CN102321004A - The compound method of a kind of L-(+)-selenomethionine - Google Patents
The compound method of a kind of L-(+)-selenomethionine Download PDFInfo
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- CN102321004A CN102321004A CN201110152981A CN201110152981A CN102321004A CN 102321004 A CN102321004 A CN 102321004A CN 201110152981 A CN201110152981 A CN 201110152981A CN 201110152981 A CN201110152981 A CN 201110152981A CN 102321004 A CN102321004 A CN 102321004A
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Abstract
The present invention relates to the compound method of a kind of L-(+)-selenomethionine, is to be raw material with L-(+)-methionine(Met), through with the methyl-sulfate reaction, methylthio group is sloughed in hydrolysis, 4-hydroxyl-a-amino acid; Ring generates alpha-amino group GBL hydrochloride to 4-hydroxyl-a-amino acid in hydrochloric acid catalysis ShiShimonoseki; Alpha-amino group GBL hydrochloride and sodium methyl-hydroselenide addition open loop, acidifying get product L-(+)-selenomethionine.Adopt methyl-sulfate as alkylating reagent among the present invention, have raw material be easy to get, inexpensive, easy for operation, advantage such as reaction conditions is gentle, product separation is simple.
Description
Technical field
The present invention relates to selenomethionine, specifically is the compound method of a kind of L-(+)-selenomethionine.
Background technology
Selenium is one of necessary trace element of human body and other animals; It can combine with the intravital glutathione peroxidase of biology; Effectively protection red blood cell and cytolemma exempt from the reaction of solubility peroxy oxygen and destroy; Panimmunity and biological function are arranged, and research shows, selenium is in anti-ageing, antiviral, prevention and treatment cardiovascular diseases, Keshan disease, Kaschin-Beck disease, cataract; Particularly has unique effect aspect prevention and anticancer (mammary cancer, cancer of the stomach, the prostate cancer etc.); L-(+)-selenomethionine is that occurring in nature selenium is present in a kind of organic selenium compounds in plant and the feed grains with organic form, compares with inorganic selenium, and L-(+)-selenomethionine has that toxicity is little, environmental pollution is little, the bioavailability advantages of higher.At present, American-European many countries advocate energetically and use organoselenium, require must use organoselenium in the piglet feed like Sweden; Japan bans use of inorganic selenium in the regulation feed.The selenomethionine stable in properties, effect is remarkable, has higher utility, and popularizing application prospect is wide.
At present selenomethionine can be obtained by biological fermentation and chemosynthesis, and the former mainly is to be raw material with the inorganic selenium Sodium Selenite, through biological fermentation; Inorganic selenium is converted into selenomethionine; The subject matter that this method exists is that the inorganic selenium transformation efficiency is low during the fermentation, and a large amount of inorganic seleniums are discharged with waste water formation, cause serious environmental pollution; Form, the purity of while product are unstable, and quality is difficult to be guaranteed; Adopt chemosynthesis to mainly contain following several method:
(a) liquid ammonia process for caustic soda purification (chemistry of selenium, biological chemistry and the application in life science thereof, Xu Bihui chief editor, the big press of Central China science and engineering, 1994): temperature of reaction is low, uses sodium Metal 99.5 and liquefied ammonia, needs special reaction device and reaction conditions.
(b) first seleno propionic aldehyde method (Chinese invention patent CN1369483A): this method is simulated old-fashioned methionine(Met) production technique fully, needs the sodium cyanide with severe toxicity, complex process.
(c) amino GBL method (Song Lianqing etc., Zhengzhou Grain College journal, 1999,20; 62): promptly from gamma-butyrolactone, through 5 steps such as bromination, amination, addition, total recovery about 33%; This technology uses comparatively cheap gamma-butyrolactone to be starting raw material, and what obtain is D, L-selenomethionine mixture, separation difficulty; And this synthetic route need add the liquid bromine of severe toxicity under near the temperature of the boiling point of bromine, and operation easier is big, and equipment requirements is high.
(d) lithium methide method (T.Koch, O.Buchardt, Synthesis; 1993,1065): promptly obtain target compound from methionine(Met) through the reaction of 7 steps, total recovery is less than 30%; Use several kinds of high chemical reagent such as lithium methide and tributoxy-boron in the technology, and have a step under strong acidic condition, to use the Hydrogen bromide halo in the technology, also have a step to need the anhydrous and oxygen-free condition; Requirement to equipment and operation is very high, is difficult to accomplish scale production.
(e) dimethyl diselenide ether method (Chinese patent; Application number 200710028734.0):, with the reaction of 4-bromo-α-An Jisuanzhi, get selenomethionine then through hydrolysis promptly with dimethyl diselenide ether and Peng Qinghuana reaction; Though this method is described simple; But the source of 4-bromo-α-An Jisuanzhi is not described, because 4-bromo-α-An Jisuanzhi does not have commercialization, building-up process is complicated.
