CN102146050A - Synthesis method, racemization method and separation method of Se-methylselenocysteine - Google Patents
Synthesis method, racemization method and separation method of Se-methylselenocysteine Download PDFInfo
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Abstract
The invention discloses a synthesis method, racemization method and separation method of Se-methylselenocysteine. The synthesis method comprises the following steps: reacting 2,3-dihalopropionitrile with methyl hydroselenide salt to obtain 2-halo-3-methylselenopropionitrile, then hydrolyzing with acid to obtain 2-halo-3-methylselenopropionic acid, and reacting with ammonia water to obtain Se-methylselenocysteine. The racemization method comprises the following steps: catalyzing Se-methylselenocysteine with aldehyde to obtain racemate; or racemizing with acetic anhydride by heating and hydrolyzing with acid to obtain racemate. The separation method comprises the following steps: using Aspergillus oryzae amino-acylase or immobilized Aspergillus oryzae enzyme to perform enzymolysis of N-acetyl-DL-Se-methylselenocysteine to obtain L-Se-methylselenocysteine and N-acetyl-D-Se-methylselenocysteine, and then hydrolyzing with acid to obtain D-Se-methylselenocysteine; or using papain and aniline to perform enzymatic reaction of N-acetyl-DL-Se-methylselenocysteine to obtain N-acetyl-L-Se-methylselenocysteine and N-acetyl-D-Se-methylselenocysteine, and hydrolyzing with acid to obtain D-Se-methylselenocysteine and L-Se-methylselenocysteine.
Description
Technical field
The invention belongs to the synthetic field of amino acid, relate to synthetic, the racemization and the method for splitting of methylselenocysteinefrom.
Background technology
Selenium is the necessary trace element of human body, have anticancer, give protection against cancer, protect heart, prevent and treat cataract, Keshan disease and Kaschin-Beck disease, delay senility, separate functions such as heavy metal poison.Selenium deficiency will cause that selenoenzyme is active and reduce that oxygen radical removing is obstructed, the microbial film damage, and detoxifcation and immunologic function a series of body function obstacles such as go down, thus cause multiple disease generation.The supplement selenium element is that prevention lacks the effective ways that selenium disease is taken place.At present, domestic selenium component extender has Sodium Selenite, sodium selenate, selenocarrageenan, selenomethionine and methylselenocysteinefrom etc.Methylselenocysteinefrom is a kind of selenium natural amino acid that contains, be present in the plants such as garlic and onion, it have supplement selenium element, anti-curing cancers, anti-oxidant, anti-ageing, prevent and treat cardiovascular and cerebrovascular diseases, separate effect such as heavy metal poison, can be applicable to aspects such as medicine and nutritive health-care.Methylselenocysteinefrom content in natural phant is very low, and the extraction separation difficulty is directly extracted the Financial cost height, therefore researchs and develops the methylselenocysteinefrom synthetic method and has important practical significance.At present methylselenocysteinefrom synthetic mainly contains following several method:
(1) chlorine L-Ala two sodium selenide methods: at first chlorine L-Ala and the reaction of two sodium selenides are generated selenocystine, use sodium Metal 99.5/liquefied ammonia (70 ℃) reductive cleavage then, get methylselenocysteinefrom with the methyl iodide alkylation again.This method relates to very low temperature and active hazardous metals sodium, severe reaction conditions, and processing unit requires high, chlorine L-Ala cost of material height, production cost height (Methods Enzymol., 1987,143,240-243; J.Med.Chem., 1996,39,2040-2046);
(2) uncle's fourth oxygen acyl group protection Serine method: in the presence of basic phosphorus of three alkane (virtue) or phosphite; uncle's fourth oxygen acyl group Serine and the reaction of azoformic acid diester generate the β lactone; generate the methylselenocysteinefrom of uncle's fourth oxygen acyl group protection then with methyl-hydroselenide or its reactant salt, last deprotection gets methylselenocysteinefrom.This method technology is tediously long, raw material thread propylhomoserin and protection reagent price height, the production cost height (A method ofusing synthetic L-Se-methylselenocysteine as a nutraceutical and a method of itssynthesis, EP 1 205 471, and 2001);
(3) sodium methyl-hydroselenide replaces chlorine L-Ala method: the chlorine with in sodium methyl-hydroselenide replacement chlorine L-Ala or the chlorine alanine methyl ester gets methylselenocysteinefrom.This method chlorine L-Ala cost of material height, production cost height (Manufacturing processes for Se-methyl-L-selenocysteine, US 6794537B1,2004).
(4) first seleno acetaldehyde method: methyl-hydroselenide salt and the reaction of halo acetaldehyde are generated first seleno acetaldehyde, the reaction of first seleno acetaldehyde and volatile salt and sodium cyanide obtains first seleno methylhydantoi then, use sodium hydroxide heating hydrolysis first seleno methylhydantoi again, make methylselenocysteinefrom after hydrochloric acid is handled.This method relates to hypertoxic raw material, as chloro acetaldehyde and sodium cyanide, to environmental hazard big (ZL 200610124942.6, a kind of method by the synthetic methylselenocysteinefrom of first seleno acetaldehyde).
(5) alpha-amino acrylic acid derivative synthesis method: at first by methyl-hydroselenide or methyl-hydroselenide salt brine solution and alpha-amino acrylic acid derivative generation addition reaction generation β-first seleno-α-An Jibingsuan derivative; then with the ester cpds in β-first seleno-α-An Jibingsuan derivative through sodium bicarbonate or sodium hydroxide or potassium hydroxide hydrolysis saponification; hydrochloric acid or sulfuric acid acidation get its carboxylic acid cpd; N-acyl group that again will be wherein with hydrochloric acid or sulfuric acid heating hydrolysis slough β-first seleno-α-An Jibingsuan hydrochloride or vitriol, at last with ammonia or triethylamine neutralize methylselenocysteinefrom.This method raw material alpha-amino acrylic acid derivative price height, production cost height (ZL200710051362.3, a kind of method of utilizing alpha-amino acrylic acid derivative to prepare methylselenocysteinefrom).
In sum, at present the cost of material height that exists that has of methylselenocysteinefrom synthetic method causes the production cost height, and what have exists operational path complexity, productive rate low, and what have exists severe reaction conditions, equipment requirements height, what have relates to hypertoxic raw material, defectives such as harm environment.
The invention provides that a kind of synthetic route is simple, easy to operate, raw material is easy to get cheaply, productive rate is high, cost is low, environmental friendliness, the methylselenocysteinefrom synthetic method that is fit to large-scale industrial production also provides the racemization and the method for splitting of methylselenocysteinefrom.The main raw material that the present invention relates to is 2, and 3-dihalo-propionitrile (as 2,3-two chloroethyl nitriles; 2,3-two bromopropionitriles; 2,3-difluoro propionitrile and 2,3-diiodo-propionitrile), 2, the industrial raw material of the existing cheapness that 3-dihalo-propionitrile has, as 2,3-two chloroethyl nitriles perhaps utilize wide material sources, cheap vinyl cyanide and the simple addition of halogen to obtain.Raw material of the present invention is cheap and easy to get, and synthesis step is few, productive rate is high, so production cost is low, is fit to suitability for industrialized production.
Summary of the invention
The present invention includes following content:
1, methylselenocysteinefrom is synthetic
(1) with 2,3-dihalo-propionitrile and methyl-hydroselenide salt generation substitution reaction generate 2-halogen-3-first seleno propionitrile; Described 2,3-dihalo-propionitrile is 2,3-two chloroethyl nitriles, 2, and 3-two bromopropionitriles, 2,3-difluoro propionitrile or 2,3-diiodo-propionitrile, described methyl-hydroselenide salt are sodium methyl-hydroselenide or methyl-hydroselenide potassium, described substitution reaction temperature is 10 ℃-100 ℃;
(2) 2-halogen-3-first seleno propionitrile is generated 2-halogen-3-first seleno-propionic acid with hydrochloric acid or sulfuric acid heating hydrolysis;
(3), with hydrochloric acid or sulfuric acid neutralization, get methylselenocysteinefrom then with 2-halogen-3-first seleno-propionic acid and ammoniacal liquor reaction; Described ammoniacal liquor substitution reaction temperature is 10 ℃-100 ℃.
