DD237677A5 - PROCESS FOR PREPARING ALPHA-ERGOKRYPTIN - Google Patents
PROCESS FOR PREPARING ALPHA-ERGOKRYPTIN Download PDFInfo
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- DD237677A5 DD237677A5 DD85276810A DD27681085A DD237677A5 DD 237677 A5 DD237677 A5 DD 237677A5 DD 85276810 A DD85276810 A DD 85276810A DD 27681085 A DD27681085 A DD 27681085A DD 237677 A5 DD237677 A5 DD 237677A5
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- German Democratic Republic
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- fermentation
- ergokryptine
- ergokryptin
- medium
- culture
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- 238000004519 manufacturing process Methods 0.000 title claims abstract 3
- 238000000855 fermentation Methods 0.000 claims abstract description 10
- 230000004151 fermentation Effects 0.000 claims abstract description 10
- 238000000034 method Methods 0.000 claims abstract description 7
- 229950001817 alpha-ergocryptine Drugs 0.000 claims abstract description 5
- YDOTUXAWKBPQJW-UHFFFAOYSA-N alpha-Ergocryptinine Natural products C1=CC(C=2C(N(C)CC(C=2)C(=O)NC2(C(=O)N3C(C(N4CCCC4C3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=CNC3=C1 YDOTUXAWKBPQJW-UHFFFAOYSA-N 0.000 claims abstract description 4
- YDOTUXAWKBPQJW-NSLWYYNWSA-N alpha-ergocryptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=CNC3=C1 YDOTUXAWKBPQJW-NSLWYYNWSA-N 0.000 claims abstract description 4
- 244000005700 microbiome Species 0.000 claims abstract description 4
- 241000124224 Claviceps paspali Species 0.000 claims abstract 2
- 238000002360 preparation method Methods 0.000 claims description 3
- 229960003133 ergot alkaloid Drugs 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 238000009413 insulation Methods 0.000 claims 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 1
- 239000002609 medium Substances 0.000 description 10
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 229930006000 Sucrose Natural products 0.000 description 6
- 239000005720 sucrose Substances 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 4
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 4
- 235000011130 ammonium sulphate Nutrition 0.000 description 4
- 229940041514 candida albicans extract Drugs 0.000 description 4
- 235000015097 nutrients Nutrition 0.000 description 4
- 239000012138 yeast extract Substances 0.000 description 4
- ZHJGWYRLJUCMRT-UHFFFAOYSA-N 5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide Chemical compound C=1C=CC=C(C(F)(F)F)C=1C(C)OC(=C(S1)C(N)=O)C=C1N(C1=C2)C=NC1=CC=C2CN1CCN(C)CC1 ZHJGWYRLJUCMRT-UHFFFAOYSA-N 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 3
- 241000221760 Claviceps Species 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 239000008272 agar Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 3
- 235000019796 monopotassium phosphate Nutrition 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 3
- RZLVQBNCHSJZPX-UHFFFAOYSA-L zinc sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Zn+2].[O-]S([O-])(=O)=O RZLVQBNCHSJZPX-UHFFFAOYSA-L 0.000 description 3
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- NHJPVZLSLOHJDM-UHFFFAOYSA-N azane;butanedioic acid Chemical compound [NH4+].[NH4+].[O-]C(=O)CCC([O-])=O NHJPVZLSLOHJDM-UHFFFAOYSA-N 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- WRUGWIBCXHJTDG-UHFFFAOYSA-L magnesium sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Mg+2].[O-]S([O-])(=O)=O WRUGWIBCXHJTDG-UHFFFAOYSA-L 0.000 description 2
- 229940061634 magnesium sulfate heptahydrate Drugs 0.000 description 2
- RVUXIPACAZKWHU-UHFFFAOYSA-N sulfuric acid;heptahydrate Chemical compound O.O.O.O.O.O.O.OS(O)(=O)=O RVUXIPACAZKWHU-UHFFFAOYSA-N 0.000 description 2
- -1 zinc cations Chemical class 0.000 description 2
- XJOOMMHNYOJWCZ-UHFFFAOYSA-N Agroclavine Natural products C1=CC(C2C=C(C)CN(C2C2)C)=C3C2=CNC3=C1 XJOOMMHNYOJWCZ-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000044541 Paspalum vaginatum Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241001149258 Sporobolus alterniflorus Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 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 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000004362 fungal culture Methods 0.000 description 1
- 230000035784 germination Effects 0.000 description 1
- 239000003630 growth substance Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- SURQXAFEQWPFPV-UHFFFAOYSA-L iron(2+) sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Fe+2].[O-]S([O-])(=O)=O SURQXAFEQWPFPV-UHFFFAOYSA-L 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000011218 seed culture Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- YWYZEGXAUVWDED-UHFFFAOYSA-N triammonium citrate Chemical compound [NH4+].[NH4+].[NH4+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O YWYZEGXAUVWDED-UHFFFAOYSA-N 0.000 description 1
