NO300894B1 - 9<alfa>-hydroksy-17-metylensteroider - Google Patents
9<alfa>-hydroksy-17-metylensteroider Download PDFInfo
- Publication number
- NO300894B1 NO300894B1 NO904333A NO904333A NO300894B1 NO 300894 B1 NO300894 B1 NO 300894B1 NO 904333 A NO904333 A NO 904333A NO 904333 A NO904333 A NO 904333A NO 300894 B1 NO300894 B1 NO 300894B1
- Authority
- NO
- Norway
- Prior art keywords
- hydroxy
- hydrogen
- dien
- alkyl
- methylene
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims description 54
- -1 cyano, isocyano, formamido Chemical group 0.000 claims description 41
- 239000001257 hydrogen Substances 0.000 claims description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims description 37
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 32
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
- 125000004043 oxo group Chemical group O=* 0.000 claims description 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 2
- FVWGKNBEKFTHBR-JRSUCEMESA-N (8s,9r,10s,13s,14s)-17-ethylidene-9-hydroxy-10,13-dimethyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@]2(O)[C@@H]1[C@@H]1CCC(=CC)[C@@]1(C)CC2 FVWGKNBEKFTHBR-JRSUCEMESA-N 0.000 claims 1
- WJNVLBQJPGFXQF-UHZRXMQZSA-N (8s,9r,10s,13s,14s)-9-hydroxy-10,13-dimethyl-17-(nitromethylidene)-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one Chemical compound O=C1CC[C@]2(C)[C@@]3(O)CC[C@](C)(C(CC4)=C[N+]([O-])=O)[C@@H]4[C@@H]3CCC2=C1 WJNVLBQJPGFXQF-UHZRXMQZSA-N 0.000 claims 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 92
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 87
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 69
- 239000000243 solution Substances 0.000 description 61
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
- 238000006243 chemical reaction Methods 0.000 description 53
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 51
- 239000000203 mixture Substances 0.000 description 49
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 47
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 46
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- 150000003431 steroids Chemical class 0.000 description 34
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 239000011541 reaction mixture Substances 0.000 description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 238000003756 stirring Methods 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 20
- 239000000741 silica gel Substances 0.000 description 20
- 229910002027 silica gel Inorganic materials 0.000 description 20
- 238000000034 method Methods 0.000 description 18
- 235000011054 acetic acid Nutrition 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 238000004587 chromatography analysis Methods 0.000 description 16
- 239000003246 corticosteroid Substances 0.000 description 16
- 239000012044 organic layer Substances 0.000 description 16
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- 238000003786 synthesis reaction Methods 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 239000002585 base Substances 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 14
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 229960001334 corticosteroids Drugs 0.000 description 13
- 239000007858 starting material Substances 0.000 description 13
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 12
- 230000002378 acidificating effect Effects 0.000 description 11
