CN110684057A - Production method of N-acetyl-D-glucosamine - Google Patents
Production method of N-acetyl-D-glucosamine Download PDFInfo
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- CN110684057A CN110684057A CN201911151949.0A CN201911151949A CN110684057A CN 110684057 A CN110684057 A CN 110684057A CN 201911151949 A CN201911151949 A CN 201911151949A CN 110684057 A CN110684057 A CN 110684057A
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- glucosamine
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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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- 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- C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
- C07H5/04—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to nitrogen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
Abstract
The invention discloses a production method of N-acetyl-D-glucosamine, which takes chitin as a raw material, hydrolyzes the chitin in concentrated hydrochloric acid to prepare glucosamine hydrochloride, and prepares the N-acetyl-D-glucosamine by acetylation; the invention provides the most suitable industrialized production way and reaction conditions, and can realize the industrialized production of the high-purity N-acetyl-D-glucosamine.
Description
Technical Field
The invention belongs to the technical field of biochemical synthesis, and particularly relates to a production method of N-acetyl-D-glucosamine.
Background
Glucosamine (GleN) is an important hexosamine formed by substituting one hydroxyl group of glucose with an amino group, and there are two main types of glucosamine on the market today, one is glucosamine hydrochloride and the other is glucosamine sulfate. D-Glucosamine Hydrochloride (D-Glucosamine Hydrochloride), molecular formula C6H13NO5HCl, a white crystal, odorless, slightly sweet, readily soluble inWater, slightly soluble in methanol, insoluble in organic solvents such as ethanol and the like, has important physiological functions for human bodies, participates in liver and kidney detoxification, plays a role in resisting inflammation and protecting liver, has good curative effect on treating rheumatic arthritis and gastric ulcer, and is a main raw material for synthesizing antibiotics and anticancer drugs; can also be used in food, cosmetic and feed additive. Glucosamine hydrochloride is extracted from natural chitin, is a marine biological agent, and is the main component of chondroitin sulfate. It can promote the synthesis of mucopolysaccharide, raise the viscosity of joint synovial fluid, improve the metabolism of joint cartilage, promote the repair of joint cartilage and has obvious antiphlogistic and analgesic effects. It has the effect of promoting the injection efficiency of antibiotics, and can be used as nutritional supplement for diabetic patients.
N-acetyl D-glucosamine is white needle crystal, has no odor, is easily soluble in water, is an important glucosamine derivative, is a basic composition unit of a plurality of important polysaccharides in biological cells, is a special monosaccharide with higher sweetness, has reducibility, is an important precursor for synthesizing bifidus factors, has important physiological functions in organisms, is clinically a medicament for treating rheumatic and rheumatoid arthritis, is also used as a food antioxidant, an infant food additive and a sweetener for diabetics. The method is widely applied to the fields of food, medicine, chemical industry and the like, and has wide market prospect. The prior production method has complex process and low yield, so that the production cost is high, and the subsequent production and application are limited.
Disclosure of Invention
In order to make up the defects of the prior art, the invention provides an industrialized preparation method of N-acetyl-D-glucosamine, which has the advantages of high production efficiency, low cost and simple operation.
The invention is realized by the following technical scheme:
a production method of N-acetyl-D-glucosamine is characterized in that:
the method comprises the following steps:
(1) taking chitin as a raw material, adding the chitin into concentrated hydrochloric acid in batches by adopting an interval feeding method under the stirring condition, slowly heating to 90-110 ℃ by adopting a gradient heating method, and reacting for 10-20min by maintaining the reaction temperature;
(2) decolorizing and recrystallizing the mixed solution obtained by the reaction to obtain glucosamine hydrochloride;
(3) dissolving the prepared glucosamine hydrochloride in pyridine, adding triethylamine, adding acetic anhydride under the stirring condition, and stirring for reaction for 1-3 h;
(4) and (4) carrying out suction filtration on the reaction product obtained in the step (3), washing with acetone, recrystallizing, and drying in vacuum to obtain the N-acetyl-D-glucosamine.
Preferably, the temperature rising rate of the gradient temperature rising method in the step (1) is 10-15 ℃/h.
Further, the concentrated hydrochloric acid in the step (1) is concentrated hydrochloric acid with the volume concentration of 30-40%.
Further, the mass ratio of the chitin to the concentrated hydrochloric acid in the step (1) is 1 (5-8).
Preferably, the decoloring process in the step (2) is as follows: adding activated carbon into the reaction mixture for decolorization and adsorption, stirring at 40-50 ℃ for 2-4h, and filtering.
Furthermore, the mass fraction of the activated carbon in the mixed solution is 4-8%.
Further, the recrystallization in the step (2) is carried out by using an 85-95% ethanol solution.
Preferably, the reaction process in the step (3) is adjusted to pH 7-8 by sodium methoxide.
Further, in the step (3), the molar ratio of the glucosamine hydrochloride to the acetic anhydride is 1: (2-5).
Preferably, the step (4) is performed by recrystallization with acetone.
