CN112458142A - Method for preparing (1R,2R) -2-hydroxycyclopentanenitrile through biocatalysis - Google Patents
Method for preparing (1R,2R) -2-hydroxycyclopentanenitrile through biocatalysis Download PDFInfo
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Abstract
The invention discloses a method for preparing (1R,2R) -2-hydroxycyclopentanenitrile through biocatalysis, which is characterized in that in a liquid phase reaction system, 2-carbonyl cyclopentanenitrile is taken as a substrate, and carbonyl reduction is catalyzed by ketoreductase in the presence of a hydrogen source and coenzyme to prepare the (1R,2R) -2-hydroxycyclopentanenitrile. The conversion rate of the (1R,2R) -2-hydroxycyclopentanenitrile prepared by the method is not less than 85%, and the diastereomer excess value is not less than 85%.
Description
Technical Field
The invention belongs to the technical field of biological pharmacy and biochemical engineering, and particularly relates to a method for preparing (1R,2R) -2-hydroxycyclopentanenitrile by reducing with ketoreductase as a catalyst.
Background
The structural formula of the (1R,2R) -2-hydroxycyclopentanenitrile is shown as a formula II, and the (1R,2R) -2-hydroxycyclopentanenitrile has chiral hydroxyl and chiral cyano and is an important chiral intermediate.
The ketoreductase can be used for asymmetrically reducing 2-carbonyl cyclopentanenitrile to prepare (1R,2R) -2-hydroxycyclopentanenitrile. The related literature (org. Lett.2016,18,3366-3369) reports that the asymmetric reduction of 2-carbonylcyclopentanenitrile to prepare (1R,2R) -2-hydroxycyclopentanenitrile using Codex KRED can achieve a final conversion of over 99% to substrate, but the diastereomer of the product is in excess, and the obtained product (1R,2R) -2-hydroxycyclopentanenitrile is only 80%.
At present, no relevant literature report exists on a biological preparation method of (1R,2R) -2-hydroxycyclopentanenitrile with high conversion rate and optical purity.
Disclosure of Invention
The invention aims to solve the technical problem of providing a method for preparing (1R,2R) -2-hydroxycyclopentanenitrile through biocatalysis, so as to solve the technical problem that (1R,2R) -2-hydroxycyclopentanenitrile cannot be prepared with high conversion rate and high optical purity through biocatalysis in the prior art.
In order to solve the technical problems, the technical scheme of the invention is as follows:
a method for preparing (1R,2R) -2-hydroxycyclopentanenitrile through biocatalysis is to prepare the (1R,2R) -2-hydroxycyclopentanenitrile (formula II) by using 2-carbonyl cyclopentanenitrile (formula I) as a substrate and catalyzing carbonyl reduction through ketoreductase in the presence of a hydrogen source and coenzyme in a liquid phase reaction system.
The reaction formula is as follows:
in particular, we have found that the ketoreductase enzymes used above have very good chiral selectivity for this reduction reaction.
Preferably, the ketoreductase is selected from the group consisting of:
1) ketoreductase from Lactobacillus kefiri, the amino acid sequence of which is shown in SEQ ID NO 1;
2) ketoreductase enzyme from Rhodococcus sp.WB1, having the amino acid sequence shown in SEQ ID NO 2;
3) and any one of the amino acid sequences shown in SEQ ID NO. 1-2 is subjected to substitution, deletion, change, insertion or addition of one or more amino acids within the range of keeping the enzyme activity to obtain the amino acid sequence.
In a preferred embodiment, the ketoreductase is added in an amount of 0.1 to 10g ketoreductase per g substrate. Preferably, the ketoreductase is added in an amount of 1 to 5g ketoreductase per g substrate. Preferably, the ketoreductase is added in an amount of 2 to 3g ketoreductase per g substrate. Preferably, the ketoreductase is added in an amount of 2.5g ketoreductase per g substrate.
In a preferred embodiment, the hydrogen source is selected from at least one of isopropanol, glucose. Preferably, the hydrogen source is glucose; preferably, when the hydrogen source is glucose, Glucose Dehydrogenase (GDH) is additionally added for combined use.