2, the racemization of methylselenocysteinefrom
(1) aldehyde catalysis racemization method
Methylselenocysteinefrom is dissolved in Glacial acetic acid or the aqueous acetic acid, adds the aldehyde catalyzer, the heating racemization, the monitoring specific rotation, complete to racemization, get the DL-methylselenocysteinefrom; The concentration of described aqueous acetic acid is 60%-100%, and the racemization temperature is 30 ℃-100 ℃, and the aldehyde catalyzer is propionic aldehyde, 2 methyl propanal, 2 methyl butyraldehyde or 3-methyl butyraldehyde, and the mol ratio of methylselenocysteinefrom and aldehyde catalyzer is 5-100.
(2) acetic anhydride racemization method
Methylselenocysteinefrom is dissolved in the Glacial acetic acid, adds acetic anhydride, the heating racemization, the monitoring specific rotation, complete to racemization, with hydrochloric acid or sulfuric acid heating hydrolysis, get the DL-methylselenocysteinefrom; Described racemization temperature is 70 ℃-150 ℃, and the mol ratio of acetic anhydride and methylselenocysteinefrom is 1-10.
3, the fractionation of DL-methylselenocysteinefrom
(1) aspergillus oryzae L-Aminoacylase Split Method
The DL-methylselenocysteinefrom is dissolved in aqueous sodium hydroxide solution, dripping acetyl chloride react N-acetyl-DL-methylselenocysteinefrom sodium, get N-acetyl-DL-methylselenocysteinefrom with hydrochloric acid or sulfuric acid acidation then;
N-acetyl-DL-methylselenocysteinefrom is dissolved in buffered soln, add the aspergillus oryzae L-Aminoacylase, carry out enzyme digestion reaction, after enzymolysis finishes, solution is separated with storng-acid cation exchange resin, and water and ammoniacal liquor wash-out get N-acetyl-D-methylselenocysteinefrom and L-methylselenocysteinefrom; With N-acetyl-D-methylselenocysteinefrom strong acid, example hydrochloric acid, Hydrogen bromide, hydroiodic acid HI or sulfuric acid etc., heating hydrolysis is complete, then with ammoniacal liquor neutralize the D-methylselenocysteinefrom; Described enzyme digestion reaction is to carry out under pH4-10, temperature are 10-60 ℃ condition.
(2) the immobilization aspergillus oryzae cell Split Method of product L-Aminoacylase
The aspergillus oryzae body and function gelatin-glutaraldehyde or the gelatin-formaldehyde fixed that adopt ordinary method will produce L-Aminoacylase, get the immobilization aspergillus oryzae cell, and dress up column type reactor, allow the solution stream that contains N-acetyl-DL-methylselenocysteinefrom cross immobilization aspergillus oryzae cell column type reactor, collect and split effluent liquid, to split effluent liquid and separate with storng-acid cation exchange resin, water and ammoniacal liquor wash-out get N-acetyl-D-methylselenocysteinefrom and L-methylselenocysteinefrom; With N-acetyl-D-methylselenocysteinefrom strong acid, example hydrochloric acid, Hydrogen bromide, hydroiodic acid HI or sulfuric acid, heating hydrolysis is complete, then with ammoniacal liquor neutralize the D-methylselenocysteinefrom; Described resolution reaction is to carry out under pH4-10, temperature are 10-60 ℃ condition.
(3) papoid Split Method
N-acetyl-DL-methylselenocysteinefrom is dissolved in the buffered soln, add aniline or to monomethylaniline, add papoid again, carry out enzymatic reaction, after reaction finishes, filter, insolubles is that N-acetyl-L-methylselenocysteinefrom aniline or N-acetyl-L-methylselenocysteinefrom are to monomethylaniline, complete with hydrochloric acid or sulfuric acid heating hydrolysis, then with ammoniacal liquor neutralize the L-methylselenocysteinefrom; Filtrate contains N-acetyl-D-methylselenocysteinefrom, and is complete with hydrochloric acid or sulfuric acid heating hydrolysis behind the concentrating under reduced pressure, then with ammoniacal liquor neutralize the D-methylselenocysteinefrom; Described enzymatic reaction is to carry out under the 20-70 ℃ of condition in pH3-9, temperature.
Description of drawings
Accompanying drawing is a synthetic route synoptic diagram of the present invention.
Embodiment
Below in conjunction with embodiment the present invention is described in further detail, but should understands the non-scope that only limits to these embodiment of scope of the present invention.
Embodiment 1:
Synthesizing of methylselenocysteinefrom:
With 2,3-two chloroethyl nitrile 12.4g are dissolved in the 200ml tetrahydrofuran (THF), add the 200ml aqueous solution contain the 11.7g sodium methyl-hydroselenide, in 10 ℃ of stirring reactions 10 hours, use ethyl acetate extraction, and decompression and solvent recovery must 2-chloro-3-first seleno propionitrile 15.3g, yield 84.06%.18.2g is dissolved in the 200ml concentrated hydrochloric acid with 2-chloro-3-first seleno propionitrile, reflux hydrolysis 5 hours, and the evaporated under reduced pressure solvent gets 2-chloro-3-first seleno-propionic acid 19.1g, yield 94.55%.20.2g is dissolved in the 300ml strong aqua with 2-chloro-3-first seleno-propionic acid, and in 10 ℃ of stirring reactions 10 hours, the pressure reducing and steaming excessive ammonia was neutralized to neutrality with concentrated hydrochloric acid, and concentrating under reduced pressure gets methylselenocysteinefrom 15.3g, yield 84.06%.
Embodiment 2:
Synthesizing of methylselenocysteinefrom:
With 2,3-two chloroethyl nitrile 12.4g are dissolved in the 200ml tetrahydrofuran (THF), add the 200ml aqueous solution contain the 11.7g sodium methyl-hydroselenide, in 50 ℃ of stirring reactions 8 hours, use ethyl acetate extraction, and decompression and solvent recovery must 2-chloro-3-first seleno propionitrile 17.2g, yield 94.50%.18.2g is dissolved in the 200ml concentrated hydrochloric acid with 2-chloro-3-first seleno propionitrile, reflux hydrolysis 5 hours, and the evaporated under reduced pressure solvent gets 2-chloro-3-first seleno-propionic acid 19.1g, yield 94.55%.20.2g is dissolved in the 300ml strong aqua with 2-chloro-3-first seleno-propionic acid, and in 50 ℃ of stirring reactions 8 hours, the pressure reducing and steaming excessive ammonia was neutralized to neutrality with concentrated hydrochloric acid, and concentrating under reduced pressure gets methylselenocysteinefrom 17.0g, yield 93.41%.
Embodiment 3:
Synthesizing of methylselenocysteinefrom:
With 2,3-two chloroethyl nitrile 12.4g are dissolved in the 200ml tetrahydrofuran (THF), add the 200ml aqueous solution contain the 11.7g sodium methyl-hydroselenide, in 100 ℃ of stirring reactions 5 hours, use ethyl acetate extraction, and decompression and solvent recovery must 2-chloro-3-first seleno propionitrile 13.2g, yield 72.53%.18.2g is dissolved in the 200ml50% sulfuric acid with 2-chloro-3-first seleno propionitrile, reflux hydrolysis 5 hours, and concentrating under reduced pressure is separated out 2-chloro-3-first seleno-propionic acid 13.8g, yield 68.32%.20.2g is dissolved in the 300ml strong aqua with 2-chloro-3-first seleno-propionic acid, and in 100 ℃ of stirring reactions 5 hours, the pressure reducing and steaming excessive ammonia was neutralized to neutrality with 50% sulfuric acid, and concentrating under reduced pressure is separated out methylselenocysteinefrom 13.1g, yield 71.98%.
Embodiment 4:
Synthesizing of methylselenocysteinefrom:
With 2,3-two chloroethyl nitrile 12.4g are dissolved in the 200ml tetrahydrofuran (THF), add the 200ml aqueous solution contain 13.3g methyl-hydroselenide potassium, in 50 ℃ of stirring reactions 8 hours, use ethyl acetate extraction, and decompression and solvent recovery must 2-chloro-3-first seleno propionitrile 16.0g, yield 87.91%.18.2g is dissolved in the 200ml concentrated hydrochloric acid with 2-chloro-3-first seleno propionitrile, reflux hydrolysis 5 hours, and concentrating under reduced pressure gets 2-chloro-3-first seleno-propionic acid 19.1g, yield 94.55%.20.2g is dissolved in the 300ml strong aqua with 2-chloro-3-first seleno-propionic acid, and in 50 ℃ of stirring reactions 5 hours, the pressure reducing and steaming excessive ammonia was neutralized to neutrality with 50% sulfuric acid, and concentrating under reduced pressure is separated out methylselenocysteinefrom 13.0g, yield 71.43%.
