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WO1999007873A1 - PROCEDE DE FABRICATION D'α-AMINOACIDES CYCLIQUES EXEMPTS ENANTIOMERES, OU DE LEURS DERIVES N-PROTEGES AU MOYEN D'UNE AMINOACYLASE D-SPECIFIQUE - Google Patents

PROCEDE DE FABRICATION D'α-AMINOACIDES CYCLIQUES EXEMPTS ENANTIOMERES, OU DE LEURS DERIVES N-PROTEGES AU MOYEN D'UNE AMINOACYLASE D-SPECIFIQUE Download PDF

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Publication number
WO1999007873A1
WO1999007873A1 PCT/EP1998/005087 EP9805087W WO9907873A1 WO 1999007873 A1 WO1999007873 A1 WO 1999007873A1 EP 9805087 W EP9805087 W EP 9805087W WO 9907873 A1 WO9907873 A1 WO 9907873A1
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WO
WIPO (PCT)
Prior art keywords
protected
proline
microorganisms
amino acid
source
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.)
Ceased
Application number
PCT/EP1998/005087
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German (de)
English (en)
Inventor
Martin Sauter
Oleg Werbitzky
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.)
Lonza AG
Original Assignee
Lonza AG
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 Lonza AG filed Critical Lonza AG
Priority to JP51171799A priority Critical patent/JP2002509441A/ja
Priority to AU93412/98A priority patent/AU9341298A/en
Priority to EP98946316A priority patent/EP1005563A1/fr
Priority to CA002299324A priority patent/CA2299324A1/fr
Publication of WO1999007873A1 publication Critical patent/WO1999007873A1/fr
Anticipated expiration legal-status Critical
Ceased 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
    • C12P13/00—Preparation of nitrogen-containing organic compounds
    • C12P13/04—Alpha- or beta- amino acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • 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
    • C12P13/24—Proline; Hydroxyproline; Histidine
    • 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
    • C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/10—Nitrogen as only ring hetero atom
    • 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
    • C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/10—Nitrogen as only ring hetero atom
    • C12P17/12—Nitrogen as only ring hetero atom containing a six-membered hetero ring
    • 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

