WO2004007741A1 - Procede de production d'un compose $g(b)-aminonitrile optiquement actif et d'un compose amide isomere actif de celui-ci - Google Patents

Procede de production d'un compose $g(b)-aminonitrile optiquement actif et d'un compose amide isomere actif de celui-ci Download PDF

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WO2004007741A1
WO2004007741A1 PCT/JP2003/008826 JP0308826W WO2004007741A1 WO 2004007741 A1 WO2004007741 A1 WO 2004007741A1 JP 0308826 W JP0308826 W JP 0308826W WO 2004007741 A1 WO2004007741 A1 WO 2004007741A1
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production method
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Noriyuki Ito
Shigeru Kawano
Yoshihiko Yasohara
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Kaneka Corporation
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    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/24—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton
    • C07C255/29—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton containing cyano groups and acylated amino groups bound to the carbon skeleton
    • 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
    • C12P13/02—Amides, e.g. chloramphenicol or polyamides; Imides or polyimides; Urethanes, i.e. compounds comprising N-C=O structural element or polyurethanes
    • 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
    • C12P41/007—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 by reactions involving acyl derivatives of racemic amines

Definitions

  • the present invention relates to a method for producing an optically active 3-aminonitrile compound which is useful as a raw material for pharmaceuticals, agricultural chemicals and the like or as a synthetic intermediate.
  • the method for producing the optically active 0-aminonitrile compound includes a chemical method and a biochemical method.
  • a chemical method for producing an optically active 0-aminonitrile compound is a method in which an optically active aminoalcohol is used as a raw material, a protecting group is introduced into an amino group, and then cyanation is performed using sodium cyanide (J . N at. Prod., 65, 29-31, 2002) have been reported.
  • this method cannot be said to be industrially advantageous because it uses expensive optically active amino alcohol as a raw material and has a problem in safety of sodium cyanide.
  • the biochemical method is generally considered to be industrially advantageous because the reaction can be carried out under mild conditions and does not easily cause side reactions such as hydrolysis of nitrile. There have been no reports on the production of 3-aminonitrile compounds. Summary of the Invention
  • An object of the present invention is to provide a new method for biochemically and efficiently producing an optically active aminonitrile compound useful as a raw material for pharmaceuticals, agricultural chemicals and the like or as a synthetic intermediate.
  • the present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, have found no enzyme having an activity to stereoselectively hydrolyze a racemic or amide compound of monoaminoethrile having low optical purity.
  • the source has been discovered and the invention has been completed. That is, the present invention provides a compound represented by the general formula (I):
  • R 2 represents an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms or an alkynyl group having 2 to 8 carbon atoms, and R 2 represents
  • the amide compound of 0-aminonitrile which is a raw material of the present invention, has the general formula (I): Is represented by In the formula (I), represents an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, or an alkynyl group having 2 to 8 carbon atoms.
  • the alkyl group having 1 to 8 carbon atoms may be linear or branched. Examples thereof include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butynole group, and an isobutynole group. Group, sec-butynole group, tert-butynole group, pentynole group, hexyl group, heptyl group, octyl group and the like.
  • alkoxy group having 1 to 8 carbon atoms examples include an alkoxy group in which an alkyl moiety is the above-described alkyl group.
  • alkenyl group having 2 to 8 carbon atoms examples include a butyl group and an aryl group.
  • alkynyl group having 2 to 8 carbon atoms examples include an ethynyl group and a propynyl group.
  • the alkyl group, alkoxy group, alkenyl group and alkynyl group may have a substituent, and examples of the substituent include a halogen atom (a fluorine atom, a chlorine atom, a bromine atom and an iodine atom), a hydroxyl group, an amino group and a nitro group. And the like.
