CN112300226A - Method for preparing beta-tetraacetyl-L-ribose - Google Patents
Method for preparing beta-tetraacetyl-L-ribose Download PDFInfo
- Publication number
- CN112300226A CN112300226A CN201910691682.8A CN201910691682A CN112300226A CN 112300226 A CN112300226 A CN 112300226A CN 201910691682 A CN201910691682 A CN 201910691682A CN 112300226 A CN112300226 A CN 112300226A
- Authority
- CN
- China
- Prior art keywords
- ribose
- tetraacetyl
- methyl
- beta
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
- C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
- C07H13/04—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 attached to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
Abstract
The invention provides a method for preparing Beta-tetraacetyl-L-ribose, which takes L-ribose as a starting material, and obtains crude Beta-tetraacetyl-L-ribose syrup through methyl reaction, three acetyl reactions, demethylation reaction and four acetyl reactions in turn; and then purifying the prepared crude Beta-tetraacetyl-L-ribose syrup to obtain refined Beta-tetraacetyl-L-ribose, wherein the process is simple, the cost is low, and the yield can reach 51-55%.
Description
Technical Field
The invention belongs to the technical field of chemical preparation, and particularly relates to a method for preparing beta-tetraacetyl-L-ribose.
Background
The compound levovirin is a known antiviral agent, and in a patented process for the preparation of ribofuranose, application No. 038191245, it is described that: 1,2,3, 5-tetra-O-acetyl-L-ribofuranose is adopted to prepare levovirin, but the prior art produces pure beta-1, 2,3, 5-tetra-O-acetyl-L-ribofuranose raw material, but the process is complex, so the price is high, and the cost for preparing levovirin is high;
smith and Guthrie also propose to convert D-ribose to beta-1, 2,3, 5-tetra-O-acetyl-L-ribofuranose, including acetal formation, acetylation and acetolysis, the existing synthesis method has low total yield and complex process; in addition, the synthesis of the above antiviral agents has also been carried out by isolating a-1,2,3, 5-tetra-O-acetyl-L-ribofuranose, but this still involves expensive isolation techniques and leads to a reduction in yield.
In short, the existing methods for preparing the intermediates for synthesizing antiviral agents are either expensive or have low yield, and therefore, the present invention aims to provide an improved method for producing the intermediates for preparing the antiviral agents, which has a simple process, low synthesis cost and high yield.
Disclosure of Invention
The invention aims to provide a method for preparing beta-tetraacetyl-L-ribose, which solves the problems of high cost and low yield of the intermediate for preparing the antiviral agent in the prior art.
The technical scheme of the invention is realized as follows:
a method for preparing beta-tetraacetyl-L-ribose, characterized in that: the preparation method takes L-ribose as a starting material, and crude Beta-tetraacetyl-L-ribose syrup is obtained by sequentially carrying out methyl reaction, three acetyl reactions, demethylation reaction and four acetyl reactions;
then purifying the prepared crude Beta-tetraacetyl-L-ribose syrup to obtain refined Beta-tetraacetyl-L-ribose.
Preferably, the methyl group reaction comprises the following steps:
a1: adding 1000ml of methanol into 50g of L-ribose, dropwise adding 5ml of sulfuric acid, stirring at room temperature for reacting for 4-5 h, adding 100g of sodium carbonate for neutralizing, filtering, and evaporating to obtain a mixture of light yellow alpha-methyl-L-ribose and beta-methyl-L-ribose;
a2: separating the mixture of alpha-methyl-L-ribose and beta-methyl-L-ribose to obtain beta-methyl-L-ribose;
a3: the purified β -methyl-L-ribose pool obtained in step a2 was concentrated.
Preferably, step a2 is performed by column chromatography to separate the mixture of α -methyl-L-ribose and β -methyl-L-ribose.
Preferably, the ratio of the mixture of α -methyl-L-ribose and β -methyl-L-ribose in step A1 is 2.5-3: 7.5-8.5.
Preferably, the specific steps of the reaction of the above three acetyl groups are: and B, taking 30g of the beta-methyl-L-ribose concentrated solution obtained in the step A3, adding 75ml of glacial acetic acid and 100ml of acid anhydride, cooling by adopting an ice bath, adding a catalyst, and stirring and reacting for 3 hours at the temperature of 100 ℃.
Preferably, the demethylation reaction is performed by the following steps: 5ml of sulfuric acid is dripped into the solution after the three acetyl reactions are finished, the temperature is raised to 80-85 ℃, and the reaction is carried out for 20-30 min.
Preferably, the fourth acetyl reaction comprises the following specific steps: and adding 25g of sodium acetate into the solution after the demethylation reaction, controlling the temperature at 100 ℃, stirring for reaction for 3 hours, and performing evaporation concentration to obtain the crude Beta-tetraacetyl-L-ribose syrup.
Preferably, the purification treatment comprises dissolution, washing with water, dehydration, evaporation, drying and crystallization to obtain white crystals.
Specifically, chloroform solution is adopted to dissolve crude Beta-tetraacetyl-L-ribose syrup, after washing, anhydrous sodium sulfate is added for dehydration, and after evaporation and drying, white crystals are obtained by ethanol crystallization.