(f) methionine(Met) method (Chinese invention patent; ZL 200510012329.5): this method is greatly simplified (d) method; And productive rate is greatly improved; But in research subsequently, find also to exist tangible deficiency; Mainly be in alkylation step, use cost an arm and a leg and the excess iodine methane of highly volatile as alkylating reagent, in subsequent step, need go out to the methyl iodide oxidation, the extracting and separating that do not act on, otherwise it is dark and unstable to cause product colour to cross with a large amount of Hazardous Chemical Substances ydrogen peroxide 50 and ether.
In a word, there is following shortcoming in existing compound method: 1, complex synthetic route; 2, raw material is difficult for obtaining or costing an arm and a leg; 3, cost is high, pollution is big, be difficult for suitability for industrialized production.
Summary of the invention
The object of the present invention is to provide a kind of reaction conditions gentleness, raw material resources to enrich, be easy to get, be fit to the compound method of L-(+)-selenomethionine of suitability for industrialized production.
The compound method of a kind of L-provided by the present invention (+)-selenomethionine, reaction equation is:
Its synthesis step is following:
(1) be raw material with L-(+)-methionine(Met), through reacting with methyl-sulfate, methylthio group is sloughed in hydrolysis, gets 4-hydroxyl-a-amino acid, and wherein the mol ratio of L (+)-methionine(Met) and methyl-sulfate is 1: 1-1.5;
(2) ring generates alpha-amino group GBL hydrochloride to 4-hydroxyl-a-amino acid in hydrochloric acid catalysis ShiShimonoseki;
(3) alpha-amino group GBL hydrochloride and sodium methyl-hydroselenide addition open loop, acidifying get product L-(+)-selenomethionine, and wherein, the mol ratio of alpha-amino group GBL hydrochloride and sodium methyl-hydroselenide is 1: 2-2.5, the pH value transfers to 5.5-6.5 during acidifying.
The acid of using during said acidifying is hydrochloric acid, sulfuric acid or acetate, preferred acetate.
Advantage compared with prior art of the present invention and effect:
Adopt methyl-sulfate as alkylating reagent among the present invention, have raw material be easy to get, inexpensive, easy for operation, advantage such as reaction conditions is gentle, product separation is simple.
Embodiment
Embodiment 1:
(75g, 0.50mol) (57mL 0.6mol), stirred 12 hours methyl-sulfate, and distillation removes and desolvates to 200mL, added 500mL water and NaHCO in the 1000mL round-bottomed flask that fills water/methyl alcohol (500/100mL), to add L-(+)-methionine(Met) (1)
3(21g, 0.25mol), reflux 5 hours changes water distilling apparatus into, distills out and desolvates; The hydrochloric acid that adds 500mL 6M, reflux 1 hour, distillation removes and desolvates, and crude product gets amino GBL hydrochloride with ethanol/water (9: 1) recrystallization; Get above-mentioned amino GBL hydrochloride (17.5g; 0.113mol) and N (57mL) place the 250mL round-bottomed flask, add first seleno sodium (27g, ethanolic soln 0.231mol) prepare in advance; Reflux 4 hours; Cooling gets the white solid crude product with the second acid for adjusting pH value to 5.5-6.0, gets L-(+)-selenomethionine with the ethanol/water recrystallization, productive rate 56%.
Embodiment 2
(75g, 0.50mol) (71.5mL 0.75mol), stirred 12 hours methyl-sulfate, and distillation removes and desolvates to 200mL, added 500mL water and NaHCO in the 1000mL round-bottomed flask that fills water/methyl alcohol (500/100mL), to add L-(+)-methionine(Met) (1)
3(21g, 0.25mol), reflux 5 hours changes water distilling apparatus into, distills out and desolvates; The hydrochloric acid that adds 500mL 6M, reflux 1 hour, distillation removes and desolvates, and crude product gets amino GBL hydrochloride with ethanol/water (9: 1) recrystallization; Get above-mentioned amino GBL hydrochloride (17.5g; 0.113mol) and N (57mL) place the 250mL round-bottomed flask, add first seleno sodium (33g, ethanolic soln 0.283mol) prepare in advance; Reflux 4 hours; Cooling gets the white solid crude product with the second acid for adjusting pH value to 5.5-6.0, gets L-(+)-selenomethionine with the ethanol/water recrystallization, productive rate 60%.
Embodiment 3
(75g, 0.50mol) (57mL 0.6mol), stirred 12 hours methyl-sulfate, and distillation removes and desolvates to 200mL, added 500mL water and NaHCO in the 1000mL round-bottomed flask that fills water/methyl alcohol (500/100mL), to add L-(+)-methionine(Met) (1)
3(21g, 0.25mol), reflux 5 hours changes water distilling apparatus into, distills out and desolvates; The hydrochloric acid that adds 500mL 6M, reflux 1 hour, distillation removes and desolvates, and crude product gets amino GBL hydrochloride with ethanol/water (9: 1) recrystallization; Get above-mentioned amino GBL hydrochloride (17.5g; 0.113mol) and N (57mL) place the 250mL round-bottomed flask, add first seleno sodium (29g, ethanolic soln 0.243mol) prepare in advance; Reflux 4 hours; Cooling gets the white solid crude product with second acid for adjusting pH value to 6.0, gets L-(+)-selenomethionine with the ethanol/water recrystallization, productive rate 58%.