- 230000007062 hydrolysis Effects 0.000 description 11
- 238000006460 hydrolysis reaction Methods 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
- 239000003638 chemical reducing agent Substances 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 238000006297 dehydration reaction Methods 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- 239000002002 slurry Substances 0.000 description 9
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 229910052783 alkali metal Inorganic materials 0.000 description 8
- 239000012280 lithium aluminium hydride Substances 0.000 description 8
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 8
- 239000012299 nitrogen atmosphere Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 239000003880 polar aprotic solvent Substances 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 6
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 6
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 6
- 244000309464 bull Species 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- FPULFENIJDPZBX-UHFFFAOYSA-N ethyl 2-isocyanoacetate Chemical compound CCOC(=O)C[N+]#[C-] FPULFENIJDPZBX-UHFFFAOYSA-N 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- UIVSHVIJYXRACC-HKWIXDGRSA-N (8s,9r,10s,13s,14s)-9-hydroxy-10,13-dimethylspiro[1,2,4,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthrene-3,2'-1,3-dioxolane]-17-one Chemical compound C([C@@H]1[C@]([C@]2(CC3)C)(O)CC[C@]4([C@H]1CCC4=O)C)C=C2CC13OCCO1 UIVSHVIJYXRACC-HKWIXDGRSA-N 0.000 description 5
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 230000018044 dehydration Effects 0.000 description 5
- YNLAOSYQHBDIKW-UHFFFAOYSA-M diethylaluminium chloride Chemical compound CC[Al](Cl)CC YNLAOSYQHBDIKW-UHFFFAOYSA-M 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 235000019253 formic acid Nutrition 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 229910052987 metal hydride Inorganic materials 0.000 description 5
- 150000004681 metal hydrides Chemical class 0.000 description 5
- 230000007935 neutral effect Effects 0.000 description 5
- 238000006053 organic reaction Methods 0.000 description 5
- 239000011698 potassium fluoride Substances 0.000 description 5
- 235000003270 potassium fluoride Nutrition 0.000 description 5
- 150000003128 pregnanes Chemical class 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 238000007127 saponification reaction Methods 0.000 description 5
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 150000001340 alkali metals Chemical class 0.000 description 4
- 150000004703 alkoxides Chemical class 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 238000006735 epoxidation reaction Methods 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- 239000008241 heterogeneous mixture Substances 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 229960003975 potassium Drugs 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 230000007306 turnover Effects 0.000 description 4
- PWDABEQXFVHNIT-CZKCSJLSSA-N (8s,9r,10s,13s,14s)-9-hydroxy-3-methoxy-10,13-dimethyl-2,7,8,11,12,14,15,16-octahydro-1h-cyclopenta[a]phenanthren-17-one Chemical compound C1C[C@]2(O)[C@](CCC(OC)=C3)(C)C3=CC[C@H]2[C@@H]2CCC(=O)[C@]21C PWDABEQXFVHNIT-CZKCSJLSSA-N 0.000 description 3
- GLVYLTSKTCWWJR-UHFFFAOYSA-N 2-carbonoperoxoylbenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1C(O)=O GLVYLTSKTCWWJR-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 238000005903 acid hydrolysis reaction Methods 0.000 description 3