Embodiment 5:
Synthesizing of methylselenocysteinefrom:
With 2,3-two chloroethyl nitrile 12.4g are dissolved in the 200ml tetrahydrofuran (THF), add the 200ml aqueous solution contain 20.0g methyl-hydroselenide potassium, in 10 ℃ of stirring reactions 10 hours, use ethyl acetate extraction, and decompression and solvent recovery must 2-chloro-3-first seleno propionitrile 15.2g, yield 83.52%.18.2g is dissolved in the 200ml50% sulfuric acid with 2-chloro-3-first seleno propionitrile, reflux hydrolysis 5 hours, and concentrating under reduced pressure is separated out 2-chloro-3-first seleno-propionic acid 13.5g, yield 66.83%.20.2g is dissolved in the 300ml strong aqua with 2-chloro-3-first seleno-propionic acid, and in 10 ℃ of stirring reactions 10 hours, the pressure reducing and steaming excessive ammonia was neutralized to neutrality with concentrated hydrochloric acid, and concentrating under reduced pressure gets methylselenocysteinefrom 15.3g, yield 84.06%.
Embodiment 6:
Synthesizing of methylselenocysteinefrom:
With 2,3-two chloroethyl nitrile 12.4g are dissolved in the 200ml tetrahydrofuran (THF), add the 200ml aqueous solution contain the 17.6g sodium methyl-hydroselenide, in 100 ℃ of stirring reactions 6 hours, use ethyl acetate extraction, and decompression and solvent recovery must 2-chloro-3-first seleno propionitrile 13.3g, yield 73.08%.18.2g is dissolved in the 200ml concentrated hydrochloric acid with 2-chloro-3-first seleno propionitrile, reflux hydrolysis 5 hours, and the evaporated under reduced pressure solvent gets 2-chloro-3-first seleno-propionic acid 19.1g, yield 94.55%.20.2g is dissolved in the 300ml strong aqua with 2-chloro-3-first seleno-propionic acid, and in 100 ℃ of stirring reactions 8 hours, the pressure reducing and steaming excessive ammonia was neutralized to neutrality with concentrated hydrochloric acid, and concentrating under reduced pressure gets methylselenocysteinefrom 15.8g, yield 86.81%.
Embodiment 7:
Synthesizing of methylselenocysteinefrom:
With 2,3-two bromopropionitrile 21.3g are dissolved in the 200ml tetrahydrofuran (THF), add the 200ml aqueous solution contain the 11.7g sodium methyl-hydroselenide, in 10 ℃ of stirring reactions 10 hours, use ethyl acetate extraction, and decompression and solvent recovery must 2-bromo-3-first seleno propionitrile 15.5g, yield 68.28%.22.7g is dissolved in the 200ml concentrated hydrochloric acid with 2-bromo-3-first seleno propionitrile, reflux hydrolysis 5 hours, and the evaporated under reduced pressure solvent gets 2-bromo-3-first seleno-propionic acid 22.3g, yield 90.65%.24.6g is dissolved in the 300ml strong aqua with 2-bromo-3-first seleno-propionic acid, and in 10 ℃ of stirring reactions 12 hours, the pressure reducing and steaming excessive ammonia was neutralized to neutrality with concentrated hydrochloric acid, and concentrating under reduced pressure gets methylselenocysteinefrom 12.9g, yield 70.88%.
Embodiment 8:
Synthesizing of methylselenocysteinefrom:
With 2,3-two bromopropionitrile 21.3g are dissolved in the 200ml tetrahydrofuran (THF), add the 200ml aqueous solution contain 13.3g methyl-hydroselenide potassium, in 50 ℃ of stirring reactions 8 hours, use ethyl acetate extraction, and decompression and solvent recovery must 2-bromo-3-first seleno propionitrile 13.8g, yield 60.79%.22.7g is dissolved in the 200ml50% sulfuric acid with 2-bromo-3-first seleno propionitrile, reflux hydrolysis 5 hours, and concentrating under reduced pressure is separated out 2-bromo-3-first seleno-propionic acid 22.3g, yield 90.65%.24.6g is dissolved in the 300ml strong aqua with 2-bromo-3-first seleno-propionic acid, and in 50 ℃ of stirring reactions 10 hours, the pressure reducing and steaming excessive ammonia was neutralized to neutrality with 50% sulfuric acid, and concentrating under reduced pressure is separated out methylselenocysteinefrom 13.5g, yield 74.18%.
Embodiment 9:
Synthesizing of methylselenocysteinefrom:
With 2,3-two bromopropionitrile 21.3g are dissolved in the 200ml tetrahydrofuran (THF), add the 200ml aqueous solution contain the 11.7g sodium methyl-hydroselenide, in 100 ℃ of stirring reactions 6 hours, use ethyl acetate extraction, and decompression and solvent recovery must 2-bromo-3-first seleno propionitrile 12.9g, yield 56.83%.22.7g is dissolved in the 200ml concentrated hydrochloric acid with 2-bromo-3-first seleno propionitrile, reflux hydrolysis 5 hours, and the evaporated under reduced pressure solvent gets 2-bromo-3-first seleno-propionic acid 23.5g, yield 95.53%.24.6g is dissolved in the 300ml strong aqua with 2-bromo-3-first seleno-propionic acid, and in 100 ℃ of stirring reactions 6 hours, the pressure reducing and steaming excessive ammonia was neutralized to neutrality with concentrated hydrochloric acid, and concentrating under reduced pressure gets methylselenocysteinefrom 11.9g, yield 65.38%.
Embodiment 10:
Synthesizing of methylselenocysteinefrom:
With 2,3-difluoro propionitrile 9.1g is dissolved in the 200ml tetrahydrofuran (THF), adds the 200ml aqueous solution contain the 11.7g sodium methyl-hydroselenide, in 10 ℃ of stirring reactions 12 hours, use ethyl acetate extraction, and decompression and solvent recovery must 2-fluoro-3-first seleno propionitrile 12.5g, yield 75.30%.16.6g is dissolved in the 200ml concentrated hydrochloric acid with 2-fluoro-3-first seleno propionitrile, reflux hydrolysis 5 hours, and the evaporated under reduced pressure solvent gets 2-fluoro-3-first seleno-propionic acid 17.6g, yield 95.14%.18.5g is dissolved in the 300ml strong aqua with 2-fluoro-3-first seleno-propionic acid, and in 10 ℃ of stirring reactions 12 hours, the pressure reducing and steaming excessive ammonia was neutralized to neutrality with concentrated hydrochloric acid, and concentrating under reduced pressure gets methylselenocysteinefrom 10.1g, yield 55.49%.
Embodiment 11:
Synthesizing of methylselenocysteinefrom:
With 2,3-difluoro propionitrile 9.1g is dissolved in the 200ml tetrahydrofuran (THF), adds the 200ml aqueous solution contain 13.3g methyl-hydroselenide potassium, in 50 ℃ of stirring reactions 10 hours, use ethyl acetate extraction, and decompression and solvent recovery must 2-fluoro-3-first seleno propionitrile 11.7g, yield 70.48%.16.6g is dissolved in the 200ml50% sulfuric acid with 2-fluoro-3-first seleno propionitrile, reflux hydrolysis 5 hours, and concentrating under reduced pressure is separated out 2-fluoro-3-first seleno-propionic acid 17.6g, yield 95.14%.18.5g is dissolved in the 300ml strong aqua with 2-fluoro-3-first seleno-propionic acid, and in 50 ℃ of stirring reactions 10 hours, the pressure reducing and steaming excessive ammonia was neutralized to neutrality with 50% sulfuric acid, and concentrating under reduced pressure is separated out methylselenocysteinefrom 11.4g, yield 62.64%.
