CN110903330A - Synthesis method of glucosamine sulfate sodium chloride double salt - Google Patents
Synthesis method of glucosamine sulfate sodium chloride double salt Download PDFInfo
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- CN110903330A CN110903330A CN201911342304.5A CN201911342304A CN110903330A CN 110903330 A CN110903330 A CN 110903330A CN 201911342304 A CN201911342304 A CN 201911342304A CN 110903330 A CN110903330 A CN 110903330A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
- C07H5/04—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to nitrogen
- C07H5/06—Aminosugars
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
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Abstract
The synthesis process of glucosamine sulfate sodium chloride double salt has safe and controllable production flow, high product purity and convenient operation. The method comprises the following steps: a) compound 1 in table 1 is liberated to give compound 2; b) salifying the compound 2 with sulfuric acid to obtain a compound 3; c) reacting the compound 3 with sodium chloride to obtain glucosamine sulfate sodium chloride double salt;
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a synthesis method of glucosamine sulfate and sodium chloride double salt.
Background
Osteoarthritis is a degenerative disease, which is caused by degenerative damage of articular cartilage and reactive hyperplasia of articular margin and subchondral bone due to aging, obesity, strain, trauma, congenital abnormality of joints, joint deformity and other factors, and is also called osteoarthropathy, degenerative arthritis, senile arthritis, hypertrophic arthritis, etc. The clinical manifestations are slowly developing joint pain, tenderness, stiffness, joint swelling, limited mobility and joint deformity.
Glucosamine, an amino monosaccharide present in the body, especially in articular cartilage, is an essential component for the synthesis of proteoglycan in the matrix of human articular cartilage, and selectively acts on the bony joints, blocks the pathological process of the bony joints, stimulates chondrocytes to produce glycoproteins with normal polymer structures, and also inhibits the activity of enzymes damaging cartilage such as collagen and phospholipase A2, and inhibits the production of superoxide radicals from damaged cells, prevents the damage of chondrocytes by corticosteroids and certain non-steroidal anti-inflammatory drugs, and reduces the release of endotoxin factors from damaged cells. Through the way, the product has direct anti-inflammatory effect, can relieve pain symptoms of bone joints, improve joint functions and prevent development of osteoarthritis course.
At present, the study on glucosamine sulfate and sodium chloride double salt is less, and two main routes for converting glucosamine hydrochloride into glucosamine sulfate and sodium chloride double salt are provided. One is British patent, which uses an ion exchange process to obtain glucosamine sulfate, which is then reacted with sodium chloride to form a double salt. The second is a U.S. patent, which utilizes the reaction of methanol and metallic sodium to prepare sodium methoxide solution, then the solution reacts with D-glucosamine hydrochloride, after the reaction is finished, the solution is centrifuged to remove sodium chloride, fuming sulfuric acid is added into the solution, after the salt formation, acetone and ether are used for crystallization to obtain glucosamine sulfate, and the sodium chloride reacts to form double salt. The two methods are complicated in actual operation, the first method is inconvenient to operate by using ion exchange resin, and the second method greatly increases the operation difficulty by using flammable and explosive metal sodium.
The U.S. patents were prepared as follows:
disclosure of Invention
The technical problem to be solved by the invention is as follows: overcomes the defects of the prior art, provides a synthesis method of glucosamine sulfate sodium chloride double salt, and has safe and controllable production flow, high purity of finished products and convenient operation.
The technical solution of the invention is as follows: the synthesis method of the glucosamine sulfate sodium chloride double salt comprises the following steps:
a) compound 1 in table 1 is liberated to give compound 2;
b) salifying the compound 2 with sulfuric acid to obtain a compound 3;
c) reacting the compound 3 with sodium chloride to obtain glucosamine sulfate sodium chloride double salt;
table 1.
The synthesis method of glucosamine sulfate sodium chloride double salt has safe and controllable production flow, high purity of finished products and convenient operation.
Detailed Description
The synthesis method of the glucosamine sulfate sodium chloride double salt comprises the following steps:
a) compound 1 in table 1 is liberated to give compound 2;
b) salifying the compound 2 with sulfuric acid to obtain a compound 3;
c) reacting the compound 3 with sodium chloride to obtain glucosamine sulfate sodium chloride double salt;
table 1.
Numerous experiments prove that the synthesis method of glucosamine sulfate sodium chloride double salt has safe and controllable production flow, high purity of finished products and convenient operation.
Preferably, said step a) free compound 1 gives compound 2, the organic base used is selected from triethylamine, diisopropylamine, di-n-propylamine, di-n-butylamine, preferably di-n-propylamine.
Preferably, said step a) free compound 1 to obtain compound 2, the solvent used is selected from methanol, ethanol, preferably methanol.
