CA2495412A1 - 5 androsten-3.beta.-ol steroid intermediates and processes for their preparation - Google Patents
5 androsten-3.beta.-ol steroid intermediates and processes for their preparation Download PDFInfo
- Publication number
- CA2495412A1 CA2495412A1 CA002495412A CA2495412A CA2495412A1 CA 2495412 A1 CA2495412 A1 CA 2495412A1 CA 002495412 A CA002495412 A CA 002495412A CA 2495412 A CA2495412 A CA 2495412A CA 2495412 A1 CA2495412 A1 CA 2495412A1
- Authority
- CA
- Canada
- Prior art keywords
- steroid
- beta
- alpha
- preparation
- formula
- 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.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 107
- 238000002360 preparation method Methods 0.000 title claims abstract description 71
- 239000000543 intermediate Substances 0.000 title abstract description 12
- -1 5 androsten-3.beta.-ol steroid Chemical class 0.000 title abstract description 8
- 150000003431 steroids Chemical group 0.000 claims description 175
- 229910052799 carbon Inorganic materials 0.000 claims description 48
- 238000000855 fermentation Methods 0.000 claims description 31
- 230000004151 fermentation Effects 0.000 claims description 31
- 150000001875 compounds Chemical class 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 241000190144 Lasiodiplodia theobromae Species 0.000 claims description 14
- 241000935926 Diplodia Species 0.000 claims description 13
- 241000122824 Aspergillus ochraceus Species 0.000 claims description 12
- 239000012141 concentrate Substances 0.000 claims description 12
- 241000228212 Aspergillus Species 0.000 claims description 11
- 241000235389 Absidia Species 0.000 claims description 7
- 241000293029 Absidia caerulea Species 0.000 claims description 7
- VWFCWHWCCOZKJZ-CAMMJAKZSA-N (8s,10s,13s,14s)-10,13-dimethyl-2,3,4,7,8,12,14,15,16,17-decahydro-1h-cyclopenta[a]phenanthrene Chemical compound C([C@H]12)C=C3CCCC[C@]3(C)C1=CC[C@@]1(C)[C@H]2CCC1 VWFCWHWCCOZKJZ-CAMMJAKZSA-N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000000686 lactone group Chemical group 0.000 claims 25
- 125000004432 carbon atom Chemical group C* 0.000 claims 16
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims 9
- 241000284466 Antarctothoa delta Species 0.000 claims 5
- OVSKIKFHRZPJSS-UHFFFAOYSA-N 2,4-D Chemical compound OC(=O)COC1=CC=C(Cl)C=C1Cl OVSKIKFHRZPJSS-UHFFFAOYSA-N 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 77
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 49
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 47
- 239000002609 medium Substances 0.000 description 34
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 32
- 239000000047 product Substances 0.000 description 27
- 239000000203 mixture Substances 0.000 description 24
- 238000011218 seed culture Methods 0.000 description 24
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- 239000013078 crystal Substances 0.000 description 21
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 20
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 20
- 235000019439 ethyl acetate Nutrition 0.000 description 18
- 239000002002 slurry Substances 0.000 description 17
- 238000004659 sterilization and disinfection Methods 0.000 description 17
- 239000000758 substrate Substances 0.000 description 17
- 238000004809 thin layer chromatography Methods 0.000 description 17
- 239000007787 solid Substances 0.000 description 16
- 241000233866 Fungi Species 0.000 description 14
- 235000013405 beer Nutrition 0.000 description 14
- 238000001914 filtration Methods 0.000 description 14
- 238000012809 post-inoculation Methods 0.000 description 14
- 238000002425 crystallisation Methods 0.000 description 13
- 230000008025 crystallization Effects 0.000 description 13
- 229910052739 hydrogen Inorganic materials 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 238000007792 addition Methods 0.000 description 12
- 239000000284 extract Substances 0.000 description 12