Embodiment 12:
Synthesizing of methylselenocysteinefrom:
With 2,3-difluoro propionitrile 9.1g is dissolved in the 200ml tetrahydrofuran (THF), adds the 200ml aqueous solution contain the 11.7g sodium methyl-hydroselenide, in 100 ℃ of stirring reactions 8 hours, use ethyl acetate extraction, and decompression and solvent recovery must 2-fluoro-3-first seleno propionitrile 8.8g, yield 53.01%.16.6g is dissolved in the 200ml concentrated hydrochloric acid with 2-fluoro-3-first seleno propionitrile, reflux hydrolysis 5 hours, and concentrating under reduced pressure gets 2-fluoro-3-first seleno-propionic acid 17.6g, yield 95.14%.18.5g is dissolved in the 300ml strong aqua with 2-fluoro-3-first seleno-propionic acid, and in 100 ℃ of stirring reactions 8 hours, the pressure reducing and steaming excessive ammonia was neutralized to neutrality with concentrated hydrochloric acid, and the evaporated under reduced pressure solvent gets methylselenocysteinefrom 9.3g, yield 51.10%.
Embodiment 13:
Synthesizing of methylselenocysteinefrom:
With 2,3-diiodo-propionitrile 30.7g is dissolved in the 200ml tetrahydrofuran (THF), adds the 200ml aqueous solution contain the 11.7g sodium methyl-hydroselenide, in 10 ℃ of stirring reactions 9 hours, use ethyl acetate extraction, and decompression and solvent recovery must 2-iodo-3-first seleno propionitrile 18.9g, yield 68.98%.27.4g is dissolved in the 200ml concentrated hydrochloric acid with 2-iodo-3-first seleno propionitrile, reflux hydrolysis 5 hours, and the evaporated under reduced pressure solvent gets 2-iodo-3-first seleno-propionic acid 27.8g, yield 94.88%.29.3g is dissolved in the 300ml strong aqua with 2-iodo-3-first seleno-propionic acid, and in 10 ℃ of stirring reactions 12 hours, the pressure reducing and steaming excessive ammonia was neutralized to neutrality with concentrated hydrochloric acid, and concentrating under reduced pressure gets methylselenocysteinefrom 14.1g, yield 77.47%.
Embodiment 14:
Synthesizing of methylselenocysteinefrom:
With 2,3-diiodo-propionitrile 30.7g is dissolved in the 200ml tetrahydrofuran (THF), adds the 200ml aqueous solution contain 13.3g methyl-hydroselenide potassium, in 50 ℃ of stirring reactions 8 hours, use ethyl acetate extraction, and decompression and solvent recovery must 2-iodo-3-first seleno propionitrile 20.2g, yield 73.72%.27.4g is dissolved in the 200ml50% sulfuric acid with 2-iodo-3-first seleno propionitrile, reflux hydrolysis 5 hours, and concentrating under reduced pressure is separated out 2-iodo-3-first seleno-propionic acid 26.8g, yield 91.47%.29.3g is dissolved in the 300ml strong aqua with 2-iodo-3-first seleno-propionic acid, and in 50 ℃ of stirring reactions 10 hours, the pressure reducing and steaming excessive ammonia was neutralized to neutrality with 50% sulfuric acid, and concentrating under reduced pressure is separated out methylselenocysteinefrom 15.5g, yield 85.16%.
Embodiment 15:
Synthesizing of methylselenocysteinefrom:
With 2,3-diiodo-propionitrile 30.7g is dissolved in the 200ml tetrahydrofuran (THF), adds the 200ml aqueous solution contain the 11.7g sodium methyl-hydroselenide, in 100 ℃ of stirring reactions 6 hours, use ethyl acetate extraction, and decompression and solvent recovery must 2-iodo-3-first seleno propionitrile 24.3g, yield 88.69%.27.4g is dissolved in the 200ml concentrated hydrochloric acid with 2-iodo-3-first seleno propionitrile, reflux hydrolysis 5 hours, and the evaporated under reduced pressure solvent gets 2-iodo-3-first seleno-propionic acid 27.2g, yield 92.83%.29.3g is dissolved in the 300ml strong aqua with 2-iodo-3-first seleno-propionic acid, and in 100 ℃ of stirring reactions 6 hours, the pressure reducing and steaming excessive ammonia was neutralized to neutrality with concentrated hydrochloric acid, and concentrating under reduced pressure gets methylselenocysteinefrom 17.1g, yield 93.96%.
Embodiment 16:
The aldehyde catalysis racemization of methylselenocysteinefrom:
The 0.1mol selenium-methyl selenium substituted aminothiopropionic is dissolved in 200ml 60% aqueous acetic acid, add 1mmol propionic aldehyde catalyzer, in 30 ℃ of racemizations, the monitoring specific rotation, complete to racemization, get solid behind the evaporated under reduced pressure solvent, use the methanol wash solid, suction filtration gets DL-methylselenocysteinefrom 16.8g, yield 92.31%.
Embodiment 17:
The aldehyde catalysis racemization of methylselenocysteinefrom:
The 0.1mol selenium-methyl selenium substituted aminothiopropionic is dissolved in 200ml 80% aqueous acetic acid, add 2mmol propionic aldehyde catalyzer, in 60 ℃ of racemizations, the monitoring specific rotation, complete to racemization, get solid behind the evaporated under reduced pressure solvent, use the methanol wash solid, suction filtration gets DL-methylselenocysteinefrom 17.8g, yield 97.80%.
Embodiment 18:
The aldehyde catalysis racemization of methylselenocysteinefrom:
The 0.1mol selenium-methyl selenium substituted aminothiopropionic is dissolved in the 200ml Glacial acetic acid, add 20mmol propionic aldehyde catalyzer, in 100 ℃ of racemizations, the monitoring specific rotation, complete to racemization, get solid behind the evaporated under reduced pressure solvent, use the methanol wash solid, suction filtration gets DL-methylselenocysteinefrom 17.0g, yield 93.41%.
Embodiment 19:
The aldehyde catalysis racemization of methylselenocysteinefrom:
The 0.1mol selenium-methyl selenium substituted aminothiopropionic is dissolved in 200ml 60% aqueous acetic acid, add 1mmol2-methylpropanal catalyzer, in 30 ℃ of racemizations, the monitoring specific rotation, complete to racemization, get solid behind the evaporated under reduced pressure solvent, use the methanol wash solid, suction filtration gets DL-methylselenocysteinefrom 17.3g, yield 95.05%.
Embodiment 20:
The aldehyde catalysis racemization of methylselenocysteinefrom:
The 0.1mol selenium-methyl selenium substituted aminothiopropionic is dissolved in 200ml 80% aqueous acetic acid, add 2mmol2-methylpropanal catalyzer, in 60 ℃ of racemizations, the monitoring specific rotation, complete to racemization, get solid behind the evaporated under reduced pressure solvent, use the methanol wash solid, suction filtration gets DL-methylselenocysteinefrom 16.9g, yield 92.86%.
Embodiment 21:
The aldehyde catalysis racemization of methylselenocysteinefrom:
The 0.1mol selenium-methyl selenium substituted aminothiopropionic is dissolved in the 200ml Glacial acetic acid, add 20mmol 2 methyl propanal catalyzer, in 100 ℃ of racemizations, the monitoring specific rotation, complete to racemization, get solid behind the evaporated under reduced pressure solvent, use the methanol wash solid, suction filtration gets DL-methylselenocysteinefrom 16.5g, yield 90.66%.
Embodiment 22:
The aldehyde catalysis racemization of methylselenocysteinefrom:
The 0.1mol selenium-methyl selenium substituted aminothiopropionic is dissolved in 200ml 60% aqueous acetic acid, add 1mmol2-methyl butyraldehyde catalyzer, in 30 ℃ of racemizations, the monitoring specific rotation, complete to racemization, get solid behind the evaporated under reduced pressure solvent, use the methanol wash solid, suction filtration gets DL-methylselenocysteinefrom 17.4g, yield 95.60%.
Embodiment 23:
The aldehyde catalysis racemization of methylselenocysteinefrom:
The 0.1mol selenium-methyl selenium substituted aminothiopropionic is dissolved in 200ml 80% aqueous acetic acid, add 2mmol2-methyl butyraldehyde catalyzer, in 60 ℃ of racemizations, the monitoring specific rotation, complete to racemization, get solid behind the evaporated under reduced pressure solvent, use the methanol wash solid, suction filtration gets DL-methylselenocysteinefrom 17.0g, yield 93.41%.
