CS258141B2 - Method of 15 alpha-hydroxyprostacycline intermediate products' microbiological production - Google Patents

Method of 15 alpha-hydroxyprostacycline intermediate products' microbiological production Download PDF

Info

Publication number: CS258141B2
Authority: CS; Czechoslovakia
Prior art keywords: hydroxyprostacycline; group; substrate; microorganisms; under
Prior art date: 1985-05-29

Application number

CS863658A

Other languages

Czech (cs)

English (en)

Other versions

CS365886A2 (en

Inventor

Karel Petzoldt

Helmut Dahl

Werner SKUBALA

Original Assignee

Schering 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.)

1985-05-29

Filing date

1986-05-20

Publication date

1988-07-15

1985-05-29 Priority claimed from DE19853519548 external-priority patent/DE3519548A1/de

1986-05-20 Application filed by Schering Ag filed Critical Schering Ag

1987-11-12 Publication of CS365886A2 publication Critical patent/CS365886A2/cs

1988-07-15 Publication of CS258141B2 publication Critical patent/CS258141B2/cs

Links

238000000034 method Methods 0.000 title claims description 13
230000002906 microbiologic effect Effects 0.000 title claims description 7
238000004519 manufacturing process Methods 0.000 title claims description 4
239000013067 intermediate product Substances 0.000 title description 2
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
239000000758 substrate Substances 0.000 claims description 13
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
244000005700 microbiome Species 0.000 claims description 10
241000512906 Candida solani Species 0.000 claims description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
239000000543 intermediate Substances 0.000 claims description 8
241000235042 Millerozyma farinosa Species 0.000 claims description 6
238000000855 fermentation Methods 0.000 claims description 5
230000004151 fermentation Effects 0.000 claims description 5
239000002904 solvent Substances 0.000 claims description 5
150000002576 ketones Chemical class 0.000 claims description 4
125000004430 oxygen atom Chemical group O* 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
238000006722 reduction reaction Methods 0.000 description 7
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 5
229960001123 epoprostenol Drugs 0.000 description 5
239000000203 mixture Substances 0.000 description 5
239000003995 emulsifying agent Substances 0.000 description 4
KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 4
AEBWATHAIVJLTA-UHFFFAOYSA-N 1,2,3,3a,4,5,6,6a-octahydropentalene Chemical compound C1CCC2CCCC21 AEBWATHAIVJLTA-UHFFFAOYSA-N 0.000 description 3
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
241000235648 Pichia Species 0.000 description 3
238000005273 aeration Methods 0.000 description 3
239000001963 growth medium Substances 0.000 description 3
150000003180 prostaglandins Chemical class 0.000 description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
238000004945 emulsification Methods 0.000 description 2
239000000284 extract Substances 0.000 description 2
239000002054 inoculum Substances 0.000 description 2
238000002156 mixing Methods 0.000 description 2
229940094443 oxytocics prostaglandins Drugs 0.000 description 2
238000011218 seed culture Methods 0.000 description 2
238000003756 stirring Methods 0.000 description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
241000222120 Candida <Saccharomycetales> Species 0.000 description 1
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical class C1CO1 IAYPIBMASNFSPL-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
241000235070 Saccharomyces Species 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
239000013543 active substance Substances 0.000 description 1
239000008272 agar Substances 0.000 description 1
BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
229910052921 ammonium sulfate Inorganic materials 0.000 description 1
239000001166 ammonium sulphate Substances 0.000 description 1
235000011130 ammonium sulphate Nutrition 0.000 description 1
230000003698 anagen phase Effects 0.000 description 1
239000002518 antifoaming agent Substances 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
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
229940041514 candida albicans extract Drugs 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
229940126214 compound 3 Drugs 0.000 description 1
229940125898 compound 5 Drugs 0.000 description 1
150000001875 compounds Chemical class 0.000 description 1
235000005822 corn Nutrition 0.000 description 1
239000012043 crude product Substances 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
239000003480 eluent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
-1 fatty acid esters Chemical class 0.000 description 1
229960001031 glucose Drugs 0.000 description 1
229960002240 iloprost Drugs 0.000 description 1
HIFJCPQKFCZDDL-ACWOEMLNSA-N iloprost Chemical compound C1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)C(C)CC#CC)[C@H](O)C[C@@H]21 HIFJCPQKFCZDDL-ACWOEMLNSA-N 0.000 description 1
238000011081 inoculation Methods 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000002609 medium Substances 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
238000013048 microbiological method Methods 0.000 description 1
TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
229920000151 polyglycol Polymers 0.000 description 1
239000010695 polyglycol Substances 0.000 description 1
229920001296 polysiloxane Polymers 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000003815 prostacyclins Chemical class 0.000 description 1
230000001012 protector Effects 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000000926 separation method Methods 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
229920002545 silicone oil Polymers 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000012138 yeast extract Substances 0.000 description 1

