EP1656456A1 - Verfahren zur trennung optischer isomere einer geschützten aminosäure - Google Patents
Verfahren zur trennung optischer isomere einer geschützten aminosäureInfo
- Publication number
- EP1656456A1 EP1656456A1 EP04748942A EP04748942A EP1656456A1 EP 1656456 A1 EP1656456 A1 EP 1656456A1 EP 04748942 A EP04748942 A EP 04748942A EP 04748942 A EP04748942 A EP 04748942A EP 1656456 A1 EP1656456 A1 EP 1656456A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- sidechain
- carboxyl
- protected
- chosen
- protected aminoacid
- 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- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/37—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from fungi
- C07K14/38—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from fungi from Aspergillus
-
- 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
- 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
- C12P41/003—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions
- C12P41/005—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions by esterification of carboxylic acid groups in the enantiomers or the inverse reaction
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Definitions
- the present invention relates to a method of enzy- matically separating optical isomers of a protected aminoacid chosen from the group of protected natural and non-natural aminoacids , wherein an enzyme is contacted with a mixture comprising R and S isomers of the protected aminoacid to be separated .
- Separation of optical isomers is an important procedure in industrial synthesis of aminoacids . Low cost and optical purity (enantiomeric excess ) are important parameters . For this reason , enzymes are used because of their selectivity . To keep cost down, it is generally preferred not to use pure enzyme but rather enzyme preparations .
- the obj ective of the present invention is to provide a method according to the preambule, allowing the separation at low cost and excellent optical purity ( e . e ) .
- the present invention is characterized in that the protected aminoacid is a (non-sidechain- carboxyl ) -protected aminoacid having the general formula ( I ) HR 1 N-CR 2 - (CH ) n -C (0) ZR 3 I wherein - R 1 is an amino-protective group or hydrogen; - R 2 is a side chain; - n is a number chosen from 0, 1, and 2; - ZR 3 is a carboxy-protective group where Z is chosen from 0 or NH; and R 1 and R 3 may be integrated, forming a heterocy-oul (non-sidechain-carboxyl) -protected ring, the ring backbone comprising 5 to 8 atoms; the (non-sidechain-carboxyl) -protected
- the (non-sidechain carboxy) deprotected product carries the now free carboxylgroup.
- the examples below demonstrate the excellent results obtained with the method according to the invention.
- the term 'enzymatically separating' is to be understood to increase the number and/or magnitude of properties in which the enzymatically converted product and starting material differ. That is, a physical separation in terms of space is not a requirement, as this may occur later, for example in case of synthesis.
- a preferred set of substrates having the formula (I) are characterized in that R 3 , with Z is O, represents a group chosen from the set consisting of a branched or unbranched (C ⁇ -C 4 ) alkylgroup, a phenylgroup, and an (C ⁇ -C 4 ) alkylphenylgroup; each of which may be substituted or not with one or more of halogen atoms, car- boxy, hydroxy and aminogroup.
- Z. is NH
- R 3 is as defined above, or hydrogen.
- the nature of the side chain R 2 is believed to be of no particular relevance for the enzymatic reaction.
- the molecular weight of the (non-sidechain- carboxyl) -protected aminoacid (I) is less than 500.
- the enzyme is derived from Aspergillus sp., preferably chosen from Aspergillus melleus and Aspergillus oryzae.
- the (non- sidechain-carboxyl) -protected aminoacid is chosen from a hy- dantoin derivative and diketopiperazine derivative.
- the enzyme is immobilized, and more preferrably comprised in a CLEA.
- a CLEA is a cross-linked enzyme aggregate. This pro- vides a cost-effective solution, allowing easy separation of the biocatalytic CLEA and the solution in which the separation is performed.
- the present invention will now be illustrated with reference to the following examples.
- use is made of a crude enzyme preparation from Aspergillus, said enzyme preparation having an aminoacylase activity and available from Fluka.