  • a halogen atom a fluorine atom, a chlorine atom, a bromine atom and an iodine atom
  • a hydroxyl group an amino group and a nitro group.
  • R 2 is an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkynyl group having 2 to 8 carbon atoms, and 6 carbon atoms. 1 to 14 aryl groups or heterocyclic residues having 5 to 14 carbon atoms.
  • the alkyl group, alkoxy group, alkenyl group, and alkynyl group of R 2 may be linear or branched, and the same groups as those described above can be mentioned.
  • Examples of the aryl group having 6 to 14 carbon atoms include a phenyl group and a naphthyl group.
  • heterocyclic residue having 5 to 14 carbon atoms examples include a pyridyl group.
  • alkyl group, alkoxy group, anorecenyl group, anorecynyl group, aryl group and heterocyclic residue of R 2 may have a substituent.
  • the same substituents as those exemplified in the above R can be mentioned.
  • R 2 is preferably an alkyl group having 1 to 8 carbon atoms, an aryl group having 6 to 14 carbon atoms, more preferably a methyl group, an n-propyl group, an isopropyl group, an isobutyl group, a t-butyl group, A pentyl group and a phenyl group, most preferably an isopropyl group.
  • the amide compound (I) of —aminonitrile described above may be in a racemic form or may have a low optical purity.
  • Racemic] 3-aminonitrile amide compound (I) can be obtained by synthesizing a racemic / 3-aminonitrile compound represented by racemic 3-aminopentanenitrile by a method described in, for example, US Pat. It can be obtained by reacting this with acid anhydride or acid chloride by the method described in (1).
  • the amide compound (III) includes both racemic forms and optically active forms. That is, the optically active amide compound (III) or a salt thereof obtained by asymmetric hydrolysis of the racemic amide compound (III) by the method of the present invention described below is included in the present invention. It is a new compound.
  • Examples of the alkyl group having 2 to 4 carbon atoms as R 3 include those corresponding to 2 to 4 carbon atoms among the above-mentioned examples of the alkyl group having 1 to 8 carbon atoms.
  • the alkyl group having 1 to 8 carbon atoms and the aryl group having 6 to 14 carbon atoms as R 4 are the same as those described above.
  • R 3 is preferably an ethyl group.
  • R 4 is preferably a methyl group, an n-propyl group, an isopropyl group, an isobutynole group, a t-butyl group, a pentyl group, or a phenyl group, and more preferably an isopropyl group.
  • the salt include a metal salt, an ammonium salt, an organic amine salt, an inorganic acid salt, an organic acid salt and the like.
  • metal salts include lithium salts and magnesium salts
  • organic amine salts include triethylamine salts and cyclohexylamine salts
  • organic acid salts include acetates and methanesulfones. Acid salts and the like can be mentioned.
  • the enzyme source having asymmetric hydrolysis activity used in the present invention may be any enzyme species having the ability to asymmetrically hydrolyze the amide compound of racemic / 3-aminonitrile represented by the above formula (I). Although not particularly limited, among them, enzymes called lipases, esterases, proteases, amidases, and acylases are particularly effective.
  • the source of such enzymes is not particularly limited, but is preferably a representative of the genus Alcaligenes (A1ca1igenes), the genus Agrobacterium grobacterium, or the genus Corynebacterium. um), Klebsiella, Nocardia, Rhodococcus, Candida, Cryptococcus, C1aV Enzyme sources derived from microorganisms belonging to the genus ispora, the genus Debarvomvces, the genus Pichia, the genus Tricosporon, and the like.
  • Alcaligenes 'Faecaris (A 1 ca 1 igenesfaeca 1 is), Agrobacterium' Ammobacterium ume faciens, Corynenoc kuterium .Ammoniagenes (C orynebacteriuma mmonia ⁇ en_es), Sierra ⁇ Planticola (K leb—siella jg 1 antic o_la) Linebacterium flovesense (C orynebacteri um f 1 av _e scens), Noka 7 rea 'Crovenorela (Nocardiagloberu 1a), Nocanoredia.
  • C andidac & ntare 1 1 ii Candita.Catenulata (C andidaeatenu 1 ata), Candida.Guiriamondi (C andidagui 1 1 iermondii), Cantigu' Moki (C andidamogii), Candida tropicaris.
  • C andidatropica 1 is), Candida versatilis (C andidaversati 1 is), Cryptococcus' Fumicoffs (Cryptococcushumico 1 us_), Cryptococcus.
  • Alcaligenes' Faecaris (A 1 ca 1 igenesfaeca 1 is) IFO 1 3 1 1 1, Agrobacterium tamefaciens (A grobacterium tumefacie ns) IF 0 1 3 2 6 3, Corynebata teredium.
  • it may be an enzyme source derived from microorganisms such as Corynebacterium flavescens (Corynebacteri um flavescens), Nocanoleia globulinera (Nocardiag 1 devisu 1a), and Nocardia asteroides (Nocardia a_steroides). Particularly preferred.
