NO127374B - - Google Patents
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- NO127374B NO127374B NO03130/70A NO313070A NO127374B NO 127374 B NO127374 B NO 127374B NO 03130/70 A NO03130/70 A NO 03130/70A NO 313070 A NO313070 A NO 313070A NO 127374 B NO127374 B NO 127374B
- Authority
- NO
- Norway
- Prior art keywords
- dehydrotetracycline
- fermentation
- lla
- aureofaciens
- chloro
- Prior art date
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- 239000004098 Tetracycline Substances 0.000 claims description 15
- 235000019364 tetracycline Nutrition 0.000 claims description 15
- 150000003522 tetracyclines Chemical class 0.000 claims description 15
- 241000186984 Kitasatospora aureofaciens Species 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 8
- 235000015097 nutrients Nutrition 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 229940040944 tetracyclines Drugs 0.000 claims description 4
- 238000010564 aerobic fermentation Methods 0.000 claims description 3
- 244000005700 microbiome Species 0.000 claims description 3
- NTNBLKOKJNSQQA-XCLVFQIOSA-N (4s,4ar,5r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5-dihydro-4h-tetracene-2-carboxamide Chemical compound C1=CC(O)=C2C(O)=C(C(=O)[C@@]3(O)[C@H]([C@@H](C(C(C(N)=O)=C3O)=O)N(C)C)[C@H]3O)C3=C(C)C2=C1 NTNBLKOKJNSQQA-XCLVFQIOSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 238000000855 fermentation Methods 0.000 description 18
- 230000004151 fermentation Effects 0.000 description 18
- CYDMQBQPVICBEU-UHFFFAOYSA-N chlorotetracycline Natural products C1=CC(Cl)=C2C(O)(C)C3CC4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-UHFFFAOYSA-N 0.000 description 14
- CYDMQBQPVICBEU-XRNKAMNCSA-N chlortetracycline Chemical compound C1=CC(Cl)=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-XRNKAMNCSA-N 0.000 description 14
- 229960002180 tetracycline Drugs 0.000 description 11
- 229930101283 tetracycline Natural products 0.000 description 11
- 239000004099 Chlortetracycline Substances 0.000 description 10
- 229960004475 chlortetracycline Drugs 0.000 description 10
- 235000019365 chlortetracycline Nutrition 0.000 description 10
- 239000003242 anti bacterial agent Substances 0.000 description 8
- 229940088710 antibiotic agent Drugs 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 6
- LJVDOBHBFMLPMI-XRNKAMNCSA-N (4s,4as,5as,6s,12ar)-7-bromo-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC(Br)=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O LJVDOBHBFMLPMI-XRNKAMNCSA-N 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000002054 inoculum Substances 0.000 description 4
- 230000003115 biocidal effect Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- UUBKWODOINKONV-UHFFFAOYSA-N 5-(furan-2-yl)-3h-1,3,4-oxadiazole-2-thione Chemical class O1C(S)=NN=C1C1=CC=CO1 UUBKWODOINKONV-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 2
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 2
- 235000011130 ammonium sulphate Nutrition 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- BIGYLAKFCGVRAN-UHFFFAOYSA-N 1,3,4-thiadiazolidine-2,5-dithione Chemical compound S=C1NNC(=S)S1 BIGYLAKFCGVRAN-UHFFFAOYSA-N 0.000 description 1
- 235000017060 Arachis glabrata Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 235000010777 Arachis hypogaea Nutrition 0.000 description 1
- 235000018262 Arachis monticola Nutrition 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 235000019733 Fish meal Nutrition 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 1
- 235000019764 Soybean Meal Nutrition 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000001166 ammonium sulphate Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000004467 fishmeal Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 239000004455 soybean meal Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25C—PROCESSES FOR THE ELECTROLYTIC PRODUCTION, RECOVERY OR REFINING OF METALS; APPARATUS THEREFOR
- C25C3/00—Electrolytic production, recovery or refining of metals by electrolysis of melts
- C25C3/06—Electrolytic production, recovery or refining of metals by electrolysis of melts of aluminium
- C25C3/20—Automatic control or regulation of cells
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25C—PROCESSES FOR THE ELECTROLYTIC PRODUCTION, RECOVERY OR REFINING OF METALS; APPARATUS THEREFOR
- C25C3/00—Electrolytic production, recovery or refining of metals by electrolysis of melts
- C25C3/06—Electrolytic production, recovery or refining of metals by electrolysis of melts of aluminium
- C25C3/08—Cell construction, e.g. bottoms, walls, cathodes
- C25C3/12—Anodes
- C25C3/125—Anodes based on carbon