- 210000003934 vacuole Anatomy 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
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
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/18—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
- C12P17/182—Heterocyclic compounds containing nitrogen atoms as the only ring heteroatoms in the condensed system
- C12P17/183—Heterocyclic compounds containing nitrogen atoms as the only ring heteroatoms in the condensed system containing an indolo[4,3-F,G]quinoleine nucleus, e.g. compound containing the lysergic acid nucleus as well as the dimeric ergot nucleus
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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)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Es wird ein Verfahren zur Herstellung von a-Ergokryptin beansprucht, das dadurch gekennzeichnet ist, dass man den Mikroorganismus Claviceps paspali DSM 2836 kultiviert und das gebildete a-Ergokryptin nach Beendigung der Fermentation isoliert.A process for the production of α-ergokryptine is claimed, which comprises cultivating the microorganism Claviceps paspali DSM 2836 and isolating the α-ergokryptin formed after the end of the fermentation.
Description
Ziel der Erfindung ist die Suche nach einem Verfahren zur Herstellung von reinem a-Ergokryptin.The aim of the invention is the search for a process for the preparation of pure a-ergokryptin.
Er wurde nun gefunden, daß ein Pilzstamm Claviceps spec. α-Ergokryptin in hohen Ausbeuten und neben Spuren von Agroclavin und ansonsten frei von anderen Ergotalkaloiden in das Kulturmedium ausscheidet. Dieser Stamm Claviceps spec, wurde aus einem Mutterkorn eines wild wachsenden Schlickgrases der Species Spartina alterniflora isoliert. Er hat die interne Bezeichnung SCHERING, MBCE 5227 und ist bei der deutschen Sammlung für Mirkoorganismen unter der Nummer DSM 2836 hinterlegt.He was now found that a fungus strain Claviceps spec. α-ergocryptine in high yields and in addition to traces of agroclavin and otherwise free from other ergot alkaloids in the culture medium excreted. This strain Claviceps spec., Was isolated from an ergot of a wild growing silt grass of the species Spartina alterniflora. It has the internal name SCHERING, MBCE 5227 and is deposited with the German collection for microorganisms under the number DSM 2836.
Der Stamm bildet auf Agrarmedien mit Saccharose als Kohlenstoffquelle und Asparagin, als Stickstoffquelle flache, gelbliche Kolonien aus kompakten Mycel. Der Koloniendurchmesser beträgt nach 7 Tagen Kulturzeit 2 bis 3cm und nach 20 Tagen Kulturzeit 6 bis 8cm.The strain forms flat, yellowish colonies of compact mycelium on agricultural media with sucrose as the carbon source and asparagine, as a source of nitrogen. The colon diameter is 2 to 3cm after 7 days culture time and 6 to 8cm after 20 days culture time.
Auf Agar-Nährmedium mit Saccharose als Kohlenstoffquelle und Ammoniumsuccinat oder Ammoniumeitrat als Stickstoffquelle bildet der Pilz langsam wachsende, gewölbte und von der Agar-Oberfläche leicht abgehobene gelblich braune Kolonien. Die Kolonie hat eine durch Luftmycelbildung rauhe, insidiöse Oberfläche. Der Kolonienrand ist ausgefranst. Der Durchmesser der Kolonie beträgt nach 14 Tagen 2 bis 3cm und nach 30 Tagen 6 bis 7cm. Neben hyphenartigen Mycel treten kurze, runde bis unregelmäßig geformte, häufig in Ketten liegende und mit stark lichtbrechenden Vakuolen angefüllte Zellen auf (sklerotialer Zelltyp). Der Hyphendurchmesser beträgt 3 bis 4pm. Die vakuolisierten Zellen haben einen Durchmesser von 6 bis 10 pm und eine Länge von 10 bis 25pm.On agar nutrient medium with sucrose as a carbon source and ammonium succinate or ammonium citrate as a nitrogen source, the fungus forms slow-growing, domed and yellowish brown colonies slightly off the agar surface. The colony has a rough, insidious surface due to aerial mycelia. The colonial margin is frayed. The diameter of the colony is 2 to 3cm after 14 days and 6 to 7cm after 30 days. In addition to hypheniform mycelium occur short, round to irregularly shaped, often in chains and filled with highly refractive vacuoles cells (sclerotial cell type). The hyphal diameter is 3 to 4pm. The vacuolated cells have a diameter of 6 to 10 pm and a length of 10 to 25pm.