Embodiment 24:
The aldehyde catalysis racemization of methylselenocysteinefrom:
The 0.1mol selenium-methyl selenium substituted aminothiopropionic is dissolved in the 200ml Glacial acetic acid, add 20mmol 2 methyl butyraldehyde catalyzer, in 100 ℃ of racemizations, the monitoring specific rotation, complete to racemization, get solid behind the evaporated under reduced pressure solvent, use the methanol wash solid, suction filtration gets DL-methylselenocysteinefrom 16.7g, yield 91.76%.
Embodiment 25:
The aldehyde catalysis racemization of methylselenocysteinefrom:
The 0.1mol selenium-methyl selenium substituted aminothiopropionic is dissolved in 200ml 60% aqueous acetic acid, add 1mmol3-methyl butyraldehyde catalyzer, in 30 ℃ of racemizations, the monitoring specific rotation, complete to racemization, get solid behind the evaporated under reduced pressure solvent, use the methanol wash solid, suction filtration gets DL-methylselenocysteinefrom 16.4g, yield 90.11%.
Embodiment 26:
The aldehyde catalysis racemization of methylselenocysteinefrom:
The 0.1mol selenium-methyl selenium substituted aminothiopropionic is dissolved in 200ml 80% aqueous acetic acid, add 2mmol3-methyl butyraldehyde catalyzer, in 60 ℃ of racemizations, the monitoring specific rotation, complete to racemization, get solid behind the evaporated under reduced pressure solvent, use the methanol wash solid, suction filtration gets DL-methylselenocysteinefrom 17.7g, yield 97.25%.
Embodiment 27:
The aldehyde catalysis racemization of methylselenocysteinefrom:
The 0.1mol selenium-methyl selenium substituted aminothiopropionic is dissolved in the 200ml Glacial acetic acid, add 20mmol 3-methyl butyraldehyde catalyzer, in 100 ℃ of racemizations, the monitoring specific rotation, complete to racemization, get solid behind the evaporated under reduced pressure solvent, use the methanol wash solid, suction filtration gets DL-methylselenocysteinefrom 17.1g, yield 93.96%.
Embodiment 28:
The acetic anhydride method racemization of methylselenocysteinefrom:
The 0.1mol selenium-methyl selenium substituted aminothiopropionic is dissolved in the 200ml Glacial acetic acid, add the 0.1mol acetic anhydride, in 70 ℃ of heating racemizations, monitoring specific rotation, complete to racemization, add the 200ml concentrated hydrochloric acid then, reflux 3h gets solid behind the evaporated under reduced pressure solvent, use the methanol wash solid, suction filtration gets DL-methylselenocysteinefrom 16.8g, yield 92.31%.
Embodiment 29:
The acetic anhydride method racemization of methylselenocysteinefrom:
The 0.1mol selenium-methyl selenium substituted aminothiopropionic is dissolved in the 200ml Glacial acetic acid, adds the 0.5mol acetic anhydride, in 100 ℃ of heating racemizations, the monitoring specific rotation, complete to racemization, add 200ml 50% sulfuric acid then, reflux 3h, separate with storng-acid cation exchange resin, the ammoniacal liquor wash-out gets solid behind the evaporated under reduced pressure solvent, use the methanol wash solid, suction filtration gets DL-methylselenocysteinefrom 15.4g, yield 84.62%.
Embodiment 30:
The acetic anhydride method racemization of methylselenocysteinefrom:
The 0.1mol selenium-methyl selenium substituted aminothiopropionic is dissolved in the 200ml Glacial acetic acid, add the 1mol acetic anhydride, in 150 ℃ of heating racemizations, monitoring specific rotation, complete to racemization, add the 200ml concentrated hydrochloric acid then, reflux 3h gets solid behind the evaporated under reduced pressure solvent, use the methanol wash solid, suction filtration gets DL-methylselenocysteinefrom 17.1g, yield 93.96%.
Embodiment 31:
The aspergillus oryzae L-Aminoacylase splits the DL-methylselenocysteinefrom:
0.1mol DL-methylselenocysteinefrom is dissolved in 200ml 20% aqueous sodium hydroxide solution, under the ice-water bath, slowly drip the 0.15mol Acetyl Chloride 98Min., be warming up to 25 ℃ of reaction 6h then, detect to there not being the amino acid reaction, regulate pH to 1-2 with concentrated hydrochloric acid with triketohydrindene hydrate, use ethyl acetate extraction then, organic phase is merged back evaporated under reduced pressure solvent, get N-acetyl-DL-methylselenocysteinefrom 20.1 grams, yield 89.73%.
0.1mol N-acetyl-DL-methylselenocysteinefrom is dissolved in the HAc-NaAc buffered soln of 500ml pH4; add 22.4mg aspergillus oryzae L-Aminoacylase; 10 ℃ of controlled temperature; react after about 12 hours solution is made the enzyme denaturation precipitation in 90 ℃ of heating; filter; filtrate is separated with storng-acid cation exchange resin, water and 5% ammoniacal liquor wash-out.After water elution liquid evaporated under reduced pressure, get N-acetyl-D-methylselenocysteinefrom, it is dissolved in 200 milliliters of concentrated hydrochloric acids, complete in 95 ℃ of hydrolysis in 3 hours that reflux, with the ammoniacal liquor neutralization, the evaporated under reduced pressure solvent gets solid, use dissolve with methanol, the elimination insolubles, concentrate D-methylselenocysteinefrom 7.5g, yield 82.42%.After 5% ammoniacal liquor elutriant evaporated under reduced pressure, get L-methylselenocysteinefrom 7.7 grams, yield 84.62%.
Embodiment 32:
The aspergillus oryzae L-Aminoacylase splits the DL-methylselenocysteinefrom:
0.1mol DL-methylselenocysteinefrom is dissolved in 200ml 20% aqueous sodium hydroxide solution, under the ice-water bath, slowly drip the 0.15mol Acetyl Chloride 98Min., be warming up to 45 ℃ of reaction 4h then, detect to there not being the amino acid reaction, regulate pH to 1-2 with concentrated hydrochloric acid with triketohydrindene hydrate, use ethyl acetate extraction then, organic phase is merged back evaporated under reduced pressure solvent, get N-acetyl-DL-methylselenocysteinefrom 20.3 grams, yield 90.62%.
0.1mol N-acetyl-DL-methylselenocysteinefrom is dissolved in the KH of 500ml pH7
2PO
4-Na
2HPO
4Buffered soln adds 0.224g aspergillus oryzae L-Aminoacylase, and 40 ℃ of controlled temperature react after about 10 hours solution is made the enzyme denaturation precipitation in 90 ℃ of heating, filter, and filtrate is separated with storng-acid cation exchange resin, water and 5% ammoniacal liquor wash-out.After water elution liquid evaporated under reduced pressure, get N-acetyl-D-methylselenocysteinefrom, it is dissolved in 200 milliliter of 30% Hydrogen bromide, complete in 95 ℃ of hydrolysis in 3 hours that reflux, with the ammoniacal liquor neutralization, the evaporated under reduced pressure solvent gets solid, use dissolve with methanol, the elimination insolubles, concentrate D-methylselenocysteinefrom 7.8g, yield 85.71%.After 5% ammoniacal liquor elutriant evaporated under reduced pressure, get L-methylselenocysteinefrom 8.0 grams, yield 87.91%.
Embodiment 33:
The aspergillus oryzae L-Aminoacylase splits the DL-methylselenocysteinefrom:
0.1mol DL-methylselenocysteinefrom is dissolved in 200ml 20% aqueous sodium hydroxide solution, under the ice-water bath, slowly drip the 0.15mol Acetyl Chloride 98Min., be warming up to 65 ℃ of reaction 3h then, detect to there not being the amino acid reaction, regulate pH to 1-2 with concentrated hydrochloric acid with triketohydrindene hydrate, use ethyl acetate extraction then, organic phase is merged back evaporated under reduced pressure solvent, get N-acetyl-DL-methylselenocysteinefrom 19.0 grams, yield 84.82%.
