CN104313078A - Method for producing chiral thiazolyl ethanol through biological catalysis - Google Patents
Method for producing chiral thiazolyl ethanol through biological catalysis Download PDFInfo
- Publication number
- CN104313078A CN104313078A CN201410594981.7A CN201410594981A CN104313078A CN 104313078 A CN104313078 A CN 104313078A CN 201410594981 A CN201410594981 A CN 201410594981A CN 104313078 A CN104313078 A CN 104313078A
- Authority
- CN
- China
- Prior art keywords
- substrate
- cotton gauze
- reaction
- thiazolyl
- ethanol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 title claims abstract description 6
- 238000006555 catalytic reaction Methods 0.000 title abstract description 12
- 238000004519 manufacturing process Methods 0.000 title abstract description 3
- -1 thiazolyl ethanol Chemical compound 0.000 title abstract 2
- 239000000758 substrate Substances 0.000 claims abstract description 57
- 229920000742 Cotton Polymers 0.000 claims abstract description 54
- 238000006243 chemical reaction Methods 0.000 claims abstract description 43
- 238000000034 method Methods 0.000 claims abstract description 20
- 241000228143 Penicillium Species 0.000 claims abstract description 15
- YTYLXXDUJXUJJJ-BYPYZUCNSA-N (1s)-1-(1,3-thiazol-2-yl)ethanol Chemical compound C[C@H](O)C1=NC=CS1 YTYLXXDUJXUJJJ-BYPYZUCNSA-N 0.000 claims abstract description 14
- MOMFXATYAINJML-UHFFFAOYSA-N 2-Acetylthiazole Chemical compound CC(=O)C1=NC=CS1 MOMFXATYAINJML-UHFFFAOYSA-N 0.000 claims description 38
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 36
- 239000000243 solution Substances 0.000 claims description 16
- 230000002210 biocatalytic effect Effects 0.000 claims description 12
- 238000009423 ventilation Methods 0.000 claims description 12
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 8
- 239000008103 glucose Substances 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 8
- 240000008042 Zea mays Species 0.000 claims description 7
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 claims description 7
- 235000002017 Zea mays subsp mays Nutrition 0.000 claims description 7
- 208000012839 conversion disease Diseases 0.000 claims description 7
- 235000005822 corn Nutrition 0.000 claims description 7
- 229960003487 xylose Drugs 0.000 claims description 7
- SRBFZHDQGSBBOR-LECHCGJUSA-N alpha-D-xylose Chemical compound O[C@@H]1CO[C@H](O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-LECHCGJUSA-N 0.000 claims description 6
- 239000000872 buffer Substances 0.000 claims description 6
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 claims description 6
- 238000003810 ethyl acetate extraction Methods 0.000 claims description 6
- 238000000605 extraction Methods 0.000 claims description 6
- 239000002953 phosphate buffered saline Substances 0.000 claims description 6
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 6
- 229920000053 polysorbate 80 Polymers 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 2
- 230000002349 favourable effect Effects 0.000 abstract 1
- 239000008055 phosphate buffer solution Substances 0.000 abstract 1
- 241000228150 Penicillium chrysogenum Species 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000005515 coenzyme Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- 101000925662 Enterobacteria phage PRD1 Endolysin Proteins 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 239000012847 fine chemical Substances 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 1
- 241000024287 Areas Species 0.000 description 1
- 239000002028 Biomass Substances 0.000 description 1
- 240000008564 Boehmeria nivea Species 0.000 description 1
- 241000790917 Dioxys <bee> Species 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 101710157860 Oxydoreductase Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000011790 ferrous sulphate Substances 0.000 description 1
- 235000003891 ferrous sulphate Nutrition 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000005389 magnetism Effects 0.000 description 1
- SQQMAOCOWKFBNP-UHFFFAOYSA-L manganese(II) sulfate Chemical compound [Mn+2].[O-]S([O-])(=O)=O SQQMAOCOWKFBNP-UHFFFAOYSA-L 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000013028 medium composition Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a method for producing chiral thiazolyl ethanol through biological catalysis. The method comprises the steps of carrying out biological catalysis by using penicillium cells to prepare photoactive (S)-1-(2-thiazolyl)ethanol; adding a phosphate buffer solution into a reaction tank; and adding cotton gauze to control the concentrations of a substrate and a product. The penicillium cells are used for biological catalytic reaction, so that the yield of the product is high, the enantiomeric excess rate (ee%) is high, and the method has a favorable application prospect.