Definitions

  • the present invention relates to microorganisms which are capable of one or more N-protected cyclic amino acid derivatives selected from the compounds of the general formula
  • a together with -N- and -CH represent an optionally substituted 4-, 5-, 6- or 7- membered saturated heterocyclic ring and R 1 each represents optionally substituted alkyl, alkoxy, aryl or aryloxy, in the form of the racemate or one of the optically active isomers as the only C source, as the only N source or as the only C and N source, and / or are able to hydrolyze them.
  • R 1 each represents optionally substituted alkyl, alkoxy, aryl or aryloxy, in the form of the racemate or one of the optically active isomers as the only C source, as the only N source or as the only C and N source, and / or are able to hydrolyze them.
  • D-amino acids such as D-Prohn are important intermediates for the manufacture of pharmaceuticals (J Org Chem 1994, 59, 7496-7498)
  • JP-A 01 005 488 encompasses a process for the preparation of D-amino acid acylases which, for example, hydrolyze N-benzyloxycarbonylmethionine in D-methionine, N-benzyloxycarbonyl-L-methionine being obtained.
  • JP-A 07 127 354 comprises a process for the preparation of D-proline starting from ornithine by means of microorganisms of the species Proteus mitajiri.
  • a disadvantage of this process is that on the one hand the educt ornithine is too expensive, and on the other hand that D-proline is inferior Yield is obtained
  • JP-A 92 183 399 discloses a process for the preparation of D-proline starting from (DL) -proline using microorganisms of the genus Candida or trichospora. This process also has the disadvantage that D-proline is obtained in low yield
  • the object of the present invention is to provide a simple and technically viable method for producing both N-protected cych L-amino acid derivatives and cych D-amino acids.
  • the corresponding products are to be isolated in good enantiomeric purity
  • microorganisms according to the invention can be isolated, for example, from soil samples, sludge or wastewater, in particular contaminated soil or clear sludge, with the aid of customary microbiological techniques cyclic amino acid derivatives of the general formula I, in the form of the racemate or one of the optically active isomers, __
  • the microorganisms are expediently first enriched in a corresponding liquid culture and the anaerobic or aerobic microorganisms are isolated from the culture obtained, the desired N-protected cychino amino acid derivatives as the only N source, as the only C source or as the only C and Can utilize the N source and / or are able to hydrolyze it
  • optionally substituted saturated 4-membered heterocyclic rings are azetidine.
  • optionally substituted saturated 5-membered heterocyclic rings are proline, hydroxyproline, pyrazolidine, methylpyrazolidine, imidazolidine, pyroglutamate, oxazolidine, isoxazolane, thiazolidine and triazolidine
  • optionally substituted saturated 6-membered heterocyclic rings are piperidine. 3-methylpiperidine, piperazine, pipecolin, 3-methylpiperazine, morpholine
  • R 1 in the N-protected cychino amino acid derivative of the general formula 1 means alkyl, alkoxy, aryl or aryloxy
  • Alkyl here means a substituted or unsubstituted C 1 -C alkyl group, preferably a substituted or unsubstituted C 1 -C alkyl group. Suitable substituents are, for. B hydroxy or halogens such as F, Cl. Br or J Examples of a Ci-is-alkyl group are methyl, chloromethyl, trifluoromethyl, co-hydroxyalkyl, ethyl, propyl, butyl, iso-butyl, iso-propyl and stearyl ⁇ -hydroxyalkyl group in the following means a hydroxymethyl, hydroxyethyl, Hydroxypropyl or Hydroxybutyl Group Preferably alkyl means methyl
  • Alkoxy means a substituted or unsubstituted C 1 8 alkoxy group, preferably a substituted or unsubstituted C 4 alkoxy group. Suitable substituents are, for example, the substituents mentioned for alkyl. Examples of an alkoxy group are methoxy, chloromethoxy, trifluoromethoxy, ethoxy, propoxy, butoxy, tert -butoxy, iso-butoxy and stearoxy
  • Aryloxy preferably means benzyloxy
  • the compounds of the general formula I are preferably N-protected cyclic D-amino acid derivatives
  • N-protected cyclic D-amino acid derivatives are N-protected D-proline derivatives, for example N-acetyl and / or N-benzyloxycarbonyl-D-proline (N-Z-D-proline), and N-protected D-pipecolinic acid derivatives
  • the microorganisms can use, for example, sugar, sugar alcohols, or carboxylic acids as a growth substrate as a suitable C source.
  • Hexose for example glucose and fructose, pentoses, for example ribose, or disaccharides, for example sucrose
  • Amino carboxylic acids, mono-, di - or tricarboxylic acids or their salts can be used.
  • mannitol or glycerin can be used as sugar alcohols.
  • proline, glutamate, lysine, glycine or their salts can be used as amino carboxylic acids.
  • Acetic acid, acetate, lactic acid can be used as mono-, di- or tricarboxylic acids. Lactate, succinic acid, succinate, malic acid, malate, citric acid, citrate or their salts are used
  • the microorganisms can, for example, ammonium, nitrate, urea as a suitable N source.
  • the media customary in the art for example the medium described in Table 1, can preferably be used as the selection and growth medium.
  • the medium described in Table 1 is preferably used
  • the active enzymes of the microorganisms are expediently induced during the cultivation and selection.
  • An N-protected cyclic amino acid derivative according to formula I, preferably its D-isomer, is expediently used as the enzyme inducer
  • the cultivation and selection is usually carried out at a temperature of 5 to 100 ° C., expediently from 10 to 75 ° C., preferably from 15 to 40 ° C., in particular from 20 to 35 ° C. and at a pH between pH 0 and pH 12, expediently from pH 4 to 10, preferably between pH 5 and pH 9
  • microorganisms are microorganisms corresponding to the microorganisms with the designation MIS1 12, MIS125, MIS132, MIS211, MIS213, MIS221, MIS222.
  • MIS231, MIS242, MIS253 Particularly preferred are microorganisms of the genus Arthrobacter, such as the species Arthrobacter oxydans GS121, Arthrobacter sp GS132, Arthrobacter pascens or ramosus GS131 (DSM 1 1637), Arthrobacter pascens or ramosus GS134, and their variant organisms and mutant mutants GS131 were deposited on 30.06.1997 with the German Collection of Microorganisms and Zellkultur GmbH, Mascheroderweg lb, D-38124 Braunschweig, according to the Budapest Treaty under the deposit number DSM 1 1637 "Flinktionally equivalent ⁇ ⁇ arianten and mutants" are understood to mean microorganisms which are derived from the described original organisms and