The invention has the beneficial effects that: the method takes chitin as a raw material, realizes the rapid preparation of the N-acetyl-D-glucosamine by controlling each reaction condition, obtains the high-purity reaction condition which is most suitable for industrialization by a large amount of groping, not only reduces the reaction cost, but also improves the purity of the N-acetyl-D-glucosamine, has easily controlled reaction process, and is beneficial to industrialized production.
Detailed Description
The present invention will be described in further detail with reference to specific embodiments thereof to assist those skilled in the art in providing a more complete, accurate and thorough understanding of the inventive concept and aspects thereof, and the scope of the present invention includes, but is not limited to, the following examples, and any modifications in the details and form of the technical aspects thereof that fall within the spirit and scope of the present application are intended to be included therein.
Example 1
Chitin according to the mass ratio: 1:3 of concentrated hydrochloric acid, adding 5kg of 30 percent concentrated hydrochloric acid into a reaction kettle, adding chitin into the reaction kettle in 3 batches, slowly heating to 110 ℃ by adopting a gradient heating method, wherein the heating rate is 10 ℃/h, maintaining the reaction temperature for 20min, and then cooling to finish the reaction; adding activated carbon into the reaction mixed solution for decolorization and adsorption, wherein the mass fraction of the activated carbon in the mixed solution is 6%, stirring for 3h at 45 ℃, filtering, and recrystallizing by using a 95% ethanol solution to obtain glucosamine hydrochloride; dissolving the prepared glucosamine hydrochloride into pyridine, adding a proper amount of triethylamine, adding acetic anhydride under the stirring condition, wherein the molar ratio of the glucosamine hydrochloride to the acetic anhydride is 1:3, adjusting the pH value to 8 by using sodium methoxide, and stirring for reaction for 2 hours; and (3) carrying out suction filtration on the obtained reaction product, washing with acetone, recrystallizing with acetone, and drying in vacuum to obtain the N-acetyl-D-glucosamine with the purity of 97.7%.
Example 2
Chitin according to the mass ratio: 1:3.6 of concentrated hydrochloric acid, adding 35% of concentrated hydrochloric acid into a reaction kettle, adding the prepared chitin in 5 batches, slowly heating to 95 ℃ by adopting a gradient heating method, wherein the heating rate is 14 ℃/h, maintaining the reaction temperature for 17min, and then cooling to finish the reaction; adding activated carbon into the reaction mixed solution for decolorization and adsorption, wherein the mass fraction of the activated carbon in the mixed solution is 7%, stirring at 50 ℃ for 2h, filtering, and recrystallizing by using 85-95% ethanol solution to obtain glucosamine hydrochloride; dissolving the prepared glucosamine hydrochloride into pyridine, adding a proper amount of triethylamine, adding acetic anhydride under the stirring condition, wherein the molar ratio of the glucosamine hydrochloride to the acetic anhydride is 1: 2, adjusting the pH value to 8 by using sodium methoxide, and stirring for reaction for 3 hours; and (3) carrying out suction filtration on the obtained reaction product, washing with acetone, recrystallizing with acetone, and drying in vacuum to obtain the N-acetyl-D-glucosamine with the purity of 97.9%.
Example 3
Chitin according to the mass ratio: 1:5 of concentrated hydrochloric acid, adding 35% of concentrated hydrochloric acid into a reaction kettle, adding chitin in batches, slowly heating to 95 ℃ by adopting a gradient heating method, wherein the heating rate is 15 ℃/h, maintaining the reaction temperature for 20min, and then cooling to finish the reaction; adding active carbon into the reaction mixed solution for decolorization and adsorption, wherein the mass fraction of the active carbon in the mixed solution is 5%, stirring for 4h at 40 ℃, filtering, and recrystallizing by using a 95% ethanol solution to obtain glucosamine hydrochloride; dissolving the prepared glucosamine hydrochloride into pyridine, adding a proper amount of triethylamine, adding acetic anhydride under the stirring condition, wherein the molar ratio of the glucosamine hydrochloride to the acetic anhydride is 1:5, adjusting the pH value to 8 by using sodium methoxide, and stirring for reaction for 3 hours; and (3) carrying out suction filtration on the obtained reaction product, washing with acetone, recrystallizing with acetone, and drying in vacuum to obtain the N-acetyl-D-glucosamine with the purity of 98.1%.
Example 4
Chitin according to the mass ratio: 1:4.5 of concentrated hydrochloric acid, adding 40% concentrated hydrochloric acid into a reaction kettle, adding chitin into the reaction kettle in 3 batches, slowly heating to 100 ℃ by adopting a gradient heating method, wherein the heating rate is 13 ℃/h, maintaining the reaction temperature for 15min, and then cooling to finish the reaction; adding activated carbon into the reaction mixed solution for decolorization and adsorption, wherein the mass fraction of the activated carbon in the mixed solution is 4-8%, stirring at 45 ℃ for 2h, filtering, and recrystallizing with 95% ethanol solution to obtain glucosamine hydrochloride; dissolving the prepared glucosamine hydrochloride into pyridine, adding a proper amount of triethylamine, adding acetic anhydride under the stirring condition, wherein the molar ratio of the glucosamine hydrochloride to the acetic anhydride is 1:4, adjusting the pH value to 7 by using sodium methoxide, and stirring for reaction for 3 hours; and (3) carrying out suction filtration on the obtained reaction product, washing with acetone, recrystallizing with acetone, and drying in vacuum to obtain the N-acetyl-D-glucosamine with the purity of 97.2%.