In summary, the invention has the advantages that:
the invention relates to a method for preparing Beta-tetraacetyl-L-ribose, which takes L-ribose as a starting material, and obtains crude Beta-tetraacetyl-L-ribose syrup through methyl reaction, three acetyl reactions, demethylation reaction and the fourth acetyl reaction in turn; and then purifying the prepared crude Beta-tetraacetyl-L-ribose syrup to obtain refined Beta-tetraacetyl-L-ribose, wherein the process is simple, the cost is low, and the yield can reach 51-55%.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
A method for preparing beta-tetraacetyl-L-ribose, characterized in that: the preparation method takes L-ribose as a starting material, and crude Beta-tetraacetyl-L-ribose syrup is obtained by sequentially carrying out methyl reaction, three acetyl reactions, demethylation reaction and four acetyl reactions;
then purifying the prepared crude Beta-tetraacetyl-L-ribose syrup to obtain refined Beta-tetraacetyl-L-ribose.
Specifically, the methyl reaction comprises the following steps:
a1: adding 1000ml of methanol into 50g of L-ribose, dropwise adding 5ml of sulfuric acid, stirring at room temperature for reacting for 4-5 h, adding 100g of sodium carbonate for neutralizing, filtering, and evaporating to obtain a mixture of light yellow alpha-methyl-L-ribose and beta-methyl-L-ribose;
a2: separating the mixture of alpha-methyl-L-ribose and beta-methyl-L-ribose to obtain beta-methyl-L-ribose;
a3: the purified β -methyl-L-ribose pool obtained in step a2 was concentrated.
Step A2 is a column chromatography method to separate the mixture of alpha-methyl-L-ribose and beta-methyl-L-ribose. The ratio of the mixture of alpha-methyl-L-ribose and beta-methyl-L-ribose in step A1 is 2.5-3: 7.5-8.5.
The three acetyl reactions comprise the following specific steps: and B, taking 30g of the beta-methyl-L-ribose concentrated solution obtained in the step A3, adding 75ml of glacial acetic acid and 100ml of acid anhydride, cooling by adopting an ice bath, adding a catalyst, and stirring and reacting for 3 hours at the temperature of 100 ℃. The demethylation reaction comprises the following specific steps: 5ml of sulfuric acid is dripped into the solution after the three acetyl reactions are finished, the temperature is raised to 80-85 ℃, and the reaction is carried out for 20-30 min. The fourth acetyl reaction comprises the following specific steps: and adding 25g of sodium acetate into the solution after the demethylation reaction, controlling the temperature at 100 ℃, stirring for reaction for 3 hours, and performing evaporation concentration to obtain the crude Beta-tetraacetyl-L-ribose syrup.
The purification treatment comprises dissolving, washing, dehydrating, evaporating, drying and crystallizing to obtain white crystals, namely refined Beta-tetraacetyl-L-ribose syrup.
Specifically, chloroform solution is adopted to dissolve crude Beta-tetraacetyl-L-ribose syrup, after washing, anhydrous sodium sulfate is added for dehydration, and after evaporation and drying, white crystals are obtained by ethanol crystallization.
The performance detection result of the obtained refined Beta-tetraacetyl-L-ribose syrup is as follows:
RF ═ 0.58(1:1 ethyl acetate/n-hexane);
the melting point is 80-83 ℃.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (8)
1. A method for preparing beta-tetraacetyl-L-ribose, characterized in that: the preparation method takes L-ribose as a starting material, and crude Beta-tetraacetyl-L-ribose syrup is obtained by sequentially carrying out methyl reaction, three acetyl reactions, demethylation reaction and four acetyl reactions;
then purifying the prepared crude Beta-tetraacetyl-L-ribose syrup to obtain refined Beta-tetraacetyl-L-ribose.
2. The process for producing β -tetraacetyl-L-ribose according to claim 1, wherein: the methyl reaction comprises the following steps:
a1: adding 1000ml of methanol into 50g of L-ribose, dropwise adding 5ml of sulfuric acid, stirring at room temperature for reacting for 4-5 h, adding 100g of sodium carbonate for neutralizing, filtering, and evaporating to obtain a mixture of light yellow alpha-methyl-L-ribose and beta-methyl-L-ribose;
a2: separating the mixture of alpha-methyl-L-ribose and beta-methyl-L-ribose to obtain beta-methyl-L-ribose;
a3: the purified β -methyl-L-ribose pool obtained in step a2 was concentrated.
3. The process for producing β -tetraacetyl-L-ribose according to claim 2, wherein: step A2 is a column chromatography method to separate the mixture of alpha-methyl-L-ribose and beta-methyl-L-ribose.
4. The process for producing β -tetraacetyl-L-ribose according to claim 2, wherein: the ratio of the mixture of alpha-methyl-L-ribose and beta-methyl-L-ribose in step A1 is 2.5-3: 7.5-8.5.