Landscapes

Preparation Of Compounds By Using Micro-Organisms (AREA)
Micro-Organisms Or Cultivation Processes Thereof (AREA)

CS863658A 1985-05-29 1986-05-20 Method of 15 alpha-hydroxyprostacycline intermediate products' microbiological production CS258141B2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE19853519548 DE3519548A1 (de)	1985-05-29	1985-05-29	Mikrobiologische reduktion von prostacyclin-zwischenprodukten mit einer 15-ketogruppe

Publications (2)

Publication Number	Publication Date
CS365886A2 CS365886A2 (en)	1987-11-12
CS258141B2 true CS258141B2 (en)	1988-07-15

Family

ID=6272112

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS863658A CS258141B2 (en)	1985-05-29	1986-05-20	Method of 15 alpha-hydroxyprostacycline intermediate products' microbiological production

Country Status (4)

Country	Link
CS (1)	CS258141B2 (de)
DD (1)	DD247465A5 (de)
DE (1)	DE3680110D1 (de)
HU (1)	HU201353B (de)

1986
- 1986-05-16 DE DE8686903219T patent/DE3680110D1/de not_active Expired - Lifetime
- 1986-05-16 HU HU863159A patent/HU201353B/hu not_active IP Right Cessation
- 1986-05-20 CS CS863658A patent/CS258141B2/cs unknown
- 1986-05-27 DD DD86290625A patent/DD247465A5/de unknown

Also Published As

Publication number	Publication date
DD247465A5 (de)	1987-07-08
HUT45561A (en)	1988-07-28
HU201353B (en)	1990-10-28
DE3680110D1 (de)	1991-08-08
CS365886A2 (en)	1987-11-12

Publication	Publication Date	Title
US4585789A (en)	1986-04-29	New furanone derivatives, process for preparation thereof and use thereof
US6844174B2 (en)	2005-01-18	Fermentation process for lipstatin and method of extracting lipstatin from a fermentation broth
CH651005A5 (fr)	1985-08-30	Terpenoides contenant deux groupes fonctionnels et procede pour leur preparation.
US4933282A (en)	1990-06-12	Process for preparing an optically active γ-halo-β-hydroxybutyric acid ester
EP1062358B1 (de)	2003-06-04	Verfahren zur herstellung von fexofenadin
CS258141B2 (en)	1988-07-15	Method of 15 alpha-hydroxyprostacycline intermediate products' microbiological production
US5403724A (en)	1995-04-04	Microbiological reduction of prostacyclin intermediate products with a 15-keto group
US4247635A (en)	1981-01-27	Microbiological reduction of 15-ketoprostaglandin intermediates
CS258482B2 (en)	1988-08-16	Method of 4-androstane-3,17-dione and 1,4-androstadiene-3,17-dione production
US6262288B1 (en)	2001-07-17	Process for the preparation of chiral epoxides
US5102793A (en)	1992-04-07	Stereospecific keto reduction of bicyclooctandione-carboxylic acid esters by microorganisms
EP0271432B1 (de)	1992-09-16	Racematspaltung von 3-Acyloxy-Bicyclo[3.3.0]octan-7-on-2-carbonsäureestern durch stereospezifische enzymatische oder mikrobiologische Acylat-Hydrolyse
US5258290A (en)	1993-11-02	Fermentation process for the production of β-carboline derivatives by Myrothecium verrucaria
EP0570593B1 (de)	1998-09-09	Verfahren zur herstellung von optisch aktivem norborneol
EP0208662A1 (de)	1987-01-14	Verfahren zur Herstellung von R(-)-Norcarnitin-tert-butylester
SU1679977A3 (ru)	1991-09-23	Способ получени 4-андростен-3,17-диона или 1,4-андростадиен-3,17-диона
RU2082762C1 (ru)	1997-06-27	Способ получения 17-оксостероидов
US5472854A (en)	1995-12-05	Process for the production of 17-oxosteroids via the fermentative oxidation of 17β-hydroxysteroids by Mycobacterium
US5429934A (en)	1995-07-04	Process for the production of 20-methyl-5,7-pregnadiene-3β,21-diol derivatives using mycobacterium