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WO2001009365A1 - Procede de preparation de 2-cyano-5-hydroxypyrazine - Google Patents

Procede de preparation de 2-cyano-5-hydroxypyrazine Download PDF

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Publication number
WO2001009365A1
WO2001009365A1 PCT/EP2000/006862 EP0006862W WO0109365A1 WO 2001009365 A1 WO2001009365 A1 WO 2001009365A1 EP 0006862 W EP0006862 W EP 0006862W WO 0109365 A1 WO0109365 A1 WO 0109365A1
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WO
WIPO (PCT)
Prior art keywords
cyanopyrazine
iam
microorganisms
cyano
serratia
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/EP2000/006862
Other languages
English (en)
Inventor
Andreas Kiener
Toru Magasawa
Eva Maria Urban
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 AU62753/00A priority Critical patent/AU6275300A/en
Publication of WO2001009365A1 publication Critical patent/WO2001009365A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • 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

Definitions

  • the invention relates to a novel process for the microbiological preparation of 2-cyano-5- hydroxypyrazine of the formula
  • 2-Cyano-5-hydroxypyrazine is a promising intermediate for the preparation of analogues of pyrazineamide for the treatment of tuberculosis (Cynamon et al , J Med Chem 39, 1996, 3394-3400)
  • EP-A 0 558 022 describes the conversion of 3-cyanopyridine to 3-cyano-6-hydroxypyridine by means of microorganisms of the species Micrococcus morrhuae (IAM 171 1), Comamonas acidovorans (NCIMB 9289), Comamonas testosteroni (ATCC 1 1996), Pseudomonas dacunhae (ATCC 13261), Pseudomonas maltophila (ATCC 13637), Pseudomonas chlororaphis (IFO 3904), Pseudomonas hydantoinophilum (FER.MP-4347), Pseudomonas putida (ATCC 21244), Sarcina lutea (ATCC 9341), Serratia liquefaciens (IFO 12979), Serratia marcescens (IFO 3054), Serratia marcescens (IFO 12648) and Xanthobacter flavus (
  • Microorganisms used in the present invention are selected from the genera Alcaligenes, Comamonas, Delftia, Pseudomonas, Serratia, Acinetobacter, Agrobacterium, Brevibacterium, Micrococcus, Kocuria and Rhodococcus Alternatively, also the relevant enzyme extracts derived from the microorganisms mentioned above can be used Methods for recovering the enzyme extracts from the cells such as ultrasonic- or frenchpress-method are known to those skilled in the art
  • Possible microorganisms for the biotransformation belonging to the genus Alcaligenes are Alcaligenes faecalis or Alcaligenes xylosoxydans as exemplified by the species Alcaligenes faecalis IAM 1446 (Research Institute of Applied Microbiology, Tokyo, Japan), Alcaligenes faecalis IAM 12369 (Research Institute of Applied Microbiology, Tokyo, Japan), Alcaligenes faecalis IFO 14479 (Institute for Fermentation Osaka, Japan), Alcaligenes xylosoxydans IFO 13495 (Institute for Fermentation Osaka, Japan) and Alcaligenes sp IFO 14130 (Institute for Fermentation Osaka, Japan)
  • Comamonas testosteroni Possible microorganisms for the biotransformation belonging to the genus Comamonas are Comamonas testosteroni as exemplified by the species Comamonas testosteroni IAM 12419 (Research Institute of Applied Microbiology, Tokyo, Japan) and Comamonas acidovorans (Pseudomonas fluorescens)
  • Pseudomonas fluorescens or Pseudomonas putida are Pseudomonas fluorescens or Pseudomonas putida as exemplified by the species Pseudomonas fluorescens TN5 (Isolation described in Nagasawa et al , Biosci Biotech Biochem 58(4), 1994, 665-668), this one was also identified belonging to Delftia acidovorans, formerly Comamonas acidovorans, Pseudomonas putida 870, and Pseudomonas putida CRl-1 (Isolation described in Nagasawa et al , J Biol Chem 257 (22), 1982, 13749-13756)
  • Possible microorganisms for the biotransformation belonging to the genus Serratia are Serratia marcescens or Serratia fonticola as exemplified by
  • Serratia marcescens IAM 1162 (Research Institute of Applied Microbiology, Tokyo, Japan), Serratia marcescens IAM 12143 (Research Institute of Applied Microbiology, Tokyo, Japan), Serratia marcescens IAM 13543 (Research Institute of Applied Microbiology, Tokyo, Japan), Serratia fonticola IAM 13541 (Research Institute of Applied Microbiology, Tokyo, Japan)
  • Acinetobacter cycloclastes Possible microorganisms for the biotransformation belonging to the genus Acinetobacter are Acinetobacter cycloclastes as exemplified by
  • Acinetobacter cycloclastes IAM 1013 (Research Institute of Applied Microbiology, Tokyo, Japan)
  • Agrobacterium Possible microorganisms belonging to genus Agrobacterium are Agrobacterium tumefaciens as exemplified by