  • a together with -N- and -CH and R 1 have the meaning given, comprises the reaction of a racemic N-protected cych aminosaur derivative of the general formula
  • a together with -N- and -CH and R 1 have the meaning given, by means of the microorganisms already described and / or an enzyme preparation thereof, into a cyclic D-amino acid (formula III) and / or the N- protected cychschen L-amino acid derivatives (formula II), and optionally isolation of these compounds
  • N-protected cyclic amino acid derivatives of the formula I are used as N-protected cyclic amino acid derivatives of the formula I.
  • the educts, the racemic N-protected cyclic amino acid derivatives of the general formula I such as, for example, NZ- (DL) -proline, are commercial compounds
  • biotransformation is possible with all microorganisms that utilize and / or hydrolyze an N-protected cyclic amino acid derivative in the form of the racemate or its optically active isomers as the only N source, as the only C source or as the only C and N source Enzyme extracts from these microorganisms are also suitable.
  • Biotransformation is preferably carried out with the microorganisms described above, in particular with the microorganisms described above of the species Arthrobacter pascens or ramosus GS131 (DSM 1 1637) or with their functions! equivalent variants and mutants
  • the biotransformation can be carried out with resting cells (non-growing cells which no longer require a carbon and energy source) or with growing cells under aerobic or anaerobic conditions.
  • the biotransformation is preferably carried out with resting cells under aerobic conditions
  • Biotransformation for example low-molar buffers such as low-molar phosphate buffer, Tris buffer or the medium described in Table 1.
  • the biotransformation is preferably carried out in the medium according to Table 1
  • the biotransformation is expediently carried out by adding an N-protected amino acid derivative so that the concentration does not exceed 50% by weight, preferably 20% by weight.
  • the N-protected amino acid derivative is expediently added once or continuously
  • the pH of the medium can be in a range from 3 to 12, preferably from 5 to 9.
  • the biotransformation is expediently carried out at a temperature of 10 to 70 ° C., preferably 20 to 50 ° C.
  • an N-protected cyclic amino acid derivative is converted into a cyclic D-amino acid.
  • An N-protected L-amino acid derivative is obtained.
  • the cyclic D-amino acid and the N-protected L-amino acid derivative can be obtained in good yield and Enantiomeric purity (ee greater than 98%) can be isolated
  • N-protected L-amino acid derivative obtained in this way and / or the D-amino acid obtained in this way can be isolated by customary workup methods, such as, for example, by extraction
  • Vitamin solution 1.0 ml / 1 pH 7.0
  • C and N sources were added to this basic medium
  • the isolates obtained with the method described in Example 1 (A) were multiplied in the medium described there.
  • the cells produced in this way were harvested by centrifugation and then resuspended in saline solution (8.5 g / l) and washed after resuspending in saline solution the ability to hydrolysis of N-protected cych amino acids was tested with resting cells
  • a suitable amount of cells with 25 mM N-acetyl- (DL) -proline, NZ- (DL) -proline and NZ- (DL) -pipecolinic acid or 12.5 mM N-acetyl- (DL) -pipecolinic acid incubated in buffer solution (50 mM phosphate buffer, pH 7.0) under rubble (30 ° C).
  • Figure 1 shows the reaction of MIS132 and MIS222 with N-Z- (DL) -pipecolinic acid
  • the isolates obtained with the method described in Example 1 (B) were multiplied in the medium described there.
  • the cells produced in this way were harvested by centrifugation and then resuspended in saline solution (8.5 g / l) and washed. After resuspending in saline solution the ability to hydrolysis of N-protected cycho amino acids was tested with resting cells.
  • a suitable amount of cells with 100 mM NZ-DL-proline or 50 mM NZ-DL-pipecolic acid in buffer solution (50 mM phosphate buffer, pH 7.0) below
  • GS131 In order to characterize bacterial strain GS131 in more detail, the growth of this strain was investigated with different C and N sources.
  • the basic medium described in Table 1 was used and the C sources were added to 10 g / 1 each and the N sources to a final concentration of 40 mM. The cultures were then incubated at 30 ° C. GS131 was able to utilize a wide variety of C and N sources and even showed good growth in most of the media examined.
  • Bacterial strain GS131 was grown under variation of different media components or their concentration at 30 ° C. The cells produced in this way were harvested by centrifugation and then resuspended in saline solution (8.5 g / l) and washed. After resuspending in saline solution, the ability to hydrolyze N-Z-D-proline was examined with resting cells under aerobic conditions.
  • Bacterial strain GS131 was propagated in the medium described in Example 1 (B). The cells produced in this way were harvested by centrifugation and then resuspended in saline solution (8.5 g / l) and washed. After resuspending in saline solution, the ability to Hydrolysis of N-protected cych amino acids was tested. A suitable amount of cells with the respective substrate (10 mM NZL-proline or NZD-proline or 5 mM NZL-pipecolic acid or N-ZD-pipecolic acid) in buffer solution (50 mM phosphate buffer , pH 7.0) (30 ° C.) Aliquots were removed at various times and the wetting of the substrates was monitored by HPLC
  • Figure 2 shows the enantioselectivity of D-aminoacylase from bacterial strain GS 131
  • Bacterial Strain GS131 was propagated in the medium described in Example 1 (B). The cells thus produced were harvested by centrifugation and then in saline solution (8.5 g / 1) Resuspended and washed After resuspending in saline solution, the ability to hydrolize N-protected cych amino acids was tested with resting cells.
  • NZL-pipecolic acid was then obtained by extraction three times (40 ml each) with butyl acetate. The organic phases were combined, dried over sodium sulfate and finally until evaporated to dryness After dissolving the solid in 10 ml of ethyl acetate and adding 9 ml of hexane, NZL-pipecolic acid was crystallized by cooling to a temperature ⁇ 10 ° C. After filtration and drying, 13.22 g of NZL-pipecolinic acid (64.9% of theory Th) received