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/02—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance
- G01N27/04—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating resistance
- G01N27/041—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating resistance of a solid body
-
- H—ELECTRICITY
- H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
- H05B—ELECTRIC HEATING; ELECTRIC LIGHT SOURCES NOT OTHERWISE PROVIDED FOR; CIRCUIT ARRANGEMENTS FOR ELECTRIC LIGHT SOURCES, IN GENERAL
- H05B7/00—Heating by electric discharge
- H05B7/02—Details
- H05B7/06—Electrodes
- H05B7/08—Electrodes non-consumable
- H05B7/085—Electrodes non-consumable mainly consisting of carbon
- H05B7/09—Self-baking electrodes, e.g. Söderberg type electrodes
-
- 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
- Y02P10/00—Technologies related to metal processing
- Y02P10/25—Process efficiency
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- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Electrochemistry (AREA)
- Physics & Mathematics (AREA)
- Organic Chemistry (AREA)
- Metallurgy (AREA)
- Materials Engineering (AREA)
- Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Plasma & Fusion (AREA)
- Discharge Heating (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Fremgangsmåte for fremstilling av forbindelser av tetracyclinserien. Process for the preparation of compounds of the tetracycline series.
Oppfinnelsen vedrører en ny fremgangsmåte for fremstilling av forbindelser The invention relates to a new method for producing compounds
av tetracyclinserien, nemlig det bred-spekt- of the tetracycline series, namely the broad-spectrum
rede antibiotikum tetracyclin, klortetracyclin og bromtetracyclin. ready antibiotic tetracycline, chlortetracycline and bromotetracycline.
Disse tetracycliner har formelen: These tetracyclines have the formula:
hvor Z er hydrogen, klor eller brom. Disse where Z is hydrogen, chlorine or bromine. These
tetracycliner er tidligere blitt fremstillet tetracyclines have previously been prepared
ved aerobisk fermentering av et vandig by aerobic fermentation of an aqueous
næringsmedium med en mikroorganisme nutrient medium with a microorganism
av arten S. aureofaciens under kontrollerte of the species S. aureofaciens during controlled
forhold med hensyn til innholdet av klorid conditions with regard to the content of chloride
og/eller bromidioner i mediet. and/or bromide ions in the medium.
I overensstemmelse med . foreliggende oppfinnelse fremstilles disse tetracycliner med formelen I ved biologisk hydrering av et tilsvarende 5a(lla)-dehydrotetracyclin med formelen: In accordance with . according to the present invention, these tetracyclines with the formula I are prepared by biological hydrogenation of a corresponding 5a(lla)-dehydrotetracycline with the formula:
hvor Z har den ovenfor angitte betydning, ved aerobisk fermentering av et vandig næringsmedium med en mikroorganisme av arten S. aureofaciens. where Z has the above meaning, by aerobic fermentation of an aqueous nutrient medium with a microorganism of the species S. aureofaciens.
Disse 5a (1 la) -dehydrotetracycliner som har formelen II er selv nye' antibiotika, som fremstilles ved en fermenteringsprosess,, som er beskrevet i norsk patent nr. 103 090i av samme dato som nærværende patent. Som beskrevet mer detaljert i patent nr. 103 090, omfatter disse nye antibiotika 7-klor-5a'(.lla)-dehydrotetracyclin, 5 a-(lla)dehydrotetracyclin og 7-brom-5a.(ll-a)-dehydrotetracyclin, og.de fremstilles under skikkete fermenteringsforhold ved hjelp av visse mutantstammer av S. aureofaciens, hvorav enkelte er gitt betegnelsen S1308, S1308—29, S1308—VI 46 og S1308— V237, og kulturer av disse er deponert i American Type Culture Collection i Wash> ington D. C, hvor de er gitt ATCC-rekke-følgenumrene 12748, 12749, 12750 og 12751. These 5a (1 la)-dehydrotetracyclines having the formula II are themselves new antibiotics, which are produced by a fermentation process, which are described in Norwegian patent no. 103 090i of the same date as the present patent. As described in more detail in Patent No. 103,090, these new antibiotics include 7-chloro-5a'(.lla)-dehydrotetracycline, 5a-(lla)dehydrotetracycline and 7-bromo-5a.(lla)-dehydrotetracycline, and.they are prepared under suitable fermentation conditions by means of certain mutant strains of S. aureofaciens, some of which have been designated S1308, S1308—29, S1308—VI 46, and S1308—V237, and cultures of which are deposited in the American Type Culture Collection at Wash. > ington D. C, where they are given ATCC serial numbers 12748, 12749, 12750 and 12751.