  • the enzyme source is derived from a microorganism of Nocardiaasteroides IFO3384.
  • Nocardia'globerula Nocadariagloberu1a IFO13510.
  • microorganisms can be obtained from the Fermentation Research Institute (IFO), the Microbial Microalgae Center (IAM), the Institute of Applied Microbiology, The University of Tokyo, or can be isolated from nature. Mutations can be generated in these microorganisms to obtain strains having advantageous properties by this reaction.
  • IFO Fermentation Research Institute
  • IAM Microbial Microalgae Center
  • Mutations can be generated in these microorganisms to obtain strains having advantageous properties by this reaction.
  • the enzyme source a microorganism culture obtained by culturing the microorganism in an appropriate medium can be used, and a treated product of the culture can also be used.
  • the processed product include a culture supernatant obtained by a cell collection operation such as centrifugation from a microbial culture solution, microbial cells, a crushed microbial cell, a cell-free extract obtained from the crushed product, and an immobilized bacterium. Body, purified purified enzyme, immobilized enzyme and the like.
  • Microbial cells are preferred as the enzyme source.
  • the asymmetric hydrolysis reaction is usually carried out using one kind of the enzyme source, but it is also possible to carry out the reaction by mixing two or more kinds of enzyme sources having the same ability.
  • any medium can be used as long as these microorganisms can grow.
  • the carbon source of the medium include sugars such as glucose, sucrose, and maltose; organic acids such as acetic acid, citric acid, and fumaric acid and salts thereof; and alcohols such as ethanol and glycerol.
  • the nitrogen source of the above-mentioned medium for example, various inorganic acid ammonium salts, various organic acid ammonium salts and the like can be used in addition to general natural nitrogen sources such as peptone, meat extract, yeast extract, amino acids and the like.
  • inorganic salts, trace metal salts, vitamins and the like can be added to the above-mentioned medium as needed.
  • a compound having an ester bond or an amide bond for example, it is also effective to add a / 3-aminonitrile amide compound represented by the above formula (I) to the medium as an inducer of enzyme production.
  • the microorganism may be cultured according to a conventional method. For example, it is preferable to culture at pH 4 to 10 and at a temperature of 15 to 45 ° for 6 to 96 hours.
  • an enzymatic source having an asymmetric hydrolysis activity is allowed to act on a racemic [3-aminonitrile amide compound represented by the above formula (I)] to cause optically selective hydrolysis (asymmetric hydrolysis).
  • a racemic 0-aminonitrile amide compound represented by the above formula (I) as a substrate is dissolved or suspended in a reaction solvent. Before or after the substrate is added to the reaction solvent, an enzyme source having the above-mentioned asymmetric hydrolysis ability as a catalyst is added. The reaction is performed while controlling the reaction temperature and, if necessary, the reaction pH.
  • the substrate concentration of the reaction solution is not particularly limited as long as it is between 0.01 and 50% by weight, but is preferably 0.1 to 30% by weight in consideration of productivity.
  • the enzyme concentration of the reaction solution is usually 0.01 to 50% by weight, preferably 0.05 to 30% by weight.
  • the pH of the reaction solution depends on the optimum pH of the enzyme to be used, but is generally in the range of pH 4 to 11. From the viewpoint of suppressing a decrease in yield due to chemical hydrolysis and a decrease in optical purity due to racemization, etc., it is preferable to perform the reaction at pH 5 to 9.
  • the pH changes as the hydrolysis proceeds. In this case, it is desirable to adjust the pH to an optimum value by adding an appropriate neutralizing agent, for example, an aqueous solution of sodium hydroxide, an aqueous solution of potassium hydroxide, or hydrochloric acid.
  • the reaction temperature is preferably 5 to 70 ° C, more preferably 10 to 50.
  • reaction solvent an aqueous medium such as water or a buffer (phosphate buffer, Tris buffer, glycine buffer, etc.) is usually used, but an asymmetric hydrolysis reaction can be performed even in a system containing an organic solvent. it can.
  • a buffer phosphate buffer, Tris buffer, glycine buffer, etc.
  • organic solvent examples include alcohol solvents such as methanol, ethanol, propanol, isopropanol, and butanol; and aliphatic solvents such as pentane and hexane.