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Virology (AREA)
  • Biomedical Technology (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

L'invention concerne de nouveaux micro-organismes capables d'utiliser, sous forme d'une source C unique ou d'une source N unique, ou d'une source C et N, un dérivé aminoacide cyclique N-protégé, choisi parmi des composés de formule générale (I), sous forme du racémate ou de l'un de ses isomères optiques, dans laquelle A désigne, conjointement avec -N- et -CH-, un noyau hétérocyclique saturé à 4, 5, 6 ou 7 chaînons éventuellement substitué, et R<1> désigne un alkyle, alcoxy, aryle ou aryloxy, respectivement, éventuellement substitué, et/ou capables d'hydrolyser un dérivé aminoacide cyclique N-protégé, ainsi que des extraits enzymatiques de ces produits. L'invention concerne en outre un nouveau procédé de fabrication de dérivés de L-aminoacides cycliques N-protégés et de D-aminoacides cycliques en utilisant lesdits micro-organismes.
PCT/EP1998/005087 1997-08-11 1998-08-11 PROCEDE DE FABRICATION D'α-AMINOACIDES CYCLIQUES EXEMPTS ENANTIOMERES, OU DE LEURS DERIVES N-PROTEGES AU MOYEN D'UNE AMINOACYLASE D-SPECIFIQUE Ceased WO1999007873A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP51171799A JP2002509441A (ja) 1997-08-11 1998-08-11 Ｄ−特異的アミノアシラーゼを使用するエナンチオマー的に純粋な環状α−アミノ酸およびそのＮ−保護誘導体の製造方法
AU93412/98A AU9341298A (en) 1997-08-11 1998-08-11 Method for producing cyclic alpha-amino acids free from enantiomers or their n-protected derivatives by means of d-specific aminoacylase
EP98946316A EP1005563A1 (fr) 1997-08-11 1998-08-11 PROCEDE DE FABRICATION D'alpha-AMINOACIDES CYCLIQUES EXEMPTS ENANTIOMERES, OU DE LEURS DERIVES N-PROTEGES AU MOYEN D'UNE AMINOACYLASE D-SPECIFIQUE
CA002299324A CA2299324A1 (fr) 1997-08-11 1998-08-11 Procede de fabrication d'.alpha.-aminoacides cycliques exempts enantiomeres, ou de leurs derives n-proteges au moyen d'une aminoacylase d-specifique