  • Brevibacterium acetylicum or Brevibacterium lines as exemplified by Brevibacterium acetylicum IAM 1790 (Research Institute of Applied Microbiology, Tokyo, Japan) and Brevibacterium lines IAM 12437 (Research Institute of Applied Microbiology, Tokyo, Japan)
  • Micrococcus roseus Possible microorganisms for the biotransformation belonging to the genus Micrococcus are Micrococcus roseus or Micrococcus varians as exemplified by
  • Micrococcus roseus IAM 13 15 (Research Institute of Applied Microbiology, Tokyo, Japan), this one was also identified belonging to Kocuria rosea and Micrococcus varians IAM 13594 (Research Institute of Applied Microbiology, Tokyo, Japan)
  • Rhodococcus Possible microorganisms for the biotransformation belonging to the genus Rhodococcus are Rhodococcus luteus or Rhodococcus sp as exemplified by
  • Rhodococcus luteus NCIB 1 1743 National Collection of Industrial Bacteria, Aberdeen, UK.
  • Rhodococcus sp NCIB 10554 National Collection of Industrial Bacteria, Aberdeen, UK
  • Preferred microorganisms for the biotransformation are microorganisms of the species Serratia fonticola IAM 13541 , deposited at the DSMZ (Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, Mascheroder Weg lb, D-38124 Braunschweig) on June 4, 1999 under DSM No 12855, Delftia acidovorans (Comamonas acidovorans, Pseudomonas fluorescens TN 5), deposited at the DSMZ on June 4, 1999 under DSM No 12853, Kocuria rosea (Micrococcus roseus) IAM 1315, deposited at the DSMZ on June 4, 1999 under DSM No 12854, and its functional equivalent variants and mutants
  • the most preferred microorganisms for the biotransformation are Serratia fonticola IAM 13541 (DSM 12855) and Kocuria rosea (Micrococcus roseus) JAM 13 15 (DSM 12854)
  • variants and mutants designates microorganisms having essentially the same properties and functions as the original microorganism Such variants and mutants can be formed incidentally e g by UV radiation
  • ONPG O-nitrophenylgalactosidase
  • ADH alcohol dehydrogenase
  • LDC lactate decarboxylase
  • microorganisms are usually cultivated before the biotransformation takes place However, it is also possible that cultivation and biotransformation is performed during the growth of the
  • the cultivation is conveniently performed in standard media known to the skilled artisan such as for example low molecular weight phosphate buffers, HEPES buffers, citrate buffers, borate buffers, Tris-HCl or Glycine-NaOH containing conventional nutrients like the conventional carbon-, nitrogen-, energy- and mineral sources, or in complete media
  • Preferred media are mineral salt media with a defined carbon- and nitrogen source, for example complete media containing, for example, yeast extract as exemplified in example 1 Cultivation is expediently effected under aerobic conditions at a temperature from 15 °C to 50 °C and at a pH from 4 0 to 9 0 over a period of up to 96 h
  • the effective enzymes are induced before the biotransformation takes place
  • Effective inducers are, e g , nicotinic acid, pyrazinecarboxylic acid, 3-cyanopyridine, 2-cyanopyrazine, nicotinamide or pyrazine amide
  • the biotransformation can be performed with growing or with resting cells, the biotransformation with resting cells is preferred
  • Appropriate concentration of 2-cyanopyrazine is between 0 1 % by weight and 30 % by weight, preferably between 0 5 % by weight and 15 % by weight
  • the biotransformation is expediently carried out under aerobic conditions at a temperature from 15 °C to 50 °C, preferably from 25 °C to 45 °C, and at pH values in the range of 4 0 to 9 0, preferably 5 0 to 8 0
  • the biotransformation can be performed in standard media known in the art as mentioned above or in complete media such as "Nutrient Yeast Broth” (NYB)
  • the standard reaction mixture (2 ml) was composed of 0 4 ml of an 1 M aqueous solution of 2-cyanopyrazine, 0 6 ml of 0 3 M potassium phosphate buffer (pH 6 5) and 1 ml of the concentrated cell suspension obtained after centrifugation from 10 ml of the culture broth mentioned above
  • the reaction started with the addition of the 2-cyanopyrazine as substrate and was carried out at 35 °C for 30 minutes
  • Table 1 shows the results of the hydroxylation activity of each microorganism
  • the optimum temperature was tested in 2 ml of the standard reaction mixture (see Example 1 ) containing 90 mM sodium citrate-citrate buffer (pH 5 5) and 200 mM 2-cyanopyrazine and 68.2 mg of the respective cells (dry weight) The reaction was performed for 30 min on a shaker (180 rpm's) at various temperatures. As shown in Fig 5, the optimum temperature was determined to be 50 °C

