NO143503B - Analogifremgangsmaate ved fremstilling av 13-alkyl-d-homo-gona-diener med hormonvirkning - Google Patents
Analogifremgangsmaate ved fremstilling av 13-alkyl-d-homo-gona-diener med hormonvirkning Download PDFInfo
- Publication number
- NO143503B NO143503B NO792125A NO792125A NO143503B NO 143503 B NO143503 B NO 143503B NO 792125 A NO792125 A NO 792125A NO 792125 A NO792125 A NO 792125A NO 143503 B NO143503 B NO 143503B
- Authority
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- Norway
- Prior art keywords
- homo
- gona
- alkyl
- ethyl
- formula
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title description 2
- 230000003054 hormonal effect Effects 0.000 title 1
- 150000000795 D-homosteroids Chemical class 0.000 claims description 5
- 150000002902 organometallic compounds Chemical class 0.000 claims description 5
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 4
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 230000002124 endocrine Effects 0.000 claims description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- -1 alkane carboxylic acids Chemical class 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 239000000243 solution Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- DHBXNPKRAUYBTH-UHFFFAOYSA-N 1,1-ethanedithiol Chemical compound CC(S)S DHBXNPKRAUYBTH-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 239000003810 Jones reagent Substances 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 244000126014 Valeriana officinalis Species 0.000 description 1
- 235000013832 Valeriana officinalis Nutrition 0.000 description 1
- WAHQVRCNDCHDIB-QZYSPNBYSA-N [(3s,8r,9s,10r,13s,14s,17r)-17-acetyl-17-acetyloxy-6,10,13-trimethyl-1,2,3,8,9,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-yl] 3-cyclopentylpropanoate Chemical compound O([C@@H]1C=C2C(C)=C[C@H]3[C@@H]4CC[C@]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)(OC(=O)C)C(C)=O)C(=O)CCC1CCCC1 WAHQVRCNDCHDIB-QZYSPNBYSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- SMZOGRDCAXLAAR-UHFFFAOYSA-N aluminium isopropoxide Chemical compound [Al+3].CC(C)[O-].CC(C)[O-].CC(C)[O-] SMZOGRDCAXLAAR-UHFFFAOYSA-N 0.000 description 1
- DNEHKUCSURWDGO-UHFFFAOYSA-N aluminum sodium Chemical compound [Na].[Al] DNEHKUCSURWDGO-UHFFFAOYSA-N 0.000 description 1
- 230000001548 androgenic effect Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- VWWMOACCGFHMEV-UHFFFAOYSA-N dicarbide(2-) Chemical compound [C-]#[C-] VWWMOACCGFHMEV-UHFFFAOYSA-N 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- WMWSRIHFAVOHSW-UHFFFAOYSA-N lithium;ethane-1,2-diamine;ethyne Chemical compound [Li+].[C-]#C.NCCN WMWSRIHFAVOHSW-UHFFFAOYSA-N 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- RMGJCSHZTFKPNO-UHFFFAOYSA-M magnesium;ethene;bromide Chemical compound [Mg+2].[Br-].[CH-]=C RMGJCSHZTFKPNO-UHFFFAOYSA-M 0.000 description 1
- LROBJRRFCPYLIT-UHFFFAOYSA-M magnesium;ethyne;bromide Chemical compound [Mg+2].[Br-].[C-]#C LROBJRRFCPYLIT-UHFFFAOYSA-M 0.000 description 1
- QBNOPZJAURRQCE-UHFFFAOYSA-M magnesium;prop-1-yne;bromide Chemical compound [Mg+2].[Br-].CC#[C-] QBNOPZJAURRQCE-UHFFFAOYSA-M 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 150000007524 organic acids Chemical group 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000000583 progesterone congener Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000016788 valerian Nutrition 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- PGOLTJPQCISRTO-UHFFFAOYSA-N vinyllithium Chemical compound [Li]C=C PGOLTJPQCISRTO-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
- C07J63/008—Expansion of ring D by one atom, e.g. D homo steroids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Description
Foreliggende oppfinnelse vedrører en analogifremgangsmåte ved frem-
stilling av 13-alkyl-D-homo-gonadiener med endokrin virkning med formel
3 13
hvor R er (H,H) eller (a-H,0-0-C _-acyl), R lavere-alkyl,
„17aØ „ ^llaa .. , , n i
R H, R etinyl, lavere-alkyl.