- 150000008064 anhydrides Chemical class 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- SJMLNDPIJZBEKY-UHFFFAOYSA-N ethyl 2,2,2-trichloroacetate Chemical compound CCOC(=O)C(Cl)(Cl)Cl SJMLNDPIJZBEKY-UHFFFAOYSA-N 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000036571 hydration Effects 0.000 description 3
- 238000006703 hydration reaction Methods 0.000 description 3
- 230000002906 microbiologic effect Effects 0.000 description 3
- 150000004965 peroxy acids Chemical class 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 0.000 description 3
- ROKZYYXSYCPORA-PDTTZXLYSA-N (8's,9'r,10's,13's,14's)-17'-(2-hydroxy-1-nitroethyl)-10',13'-dimethylspiro[1,3-dioxolane-2,3'-2,4,7,8,11,12,14,15-octahydro-1h-cyclopenta[a]phenanthrene]-9'-ol Chemical compound C([C@@H]1[C@]([C@]2(CC3)C)(O)CC[C@]4([C@H]1CC=C4C(CO)[N+]([O-])=O)C)C=C2CC13OCCO1 ROKZYYXSYCPORA-PDTTZXLYSA-N 0.000 description 2
- FGRXZBRBGRREJW-KHYDEXNFSA-N (8s,9r,10s,13s,14s)-17-ethylidene-10,13-dimethylspiro[1,2,4,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthrene-3,2'-1,3-dioxolane]-9-ol Chemical compound C([C@H]1[C@@H]2CCC([C@]2(CC[C@]1(O)[C@@]1(C)CC2)C)=CC)C=C1CC12OCCO1 FGRXZBRBGRREJW-KHYDEXNFSA-N 0.000 description 2
- RDBRKMZIODRVBD-LJGAWZCMSA-N (8s,9r,10s,13s,14s,17s)-17-acetyl-9-hydroxy-10,13-dimethyl-2,6,7,8,11,12,14,15,16,17-decahydro-1h-cyclopenta[a]phenanthren-3-one Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@]2(O)[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RDBRKMZIODRVBD-LJGAWZCMSA-N 0.000 description 2
- MRWDEOAXKLDOJY-LZQVICCCSA-N (8s,9r,10s,13s,14s,17s)-9-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-2,6,7,8,11,12,14,15,16,17-decahydro-1h-cyclopenta[a]phenanthren-3-one Chemical compound O=C1CC[C@]2(C)[C@@]3(O)CC[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MRWDEOAXKLDOJY-LZQVICCCSA-N 0.000 description 2
- NKJQHUFTMYMELT-GXHPBCKASA-N (8s,9r,10s,13s,14s,17z)-17-(2-hydroxy-1-methoxyethylidene)-10,13-dimethylspiro[1,2,4,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthrene-3,2'-1,3-dioxolane]-9-ol Chemical compound C([C@H]1[C@@H]2CC/C([C@]2(CC[C@]1(O)[C@@]1(C)CC2)C)=C(CO)/OC)C=C1CC12OCCO1 NKJQHUFTMYMELT-GXHPBCKASA-N 0.000 description 2
- SNMVJSSWZSJOGL-PLOWYNNNSA-N 9alpha-hydroxyandrost-4-en-3,17-dione Chemical compound O=C1CC[C@]2(C)[C@@]3(O)CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 SNMVJSSWZSJOGL-PLOWYNNNSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229910021554 Chromium(II) chloride Inorganic materials 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- 239000004157 Nitrosyl chloride Substances 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- 229930182558 Sterol Natural products 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 150000001263 acyl chlorides Chemical class 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 125000005910 alkyl carbonate group Chemical group 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- 239000000010 aprotic solvent Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
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- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- UZEDIBTVIIJELN-UHFFFAOYSA-N chromium(2+) Chemical compound [Cr+2] UZEDIBTVIIJELN-UHFFFAOYSA-N 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- WQLVFSAGQJTQCK-VKROHFNGSA-N diosgenin Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CC[C@H](O)CC4=CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 WQLVFSAGQJTQCK-VKROHFNGSA-N 0.000 description 1
