ratio of the dichloromethane to the isopropanol is 1:1;
washing the organic phase A with water, collecting the organic phase B, and concentrating the organic phase B at 35 ℃ to obtain an oily concentrate; refrigerating the oily concentrate at 2deg.C for 48 hr to obtain white to yellow powdery viscous solid; washing the viscous solid with ethyl acetate, and then drying to obtain an intermediate C-glycoside;
(2) Placing the ethanol and acetic acid mixed solution into a reactor, wherein the volume ratio of the ethanol to the acetic acid is 10:1; the temperature in the reactor was cooled to below 0℃in an ice-water bath and 1.2 equivalents of NaBH was added to the reactor 4 Stirring for 10 minutes; 1 equivalent of intermediate C-glycoside is dissolved in the mixed solution of ethanol and acetic acid, and then is dripped into the reactor, and the temperature in the reactor is controlledThe temperature is less than or equal to 20 ℃, after the dripping is finished, stirring is continued for 6 hours, 5mL of water is added into the reactor, and stirring is continued for 30 minutes, so that a mixture is obtained; quenching the mixture with 1N HCl aqueous solution, collecting a water phase C, extracting the water phase C with N-butanol, collecting an organic phase C, and removing a solvent in the organic phase C by a rotary evaporation method to obtain a crude hydroxypropyl tetrahydropyran triol;
in the crude hydroxypropyl tetrahydropyran triol, the configuration beta, S is beta, and S is more than 95:5;
(3) Adding 1kg of crude hydroxypropyl tetrahydropyran triol into a raw material bottle of a molecular distillation system, starting a vacuum pump, and when the vacuum degree reaches 0.1Pa, carrying out molecular distillation at the set feeding rate of 200mL/h, the film scraping rotating speed of 310r/min and the distillation temperature of 270 ℃, and collecting a heavy phase at a condensation temperature (100 ℃) to obtain refined hydroxypropyl tetrahydropyran triol, wherein the weight is 811.7g, and the yield is 81.1%.
Example 6
The difference from example 5 is that in step (2), the mixed solution of isopropanol and acetic acid is used to replace the mixed solution of ethanol and acetic acid, and the volume ratio of isopropanol to acetic acid is 10:1;
the weight of the C-glycoside obtained in the step (1) is 1.02kg, and the yield is 68.3%;
in the crude hydroxypropyl tetrahydropyran triol obtained in the step (2), the configuration beta, S is the configuration beta, and S is more than 95:5;
the weight of the refined hydroxypropyl tetrahydropyran triol obtained in the step (3) is 819.1g, and the yield is 81.9 percent
Example 7
The difference from example 5 is that in step (2), a mixed solution of propanol and acetic acid is used instead of a mixed solution of ethanol and acetic acid, and the volume ratio of propanol and acetic acid is 10:1;
the weight of the C-glycoside obtained in the step (1) is 1.0kg, and the yield is 67.3%;
in the crude hydroxypropyl tetrahydropyran triol obtained in the step (2), the configuration beta, S is beta, and S is more than 95:5, a step of;
the weight of the refined hydroxypropyl tetrahydropyran triol obtained in the step (3) is 792g, and the yield is 79.2 percent
Although the present invention has been described in detail by way of reference to preferred embodiments, the present invention is not limited thereto. Various equivalent modifications and substitutions may be made in the embodiments of the present invention by those skilled in the art without departing from the spirit and scope of the present invention, and it is intended that all such modifications and substitutions be within the scope of the present invention/be within the scope of the present invention as defined by the appended claims. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.
Claims (8)
1. The method for synthesizing and purifying the hydroxypropyl tetrahydropyran triol is characterized by comprising the following steps of:
(1) Mixing xylose, acetylacetone and sodium bicarbonate, refluxing, and collecting water phase A; washing the aqueous phase A with ethyl acetate, and collecting the aqueous phase B; extracting the aqueous phase B with an extractant, and collecting the organic phase A; washing the organic phase A with water, collecting the organic phase B, concentrating the organic phase B to obtain an oily concentrate, refrigerating to obtain a viscous solid, washing with ethyl acetate, and drying the solid to obtain an intermediate C-glycoside;
(2) Dissolving an intermediate C-glycoside in a solvent to obtain a solution A; solution A was reacted with NaBH 4 Mixing and reacting, controlling the temperature in the reaction process to be less than or equal to 20 ℃, and continuously stirring for 4-6 hours to obtain a mixture; quenching the mixture with HCl aqueous solution, collecting water phase C, extracting water phase C with n-butanol, collecting organic phase C, concentrating organic phase C to obtain crude hydroxypropyl tetrahydropyran triol;
(3) Adding the crude hydroxypropyl tetrahydropyran triol into a raw material bottle of a molecular distillation system, starting a vacuum pump, and when the vacuum degree reaches 0.1Pa, carrying out molecular distillation at the set feeding rate of 200mL/h, the film scraping rotating speed of 310r/min and the distillation temperature of 270 ℃, condensing and collecting a heavy phase to obtain the refined hydroxypropyl tetrahydropyran triol.
2. The method for synthesizing and purifying hydroxypropyl tetrahydropyran triol according to claim 1, wherein in the step (1), the equivalent ratio of xylose, acetylacetone and sodium bicarbonate is 1:1.2:1.5, and the reflux time is 1 to 10 hours.
3. The method for synthesizing and purifying hydroxypropyl tetrahydropyran triol according to claim 1, wherein in the step (1), the extractant consists of dichloromethane and isopropanol, and the volume ratio of the dichloromethane to the isopropanol is 1:0.1-1.
4. The process for the synthesis and purification of hydroxypropyltetrahydropyran triol according to claim 1, wherein in step (1), the concentration temperature of the organic phase B is not more than 40 ℃, and the oily concentrate is refrigerated at 2-8 ℃ for 48 hours, obtaining a white to yellow powdery viscous solid.
5. The method for synthesizing and purifying hydroxypropyl tetrahydropyran triol according to claim 1, wherein in the step (2), the solvent is one of ethanol, methanol, a mixture of ethanol and acetic acid, a mixture of isopropanol and acetic acid, and a mixture of propanol and acetic acid.
6. The method for synthesizing and purifying hydroxypropyl tetrahydropyran triol according to claim 5, wherein the volume ratio of ethanol to acetic acid in the ethanol and acetic acid mixed solution is 10:1; in the mixed solution of the isopropanol and the acetic acid, the volume ratio of the isopropanol to the acetic acid is 10:1; in the mixed solution of the propanol and the acetic acid, the volume ratio of the propanol to the acetic acid is 10:1.
7. The method for synthesizing and purifying hydroxypropyl tetrahydropyran triol according to claim 1, wherein in step (2), an intermediate C-glycoside and NaBH are prepared 4 The equivalent ratio of (2) is 1:1.2.
8. The method for synthesizing and purifying hydroxypropyl tetrahydropyran triol according to claim 1, wherein in step (2), the temperature during the reaction is controlled by using an ice-water bath; in the aqueous HCl quench, the equivalent concentration of HCl was 1N.
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