In a preferred embodiment, the hydrogen source is added in an amount of 0.5-50 g per g of substrate; or additionally adding 0.01-1 g of Glucose Dehydrogenase (GDH).
In a preferred embodiment, the coenzyme is any one or more selected from NAD, NADH, NADP or NADPH.
In a preferred embodiment, the coenzyme is NADP or NAD.
In a preferred embodiment, the coenzyme is added in an amount of 0.01 to 1.0g of coenzyme per g of substrate.
In a preferred embodiment, the ketoreductase catalytic reaction is carried out at a pH in the range of 7 to 9. When the pH is less than 7, the catalytic activity of the enzyme may be significantly reduced. When the pH is more than 9, the enzyme activity may be decreased.
Preferably, the pH of the ketoreductase catalyzed reaction is 6.2-7.5. The pH control is carried out by adding a buffer to the reaction solvent.
In a preferred embodiment, the reaction is pH controlled by adding a buffer to the reaction solvent.
In a preferred embodiment, the buffer includes, but is not limited to, KH2PO4-K2HPO4Buffer or NaH2PO4-Na2HPO4And (4) a buffer solution.
In a preferred embodiment, the ketoreductase catalytic reaction is carried out at a temperature of 15-60 ℃. When the temperature is lower than 15 ℃, the reaction speed is slow. However, above 60 ℃ the enzyme is irreversibly inactivated.
Preferably, the reaction temperature is 20-40 ℃, so that the reaction can be carried out stably and efficiently. More preferably, the reaction temperature is 25-35 ℃,
in a preferred embodiment, the reaction solvent of the reaction system is water or a buffered saline solution. The pH of the reaction system is controlled by a buffer. Commonly used buffers include, but are not limited to, KH2PO4-K2HPO4Or NaH2PO4-Na2HPO4And (4) a buffer solution. Wherein the concentration of phosphate in the phosphate buffer solution is 0.1-2 mmol/L, preferably 0.2 mol/L; the pH of the phosphate buffer solution is 7-9, preferably 6.2-7.5.
In a preferred embodiment, the reaction system further comprises a cosolvent. The cosolvent is an organic solvent.
In a preferred embodiment, the co-solvent is selected from the group consisting of: n, N-dimethylformamide, dimethyl sulfoxide, methanol, ethanol, isopropanol, acetone, or a combination thereof. Preferably, the cosolvent is selected from N, N-dimethylformamide or dimethyl sulfoxide. Co-solvents are used to further increase the solubility of the substrate.
In a preferred embodiment, the preparation process of the present invention further comprises the step of isolating (1R,2R) -2-hydroxycyclopentanenitrile.
The conversion rate of the (1R,2R) -2-hydroxycyclopentanenitrile prepared by the method is not less than 85%, and the diastereomer excess value is not less than 85%; preferably, the conversion rate is not lower than 90%, and the diastereomer excess value is not lower than 90%; more preferably, the conversion is not less than 95% and the diastereomeric excess is not less than 95%.
The invention realizes the selective reduction of 2-carbonyl cyclopentanenitrile by a novel enzyme catalysis process technology, thereby realizing the purpose of preparing pure (1R,2R) -2-hydroxycyclopentanenitrile in a large scale.
The method has the advantages that the conversion rate of the (1R,2R) -2-hydroxycyclopentanenitrile prepared by the method is not lower than 85%, and the diastereomer excess value is not lower than 85%. The method for efficiently producing the (1R,2R) -2-hydroxycyclopentanenitrile with enantiomer purity by a novel enzyme catalysis technology has important significance. The method has the advantages of simple and easy operation, high yield and good selectivity.
Drawings
FIG. 1 is a high performance gas chromatography spectrum of (1R,2R) -2-hydroxycyclopentanenitrile in example 1.
Detailed Description
The technical solutions of the present invention will be described clearly and completely below, and it should be apparent that the described embodiments are some, but not all, embodiments of the present invention. All other embodiments, which can be obtained by a person skilled in the art without any inventive step based on the embodiments of the present invention, are within the scope of the present invention.