D-homosteroidene med formel I kan ifølge oppfinnelsen erholdes
ved at man omsetter et D-homosteroid med formel
13 3
hvor R , R og den prikkede linje i A-ringen har den an-
gitte betydning
1V 3. CL
med en metallorganisk forbindelse som avgir en rest R , og at man om ønsket forestrer et erholdt D-homosteroid med formel
<_> , n<17aØ> er H.
I hvor R er H.
Uttrykket C^_^-acyl skal spesielt betegne organiske syrerester, f.eks. rester av alkankarboksylsyrer som eddiksyre, propion-syre, kapronsyre, valeriansyre, eller oxalsyre, ravsyre, sitronsyre eller rester av aromatiske karboksylsyrer som benzo-syre.
Lavere alkylrester kan inneholde opp til 7 C-atomer og være rettkjedede eller forgrenede. Eksempler på dette er metyl,, etyl, <p>ropyl, isopropyl, butyl og isomere. Foretrukne rester R"*"3 er metyl og etyl. ;En foretrukket forbindelsesgruppe innenfor formel I er de forbindelser hvor R^~^ er metyl eller etyl og dobbeltbindinqen i ring A er i 4,5-stilling. Videre er slike forbindelser med formel I foretrukket hvori R"<*>"^<act> er hydrogen, etinyl, klor-etinyl eller butadiinyl og R er hydrogen.
Eksempler på forbindelser med formel I er: 17aØ-hydroksy-13-metyl-D-homo-qona-4 ,16-dien,
17aa-etinyl-17aØ-hydroksy-13-metyl-D-homo-gona-4,16-dien, 17aa-etinyl-13-etyl-17aØ-hydroksy-D-homo-gona-4,16-dien, 17aØ-acetoksy-17aa-etinyl-13-etyl-D-homo-gona-4,16-dien, 30,17aØ-diacetoksy-13-metyl-D-homo-gona-4,6-dien, 30,17aØ-diacetoksy-17aa-etinyl-13-metyl-D-homo-gona-4,6-dien, 30,17aØ-diacetoksy-17aa-etinyl-13-etyl-D-homo-gona-4,6-dien.
Omsetningen av 17a-ketogruppen i en forbindelse med formel III med en metallorganisk forbindelse kan utføres på i og for seg kjent måte. Den metallorganiske forbindelsen kan være en Grignardfprbindelse (f.eks. etinylmagnesiumbromid, propinyl-magnesiumbromid, vinylmagnesiumbromid) eller en alkalimetall-organisk forbindelse som Na-, K- eller Li-acetylid, eller vinyl-litium. For fremstilling av 17aa-usubstituerte forbindelser med formler I kan det som metallorganiske forbindelser anvendes komplekse metallhydrider, f.eks. di-(lavere-alkyl)-aluminium-hydrider som di-isobutylaluminiumhydrid; tri-laverealkoksy-alu-minium som triisopropoksyaluminium; litium-aluminiumhydrid;'• natriualuminium-(eller bor-)hydrid; eller trimetoksy- eller tributoksy-litiumaluminiumhydrid. Egnedé løsningsmidler for dette er hydrokarboner, f.eks. cykloheksan, benzen, toluen; og etere, f.eks. dietyleter eller tetrahydrofuran. D-homosteroidene med formler III som anvendes som utgangsmat-eriale kan fremstilles som beskrevet i eksemplene eller ana-logt med disse.
Forbindelsene med formel I har alle endokrin virkning. Således er de f.eks. sterkt gestagene. De kan f.eks. finne anvendelse som cyklusregulatatorer. For disse formål kommer doseringer på 0,01 til 0,1 mg/kg i betrakning. Videre ble det observert en androgen virkning, spesielt ved forbindelsene med R<17act>= h.
Fremgangsmåteproduktene kan finne anvendelse i form av farma-søytiske preparater som.inneholder dem i blanding med et for enteral eller parenteral applikasjon egnet farmasøytisk, or-ganisk eller uorganisk inert bæremateriale som f.eks. vann, gelatin, gummi arabikum, melkesukker, stivelse, magnesiumstea-rat, talkum, planteoljer, polyalkylenglykoler, vaseliner osv. og kan foreligge i fast form, f.eks. som tabletter, drageer, supositorier, kapsler; eller i flytende form, f.eks. som løs-ninger, suspensjoner eller emulsjoner.