- This preparation also contains an hydrolase activity exploited in the present invention, more specifically an esterase and/or an amidase activity. Immobilization of enzyme was performed by making a CLEA, according to standard procedures (Cao L. et al, Org. Lett. 2, pp. 1361-1364, (2000) ) .
- a 10 m solution of D, L-phenylglycine amide (D,L- PGA) was prepared in 5 ml of 50 mM TRIS buffer pH 7.5. Enzymatic reaction was started by addition of 50 U of A inoa- cylase I from Aspergillus melleus (Fluka, 1.3U/mg) and performed at permanent stirring at room temperature. Periodically, samples were taken, diluted by eluent in order to stop enzymatic reaction and subjected to chiral HPLC analysis (Crownpack CR+, pH 2, 25°C) . After 4 hours reaction reached 50.6% conversion, and further hydrolysis was negligible (51% after 18 hours) . Optical purity of remaining D-phenylglycine amide was 99+%, optical purity of converted L-phenylglycine was 99%.
- D,L-2-aminobutyric acid ethyl ester was prepared by esterification of D, L-2-aminobutyric acid (D,L-ABA, obtained from ACROS) in ethanol in the presence of sulfuric acid. The excess of ethanol was evaporated under reduced pressure. The obtained D,L-ABAE sulfuric salt (24 mmol) was dissolved in 100 ml water and pH was adjusted to 6.7 using NaOH. The reaction was started by adding 1 g of Aminoacylase I from Aspergillus melleus (Fluka, 1.3U/mg) and was performed at the room temperature, at continuous stirring and automated pH-control.
- Aminoacylase I from Aspergillus melleus
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Analytical Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Mycology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
NL1023767A NL1023767C1 (nl) | 2003-06-27 | 2003-06-27 | Werkwijze voor het scheiden van optische isomeren van een beschermd aminozuur. |
PCT/RU2004/000244 WO2005001107A1 (en) | 2003-06-27 | 2004-06-25 | Method of separating optical isomers of a protected aminoacid |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1656456A1 true EP1656456A1 (de) | 2006-05-17 |
Family
ID=33550490
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP04748942A Withdrawn EP1656456A1 (de) | 2003-06-27 | 2004-06-25 | Verfahren zur trennung optischer isomere einer geschützten aminosäure |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP1656456A1 (de) |
NL (1) | NL1023767C1 (de) |
RU (1) | RU2006100556A (de) |
WO (1) | WO2005001107A1 (de) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8934512B2 (en) * | 2011-12-08 | 2015-01-13 | Binoptics Corporation | Edge-emitting etched-facet lasers |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP3647065B2 (ja) * | 1994-07-20 | 2005-05-11 | 株式会社武蔵野化学研究所 | 光学活性アラニンの製造方法 |
JP3160879B2 (ja) * | 1996-01-30 | 2001-04-25 | 田辺製薬株式会社 | 光学活性アミノ酸誘導体の製法 |
-
2003
- 2003-06-27 NL NL1023767A patent/NL1023767C1/nl not_active IP Right Cessation
-
2004
- 2004-06-25 WO PCT/RU2004/000244 patent/WO2005001107A1/en active Application Filing
- 2004-06-25 EP EP04748942A patent/EP1656456A1/de not_active Withdrawn
- 2004-06-25 RU RU2006100556/13A patent/RU2006100556A/ru not_active Application Discontinuation
Non-Patent Citations (1)
Title |
---|
See references of WO2005001107A1 * |
Also Published As
Publication number | Publication date |
---|---|
RU2006100556A (ru) | 2007-08-27 |
WO2005001107A1 (en) | 2005-01-06 |
NL1023767C1 (nl) | 2004-12-28 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
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17P | Request for examination filed |
Effective date: 20060127 |
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AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): DE FR NL |
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DAX | Request for extension of the european patent (deleted) | ||
RBV | Designated contracting states (corrected) |
Designated state(s): DE FR NL |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN |
|
18W | Application withdrawn |
Effective date: 20100326 |