0.1mol N-acetyl-DL-methylselenocysteinefrom is dissolved in the NaHCO of 500ml pH10
3-NaHCO
3Buffered soln adds 2.24g aspergillus oryzae L-Aminoacylase, and 60 ℃ of controlled temperature react after about 8 hours solution is made the enzyme denaturation precipitation in 90 ℃ of heating, filter, and filtrate is separated with storng-acid cation exchange resin, water and 5% ammoniacal liquor wash-out.After water elution liquid evaporated under reduced pressure, get N-acetyl-D-methylselenocysteinefrom, it is dissolved in 200 milliliter of 30% hydroiodic acid HI, complete in 95 ℃ of hydrolysis in 3 hours that reflux, with the ammoniacal liquor neutralization, the evaporated under reduced pressure solvent gets solid, use dissolve with methanol, the elimination insolubles, concentrate D-methylselenocysteinefrom 8.1g, yield 89.01%.After 5% ammoniacal liquor elutriant evaporated under reduced pressure, get L-methylselenocysteinefrom 8.4 grams, yield 92.31%.
Embodiment 34:
The aspergillus oryzae L-Aminoacylase splits the DL-methylselenocysteinefrom:
0.1mol N-acetyl-DL-methylselenocysteinefrom is dissolved in the KH of 500ml pH7
2PO
4-Na
2HPO
4Buffered soln adds 0.224g aspergillus oryzae L-Aminoacylase, and 40 ℃ of controlled temperature react after about 10 hours solution is made the enzyme denaturation precipitation in 90 ℃ of heating, filter, and filtrate is separated with storng-acid cation exchange resin, water and 5% ammoniacal liquor wash-out.After water elution liquid evaporated under reduced pressure, get N-acetyl-D-methylselenocysteinefrom, it is dissolved in 200 milliliter of 50% sulfuric acid, complete in 95 ℃ of hydrolysis in 3 hours that reflux, with the ammoniacal liquor neutralization, concentrating under reduced pressure gets solid, use dissolve with methanol, the elimination insolubles, concentrate D-methylselenocysteinefrom 6.8g, yield 74.72%.After 5% ammoniacal liquor elutriant evaporated under reduced pressure, get L-methylselenocysteinefrom 7.4 grams, yield 81.34%.
Embodiment 35:
The immobilization aspergillus oryzae cell that produces L-Aminoacylase splits the DL-methylselenocysteinefrom:
The aspergillus oryzae body and function gelatin-glutaraldehyde or the gelatin-formaldehyde fixed that adopt ordinary method will produce L-Aminoacylase must be produced the immobilization aspergillus oryzae cell of L-Aminoacylase, and the immobilization aspergillus oryzae cell is dressed up column type reactor.0.1mol N-acetyl-DL-methylselenocysteinefrom is dissolved in the HAc-NaAc buffered soln of 500ml pH4,10 ℃ of controlled temperature, slowly, split liquid and separate water and 5% ammoniacal liquor wash-out with storng-acid cation exchange resin by immobilization aspergillus oryzae cell column type reactor.After water elution liquid evaporated under reduced pressure, get N-acetyl-D-methylselenocysteinefrom, it is dissolved in 200 milliliters of concentrated hydrochloric acids, complete in 95 ℃ of hydrolysis in 3 hours that reflux, with the ammoniacal liquor neutralization, the evaporated under reduced pressure solvent gets solid, use dissolve with methanol, the elimination insolubles, concentrate D-methylselenocysteinefrom 7.8g, yield 85.71%.After 5% ammoniacal liquor elutriant evaporated under reduced pressure, get L-methylselenocysteinefrom 8.0 grams, yield 87.91%.
Embodiment 36:
The immobilization aspergillus oryzae cell that produces L-Aminoacylase splits the DL-methylselenocysteinefrom:
0.1mol N-acetyl-DL-methylselenocysteinefrom is dissolved in the KH of 500ml pH7
2PO
4-Na
2HPO
4Buffered soln, 40 ℃ of controlled temperature slowly by immobilization aspergillus oryzae cell column type reactor, split liquid and separate water and 5% ammoniacal liquor wash-out with storng-acid cation exchange resin.After water elution liquid evaporated under reduced pressure, get N-acetyl-D-methylselenocysteinefrom, it is dissolved in 200 milliliter of 30% Hydrogen bromide, complete in 95 ℃ of hydrolysis in 3 hours that reflux, with the ammoniacal liquor neutralization, the evaporated under reduced pressure solvent gets solid, use dissolve with methanol, the elimination insolubles concentrates to such an extent that separate out D-methylselenocysteinefrom 7.5g, yield 82.42%.After 5% ammoniacal liquor elutriant evaporated under reduced pressure, get L-methylselenocysteinefrom 8.4 grams, yield 92.31%.
Embodiment 37:
The immobilization aspergillus oryzae cell that produces L-Aminoacylase splits the DL-methylselenocysteinefrom:
0.1mol N-acetyl-DL-methylselenocysteinefrom is dissolved in the NaHCO of 500ml pH10
3-NaHCO
3Buffered soln, 60 ℃ of controlled temperature slowly by immobilization aspergillus oryzae cell column type reactor, split liquid and separate water and 5% ammoniacal liquor wash-out with storng-acid cation exchange resin.After water elution liquid evaporated under reduced pressure, get N-acetyl-D-methylselenocysteinefrom, it is dissolved in 200 milliliter of 30% hydroiodic acid HI, complete in 95 ℃ of hydrolysis in 3 hours that reflux, with the ammoniacal liquor neutralization, the evaporated under reduced pressure solvent gets solid, use dissolve with methanol, the elimination insolubles concentrates to such an extent that separate out D-methylselenocysteinefrom 6.7g, yield 73.63%.After 5% ammoniacal liquor elutriant evaporated under reduced pressure, get L-methylselenocysteinefrom 7.0 grams, yield 76.92%.
Embodiment 38:
The immobilization aspergillus oryzae cell that produces L-Aminoacylase splits the DL-methylselenocysteinefrom:
0.1mol N-acetyl-DL-methylselenocysteinefrom is dissolved in the KH of 500ml pH7
2PO
4-Na
2HPO
4Buffered soln, 40 ℃ of controlled temperature slowly by immobilization aspergillus oryzae cell column type reactor, split liquid and separate water and 5% ammoniacal liquor wash-out with storng-acid cation exchange resin.After water elution liquid evaporated under reduced pressure, get N-acetyl-D-methylselenocysteinefrom, it is dissolved in 200 milliliter of 50% sulfuric acid, complete in 95 ℃ of hydrolysis in 3 hours that reflux, with the ammoniacal liquor neutralization, the evaporated under reduced pressure solvent gets solid, use dissolve with methanol, the elimination insolubles concentrates to such an extent that separate out D-methylselenocysteinefrom 6.3g, yield 69.23%.After 5% ammoniacal liquor elutriant evaporated under reduced pressure, get L-methylselenocysteinefrom 6.4 grams, yield 70.33%.
Embodiment 39:
Papoid splits the DL-methylselenocysteinefrom:
0.1mol N-acetyl-DL-methylselenocysteinefrom is dissolved in the hydrochloric acid soln of 500ml pH3, adds 0.1mol aniline and 22.4mg papoid, 20 ℃ of controlled temperature, enzymatic reaction 10h, after reaction finishes, filter, filtering insolubles is complete with the hydrolysis of 200ml concentrated hydrochloric acid reflux, neutralize with ammoniacal liquor then, the evaporated under reduced pressure solvent gets solid, uses dissolve with methanol, the elimination insolubles, concentrate L-methylselenocysteinefrom 6.7g, yield 73.63%.After filtrate decompression concentrates, add the 200ml concentrated hydrochloric acid, the reflux hydrolysis is complete, and with the ammoniacal liquor neutralization, the evaporated under reduced pressure solvent gets solid, use dissolve with methanol then, elimination insolubles, concentrated D-methylselenocysteinefrom 6.9g, yield 75.82%.
Embodiment 40:
Papoid splits the DL-methylselenocysteinefrom:
0.1mol N-acetyl-DL-methylselenocysteinefrom is dissolved in the HAc-NaAc buffered soln of 500ml pH5, adds 0.2mol aniline and 0.224g papoid, 50 ℃ of controlled temperature, enzymatic reaction 8h, after reaction finishes, filter, filtering insolubles is complete with 200ml 50% sulfuric acid reflux hydrolysis, neutralize with ammoniacal liquor then, concentrating under reduced pressure gets solid, uses dissolve with methanol, the elimination insolubles, concentrate L-methylselenocysteinefrom 7.3g, yield 80.22%.After filtrate decompression concentrates, add 200ml50% sulfuric acid, the reflux hydrolysis is complete, and with the ammoniacal liquor neutralization, concentrating under reduced pressure gets solid, use dissolve with methanol then, elimination insolubles, concentrated D-methylselenocysteinefrom 8.4g, yield 92.31%.
