CN1146447A - Process for preparation of optically active amino-acid by hot- hydrolysis of nitrogen-ammonia formyl-amino acid - Google Patents
Process for preparation of optically active amino-acid by hot- hydrolysis of nitrogen-ammonia formyl-amino acid Download PDFInfo
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- CN1146447A CN1146447A CN 95116833 CN95116833A CN1146447A CN 1146447 A CN1146447 A CN 1146447A CN 95116833 CN95116833 CN 95116833 CN 95116833 A CN95116833 A CN 95116833A CN 1146447 A CN1146447 A CN 1146447A
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Abstract
The preparation method of optical active amino acid is characterized by using thermal hydrolytic reaction of nitrogen-carbamyl amino acid to prepare aliphatic and aromatic D-type or L-type amino acids with optical activity. Its reactant concentration is 0.1-45% (w/V), and reaction temp. is 80-140 deg.C, its reaction process must be always retained in the range of weak acid pH 3.0-6.0 or weak base pH 9.6-10.8, and its reaction time is 4-72 hr. After the above-mentioned reaction is completed, under the condition of 10-600 mmHg pressure its reaction product is concentrated by vacuum to 1/20 to 1/2 of initital volume, then the obtained concentrate is mixed with 30% NaOH or 3NHCl to regulate pH to isoelectric point of said amino acid, and then cooling-crystallized at room temp. or in cold-water bath, and its crystallizing temp. is 2-30 deg.C, so that the invented amino acid can be obtained.
Description
The present invention relates to amino acid whose preparation method, relate in particular to a kind of chiral compounds-optical activity D type or the amino acid whose preparation method of L type.
As is generally known the development work for preparing optically active amino acids in recent years has suitable progress.As hydantoin derivative from 5 replacements; generate nitrogen carbamyl-D (or L)-amino acid through single-minded glycolylurea enzyme open loop; hydrolysis obtains D (or L)-amino acid again; be the new way (Syldatk of a preparation optically active amino acids of nearly more than ten years exploitation; C.et al; Biotechnol.Fiechter, vol.41,291-316 (1990)):
Racemic hydantoin derivative can synthesize (Bucherer with cheap raw material aldehyde, H.T., Steiner, W., J.Prakt.Chem., 140,291-316 (1934)). reaction (1) can spontaneously be carried out. and reaction (2) used glycolylurea enzyme claims dihydropyrimidinase (EC3.5.2.2.) again, substrate stereospecificity with D or L, moving, discovery (Waltach, D., Grisoloia are all arranged in plant and the microorganism, S.J., biol.Chem., 226,277-288 (1957)), at present obtained producing the higher microorganism (Sun Wanru of enzyme activity, the microorganism journal, 23 (2), 133-142 (1983); Jiangning etc., the microorganism journal, 35 (5) .347-350 (1995)). reaction (3) can be passed through chemical method (Takahashi, S.et al., J.Ferment.Technol., 4,328-332 (1979)) or enzyme process (Olivieri, R.et al, Enzyme Mirob. Technol., 1,201-204 (1979)) to carry out. its reaction is as follows: chemical method:
Enzyme process:
These two synthetic routes are longer for producing non-natural D type amino acid or pathways metabolism, have important use with the not high L type amino acid of fermentative Production rate and are worth.
But there is following problem in these two lines in practical application:
Carcinogens nitrous acid has been used in reaction (3-1), can bring serious environmental to pollute.The enzyme that reaction (3-2) is used, because microbial metabolism itself, its vigor has only 1/100 to 1/10 of glycolylurea enzyme, causes reaction (3) and reaction (2) to be difficult to coupling, has limited the practical application of this route.
The objective of the invention is to a non-environmental-pollution, effectively reaction replaces the chemical reaction of (3-1) or enzyme reaction (3-2) again.This reaction is exactly the nitrogen carbamyl amino acid thermal hydrolysis reaction that we find:
When temperature surpassed 80 ℃, reaction (3-3) can be carried out, and reaches balance very soon, but as long as maintenance system under weak acid or weak base condition, constantly adds 3NHCl in reaction process, the PH of maintenance system makes CO between 3.0-6.0
2Constantly discharge:
Or constantly adding 30%NaOH, the PH that keeps reaction system makes NH between 9.6-10.8
3Gas is constantly discharged:
Just can disequilibrate, reaction is carried out fully.