Den biologiske aktivitet av disse 5a-(11a)-dehydrotetracycliner er forholdsvis lav. Som følge av at de nye mutantstammer av S. aureofaciens som danner disse nye antibiotika, er høy-produserende stammer, som ofte fremstiller så meget som 9000— 10 000 gamma pr. milliliter av 7-klor-5a-(lla)-dehydrotetracycliner, er det gjort forsøk på å omdanne disse antibiotika til antibiotika som er i besittelse av den ønskete bred-spektrete antibakterielle aktivitet. The biological activity of these 5a-(11a)-dehydrotetracyclines is relatively low. As a result, the new mutant strains of S. aureofaciens that form these new antibiotics are high-producing strains, often producing as much as 9,000-10,000 gamma per milliliters of 7-chloro-5a-(lla)-dehydrotetracyclines, attempts have been made to convert these antibiotics into antibiotics possessing the desired broad-spectrum antibacterial activity.
Foreliggende oppfinnelse tilveiebringer det ønskete resultat ved en biologisk omdannelse av disse nye antibiotika til- det ønskete bred-spektrede antibiotikum. På den i det følgende spesielt angitte måte omdannes således 7-klor-5a(lla)-dehydrotetracyclin til klortetracyclin, 5a(lla)-dehydrotetracyclin omdannes, tili tetracyclin og 7-brom-5a(l!la)-dehydrotetracyclim omdannes-til bromtetracyclin. The present invention provides the desired result by a biological transformation of these new antibiotics into the desired broad-spectrum antibiotic. In the manner specified below, 7-chloro-5a(lla)-dehydrotetracycline is thus converted into chlorotetracycline, 5a(lla)-dehydrotetracycline is converted into tetracycline and 7-bromo-5a(lla)-dehydrotetracycline is converted into bromotetracycline .
Fremgangsmåten ifølge oppfinnelsen-utføres ved at de nye antibiotika tilsettes et fermenteringsssystem hvor der anvendes vanlige stammer av S. aureofaciens. Når således 7-klor-5a (1 la) -dehydrotetracyclin tilsettes til et vanlig fermenteringssystem,, hvor der anvendes vanlige klortetracyclin-frembringende stammer av S. aureofaciens, så omdannes det til klortetracyclin. Omdannelsen på denne måten er langt fra fullstendig, men har vist seg i de fleste til-feller å føre til en omdannelse' i. området fra 18 % opp til 48 %. The method according to the invention is carried out by adding the new antibiotics to a fermentation system where common strains of S. aureofaciens are used. Thus, when 7-chloro-5a (1 la)-dehydrotetracycline is added to a common fermentation system, where common chlortetracycline-producing strains of S. aureofaciens are used, it is converted to chlortetracycline. The transformation in this way is far from complete, but has been shown in most cases to lead to a transformation in the range from 18% up to 48%.
Når 7-brom-5a(lia)-dehydrotetracyclin tilsettes til et fermenteringssystem, hvor der anvendes de vanlige stammer av S. aureofaciens, omdannes dette på lignende måte til bromtetracyclin. When 7-bromo-5a(lia)-dehydrotetracycline is added to a fermentation system, where the usual strains of S. aureofaciens are used, this is converted in a similar way to bromotetracycline.
Likeledes omdannes 5a(lla)-dehydrotetracyclin under de samme forhold til 'tetracyclin. Likewise, 5a(11a)-dehydrotetracycline is converted under the same conditions to 'tetracycline.