- 239000001257 hydrogen Substances 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 230000001954 sterilising effect Effects 0.000 description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 11
- 238000013019 agitation Methods 0.000 description 11
- 150000002576 ketones Chemical class 0.000 description 11
- 150000002596 lactones Chemical group 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 150000001721 carbon Chemical group 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 125000000217 alkyl group Chemical group 0.000 description 9
- 238000005119 centrifugation Methods 0.000 description 9
- 238000005805 hydroxylation reaction Methods 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 8
- 230000002538 fungal effect Effects 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 239000003599 detergent Substances 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 238000011081 inoculation Methods 0.000 description 6
- 239000003549 soybean oil Substances 0.000 description 6
- 235000012424 soybean oil Nutrition 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- 239000013530 defoamer Substances 0.000 description 5
- 238000004821 distillation Methods 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 229920001296 polysiloxane Polymers 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- FBWNMEQMRUMQSO-UHFFFAOYSA-N tergitol NP-9 Chemical compound CCCCCCCCCC1=CC=C(OCCOCCOCCOCCOCCOCCOCCOCCOCCO)C=C1 FBWNMEQMRUMQSO-UHFFFAOYSA-N 0.000 description 5
- AFGDPPHTYUQKOF-QAGGRKNESA-N (8r,9s,10r,13s,14s)-10,13-dimethyl-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one Chemical class C1CCC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 AFGDPPHTYUQKOF-QAGGRKNESA-N 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 238000012258 culturing Methods 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 4
- 229920000053 polysorbate 80 Polymers 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 239000004375 Dextrin Substances 0.000 description 3
- 229920001353 Dextrin Polymers 0.000 description 3
- 102000008109 Mixed Function Oxygenases Human genes 0.000 description 3
- 108010074633 Mixed Function Oxygenases Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 235000019425 dextrin Nutrition 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- JUKPWJGBANNWMW-VWBFHTRKSA-N eplerenone Chemical compound C([C@@H]1[C@]2(C)C[C@H]3O[C@]33[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)C(=O)OC)C[C@@]21CCC(=O)O1 JUKPWJGBANNWMW-VWBFHTRKSA-N 0.000 description 3
- 229960001208 eplerenone Drugs 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000011877 solvent mixture Substances 0.000 description 3
- 238000005507 spraying Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- FMGSKLZLMKYGDP-UHFFFAOYSA-N 3-hydroxy-10,13-dimethyl-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one Chemical class C1C(O)CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CC=C21 FMGSKLZLMKYGDP-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241000935930 Lasiodiplodia Species 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 235000019483 Peanut oil Nutrition 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 235000019484 Rapeseed oil Nutrition 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 229940125773 compound 10 Drugs 0.000 description 2
- 235000005687 corn oil Nutrition 0.000 description 2
- 239000002285 corn oil Substances 0.000 description 2
- 235000012343 cottonseed oil Nutrition 0.000 description 2
- 239000002385 cottonseed oil Substances 0.000 description 2
- 238000005906 dihydroxylation reaction Methods 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 2
- 239000010699 lard oil Substances 0.000 description 2
- 239000000944 linseed oil Substances 0.000 description 2
- 235000021388 linseed oil Nutrition 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
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 2