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CH1888/97 1997-08-11
CH188897 1997-08-11
CH286897 1997-12-12
CH2868/97 1997-12-12

Publications (1)

Publication Number Publication Date
WO1999007873A1 true WO1999007873A1 (fr) 1999-02-18

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PCT/EP1998/005087 Ceased WO1999007873A1 (fr) 1997-08-11 1998-08-11 PROCEDE DE FABRICATION D'α-AMINOACIDES CYCLIQUES EXEMPTS ENANTIOMERES, OU DE LEURS DERIVES N-PROTEGES AU MOYEN D'UNE AMINOACYLASE D-SPECIFIQUE

Country Status (5)

Country Link
EP (1) EP1005563A1 (fr)
JP (1) JP2002509441A (fr)
AU (1) AU9341298A (fr)
CA (1) CA2299324A1 (fr)
WO (1) WO1999007873A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002101003A3 (fr) * 2001-06-08 2004-02-26 Rhodia Chimie Sa Preparation stereoselective de l-acides amines cycliques

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0416282A1 (fr) * 1989-09-06 1991-03-13 Degussa Aktiengesellschaft N-Acyl-L-proline-acylase préparée microbiologiquement, procédé de sa production et son utilisation
WO1995010604A1 (fr) * 1993-10-15 1995-04-20 Chiroscience Limited Enzyme et son utilisation dans la preparation de l'acide (s) - pipecolique
EP0686698A2 (fr) * 1994-06-09 1995-12-13 Lonza Ag Procédé biotechnologique pour la préparation des acides S-alpha-aminocarboxyliques et des amides d'acides R-alpha-aminocarboxyliques
WO1997033987A1 (fr) * 1996-03-13 1997-09-18 Lonza Ag Procede de preparation de derives de d-proline proteges en n

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0416282A1 (fr) * 1989-09-06 1991-03-13 Degussa Aktiengesellschaft N-Acyl-L-proline-acylase préparée microbiologiquement, procédé de sa production et son utilisation
WO1995010604A1 (fr) * 1993-10-15 1995-04-20 Chiroscience Limited Enzyme et son utilisation dans la preparation de l'acide (s) - pipecolique
EP0686698A2 (fr) * 1994-06-09 1995-12-13 Lonza Ag Procédé biotechnologique pour la préparation des acides S-alpha-aminocarboxyliques et des amides d'acides R-alpha-aminocarboxyliques
WO1997033987A1 (fr) * 1996-03-13 1997-09-18 Lonza Ag Procede de preparation de derives de d-proline proteges en n

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002101003A3 (fr) * 2001-06-08 2004-02-26 Rhodia Chimie Sa Preparation stereoselective de l-acides amines cycliques
US7425530B2 (en) 2001-06-08 2008-09-16 Rhodia Chimie Stereoselective preparation of cyclic L-amino acids
CN100482800C (zh) * 2001-06-08 2009-04-29 罗狄亚化学公司 环状l-氨基酸的立体选择性制备

Also Published As

Publication number Publication date
CA2299324A1 (fr) 1999-02-18
JP2002509441A (ja) 2002-03-26
EP1005563A1 (fr) 2000-06-07
AU9341298A (en) 1999-03-01

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