Forholdene ved fermenteringen er gene-relt de samme som for de nå for tiden kjen-te fremgangsmåter for fremstilling av klor-itetracyclin og tetracyclin ved fermentering med den unntagelse at det nye antibiotikum tilsettes, fortrinnsvis ved begynnelsen 'av fermenteringen. Fermenteringsmediet inneholder de vanlige næringsstoffer og mlneralsubstanser. Skikkete- næringssub-stanser som kan tilveiebringe disse nød-vendi<g>e- stoffer, omfatter stivelse, dekstro-■se, rørsukker, glukose, melasse, soyabønne-mel, jordnøttmel, gjær, kjøttekstrakt, pep-■ton, ammoniumsulfat, urinstoff, maisut-lutningsvæske, «distillers solubles», fiske-,mel og andre vanlige stoffer. De anorganis-ke salter omfatter slike stoffer som kal-siumkarbonat, ammoniumsulfat, ammo-niumklorid, natriumdihydrogenfosfat og de forskjellige sporelementer som mangan, kobolt, sink,.kobber, jern og. lignende. The conditions for the fermentation are generally the same as for the currently known methods for the production of chlorotetracycline and tetracycline by fermentation, with the exception that the new antibiotic is added, preferably at the beginning of the fermentation. The fermentation medium contains the usual nutrients and mineral substances. Suitable nutrients that can provide these necessary substances include starch, dextrose, cane sugar, glucose, molasses, soybean meal, peanut meal, yeast, meat extract, peptone, ammonium sulfate, urea, corn leaching liquid, "distillers solubles", fish meal and other common substances. The inorganic salts include substances such as calcium carbonate, ammonium sulphate, ammonium chloride, sodium dihydrogen phosphate and the various trace elements such as manganese, cobalt, zinc, copper, iron and the like.
De andre generelle fermenteringsforhold, som hydrogenionkonsentrasjonen, temperaturen, tiden, luftningsgraden, fremstillingen av inokulatet, steriliseringen, inokuleringen og lignende er som vanlige og kan være av lignende art som de som anvendes ved fremstillingen av klortetracyclin, som vist i USA patent nr. 2 482 055, og for fremstillingen av tetracyclin som-er vist i TJ. S. patent nr. 2 734 018. The other general fermentation conditions, such as the hydrogen ion concentration, the temperature, the time, the degree of aeration, the preparation of the inoculum, the sterilization, the inoculation and the like are as usual and may be of a similar nature to those used in the preparation of chlortetracycline, as shown in United States Patent No. 2,482 055, and for the preparation of tetracycline which is shown in TJ. S. Patent No. 2,734,018.
Utvinningen av klortetracyclinet og tetracyclinet fra fermenteringsvæsken er likeledes som vanlig og er derfor ikke nød-vendig å omtales nærmere, da forskjellige fremgangsmåter for utvinning av disse antibiotika fra férmenteringsvæskene- er tidligere' offentliggjort. Bromtetracyclin- kan utvinnes på lignende-måte-. The extraction of the chlortetracycline and the tetracycline from the fermentation liquid is likewise as usual and is therefore not necessary to be described in more detail, as different methods for the extraction of these antibiotics from the fermentation liquids have previously been published. Bromotetracycline can be extracted in a similar way.
Med hensyn til de eksempler, som føl-ger, skal' bemerkes at enkelte av fermente-ringsforsøkene ble utført i nærvær av visse kloreringshemmende stoffer, såkalte inhibitorer, dvs. 2,5-dimercapto-l,3,4,-tiadiazo-ler og 2-(2-furyl)-5-mercapto-l,3,4-oksa-diazoler. Disse inhibitorer medfører den With regard to the examples that follow, it should be noted that some of the fermentation experiments were carried out in the presence of certain chlorination-inhibiting substances, so-called inhibitors, i.e. 2,5-dimercaptol-1,3,4,-thiadiazoles and 2-(2-furyl)-5-mercapto-1,3,4-oxa-diazoles. These inhibitors cause it
.virkning at forholdet mellom klortetracyclin og tetracyclin endres, ved den normale klortetracyclinfermentering, slik at der .effect that the ratio between chlortetracycline and tetracycline changes, in the normal chlortetracycline fermentation, so that there
dannes en stor mengde av tetracyclin. På a large amount of tetracycline is formed. On
i,denne måten er det lettere å overvåke dan-nelsen, av klortetracyclin som skyldes dets omdannelse fra 7-klor-5a(lia)-dehydrotetracyclin, da der ved fravær av slike inhibitorer vil kunne inntre en uforutsett øk- in this way it is easier to monitor the formation of chlortetracycline which is due to its conversion from 7-chloro-5a(lia)-dehydrotetracycline, since in the absence of such inhibitors an unforeseen increase
ning av klortetracyclin ved omdannelsen! ning of chlortetracycline during the conversion!