- WQLVFSAGQJTQCK-UHFFFAOYSA-N diosgenin Natural products CC1C(C2(CCC3C4(C)CCC(O)CC4=CCC3C2C2)C)C2OC11CCC(C)CO1 WQLVFSAGQJTQCK-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 239000012374 esterification agent Substances 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- DKBBBMWNVFSFTP-DBCRMRJASA-N ethyl (2Z)-2-formamido-2-[(8S,9R,10S,13S,14S)-9-hydroxy-3-methoxy-10,13,16-trimethyl-2,7,8,11,12,14,15,16-octahydro-1H-cyclopenta[a]phenanthren-17-ylidene]acetate Chemical compound C(=O)N\C(\C(=O)OCC)=C/1\C(C[C@H]2[C@@H]3CC=C4C=C(CC[C@]4(C)[C@]3(CC[C@]\12C)O)OC)C DKBBBMWNVFSFTP-DBCRMRJASA-N 0.000 description 1
- SEHFWGSSLCNYKG-LFOUTOQPSA-N ethyl (2z)-2-formamido-2-[(8s,9r,10s,13s,14s)-9-hydroxy-10,13-dimethyl-3-oxo-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-17-ylidene]acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@]2(O)[C@@H]1[C@@H]1CC\C(=C(\NC=O)C(=O)OCC)[C@@]1(C)CC2 SEHFWGSSLCNYKG-LFOUTOQPSA-N 0.000 description 1
- SIGVKPAIRRIEFB-ISMRYTLVSA-N ethyl (2z)-2-formamido-2-[(8s,9r,10s,13s,14s)-9-hydroxy-3-methoxy-10,13-dimethyl-2,7,8,11,12,14,15,16-octahydro-1h-cyclopenta[a]phenanthren-17-ylidene]acetate Chemical compound C1C=C2C=C(OC)CC[C@]2(C)[C@]2(O)[C@@H]1[C@@H]1CC\C(=C(\NC=O)C(=O)OCC)[C@@]1(C)CC2 SIGVKPAIRRIEFB-ISMRYTLVSA-N 0.000 description 1
- DNVNYSTZNLCZBU-UHFFFAOYSA-N ethyl 2,2-dichloro-2-methoxyacetate Chemical compound CCOC(=O)C(Cl)(Cl)OC DNVNYSTZNLCZBU-UHFFFAOYSA-N 0.000 description 1
- VMRIJTATUAJDAC-KQACMTORSA-N ethyl 2-cyano-2-[(8's,9'r,10's,13's,14's,17'r)-9'-hydroxy-10',13'-dimethylspiro[1,3-dioxolane-2,3'-2,4,7,8,11,12,14,15,16,17-decahydro-1h-cyclopenta[a]phenanthrene]-17'-yl]acetate Chemical compound C([C@H]1[C@@H]2CC[C@@H]([C@]2(CC[C@]1(O)[C@@]1(C)CC2)C)C(C#N)C(=O)OCC)C=C1CC12OCCO1 VMRIJTATUAJDAC-KQACMTORSA-N 0.000 description 1
- KILBCBVQGMTOEY-NZSGCPIUSA-N ethyl 2-cyano-2-[(8s,9r,10s,13s,14s)-9-hydroxy-10,13-dimethylspiro[1,2,4,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthrene-3,2'-1,3-dioxolane]-17-ylidene]acetate Chemical compound C([C@H]1[C@@H]2CCC([C@]2(CC[C@]1(O)[C@@]1(C)CC2)C)=C(C#N)C(=O)OCC)C=C1CC12OCCO1 KILBCBVQGMTOEY-NZSGCPIUSA-N 0.000 description 1
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 1
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- JZXHYLWBIIWFCS-IOIRJSPFSA-N methyl (2E)-2-[(8S,9R,10S,13S,14S)-9-hydroxy-10,13-dimethylspiro[1,2,4,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthrene-3,2'-1,3-dioxolane]-17-ylidene]-2-methoxyacetate Chemical compound C1OC2(CC3=CC[C@H]4[C@@H]5CCC(=C(C(=O)OC)/OC)[C@]5(CC[C@@]4([C@]3(CC2)C)O)C)OC1 JZXHYLWBIIWFCS-IOIRJSPFSA-N 0.000 description 1
- VHFUHRXYRYWELT-UHFFFAOYSA-N methyl 2,2,2-trichloroacetate Chemical compound COC(=O)C(Cl)(Cl)Cl VHFUHRXYRYWELT-UHFFFAOYSA-N 0.000 description 1
- FWIGIASHGJFYOL-UHFFFAOYSA-N methyl 2,2-dichloro-2-methoxyacetate Chemical compound COC(=O)C(Cl)(Cl)OC FWIGIASHGJFYOL-UHFFFAOYSA-N 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- ANGDWNBGPBMQHW-UHFFFAOYSA-N methyl cyanoacetate Chemical compound COC(=O)CC#N ANGDWNBGPBMQHW-UHFFFAOYSA-N 0.000 description 1