Das erfindungsgemäße Verfahren wird unter Bedingungen durchgeführt, die man überlicherweise zur Anzucht von Pilzkulturen für eine Stoffwechselsynthese anwendet. So werden zunächst in allgemein üblichen Vorversuchen die günstigsten Fermentionsbedingungen, wie z. B. die Auswahl des günstigsten Nährmediums, der technischen Bedingungen wie Temperatur, Belüftung pH-Wert und der optimalen Zeiten für die Germination und die Entwicklung des Mikroorganismus ermittelt.The process according to the invention is carried out under conditions which are customarily used for the cultivation of fungal cultures for a metabolic synthesis. Thus, the most favorable fermentation conditions, such as. As the selection of the cheapest nutrient medium, the technical conditions such as temperature, aeration pH and the optimal times for the germination and development of the microorganism determined.
Als Kohlenstoffquelle kann für das Fermentationsmedium beispielsweise Glucose oder Saccharose verwendet werden. Als Stickstoffquelle dient unter anderem Asparagin, Ammoniumsuccinat oder Ammoniumsulfat. Ferner enthält das Medium die nötigen Wuchsstoffe (beispielsweise Hefeextrakt) und Mineralstoffe (Kalium-, Magnesium-, Kalzium-, Eisen- und Zink-Kationen, sowie Sulfat, Phosphat, Nitrat und Chlorid-Anionen) in der üblicherweise angewendeten Konzentration.As the carbon source, for example, glucose or sucrose may be used for the fermentation medium. The nitrogen source used is, among others, asparagine, ammonium succinate or ammonium sulfate. Furthermore, the medium contains the necessary growth substances (for example yeast extract) and minerals (potassium, magnesium, calcium, iron and zinc cations, as well as sulfate, phosphate, nitrate and chloride anions) in the concentration commonly used.
Die Fermentation kann ein- oder zweistufig erfolgen, wobei das für die Vorkultur verwendete Medium mit dem der Hauptkultur identisch sein oder von diesem verschieden sein kann. Für die Vorkultur wird vorzugsweise Glucose als Kohlenstoffquelle verwendet, für die Hauptkultur vorzugsweise Saccharose. Das Vorkulturmedium enthält vorzugsweise 10 bis 100mg/l Kohlenstoffquelle, das Hauptkulturmedium vorzugsweise 100 bis 300mg.The fermentation can be carried out in one or two stages, wherein the medium used for the preculture may be identical to or different from the main culture. For the preculture glucose is preferably used as carbon source, for the main culture preferably sucrose. The preculture medium preferably contains 10 to 100 mg / l carbon source, the main culture medium preferably 100 to 300 mg.
Zu Beginn der Fermentation wird der pH-Wert des Mediums vorzugsweise in einem Bereich von 4 bis 6 eingestellt. Die Züchtungstemperatur liegt im Bereich von etwa 10 bis 35°C, vorzugsweise im Bereich von 20 bis 300C. Die Kulturbedingungen sind streng aerob. Die optimale Fermentationszeit wird durch Analyse des gebildeten a-Ergokryptins in üblicher Weise ermittelt.At the beginning of the fermentation, the pH of the medium is preferably adjusted in a range of 4 to 6. The cultivation temperature is in the range of about 10 to 35 ° C, preferably in the range 20-30 0 C. The culture conditions are strictly aerobic. The optimal fermentation time is determined by analysis of the formed a-ergokryptins in the usual way.