  • Hydrocarbon solvents Aromatic hydrocarbon solvents such as benzene and toluene; Halogenated hydrocarbon solvents such as methylene chloride and chloroform; Ether solvents such as getyl ether and diisopropyl ether; Ester solvents such as acetone; ketone solvents such as acetone and methyl ethyl ketone; and other solvents such as acetate-tolyl.
  • the asymmetric hydrolysis reaction is preferably performed until about half the amount of the racemic amide compound (I) is hydrolyzed.
  • the reaction time is generally 1 hour to 1 week, preferably 1 to 72 hours, and it is preferable to select reaction conditions under which the reaction is completed.
  • the reaction may be interrupted at the initial stage of the reaction or may be caused to proceed excessively depending on the required optical purity and yield of the product.
  • the amide compound of the above formula (I)] is hydrolyzed stereoselectively, and the optically active / 3-aminoetrile compound (II) and the unreacted enantiomer are hydrolyzed.
  • An amide compound is formed.
  • the unreacted enantiomer amide compound is, particularly, a compound represented by the general formula (1 ′):
  • the generated optically active / 8-aminonitrile compound (II) and the unreacted enantiomeric amide compound should be isolated from the reaction mixture by a known method such as extraction, distillation, recrystallization, or column separation. Can be.
  • ⁇ ⁇ to acidic acetyl ether, diisopropyl ether, etc.
  • Ethers esters such as ethyl acetate and butyl acetate
  • hydrocarbons such as hexane, octane, and benzene
  • optically active monoamino acids formed by common solvents such as halogenated hydrocarbons such as methylene chloride.
  • Unreacted enantiomeric amide compounds can be selectively extracted while the nitrile compound (II) remains in the aqueous phase.
  • the optically active aminonitrile compound (II) remaining in the aqueous phase can be extracted and separated with a common organic solvent in the same manner, for example, after adjusting ⁇ to basicity.
  • the optical purity of the product can be measured by high-performance liquid chromatography (HPLC) using an optically active column after conversion to a derivative by acylation if necessary.
  • HPLC high-performance liquid chromatography
  • the optically active 3-aminopentane ditrinole obtained by this reaction is acylated with a benzoyl compound and then subjected to high performance liquid chromatography (HPLC) using an optical resolution column (Daicel Chemical Industry Co., Ltd., Chiral Cell OD).
  • HPLC high performance liquid chromatography
  • the unreacted enantiomeric amide compound can be hydrolyzed by an ordinary method while maintaining the optical activity, and the optically active compound obtained by the above-described asymmetric hydrolysis reaction] 3-aminonitrile compound ] -Aminonitrile compounds having a configuration opposite to that of (II).
  • Optical activity] 3-aminonitrile compound (II) can be amidated while maintaining the optical activity.
  • a target compound having higher optical purity is obtained. It is also possible.
  • optically active] 3-aminonitrile compound obtained by the present invention can be easily converted into an optically active] 3-amino acid carboxylic acid by hydrolyzing nitrile by acid treatment or the like while maintaining its optical activity.
  • Amide compounds and optically active] 3-amino acids can be produced.
  • Carrier gas Helium (lOOkPa)
  • Infrared absorption spectrum (cm- 1 ): 3288, 2968, 2934, 224, 1651, 1549, 1375, 1306, 1138, 1078, 962, 748, 621, 608.
  • the microorganisms listed in Table 1 were combined with 10 g of peptone, 10 g of meat extract, 5 g of yeast extract, and 3 g of sodium chloride (each 1 L) in sterile medium 1 Om 1 (pH 7.2).
  • the inoculated test tube was inoculated, and cultured at 30 at 2 days with reciprocal shaking. Next, 2 mL of the culture solution was taken from each test tube, the cells were collected by centrifugation, and washed once with 1 mL of 100 mM phosphate buffer (pH 7.0). The cells are suspended in 0.5 mL of lO OmM phosphate buffer (pH 7.0), and the racemic N-acetyl
  • 3-aminopentanenitrile was added to a test tube containing 2.5 mg, and reacted at 30 ° C. with shaking for 18 hours.
  • Alcal 1 genes faecai is IFO 13111 ku 88 34 R
  • Rhodococcus erythropol is IFO 12320 875 18 R
  • Rhodococcus erythropol is 1AM 1474 175 15 R
  • glucose 40 g yeast extract 3 g, diammonium hydrogen phosphate 6.5 g, potassium dihydrogen phosphate 1 g, magnesium sulfate heptahydrate 0.8 g, zinc sulfate water
