US3853707A - Method for producing hexanor-5,9-seco-pregnan-5-oic acid - Google Patents
Method for producing hexanor-5,9-seco-pregnan-5-oic acid Download PDFInfo
- Publication number
- US3853707A US3853707A US00389041A US38904173A US3853707A US 3853707 A US3853707 A US 3853707A US 00389041 A US00389041 A US 00389041A US 38904173 A US38904173 A US 38904173A US 3853707 A US3853707 A US 3853707A
- Authority
- US
- United States
- Prior art keywords
- hexanor
- pregnan
- seco
- oic acid
- fermentation
- 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.)
- Expired - Lifetime
Links
- 239000002253 acid Substances 0.000 title claims abstract description 14
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- 238000000034 method Methods 0.000 claims description 16
- 238000000855 fermentation Methods 0.000 claims description 14
- 230000004151 fermentation Effects 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- 235000015097 nutrients Nutrition 0.000 claims description 7
- 230000002269 spontaneous effect Effects 0.000 claims description 4
- 150000003431 steroids Chemical class 0.000 abstract description 14
- 238000013048 microbiological method Methods 0.000 abstract description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 229920001817 Agar Polymers 0.000 description 7
- 239000008272 agar Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 241000187481 Mycobacterium phlei Species 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 229940055036 mycobacterium phlei Drugs 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 239000008103 glucose Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000005273 aeration Methods 0.000 description 3
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000011573 trace mineral Substances 0.000 description 3
- 235000013619 trace mineral Nutrition 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- -1 cornsteep Substances 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 235000011118 potassium hydroxide Nutrition 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000008399 tap water Substances 0.000 description 2
- 235000020679 tap water Nutrition 0.000 description 2
- RWBRUCCWZPSBFC-SJOKZOANSA-N (20R)-20-hydroxypregn-4-en-3-one Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](O)C)[C@@]1(C)CC2 RWBRUCCWZPSBFC-SJOKZOANSA-N 0.000 description 1
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 229930192334 Auxin Natural products 0.000 description 1
- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 description 1
- 239000002028 Biomass Substances 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- VZUNGTLZRAYYDE-UHFFFAOYSA-N N-methyl-N'-nitro-N-nitrosoguanidine Chemical compound O=NN(C)C(=N)N[N+]([O-])=O VZUNGTLZRAYYDE-UHFFFAOYSA-N 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 238000010564 aerobic fermentation Methods 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000002363 auxin Substances 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- SEOVTRFCIGRIMH-UHFFFAOYSA-N indole-3-acetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CNC2=C1 SEOVTRFCIGRIMH-UHFFFAOYSA-N 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910017464 nitrogen compound Inorganic materials 0.000 description 1
- 150000002830 nitrogen compounds Chemical class 0.000 description 1
- HVFSJXUIRWUHRG-UHFFFAOYSA-N oic acid Natural products C1CC2C3CC=C4CC(OC5C(C(O)C(O)C(CO)O5)O)CC(O)C4(C)C3CCC2(C)C1C(C)C(O)CC(C)=C(C)C(=O)OC1OC(COC(C)=O)C(O)C(O)C1OC(C(C1O)O)OC(COC(C)=O)C1OC1OC(CO)C(O)C(O)C1O HVFSJXUIRWUHRG-UHFFFAOYSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 235000008160 pyridoxine Nutrition 0.000 description 1
- 239000011677 pyridoxine Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 239000012138 yeast extract Substances 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
- C12P33/00—Preparation of steroids
-
- 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
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/8215—Microorganisms
- Y10S435/822—Microorganisms using bacteria or actinomycetales
- Y10S435/863—Mycobacterium
- Y10S435/866—Mycobacterium smegmatis
Definitions
- the present invention relates to a microbiological method for producing 2Obeta-hydr0xy- 9-ox0- 1,2,3,4,10,l9-hexanor-5,9-seco-pregnan-5-oic acid, an
- the compound of formula I is utilized as an intermediate in the preparation of known steroids by procedures described in Belgian Pat. No. 741,826.
- Mycobacterium phlei ATCC 19249 it is intended to cover all microorganisms of the genus Mycobacterium phlei which produce the compound of formula land which cannot be definitely differentiated from the strain deposited with the American Type Culture Collection, Rockville, Maryland under ATCC No. 19249 and its subcultures includingmutants and variants.
- the hexanor-S,9-seco-pregnan-5-oic acid of formula I is manufactured by fermenting 3beta,20betadihydrOXypregn-S-ene or 2Obeta-hydroxypregn-4-en- 3-one with Mycobacterium phlei ATCC 19249 adapted to aliphatic hydrocarbons.
- the adaption of Mycobacterium phlei ATCC 19249 to aliphatic hydrocarbons can be carried out in a manas the carbon source, the hexanor-S,9-seco-pregnan-5- oic acid of formula I. Those cultures which show no growth on such media are used for the present fermentation.