Embodiment 41:
Papoid splits the DL-methylselenocysteinefrom:
0.1mol N-acetyl-DL-methylselenocysteinefrom is dissolved in the NaHCO of 500ml pH9
3-NaHCO
3In the buffered soln, add 0.4mol aniline and 2.24g papoid, 70 ℃ of controlled temperature, enzymatic reaction 8h, after reaction finishes, filter, filtering insolubles is complete with the hydrolysis of 200ml concentrated hydrochloric acid reflux, neutralize with ammoniacal liquor then, the evaporated under reduced pressure solvent gets solid, uses dissolve with methanol, the elimination insolubles, concentrate L-methylselenocysteinefrom 6.0g, yield 65.93%.After filtrate decompression concentrates, add the 200ml concentrated hydrochloric acid, the reflux hydrolysis is complete, and with the ammoniacal liquor neutralization, the evaporated under reduced pressure solvent gets solid, use dissolve with methanol then, elimination insolubles, concentrated D-methylselenocysteinefrom 5.8g, yield 63.74%.
Embodiment 42:
Papoid splits the DL-methylselenocysteinefrom:
0.1mol N-acetyl-DL-methylselenocysteinefrom is dissolved in the hydrochloric acid soln of 500ml pH3, adds 0.1mol to monomethylaniline and 22.4mg papoid, 20 ℃ of controlled temperature, enzymatic reaction 10h, after reaction finishes, filter, filtering insolubles is complete with the hydrolysis of 200ml concentrated hydrochloric acid reflux, neutralize with ammoniacal liquor then, the evaporated under reduced pressure solvent gets solid, uses dissolve with methanol, the elimination insolubles, concentrate L-methylselenocysteinefrom 7.9g, yield 86.81%.After filtrate decompression concentrates, add the 200ml concentrated hydrochloric acid, the reflux hydrolysis is complete, and with the ammoniacal liquor neutralization, the evaporated under reduced pressure solvent gets solid, use dissolve with methanol then, elimination insolubles, concentrated D-methylselenocysteinefrom 7.1g, yield 78.02%.
Embodiment 43:
Papoid splits the DL-methylselenocysteinefrom:
0.1mol N-acetyl-DL-methylselenocysteinefrom is dissolved in the HAc-NaAc buffered soln of 500ml pH5, adds 0.2mol to monomethylaniline and 0.224g papoid, 50 ℃ of controlled temperature, enzymatic reaction 8h, after reaction finishes, filter, filtering insolubles is complete with the hydrolysis of 200ml concentrated hydrochloric acid reflux, neutralize with ammoniacal liquor then, the evaporated under reduced pressure solvent gets solid, uses dissolve with methanol, the elimination insolubles, concentrate L-methylselenocysteinefrom 6.7g, yield 73.63%.After filtrate decompression concentrates, add the 200ml concentrated hydrochloric acid, the reflux hydrolysis is complete, and with the ammoniacal liquor neutralization, the evaporated under reduced pressure solvent gets solid, use dissolve with methanol then, elimination insolubles, concentrated D-methylselenocysteinefrom 6.1g, yield 67.03%.
Embodiment 44:
Papoid splits the DL-methylselenocysteinefrom:
0.1mol N-acetyl-DL-methylselenocysteinefrom is dissolved in the NaHCO of 500ml pH9
3-NaHCO
3In the buffered soln, add 0.4mol to monomethylaniline and 2.24g papoid, 70 ℃ of controlled temperature, enzymatic reaction 8h, after reaction finishes, filter, filtering insolubles is complete with the hydrolysis of 200ml concentrated hydrochloric acid reflux, neutralize with ammoniacal liquor then, the evaporated under reduced pressure solvent gets solid, uses dissolve with methanol, the elimination insolubles, concentrate L-methylselenocysteinefrom 5.4g, yield 59.34%.After filtrate decompression concentrates, add the 200ml concentrated hydrochloric acid, the reflux hydrolysis is complete, and with the ammoniacal liquor neutralization, the evaporated under reduced pressure solvent gets solid, use dissolve with methanol then, elimination insolubles, concentrated D-methylselenocysteinefrom 5.1g, yield 56.04%.
Embodiment 45:
Papoid splits the DL-methylselenocysteinefrom:
0.1mol N-acetyl-DL-methylselenocysteinefrom is dissolved in the HAc-NaAc buffered soln of 500ml pH5, adds 0.2mol to monomethylaniline and 0.224g papoid, 50 ℃ of controlled temperature, enzymatic reaction 8h, after reaction finishes, filter, filtering insolubles is complete with 200ml 50% sulfuric acid reflux hydrolysis, neutralize with ammoniacal liquor then, concentrating under reduced pressure gets solid, uses dissolve with methanol, the elimination insolubles, concentrate L-methylselenocysteinefrom 5.7g, yield 62.64%.After filtrate decompression concentrates, add 200ml50% sulfuric acid, the reflux hydrolysis is complete, and with the ammoniacal liquor neutralization, concentrating under reduced pressure gets solid, use dissolve with methanol then, elimination insolubles, concentrated D-methylselenocysteinefrom 5.1g, yield 56.04%.
Claims (6)
1. the synthetic method of methylselenocysteinefrom is characterized in that may further comprise the steps:
(1) with 2,3-dihalo-propionitrile and methyl-hydroselenide salt generation substitution reaction generate 2-halogen-3-first seleno propionitrile; Described 2,3-dihalo-propionitrile is 2,3-two chloroethyl nitriles, 2, and 3-two bromopropionitriles, 2,3-difluoro propionitrile or 2,
3-diiodo-propionitrile, described methyl-hydroselenide salt are sodium methyl-hydroselenide or methyl-hydroselenide potassium, and described substitution reaction temperature is 10 ℃-100 ℃;
(2) 2-halogen-3-first seleno propionitrile is generated 2-halogen-3-first seleno-propionic acid with hydrochloric acid or sulfuric acid heating hydrolysis;
(3), with hydrochloric acid or sulfuric acid neutralization, get methylselenocysteinefrom then with 2-halogen-3-first seleno-propionic acid and ammoniacal liquor reaction; Described ammoniacal liquor substitution reaction temperature is 10 ℃-100 ℃.
2. the racemization method of methylselenocysteinefrom is characterized in that may further comprise the steps:
Methylselenocysteinefrom is dissolved in Glacial acetic acid or the aqueous acetic acid, adds the aldehyde catalyzer, the heating racemization, the monitoring specific rotation, complete to racemization, get the DL-methylselenocysteinefrom; The concentration of described aqueous acetic acid is 60%-100%, and the racemization temperature is 30 ℃-100 ℃, and the aldehyde catalyzer is propionic aldehyde, 2 methyl propanal, 2 methyl butyraldehyde or 3-methyl butyraldehyde, and the mol ratio of selenium-methyl selenium substituted aminothiopropionic and aldehyde catalyzer is 5-100.
3. the racemization method of methylselenocysteinefrom is characterized in that may further comprise the steps:
Methylselenocysteinefrom is dissolved in the Glacial acetic acid, adds acetic anhydride, the heating racemization, the monitoring specific rotation, complete to racemization, with hydrochloric acid or sulfuric acid heating hydrolysis, get the DL-methylselenocysteinefrom; Described racemization temperature is 70 ℃-150 ℃, and the mol ratio of acetic anhydride and selenium-methyl selenium substituted aminothiopropionic is 1-10.
