Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Preparing compound containing saccharide radical
Reexamination Certificate
1998-11-15
2001-03-06
Prats, Francisco (Department: 1651)
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Preparing compound containing saccharide radical
C435S084000, C435S085000, C435S087000
Reexamination Certificate
active
06197552
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a process for preparing 2,6-diaminopurine-2′-deoxyriboside and 2′-deoxyguanosine. These compounds are used as materials for pharmaceuticals such as antiviral agents and the like, and particularly as starting materials for antisense drugs, which are highly desired pharmaceuticals.
2. Discussion of the Related Art
Since the yield in chemical synthesis for producing 2′-deoxyguanosine is very low, the industrial production thereof has mainly been performed via extraction of a hydrolysate of DNA (deoxyribonucleic acid). In the conventional extraction process, however, the hydrolysate of DNA contains 2′-deoxyadenosine, 2′-deoxycytidine and thymidine, in addition to the desired 2′-deoxyguanosine. Therefore, from the viewpoint of this troublesome and costly extraction step for collecting 2′-deoxyguanosine alone, the development of a more effective process has been in great demand.
SUMMARY OF THE INVENTION
Accordingly, an object of the present invention is to provide a process for producing 2,6-diaminopurine-2′-deoxyriboside and 2′-deoxyguanosine in high yield and with good efficiency.
As the result of an extensive research for establishing a process for preparing 2′-deoxyguanosine with good efficiency, the present inventors have found that:
(1) 2,6-diaminopurine-2′-deoxyriboside can be produced with good efficiency by contacting 2′-deoxyribose-1-phosphoric acid or a salt thereof and 2,6-diaminopurine or a salt thereof with a microorganism;
(2) 2,6-diaminopurine-2′-deoxyriboside can be produced with good efficiency by contacting 2′-deoxyuridine or thymidine and 2,6-diaminopurine or a salt thereof with a microorganism, in the presence of an inorganic phosphoric acid or a salt thereof, and
(3) 2′-deoxyguanosine can be produced in a high yield by putting 2,6-diaminopurine-2′-deoxyriboside, used as a substrate, produced and provided steadily and at low costs by processes (1) and (2) as described above, under the action of adenosine deaminase; and have thus completed the present invention.
Accordingly, the present invention relates to:
(1) a process for preparing 2,6-diaminopurine-2′-deoxyriboside which comprises contacting 2′-deoxyribose-1-phosphoric acid or a salt thereof and 2,6-diaminopurine with a culture of a microorganism having an ability of producing 2,6-diaminopurine-2′-deoxyriboside from 2′-deoxyribose-1-phosphoric acid or a salt thereof and 2,6-diaminopurine, and preferably belonging to a genus selected from the group consisting of Achromobacter, Agrobacterium, Acinetobacter, Alcaligenes, Arthrobacter, Aeromonas, Escherichia, Enterobacter, Erwinia, Xanthomonas, Klebsiella, Kurthia, Kluyvera, Corynebacterium, Sartina, Salmonella, Citrobacter, Pseudomonas, Streptomyces, Sporosarcina, Staphyrococcus, Serratia, Cellulomonas, Nocardia, Bacillus, Hafnia, Vibrio, Flavobacterium, Planococcus, Brevibacterium, Protaminobacter, Proteus, Haemophilus, Micrococcus, Mycoplana, Mycobacterium, Rhizobium and Rhodococcus, or of cells of the microorganism separated from said culture, or of a treatment product of said cells of the microorganism, and collecting the produced 2,6-diaminopurine-2′-deoxyriboside;
(2) a process for preparing 2,6-diaminopurine-2′-deoxyriboside which comprises contacting 2′-deoxyuridine or thymidine and 2,6-diaminopurine with a culture of a microorganism having an ability of producing 2,6-diaminopurine-2′-deoxyriboside from 2′-deoxyuridine or thymidine and 2,6-diaminopurine in the presence of an inorganic phosphoric acid or a salt thereof, and preferably belonging to a genus selected from the group consisting of Achromobacter, Agrobacterium, Acinetobacter, Alcaligenes, Arthrobacter, Aeromonas, Escherichia, Enterobacter, Erwinia, Xanthomonas, Klebsiella, Kurthia, Kluyvera, Corynebacterium, Sartina, Salmonella, Citrobacter, Pseudomonas, Streptomyces, Sporosarcina, Staphyrococcus, Serratia, Cellulomonas, Nocardia, Bacillus, Hafnia, Vibrio, Flavobacterium, Planococcus, Brevibacterium, Protaminobacter, Proteus, Haemophilus, Micrococcus, Mycoplana, Mycobacterium, Rhizobium or Rhodococcus, or of cells of the microorganism separated from said culture, or of a treatment product of said cells of the microorganism, in the presence of an inorganic phosphoric acid or a salt thereof, and collecting the produced 2,6-diaminopurine-2′-deoxyriboside; and
(3) a process for preparing 2′-deoxyguanosine which comprises preparing 2,6-diaminopurine-2′-deoxyriboside according to process (1) or (2) above, and then contacting the produced 2,6-diaminopurine-2′-deoxyriboside with an adenosine deaminase or a material containing said enzyme in an aqueous medium to produce and accumulate 2′-deoxyguanosine.