- the present process can be carried out by any conventional procedure of aerobic fermentation.
- suitable culture substrates are liquid media which contain a source of assimilable nitrogen and a source of assimilable carbon as well as inorganic salts.
- Any conventional source of assimilable nitrogen and assimilablecarbon can be utilized.
- As the source of assimilable nitrogen there can be used animal, vegetable, microbial and inorganic nitrogen compounds such as meat extracts, peptone, cornsteep, yeast extract, glycine and sodium nitrate.
- As the source of assimilable carbon there can be used sugars such as glucose and, especially, the steroid starting material to be fermented.
- the nutrient medium may, if desired, also contain trace elements such as iron, sulfur and phosphorus as well as growth factors (e.g., vitamins such as biotin or pyridoxine) or auxins (e.g., indolylacetic acid).
- growth factors e.g., vitamins such as biotin or pyridoxine
- auxins e.g., indolylacetic acid.
- the medium can be sterilized and/or can be provided with substances such as benzoates, antibiotics, etc., which inhibit the growth of foreign organisms.
- the fermentation is preferably carried out in a neutral or weakly acidic pI-I-range (e.g.,
- the fermentation can be carried out at a temperature of between 18C. and 40C. It is preferably carried out at about 28C.
- the steroid used as the starting material is preferably added to the fermentation culture in solution.
- Any conventional inert organic solvent can be used as the solvent medium in accordance with this invention.
- the preferred solvents are included dimethyl sulfoxide, dimethylformamide, ethanol or acetone. It has proved to be advantageous to add the steroid gradually to the fermentation solution and to wait for the complete decomposition of the previously added steroid before each new addition.
- the hexanor-5,9- seco-pregnan-S-oic acid aforesaid can be isolated from the culture solution by conventional procedures.
- ner known per se by inoculating the microorganism from culture substrates which contain glucose on to those substrates in which the glucose is replaced in increasing quantity by aliphatic hydrocarbons, especially C -C alkanes.
- mutants as used herein can be spontaneous' mutants or mutants produced in a physical or chemical manner. Mutants can be produced by irradiation (e.g., with ultraviolet light or gamma rays) or by treatment with mutating agents (e.g., N-methyl-nitronitrosoguanidine or bromouracil). Spontaneous mutants are preferably used in the present process. The selection of the mutants can be carried out by spreading single colonies on agar plates which contain, as the carbon source, the steroid starting material to be fermented. Single colonies obtained from such agar substrates are finally spread on agar plates which contain,
- Mycobacterium phlei ATCC 19249 adapted to C C n-aIkane, was incoluated from sloping agar cultures on to a culture medium 'of the following composition:
- the cultures were incubated for days at 28C. with aeration and stirring. From the thus-obtained cultures, there were taken plate-cultures on agar plates which contained only 3B,20B-dihydroxypregn-S-ene as the carbon source. The plate-cultures were repeated several times, by which means the steroid content in the agar plates was increased. Finally, further platecultures were used in which the agar contained only B-hydroxy-9-oxo-l ,2,3,4, 1 0,l9-hexanor-5,9-secopregnan-S-oic acid'as the carbon source. Those cultures which showed no growth on these plates were used for the fermentation. In order to store the cultures, a suspension in sterile 10 percent skim milk was prepared from the biomass and was filled into 2 ml. ampoules and stored under liquid nitrogen.
- Example 2 in tap water. pH 7.0 (adjusted with sodium hydroxide), was inoculated with the contents of 2 ampoules prepared according to Example 1. The culture was incubated for 48 hours at 28C. with shaking. This preculture .was used to inoculate 8 liters of nutrient medium in a small fermenter following which incubation was carried out for 2 days at 28C. with stirring and aeration (640 r.p.m., 2 liters air/minute), the pH value being adjusted to pH 7.0 by the addition of 28 percent sodium hydroxide. The contents of this fermenter were used as the inoculant for 180 liter fermenter containing the same nutrient solution.
- pH 7.0 adjusted with sodium hydroxide
- the fermentation mass was centrifuged, rinsed with 20 liters of water and adjusted to pH 2.0 with concentrated aqueous hydrochloric acid.
- the solution was extracted twice with the same volume and once with half the volume of methylene chloride.
- the extracts were concentrated in a rotary evaporator and worked up by countercurrent extractionv
- the yield of 20,8-hydroxy-9- oxo-1,2,3,4, l0,l9-hexanor-5,9-seco-pregnan-5-oic acid amounted to 82 percent. 10 percent of9,20-dioxo- 1,2,3,4,l0,l9-hexanor-5-seco-pregnan-5-oic acid was also isolated.
- a solution of 13.4 g of 20beta-hydroxy-9-oxo- 1,2,3,4,1O,19-hexan0r-5,9-seco-pregnan-5oic acid and 4 g of sodium acetate in 250 ml of acetic anhydride is boiled at reflux under nitrogen for 4 hours.
