CN102675391A - Technique for synthesizing adenosin by chemical method - Google Patents
Technique for synthesizing adenosin by chemical method Download PDFInfo
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- CN102675391A CN102675391A CN2012101601374A CN201210160137A CN102675391A CN 102675391 A CN102675391 A CN 102675391A CN 2012101601374 A CN2012101601374 A CN 2012101601374A CN 201210160137 A CN201210160137 A CN 201210160137A CN 102675391 A CN102675391 A CN 102675391A
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Abstract
The invention relates to a technique for synthesizing adenosin by a chemical method, belonging to the field of synthesis in chemical industry. The technique is characterized by comprising the following steps: carrying out acetylation reaction on the initial raw material inosine to generate 2',3',5'-triacetylinosine; in the presence of dual catalysts, generating a transition-state salt in a saturated ammonia-methanol solution; and carrying out ammonolysis to generate the adenosin, wherein the content is higher than 99%, and the yield is higher than 72%. The invention only uses catalytic amounts of pyridine and other nitrogenous heteroaromatic compounds and catalytic amounts of Lewis acid, and the generated transition state salt is directly subjected to ammonolysis without separation to generate the adenosin, thereby achieving the goals of shortening the technological process, reducing the equipment investment and material loss, enhancing the product yield and the like.
Description
Technical field
The present invention relates to a kind of chemical method synthesizing adenosine technology, belong to the synthetic field of chemical industry.
Background technology
The chemosynthesis of adenosine has multiple route, comparative maturity have two big types: the one, the xanthoglobulin method, xanthoglobulin is separated the generation VITAMIN B4 through chlorination, ammonia; Again with 1; 2,3,5-tetrem acyl-β-D-ribofuranose (being called for short tetrem acyl ribose) reaction, hydrolysis obtain adenosine.The 2nd, the inosine method, inosine at first carries out acetylize protection, generates the triacetyl inosine, and two kinds of methods are arranged then: 1. chlorination: the triacetyl inosine solves adenosine through the chlorination of Vilsmeier reagent, ammonia; 2. pyridine method: the triacetyl inosine in the presence of condensing agent with the anhydrous pyridine reaction, hydroxyl is replaced by pyridine, generates triacetyl inosine pyridinium salt, ammonia is separated and is obtained adenosine then.
In above-mentioned two big class methods, raw materials used xanthoglobulin of xanthoglobulin method and tetrem acyl ribose obtain by the inosine decomposition, thereby do not have cost advantage.Inosine method 1. chlorination uses Vilsmeier reagent to make chlorizating agent, tail gas sulphur dioxide and hydrogenchloride that sulfur oxychloride produces, and it is higher to absorb the treatment facility investment; 2. the pyridine method is to be reactant double as solvent with the anhydrous pyridine, and the pyridine usage quantity is big, and ammonia is separated and contained a large amount of pyridines in the processed waste water, and cost for wastewater treatment is high; The pyridine method also uses POCl3 or sulfur oxychloride as chlorizating agent simultaneously.Though the inosine method is the method that generally adopts at present, but still exists operational path long, the low shortcomings such as (＜65%) of yield.
Summary of the invention
According to the deficiency of prior art, the technical problem that the present invention will solve is: a kind of chemical method synthesizing adenosine technology is provided, without chlorination reaction; In saturated ammonia-methanol solution, in the presence of dual catalyst, ammonia is separated the generation adenosine; Shorten operational path, improve yield.
The technical solution adopted for the present invention to solve the technical problems is: a kind of chemical method synthesizing adenosine technology is provided, it is characterized in that with the inosine being starting raw material, at first carry out acetylization reaction generate 2 '; 3 '; 5 '-the triacetyl inosine, then in saturated ammonia-methanol solution, in the presence of dual catalyst; Generate transition state salt, ammonia is separated the generation adenosine then.
One of described dual catalyst is nitrogenous heteroaromatic compound.
The preferred pyridine of described nitrogenous heteroaromatic compound or pyrroles and verivate thereof.
Described nitrogenous heteroaromatic compound consumption is 0.05% ~ 10% of an inosine quality.