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 2
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 description 2
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
- UYDLBVPAAFVANX-UHFFFAOYSA-N octylphenoxy polyethoxyethanol Chemical compound CC(C)(C)CC(C)(C)C1=CC=C(OCCOCCOCCOCCO)C=C1 UYDLBVPAAFVANX-UHFFFAOYSA-N 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000000312 peanut oil Substances 0.000 description 2
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000001965 potato dextrose agar Substances 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000003813 safflower oil Substances 0.000 description 2
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 235000020238 sunflower seed Nutrition 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 239000010497 wheat germ oil Substances 0.000 description 2
- FMGSKLZLMKYGDP-HQEMIIEJSA-N (8r,9s,10r,13s,14s)-3-hydroxy-10,13-dimethyl-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one Chemical class C1C(O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 FMGSKLZLMKYGDP-HQEMIIEJSA-N 0.000 description 1
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-Bis(diphenylphosphino)propane Substances C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 1
- VUZNLSBZRVZGIK-UHFFFAOYSA-N 2,2,6,6-Tetramethyl-1-piperidinol Chemical group CC1(C)CCCC(C)(C)N1O VUZNLSBZRVZGIK-UHFFFAOYSA-N 0.000 description 1
- TVEXGJYMHHTVKP-UHFFFAOYSA-N 6-oxabicyclo[3.2.1]oct-3-en-7-one Chemical compound C1C2C(=O)OC1C=CC2 TVEXGJYMHHTVKP-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- 241001674393 Diplodia mutila Species 0.000 description 1
- 102000003979 Mineralocorticoid Receptors Human genes 0.000 description 1
- 108090000375 Mineralocorticoid Receptors Proteins 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- QYTDEUPAUMOIOP-UHFFFAOYSA-N TEMPO Chemical group CC1(C)CCCC(C)(C)N1[O] QYTDEUPAUMOIOP-UHFFFAOYSA-N 0.000 description 1
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 229940068911 chloride hexahydrate Drugs 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- GFHNAMRJFCEERV-UHFFFAOYSA-L cobalt chloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Co+2] GFHNAMRJFCEERV-UHFFFAOYSA-L 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000006735 epoxidation reaction Methods 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- OSVMTWJCGUFAOD-KZQROQTASA-N formestane Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1O OSVMTWJCGUFAOD-KZQROQTASA-N 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- VOAPTKOANCCNFV-UHFFFAOYSA-N hexahydrate;hydrochloride Chemical compound O.O.O.O.O.O.Cl VOAPTKOANCCNFV-UHFFFAOYSA-N 0.000 description 1
- 238000007037 hydroformylation reaction Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 238000001223 reverse osmosis Methods 0.000 description 1
- SYBXSZMNKDOUCA-UHFFFAOYSA-J rhodium(2+);tetraacetate Chemical compound [Rh+2].[Rh+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O SYBXSZMNKDOUCA-UHFFFAOYSA-J 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- HWCKGOZZJDHMNC-UHFFFAOYSA-M tetraethylammonium bromide Chemical compound [Br-].CC[N+](CC)(CC)CC HWCKGOZZJDHMNC-UHFFFAOYSA-M 0.000 description 1
- ILJSQTXMGCGYMG-UHFFFAOYSA-N triacetic acid Chemical compound CC(=O)CC(=O)CC(O)=O ILJSQTXMGCGYMG-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0003—Androstane derivatives
- C07J1/0011—Androstane derivatives substituted in position 17 by a keto group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J21/001—Lactones
- C07J21/003—Lactones at position 17
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US40399002P | 2002-08-16 | 2002-08-16 | |
| US60/403,990 | 2002-08-16 | ||
| US41529302P | 2002-10-01 | 2002-10-01 | |
| US60/415,293 | 2002-10-01 | ||
| PCT/US2003/007791 WO2004016640A2 (en) | 2002-08-16 | 2003-03-21 | 5 ANDROSTEN-3β-OL STEROID INTERMEDIATES AND PROCESSES FOR THEIR PREPARATION |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2495412A1 true CA2495412A1 (en) | 2004-02-26 |