Above-mentioned two reactions (3-3-1) and temperature (3-3-2) are high more, speed of response is fast more, but consider the withstand voltage and molecular balance of equipment, temperature is also unsuitable too high, be suitable generally with 80 ℃-140 ℃, 95 ℃-120 ℃ more suitable, is suitable with 4-72hr. generally in this kind following reaction times of condition, and 16-48hr. is more suitable.Another key of this reaction is control PH, and strong excessively as acidity, carbamyl amino acid becomes hydantoin derivative with closed loop, promptly reacts the reversed reaction of (2).Strong excessively as alkalescence, the amino acid that obtains loses optical activity with racemization.
Reaction generally under 10-600mmHg pressure, better is evaporated to 1/20 to 1/2 of original volume after finishing under 10-200mmHg pressure, concentrating degree can be determined according to the starting point concentration of reactant.Transfer PH to this amino acid whose iso-electric point (can find or record) with 3NHCl or 30%NaOH again from relevant handbook with experiment, then, crystallisation by cooling in room temperature or cooling bath or ice-water bath or cryosel bath, Tc is-2 ℃-30 ℃, can obtain optically active amino acid after the filtration.
The invention solves the pollution problem of chemical method, except the soda acid of transferring PH to use, do not need any chemical reagent.Its efficient has increased significantly than enzyme process again.
For technology contents of the present invention further is described in further detail, for following embodiment:
Embodiment 1
In the 250ml round-bottomed flask, add 4.0g nitrogen carbamyl-D-(-)-phenylglycine, add 100ml distilled water again, thorough mixing is transferred liquid PH to 10.0 with 30%NaOH.
Above-mentioned flask is loaded onto reflux, in electrically heated put be heated to 100 ℃ of boilings after, reheat back flow reaction 35hr. constantly adds 30%NaOH therebetween and keeps PH between 10.0-10.6, reaction conversion ratio is 65% when stopping.
Above-mentioned reaction solution is concentrated under 80mmHg pressure reduced pressure, stop when being concentrated into 30ml, change in the beaker, add 3NHCl accent PH to 5.0 down in stirring, have a large amount of D-(-)-phenylglycine crystal to separate out, beaker is cooled off in ice-water bath, suction filtration gets D-(-)-phenylglycine crystal after liquid is crossed in 4 ℃ of placement crystallizations, get crystal 1.78g, polarimetry purity 80%, yield 56% after the drying.
Embodiment 2
In the 250ml round-bottomed flask, add 4.0gN-carbamyl-D-(-)-phenylglycine; add 100ml distilled water again; behind the thorough mixing; transfer PH=3.0 with 3NHCl; in thermoelectricity put be heated to 100 ℃ the boiling 30hr.; constantly add 3NHCl therebetween and keep PH between 3.0-5.0, reaction records transformation efficiency when stopping be 90%.
Above-mentioned reaction solution is concentrated into about 30ml under 80mmHg pressure reduced pressure, change in the beaker, add 30%NaOH solution while stirring, transfer PH=5.0, have a large amount of D-(-)-phenylglycine crystal to separate out, beaker is cooled off in ice-water bath, after 4 ℃ of placement crystallizations were spent the night, suction filtration got D-(-)-phenylglycine crystal, got crystal 2 .40g after the drying, polarimetry purity 97%, yield 75%.
Embodiment 3
In the 250ml beaker, add 4.0g racemization benzene glycolylurea, and add 50ml 0.05MNaHPO
4The aqueous solution, thorough mixing.
Little thing cell 50ml 0.05MNaHPO of going out that will have D-glycolylurea enzyme activity
4The aqueous solution suspends, and this bacteria suspension and benzene glycolylurea solution merge, and uses the constant reaction solution PH of NaOH in 8.5 at 35 ℃ of following stirring reactions, and transformation efficiency reaches more than 90% stopped reaction after the 8hr..
Transfer reaction solution PH=5.0 with HCl, boil, take advantage of heat filtering, must contain the solution of 3.70g nitrogen carbamyl-D-(-)-phenylglycine.
Transfer this solution PH=3.0 with 3NHCl, change in the 250ml round-bottomed flask, be heated to 100 ℃ of boiling 30hr. on electric mantle, constantly add 3NHCl therebetween and keep PH between 3.0-5.0, reaction conversion ratio is 90%.