EKSEMPEL 1
Til en løsning av 2,6 g 13-etyl-D-homogona-4,16~dien-17a-on i 50 ml absolutt tetrahydrofuran satte man 1,66 g litiumacetylid-etylendiamin-kompleks og rørte blandingen under stadig gjénnom-blåsning av acetylen 90 minutter ved romtemperatur. For opp-arbeiding ble blandingen forsiktig helt i 250 ml vann og ekstrahert 3 ganger med eter. Eter-ekstraktene ble vasket med vann, tørket med Na2S04 og inndampet i våkum. Resten ble kromatografert på 100 g kiselgel. Med heksan-aceton (95:5) eluertes 1,8 g rent 17act-etinyl-13-etyl-17a-hydroksy-D-homo-gona-4,16-dien. Smp. 95-97° (eter-heksan), [a]D25° = - 193°
(C = 1,0 i dioksan).
Utgangsmaterialet kan fremstilles som følger:
En løsning av 3,14 g 13-etyl-3-metoksy-D-homogona-2,5(10),16-trien-17af}-ol i 150 ml metanol ble blandet med 10 ml 1 N og 3 ml kons. vandig saltsyre og rørt 12 timer ved 25°C. Metan-olen ble inndampet på rotasjonsfordamper oq den vandige resten ekstrahert 3 ganger med diklormetan. De organiske fasene ga etter vask med bikarbonatløsning, tørking over natriumsul-fat og inndampning på rotas jonsf ordamper 2,9 g 13-etyl-17a(3-hydroksy-D-homogona-4,16-dien-3-on, smp. 191-192°C.
4,0 g 17aØ-hydroksy-13-etyl-D-homo-gona-4,16-dien-3-on ble om-satt med etanditiol i metanol og bortrifluorideterat som kata-lysator til 3,3-etylenditio-13-etyl-17a[3-hydroksy-D-homo-gona-4,16-dien med smp. 156-158°C. Dette ble løst i tetrahydrofuran, satt til en blanding av 150 ml flytende ammoniakk og 30 ml tetrahydrofuran ved -50°C og deretter redusert ved til-setning av 300 mg litium i 50 ml flytende ammoniakk til det amorfe 13-etyl-17a@-hydroksy-D-homo-qona-4,16-dien. 1,90 q av denne substansen ble løst i 65 ml aceton, kjølt til 0°C og i løpet av 5 minutter blandet med 2,0 ml Jones-Reagens (CrO-j i 8 N t^SO^) . Råproduktet ga etter omkrystallisasjon 1,3 g rent 13-etyl-D-homo-gona-4,16-dien-17a-on. Smp. 78-79°C (metanol), [a]D25° = - 10,1° (c - 1,0 i dioksan), 62?5 = 7870.
EKSEMPEL 2
På analog måte med eksempel 1 kan 3|3-acetoksy-13-etyl-17a3-hydroksy-17a-metyl-D-homo-gona-4,16-dien, smp. 119-l21°C, [a]D25= - 103°C (c = 1,0 i dioksan) fremstilles.
Claims (1)
- Analogifremgangsmåte ved fremstilling av 13-alkyl-D-homo-gonadiener med endokrin virkning med formelhvor R<3> betyr (H,H) eller (a-H, 3-O-C^-acyl) , R<13> lavere-alkyl, R"'"73'3 H, R^<7aa> etinyl, lavere-alkyl, karakterisert ved at man omsetter et D-homo-steroid med formel 13 3 hvor R , R og den prikkede linjen i A-ringen har den foran angitte betydning, med en metallorganisk forbindelse som avgir resten R^<7aa>, og at man om ønsket forestrer et erholdt D-homosteroid med formel I hvor R<17a0> er H.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1398974A CH606113A5 (no) | 1974-10-18 | 1974-10-18 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO792125L NO792125L (no) | 1976-04-21 |
| NO143503B true NO143503B (no) | 1980-11-17 |
| NO143503C NO143503C (no) | 1981-02-25 |
Family
ID=4397020
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO753505A NO142349C (no) | 1974-10-18 | 1975-10-17 | Analogifremgangsmaate for fremstilling av terapeutisk virksomme 13-alkyl d-homogonadiener |