Nach erfolgter Fermentation wird das gebildete α-Ergokryptin in an sich bekannter Weise isoliert, beispielsweise indem man die Fermentationsansätze mit einem nicht mit Wasser mischbaren organischen Lösungsmittel, wie Ethylacetat, Methylisobutylketon, Dichlormethan, Chloroform oder Tetrachlorethan extrahiert, die Extrakte einengt und das erhaltene Rohprodukt durch Chromatographie und/oder Kristallisation reinigt.After the fermentation, the α-ergokryptin formed is isolated in a conventional manner, for example by extracting the fermentation mixtures with a water-immiscible organic solvent such as ethyl acetate, methyl isobutyl ketone, dichloromethane, chloroform or tetrachloroethane, the extracts are concentrated and the crude product obtained Purifies chromatography and / or crystallization.
Das nachfolgende Ausführungsbeispiel dient zur Erläutertung des erfindungsgemäßen Verfahrens.The following embodiment serves to explain the method according to the invention.
Claviceps spec. DSM 2836 wird auf einem Nährmedium angezüchtet, welches folgende Komponenten enthält:Claviceps spec. DSM 2836 is grown on a nutrient medium containing the following components:
Saccharose (100g/l), Citronensäure (10g/l), Hefeextrakt (0,1 g/l), Kaliumdihydrogenphosphat (500mg/l), Magnesiumsulfat-Heptahydrat (300mg/l), Ammoniumsulfat (6g/l), Calciumnitrat-Tetrahydrat (1 g/l), Einensulfat-Heptahydrat (7mg/l), Zinksulfat-Heptahydrat(6mg/I), Agar (16 g/l). Das Nährmedium ist auf pH 5,1 eingestellt. Die Anzuchtskultur wird 5 bis 20 Tagelang bei 300C im Brutschrank aufbewahrt.Sucrose (100 g / l), citric acid (10 g / l), yeast extract (0.1 g / l), potassium dihydrogen phosphate (500 mg / l), magnesium sulfate heptahydrate (300 mg / l), ammonium sulfate (6 g / l), calcium nitrate tetrahydrate (1 g / l), one sulfate heptahydrate (7 mg / l), zinc sulfate heptahydrate (6 mg / l), agar (16 g / l). The nutrient medium is adjusted to pH 5.1. The seed culture is stored for 5 to 20 days at 30 0 C in the incubator.
Ein ca. 1 cm2 großes Mycelstückwird mittels eines Ultraturrax unter sterilen Bedingungen in 5 ml physiologischerAn approximately 1 cm 2 large piece of mycelium is physiological by means of an Ultraturrax under sterile conditions in 5 ml
Kochsalzlösung zerkleinert und damit 50ml eine Vorkultur enthaltend Glucose (HOg/l). Citronensäure (7,5g/l). Kaliumdihydrogenphosphat (0,59g/l), Magnesiumsulfat-Heptahydrat (300mg/l), Ammoniumsulfat (6g/l), Eisen(ll)-sulfat-Heptahydrat (7 mg/1), Zinksulfat-Heptahydrat (7 mg/1). Calziumnitrat-Tetrahydrat(1 g/l), Hefeextrakt (0,1 g/l) — eingestellt auf pH 5,1 —die sich in einem 500 ml Erlenmeyerkolben befindet, beimpft und auf einem Rundschüttler 4 Tage lang bei24°Cund 220 Umdrehungen pro Minute kultiviert.Saline solution comminuted and thus 50ml a preculture containing glucose (HOg / l). Citric acid (7.5g / l). Potassium dihydrogen phosphate (0.59 g / l), magnesium sulfate heptahydrate (300 mg / l), ammonium sulfate (6 g / l), ferrous sulfate heptahydrate (7 mg / l), zinc sulfate heptahydrate (7 mg / l). Calcium nitrate tetrahydrate (1 g / L), yeast extract (0.1 g / L) - adjusted to pH 5.1 - which is in a 500 ml Erlenmeyer flask, inoculated and placed on a rotary shaker for 4 days at 24 ° C and 220 revolutions per minute Cultivated minute.
