CN109384811A - A kind of preparation method of L-glufosinate-ammonium - Google Patents
A kind of preparation method of L-glufosinate-ammonium Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 13
- 108010024026 Nitrile hydratase Proteins 0.000 claims abstract description 10
- 102000004879 Racemases and epimerases Human genes 0.000 claims abstract description 9
- 108090001066 Racemases and epimerases Proteins 0.000 claims abstract description 9
- 108090000790 Enzymes Proteins 0.000 claims abstract description 8
- 102000004190 Enzymes Human genes 0.000 claims abstract description 8
- 230000007062 hydrolysis Effects 0.000 claims abstract description 5
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 5
- 238000005580 one pot reaction Methods 0.000 claims abstract description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 7
- 230000008859 change Effects 0.000 claims description 6
- 125000006239 protecting group Chemical group 0.000 claims description 6
- 239000005515 coenzyme Substances 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- FNIQKHXZAHAFCZ-UHFFFAOYSA-N phosphoric acid;1h-pyrrole Chemical compound C=1C=CNC=1.OP(O)(O)=O FNIQKHXZAHAFCZ-UHFFFAOYSA-N 0.000 claims description 2
- APRRQJCCBSJQOQ-UHFFFAOYSA-N 4-amino-5-hydroxynaphthalene-2,7-disulfonic acid Chemical group OS(=O)(=O)C1=CC(O)=C2C(N)=CC(S(O)(=O)=O)=CC2=C1 APRRQJCCBSJQOQ-UHFFFAOYSA-N 0.000 claims 1
- 206010044565 Tremor Diseases 0.000 claims 1
- 230000002255 enzymatic effect Effects 0.000 claims 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- -1 Glufosinate-ammonium nitrile amine Chemical class 0.000 abstract description 23
- 238000000034 method Methods 0.000 abstract description 20
- 230000000694 effects Effects 0.000 abstract description 11
- 230000008569 process Effects 0.000 abstract description 6
- 230000006340 racemization Effects 0.000 abstract description 6
- 230000009471 action Effects 0.000 abstract description 4
- 230000003301 hydrolyzing effect Effects 0.000 abstract description 2
- 238000006243 chemical reaction Methods 0.000 description 17
- 239000000243 solution Substances 0.000 description 9
- ZBMRKNMTMPPMMK-UHFFFAOYSA-N 2-amino-4-[hydroxy(methyl)phosphoryl]butanoic acid;azane Chemical compound [NH4+].CP(O)(=O)CCC(N)C([O-])=O ZBMRKNMTMPPMMK-UHFFFAOYSA-N 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- HZUKSQHMCTUZJL-UHFFFAOYSA-N P(=O)(O)(O)OCC=1C(=C(C(=NC1)C)O)C=O.P(=O)(O)(O)OC=1C(=NC=C(C1C=O)CO)C Chemical compound P(=O)(O)(O)OCC=1C(=C(C(=NC1)C)O)C=O.P(=O)(O)(O)OC=1C(=NC=C(C1C=O)CO)C HZUKSQHMCTUZJL-UHFFFAOYSA-N 0.000 description 4
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000005194 fractionation Methods 0.000 description 3
- 230000002363 herbicidal effect Effects 0.000 description 3
- 239000004009 herbicide Substances 0.000 description 3
- 239000003456 ion exchange resin Substances 0.000 description 3
- 229920003303 ion-exchange polymer Polymers 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 238000010792 warming Methods 0.000 description 3
- 244000025254 Cannabis sativa Species 0.000 description 2
- 235000001258 Cinchona calisaya Nutrition 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- QLULGSLAHXLKSR-UHFFFAOYSA-N azane;phosphane Chemical compound N.P QLULGSLAHXLKSR-UHFFFAOYSA-N 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 239000003444 phase transfer catalyst Substances 0.000 description 2
- 229960000948 quinine Drugs 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000003929 Transaminases Human genes 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000011953 bioanalysis Methods 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 1
- KMPWYEUPVWOPIM-LSOMNZGLSA-N cinchonine Chemical compound C1=CC=C2C([C@@H]([C@H]3N4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-LSOMNZGLSA-N 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- QPILZZVXGUNELN-UHFFFAOYSA-M sodium;4-amino-5-hydroxynaphthalene-2,7-disulfonate;hydron Chemical group [Na+].OS(=O)(=O)C1=CC(O)=C2C(N)=CC(S([O-])(=O)=O)=CC2=C1 QPILZZVXGUNELN-UHFFFAOYSA-M 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/301—Acyclic saturated acids which can have further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P13/00—Preparation of nitrogen-containing organic compounds
- C12P13/04—Alpha- or beta- amino acids
