CN1940079A - Synthesis of (2S,3S)-2-benzoyl aminometh-3-hydroxy-butyrate ester series compound by asymmetric yeast cell - Google Patents
Synthesis of (2S,3S)-2-benzoyl aminometh-3-hydroxy-butyrate ester series compound by asymmetric yeast cell Download PDFInfo
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 39
- 210000005253 yeast cell Anatomy 0.000 title claims abstract description 4
- 230000015572 biosynthetic process Effects 0.000 title abstract description 3
- 238000003786 synthesis reaction Methods 0.000 title abstract description 3
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 claims abstract description 22
- -1 (2S,3S)-2-benzoyl-aminomethyl-3-hydroxy-butyrate ester Chemical class 0.000 claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 5
- 239000002994 raw material Substances 0.000 claims abstract 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 230000036983 biotransformation Effects 0.000 claims description 6
- 239000006227 byproduct Substances 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 4
- 241000894006 Bacteria Species 0.000 claims description 2
- 230000001580 bacterial effect Effects 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 210000004027 cell Anatomy 0.000 claims description 2
- 150000002170 ethers Chemical group 0.000 claims description 2
- 150000005826 halohydrocarbons Chemical group 0.000 claims description 2
- 210000001822 immobilized cell Anatomy 0.000 claims description 2
- CCZVEWRRAVASGL-UHFFFAOYSA-N lithium;2-methanidylpropane Chemical compound [Li+].CC(C)[CH2-] CCZVEWRRAVASGL-UHFFFAOYSA-N 0.000 claims description 2
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 claims description 2
- 150000007530 organic bases Chemical class 0.000 claims description 2
- 238000000711 polarimetry Methods 0.000 claims description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 239000000758 substrate Substances 0.000 abstract description 2
- 238000010170 biological method Methods 0.000 abstract 1
- 239000012467 final product Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000011324 bead Substances 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 239000008399 tap water Substances 0.000 description 4
- 235000020679 tap water Nutrition 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical compound C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000011914 asymmetric synthesis Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000002860 competitive effect Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 150000002961 penems Chemical class 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- WFRNRWHEMQWFRH-IMJSIDKUSA-N (2S,3S)-2-(aminomethyl)-3-hydroxybutanoic acid Chemical compound C[C@H](O)[C@H](CN)C(O)=O WFRNRWHEMQWFRH-IMJSIDKUSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- HGGAKXAHAYOLDJ-FHZUQPTBSA-N 6alpha-[(R)-1-hydroxyethyl]-2-[(R)-tetrahydrofuran-2-yl]pen-2-em-3-carboxylic acid Chemical compound S([C@@H]1[C@H](C(N1C=1C(O)=O)=O)[C@H](O)C)C=1[C@H]1CCCO1 HGGAKXAHAYOLDJ-FHZUQPTBSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- TYMABNNERDVXID-DLYFRVTGSA-N Panipenem Chemical compound C([C@@H]1[C@H](C(N1C=1C(O)=O)=O)[C@H](O)C)C=1S[C@H]1CCN(C(C)=N)C1 TYMABNNERDVXID-DLYFRVTGSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- DPDMMXDBJGCCQC-UHFFFAOYSA-N [Na].[Cl] Chemical compound [Na].[Cl] DPDMMXDBJGCCQC-UHFFFAOYSA-N 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical class O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 1
- 229960003328 benzoyl peroxide Drugs 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000003570 biosynthesizing effect Effects 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000009189 diving Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 229960000379 faropenem Drugs 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- DMJNNHOOLUXYBV-PQTSNVLCSA-N meropenem Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)S[C@@H]1CN[C@H](C(=O)N(C)C)C1 DMJNNHOOLUXYBV-PQTSNVLCSA-N 0.000 description 1
- 229960002260 meropenem Drugs 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
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- 229950011346 panipenem Drugs 0.000 description 1
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- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Synthesis of (2S,3S)-2-benzoyl-aminomethyl-3-hydroxy-butyrate ester series compound by yeast cell asymmetry is carried out by taking baker yeast as raw material and converting to obtain the final product by one-step biological method. It's effective and efficient and has better substrate percent conversion.
Description
Technical field
The present invention relates to shown in the formula (I) (2S, 3S)-the biological asymmetric synthesis of 2-benzoyl aminomethyl-3-butyric ester.Formula (I) compound of invention preparation is the key intermediate of industrial production formula (II) compound (abbreviating 4-AA as); Formula (II) compound can be used as intermediate (seeing formula 1) in carbapenem and penems medicine synthetic.
Formula 1.