4. the method for splitting of methylselenocysteinefrom is characterized in that may further comprise the steps:
The DL-methylselenocysteinefrom is dissolved in aqueous sodium hydroxide solution, dripping acetyl chloride react N-acetyl-DL-methylselenocysteinefrom sodium, get N-acetyl-DL-methylselenocysteinefrom with hydrochloric acid or sulfuric acid acidation then;
N-acetyl-DL-methylselenocysteinefrom is dissolved in buffered soln, add the aspergillus oryzae L-Aminoacylase, carry out enzyme digestion reaction, after enzymolysis finishes, solution is separated with storng-acid cation exchange resin, and water and ammoniacal liquor wash-out get N-acetyl-D-methylselenocysteinefrom and L-methylselenocysteinefrom; With N-acetyl-D-methylselenocysteinefrom strong acid, example hydrochloric acid, Hydrogen bromide, hydroiodic acid HI or sulfuric acid etc., heating hydrolysis is complete, then with ammoniacal liquor neutralize the D-methylselenocysteinefrom; Described enzyme digestion reaction is to carry out under pH4-10, temperature are 10-60 ℃ condition.
5. the method for splitting of methylselenocysteinefrom is characterized in that may further comprise the steps:
The aspergillus oryzae body and function gelatin-glutaraldehyde or the gelatin-formaldehyde fixed that adopt ordinary method will produce L-Aminoacylase, must produce the immobilization aspergillus oryzae cell of L-Aminoacylase, and the immobilization aspergillus oryzae cell dressed up column type reactor, allow the solution stream that contains N-acetyl-DL-methylselenocysteinefrom cross immobilization aspergillus oryzae cell column type reactor, collect and split effluent liquid, to split effluent liquid and separate with storng-acid cation exchange resin, water and ammoniacal liquor wash-out get N-acetyl-D-methylselenocysteinefrom and L-methylselenocysteinefrom; With N-acetyl-D-methylselenocysteinefrom strong acid, example hydrochloric acid, Hydrogen bromide, hydroiodic acid HI or sulfuric acid, heating hydrolysis is complete, then with ammoniacal liquor neutralize the D-methylselenocysteinefrom; Described resolution reaction is to carry out under pH4-10, temperature are 10-60 ℃ condition.
6. the method for splitting of methylselenocysteinefrom is characterized in that may further comprise the steps:
N-acetyl-DL-methylselenocysteinefrom is dissolved in the buffered soln, add aniline or to monomethylaniline, add papoid again, carry out enzymatic reaction, after reaction finishes, filter, insolubles is that N-acetyl-L-methylselenocysteinefrom aniline or N-acetyl-L-methylselenocysteinefrom are to monomethylaniline, complete with hydrochloric acid or sulfuric acid heating hydrolysis, then with ammoniacal liquor neutralize the L-methylselenocysteinefrom; Filtrate contains N-acetyl-D-methylselenocysteinefrom, and is complete with hydrochloric acid or sulfuric acid heating hydrolysis behind the concentrating under reduced pressure, then with ammoniacal liquor neutralize the D-methylselenocysteinefrom; Described enzymatic reaction is to carry out under the 20-70 ℃ of condition in pH3-9, temperature.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103976991A (en) * | 2014-05-13 | 2014-08-13 | 深圳大学 | Application of SMC (L-Se-methylselenocysteine) as well as medicament and health-care product for preventing and treating Alzheimer disease |
| CN108866118A (en) * | 2018-07-19 | 2018-11-23 | 由永峰 | A kind of enzymatic synthesis method of L- selenium-methyl selenium substituted aminothiopropionic |
| CN108947881A (en) * | 2018-08-08 | 2018-12-07 | 济源希健生物医药科技发展有限公司 | A method of preparing optical voidness L-type selenium-methyl selenium substituted aminothiopropionic |
| CN110628839A (en) * | 2019-11-04 | 2019-12-31 | 济源市万洋华康生物科技有限公司 | Method for green and efficient preparation of L-selenium methyl selenocysteine |
| CN114213300A (en) * | 2022-01-07 | 2022-03-22 | 西安交通大学 | Mechanochemical synthesis of organic selenium compound |
| CN115594621A (en) * | 2022-11-04 | 2023-01-13 | 西安交通大学（Cn） | Ball-milling mechanochemical synthesis method of diselenide compound |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| US6794537B1 (en) * | 2002-11-07 | 2004-09-21 | Sami Labs Limited | Manufacturing processes for Se-methyl-L-selenocysteine |
| CN1948282A (en) * | 2006-11-02 | 2007-04-18 | 江西川奇药业有限公司 | Method of synthesizing selenium methyl selenium substituted cysteine through methyl seleno acetaldehyde |
| CN101157950A (en) * | 2007-09-11 | 2008-04-09 | 江西川奇药业有限公司 | Method for preparing optical pure selenium - methyl selenium substituted aminothiopropionic acid by employing enzymatic resolution of racemic selenium- methyl selenium substituted aminothiopropionic a |
| CN100554250C (en) * | 2007-01-22 | 2009-10-28 | 江西川奇药业有限公司 | A kind of method of utilizing alpha-amino acrylic acid derivative to prepare methylselenocysteinefrom |
-
2010
- 2010-02-10 CN CN2010101079008A patent/CN102146050A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| US6794537B1 (en) * | 2002-11-07 | 2004-09-21 | Sami Labs Limited | Manufacturing processes for Se-methyl-L-selenocysteine |
| CN1948282A (en) * | 2006-11-02 | 2007-04-18 | 江西川奇药业有限公司 | Method of synthesizing selenium methyl selenium substituted cysteine through methyl seleno acetaldehyde |
| CN100417645C (en) * | 2006-11-02 | 2008-09-10 | 江西川奇药业有限公司 | Method of synthesizing selenium methyl selenium substituted cysteine through methyl seleno acetaldehyde |
| CN100554250C (en) * | 2007-01-22 | 2009-10-28 | 江西川奇药业有限公司 | A kind of method of utilizing alpha-amino acrylic acid derivative to prepare methylselenocysteinefrom |
| CN101157950A (en) * | 2007-09-11 | 2008-04-09 | 江西川奇药业有限公司 | Method for preparing optical pure selenium - methyl selenium substituted aminothiopropionic acid by employing enzymatic resolution of racemic selenium- methyl selenium substituted aminothiopropionic a |
Non-Patent Citations (4)
| Title |
|---|
| 《Chemische Berichte》 19541231 Brockmann, Hans等 Versuche zur Synthese von Yolypeptiden durch Hondehsation von Aminos�ure- und Peptidestern,I. Mitteil. 第590页-591页 1 第87卷, * |
| BROCKMANN, HANS等: "Versuche zur Synthese von Yolypeptiden durch Hondehsation von Aminosäure- und Peptidestern,I. Mitteil.", 《CHEMISCHE BERICHTE》 * |
| BROCKMANN, HANS等: "Versuche zur Synthese von Yolypeptiden durch Hondehsation von Aminosäure- und Peptidestern,I. Mitteil.", 《CHEMISCHE BERICHTE》, vol. 87, 31 December 1954 (1954-12-31), pages 590 - 591 * |
| 孔祥文: "《有机化学》", 31 March 2010, 化学工业出版社 * |
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| CN103976991A (en) * | 2014-05-13 | 2014-08-13 | 深圳大学 | Application of SMC (L-Se-methylselenocysteine) as well as medicament and health-care product for preventing and treating Alzheimer disease |
| CN108866118A (en) * | 2018-07-19 | 2018-11-23 | 由永峰 | A kind of enzymatic synthesis method of L- selenium-methyl selenium substituted aminothiopropionic |
| CN108947881A (en) * | 2018-08-08 | 2018-12-07 | 济源希健生物医药科技发展有限公司 | A method of preparing optical voidness L-type selenium-methyl selenium substituted aminothiopropionic |
| CN108947881B (en) * | 2018-08-08 | 2020-10-27 | 济源希健生物医药科技发展有限公司 | Method for preparing optically pure L-type selenium-methyl selenocysteine |
| CN110628839A (en) * | 2019-11-04 | 2019-12-31 | 济源市万洋华康生物科技有限公司 | Method for green and efficient preparation of L-selenium methyl selenocysteine |
| CN110628839B (en) * | 2019-11-04 | 2023-05-30 | 河南希百康健康产业有限公司 | Method for preparing L-selenomethylselenocysteine |
| CN114213300A (en) * | 2022-01-07 | 2022-03-22 | 西安交通大学 | Mechanochemical synthesis of organic selenium compound |
| CN115594621A (en) * | 2022-11-04 | 2023-01-13 | 西安交通大学（Cn） | Ball-milling mechanochemical synthesis method of diselenide compound |
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