- 239000012022 methylating agents Substances 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- UWCMMAUNFGEZOE-KXJSDLPRSA-N n-[1-[(8s,9r,10s,13s,14s)-9-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,11,12,14,15-dodecahydrocyclopenta[a]phenanthren-17-yl]ethenyl]acetamide Chemical compound C1CC2CCCC[C@]2(C)[C@]2(O)[C@@H]1[C@@H]1CC=C(C(=C)NC(=O)C)[C@@]1(C)CC2 UWCMMAUNFGEZOE-KXJSDLPRSA-N 0.000 description 1
- XQTCKWLXWIKKNF-BIRZXAFVSA-N n-[1-[(8s,9r,10s,13s,14s)-9-hydroxy-10,13-dimethyl-3-oxo-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-17-ylidene]ethyl]formamide Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@]2(O)[C@@H]1[C@@H]1CCC(=C(NC=O)C)[C@@]1(C)CC2 XQTCKWLXWIKKNF-BIRZXAFVSA-N 0.000 description 1
- QHFUDCWZPNWPCD-TXQCIHRXSA-N n-acetyl-n-[1-[(8s,9r,10s,13s,14s)-9-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,11,12,14,15-dodecahydrocyclopenta[a]phenanthren-17-yl]ethenyl]acetamide Chemical compound C1CC2CCCC[C@]2(C)[C@]2(O)[C@@H]1[C@@H]1CC=C(C(=C)N(C(C)=O)C(=O)C)[C@@]1(C)CC2 QHFUDCWZPNWPCD-TXQCIHRXSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- RAIYODFGMLZUDF-UHFFFAOYSA-N piperidin-1-ium;acetate Chemical compound CC([O-])=O.C1CC[NH2+]CC1 RAIYODFGMLZUDF-UHFFFAOYSA-N 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical class [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- LCXMRSLFWMMCAS-WRJHFWDFSA-N pregna-4,9(11)-diene-3,20-dione Chemical compound O=C1CC[C@]2(C)C3=CC[C@]4(C)[C@@H](C(=O)C)CC[C@H]4[C@@H]3CCC2=C1 LCXMRSLFWMMCAS-WRJHFWDFSA-N 0.000 description 1
- AOHJOMMDDJHIJH-UHFFFAOYSA-N propylenediamine Chemical compound CC(N)CN AOHJOMMDDJHIJH-UHFFFAOYSA-N 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 description 1
- 235000015500 sitosterol Nutrition 0.000 description 1
- 229950005143 sitosterol Drugs 0.000 description 1
- NLQLSVXGSXCXFE-UHFFFAOYSA-N sitosterol Natural products CC=C(/CCC(C)C1CC2C3=CCC4C(C)C(O)CCC4(C)C3CCC2(C)C1)C(C)C NLQLSVXGSXCXFE-UHFFFAOYSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 239000001476 sodium potassium tartrate Substances 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- HCXVJBMSMIARIN-PHZDYDNGSA-N stigmasterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)/C=C/[C@@H](CC)C(C)C)[C@@]1(C)CC2 HCXVJBMSMIARIN-PHZDYDNGSA-N 0.000 description 1
- 235000016831 stigmasterol Nutrition 0.000 description 1
- 229940032091 stigmasterol Drugs 0.000 description 1
- BFDNMXAIBMJLBB-UHFFFAOYSA-N stigmasterol Natural products CCC(C=CC(C)C1CCCC2C3CC=C4CC(O)CCC4(C)C3CCC12C)C(C)C BFDNMXAIBMJLBB-UHFFFAOYSA-N 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000000126 substance Substances 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
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 229940066528 trichloroacetate Drugs 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J13/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
- C07J5/0007—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa
- C07J5/0023—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa substituted in position 16
- C07J5/003—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group including 16-alkylidene substitutes
- C07J5/0038—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group including 16-alkylidene substitutes by an alkyl group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J13/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17
- C07J13/005—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17 with double bond in position 16 (17)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J13/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17