Background technology
Azetidinones 3R, 4R-3-[(1R)-tert-butyl dimethyl silica ethyl]-4-acetoxyl group-2-azetidinone (formula (II), abbreviate 4-AA as) be new and effective antibiotic medicine carbapenem and penems medicine synthetic key intermediate, as be used for synthesizing carbapenem microbiotic imipenum, meropenem, Faropenem and panipenem etc.
Formula (II) compound has 3 chiral centres, therefore has 8 steric isomers, and very big synthetic difficulty is arranged.About the existing literature review of the synthesis technique of (II), but most of technology all exists shortcomings such as synthetic route is long, total recovery is low, complex operation, cost height, thereby limited the suitability for industrialized production of formula (II) compound.Japan Takasago company adopts chiral catalyst (R)-BINAP-Ru asymmetry catalysis 2-benzene carbon amide ylmethyl-3-carbonyl butyric ester (formula (III)) preparation (2S, 3R)-and 2-benzene carbon amide ylmethyl-3-butyric ester (formula (IV)), thus preparation formula (II) compound.But this method needs at high pressure (100kg/cm
2) just can obtain under the situation highly-solid selectively (＞97%ee), formula (IV) compound (seeing formula 2) of high chemo-selective (94: 6).R is low alkyl group or branching low alkyl group in the formula.
In the production process of chipal compounds, bio-transformation is one of the most competitive means.Compare remarkable advantage such as that bio-transformation has is efficient, single-minded, mild condition with chemical process.Abroad begin one's study from the nineties in 20th century formula (III) compound is carried out biological asymmetric reduction research, biosynthesizing mainly refers to enzyme technology.But result of study shows that through bio-transformation, most of condition following formula (III) compound mainly is reduced to the formula V compound; The formula V compound is the steric isomer (seeing formula 3) of formula (IV) compound.R is low alkyl group or branching low alkyl group in the formula.
Formula 3.
Studies show that in a large number, in optically active ester derivative synthetic, utilize bread yeast reduction 'beta '-ketoester to become the optics beta-hydroxy esters to become one of the most frequently used method.Because its cost is low, be easy to get and practicality, bread yeast is considered to the easier reagent of a kind of easy to handle.Facts have proved that if directly use yeast, product separation usually can be very difficult, and use immobilized yeast, just can easy handling, and the product yield height.
Summary of the invention
Defective in view of the synthetic method of present formula (H) compound exists the invention provides a kind of method of utilizing bread yeast catalysis formula (III) compound mainly to be converted into formula (I) compound with two chiral centres.This method operation steps is very simple, and product separation is easier to, and can be used for scale operation.By product after bread yeast transforms is the formula V compound; The present invention provides a kind of method (seeing formula 4) that the formula V compound chemistry is converted into formula (I) compound simultaneously.R is low alkyl group or branching low alkyl group in the formula.
Formula 4.
This method may further comprise the steps:
(a) bread yeast bio-transformation;
(b) a is gone on foot the gained by product and carry out C
-2The position configuration reversal;
Adopting yeast among the step a is biological transformed bacteria kind, and this bacterial classification can be free cell or immobilized cell; The organic bases that is adopted among the step b is one or more in n-Butyl Lithium, isobutyl-lithium, tert-butyl lithium, potassium tert.-butoxide, sodium methylate, triethylamine or the pyridine; The solvent that adopts is ethers or halohydrocarbon, is specially in tetrahydrofuran (THF), ether, chloroform, the methylene dichloride one or more; Temperature of reaction is-100 ℃～50 ℃; Reaction times is 0.05～24 hour.
This method is biological asymmetric reduction, have that cost is low, yield is high, easy and simple to handle, reaction conditions is easy to realize and be suitable for advantage such as large-scale industrial production formula (I) compound.Compared with prior art, has bigger competitive edge.
The objective of the invention is to use bread yeast prepare have single polarimetry nature (2S, 3S)-2-benzoyl aminomethyl-3-hydroxybutyric acid ester series compound.Adopt this technology, with one step of bread yeast bio-transformation preparation (2S, 3S)-2-benzoyl aminomethyl-3-hydroxybutyric acid ester series compound, the chiral substrates transformation efficiency of diving can reach more than 90%, by product is few, target product (2S, 3S)-2-benzoyl aminomethyl-3-butyric ester accounts for more than 75% of gross product.The present invention provides the method that effectively the catalysis by product is converted into target product simultaneously.
Embodiment
Further elaborate preparation method of the present invention below by embodiment.