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (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)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

L'invention concerne un procédé de préparation de 2-cyano-5-hydroxypyrazine de la formule (I), qui consiste à faire réagir 2-cyanopyrazine de la formule (II) avec un micro-organisme choisi parmi les genres Alcaligenes, Comamonas, Delftia, Pseudomonas, Serratia, Acinetobacter, Agrobacterium, Brevibacterium, Micrococcus et Rhodocossus, ou avec des extraits d'enzymes correspondants dérivés de l'un ou l'autre de ces micro-organismes.
PCT/EP2000/006862 1999-07-29 2000-07-18 Procede de preparation de 2-cyano-5-hydroxypyrazine Ceased WO2001009365A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU62753/00A AU6275300A (en) 1999-07-29 2000-07-18 Process for the preparation of 2-cyano-5-hydroxypyrazine

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
EP99114840.4 1999-07-29
EP99114840 1999-07-29
EP99120770.5 1999-10-20
EP99120770 1999-10-20
US18667900P 2000-03-03 2000-03-03
US60/186,679 2000-03-03

Publications (1)

Publication Number Publication Date
WO2001009365A1 true WO2001009365A1 (fr) 2001-02-08

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2000/006862 Ceased WO2001009365A1 (fr) 1999-07-29 2000-07-18 Procede de preparation de 2-cyano-5-hydroxypyrazine

Country Status (2)

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AU (1) AU6275300A (fr)
WO (1) WO2001009365A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106222239A (zh) * 2016-08-09 2016-12-14 西南科技大学 重金属铀污染的可视化检测方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0558022A2 (fr) * 1992-02-26 1993-09-01 Mitsubishi Chemical Corporation Procédé de préparation de 3-cyano-6-hydroxypyridine
EP0578137A1 (fr) * 1992-07-08 1994-01-12 Lonza Ag Procédé microbiologique de la production d'acide carboxylique de 5-hydroxy-2-pyrazine

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0558022A2 (fr) * 1992-02-26 1993-09-01 Mitsubishi Chemical Corporation Procédé de préparation de 3-cyano-6-hydroxypyridine
EP0578137A1 (fr) * 1992-07-08 1994-01-12 Lonza Ag Procédé microbiologique de la production d'acide carboxylique de 5-hydroxy-2-pyrazine

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
APPL. MICROBIOL. BIOTECHNOL. (1997), 48(2), 174-176 *
DATABASE CHEMABS [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; HURH, BYUNGSERK ET AL: "Purification and characterization of nicotinic acid dehydrogenase from Pseudomonas fluorescens TN5", XP002147136, retrieved from STN Database accession no. 121:199124 *
DATABASE CHEMABS [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; WIESER, M. ET AL: "Bioconversion of 2- cyanopyrazine to 5- hydroxypyrazine -2-carboxylic acid with Agrobacterium sp. DSM 6336", XP002147135, retrieved from STN Database accession no. 127:261755 *
J. FERMENT. BIOENG. (1994), 78(1), 19-26 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106222239A (zh) * 2016-08-09 2016-12-14 西南科技大学 重金属铀污染的可视化检测方法

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Publication number Publication date
AU6275300A (en) 2001-02-19

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