Claims (3)
1. the compound method of a L-(+)-selenomethionine is characterized in that, reaction equation is:
Synthesis step comprises:
(1) be raw material with L-(+)-methionine(Met), through reacting with methyl-sulfate, methylthio group is sloughed in hydrolysis, gets 4-hydroxyl-a-amino acid, and wherein the mol ratio of L (+)-methionine(Met) and methyl-sulfate is 1: 1-1.5;
(2) ring generates alpha-amino group GBL hydrochloride to 4-hydroxyl-a-amino acid in hydrochloric acid catalysis ShiShimonoseki;
(3) alpha-amino group GBL hydrochloride and sodium methyl-hydroselenide addition open loop, acidifying get product L-(+)-selenomethionine, and wherein, the mol ratio of alpha-amino group GBL hydrochloride and sodium methyl-hydroselenide is 1: 2-2.5, the pH value transfers to 5.5-6.5 during acidifying.
2. the compound method of a kind of L-as claimed in claim 1 (+)-selenomethionine is characterized in that, the acid of using during acidifying described in the step (3) is hydrochloric acid, sulfuric acid or acetate.
3. the compound method of a kind of L-as claimed in claim 1 (+)-selenomethionine is characterized in that, the acid of using during acidifying described in the step (3) is acetate.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201110152981A CN102321004A (en) | 2011-06-04 | 2011-06-04 | The compound method of a kind of L-(+)-selenomethionine |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104744329A (en) * | 2015-03-24 | 2015-07-01 | 山西大学 | Preparation method and application of 2-phenylcarbamido-4-selenium methyl butyrate |
| CN106220539A (en) * | 2016-07-25 | 2016-12-14 | 四川新美生物科技有限公司 | A kind of preparation method of selenomethionine |
| CN106928110A (en) * | 2017-03-16 | 2017-07-07 | 安徽至善新材料有限公司 | A kind of preparation method of high-optical-purity D or L selenomethionines |
| CN110283088A (en) * | 2019-07-26 | 2019-09-27 | 成都百事兴科技实业有限公司 | A kind of preparation method of L- homoserine |
| CN110878071A (en) * | 2019-11-21 | 2020-03-13 | 华南农业大学 | Preparation method of α -amino-gamma-butyrolactone and salt thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3898276A (en) * | 1969-06-06 | 1975-08-05 | Philips Corp | Process for the preparation of selenomethionine-Se{hu 75 |
| CN1343665A (en) * | 2000-09-15 | 2002-04-10 | 台州市沙星化工有限公司 | Process for preparing 4,6-dichloro-2-methiopyrimidine |
| EP1205471A1 (en) * | 2000-10-02 | 2002-05-15 | PharmaSe, Incorporated | A method of using synthetic L-SE-Methylselenocysteine as a nutriceutical and a method of its synthesis |
| CN1680312A (en) * | 2005-01-21 | 2005-10-12 | 山西大学 | Synthesis of seleno-methionine |
-
2011
- 2011-06-04 CN CN201110152981A patent/CN102321004A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3898276A (en) * | 1969-06-06 | 1975-08-05 | Philips Corp | Process for the preparation of selenomethionine-Se{hu 75 |
| CN1343665A (en) * | 2000-09-15 | 2002-04-10 | 台州市沙星化工有限公司 | Process for preparing 4,6-dichloro-2-methiopyrimidine |
| EP1205471A1 (en) * | 2000-10-02 | 2002-05-15 | PharmaSe, Incorporated | A method of using synthetic L-SE-Methylselenocysteine as a nutriceutical and a method of its synthesis |
| CN1680312A (en) * | 2005-01-21 | 2005-10-12 | 山西大学 | Synthesis of seleno-methionine |
Non-Patent Citations (1)
| Title |
|---|
| 舒绪刚等: "硒代蛋氨酸的合成方法研究进展", 《广州化工》, vol. 38, no. 10, 15 October 2010 (2010-10-15), pages 70 - 71 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104744329A (en) * | 2015-03-24 | 2015-07-01 | 山西大学 | Preparation method and application of 2-phenylcarbamido-4-selenium methyl butyrate |
| CN106220539A (en) * | 2016-07-25 | 2016-12-14 | 四川新美生物科技有限公司 | A kind of preparation method of selenomethionine |
| CN106928110A (en) * | 2017-03-16 | 2017-07-07 | 安徽至善新材料有限公司 | A kind of preparation method of high-optical-purity D or L selenomethionines |
| CN110283088A (en) * | 2019-07-26 | 2019-09-27 | 成都百事兴科技实业有限公司 | A kind of preparation method of L- homoserine |
| CN110283088B (en) * | 2019-07-26 | 2023-02-24 | 成都百事兴科技实业有限公司 | Preparation method of L-homoserine |
| CN110878071A (en) * | 2019-11-21 | 2020-03-13 | 华南农业大学 | Preparation method of α -amino-gamma-butyrolactone and salt thereof |
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Application publication date: 20120118 |