(2S, 3S)-2-benzoyl aminomethyl-ethyl 3-hydroxybutanoate be formula (I) compound, (2R, 3S)-2-benzoyl aminomethyl-ethyl 3-hydroxybutanoate is the preparation (R=Et) of formula V compound:
In 5 liters of three mouthfuls of round-bottomed flasks that bubbler and thermometer are housed, add tap water (2500ml), sucrose (600g), bread yeast (supermarket is bought for 100g, Angel Yeast) successively, with mixture gentle agitation (120r/min).
After 1 hour, make the CO of generation
2Gas is overflowed with the speed of about 1～2 bubbles per second.(III 35g), stirs mixture 24 hours down at 33～36 ℃ to wherein adding 2-benzene carbon amide ylmethyl-3-carbonyl butyric ester then.
(150g) is dissolved in the 500ml tap water with sucrose, and joins in the reaction mixture, continue to stir down at 33～36 ℃, and with the TLC monitoring reaction to reacting completely about 72 hours.In reaction mixture, add diatomite (150g), and filter, remove solid with the diatomite packing layer.Filtrate is used ethyl acetate extraction (600ml * 6), and water (600ml), saturated brine (600ml) washing successively, the organic phase anhydrous sodium sulfate drying, after the filtration,, separate with silica gel column chromatography through concentrating under reduced pressure, obtain formula (I) compound (28.15g, 80%; Optical purity: 99.2%, HPLC); Formula V compound (7.05g, 20%; Optical purity: 98.6%, HPLC).
With the preparation of immobilized bread yeast (2S, 3S)-2-benzoyl aminomethyl-ethyl 3-hydroxybutanoate be formula (I) compound, (2R, 3S)-2-benzoyl aminomethyl-ethyl 3-hydroxybutanoate is formula V compound (R=Et):
A) bread yeast is immobilized:
With Angel Yeast (or the dry yeast bought of other supermarket, 20g), sodiun alginate (5g) slowly joins respectively in the 200ml tap water of quick stirring, is made into two solution.When two solution all become the homogeneous phase thick liquid, they are merged, be added drop-wise in calcium chloride (665ml, 10% (the mass volume ratio)) aqueous solution by dropping funnel then.The dropping liquid that splashes into forms the gel bead with after salts solution contacts, and the size of bead and shape can be controlled by rate of addition.
Bead washs with tap water (500ml * 5), and is used for the reduction of ketone immediately.
B) immobilized bread yeast is used for the reduction reaction of III:
The bead (about 200g) that preceding method makes is put into three mouthfuls of round-bottomed flasks of 2L.Add distilled water (700ml), sucrose (40g) successively, in 33～36 ℃ of following vigorous stirring said mixtures.After 3 hours, and adding 2-benzene carbon amide ylmethyl-3-carbonyl butyric ester (III, 6g).Continue vigorous stirring, TLC monitors to reacting completely.
The aqueous solution is poured on the diatomite in the B into suction filtration.The yeast filter cake that obtains is washed with ethyl acetate (100ml * 3); Water layer by diatomite filtration, is removed gel milk sap with the saturated back of sodium-chlor, and filtrate is washed with ethyl acetate (200ml * 3); Ethyl acetate is merged, water (200ml), saturated brine (200ml) washing successively, the organic phase anhydrous sodium sulfate drying after the filtration, through concentrating under reduced pressure, separates with silica gel column chromatography, obtains formula (I) compound (4.75g, 80%; Optical purity: 99.3%, HPLC); Formula V compound (1.20g, 20%; Optical purity: 98.8%, HPLC).
By (2R, 3S)-2-benzoyl aminomethyl-ethyl 3-hydroxybutanoate be the formula V compound (2S, 3S)-2-aminomethyl-3-hydroxybutyric acid is formula (I) compound (R=Et):
Under nitrogen protection, under-60 ℃ to (2R, 3S)-2-benzene carbon amide ylmethyl-ethyl 3-hydroxybutanoate V (R=Et) (5.30g, add 2.5M n-Butyl Lithium (28ml in anhydrous tetrahydro furan 20mmol) (100ml) solution, 70mmol), stirred 0.5 hour down at-60 ℃, be warmed up to room temperature naturally, at room temperature stirred two hours, add saturated ammonium chloride solution 30ml, continue then to stir after 0.5 hour, extract with ether (200ml * 3), successively water (100ml), saturated sodium-chloride water solution (100ml) washing, organic phase is after concentrating, separate with silica gel column chromatography, obtain formula (I) compound (4.52g, 85%; Optical purity: 99.0%, HPLC), and reclaim formula V compound (0.65g).
Owing to described the present invention according to its special embodiment, some modification and equivalent variations are conspicuous and comprise within the scope of the invention for the those of ordinary skill in this field.