Preferably, the step a) of dissociating the compound 1 to obtain the compound 2 is carried out at a low temperature of 0-15 ℃.
Preferably, the reaction temperature in step a) is 15 ℃.
Preferably, in step b), compound 2 is salified with sulfuric acid to obtain compound 3, and the sulfuric acid used is dilute sulfuric acid.
Preferably, the compound 2 and sulfuric acid are salified to obtain the compound 3, and the reaction is carried out at low temperature, wherein the reaction temperature is 0-5 ℃.
Preferably, the compound 2 is salified with sulfuric acid to obtain a compound 3, and the reaction temperature is 3 ℃.
Preferably, the reaction temperature of the compound 3 in the step c) and sodium chloride to obtain the glucosamine sulfate sodium chloride double salt is 20-40 ℃.
Preferably, the reaction temperature of the compound 3 and sodium chloride to obtain glucosamine sulfate sodium chloride double salt in the step c) is 30 ℃.
Preferably, said step c) uses water as solvent.
The technical content of the present invention is further described below with reference to specific examples for better understanding of the content of the present invention, but the scope of the present invention is not limited thereto.
EXAMPLE 1 preparation of Compound 2
250ml of glucosamine hydrochloride (80.00g, 0.37mol) methanol is added into a 500ml single-neck flask, the temperature is reduced to 15 ℃, di-n-propylamine (56.00g,0.55mol) is added with stirring, the temperature is reduced to 10 ℃ for reaction for 3h, 200ml of dichloromethane is added with stirring for 10min, and the mixture is kept stand for 2 h. Filtered and washed with 40ml × 4 ethanol. The filter cake was dried at 40 ℃ to give 64.27g of product as a white powder with a yield of 96.7%.
EXAMPLE 2 preparation of Compound 3
Glucosamine (55.00g, 0.31mol) in 165.0g water was added to a 250ml three-necked flask equipped with a thermometer, dropping funnel. Cooling the low-temperature reaction bath to the internal temperature of 0 ℃, dropwise adding dilute sulfuric acid (15.04g of concentrated sulfuric acid and 60g of water), keeping the dropwise adding temperature at 0-5 ℃, dropwise adding for 30 minutes, keeping the temperature for reaction for 1 hour after the dropwise adding is finished, evaporating half of water in the system, and freeze-drying by a freeze dryer. Yield 72.00g product: 102.7 percent.
EXAMPLE 3 preparation of glucosamine sulfate sodium chloride double salt
Glucosamine sulfate (23.63g, 0.052mol) was weighed and dissolved in 60.8g of water, and sodium chloride (5.57g, 0.095) was added thereto and stirred at 30 ℃ until dissolved. The reaction system was stirred for 1 hour, and after distilling out the first half water of the system, 75.0g of acetone was added and stirred for 10 min. Standing at room temperature for 3h, and filtering. The filter cake was washed with 50ml acetone. Oven drying to obtain 27.27g product with yield of 99.9%.
EXAMPLE 4 preparation of Compound 2
Adding 20g of glucosamine hydrochloride into a three-necked bottle, adding a mixed solution of ethanol and water, adding 11.2 triethylamine at the temperature of 25-30 ℃, keeping the temperature after the addition to react for 3 hours, filtering, leaching a filter cake by using 20ml of ethanol, adding 50ml of dichloromethane into the filter cake, stirring for 20 minutes, filtering, and drying the filter cake to obtain the product with the yield of 14.6g and 87%.
EXAMPLE 5 preparation of Compound 2
Adding 20g of glucosamine hydrochloride into a three-necked bottle, adding a mixed solution of ethanol and water, adding 11.3g of diisopropylamine at the temperature of 25-30 ℃, keeping the temperature after the addition to react for 3 hours, filtering, leaching a filter cake by using 20ml of ethanol, adding 50ml of dichloromethane into the filter cake, stirring for 20 minutes, filtering, and drying the filter cake to obtain a product with the yield of 14.8g and 88%.
EXAMPLE 6 preparation of Compound 2
Adding 20g of glucosamine hydrochloride into a three-necked bottle, adding methanol at the temperature of 15 ℃, adding 11.3g of diisopropylamine, keeping the temperature after the addition for reacting for 3 hours, filtering, leaching a filter cake by using 20ml of ethanol, adding 50ml of dichloromethane into the filter cake, stirring for 20 minutes, filtering, and drying the filter cake to obtain the product with the yield of 15.6g and 95%.
The above description is only a preferred embodiment of the present invention, and is not intended to limit the present invention in any way, and all simple modifications, equivalent variations and modifications made to the above embodiment according to the technical spirit of the present invention still belong to the protection scope of the technical solution of the present invention.