5. The process for producing β -tetraacetyl-L-ribose according to claim 2, wherein: the three acetyl reactions comprise the following specific steps: and B, taking 30g of the beta-methyl-L-ribose concentrated solution obtained in the step A3, adding 75ml of glacial acetic acid and 100ml of acid anhydride, cooling by adopting an ice bath, adding a catalyst, and stirring and reacting for 3 hours at the temperature of 100 ℃.
6. The process for producing β -tetraacetyl-L-ribose according to claim 5, wherein: the demethylation reaction comprises the following specific steps: 5ml of sulfuric acid is dripped into the solution after the three acetyl reactions are finished, the temperature is raised to 80-85 ℃, and the reaction is carried out for 20-30 min.
7. The process for producing β -tetraacetyl-L-ribose according to claim 6, wherein: the fourth acetyl reaction comprises the following specific steps: and adding 25g of sodium acetate into the solution after the demethylation reaction, controlling the temperature at 100 ℃, stirring for reaction for 3 hours, and performing evaporation concentration to obtain the crude Beta-tetraacetyl-L-ribose syrup.
8. The process for producing β -tetraacetyl-L-ribose according to claim 1, wherein: the purification treatment comprises dissolving, washing, dehydrating, evaporating, drying and crystallizing to obtain white crystals.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910691682.8A CN112300226A (en) | 2019-07-30 | 2019-07-30 | Method for preparing beta-tetraacetyl-L-ribose |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910691682.8A CN112300226A (en) | 2019-07-30 | 2019-07-30 | Method for preparing beta-tetraacetyl-L-ribose |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112300226A true CN112300226A (en) | 2021-02-02 |
Family
ID=74330095
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910691682.8A Pending CN112300226A (en) | 2019-07-30 | 2019-07-30 | Method for preparing beta-tetraacetyl-L-ribose |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112300226A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101148465A (en) * | 2007-11-01 | 2008-03-26 | 上海交通大学 | 3-Benzyl-L-uridine and preparation method thereof |
| CN101595117A (en) * | 2006-12-08 | 2009-12-02 | 株式会社Api | The manufacture method of furanose derivative |
| CN101875680A (en) * | 2009-04-28 | 2010-11-03 | 上海信旗医药科技有限公司 | Nucleoside compound, preparation method and application thereof |
-
2019
- 2019-07-30 CN CN201910691682.8A patent/CN112300226A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101595117A (en) * | 2006-12-08 | 2009-12-02 | 株式会社Api | The manufacture method of furanose derivative |
| CN101148465A (en) * | 2007-11-01 | 2008-03-26 | 上海交通大学 | 3-Benzyl-L-uridine and preparation method thereof |
| CN101875680A (en) * | 2009-04-28 | 2010-11-03 | 上海信旗医药科技有限公司 | Nucleoside compound, preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN113735811B (en) | Method for synthesizing vitrochromic factor through acylation protection and reduction | |
| JP2012508695A (en) | Process for producing 4- (1-hydroxy-1-methylethyl) -2-propylimidazole-5-carboxylic acid ester | |
| CN102395591B (en) | Method for preparing prasugrel | |
| CN107011404A (en) | A kind of method using cholic acid as Material synthesis lithocholic acid | |
| CN103539773B (en) | Method for preparing ticagrelor key intermediate | |
| WO2016109990A1 (en) | Method for catalytic synthesis of salidroside | |
| CN103601766B (en) | Fondaparinux sodium pentasaccharide intermediate and preparation method thereof | |
| CN109320564B (en) | Preparation process of L-lyxose | |
| CN112300226A (en) | Method for preparing beta-tetraacetyl-L-ribose | |
| CN109553610B (en) | Preparation method of emtricitabine isomer | |
| CN106366057A (en) | Synthetic method of sofosbuvir intermediate | |
| JPH0250908B2 (en) | ||
| CN110845562B (en) | Method for recycling betamethasone or dexamethasone synthetic mother liquor material | |
| CN114195844A (en) | Preparation method of dehydroepiandrosterone | |
| US20090112002A1 (en) | Process for preparation of aldonic acids and derivatives thereof | |
| WO2021062882A1 (en) | Method for synthesizing rosavin | |
| CN111944004A (en) | Preparation method of halometasone | |
| CN114644679B (en) | Glucuronide compound, preparation method and application thereof | |
| US6090952A (en) | (2R, 3S, 22R, 23R)-2,3,22,23-tetrahydroxy-24-ethyl-β-homo-7-oxa-5α-cholesta n-6-one and a process for preparing the same | |
| WO2007076655A1 (en) | METHOD FOR SYNTHESIS OF CHOLEST-3β,5α,6β,19-TETRAHYDROXY-24-ONE AND ITS DERIVATIVES | |
| CN109081860A (en) | A kind of preparation method of 16a, 21- biacetyl oxygroup prednisolone product | |
| CN109180764A (en) | It is a kind of to prepare 16a, the method for 21- biacetyl oxygroup prednisolone product | |
| CN107011138B (en) | Preparation method of sitagliptin intermediate | |
| IL36330A (en) | The preparation of acetyl derivatives of steroidal cardiac active glycosides | |
| CN112679513B (en) | Method for preparing key intermediate of koji Bei Ti |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20210202 |