5ml der so erhaltenen Vorkultur werden in 80 ml eines Mediums enthaltend Saccharose (200g/l), Citronensäure (10g/l), Hefeextrakt (0,1 g/l), Kaliumdihydrogenphosphat (500mg/l), Magnesiumsulfat-Haptahydrat (300mg/l), Ammoniumsulfat (6g/l), Calciumnitrat-Tetrahydrat (1 g/l), Eisensulfat-Heptahydrat (7 mg/l) und Zinksulfat-Heptahydrat (6mg/l) — eingestellt auf ph 5,1 — die sich in einem 500ml Erlenmeyerkolben befindet, überführt und 9 Tage lang bei 240C auf einem Rundschuttier mit 240 Umdrehungen pro Minute geschüttelt. Dann wird das Kulturmedium abfiltriert und der Gehalt an a-Ergokryptin mittels Hochdruckflüssigkeitschromatographie (FreseniusZ. Anal. Chem. 303,1980,208) ermittelt. Die Konzentration des Kulturfiltrates beträgt 525 mg/l.5 ml of the preculture thus obtained are dissolved in 80 ml of a medium containing sucrose (200 g / l), citric acid (10 g / l), yeast extract (0.1 g / l), potassium dihydrogen phosphate (500 mg / l), magnesium sulfate haptahydrate (300 mg / l ), Ammonium sulfate (6g / l), calcium nitrate tetrahydrate (1g / l), ferric sulphate heptahydrate (7mg / l) and zinc sulphate heptahydrate (6mg / l) - adjusted to pH 5.1 - resulting in a 500ml Erlenmeyer flask is located, transferred and shaken for 9 days at 24 0 C on a round decker at 240 revolutions per minute. The culture medium is then filtered off and the content of α-ergokryptin is determined by means of high pressure liquid chromatography (FreseniusZ, Anal. Chem., 303, 1980,208). The concentration of the culture filtrate is 525 mg / l.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19843420953 DE3420953A1 (en) | 1984-06-01 | 1984-06-01 | METHOD FOR PRODUCING (ALPHA) ERGOKRYPTIN |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DD237677A5 true DD237677A5 (en) | 1986-07-23 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD85276810A DD237677A5 (en) | 1984-06-01 | 1985-05-30 | PROCESS FOR PREPARING ALPHA-ERGOKRYPTIN |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0183739B1 (en) |
| JP (1) | JPS61502374A (en) |
| CS (1) | CS272206B2 (en) |
| DD (1) | DD237677A5 (en) |
| DE (2) | DE3420953A1 (en) |
| HU (1) | HU198100B (en) |
| WO (1) | WO1985005635A1 (en) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1133916A (en) * | 1966-07-22 | 1968-11-20 | Farmaceutica Italia Soc | Ergocryptine |
| SE332403B (en) * | 1966-07-22 | 1971-02-08 | Farm Italia Soc | |
| HU178405B (en) | 1980-02-08 | 1982-04-28 | Richter Gedeon Vegyeszet | Process for preparing ergocornine and beta-ergocryptine by fermentation |
| DE3104215A1 (en) * | 1981-02-06 | 1982-08-19 | Richter Gedeon Vegyészeti Gyár R.T., 1103 Budapest | Process for the preparation of alkaloids in controlled amount and controlled ratio of amounts by fermentation |
-
1984
- 1984-06-01 DE DE19843420953 patent/DE3420953A1/en not_active Withdrawn
-
1985
- 1985-05-30 HU HU852884A patent/HU198100B/en not_active IP Right Cessation
- 1985-05-30 DD DD85276810A patent/DD237677A5/en not_active IP Right Cessation
- 1985-05-30 WO PCT/DE1985/000193 patent/WO1985005635A1/en not_active Ceased
- 1985-05-30 JP JP60502496A patent/JPS61502374A/en active Pending
- 1985-05-30 EP EP85902482A patent/EP0183739B1/en not_active Expired
- 1985-05-30 DE DE8585902482T patent/DE3567226D1/en not_active Expired
- 1985-05-31 CS CS853919A patent/CS272206B2/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| DE3420953A1 (en) | 1985-12-05 |
| HUT38396A (en) | 1986-05-28 |
| WO1985005635A1 (en) | 1985-12-19 |
| JPS61502374A (en) | 1986-10-23 |
| CS391985A2 (en) | 1990-04-11 |
| DE3567226D1 (en) | 1989-02-09 |
| EP0183739A1 (en) | 1986-06-11 |
| HU198100B (en) | 1989-07-28 |
| EP0183739B1 (en) | 1989-01-04 |
| CS272206B2 (en) | 1991-01-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| VZ | Disclaimer of patent (art. 11 and 12 extension act) |