The inventor of the present application has conducted intensive studies and unexpectedly found a method for preparing (1R,2R) -2-hydroxycyclopentanenitrile through biocatalysis for the first time. Specifically, the method of the present invention broadly comprises the steps of:
(1) catalytic reduction of 2-carbonyl cyclopentanecarbonitrile using ketoreductases. The addition amount of ketoreductase is 0.1-10 g ketoreductaseProenzyme/g substrate (preferably in the range of 2.5g ketoreductase/g substrate). Selecting 0.5-50 g of glucose/g of substrate as a hydrogen source, and further adding 0.01-1 g of Glucose Dehydrogenase (GDH)/g of substrate as the hydrogen source, 0.01-1.0 g of Nicotinamide Adenine Dinucleotide Phosphate (NADP)/g of substrate and 0.01-1.0 g of Nicotinamide Adenine Dinucleotide (NAD)/g of substrate as coenzymes. The reaction temperature is 15-60 ℃, and preferably 25-35 ℃. The reaction medium is pure water or KH with phosphate concentration of 0.02-2 mol/L (preferably 0.2mol/L) and pH of 5-9 (preferably pH of 6.2-7.5)2PO4-K2HPO4Or NaH2PO4-Na2HPO4The buffer solution may be pure water or a two-phase system composed of the above buffer solution and a water-immiscible organic solvent (e.g., N-dimethylformamide or dimethylsulfoxide).
(2) And after the reaction is finished, extracting by using methyl tert-butyl ether, collecting an organic phase, and evaporating the solvent to dryness to obtain the product.
The reagents and starting materials used in the present invention are commercially available. The ketoreductases used in the present invention are all derived from the synthetic full-pharmaceutical enzyme library.
Example 1
First, 120mg of 2-carbonylcyclopentonitrile was dissolved in 0.3mL of dimethyl sulfoxide to prepare a raw material solution. In a 15mL glass reaction flask, 6mL phosphate buffer (6 mL water, 0.064g KH) was added2PO4And 0.167g K2HPO4Stirring until the solid is dissolved; adding potassium hydroxide to adjust the pH value to 6.2-7.5); adding 360mg of glucose, 12mg of NADP, 12mg of GDH and 5mg of Lactobacillus kefiri ketoreductase into the reaction solution, shaking and uniformly mixing, and adding 0.3mL of raw material solution; the reaction mixture was stirred continuously for 18 hours while adjusting and controlling the temperature of the reaction mixture at 30 ℃ and pH 7.0.
The reaction solution was extracted with 2mL of methyl t-butyl ether, and the organic phase was collected and analyzed by high performance gas chromatography, the conversion was 95%, and the excess of the cis-enantiomer was 99.1%. Analysis conditions were as follows: shimadzu gas chromatograph, Alpha DEX120(30 × 0.25mm, 0.25 μm) chiral chromatographic column, keeping the temperature at 150 deg.C for 5min, heating to 180 deg.C at 5 deg.C per minute for 1 min, and using nitrogen as carrier gas (carrier gas flow rate 30 mL/min); hydrogen (carrier gas flow rate 40 mL/min). The product has gas chromatography pattern shown in figure 1
Example 2
First, 120mg of 2-carbonylcyclopentonitrile was dissolved in 0.3mL of dimethyl sulfoxide to prepare a raw material solution. In a 15mL glass reaction flask, 6mL phosphate buffer (6 mL water, 0.064g KH) was added2PO4And 0.167g K2HPO4Stirring until the solid is dissolved; adding potassium hydroxide to adjust the pH value to 6.2-7.5); adding 360mg of glucose, 12mg of NADP, 12mg of GDH and 5mg of reductase from Rhodococcus sp.WB1 ketone into the reaction solution, shaking and mixing uniformly, and adding 0.3mL of raw material solution; the reaction mixture was stirred continuously for 18 hours while adjusting and controlling the temperature of the reaction mixture at 30 ℃ and pH 7.0.