Family
ID=31891414
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002495412A Abandoned CA2495412A1 (en) | 2002-08-16 | 2003-03-21 | 5 androsten-3.beta.-ol steroid intermediates and processes for their preparation |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US20040034215A1 (enExample) |
| EP (1) | EP1534732B1 (enExample) |
| JP (1) | JP2006507369A (enExample) |
| AT (1) | ATE339437T1 (enExample) |
| AU (1) | AU2003285485A1 (enExample) |
| BR (1) | BR0313523A (enExample) |
| CA (1) | CA2495412A1 (enExample) |
| DE (1) | DE60308388T2 (enExample) |
| ES (1) | ES2271636T3 (enExample) |
| MX (1) | MXPA05001857A (enExample) |
| TW (1) | TW200406419A (enExample) |
| WO (1) | WO2004016640A2 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ITMI20042338A1 (it) * | 2004-12-06 | 2005-03-06 | Ind Chimica Srl | Processo per la preparazione di drospirenone |
| US8084446B2 (en) * | 2005-04-26 | 2011-12-27 | Eric Marchewitz | Use of DHEA derivatives for enhancing physical performance |
| PL2527356T3 (pl) * | 2005-07-21 | 2018-06-29 | Bayer Intellectual Property Gmbh | Sposób wytwarzania 3-okso-pregn-4-eno-21,17-karbolaktonów za pomocą wolnego od metali utleniania 17-(3-hydroksypropylo)-3,17- dihydroksyandrostanów |
| ATE403668T1 (de) | 2005-07-21 | 2008-08-15 | Bayer Schering Pharma Ag | Verfahren zur herstellung von 3-oxo-pregn-4-en-21,17-carbolactonen durch die metallfreie oxidation von 17-(3-hydroxypropyl)-3,17- dihydroxyandrostanen |
| US7319154B2 (en) | 2005-07-21 | 2008-01-15 | Bayer Schering Pharma Ag | Process for the production of 3-oxo-pregn-4-ene-21, 17-carbolactones by the metal free oxidation of 17-(3-hydroxypropyl)-3, 17-dihydroxyandrostanes |
| CN110331182A (zh) * | 2019-08-06 | 2019-10-15 | 江苏远大仙乐药业有限公司 | 一种甾体中间体的生物转化制备方法 |
| CN110885869A (zh) * | 2019-12-24 | 2020-03-17 | 天津科技大学 | 一种利用微生物转化生产7α-羟基-脱氢表雄酮的方法 |
| CN111057734A (zh) * | 2019-12-24 | 2020-04-24 | 天津科技大学 | 一种甲基睾丸素高效转化生产11α-羟基-甲基睾丸素的方法 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3294646A (en) * | 1963-10-23 | 1966-12-27 | American Home Prod | Microbiological hydroxylation of norsteroids using aspergillus ochraceus |
| DE2349022A1 (de) * | 1973-09-26 | 1975-04-10 | Schering Ag | Neue d-homo-steroide |
| DK134348C (da) * | 1973-11-30 | 1977-03-21 | Schering Ag | Analogifremgangsmade til fremstilling af d-homo-20-ketopregnaner |
| US4031074A (en) * | 1974-09-02 | 1977-06-21 | Akzona Incorporated | Process for the preparation of 11β-hydroxy-18-alkyl-estrane compounds |
| IL48628A0 (en) * | 1974-12-23 | 1976-02-29 | Schering Ag | D-homo-20-keto-pregnanes and process for their manufactur |
| US4054563A (en) * | 1975-04-25 | 1977-10-18 | Ciba-Geigy Corporation | Process for the manufacture of spiro compounds of the steroid series |
| CH633562A5 (de) * | 1976-12-10 | 1982-12-15 | Schering Ag | Verfahren zur herstellung neuer kortikoide. |
| US4336332A (en) * | 1979-02-20 | 1982-06-22 | Hoffmann-La Roche, Inc. | Process for the manufacture of hydroxylated steroids |
| DE3042136A1 (de) * | 1980-11-03 | 1982-06-09 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Verfahren zur herstellung von 3 (beta), 7 (beta) -dihydroxy- (delta) (pfeil hoch)5(pfeil hoch) -steroiden |
| US4559332A (en) * | 1983-04-13 | 1985-12-17 | Ciba Geigy Corporation | 20-Spiroxanes and analogues having an open ring E, processes for their manufacture, and pharmaceutical preparations thereof |
| AU7978794A (en) * | 1993-10-13 | 1995-05-04 | Neurocrine Biosciences, Inc. | 3,17-dihydroxy-3,7,16 and/or 17-methyl-androst-5-ene compounds, derivatives thereof, and their use |
| PT973791E (pt) * | 1995-12-11 | 2007-09-26 | Searle Llc | Processo para a preparação de um composto epoxi |
| DE69620474T2 (de) * | 1995-12-12 | 2002-11-14 | Akzo Nobel N.V., Arnhem | Mikrobielle 11alpha-hydroxylierung von steroiden |