- C07J13/007—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17 with double bond in position 17 (20)
-
- 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
- C07J21/005—Ketals
- C07J21/006—Ketals at position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of only two carbon atoms, e.g. pregnane derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
- C07J5/0007—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa
- C07J5/0015—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa not substituted in position 16
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
- C07J7/0005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21
- C07J7/001—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group
- C07J7/0015—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa
- C07J7/002—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa not substituted in position 16
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
- C07J7/0005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21
- C07J7/001—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group
- C07J7/004—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group substituted in position 17 alfa
- C07J7/0045—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group substituted in position 17 alfa not substituted in position 16
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
- C07J7/008—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms substituted in position 21
- C07J7/009—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms substituted in position 21 by only one oxygen atom doubly bound
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP88200675 | 1988-04-08 | ||
| PCT/NL1989/000020 WO1989009781A1 (en) | 1988-04-08 | 1989-04-07 | 9-alpha-hydroxy-17-methylene steroids, their preparation and utilization |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO904333D0 NO904333D0 (no) | 1990-10-05 |
| NO904333L NO904333L (no) | 1990-12-03 |
| NO300894B1 true NO300894B1 (no) | 1997-08-11 |
Family
ID=8199778
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO904333A NO300894B1 (no) | 1988-04-08 | 1990-10-05 | 9<alfa>-hydroksy-17-metylensteroider |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US5194602A (de) |
| EP (1) | EP0336521B1 (de) |
| JP (1) | JP2812397B2 (de) |
| KR (1) | KR0138777B1 (de) |
| CN (2) | CN1187365C (de) |
| AU (1) | AU618350B2 (de) |
| CA (1) | CA1332409C (de) |
| DE (1) | DE68901104D1 (de) |
| DK (1) | DK175401B1 (de) |
| ES (1) | ES2033516T3 (de) |
| FI (1) | FI108436B (de) |
| GR (1) | GR3004539T3 (de) |
| HU (1) | HU208437B (de) |
| IE (1) | IE62277B1 (de) |
| IL (1) | IL89880A (de) |
| NO (1) | NO300894B1 (de) |
| PT (1) | PT90227B (de) |
| WO (1) | WO1989009781A1 (de) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MY105302A (en) * | 1989-11-27 | 1994-09-30 | Schering Corp | Process for dehydrating corticosteroid intermediates. |
| FR2677029B1 (fr) * | 1991-05-23 | 1994-01-21 | Roussel Uclaf | Nouveaux derives sterouides de l'andostra-4,9(11),16-trien-3-one. |
| FR2677028B1 (fr) * | 1991-05-23 | 1994-01-21 | Roussel Uclaf | Nouveaux derives sterouides du pregna-4,9(11),17(20)-trien-3-one. |
| FR2676740B1 (fr) * | 1991-05-23 | 1993-11-05 | Roussel Uclaf | Nouveaux derives sterouides du pregna-4,9(11),17(20)-trie-3-one, leur preparation, leur application a la preparation de composes sterouides de type pregna-4,9(11),16-triene-3,20-dione et nouveaux intermediaires. |
