CN102675391B - Chemical method synthesizing adenosine technique - Google Patents
Chemical method synthesizing adenosine technique Download PDFInfo
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- CN102675391B CN102675391B CN201210160137.4A CN201210160137A CN102675391B CN 102675391 B CN102675391 B CN 102675391B CN 201210160137 A CN201210160137 A CN 201210160137A CN 102675391 B CN102675391 B CN 102675391B
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Abstract
The present invention relates to a kind of chemical method synthesizing adenosine technique; belong to chemical industry synthesis field, it is characterized in that taking inosine as starting raw material, first carry out acetylization reaction and generate 2 '; 3 '; 5 '-triacetyl inosine, then in saturated ammonia-methanol solution, under dual catalyst exists; generate transition state salt; then ammonia solution generates adenosine, and content is greater than 99%, and yield is greater than 72%.The present invention only uses the Lewis acid of the nitrogenous heteroaromatic compounds such as the pyridine of catalytic amount and catalytic amount, the transition state salt generated is without separation, direct ammonia solution generates adenosine, reaches shortened process, reduces facility investment and the object such as loss of material, raising product yield.
Description
Technical field
The present invention relates to a kind of chemical method synthesizing adenosine technique, belong to chemical industry synthesis field.
Background technology
The chemosynthesis of adenosine has multiple route, comparative maturity have two large classes: one is xanthoglobulin method, xanthoglobulin through chlorination, ammonia solution generate VITAMIN B4, again with 1,2,3,5-tetra-acetyl-β-D-RIBOSE (abbreviation 1,2,3,5-Tetra-O-Acetyl-D-Ribose) reaction, hydrolysis obtain adenosine.Two is inosine methods, and first inosine carries out acetylize protection, generates triacetyl inosine, then has two kinds of methods: 1. chlorination process: triacetyl inosine solves adenosine through the chlorination of Vilsmeier reagent, ammonia; 2. pyridine method: triacetyl inosine reacts with anhydrous pyridine under condensing agent exists, and hydroxyl is replaced by pyridine, generate triacetyl inosine pyridinium salt, then ammonia solution obtains adenosine.
In above-mentioned two large class methods, the raw materials used xanthoglobulin of xanthoglobulin method and 1,2,3,5-Tetra-O-Acetyl-D-Ribose obtain by inosine decomposition, thus do not have cost advantage.Inosine method 1. chlorination process uses Vilsmeier reagent to make chlorizating agent, and the tail gas sulphur dioxide that sulfur oxychloride produces and hydrogenchloride absorb treatment facility investment higher; 2. pyridine method is that reactant doubles as solvent with anhydrous pyridine, and pyridine usage quantity is large, and containing a large amount of pyridine in ammonia solution processed waste water, cost for wastewater treatment is high; Pyridine method also uses phosphorus oxychloride or sulfur oxychloride as chlorizating agent simultaneously.Although inosine method is the method generally adopted at present, but still the shortcoming such as it is long to there is operational path, yield low (< 65%).
Summary of the invention
According to the deficiencies in the prior art, the technical problem to be solved in the present invention is: provide a kind of chemical method synthesizing adenosine technique, without chlorination reaction, in saturated ammonia-methanol solution, under dual catalyst exists, ammonia solution generates adenosine, shorten operational path, improve yield.
The technical solution adopted for the present invention to solve the technical problems is: provide a kind of chemical method synthesizing adenosine technique; it is characterized in that taking inosine as starting raw material; first carry out acetylization reaction and generate 2 '; 3 '; 5 '-triacetyl inosine, then in saturated ammonia-methanol solution, under dual catalyst exists; generate transition state salt, then ammonia solution generates adenosine.
One of described dual catalyst is nitrogenous heteroaromatic compound.
The described preferred pyridine of nitrogenous heteroaromatic compound or pyrroles and derivative thereof.
Described nitrogenous heteroaromatic compound consumption is 0.05% ~ 10% of inosine quality.
One of described dual catalyst is 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 inosine quality.
The direct ammonia solution of transition state salt of described generation generates adenosine.
The present invention relates to a kind of synthetic method of adenosine, have following steps: be 1. starting raw material with inosine, adopt acetic anhydride to carry out acetylization reaction and generate 2 ', 3 ', 5 '-triacetyl inosine.2. by calculated amount 2 ', 3 ', 5 '-triacetyl inosine is placed in autoclave, adds quantitative saturation methanolic ammonia solution, Lewis acid and nitrogenous heteroaromatic compound, 60 DEG C ~ 80 DEG C, reacts 4 ~ 8 hours.3. react end, reclaim excess of ammonia and methyl alcohol, obtain adenosine crude product.4. crude product refining obtains adenosine salable product.