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Glufosinate-ammonium nitrile amine intermediate cheap and easy to get is hydrolyzed with biological enzyme the invention discloses a kind of, one pot is changed the method for obtaining the L-glufosinate-ammonium of single configuration.Specific step is as follows for above-mentioned hydrolytic process: step 1: the glufosinate-ammonium nitrile amine intermediate of racemization obtains the raceme of glufosinate-ammonium amide under the effect of non-selective nitrile hydratase；Step 2: L- hydroamidase selective hydrolysis L-type glufosinate-ammonium amide intermediate, obtain L-type glufosinate-ammonium phosphonate ester, at the same time, unhydrolysed D- type glufosinate-ammonium amide intermediate racemization under the action of ACL racemase is constantly converted to L-type glufosinate-ammonium amide intermediate.Single L-type glufosinate-ammonium phosphonate ester is finally obtained by this DKR process；Step 3: L-type glufosinate-ammonium phosphonate ester hydrolyzes under the action of dilute hydrochloric acid and obtains L-glufosinate-ammonium.
Description
Technical field
The invention belongs to bio-pharmaceuticals and technical field of biochemical industry, and in particular to a kind of preparation method of L- phosphine oxamate.
Background technique
Glufosinate-ammonium is succeeded in developing by Hirst company the eighties, and phosphonic acid herbicide is belonged to, and is that glutamine synthesis inhibits
Agent, natural disposition of going out contact killing type herbicide are that a kind of wide spectrum, low toxicity, non-selective herbicide and world's second largest transgenosis are made
Object herbicide-tolerant, application prospect are very wide.
Currently, glufosinate-ammonium available on the market is typically all racemic mixture.If glufosinate-ammonium product can be with L- configuration
Pure optical isomer use (structural formula), the usage amount of glufosinate-ammonium can be made to reduce by 50%, this is right
It is all had a very important significance in improving Atom economy, reduction use cost, mitigating environmental pressure.
Method is mainly the following about the synthesis of L-glufosinate-ammonium at present.
(1) fractionation of raceme
1. chemical resolution
Hirst company (US5767309) uses quinine to be split as glufosinate-ammonium of the chiral resolving agent to racemization.
This process is needed using expensive chiral resolving agent quinine, and the theoretical yield split only has 50%, this leads to this road
The industrial value of line is relatively low；In addition, the step of fractionation is very cumbersome, needs to undergo into salt, induction crystallization, solution salt,
Big inconvenience is brought to industrial production；
2. bioanalysis is split
Chinese patent (CN104558033A) reports the glufosinate-ammonium-using thermophilic nicotine arthrobacterium ester hydrolase to racemization
N- carboxylic acid anhydrides carries out selective hydrolysis, prepares optically pure L-glufosinate-ammonium.Although the method can obtain optically pure L- grass ammonium
Phosphine, but its total recovery is lower to cause its industrialized value relatively low.Its reaction equation is as follows:
(2) asymmetric syntheses
1. Japanese Scientists reported (J.Org.Chem, 1991,56,1783-1788) in 1991, asymmetry is utilized
Hydrogenation has synthesized L-glufosinate-ammonium, and total reaction equation is as follows:
There are following disadvantages for the method: moiety intermediate water solubility is very strong, and separating-purifying is difficult；The asymmetry of double bond
Reduction needs to use expensive noble metal and ligand, uneconomical；The enantioselectivity of product is low (only 84%ee), total receipts of reaction
Rate is lower (only 26.7%).Therefore this method industrial applications is relatively difficult.
2. Chinese patent (CN105603015A) is reported with the transaminase-catalyzed preparation L- glufosinate-ammonium of biology, total is anti-
Answer equation as follows:
There are following disadvantages for the method: substrate synthesis is difficult, and reaction needs the donor with transaminase, coenzyme and amine
Etc. multiple co-factors, there is no advantage in cost.