| FR2681069B1 (fr) * | 1991-09-06 | 1995-04-28 | Roussel Uclaf | Nouveau procede de preparation de l'hydrocortisone et nouveaux intermediaires. |
| FR2683530B1 (fr) * | 1991-11-08 | 1994-01-21 | Roussel Uclaf | Nouveau procede de preparation de derives 20-oxo 17 alpha, 21-dihydroxyles du pregnane et nouveaux intermediaires. |
| WO1993015103A2 (en) * | 1992-01-28 | 1993-08-05 | Schering Corporation | Novel steroid intermediates and processes for their preparation |
| CN1061984C (zh) * | 1996-04-18 | 2001-02-14 | 上海华联制药有限公司 | 甾体激素化合物中引入9-11双键的一种方法 |
| CA2330611A1 (en) | 1998-05-22 | 1999-12-02 | The Board Of Trustees Of The Leland Stanford Junior University | Bifunctional molecules and therapies based thereon |
| US6855836B2 (en) * | 2000-10-26 | 2005-02-15 | Jenapharm Gmbh & Co. Kg | 17-Methylene steroids, process for their production and pharmaceutical compositions that contain these compounds |
| SI1889198T1 (sl) | 2005-04-28 | 2015-02-27 | Proteus Digital Health, Inc. | Farma-informacijski sistem |
| WO2007035716A2 (en) | 2005-09-16 | 2007-03-29 | Raptor Pharmaceutical Inc. | Compositions comprising receptor-associated protein (rap) variants specific for cr-containing proteins and uses thereof |
| US20080318870A1 (en) | 2007-06-19 | 2008-12-25 | Kythera Biopharmaceuticals, Inc. | Synthetic bile acid compositions and methods |
| MX360094B (es) * | 2007-06-19 | 2018-10-19 | Kythera Biopharmaceuticals Inc Star | Composición, método y preparación del ácido biliar sintético. |
| JOP20180077A1 (ar) | 2007-06-19 | 2019-01-30 | Kythera Biopharmaceuticals Inc | تركيبات وطرق لحمض صفراوي تخليقي |
| US8242294B2 (en) | 2007-06-19 | 2012-08-14 | Kythera Biopharmaceuticals, Inc. | Synthetic bile acid compositions and methods |
| WO2010095940A2 (en) | 2009-02-20 | 2010-08-26 | To-Bbb Holding B.V. | Glutathione-based drug delivery system |
| NZ596876A (en) | 2009-05-06 | 2014-01-31 | Lab Skin Care Inc | Dermal delivery compositions comprising active agent-calcium phosphate particle complexes and methods of using the same |
| GB2480632A (en) | 2010-05-25 | 2011-11-30 | Kythera Biopharmaceuticals Inc | Preparation of 12-keto and 12-alpha-hydroxy steroids |
| BR112013003216A2 (pt) | 2010-08-12 | 2016-05-17 | Kythera Biopharmaceuticals Inc | composições sintéticas de ácido biliar e métodos |
| WO2013044119A1 (en) * | 2011-09-22 | 2013-03-28 | Kythera Biopharmaceuticals, Inc. | Compositions and methods related to deoxycholic acid and its polymorphs |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL103170C (de) * | 1958-11-14 | |||
| DE1568506A1 (de) * | 1966-03-23 | 1970-07-16 | Hoechst Ag | Verfahren zur Herstellung von delta?-Pregnen-3,21-diol-20-on-21-acylaten |
| US3445907A (en) * | 1967-02-16 | 1969-05-27 | Ind Tectonics Inc | Roller retaining method for roller bearing separators |
| US4255344A (en) * | 1978-11-08 | 1981-03-10 | Mitsubishi Chemical Industries, Limited | 9-α-Hydroxy steroids |
| FR2462445A1 (fr) * | 1979-07-31 | 1981-02-13 | Roussel Uclaf | Nouveaux derives 17-/(hydroxymethyl) (formamido) methylene/steroides, leur procede de preparation et leur application a l'introduction de la chaine laterale hydroxyacetyle |
| FR2486947A1 (fr) * | 1980-07-15 | 1982-01-22 | Roussel Uclaf | Nouveaux derives steroides 20-isonitriles 17(20) insatures, leur procede de preparation et leur application a la preparation des steroides 17a-hydroxy 20-ceto |