Reaction process is as follows:
This reaction is without chlorination reaction, in saturated ammonia-methanol solution, in the presence of a lewis acid, generate transition state pyridinium salt with pyridine, without the need to being separated, ammonolysis reaction occurring immediately and generates adenosine, and discharge pyridine, this pyridine reacts with triacetyl inosine again and generates transition state pyridinium salt, ammonia solution, goes round and begins again, until reaction terminates.
The invention has the beneficial effects as follows: the Lewis acid only using the nitrogenous heteroaromatic compounds such as the pyridine of catalytic amount and catalytic amount, the transition state salt generated is without separation, direct ammonia solution generates adenosine, reaches shortened process, reduces facility investment and the object such as loss of material, raising product yield.
Embodiment
Below in conjunction with embodiment, the present invention is described further:
Embodiment 1
(1) preparation of triacetyl inosine:
Thermometer installed by 1000ml tetra-mouthfuls of reaction flasks, condenser, drop into 200g inosine, 300ml acetic anhydride, 2g anhydrous sodium acetate, be heated to backflow, react 1.5 hours, the acetic acid reclaiming excessive acetic anhydride and produce, solids is extremely neutral with 200ml cold wash, vacuum-drying obtains the white crystals 286g of triacetyl inosine, yield 97.27%.
(2) preparation of adenosine:
In 1000ml autoclave, accurately add gained triacetyl inosine 50g in (1), add 500ml anhydrous methanol, 0.4gAlCl
3, 2ml anhydrous pyridine, stir and be cooled to 0 ± 2 DEG C, logical ammonia is to saturated, and sealing, is warming up to 65 ± 2 DEG C, reacts 5 hours.Reaction is finished, and reclaims excessive methyl alcohol and ammonia, obtains crude product, and through the white crystals 25.23g of refining adenosine, HPLC 99.78%, yield 72.44%(is in inosine).
Embodiment 2
In 1000ml autoclave, accurately add embodiment 1(1) middle gained triacetyl inosine 50g, add 500ml anhydrous methanol, 3g ZnCl
2, the anhydrous pyrroles of 5ml, stirs and is cooled to 0 ± 2 DEG C, and logical ammonia, to saturated, seals, be warming up to 78 ± 2 DEG C, react 5 hours, reaction is finished, and reclaims excessive methyl alcohol and ammonia, crude product, through the white crystals 25.56g of refining adenosine, HPLC99.62%, yield 73.38%(is in inosine).
Embodiment 3
In 1000ml autoclave, accurately add embodiment 1(1) middle gained triacetyl inosine 50g, add 500ml anhydrous methanol, the anhydrous SnCl of 2g
4, 3ml anhydrous pyridine, stirs and is cooled to 0 ± 2 DEG C, and logical ammonia, to saturated, seals, be warming up to 70 ± 2 DEG C, react 4 hours, reaction is finished, and reclaims excessive methyl alcohol and ammonia, crude product, through the white crystals 25.78g of refining adenosine, HPLC 99.62%, yield 74.01%(is in inosine).
Claims (1)
1. a method for chemical method synthesizing adenosine, is characterized in that taking inosine as starting raw material, first carries out acetylization reaction and generates 2 ', 3 ', 5 '-triacetyl inosine, then in saturated ammonia-methanol solution, under dual catalyst exists, generate transition state salt, then ammonia solution generates adenosine;
One of described dual catalyst is nitrogenous heteroaromatic compound;
Described nitrogenous heteroaromatic compound is pyridine;
Described nitrogenous heteroaromatic compound consumption is 0.05% ~ 10% of inosine quality;
One of described dual catalyst is 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 inosine quality;
The direct ammonia solution of transition state salt of described generation generates 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 CN102675391A (en) | 2012-09-19 |
| CN102675391B true 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》.2007,第24卷(第8期),971-973. * |
| 廖本仁,等.由肌苷制取腺苷.《化学试剂》.2006,第28卷(第10期),633-634. * |
| 施庆珊,等.腺苷的微生物合成研究.《发酵科技通讯》.2005,第34卷(第2期),全文. * |
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| CN102675391A (en) | 2012-09-19 |
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Address after: Double Yang Zichuan District 255190 Shandong city of Zibo Province Applicant after: SHANDONG KAISHENG NEW MATERIALS CO., LTD. Address before: Double Yang Zichuan District 255190 Shandong city of Zibo Province Applicant before: Shandong Kaisheng New Materials Co.,Ltd. |
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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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Free format text: CORRECT: INVENTOR; FROM: ZHANG ZHENXIA XUE JUQIANG WANG JIARONG ZHANG BAO YANG DEYAO LI XUEYAN TO: BI YIXIA WANG RONGHAI XUE JUQIANG WANG JIARONG ZHANG SHANMIN YANG DEYAO JIA YUANCHAO ZHANG QINGXIN |
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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. |