Description
Technical field
The invention belongs to technology of pharmaceutical engineering field, be related specifically to Penicillium cell biocatalysis and prepare chiral medicinal intermediate (S)-1-(2-thiazolyl) technology of ethanol.
Background technology
Chirality (S)-1-(2-thiazolyl) ethanol is the important intermediate of synthesis of chiral medicine, fine chemicals, agricultural chemicals product and other exotic materialss.Biocatalysis asymmetric reaction has environmental friendliness, mild condition, selectivity advantages of higher, prepares the first approach of hydroxyl chipal compounds as green high-efficient, is applied to the chipal compounds producing some high added values more and more.Biocatalysis prepares chirality (S)-1-(2-thiazolyl) ethanol has good application prospect.
Biocatalysis has the outstanding advantages such as catalytic efficiency is high, selectivity strong, mild condition, environmental friendliness, is the important method substituting and expand traditional organic chemical synthesis in process of sustainable development.Wherein chiral separation and asymmetric synthesis are the Application Areass of biocatalysis most magnetism.As in six large fermentoids of biological catalyst, lytic enzyme catalytic kinetics resolution of racemates can obtain quiral products, in industrial biocatalytic, play key player always.In recent years, oxydo-reductase application industrially obtained and increased rapidly.At present, the ratio adopting the industry of lytic enzyme Kinetic Resolution, biological catalysis and biological oxidation process to prepare optical activity chirality compound is 4:2:1.Biomass cells reduction method is for Kinetic Resolution, and maximum advantage is that theoretical yield can reach 100%, and Atom economy is good.But bioreduction needs the participation of coenzyme or cofactor, limit its application to a certain extent.Due to the dependent cause of coenzyme, in bioreduction, many Bian intact cells are as catalyzer, realize the purification procedures eliminating enzyme in body while coenzyme cyclic regeneration.
(S)-1-(2-thiazolyl) ethanol is the important chiral building block of synthesis of chiral medicine, fine chemicals, agricultural chemicals product, owing to there being 2 chiral centres, make chemosynthesis comparatively difficult, cost is high.The present invention will adopt biocatalysis to prepare (S)-1-(2-thiazolyl) ethanol.
Summary of the invention
The present invention adopts Penicillium cell catalysis to prepare (S)-1-(2-thiazolyl) ethanol, reaction formula is as follows:
Substrate 2-acetylthiazole (1), through Penicillium notatum catalyzed reaction, obtains product (S)-1-(2-thiazolyl) ethanol (2).Have multiple-microorganism can catalysis this reaction, through great many of experiments screening, finally determine adopt Penicillium notatum as catalyzer because its catalysis 1 reaction effect best, reaction yield, enantiomeric excess rate (ee%) are all very high.
Many Penicillium notatums can carry out this reaction of biocatalysis, but its effect is different, differs greatly, and through experiment, the present invention selects Penicillium strain to be ATCC 11594, and its this reaction effect of catalysis is best.
developing medium:
1, nutrient solution composition: corn steep liquor (with dry basis) content is 35-45g/L; yeast extract 8-10 g/L; glucose 18-22 g/L; malt extract 25-30 g, ammonium sulfate 0.5-0.7g/L, magnesium sulfate 0.3-0.4g/L; phosphoric acid dioxy potassium 1.8-2.3g/L; calcium carbonate 0.7 g/L, ferrous sulfate 0.18 g/L, manganous sulfate 0.025 g/L; PH 4.7-4.9.
2, solid medium composition: the agar powder adding 1.5-2% in liquid medium within.
Prepared by Penicillium cell.Penicillium notatum through inclined-plane, shaking flask, seed tank culture obtain seed liquor; Fermentor tank adds nutrient solution, and coefficient is 0.6-0.7, and 121 DEG C of autoclavings 30 minutes, are cooled to 25-26 DEG C, by Penicillium notatum
aTCC 11594seed liquor is seeded to fermentor tank, and inoculative proportion is 10-15%, and ventilation ratio is 0.5-1V/(V minute), namely per minute air flow is 0.5-1 times of fermentating liquid volume, cultivate 32-40 hour, obtain wet Penicillium cell, as biocatalytic reaction catalyzer with filtering centrifuge is centrifugal for 25-26 DEG C.Wet cell preparation technique is mature technology.
Because substrate, product all have restraining effect to Penicillium cell, in order to reduce the suppression of substrate, products upon cell, the present invention adopts cotton gauze immunoabsorbent substrate, in reaction, when substrate is reacted by cell catalysis, when concentration reduces, substrate from cotton gauze stripping, postreaction consume substrate.Meanwhile, product is adsorbed by cotton gauze, decreases its concentration in water, thus considerably reduces the suppression of substrate, products upon cell.The ratio of substrate and cotton gauze, determines the concentration of substrate in reaction solution, product, and concentration is also relevant with temperature of reaction, reaction solution composition.Different cell is different to the susceptibility of substrate, product, so, great many of experiments be carried out, best substrate and the ratio of cotton gauze could be determined.Experiment shows, for bacterial strain of the present invention, reaction solution composition, temperature of reaction, best substrate and the ratio of cotton gauze are 0.34-0.35.During concrete absorption, the substrate 2-acetylthiazole cotton gauze being of a size of 0.5cmX0.5cm is absorbed, namely obtains the cotton gauze having adsorbed substrate.Regulate substrate and cotton gauze consumption, make the quality ratio of substrate and cotton gauze be 0.34-0.35.Cotton gauze used is common cotton gauze, and commercially, be cut into 0.5cmX0.5cm fritter, sterilizing, Preservation in sterile condition is stand-by.
Phosphate buffered saline buffer is added in bottom ventilation stirred tank, pH is 6.0, add the cotton gauze having adsorbed substrate 2-acetylthiazole, substrate 2-acetylthiazole addition is made to be 80-90 g/L, corn steep liquor (with dry basis) content is 20-22g/L, and glucose content is 10-12g/L, wood sugar 11-12 g/L, tween 80 content is 17-19g/L, 121 DEG C of autoclavings 30 minutes; When being cooled to 28-29 DEG C, add wet Penicillium cell and make concentration be 30-35g/L, ventilation ratio is 0.2-0.22V/(V minute), namely per minute air flow is 0.2-0.22 times of reaction solution volume, carries out biocatalytic reaction, and the reaction times is 50-56 hour; After reaction terminates, leach cell, cotton gauze respectively, be extracted with ethyl acetate reaction solution, extraction gauze, combined ethyl acetate extraction liquid, steam ethyl acetate, obtain product (S)-1-(2-thiazolyl) ethanol, reaction conversion ratio 96-98%, product yield 94-96%, enantiomeric excess rate (ee%) 98-99%.
The present invention carries out the work and comprises bacterial strain selection (selecting from more or less a hundred bacterial strain), catalytic reaction condition optimizes (temperature of reaction, air flow, pH), reaction medium is selected and concentration optimization (concentration of substrate, glucose content, Xylose Content, kinds of surfactants (more than 20, kind selects 1) and concentration, other multiple components is selected to get rid of), solid absorption is adopted to control substrate product concentration, thus the suppression reduced cell, test carclazyte, diatomite, cotton gauze, ramie gauze, the many kinds of solids materials such as macropore resin, also once carried out the test of water-organic solvent 2 phase system.Because tested number is very large, although have employed response surface optimization design experiment, drastically reduce the area tested number, tested number is still very large, and total Test carries out just completing more than 2 years, reaches current technical scheme.For photolytic activity product, as reaction conversion ratio 96-98%, during product yield 94-96%, enantiomeric excess rate (ee%), still up to 98-99%, is very not easily, and our work achieves marked improvement.
embodiment 1
Wet Penicillium notatum is produced by ordinary method
aTCC 11594cell, as biocatalytic reaction catalyzer.
The cotton gauze making method of having adsorbed substrate is, is absorbed by the substrate 2-acetylthiazole cotton gauze being of a size of 0.5cmX0.5cm, namely obtains the cotton gauze having adsorbed substrate, regulate substrate and cotton gauze consumption, make the quality ratio of substrate and cotton gauze be 0.34.Cotton gauze used is common cotton gauze, and commercially, be cut into 0.5cmX0.5cm fritter, sterilizing, Preservation in sterile condition is stand-by, and other embodiment cotton gauze process is identical.
Phosphate buffered saline buffer is added in 15L bottom ventilation stirred tank, pH is 6.7, add the cotton gauze having adsorbed substrate 2-acetylthiazole, substrate 2-acetylthiazole addition is made to be 80 g/L, corn steep liquor (with dry basis) content is 20g/L, and glucose content is 10g/L, wood sugar 11 g/L, tween 80 content is 17g/L, 121 DEG C of autoclavings 30 minutes; When being cooled to 28 DEG C, add wet Penicillium cell and make concentration be 30g/L, ventilation ratio is 0.2V/(V minute), namely per minute air flow is 0.2 times of reaction solution volume, carries out biocatalytic reaction, and the reaction times is 50 hours; After reaction terminates, leach cell, cotton gauze respectively, be extracted with ethyl acetate reaction solution, extraction gauze, combined ethyl acetate extraction liquid, steam ethyl acetate, obtain product (S)-1-(2-thiazolyl) ethanol, reaction conversion ratio 96%, product yield 94%, enantiomeric excess rate (ee%) 99%.
embodiment 2
Wet Penicillium notatum is produced by ordinary method
aTCC 11594cell, as biocatalytic reaction catalyzer.
The cotton gauze making method of having adsorbed substrate is, is absorbed by the substrate 2-acetylthiazole cotton gauze being of a size of 0.5cmX0.5cm, namely obtains the cotton gauze having adsorbed substrate, regulate substrate and cotton gauze consumption, make the quality ratio of substrate and cotton gauze be 0.35.
Phosphate buffered saline buffer is added in 100L bottom ventilation stirred tank, pH is 6.7, add the cotton gauze having adsorbed substrate 2-acetylthiazole, substrate 2-acetylthiazole addition is made to be 90 g/L, corn steep liquor (with dry basis) content is 22g/L, and glucose content is 12g/L, wood sugar 12 g/L, tween 80 content is 19g/L, 121 DEG C of autoclavings 30 minutes; When being cooled to 29 DEG C, add wet Penicillium cell and make concentration be 35g/L, ventilation ratio is 0.22V/(V minute), namely per minute air flow is 0.22 times of reaction solution volume, carries out biocatalytic reaction, and the reaction times is 56 hours; After reaction terminates, leach cell, cotton gauze respectively, be extracted with ethyl acetate reaction solution, extraction gauze, combined ethyl acetate extraction liquid, steam ethyl acetate, obtain product (S)-1-(2-thiazolyl) ethanol, reaction conversion ratio 98%, product yield 96%, enantiomeric excess rate (ee%) 98%
embodiment 3
Wet Penicillium notatum is produced by ordinary method
aTCC 11594cell, as biocatalytic reaction catalyzer.
The cotton gauze making method of having adsorbed substrate is; the substrate 2-acetylthiazole cotton gauze being of a size of 0.5cmX0.5cm is absorbed; namely obtain the cotton gauze having adsorbed substrate, regulate substrate and cotton gauze consumption, make the quality ratio of substrate and cotton gauze be 0.345.
Phosphate buffered saline buffer is added in 500L bottom ventilation stirred tank, pH is 6.7, add the cotton gauze having adsorbed substrate 2-acetylthiazole, substrate 2-acetylthiazole addition is made to be 80-90 g/L, corn steep liquor (with dry basis) content is 21g/L, and glucose content is 11g/L, wood sugar 11.5 g/L, tween 80 content is 18g/L, 121 DEG C of autoclavings 30 minutes; When being cooled to 28.5 DEG C, add wet Penicillium cell and make concentration be 33g/L, ventilation ratio is 0.212V/(V minute), namely per minute air flow is 0.21 times of reaction solution volume, carries out biocatalytic reaction, and the reaction times is 503 hours; After reaction terminates, leach cell, cotton gauze respectively, be extracted with ethyl acetate reaction solution, extraction gauze, combined ethyl acetate extraction liquid, steam ethyl acetate, obtain product (S)-1-(2-thiazolyl) ethanol, reaction conversion ratio 97%, product yield 95%, enantiomeric excess rate (ee%) 98.6%
embodiment 4
Wet Penicillium notatum is produced by ordinary method
aTCC 11594cell, as biocatalytic reaction catalyzer.
The cotton gauze making method of having adsorbed substrate is, is absorbed by the substrate 2-acetylthiazole cotton gauze being of a size of 0.5cmX0.5cm, namely obtains the cotton gauze having adsorbed substrate, regulate substrate and cotton gauze consumption, make the quality ratio of substrate and cotton gauze be 0.35.
Phosphate buffered saline buffer is added in 1000L bottom ventilation stirred tank, pH is 6.7, add the cotton gauze having adsorbed substrate 2-acetylthiazole, substrate 2-acetylthiazole addition is made to be 89 g/L, corn steep liquor (with dry basis) content is 22g/L, and glucose content is 11.5g/L, wood sugar 12 g/L, tween 80 content is 9g/L, 121 DEG C of autoclavings 30 minutes; When being cooled to 29 DEG C, add wet Penicillium cell and make concentration be 34g/L, ventilation ratio is 0.22V/(V minute), namely per minute air flow is 0.22 times of reaction solution volume, carries out biocatalytic reaction, and the reaction times is 55 hours; After reaction terminates, leach cell, cotton gauze respectively, be extracted with ethyl acetate reaction solution, extraction gauze, combined ethyl acetate extraction liquid, steam ethyl acetate, obtain product (S)-1-(2-thiazolyl) ethanol, reaction conversion ratio 97.5%, product yield 95.4%, enantiomeric excess rate (ee%) 98.7%.
Claims (2)
1. Penicillium cell biocatalysis preparation (S)-1-(2-thiazolyl) method of ethanol, it is characterized in that adding phosphate buffered saline buffer in retort, pH is 6.7, add the cotton gauze having adsorbed substrate 2-acetylthiazole, substrate 2-acetylthiazole addition is made to be 80-90 g/L, corn steep liquor (with dry basis) content is 20-22g/L, glucose content is 10-12g/L, wood sugar 11-12 g/L, tween 80 content is 17-19g/L, 121 DEG C of autoclavings 30 minutes; When being cooled to 28-29 DEG C, add wet Penicillium cell and make concentration be 30-35g/L, ventilation ratio is 0.2-0.22V/(V minute), carry out biocatalytic reaction, the reaction times is 50-56 hour; After reaction terminates, leach cell, cotton gauze respectively, be extracted with ethyl acetate reaction solution, extraction gauze, combined ethyl acetate extraction liquid, steam ethyl acetate, obtain product (S)-1-(2-thiazolyl) ethanol, reaction conversion ratio 96-98%, product yield 94-96%, enantiomeric excess rate (ee%) 98-99%.
2. method according to claim 1; it is characterized in that described cotton gauze making method of having adsorbed substrate is; the substrate 2-acetylthiazole cotton gauze being of a size of 0.5cmX0.5cm is absorbed; namely the cotton gauze having adsorbed substrate is obtained; regulate substrate and cotton gauze consumption, make the quality ratio of substrate and cotton gauze be 0.34-0.35.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410594981.7A CN104313078A (en) | 2014-10-30 | 2014-10-30 | Method for producing chiral thiazolyl ethanol through biological catalysis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410594981.7A CN104313078A (en) | 2014-10-30 | 2014-10-30 | Method for producing chiral thiazolyl ethanol through biological catalysis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104313078A true CN104313078A (en) | 2015-01-28 |
Family
ID=52368388
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410594981.7A Pending CN104313078A (en) | 2014-10-30 | 2014-10-30 | Method for producing chiral thiazolyl ethanol through biological catalysis |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104313078A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1793355A (en) * | 2005-12-01 | 2006-06-28 | 华东理工大学 | Organic solvent slow-releasing system and its preparation and application for catalyzing reaction of enzyme thereof |
-
2014
- 2014-10-30 CN CN201410594981.7A patent/CN104313078A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1793355A (en) * | 2005-12-01 | 2006-06-28 | 华东理工大学 | Organic solvent slow-releasing system and its preparation and application for catalyzing reaction of enzyme thereof |
Non-Patent Citations (4)
| Title |
|---|
| DAVE CARON ET AL.: "Stereoselective reduction of ketones by Daucus carota hairy root cultures", 《BIOTECHNOLOGY LETTERS》 * |
| KEN-ICHI ITOH ET AL.: "Biocatalytic asymmetric reduction of 3-acetylisoxazoles", 《TETRAHEDRON: ASYMMETRY》 * |
| MOHAN PAL ET AL.: "Bioreduction of methyl heteroaryl and aryl heteroaryl ketones in high enantiomeric excess with newly isolated fungal strains", 《BIORESOURCE TECHNOLOGY》 * |
| 杨忠华等: "活性酵母细胞不对称催化苯乙酮还原及树脂吸附对反应的促进作用", 《催化学报》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104293851A (en) | Method for producing hydroxyethyl pyridine by alternaria alternata | |
| CN104313074A (en) | Method for producing pyridylethanol through penicillium catalysis | |
| CN104342464A (en) | Method for producing chiral phenyl methanol employing catalysis of tarlaromyces flavus | |
| CN104263776A (en) | Method for producing chiral pyridine ethanol through biological catalysis | |
| CN104313078A (en) | Method for producing chiral thiazolyl ethanol through biological catalysis | |
| CN104212843B (en) | A kind of method of saccharomyces cerevisiae also original production bromophenyl methyl propionate | |
| CN104313076A (en) | Method for producing methylpyridinyl ethanol through biological catalysis | |
| CN104263775A (en) | Method for producing 4-pyridineethanol by black mould through catalysis | |
| CN104313075A (en) | Cell production method for photoactive bromopyridyl ethanol | |
| CN104313062A (en) | Method for producing photoactive phenylethanol through cell catalysis | |
| CN104313077A (en) | Biological method for producing isoxazolyl ethanol | |
| CN104388490A (en) | Method for producing chiral pyrazinyl ethanol by biological catalysis | |
| CN104357504A (en) | Cell catalysis for producing chirality methoxyl pyridine ethanol | |
| CN104328147A (en) | Production method of chlorine-contaning (2R,3S) methyl methylpropionate | |
| CN104328154A (en) | Method for producing (S)-phenyl methanol from blue mold | |
| CN104293856A (en) | Method for producing fluoropyridine ethanone through cell catalysis | |
| CN104293852A (en) | Method for producing isoquinoline methyl alcohol through cell catalysis | |
| CN104328151A (en) | Method for producing benzothiophene ethanol by using cells as catalyst | |
| CN104263769A (en) | Method of producing chlorphenyl methyl propionate by biological process | |
| CN105132471A (en) | Method for producing photo-active chloro-benzene chloroethanol by virtue of microorganisms | |
| CN105039449A (en) | Method for producing (S)-furan ethanol with penicillium | |
| CN104263774A (en) | Method for catalytic production of chiral cyclohexylidene enol with saccharomyces cerevisiae | |
| CN105177060A (en) | Method for cell production of (S)-tetrahydronaphthol | |
| CN104263773A (en) | Biological method for producing dioxy-heptenal | |
| CN105039446A (en) | Method for producing (S)-cyanobenzene alcohol through cells |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20150128 |