Example 5
Chitin according to the mass ratio: 1:4.5 of concentrated hydrochloric acid, adding 40% concentrated hydrochloric acid into a reaction kettle, adding chitin into the reaction kettle in 4 batches, slowly heating to 100 ℃ by adopting a gradient heating method, wherein the heating rate is 13 ℃/h, maintaining the reaction temperature for 20min, and then cooling to finish the reaction; adding active carbon into the reaction mixed solution for decolorization and adsorption, wherein the mass fraction of the active carbon in the mixed solution is 5%, stirring for 4h at 50 ℃, filtering, and recrystallizing by using 85% ethanol solution to obtain glucosamine hydrochloride; dissolving the prepared glucosamine hydrochloride into pyridine, adding a proper amount of triethylamine, adding acetic anhydride under the stirring condition, wherein the molar ratio of the glucosamine hydrochloride to the acetic anhydride is 1:3, adjusting the pH value to 8 by using sodium methoxide, and stirring for reaction for 2 hours; and (3) carrying out suction filtration on the obtained reaction product, washing with acetone, recrystallizing with acetone, and drying in vacuum to obtain the N-acetyl-D-glucosamine with the purity of 97.6%.
Claims (10)
1. A production method of N-acetyl-D-glucosamine is characterized in that: the method comprises the following steps:
(1) taking chitin as a raw material, adding the chitin into concentrated hydrochloric acid in batches by adopting an interval feeding method under the stirring condition, slowly heating to 90-110 ℃ by adopting a gradient heating method, and reacting for 10-20min by maintaining the reaction temperature;
(2) decolorizing and recrystallizing the mixed solution obtained by the reaction to obtain glucosamine hydrochloride;
(3) dissolving the prepared glucosamine hydrochloride in pyridine, adding triethylamine, adding acetic anhydride under the stirring condition, and stirring for reaction for 1-3 h;
(4) and (4) carrying out suction filtration on the reaction product obtained in the step (3), washing with acetone, recrystallizing, and drying in vacuum to obtain the N-acetyl-D-glucosamine.
2. The process for producing N-acetyl-D-glucosamine according to claim 1, wherein: the temperature rising rate of the gradient temperature rising method in the step (1) is 10-15 ℃/h.
3. The process for producing N-acetyl-D-glucosamine according to claim 1 or 2, wherein: the concentrated hydrochloric acid in the step (1) is concentrated hydrochloric acid with the volume concentration of 30-40%.
4. The process according to claim 3, wherein the N-acetyl-D-glucosamine is produced by: in the step (1), the mass ratio of the chitin to the concentrated hydrochloric acid is 1 (5-8).
5. The process for producing N-acetyl-D-glucosamine according to claim 1, wherein: the decoloring process in the step (2) comprises the following steps: adding activated carbon into the reaction mixture for decolorization and adsorption, stirring at 40-50 ℃ for 2-4h, and filtering.
6. The process according to claim 5, wherein the N-acetyl-D-glucosamine is produced by: the mass fraction of the activated carbon in the mixed solution is 4-8%.
7. The process for producing N-acetyl-D-glucosamine according to claim 1, wherein: and (3) recrystallizing in the step (2) by using an 85-95% ethanol solution.
8. The process for producing N-acetyl-D-glucosamine according to claim 1, wherein: and (3) adjusting the pH value to 7-8 by using sodium methoxide in the reaction process.
9. The process according to claim 8, wherein the N-acetyl-D-glucosamine is produced by: the mol ratio of glucosamine hydrochloride to acetic anhydride in the step (3) is 1: (2-5).
10. The process for producing N-acetyl-D-glucosamine according to claim 1, wherein: and (4) recrystallizing with acetone.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111393489A (en) * | 2020-05-08 | 2020-07-10 | 马鞍山市天泰生物科技有限公司 | Purification and separation method of N-acetyl-D-glucosamine |
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| US6486307B1 (en) * | 2001-08-23 | 2002-11-26 | Alberta Research Council Inc. | Preparation of glucosamine hydrochloride |
| CA2456544A1 (en) * | 2001-08-08 | 2003-02-20 | Cargill, Incorporated | N-acetyl-d-glucosamine and process for producing n-acetyl-d-glucosamine |
| CN1796395A (en) * | 2004-12-22 | 2006-07-05 | 济南海得贝海洋生物工程有限公司 | Method for preparing N - acetyl - D - glucosamine (NAG) |
| CN1847255A (en) * | 2006-05-17 | 2006-10-18 | 扬州日兴生物化工制品有限公司 | Production process of N-acetyl D-amino glucose |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111393489A (en) * | 2020-05-08 | 2020-07-10 | 马鞍山市天泰生物科技有限公司 | Purification and separation method of N-acetyl-D-glucosamine |
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