Above-mentioned reaction solution is concentrated into about 30ml under 80mmHg pressure reduced pressure, change in the beaker, transfer PH=5.0 in stirring down with 30%NaOH, have a large amount of D-(-)-phenylglycine crystal to separate out, beaker is cooled off in ice-water bath, place 4 ℃ of crystallizations to spend the night, suction filtration after the crystal drying, gets D-(-)-phenylglycine crystal 2 .17g, polarimetry purity 94%, yield 60%.
Embodiment 4
In the 100ml round-bottomed flask, add 0.4g nitrogen carbamyl-L-(+)-phenylalanine; add 20ml distilled water again; thorough mixing; transfer PH3.0 with 3NHCl; on electric mantle, be heated to 100 ℃ of boilings; reaction 35hr. constantly adds 3NHCl therebetween and keeps PH between 3.0-5.0, and recording reaction conversion ratio when stopping is 88%.
Above-mentioned reaction solution is concentrated into about 30ml under 80mmHg pressure reduced pressure, transform in the beaker, add 3NHCl while stirring and transfer PH=5.5, have a large amount of L-(-)-phenylalanine crystal to separate out, beaker is cooled off in ice-water bath, after placing 4 ℃ of crystallizations to spend the night, suction filtration after the crystal drying, gets L-(-)-phenylalanine 0.24g, polarimetry purity 97%, yield 73%.
Claims (5)
1. the preparation method of an optically active amino acids is characterized in that will having optically active nitrogen carbamyl amino acid to slough carbamyl by the amino acid whose thermal hydrolysis reaction of nitrogen carbamyl, and optically active amino acid is arranged accordingly, and this method comprises:
1) the amino acid whose concentration of reactant nitrogen carbamyl is 0.1-45% (W/V);
2) temperature of reaction is suitable with 80-140 ℃;
3) with the PH of 3NHCl or 30%NaOH conditioned reaction system, in reaction process, PH is remained in the scope of weak acid PH3.0-6.0 or weak base PH9.6-10.8;
4) reaction times was suitable with 4-72 hour;
5) after reaction finishes, under 10-600mmHg pressure, be evaporated to the 1/20-1/2 of original volume;
6) concentrated solution transfers PH to this amino acid whose iso-electric point with 30%NaOH or 3NHCl;
7) crystallisation by cooling in room temperature or cooling bath or ice-water bath or cryosel are bathed, Tc be-2-30 ℃, promptly obtain optically active amino acids.
2. the preparation method of optically active amino acids as claimed in claim 1 is characterized in that said optically active amino acids can be D type or L type, and its structure is:
Wherein the R-base can be aliphatic group, as CH
3-,
, also can be fragrance bunch group, as
3. the preparation method of optically active amino acids as claimed in claim 1 is characterized in that said temperature of reaction is more suitable with 40-121 ℃.
4. the preparation method of optically active amino acids as claimed in claim 1 is characterized in that the said reaction times is more suitable with 16-48 hour.
5. the preparation method of optically active amino acids as claimed in claim 1 is characterized in that said pressure is more suitable with 10-200mmHg.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN95116833A CN1057518C (en) | 1995-09-29 | 1995-09-29 | Process for preparation of optically active amino-acid by hot- hydrolysis of nitrogen-ammonia formyl-amino acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN95116833A CN1057518C (en) | 1995-09-29 | 1995-09-29 | Process for preparation of optically active amino-acid by hot- hydrolysis of nitrogen-ammonia formyl-amino acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1146447A true CN1146447A (en) | 1997-04-02 |
| CN1057518C CN1057518C (en) | 2000-10-18 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN95116833A Expired - Fee Related CN1057518C (en) | 1995-09-29 | 1995-09-29 | Process for preparation of optically active amino-acid by hot- hydrolysis of nitrogen-ammonia formyl-amino acid |
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Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1037176B (en) * | 1975-04-09 | 1979-11-10 | Snam Progetti | PROCEDURE FOR THE PREPARATION OF AMINDACIDS |
| JPS584707B2 (en) * | 1977-02-21 | 1983-01-27 | 鐘淵化学工業株式会社 | Method for producing optically active phenylglycines |
| IT1209495B (en) * | 1984-02-02 | 1989-08-30 | A San Donato Milanese Milano | PROCEDURE FOR THE PREPARATION OF L-ALPHA-AMINO ACIDS. |
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1995
- 1995-09-29 CN CN95116833A patent/CN1057518C/en not_active Expired - Fee Related
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