3. Chinese patent (CN104558033A) is reported, with chiral phase-transfer catalyst, (cinchonine fourth chiral quaternary ammonium salt spreads out
Biology), it is catalyzed the addition of methyl second dilute base phosphonate ester and benzylidene glycine.The hydrolysis that addition product passes through hydrochloric acid again obtains L-
Glufosinate-ammonium, total reaction equation are as follows:
The method is needed using a large amount of expensive chiral phase-transfer catalyst, and the total recovery reacted is relatively low,
Resulting cost is higher, without industrialized application prospect.
(3) it is set out with chiral amino acid, is synthetically prepared L-glufosinate-ammonium by multistep.
(Chinese Chemical Letters, 2006,17,177-179) is reported within 1996, logical from methionine
The chemical synthesis for crossing multistep prepares L-glufosinate-ammonium, and total reaction equation is as follows:
The method needs using expensive methionine to be starting material, and reacts that synthetic route is longer, total receipts
Rate is relatively low, higher cost, without industrialized application prospect.
Summary of the invention
In view of the deficiencies of the prior art, the present invention provides a kind of new method of simple and easy synthesis L-glufosinate-ammonium, institutes
It is as follows to state chiral L-glufosinate-ammonium structural formula:
Glufosinate-ammonium nitrile amine intermediate cheap and easy to get is hydrolyzed with biological enzyme the invention discloses a kind of, one pot of change obtains
The method of the L-glufosinate-ammonium of single configuration, reaction equation are as follows:
In particular:
By intermediateIn water phase, enzymic catalytic reaction is obtainedSelectively water again
It solves (when R is not H), one pot of change obtains L-glufosinate-ammoniumWherein, R is selected from H or phosphonic acid base protecting group.
Above-mentioned hydrolytic process is related to fractionation (DKR) process of Dynamic Kinetic, and reaction equation is as follows:In particular:
Step 1: the glufosinate-ammonium nitrile amine intermediate of racemization obtains glufosinate-ammonium amide under the effect of non-selective nitrile hydratase
Raceme；
Step 2: L- hydroamidase selective hydrolysis L-type glufosinate-ammonium amide intermediate obtains L-type glufosinate-ammonium phosphine
Acid esters, at the same time, racemization under the action of ACL racemase of unhydrolysed D- type glufosinate-ammonium amide intermediate is constantly converted
For L-type glufosinate-ammonium amide intermediate.Single L-type glufosinate-ammonium phosphonate ester is finally obtained by this DKR process；
Step 3: L-type glufosinate-ammonium phosphonate ester hydrolyzes under the action of dilute hydrochloric acid and obtains L-glufosinate-ammonium.
Method of the invention finally can be up to 87% total recovery, 98% enantioselectivity (Ee) obtains L- grass ammonium
Phosphine.
Wherein, Ee=L- glufosinate-ammonium/[L-glufosinate-ammonium+D- glufosinate-ammonium].
In above-mentioned reaction, the phosphonic acid base protecting group is selected from C1-C6 alkyl, aryl, preferably ethyl, normal-butyl, phenyl.
Preferably, coenzyme of the phosphopyridoxal pyridoxal phosphate as ACL racemase is added in reaction process；
Preferably, the order of addition of enzyme is followed successively by nitrile hydratase, L- hydroamidase and ACL racemase or phosphoric acid pyrrole is trembled
Aldehyde, nitrile hydratase, L- hydroamidase and ACL racemase；
Preferably, the nitrile hydratase is purchased from Suzhou pilotage Biotechnology Co., Ltd, goods number YH1603；
Preferably, the ACL racemase is purchased from Suzhou pilotage Biotechnology Co., Ltd, goods number YH1507；
Preferably, the L- hydroamidase is purchased from Suzhou pilotage Biotechnology Co., Ltd, goods number YH1411；
Preparation method of the invention is easy to operate, is continuous one pot of change reaction, without separating any intermediate；It should
Method carries out in water phase, does not need using any organic solvent, very green, environmental protection.In addition, the method considerably reduces
The cost of production, it is easy to accomplish industrialization.