The reaction solution was extracted with 2mL of methyl t-butyl ether, and the organic phase was collected and analyzed by high performance gas chromatography, whereby the conversion was 99% and the excess of the cis enantiomer was 95.1%. Analysis conditions were as follows: shimadzu gas chromatograph, Alpha DEX120(30 × 0.25mm, 0.25 μm) chiral chromatographic column, keeping the temperature at 150 deg.C for 5min, heating to 180 deg.C at 5 deg.C per minute for 1 min, and using nitrogen as carrier gas (carrier gas flow rate 30 mL/min); hydrogen (carrier gas flow rate 40 mL/min); air (carrier gas flow rate 400mL/min) and methanol as diluent.
In summary, the above embodiments are merely preferred embodiments of the present invention, and are not intended to limit the scope of the present invention, and any modifications, equivalents, improvements, etc. made within the spirit and principle of the present invention should be included in the scope of the present invention.
Sequence listing
<110> Shanghai Hequan drug development Co Ltd
<120> method for preparing (1R,2R) -2-hydroxycyclopentanenitrile by biocatalysis
<130> CPC-NP-20-101843
<160> 2
<170> SIPOSequenceListing 1.0
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<212> PRT
<213> ketoreductase (Lactobacillus kefir)
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Val Val Ile Thr Gly Arg His Ala Asp Val Gly Glu Lys Ala Ala Lys
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Ser Ile Gly Gly Thr Asp Val Ile Arg Phe Val Gln His Asp Ala Ser
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Asp Glu Ala Gly Trp Thr Lys Leu Phe Asp Thr Thr Glu Glu Ala Phe
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Gly Pro Val Thr Thr Val Val Asn Asn Ala Gly Ile Ala Val Ser Lys
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Asn Leu Asp Gly Val Phe Phe Gly Thr Arg Leu Gly Ile Gln Arg Met
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Ile Cys Val Tyr Leu Ala Ser Asp Glu Ser Lys Phe Ala Thr Gly Ala
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Glu Phe Val Val Asp Gly
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Claims (12)
1. A method for preparing (1R,2R) -2-hydroxycyclopentanenitrile through biocatalysis is characterized in that in a liquid phase reaction system, 2-carbonyl-cyclopentanenitrile is used as a substrate, and carbonyl reduction is catalyzed by ketoreductase in the presence of a hydrogen source and coenzyme to prepare the (1R,2R) -2-hydroxycyclopentanenitrile.
2. The method of claim 1, wherein the ketoreductase is selected from the group consisting of:
1) ketoreductase from Lactobacillus kefiri, the amino acid sequence of which is shown in SEQ ID NO 1;
2) ketoreductase enzyme from Rhodococcus sp.WB1, having the amino acid sequence shown in SEQ ID NO 2;
3) and any one of the amino acid sequences shown in SEQ ID NO. 1-2 is subjected to substitution, deletion, change, insertion or addition of one or more amino acids within the range of keeping the enzyme activity to obtain the amino acid sequence.
3. The method of claim 1, wherein the ketoreductase is added in an amount of 0.1 to 10g ketoreductase per g substrate; preferably, the addition amount of the ketoreductase is 1-5 g of ketoreductase per g of substrate; preferably, the addition amount of the ketoreductase is 2-3 g of ketoreductase per g of substrate; preferably, the ketoreductase is added in an amount of 2.5g ketoreductase per g substrate.
4. The method of claim 1, wherein the hydrogen source is selected from at least one of isopropanol, glucose. Preferably, the hydrogen source is glucose; preferably, when the hydrogen source is glucose, glucose dehydrogenase is additionally added for combined use.
5. The method of claim 1, wherein the hydrogen source is added in an amount of 0.5 to 50g hydrogen source per g substrate; or additionally adding 0.01-1 g of glucose dehydrogenase.
6. The method of claim 1, wherein the coenzyme is any one or more selected from NAD, NADH, NADP or NADPH; preferably, the coenzyme is NADP or NAD.
7. The method of claim 1, wherein the coenzyme is added in an amount of 0.01 to 1.0g coenzyme per g substrate.
8. The method of claim 1, wherein the ketoreductase catalyzed reaction is performed at a pH in the range of 7 to 9; preferably, the pH of the ketoreductase catalyzed reaction is 6.2-7.5.