| FR2771105A1 (fr) | 1997-11-20 | 1999-05-21 | Vitasterol | Utilisation du fusarium monoliforme pour la preparation des derives 7alpha-hydroxyles de la dehydroepiandrosterone et de la pregnenolone |
-
2003
- 2003-03-21 DE DE60308388T patent/DE60308388T2/de not_active Expired - Fee Related
- 2003-03-21 CA CA002495412A patent/CA2495412A1/en not_active Abandoned
- 2003-03-21 TW TW092106331A patent/TW200406419A/zh unknown
- 2003-03-21 MX MXPA05001857A patent/MXPA05001857A/es unknown
- 2003-03-21 WO PCT/US2003/007791 patent/WO2004016640A2/en not_active Ceased
- 2003-03-21 AU AU2003285485A patent/AU2003285485A1/en not_active Abandoned
- 2003-03-21 US US10/392,955 patent/US20040034215A1/en not_active Abandoned
- 2003-03-21 AT AT03756776T patent/ATE339437T1/de not_active IP Right Cessation
- 2003-03-21 ES ES03756776T patent/ES2271636T3/es not_active Expired - Lifetime
- 2003-03-21 JP JP2005502036A patent/JP2006507369A/ja not_active Abandoned
- 2003-03-21 EP EP03756776A patent/EP1534732B1/en not_active Expired - Lifetime
- 2003-03-21 BR BR0313523-3A patent/BR0313523A/pt not_active IP Right Cessation
-
2004
- 2004-06-01 US US10/858,177 patent/US7002028B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP2006507369A (ja) | 2006-03-02 |
| MXPA05001857A (es) | 2005-06-03 |
| WO2004016640A3 (en) | 2004-07-08 |
| BR0313523A (pt) | 2005-06-28 |
| DE60308388T2 (de) | 2007-09-20 |
| US20040034215A1 (en) | 2004-02-19 |
| EP1534732A2 (en) | 2005-06-01 |
| US7002028B2 (en) | 2006-02-21 |
| ES2271636T3 (es) | 2007-04-16 |
| WO2004016640A2 (en) | 2004-02-26 |
| AU2003285485A1 (en) | 2004-03-03 |
| US20040220158A1 (en) | 2004-11-04 |
| ATE339437T1 (de) | 2006-10-15 |
| DE60308388D1 (de) | 2006-10-26 |
| TW200406419A (en) | 2004-05-01 |
| EP1534732B1 (en) | 2006-09-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4416985A (en) | Process for preparing 3β,7β-dihydroxy-Δ5 -steroids | |
| EP1562974B1 (en) | Processes for preparing c-7 substituted 5-androstenes | |
| EP1534732B1 (en) | 5 androsten-3-ol steroid intermediates and processes for their preparation | |
| IL27858A (en) | Microbiological process for the preparation of 11beta-hydroxysteroids | |
| US20070066579A1 (en) | 5-androsten-3beta-ol steroid intermediates and processs for their preparation | |
| US6828120B2 (en) | Process to prepare 11β, 17α,21-trihydroxy-6α-methylpregna-1,4-diene-3,20-dione 21-acetate | |
| US20060100185A1 (en) | 5-Androsten-3beta-ol steroid intermediates and processes for their preparation | |
| US4124607A (en) | Preparation of sterol substrates for bioconversion | |
| US20040265948A1 (en) | Microbial method for hydrolysis and oxidation of androst-5-ene and pregn-5-ene steroid esters | |
| EP1679317A2 (en) | 5-Androsten-3 -ol steroid intermediates and processes for fheir preparation | |
| US4284720A (en) | Process for the preparation of 19-hydroxy steroids of the androstane and pregnane series | |
| JPH0460480B2 (enExample) | ||
| US5250712A (en) | 1β,15α-dihydroxy-1α-methyl-5α-androstane-3,17-dione, its production and use | |
| US3198809A (en) | Microbiological reduction process and steroid products produced thereby | |
| WO1996012034A1 (en) | A microbiological process for the preparation of 17beta-carboxy substituted 3-oxo-4-azasteroids and the use of such products as inhibitors of the enzyme 5alpha-reductase | |
| MXPA06003504A (es) | Metodo de fermentacion para la preparacion de testolactona por especies de fusarium. | |
| EP0114984A2 (de) | Verfahren zur Herstellung von 3,11-alpha-Dihydroxy-1,3,5(10)-östratrien-Derivaten | |
| AU2002311917A1 (en) | Process to prepare 11beta,17alpha,21-trihydroxy-6alpha-Methylpregna-1,4-diene-3,20-dione 21-acetate | |
| JPH02504519A (ja) | １β，１５α‐ジヒドロキシ‐１α‐メチル‐５α‐アンドロスタン‐３，１７‐ジオン、その製造及び使用 | |
| HU183154B (en) | Process for preparing 11beta-hydroxy-steroids | |
| JPS6224077B2 (enExample) | ||
| SE183083C1 (enExample) | ||
| JPH0148277B2 (enExample) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |