EP0576638A1 - Verfahren zur herstellung von optisch aktiven cyanhydrinen durch racemattrennung in gegenwart von oxynitrilasen - Google Patents

Verfahren zur herstellung von optisch aktiven cyanhydrinen durch racemattrennung in gegenwart von oxynitrilasen

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Publication number
EP0576638A1
EP0576638A1 EP19920924554 EP92924554A EP0576638A1 EP 0576638 A1 EP0576638 A1 EP 0576638A1 EP 19920924554 EP19920924554 EP 19920924554 EP 92924554 A EP92924554 A EP 92924554A EP 0576638 A1 EP0576638 A1 EP 0576638A1
Authority
EP
European Patent Office
Prior art keywords
carbonyl compound
hydrocyanic acid
oxynitrilases
reaction
cyanohydrin
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.)
Withdrawn
Application number
EP19920924554
Other languages
German (de)
English (en)
French (fr)
Inventor
Uwe Niedermeyer
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of EP0576638A1 publication Critical patent/EP0576638A1/de
Withdrawn legal-status Critical Current

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Classifications

    • 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
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/24—Preparation of oxygen-containing organic compounds containing a carbonyl group
    • 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
    • C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
    • C12P41/006—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by reactions involving C-N bonds, e.g. nitriles, amides, hydantoins, carbamates, lactames, transamination reactions, or keto group formation from racemic mixtures

Definitions

  • Optically active cyanohydrins serve as intermediates for the synthesis of optically active ⁇ -hydroxy acids and optically active ⁇ -ethanolamines.
  • the derivatives of (S) -meta-phenoxybenzaldehyde cyanohydrin and substituted analogs are also of particular interest as building blocks for the preparation of phctostable pyrethroids.
  • optically active cyanohydrins are mostly formed from carbonyl compounds and hydrocyanic acid in the presence of oxynitrilase or other asymmetric catalysts. After V.I.
  • cyanohydrins such as e.g. Use acetone cyanohydrin as a cyanide source in enzyme-catalyzed synthesis.
  • the aim of this invention is therefore to provide a method for
  • asymmetric cyanohydrins can be expanded considerably.
  • the process according to the invention developed for this purpose is based on aliphatic, aromatic or heteroaromatic cyanohydrins and in the presence of (R) -oxynitrilase (4.1.2.10) from almonds or another oxynitrilase from rosaceae, the (S) -oxynitrilase (4.1 2. 11) from Sorghum bicolor, the oxynitrilase from Linum ussitatissimum or other oxynitrilases that are widespread in nature.
  • the process is characterized in that only one enantiomer of the mixture is split into carbonyl compound and hydrocyanic acid and the resulting one
  • the hydrocyanic acid can be particularly advantageous for reactive aldehydes such as formaldehyde, acetaldehyde, substituted acetaldehyde analogs such as 3. Cl-acetaldehyde as well as higher heraldologists of acetaldehyde such as e.g. Transfer Propanal.
  • reactive aldehydes such as formaldehyde, acetaldehyde, substituted acetaldehyde analogs such as 3.
  • Cl-acetaldehyde as well as higher heraldologists of acetaldehyde such as e.g. Transfer Propanal.
  • I also like bifunctional carbonyl compounds such as Glutardialdehyde and polyhydroxycarbonyl compounds such as e.g.
  • these carbonyl compounds and the cyanohydrin compounds derived therefrom have great hydrophilicity. Thus, they can easily be separated from many other cyanohydrins or aldehydes by extraction, advantageously with water or aqueous buffer, from water-immiscible organic solvents.
  • a further advantage is that the cyanohydrins formed from the cyanide scavengers e.g. can be easily saponified to the corresponding ⁇ -hydroxy acids and thus themselves valuable compounds
  • the process according to the invention is suitable for cyanohydrins which are accepted as substrates by the enzymes, but especially for those which are
  • the initial cyanohydrin concentration can be between 50 and 1000 mM.
  • Carbonyl compound is one tenth to two molar equivalents based on the initial concentration of the cyanohydrin.
  • the inventive method can be carried out at a temperature between -30 ° and 90 ° C, preferably at room temperature.
  • the process according to the invention can be carried out in all reaction media in which the synthesis reaction in the presence of oxynitrilase to chiral cyanohydrins is also described. These are aqueous, aqueous organic and organic solvents that are saturated with aqueous buffers or with water.
  • aqueous, aqueous organic and organic solvents that are saturated with aqueous buffers or with water.
  • the method according to the invention can be carried out with both the native and with modified enzymes.
  • modified enzymes is advantageous.
  • the enzymes are therefore advantageously immobilized by adsorption, by ion binding or by covalent binding on supports and by methods which are described in numerous numbers in the relevant literature.
  • the method is also particularly easy to transfer into a continuously working and technically simple method.
  • An advantageous variant consists in firstly removing the carbonyl compound used as the cyanide scavenger or the cyanohydrin formed therefrom by extraction.
  • Suitable are aqueous buffers with an acidic pH in which the auxiliary compounds used accumulate, and organic non-water-miscible solvents in which the cyanohydrin and the carbonyl compound formed during the cleavage accumulate.
  • Suitable organic solvents are, for example, chlorinated hydrocarbons, aliphatic hydrocarbons, aromatic hydrocarbons, and also aliphatic and aromatic ethers, esters and alcohols.
  • the cyanohydrin and the carbonyl compound formed during the cleavage can be separated via the bisulfite adduct of the carbonyl compounds, as described in
  • Another way to separate cyanohydrin and cabonyl compound is to mix the mixture with solvents such as. B. pentane, hexane, isooctane or similar solvents. Since the cyanohydrin compounds in these solvents are almost insoluble, whereas the carbonyl compounds are soluble, the cyanohydrin can also be isolated using this variant.
  • solvents such as. B. pentane, hexane, isooctane or similar solvents. Since the cyanohydrin compounds in these solvents are almost insoluble, whereas the carbonyl compounds are soluble, the cyanohydrin can also be isolated using this variant.
  • the catalyst was filtered off, the organic phase was extracted three times with 50 ml of 10 mM citrate buffer pH 4.0, the organic phase was dried with sodium sulfate and then the solvent was evaporated off under reduced pressure. The remaining light brown oily substance was washed three times with 50 ml of ice-cold pentane and then taken up again with 20 ml of pentane.
  • the (S) -mandelic acid nitrile crystallized from this mixture at -18 ° C in the freezer.
  • optical purity of the (S) -mandelic acid nitrile was determined by gas chromatography both from the reaction solution and from the purified (S) -mandelic acid nitrile. Enantiomeric excess of the crude solution: 94.2%
  • Trifluoroacetyl derivatives of almond acid nitrile on one Lipodex B separation phase 25 m * 0.32 mm from Macherey-Nagel.
  • the derivatization was carried out as follows:
  • Example 2 1.3 g (10 mmol) of (R / S) mandelonitrile were dissolved in 100 ml of 25% methanolic citrate buffer of pH 4.5, with 0.44 g (10 mmol) of acetaldehyde and 5 ml of (R) - Oxynitrilase (8.5 mg protein / ml) added. The mixture was then stirred at room temperature until a constant rotary value was established, the (S) -mandelic acid nitrile and the benzaldehyde were then extracted from the aqueous phase with chloroform and the latter was separated off with saturated sodium bisulfite solution (pH 3.5). After drying with sodium sulfate and evaporation of the solvent, the residue was mixed with 10 ml of pentane. The (S) -mandelic acid nitrile crystallized from this mixture at -18 ° C in the freezer.
  • Example 2 74 mg (0.5 mmol) (R / S) - para-hydroxy-mandelonitrile with 22 mg (0.5 mmol) acetaldehyde in 10 ml citrate buffer of pH. 4.5 dissolved and mixed with (S) -oxynitrilase from Sorghum bicolor immobilized on Eupergit C. The reaction was complete after about 45 minutes.
  • the derivatization was carried out as follows:
  • Example 4 200 ml of 200 mM (R / S) -meta- methoxy-mandelonitrile and 125 mM acetaldehyde were reacted. The reaction was complete after 6 hours.
  • Example 4 100 ml of 200 mM (R / S) -meta-phenoxy-mandelonitrile and 125 mM acetaldehyde
  • optical purity was determined by correlating the specific rotation with literature data from F. Effenberger et al. OS 37 01 383, which is a 98% ee of (R) -meta-phenoxy-mandelonitrile

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Microbiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biotechnology (AREA)
  • Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Analytical Chemistry (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
EP19920924554 1991-12-04 1992-12-03 Verfahren zur herstellung von optisch aktiven cyanhydrinen durch racemattrennung in gegenwart von oxynitrilasen Withdrawn EP0576638A1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19914139987 DE4139987C1 (enExample) 1991-12-04 1991-12-04
DE4139987 1991-12-04

Publications (1)

Publication Number Publication Date
EP0576638A1 true EP0576638A1 (de) 1994-01-05

Family

ID=6446261

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19920924554 Withdrawn EP0576638A1 (de) 1991-12-04 1992-12-03 Verfahren zur herstellung von optisch aktiven cyanhydrinen durch racemattrennung in gegenwart von oxynitrilasen

Country Status (4)

Country Link
EP (1) EP0576638A1 (enExample)
AU (1) AU4028893A (enExample)
DE (1) DE4139987C1 (enExample)
WO (1) WO1993011255A1 (enExample)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AT396252B (de) * 1991-10-31 1993-07-26 Chemie Linz Gmbh Enzymatisches verfahren zur enantioselektiven herstellung optisch aktiver cyanhydrine
US5241087A (en) * 1992-03-09 1993-08-31 Bend Research, Inc. Enantiomeric enrichment of cyanohydrins
DE19529116A1 (de) * 1995-08-08 1997-03-06 Chemie Linz Deutschland Gmbh I (S)-Hydroxynitrillyase aus Hevea brasiliensis
DE19824491A1 (de) * 1998-06-02 1999-12-09 Bayer Ag Verfahren zur stereoselektiven Herstellung von substituierten Cyclohexylcyanhydrinen

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1593260A1 (de) * 1966-09-19 1969-09-25 Becker Dr Wolfgang Verfahren und Katalysator zur Darstellung von Cyanhydrinen sowie Verfahren zur Darstellung des Katalysators

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9311255A1 *

Also Published As

Publication number Publication date
DE4139987C1 (enExample) 1993-04-15
AU4028893A (en) 1993-06-28
WO1993011255A1 (de) 1993-06-10

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