- the acetic anhydride is removed in vacuum, the residue twice evaporated with toluene and finally taken up in 750 ml of methylene chloride.
- the methylene chloride solution is washed five times with water, dried over Na SO and evaporated in vacuum.
Landscapes
- 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)
- Steroid Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1283872A CH585171A5 (enrdf_load_html_response) | 1972-08-31 | 1972-08-31 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3853707A true US3853707A (en) | 1974-12-10 |
Family
ID=4386844
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US00389041A Expired - Lifetime US3853707A (en) | 1972-08-31 | 1973-08-16 | Method for producing hexanor-5,9-seco-pregnan-5-oic acid |
Country Status (16)
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4039381A (en) * | 1975-11-17 | 1977-08-02 | The Upjohn Company | Composition of matter and process |
| US4042459A (en) * | 1975-11-17 | 1977-08-16 | The Upjohn Company | Composition of matter and process |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3379621A (en) * | 1964-06-12 | 1968-04-23 | Syntex Corp | Microbiological preparation of delta1, 3, 5(10)-3-hydroxy steroids |
| US3616228A (en) * | 1968-09-26 | 1971-10-26 | Kurt Schubert | Beta-substituted propionic acids and method of making the same |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH57A (fr) * | 1889-01-08 | Richardson Dinsmore John Henry | Appareil pour le perfectionnement de la fabrication du gaz d'éclairage | |
| DE1793427A1 (de) * | 1968-07-11 | 1972-02-24 | Akad Wissenschaften Ddr | Verfahren zur Herstellung von neuen ss-Substituierten Propionsaeuren |
| CH527147A (de) * | 1968-11-19 | 1972-08-31 | Hoffmann La Roche | Verfahren zur Herstellung von Indanderivaten |
-
1972
- 1972-08-31 CH CH1283872A patent/CH585171A5/xx not_active IP Right Cessation
-
1973
- 1973-07-10 ZA ZA734650A patent/ZA734650B/xx unknown
- 1973-07-10 IL IL42711A patent/IL42711A/en unknown
- 1973-07-24 AU AU58431/73A patent/AU468583B2/en not_active Expired
- 1973-08-08 DE DE19732340162 patent/DE2340162A1/de active Pending
- 1973-08-16 HU HUHO1605A patent/HU168234B/hu unknown
- 1973-08-16 US US00389041A patent/US3853707A/en not_active Expired - Lifetime
- 1973-08-20 CA CA179,199A patent/CA992480A/en not_active Expired
- 1973-08-24 PH PH14956*UA patent/PH9700A/en unknown
- 1973-08-28 FR FR7331045A patent/FR2197868B1/fr not_active Expired
- 1973-08-29 SE SE7311760A patent/SE410731B/xx unknown
- 1973-08-30 BE BE135087A patent/BE804196A/xx unknown
- 1973-08-30 JP JP48096788A patent/JPS4962692A/ja active Pending
- 1973-08-30 AT AT752773A patent/AT332001B/de not_active IP Right Cessation
- 1973-08-30 GB GB4093173A patent/GB1397163A/en not_active Expired
- 1973-08-31 NL NL7312061A patent/NL7312061A/xx not_active Application Discontinuation
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3379621A (en) * | 1964-06-12 | 1968-04-23 | Syntex Corp | Microbiological preparation of delta1, 3, 5(10)-3-hydroxy steroids |
| US3616228A (en) * | 1968-09-26 | 1971-10-26 | Kurt Schubert | Beta-substituted propionic acids and method of making the same |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4039381A (en) * | 1975-11-17 | 1977-08-02 | The Upjohn Company | Composition of matter and process |
| US4042459A (en) * | 1975-11-17 | 1977-08-16 | The Upjohn Company | Composition of matter and process |
Also Published As
| Publication number | Publication date |
|---|---|
| GB1397163A (en) | 1975-06-11 |
| HU168234B (enrdf_load_html_response) | 1976-03-28 |
| CH585171A5 (enrdf_load_html_response) | 1977-02-28 |
| CA992480A (en) | 1976-07-06 |
| JPS4962692A (enrdf_load_html_response) | 1974-06-18 |
| NL7312061A (enrdf_load_html_response) | 1974-03-04 |
| SE410731B (sv) | 1979-10-29 |
| DE2340162A1 (de) | 1974-03-28 |
| ATA752773A (de) | 1975-12-15 |
| AU5843173A (en) | 1975-01-30 |
| FR2197868B1 (enrdf_load_html_response) | 1978-02-17 |
| FR2197868A1 (enrdf_load_html_response) | 1974-03-29 |
| AU468583B2 (en) | 1976-01-15 |
| PH9700A (en) | 1976-02-19 |
| AT332001B (de) | 1976-09-10 |
| IL42711A (en) | 1976-10-31 |
| ZA734650B (en) | 1974-04-24 |
| BE804196A (fr) | 1974-02-28 |
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