9. The method of claim 1, wherein the reaction temperature of the ketoreductase-catalyzed reaction is 15 to 60 ℃; preferably, the reaction temperature is 20-40 ℃; more preferably, the reaction temperature is 25-35 ℃.
10. The method of claim 1, wherein the reaction solvent of the reaction system is water or a buffered saline solution; preferably, the buffered saline solution is KH2PO4-K2HPO4Buffer or NaH2PO4-Na2HPO4And (4) a buffer solution.
11. The method of claim 1, wherein the reaction system further comprises a co-solvent; preferably, the cosolvent is an organic solvent; preferably, the cosolvent is selected from the following group: n, N-dimethylformamide, dimethyl sulfoxide, methanol, ethanol, isopropanol, acetone, or a combination thereof; preferably, the co-solvent is selected from N, N-dimethylformamide or dimethyl sulfoxide.
12. The process of claim 1, further comprising the step of isolating the (1R,2R) -2-hydroxycyclopentanenitrile.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090093031A1 (en) * | 2007-08-24 | 2009-04-09 | Codexis, Inc. | Ketoreductase Polypeptides for the Production of (R)-3-Hydroxythiolane |
| WO2011071058A1 (en) * | 2009-12-08 | 2011-06-16 | 株式会社カネカ | Preparation method for optically active 2-hydroxycycloalkane carboxylic acid ester |
| CN103923957A (en) * | 2013-05-10 | 2014-07-16 | 苏州汉酶生物技术有限公司 | Chirality N-protective pipradrol biologically-preparing method |
| CN104496904A (en) * | 2014-11-28 | 2015-04-08 | 上海北卡医药技术有限公司 | Synthesis method of ruxolitinib intermediate |
| CN110229796A (en) * | 2019-05-23 | 2019-09-13 | 南京趣酶生物科技有限公司 | Ketoreductase mutant and its preparing the application in Duloxetine chirality alcohol intermediate and the like |
| CN111377839A (en) * | 2018-12-26 | 2020-07-07 | 苏州引航生物科技有限公司 | Method for preparing 3-phenyl-L-serine or derivative and ethyl ester thereof |
-
2020
- 2020-12-11 CN CN202011446019.0A patent/CN112458142B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090093031A1 (en) * | 2007-08-24 | 2009-04-09 | Codexis, Inc. | Ketoreductase Polypeptides for the Production of (R)-3-Hydroxythiolane |
| WO2011071058A1 (en) * | 2009-12-08 | 2011-06-16 | 株式会社カネカ | Preparation method for optically active 2-hydroxycycloalkane carboxylic acid ester |
| CN103923957A (en) * | 2013-05-10 | 2014-07-16 | 苏州汉酶生物技术有限公司 | Chirality N-protective pipradrol biologically-preparing method |
| CN104496904A (en) * | 2014-11-28 | 2015-04-08 | 上海北卡医药技术有限公司 | Synthesis method of ruxolitinib intermediate |
| CN111377839A (en) * | 2018-12-26 | 2020-07-07 | 苏州引航生物科技有限公司 | Method for preparing 3-phenyl-L-serine or derivative and ethyl ester thereof |
| CN110229796A (en) * | 2019-05-23 | 2019-09-13 | 南京趣酶生物科技有限公司 | Ketoreductase mutant and its preparing the application in Duloxetine chirality alcohol intermediate and the like |
Non-Patent Citations (4)
| Title |
|---|
| ELISA LIARDO等: ""Developing a Biocascade Process: Concurrent Ketone Reduction-Nitrile Hydrolysis of 2-Oxocycloalkanecarbonitriles"", 《ORG. LETT.》 * |
| GENBANK: "MULTISPECIES: NAD(P)-dependent alcohol dehydrogenase [unclassified]，NCBI Reference Sequence: WP_065922367.1", 《GENBANK》 * |
| 严阳等: "四氢噻吩-3-酮还原酶的筛选与表征" * |
| 牛婷婷等: "光学纯(R)-3-奎宁醇制备技术研究进展" * |
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