Specific embodiment
With reference to embodiments, the present invention is further described in detail, but not limited to this.
It should be noted that chirality L-glufosinate-ammonium structural formula described in embodiment 1-3 is as follows:
Response path are as follows:
Embodiment 1:(R=Et)
Glufosinate-ammonium nitrile amine intermediate 760mg (4mmol) is taken to be dissolved in 40mlPBS buffer (0.2M, pH=8.0) solution.
Phosphopyridoxal pyridoxal phosphate 20mg is sequentially added into reaction solution, the nitrile hydratase 50mg being dissolved in 1ml water is (raw purchased from Suzhou pilotage
Object Science and Technology Ltd., goods number YH1603, only provide herein one of model product illustrated it is of the invention
Effect), the L- hydroamidase 38mg being dissolved in 1ml water (is purchased from Suzhou pilotage Biotechnology Co., Ltd, goods number is
YH1411, the product for only providing one of model herein are illustrated effect of the invention), the ACL being dissolved in 1ml water disappears
It revolves enzyme 76mg and (is purchased from Suzhou pilotage Biotechnology Co., Ltd, goods number YH1507 only provides one of model herein
Product illustrated effect of the invention).Charging finishes, and system is reacted after being warming up to 30 DEG C, 8 hours to be completed.Toward reactant
20ml concentrated hydrochloric acid is added in system, is heated to reflux 1 hour.Reaction terminates, and aqueous hydrochloric acid solution is concentrated and is done, ion exchange resin is passed through
Purifying obtains L-glufosinate-ammonium 629mg, yield 87%, Ee98%.
Embodiment 2:(R=n-Bu)
Glufosinate-ammonium nitrile amine intermediate 872mg (4mmol) is taken to be dissolved in 40mlPBS buffer (0.2M, pH=8.0) solution.
Phosphopyridoxal pyridoxal phosphate 20mg is sequentially added into reaction solution, the nitrile hydratase 50mg being dissolved in 1ml water is (raw purchased from Suzhou pilotage
Object Science and Technology Ltd., goods number YH1603, only provide herein one of model product illustrated it is of the invention
Effect), the L- hydroamidase 38mg being dissolved in 1ml water (is purchased from Suzhou pilotage Biotechnology Co., Ltd, goods number is
YH1411, the product for only providing one of model herein are illustrated effect of the invention), the ACL being dissolved in 1ml water disappears
It revolves enzyme 87mg and (is purchased from Suzhou pilotage Biotechnology Co., Ltd, goods number YH1507 only provides one of model herein
Product illustrated effect of the invention).Charging finishes, and system is reacted after being warming up to 30 DEG C, 8 hours to be completed.Toward reactant
20ml concentrated hydrochloric acid is added in system, is heated to reflux 1 hour.Reaction terminates, and aqueous hydrochloric acid solution is concentrated and is done, ion exchange resin is passed through
Purifying obtains L-glufosinate-ammonium 593mg, yield 82%, Ee97%.
Embodiment 3:(R=H)
Glufosinate-ammonium nitrile amine intermediate 648mg (4mmol) is taken to be dissolved in 40mlPBS buffer (0.2M, pH=8.0) solution.
Phosphopyridoxal pyridoxal phosphate 20mg is sequentially added into reaction solution, the nitrile hydratase 50mg being dissolved in 1ml water is (raw purchased from Suzhou pilotage
Object Science and Technology Ltd., goods number YH1603, only provide herein one of model product illustrated it is of the invention
Effect), the L- hydroamidase 38mg being dissolved in 1ml water (is purchased from Suzhou pilotage Biotechnology Co., Ltd, goods number is
YH1411, the product for only providing one of model herein are illustrated effect of the invention), the ACL being dissolved in 1ml water disappears
It revolves enzyme 65mg and (is purchased from Suzhou pilotage Biotechnology Co., Ltd, goods number YH1507 only provides one of model herein
Product illustrated effect of the invention).Charging finishes, and system is reacted after being warming up to 30 DEG C, 8 hours to be completed.Reaction knot
Beam is concentrated aqueous solution and does, obtains L-glufosinate-ammonium 513mg, yield 71%, Ee95% by ion-exchange resin purification.