Claims (8)
1. the compound that is expressed from the next by the bread yeast biocatalysis of a utilization is a raw material, preparation have single polarimetry nature (2S, 3S)-method of 2-benzoyl aminomethyl-3-hydroxybutyric acid ester series compound.
R is low alkyl group or branching low alkyl group in the formula.
2. method according to claim 1 is characterized in that wherein " low alkyl group or branching low alkyl group " is meant the saturated alkyl that contains 1～6 carbon atom.
3. method according to claim 1 is characterized in that this method may further comprise the steps:
(a) bread yeast bio-transformation;
(b) a is gone on foot the gained by product and carry out C
-2The position configuration reversal.
4. method according to claim 1 is characterized in that adopting yeast among the step a is biological transformed bacteria kind, and this bacterial classification can be free cell or immobilized cell.
5. method according to claim 4 is characterized in that described yeast cell is a saccharomyces yeast.
6. method according to claim 1 is characterized in that the organic bases that is adopted among the step b is one or more in n-Butyl Lithium, isobutyl-lithium, tert-butyl lithium, potassium tert.-butoxide, sodium methylate, triethylamine or the pyridine.
7. method according to claim 1 is characterized in that the solvent that is adopted among the step b is ethers or halohydrocarbon, is specially in tetrahydrofuran (THF), ether, chloroform, the methylene dichloride one or more.
8. method according to claim 1 is characterized in that temperature of reaction is-100 ℃～50 ℃ among the step b; Reaction times is 0.05～24 hour.
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| CN2006100686774A CN1940079B (en) | 2006-09-08 | 2006-09-08 | Synthesis of (2S,3S)-2-benzoyl aminometh-3-hydroxy-butyrate ester series compound by asymmetric yeast cell |
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| CN2006100686774A CN1940079B (en) | 2006-09-08 | 2006-09-08 | Synthesis of (2S,3S)-2-benzoyl aminometh-3-hydroxy-butyrate ester series compound by asymmetric yeast cell |
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| CN1940079B CN1940079B (en) | 2010-10-13 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103045504A (en) * | 2012-12-05 | 2013-04-17 | 浙江工业大学 | Microorganism catalysis prepared (2S,3R)-2-benzoyl aminomethyl-3-hydroxybutyric acid ester and bacterial strain |
| CN103373934A (en) * | 2013-06-14 | 2013-10-30 | 苏州汇和药业有限公司 | Catalytic synthesis method of chiral intermediate for carbapenem and penem medicaments |
| CN104846025A (en) * | 2015-03-31 | 2015-08-19 | 浙江大学 | Method for preparing (2S, 3R)-2-benzoyl aminomethyl-3-hydroxy methyl butyrate |
| CN113528592A (en) * | 2021-06-08 | 2021-10-22 | 复旦大学 | Method for synthesizing (2S,3R) -2-substituted aminomethyl-3-hydroxybutyrate under enzyme catalysis |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3875373D1 (en) * | 1987-05-04 | 1992-11-26 | Ciba Geigy Ag | NEW METHOD FOR PRODUCING 4-ACYLOXY-3-HYDROXYETHYL AZETIDINONES. |
| JPH0623150B2 (en) * | 1988-11-15 | 1994-03-30 | 高砂香料工業株式会社 | Process for producing optically active 3-hydroxybutanoic acids |
-
2006
- 2006-09-08 CN CN2006100686774A patent/CN1940079B/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103045504A (en) * | 2012-12-05 | 2013-04-17 | 浙江工业大学 | Microorganism catalysis prepared (2S,3R)-2-benzoyl aminomethyl-3-hydroxybutyric acid ester and bacterial strain |
| CN103373934A (en) * | 2013-06-14 | 2013-10-30 | 苏州汇和药业有限公司 | Catalytic synthesis method of chiral intermediate for carbapenem and penem medicaments |
| CN104846025A (en) * | 2015-03-31 | 2015-08-19 | 浙江大学 | Method for preparing (2S, 3R)-2-benzoyl aminomethyl-3-hydroxy methyl butyrate |
| CN104846025B (en) * | 2015-03-31 | 2018-06-01 | 浙江大学 | A kind of method for preparing (2S, 3R) -2- benzoyl aminomethyls -3-hydroxybutyrate methyl esters |
| CN113528592A (en) * | 2021-06-08 | 2021-10-22 | 复旦大学 | Method for synthesizing (2S,3R) -2-substituted aminomethyl-3-hydroxybutyrate under enzyme catalysis |
| CN113528592B (en) * | 2021-06-08 | 2022-08-19 | 复旦大学 | Enzyme-catalyzed (2)S,3R) Synthesis method of (E) -2-substituted aminomethyl-3-hydroxybutyrate |
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