A more complete appreciation of the invention and many of the attendant advantages thereof will be readily obtained as the same becomes better understood by reference to the following detailed description.
DETAILED DESCRIPTION OF THE INVENTION
A wide variety of microorganisms may be used for the production of 2,6-diaminopurine-2′-deoxyriboside according to the present invention, insofar as they have the ability of producing 2,6-diaminopurine-2′-deoxyriboside from 2′-deoxyribose-1-phosphoric acid or a salt thereof and 2,6-diaminopurine or an ability of producing 2,6-diaminopurine-2′-deoxyriboside from 2′-deoxyuridine or thymidine and 2,6-diaminopurine in the presence of an inorganic phosphoric acid or a salt thereof. Microorganisms, for example, belonging to the genus Achromobacter, Agrobacterium, Acinetobacter, Alcaligenes, Arthrobacter, Aeromonas, Escherichia, Enterobacter, Erwinia, Xanthomonas, Klebsiella, Kurthia, Kluyvera, Corynebacterium, Sartina, Salmonella, Citrobacter, Pseudomonas, Streptomyces, Sporosarcina, Staphyrococcus, Serratia, Cellulomonas, Nocardia, Bacterium, Bacillus, Hafnia, Vibrio, Flavobacterium, Planococcus, Brevibacterium, Protaminobacter, Proteus, Haemophilus, Micrococcus, Mycoplana, Microbacterium, Rhizobium or Rhodococcus have such an ability. Specifically, examples may include the microorganisms listed below:
Achromobacter viscosus
ATCC 12448,
Agrobacterium tumefaciens
ATCC 4720,
Acinetobacter johnsonii
ATCC 9036,
Alcaligenes faecalis subsp. faecalis
ATCC 8750,
Arthrobacter oxydans
ATCC 14358,
Aeromonas salmonicida subsp. salmonicida
ATCC 14174,
Escherichia coli
ATCC 10798,
Enterobacter cloacae
ATCC 7256,
Erwinia herbicola
ATCC 1453,
Xanthomonas citri
AJ 2785 (FERM BP-6560),
Klebsiella pneumoniae
IFO 3321,
Kurthia zopfii
ATCC 6900,
Kluyvera citrophila
AJ 2626 (FERM BP-6564),
Corynebacterium acetoacidophilum
ATCC 21407,
Sartina lutea
AJ 1218 (FERM BP-6562),
Salmonella typhimurium
AJ 2636 (FERM BP-6561),
Citrobacter freundi
ATCC 8090,
Pseudomonas diminuta
ATCC 11568,
Streptomyces tanashiens
ATCC 15238,
Sporosarcina ureae
IFO 12698,
Staphyrococcus epidermidis
ATCC 155,
Serratia marcescens
ATCC 14226,
Cellulomonas flavigera
ATCC 486,
Nocardia asteroides
ATCC 19247,
Bacillus subtilis
ATCC 6633,
Hafnia alvei
ATCC 9760,
Vibrio metschnikovii
ATCC 7708,
Flavobacterium breve
ATCC 14234,
Planococcus eucinatus
AJ 1656 (FERM BP-6493),
Brevibacterium pusillum
ATCC 19096,
Protaminobacter alboflavus
ATCC 8458,
Proteus rettegeri
AJ 2770 (FERM BP-941),
Haemophilus influenzae
ATCC 9134,
Micrococcus luteus
ATCC 4698,
Mycoplana dimorpha
ATCC 4279,
Mycobacterium lacticum
ATCC 8180,
Rhizobium melilotti
AJ 2823 (FERM BP-6565) and
Rhodococcus rhodochraus
ATCC 19149.
Among the strains described above,
Xanthomonas citri
AJ 2785 is a strain having an accession number of FERM BP-6560, originally deposited at the Fermentation Research Institute, Agency of industrial Science and Technology, Ministry of International Trade and Industry (now the National Institute of Bioscience and Human-Technology, Agency of industrial Science and Technology, Ministry of International Trade a
Izawa Kunisuke
Tsuji Takashi
Yokozeki Kenzo
Ajinomoto Co. Inc.
Oblon & Spivak, McClelland, Maier & Neustadt P.C.
Prats Francisco
LandOfFree
Process for preparing... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for preparing..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for preparing... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2535053