Obviously, the above embodiments are merely examples for clarifying the description, rather than the restriction to embodiment.For
For those of ordinary skill in the art, other various forms of variations or change can also be made on the basis of the above description
It is dynamic.There is no necessity and possibility to exhaust all the enbodiments, and obvious variation extended from this or change
It moves still within the protection scope of the invention.
Claims (9)
1. a kind of preparation method of L-glufosinate-ammonium, which is characterized in that by intermediateIn water phase, enzymatic is anti-
It should obtainIt selectively hydrolyzes again, one pot of change obtains L-glufosinate-ammoniumWherein, R is selected from
H or phosphonic acid base protecting group.
2. preparation method as described in claim 1, which is characterized in that the phosphonic acid base protecting group is selected from C1-C6 alkyl, virtue
Base.
3. phosphonic acid base protecting group as claimed in claim 2, it is characterised in that the phosphonic acid base protecting group is selected from ethyl, positive fourth
Base, phenyl.
4. such as the described in any item preparation methods of claim 1-2, which is characterized in that the enzyme includes nitrile hydratase, L- amide
Hydrolase and ACL racemase.
5. preparation method as claimed in claim 3, which is characterized in that the enzyme further includes the coenzyme phosphoric acid pyrrole of ACL racemase
It trembles aldehyde.
6. preparation method as claimed in claim 3, which is characterized in that the nitrile hydratase has purchased from Suzhou pilotage biotechnology
Limit company, goods number YH1603.
7. preparation method as claimed in claim 3, which is characterized in that L- hydroamidase has purchased from Suzhou pilotage biotechnology
Limit company, goods number YH1411.
8. preparation method as claimed in claim 3, which is characterized in that the ACL racemase is purchased from Suzhou pilotage biotechnology
Co., Ltd, goods number YH1507.
9. preparation method as claimed in claim 3, which is characterized in that hydrolysis carries out in dilute hydrochloric acid solution.
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Cited By (5)
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| WO2023109757A1 (en) * | 2021-12-13 | 2023-06-22 | 利尔化学股份有限公司 | L-glufosinate derivative, composition comprising same, preparation method therefor and use thereof |
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Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112391438A (en) * | 2019-08-13 | 2021-02-23 | 四川利尔生物科技有限公司 | Production method of L-glufosinate-ammonium or salt thereof |
| CN112391438B (en) * | 2019-08-13 | 2023-01-13 | 四川利尔生物科技有限公司 | Production method of L-glufosinate-ammonium or salt thereof |
| CN113462730A (en) * | 2020-03-31 | 2021-10-01 | 江苏扬农化工股份有限公司 | Method for preparing L-glufosinate-ammonium by double-enzyme combination |
| CN113462730B (en) * | 2020-03-31 | 2023-08-25 | 江苏扬农化工股份有限公司 | Method for preparing L-glufosinate-ammonium by double enzyme-linked method |
| WO2022077989A1 (en) * | 2020-10-14 | 2022-04-21 | 利尔化学股份有限公司 | Method for preparing l-glufosinate |
| CN114650997A (en) * | 2020-10-14 | 2022-06-21 | 利尔化学股份有限公司 | Preparation method of L-glufosinate-ammonium |
| KR20220098244A (en) * | 2020-10-14 | 2022-07-11 | 라이어 케이컬 씨오., 엘티디. | Method for preparing L-glufosinate |
| US11655265B2 (en) | 2020-10-14 | 2023-05-23 | Lier Chemical Co., Ltd. | Method for preparing L-glufosinate |
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| KR102693943B1 (en) | 2020-10-14 | 2024-08-08 | 라이어 케이컬 씨오., 엘티디. | Method for producing L-glufosinate |
| CN112940031A (en) * | 2021-02-01 | 2021-06-11 | 河北威远生物化工有限公司 | N-naphthyl-acetyl-glufosinate-ammonium, synthesis method thereof and synthesis method for synthesizing L-glufosinate-ammonium by using N-naphthyl-acetyl-glufosinate-ammonium |
| WO2023109757A1 (en) * | 2021-12-13 | 2023-06-22 | 利尔化学股份有限公司 | L-glufosinate derivative, composition comprising same, preparation method therefor and use thereof |
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