One of described dual catalyst is a Lewis acid.
Described Lewis acid is AlCl
3, AlBr
3, ZnCl
2, FeCl
3, SnCl
4, SbCl
5Or TiCl
4
Described lewis acidic consumption is 0.5% ~ 10% of an inosine quality.
The direct ammonia of transition state salt of described generation is separated the generation adenosine.
The present invention relates to a kind of compound method of adenosine, following steps arranged: 1. be starting raw material with the inosine, adopt acetic anhydride carry out acetylization reaction generate 2 ', 3 ', 5 '-the triacetyl inosine.2. with calculated amount 2 ', 3 ', 5 '-the triacetyl inosine places autoclave, adds quantitative saturated ammonia methanol solution, Lewis acid and nitrogenous heteroaromatic compound, 60 ℃ ~ 80 ℃, reacted 4 ~ 8 hours.3. reaction finishes, and reclaims excess of ammonia and methyl alcohol, obtains the adenosine bullion.4. crude product refining gets the adenosine salable product.
Reaction process is following:
This reaction is without chlorination reaction, in saturated ammonia-methanol solution, in the presence of Lewis acid; Generate the transition state pyridinium salt with pyridine, need not to separate, ammonolysis reaction takes place immediately generate adenosine; And discharge pyridine; This pyridine generates the transition state pyridinium salt with the reaction of triacetyl inosine again, ammonia is separated, and goes round and begins again, and finishes until reaction.
The invention has the beneficial effects as follows: only use the nitrogenous heteroaromatic compound such as pyridine of catalytic amount and the Lewis acid of catalytic amount; The transition state salt that generates is without separation; Directly ammonia is separated the generation adenosine, has reached purposes such as shortened process, minimizing facility investment and loss of material, raising product yield.
Embodiment
Below in conjunction with embodiment the present invention is done and to further describe:
Embodiment 1
(1) preparation of triacetyl inosine:
Mounting temperature meter on the 1000ml four-hole reaction flask, condensing surface drops into the 200g inosine; The 300ml acetic anhydride, the 2g anhydrous sodium acetate, heat temperature raising is to refluxing; Reacted 1.5 hours, and reclaimed excessive acetic anhydride and the acetate that is produced, solids is extremely neutral with the 200ml cold wash; Vacuum-drying gets the white crystals 286g of triacetyl inosine, yield 97.27%.
(2) preparation of adenosine:
In the 1000ml autoclave, accurately add gained triacetyl inosine 50g in (1), add the 500ml anhydrous methanol, 0.4gAlCl
3, the 2ml anhydrous pyridine, stir and to be cooled to 0 ± 2 ℃, logical ammonia is to saturated, sealing is warming up to 65 ± 2 ℃, reacts 5 hours.Reaction is finished, and reclaims excessive methyl alcohol and ammonia, bullion, through make with extra care the white crystals 25.23g of adenosine, HPLC 99.78%, yield 72.44% (in inosine).
Embodiment 2
In the 1000ml autoclave, accurately add gained triacetyl inosine 50g among the embodiment 1 (1), add the 500ml anhydrous methanol, 3g ZnCl
2, the anhydrous pyrroles of 5ml stirs and is cooled to 0 ± 2 ℃, and logical ammonia seals to saturated; Be warming up to 78 ± 2 ℃, reacted 5 hours, reaction is finished, and reclaims excessive methyl alcohol and ammonia; Bullion, through the white crystals 25.56g of refining adenosine, HPLC99.62%, yield 73.38% (in inosine).
Embodiment 3
In the 1000ml autoclave, accurately add gained triacetyl inosine 50g among the embodiment 1 (1), add the 500ml anhydrous methanol, the anhydrous SnCl of 2g
4, the 3ml anhydrous pyridine stirs and is cooled to 0 ± 2 ℃, and logical ammonia seals to saturated; Be warming up to 70 ± 2 ℃, reacted 4 hours, reaction is finished, and reclaims excessive methyl alcohol and ammonia; Bullion, through the white crystals 25.78g of refining adenosine, HPLC 99.62%, yield 74.01% (in inosine).