| DE3136917A1 (de) * | 1980-09-27 | 1982-05-19 | Barmag Barmer Maschinenfabrik Ag, 5630 Remscheid | "kraftstoffoerderpumpe" |
| FR2493324B1 (de) * | 1980-11-05 | 1983-01-21 | Roussel Uclaf | |
| FR2521567A1 (fr) * | 1982-02-18 | 1983-08-19 | Roussel Uclaf | Nouveaux derives steroides 17(20)nitro, leur procede de preparation et leur application a la preparation de corticosteroides |
| EP0123734A1 (de) * | 1983-04-29 | 1984-11-07 | Gist-Brocades N.V. | 17-(Isocyano-sulfonylmethylen)-Steroide, 17-(Formamido-sulfonylmethylen)-Steroide und ihre Herstellung |
-
1989
- 1989-04-07 US US07/474,852 patent/US5194602A/en not_active Expired - Lifetime
- 1989-04-07 KR KR1019890702133A patent/KR0138777B1/ko not_active IP Right Cessation
- 1989-04-07 EP EP89200891A patent/EP0336521B1/de not_active Expired - Lifetime
- 1989-04-07 AU AU34313/89A patent/AU618350B2/en not_active Expired
- 1989-04-07 WO PCT/NL1989/000020 patent/WO1989009781A1/en active IP Right Grant
- 1989-04-07 JP JP1504593A patent/JP2812397B2/ja not_active Expired - Lifetime
- 1989-04-07 DE DE8989200891T patent/DE68901104D1/de not_active Expired - Lifetime
- 1989-04-07 HU HU892602A patent/HU208437B/hu unknown
- 1989-04-07 ES ES198989200891T patent/ES2033516T3/es not_active Expired - Lifetime
- 1989-04-07 IL IL8988089A patent/IL89880A/en unknown
- 1989-04-07 PT PT90227A patent/PT90227B/pt not_active IP Right Cessation
- 1989-04-08 CN CNB951202561A patent/CN1187365C/zh not_active Expired - Lifetime
- 1989-04-08 CN CN89102092A patent/CN1032211C/zh not_active Expired - Lifetime
- 1989-04-10 CA CA000596257A patent/CA1332409C/en not_active Expired - Lifetime
- 1989-04-10 IE IE113489A patent/IE62277B1/en not_active IP Right Cessation
-
1990
- 1990-10-03 FI FI904877A patent/FI108436B/fi not_active IP Right Cessation
- 1990-10-05 NO NO904333A patent/NO300894B1/no not_active IP Right Cessation
- 1990-10-05 DK DK199002408A patent/DK175401B1/da not_active IP Right Cessation
-
1992
- 1992-05-08 GR GR920400800T patent/GR3004539T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL89880A (en) | 1994-06-24 |
| KR0138777B1 (ko) | 1998-04-30 |
| JP2812397B2 (ja) | 1998-10-22 |
| US5194602A (en) | 1993-03-16 |
| DK240890A (da) | 1990-10-05 |
| FI904877A0 (fi) | 1990-10-03 |
| IL89880A0 (en) | 1989-12-15 |
| GR3004539T3 (de) | 1993-04-28 |
| DK240890D0 (da) | 1990-10-05 |
| DK175401B1 (da) | 2004-09-27 |
| HUT55411A (en) | 1991-05-28 |
| IE891134L (en) | 1989-10-08 |
| KR900700499A (ko) | 1990-08-13 |
| AU618350B2 (en) | 1991-12-19 |
| NO904333L (no) | 1990-12-03 |
| DE68901104D1 (de) | 1992-05-07 |
| NO904333D0 (no) | 1990-10-05 |
| PT90227B (pt) | 1994-06-30 |
| CN1141301A (zh) | 1997-01-29 |
| PT90227A (pt) | 1989-11-10 |
| JPH03503645A (ja) | 1991-08-15 |
| IE62277B1 (en) | 1995-01-25 |
| FI108436B (fi) | 2002-01-31 |
| CN1036774A (zh) | 1989-11-01 |
| EP0336521A1 (de) | 1989-10-11 |
| WO1989009781A1 (en) | 1989-10-19 |
| EP0336521B1 (de) | 1992-04-01 |
| CN1187365C (zh) | 2005-02-02 |
| HU208437B (en) | 1993-10-28 |
| AU3431389A (en) | 1989-11-03 |
| CA1332409C (en) | 1994-10-11 |
| CN1032211C (zh) | 1996-07-03 |
| HU892602D0 (en) | 1991-03-28 |
| ES2033516T3 (es) | 1993-03-16 |
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Legal Events
| Date | Code | Title | Description |
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| MK1K | Patent expired |