Claims (11)
1. A synthesis method of glucosamine sulfate sodium chloride double salt is characterized in that: the method comprises the following steps:
a) compound 1 in table 1 is liberated to give compound 2;
b) salifying the compound 2 with sulfuric acid to obtain a compound 3;
c) reacting the compound 3 with sodium chloride to obtain glucosamine sulfate sodium chloride double salt;
table 1.
2. The method for synthesizing glucosamine sulfate and sodium chloride double salt according to claim 1, wherein the method comprises the following steps: in the step a), the compound 1 is dissociated to obtain a compound 2, and the organic base used is selected from triethylamine, diisopropylamine, di-n-propylamine and di-n-butylamine.
3. The method for synthesizing glucosamine sulfate and sodium chloride double salt according to claim 2, wherein the method comprises the following steps: in the step a), the compound 1 is dissociated to obtain a compound 2, and the solvent used is selected from methanol and ethanol.
4. The method for synthesizing glucosamine sulfate and sodium chloride double salt according to claim 3, wherein the method comprises the following steps: in the step a), the compound 1 is dissociated to obtain the compound 2, and the reaction is carried out at low temperature of 0-15 ℃.
5. The method for synthesizing glucosamine sulfate and sodium chloride double salt according to claim 4, wherein the method comprises the following steps: the reaction temperature in step a) is 15 ℃.
6. The method for synthesizing glucosamine sulfate and sodium chloride double salt according to claim 5, wherein the method comprises the following steps: in the step b), the compound 2 and sulfuric acid are salified to obtain a compound 3, and the used sulfuric acid is dilute sulfuric acid.
7. The method for synthesizing glucosamine sulfate and sodium chloride double salt according to claim 6, wherein the method comprises the following steps: the compound 2 and sulfuric acid are salified to obtain a compound 3, and the reaction is carried out at a low temperature of 0-5 ℃.
8. The method for synthesizing glucosamine sulfate and sodium chloride double salt according to claim 7, wherein the method comprises the following steps: salifying the compound 2 and sulfuric acid to obtain a compound 3, wherein the reaction temperature is 3 ℃.
9. The method for synthesizing glucosamine sulfate and sodium chloride double salt according to claim 8, wherein the method comprises the following steps: in the step c), the compound 3 reacts with sodium chloride to obtain glucosamine sulfate sodium chloride double salt, and the reaction temperature is 20-40 ℃.
10. The method for synthesizing glucosamine sulfate and sodium chloride double salt as claimed in claim 9, wherein: in the step c), the compound 3 reacts with sodium chloride to obtain glucosamine sulfate sodium chloride double salt, and the reaction temperature is 30 ℃.
11. The method for synthesizing glucosamine sulfate and sodium chloride double salt according to claim 10, wherein the method comprises the following steps: said step c) using water as solvent.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6472380B1 (en) * | 1999-11-24 | 2002-10-29 | Jame Fine Chemicals, Inc. | Glucosamine sulfate calcium chloride composition and processes for the preparation of glucosamine sulfate metal chlorides |
| CN101012251A (en) * | 2007-01-11 | 2007-08-08 | 庄建华 | Method of preparing aminoglucose composite sulphate |
| CN102850412A (en) * | 2012-10-12 | 2013-01-02 | 江苏澳新生物工程有限公司 | Preparation method of D-glucosamine sulfate sodium chloride salt |
| CN104710483A (en) * | 2014-09-11 | 2015-06-17 | 迪沙药业集团有限公司 | Preparation method for glucosamine sulfate |
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2019
- 2019-12-23 CN CN201911342304.5A patent/CN110903330A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6472380B1 (en) * | 1999-11-24 | 2002-10-29 | Jame Fine Chemicals, Inc. | Glucosamine sulfate calcium chloride composition and processes for the preparation of glucosamine sulfate metal chlorides |
| CN101012251A (en) * | 2007-01-11 | 2007-08-08 | 庄建华 | Method of preparing aminoglucose composite sulphate |
| CN102850412A (en) * | 2012-10-12 | 2013-01-02 | 江苏澳新生物工程有限公司 | Preparation method of D-glucosamine sulfate sodium chloride salt |
| CN104710483A (en) * | 2014-09-11 | 2015-06-17 | 迪沙药业集团有限公司 | Preparation method for glucosamine sulfate |
Non-Patent Citations (2)
| Title |
|---|
| SUBASH CHANDRA SAHOO ET AL.: "Glucosamine Salts: Resolving Ambiguities over the Market-Based Compositions", 《CRYSTAL GROWTH & DESIGN》 * |
| 耿作献等: "氨基葡萄糖硫酸钠盐的制备及其性质", 《上海水产大学学报》 * |
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Application publication date: 20200324 |