av 7-klor-5a(1 la) -dehydrotetracyclin. of 7-chloro-5a(11a)-dehydrotetracycline.
Oppfinnelsen skal beskrives mer detaljert i de følgende eksempler. The invention will be described in more detail in the following examples.
Eksempel 1 : Example 1 :
Der ble fremstillet et fermenterings-medium av følgende sammensetning: A fermentation medium of the following composition was produced:
Etter steriliseringen av mediet inokuleres After the sterilization of the medium is inoculated
25 ml av mediet i en 250 ml Erlenmeyer-kolbe med et vegetativt inokulat av S. aureofaciens (stamme S77). Der tilsettes 100 25 ml of the medium in a 250 ml Erlenmeyer flask with a vegetative inoculum of S. aureofaciens (strain S77). 100 is added
deler pr. million av 2,5-dimerkapto-l,3,4-tiadiazol og 500 gamma pr. ml av 7-klor-5a-(lla)-dehydrotetracyclin og forgjæringen parts per million of 2,5-dimercapto-1,3,4-thiadiazole and 500 gamma per ml of 7-chloro-5a-(lla)-dehydrotetracycline and the pre-fermentation
utføres i 120 timer ved 25° C på en roter-ende rysteinnretning. Mesken prøves fluor-ometrisk på klortetracyclin og det viser seg is carried out for 120 hours at 25° C on a rotating shaker. The mash is tested fluorometrically for chlortetracycline and it shows
at økningen ved den fluorometriske prøve that the increase in the fluorometric test
som følge av tilsetningen av 7-klor-5a(ll-a)-dehydrotetracyclin andrar til 258 gamma pr. ml, hvilket- representerer 48 % av as a result of the addition of 7-chloro-5a(ll-a)-dehydrotetracycline changes to 258 gamma per ml, which represents 48% of
den teoretiske omdannelse av 7-klor-5a-(11a)-dehydrotetracyclin til klortetracyclin. the theoretical conversion of 7-chloro-5a-(11a)-dehydrotetracycline to chlorotetracycline.
Eksempel 2: Fremgangsmåten etter det foregående eksempel anvendes med den eneste unn tagelse at der tilsettes. 10 deler pr. million av 2- (2-furyl) -5-merkapto-l,3,4-oksadiazol til mediet som kloreringsinhibitor. Øknin-,gen ved den fluorometriske prøve for klor-tetracyclimet som følge av tilsetningen av 7-klor-5a (i lia)-dehydrotetracyclin andrar .til 170 gamma pr., ml, hvilket representerer ;34' % av den teoretiske omdannelse av det tilsatte 7-klor-5a(lla)-dehydrotetracylin til klortetracyclin.. Example 2: The procedure according to the preceding example is used with the only unn assumption that it is added. 10 parts per million of 2-(2-furyl)-5-mercapto-1,3,4-oxadiazole to the medium as a chlorination inhibitor. The increase in the fluorometric test for the chlorotetracyclime as a result of the addition of 7-chloro-5a (in 1a)-dehydrotetracycline changes to 170 gamma per ml, which represents ;34% of the theoretical conversion of the added 7-chloro-5a(lla)-dehydrotetracycline to chlorotetracycline..
Eksempel 3: Fremgangsmåten, etter eksempel 1 anvendes med unntagelse av at der tilsettes 5a (lia)-dehydrotetracyclin til fermente-ringssystemet, og der anvendes ikke noen inhibitor. Mediet inokuleres derpå med et vegetativt inokulat av S. aureofaciens (stamme S77). Omdannelse av det tilsatte 5a(lla)-dehydrotetracyclin til tetracyclin Example 3: The procedure according to example 1 is used with the exception that 5a (11a)-dehydrotetracycline is added to the fermentation system, and no inhibitor is used. The medium is then inoculated with a vegetative inoculum of S. aureofaciens (strain S77). Conversion of the added 5a(lla)-dehydrotetracycline to tetracycline
•er omtrent 35 % fullstendig. •is about 35% complete.