Claims (8)
1. a chemical method synthesizing adenosine technology is characterized in that with the inosine being starting raw material, at first carry out acetylization reaction generate 2 '; 3 ', 5 '-the triacetyl inosine, then in saturated ammonia-methanol solution; In the presence of dual catalyst, generate transition state salt, ammonia is separated the generation adenosine then.
2. chemical method synthesizing adenosine technology according to claim 1 is characterized in that one of described dual catalyst is nitrogenous heteroaromatic compound.
3. chemical method synthesizing adenosine technology according to claim 2 is characterized in that the preferred pyridine of described nitrogenous heteroaromatic compound or pyrroles and verivate thereof.
4. chemical method synthesizing adenosine technology according to claim 2 is characterized in that described nitrogenous heteroaromatic compound consumption is 0.05% ~ 10% of an inosine quality.
5. chemical method synthesizing adenosine technology according to claim 1 is characterized in that one of described dual catalyst is a Lewis acid.
6. chemical method synthesizing adenosine technology according to claim 5 is characterized in that described Lewis acid is AlCl
3, AlBr
3, ZnCl
2, FeCl
3, SnCl
4, SbCl
5Or TiCl
4
7. chemical method synthesizing adenosine technology according to claim 1 is characterized in that described lewis acidic consumption is 0.5% ~ 10% of an inosine quality.
8. chemical method synthesizing adenosine technology according to claim 1 is characterized in that the direct ammonia of transition state salt of described generation is separated the generation adenosine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210160137.4A CN102675391B (en) | 2011-12-20 | 2012-05-22 | Chemical method synthesizing adenosine technique |
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|---|---|---|---|
| CN2011104276159 | 2011-12-20 | ||
| CN201110427615 | 2011-12-20 | ||
| CN201110427615.9 | 2011-12-20 | ||
| CN201210160137.4A CN102675391B (en) | 2011-12-20 | 2012-05-22 | Chemical method synthesizing adenosine technique |
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| CN102675391A true CN102675391A (en) | 2012-09-19 |
| CN102675391B CN102675391B (en) | 2015-09-02 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB534738A (en) * | 1938-09-16 | 1941-03-17 | Chem Ind Basel | Manufacture of adenosine |
| CN1629178A (en) * | 2004-09-01 | 2005-06-22 | 浙江诚意药业有限公司 | Method for preparing adenosine |
| CN1634961A (en) * | 2004-11-23 | 2005-07-06 | 华东理工大学 | Improved process for preparing adenosine |
-
2012
- 2012-05-22 CN CN201210160137.4A patent/CN102675391B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB534738A (en) * | 1938-09-16 | 1941-03-17 | Chem Ind Basel | Manufacture of adenosine |
| CN1629178A (en) * | 2004-09-01 | 2005-06-22 | 浙江诚意药业有限公司 | Method for preparing adenosine |
| CN1634961A (en) * | 2004-11-23 | 2005-07-06 | 华东理工大学 | Improved process for preparing adenosine |
Non-Patent Citations (3)
| Title |
|---|
| 冀亚飞，等: "从肌苷简便合成腺苷", 《应用化学》 * |
| 廖本仁，等: "由肌苷制取腺苷", 《化学试剂》 * |
| 施庆珊，等: "腺苷的微生物合成研究", 《发酵科技通讯》 * |
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Inventor after: Bi Yixia Inventor after: Wang Ronghai Inventor after: Xue Juqiang Inventor after: Wang Jiarong Inventor after: Zhang Shanmin Inventor after: Yang Deyao Inventor after: Jia Yuanchao Inventor after: Zhang Qingxin Inventor before: Zhang Zhenxia Inventor before: Xue Juqiang Inventor before: Wang Jiarong Inventor before: Zhang Bao Inventor before: Yang Deyao Inventor before: Li Xueyan |
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Address after: Double Yang Zichuan District 255190 Shandong city of Zibo Province Patentee after: Shandong Kaisheng New Materials Co.,Ltd. Address before: Double Yang Zichuan District 255190 Shandong city of Zibo Province Patentee before: SHANDONG KAISHENG NEW MATERIALS CO., LTD. |