  • Sterile culture medium consisting of 60 mg of hydrate, 90 mg of iron sulfate heptahydrate, 5 mg of copper sulfate pentahydrate, 1 Omg of manganese sulfate tetrahydrate, and lO Omg of sodium chloride (each per liter)
  • the cells were inoculated into a test tube containing 1 Om 1 (pH 7.0) and cultured at 30 ° C. for 2 days with reciprocal shaking.
  • Candida tropical is IFO 0618 ku 88 28 S
  • Candida versati 1 is IFO 1228 c 88 29 S
  • Infrared absorption spectrum (cm- 1 ): 3286, 2974, 2245, 1651, 1541, 1263, 242, 1136, 1095, 951, 721.
  • Example 7 Method for producing N-isopentanoyl-1-aminopentanenitrile 9.8 g of 3-aminopentanenitrile and 10.3 g of pyridine were dissolved in 10 OmL of methylene chloride, and isovaleric anhydride was added under ice-cooling. 20.5 g was added dropwise, and the mixture was stirred for 1 hour under ice cooling and for 4 hours at room temperature. After completion of the reaction, 2N hydrochloric acid 20 OmL 3 times, 2N The extract was washed three times with 20 OmL of a constant aqueous sodium hydroxide solution and once with 20 OmL of a saturated saline solution. After the washed reaction product was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure to obtain NTsopentanoyl-13-aminopentanenitrile (1.5Og). Yield 82%.
  • the microorganisms described in Table 3 were cultured as in Example 2. After taking 1 OmL of each culture solution, the cells were collected by centrifugation, and washed once with 2 mL of 10 OmM phosphate buffer (pH 7.0). The cells were suspended in 1 mL of 10 OmM phosphate buffer (pH 7.0), and added to a test tube previously filled with 37.5 ⁇ 1 of the substrate shown in Table 3 manufactured in Examples 1 and 4 to 9. The reaction was carried out with shaking at 19 ° C for 19-45 hours.
  • Substrate A (RS) -1-N-acetyl-1-3-aminopentanenitrile
  • Nocanoledia No cardiagloberula IFO 135 10 strains, 20 g of peptone, 10 g of meat extract, 5 g of yeast extract, 10 g of darcose, 3 g of sodium chloride, 1 drop of Adekinol
  • the cells were inoculated into a Sakaguchi flask containing 40 Om 1 (pH 7.2) of a sterilized medium having the following composition (per L) and cultured at 29 ° C. with reciprocal shaking for 2 days. The culture was centrifuged, and the cells were collected and washed once with 100 mL of 200 mM phosphate buffer ( ⁇ 7.0).
  • the cells were suspended in 40 mL of 20 OmM phosphate buffer (pH 7.0) to obtain a cell suspension.
  • Nokanolady completed ⁇ Grovenorella (Nocadaria_g1qberuu1a_) IFO13510 strain was cultured in the same manner as in Example 11 to prepare a cell suspension.
  • OmL of the bacterial cell suspension was added to a Sakaguchi flask containing 7.1 mmo1, and the mixture was shaken at 30 ° C for 64 hours. While reacting.
  • 3-aminopentanitrile was formed at a conversion of 28%.
  • the reaction mixture was adjusted to pH 5 by adding 2N hydrochloric acid, 3 OmL of ethyl acetate was added, and the mixture was sufficiently stirred. After centrifugation, the ethyl acetate phase was removed. After adding 2N sodium hydroxide to adjust the pH to 10, the mixture was extracted with 9 OmL of ethyl acetate. After the extraction solvent was dehydrated with anhydrous sodium sulfate, purification was carried out by distillation to obtain 139 mg of 3-aminopentanenitrinole.
  • Nocardia globulare obtained by the culture method described in Example 11 was added thereto.
  • the above cell suspension was added to a 5 L-volume jafermenter containing 30 g of racemic N-isobutylyl-3_aminopentanenitrile in advance, and the reaction was carried out with stirring at 30 ° C for 26 hours. After the completion of the reaction, the product was analyzed in the same manner as in Example 11 to find that 3-aminopentanitrile was formed at a conversion of 35%.
  • the reaction solution was adjusted to pH 4 by adding 15% sulfuric acid, and the reaction solution was extracted twice with 2.5 volumes of methylene chloride to give N- ⁇ fsobutyryl 3- 3-aminopentane nitrile. Was recovered.
  • the aqueous phase was adjusted to pH 11 using 30% sodium hydroxide, and the reaction solution was subjected to extraction using 2.5 times the volume of methylene chloride three times to recover 3-aminopentane nitrile.
  • the solvent was distilled off under reduced pressure, and 5.8 g of 3-aminopentane nitrile and 18.1 g of N-isobutyryl_-3-aminopentane nitrile were obtained. I got it.
  • Carrier gas Helium (140 kPa) Industrial applicability
  • the present invention provides an optically active aminonitrile compound and its enantiomer by reacting an enzymatic source having asymmetric hydrolysis activity to stereoselectively hydrolyze an amide compound of 0-aminonitrile.
  • Amid compounds can be produced efficiently:

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Abstract

L'invention concerne un procédé de production rentable d'un composé β-aminonitrile optiquement actif, utilisé comme produit de départ ou comme produit intermédiaire synthétique pour des médicaments, des produits chimiques pour l'agriculture, etc. L'invention concerne, en particulier, un procédé de production d'un composé β-aminonitrile optiquement actif et d'un composé amide isomère actif de celui-ci, procédé consistant à amener un composé amide β-aminonitrile, de forme racémique ou de faible pureté optique, en contact avec une source d'enzyme capable d'hydrolyse asymétrique.
PCT/JP2003/008826 2002-07-12 2003-07-11 Procede de production d'un compose $g(b)-aminonitrile optiquement actif et d'un compose amide isomere actif de celui-ci WO2004007741A1 (fr)

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AU2003280995A AU2003280995A1 (en) 2002-07-12 2003-07-11 PROCESS FOR PRODUCING OPTICALLY ACTIVE Beta-AMINONITRILE COMPOUND AND AMIDE COMPOUND AS ANTIPODE THEREOF

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JP2003047363A JP2006021999A (ja) 2002-07-12 2003-02-25 光学活性β−アミノニトリル化合物およびその対掌体アミド化合物の製造方法

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3457294A (en) * 1966-04-22 1969-07-22 Abbott Lab N-(substituted-benzoyl) aminoaceto- and aminopropionitriles
EP0654533A2 (fr) * 1993-11-18 1995-05-24 Mitsubishi Rayon Co., Ltd. Procédé de préparation de l'acide D-lactique et de L-lactamide
JP2000157294A (ja) * 1998-11-27 2000-06-13 Kanegafuchi Chem Ind Co Ltd β位に不斉炭素を持つ光学活性α−アミノ酸の製造法
WO2002088069A2 (fr) * 2001-04-30 2002-11-07 Pfizer Products Inc. Composes utiles comme intermediaires

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3457294A (en) * 1966-04-22 1969-07-22 Abbott Lab N-(substituted-benzoyl) aminoaceto- and aminopropionitriles
EP0654533A2 (fr) * 1993-11-18 1995-05-24 Mitsubishi Rayon Co., Ltd. Procédé de préparation de l'acide D-lactique et de L-lactamide
JP2000157294A (ja) * 1998-11-27 2000-06-13 Kanegafuchi Chem Ind Co Ltd β位に不斉炭素を持つ光学活性α−アミノ酸の製造法
WO2002088069A2 (fr) * 2001-04-30 2002-11-07 Pfizer Products Inc. Composes utiles comme intermediaires

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