Eksempel 4: Fremgangsmåten etter eksempel 1 anvendes med den unntagelse at der tilsettes 7-brom-5a(lla)-dehydrotetracyclin til fer-menteringssystemet. Mediet inokuleres med et vegetativt inokulat av S. aureofaciens (stamme S77). Omdannelsen av det tilsatte 7-brom-5a( lia)-dehydrotetracyclin til bromtetracyclin er ca. 30 % fullstendig. Example 4: The procedure according to example 1 is used with the exception that 7-bromo-5a(lla)-dehydrotetracycline is added to the fermentation system. The medium is inoculated with a vegetative inoculum of S. aureofaciens (strain S77). The conversion of the added 7-bromo-5a(lia)-dehydrotetracycline to bromotetracycline is approx. 30% complete.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT2115069 | 1969-08-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO127374B true NO127374B (en) | 1973-06-12 |
Family
ID=11177470
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO03130/70A NO127374B (en) | 1969-08-22 | 1970-08-17 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US3624261A (en) |
| JP (1) | JPS4815975B1 (en) |
| BE (1) | BE755140A (en) |
| CH (1) | CH510241A (en) |
| DE (1) | DE2040854C3 (en) |
| FR (1) | FR2058897A5 (en) |
| GB (1) | GB1268619A (en) |
| NL (1) | NL7012133A (en) |
| NO (1) | NO127374B (en) |
| SE (1) | SE371734B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4122294A (en) * | 1976-12-28 | 1978-10-24 | Jury Fedorovich Frolov | Method of and device for forming self-baking electrode |
| IT1243899B (en) * | 1989-11-14 | 1994-06-28 | Elkem Technology | PROCEDURE AND MEANS FOR THE CONTINUOUS PRODUCTION OF COAL BODIES. |
| CN1908239B (en) * | 2005-08-02 | 2011-03-09 | 高德金 | Method of testing voltage drop of conductive material component using aluminum cell great current |
| DE102015223692A1 (en) | 2015-11-30 | 2017-06-01 | Sms Group Gmbh | Back status monitoring of a self-baking electrode |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1751177A (en) * | 1928-09-26 | 1930-03-18 | Norske Elektrokemisk Ind As | Process in the manufacture of self-baking electrodes |
| US3513245A (en) * | 1968-11-22 | 1970-05-19 | Air Reduction | Method and apparatus for joining shell sections of soderberg electrodes |
-
0
- BE BE755140D patent/BE755140A/en unknown
-
1970
- 1970-08-12 US US63251A patent/US3624261A/en not_active Expired - Lifetime
- 1970-08-17 NO NO03130/70A patent/NO127374B/no unknown
- 1970-08-17 SE SE7011174A patent/SE371734B/xx unknown
- 1970-08-17 NL NL7012133A patent/NL7012133A/xx not_active Application Discontinuation
- 1970-08-18 DE DE2040854A patent/DE2040854C3/en not_active Expired
- 1970-08-18 FR FR7030236A patent/FR2058897A5/fr not_active Expired
- 1970-08-21 CH CH1255870A patent/CH510241A/en not_active IP Right Cessation
- 1970-08-22 JP JP45073800A patent/JPS4815975B1/ja active Pending
- 1970-08-24 GB GB40607/70A patent/GB1268619A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| CH510241A (en) | 1971-07-15 |
| SE371734B (en) | 1974-11-25 |
| GB1268619A (en) | 1972-03-29 |
| NL7012133A (en) | 1971-02-24 |
| US3624261A (en) | 1971-11-30 |
| FR2058897A5 (en) | 1971-05-28 |
| DE2040854C3 (en) | 1980-03-20 |
| DE2040854A1 (en) | 1971-03-04 |
| DE2040854B2 (en) | 1979-07-05 |
| BE755140A (en) | 1971-02-22 |
| JPS4815975B1 (en) | 1973-05-18 |
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