| NO792125A NO143503C (no) | 1974-10-18 | 1979-06-25 | Analogifremgangsmaate ved fremstilling av 13-alkyl-d-homo-gona-diener med hormonvirkning |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO753505A NO142349C (no) | 1974-10-18 | 1975-10-17 | Analogifremgangsmaate for fremstilling av terapeutisk virksomme 13-alkyl d-homogonadiener |
Country Status (27)
| Country | Link |
|---|---|
| JP (1) | JPS5165750A (no) |
| AT (1) | AT348697B (no) |
| BE (1) | BE834597A (no) |
| CA (1) | CA1052768A (no) |
| CH (2) | CH606113A5 (no) |
| DD (1) | DD123331A5 (no) |
| DE (1) | DE2546613A1 (no) |
| DK (1) | DK137088B (no) |
| ES (1) | ES441863A1 (no) |
| FI (1) | FI53974C (no) |
| FR (1) | FR2287902A1 (no) |
| GB (1) | GB1477567A (no) |
| HK (1) | HK40580A (no) |
| HU (1) | HU174009B (no) |
| IE (1) | IE42024B1 (no) |
| IL (1) | IL48239A (no) |
| KE (1) | KE3062A (no) |
| LU (1) | LU73595A1 (no) |
| MY (1) | MY8100137A (no) |
| NL (1) | NL7512221A (no) |
| NO (2) | NO142349C (no) |
| NZ (1) | NZ178880A (no) |
| PH (1) | PH13491A (no) |
| PL (1) | PL100429B1 (no) |
| SE (1) | SE7511640L (no) |
| SU (1) | SU602121A3 (no) |
| ZA (1) | ZA756243B (no) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL51468A (en) * | 1976-02-23 | 1981-01-30 | Sparamedica Ag | 17 -hydroxy- -d-homosteroid derivatives,their preparation and pharmaceutical compositions containing them |
| US4788218A (en) * | 1984-05-21 | 1988-11-29 | Sri International | 17 a β-hydroxy-7 α-methyl-d-homo-19-norandrost-4,16-diene-3-one and the 17-esters thereof: methods of preparation and uses |
| JPS61502186A (ja) * | 1984-05-21 | 1986-10-02 | エス・ア−ル・アイ・インタ−ナシヨナル | １７αβ−ヒドロキシ−７α−メチル−Ｄ−ホモ−１９−ノルアンドロスト−４，１６−ジエン−３−オンおよびその１７−エステル、ならびにその製法および使用 |
-
1974
- 1974-10-18 CH CH1398974A patent/CH606113A5/xx not_active IP Right Cessation
-
1975
- 1975-10-01 ZA ZA00756243A patent/ZA756243B/xx unknown
- 1975-10-03 IL IL48239A patent/IL48239A/xx unknown
- 1975-10-07 FI FI752797A patent/FI53974C/fi not_active IP Right Cessation
- 1975-10-15 FR FR7531502A patent/FR2287902A1/fr active Granted
- 1975-10-15 NZ NZ178880A patent/NZ178880A/xx unknown
- 1975-10-15 CA CA237,710A patent/CA1052768A/en not_active Expired
- 1975-10-16 SU SU752180252A patent/SU602121A3/ru active
- 1975-10-16 JP JP50123871A patent/JPS5165750A/ja active Pending
- 1975-10-16 SE SE7511640A patent/SE7511640L/ not_active Application Discontinuation
- 1975-10-16 LU LU73595A patent/LU73595A1/xx unknown
- 1975-10-16 DD DD188897A patent/DD123331A5/xx unknown
- 1975-10-16 PH PH17667A patent/PH13491A/en unknown
- 1975-10-17 NL NL7512221A patent/NL7512221A/xx not_active Application Discontinuation
- 1975-10-17 PL PL1975184060A patent/PL100429B1/pl unknown
- 1975-10-17 GB GB4263775A patent/GB1477567A/en not_active Expired
- 1975-10-17 BE BE161009A patent/BE834597A/xx unknown
- 1975-10-17 ES ES441863A patent/ES441863A1/es not_active Expired
- 1975-10-17 HU HU75HO1848A patent/HU174009B/hu unknown
- 1975-10-17 AT AT793775A patent/AT348697B/de not_active IP Right Cessation
- 1975-10-17 NO NO753505A patent/NO142349C/no unknown
- 1975-10-17 IE IE2264/75A patent/IE42024B1/en unknown
- 1975-10-17 DK DK469975AA patent/DK137088B/da unknown
- 1975-10-17 DE DE19752546613 patent/DE2546613A1/de not_active Withdrawn
-
1977
- 1977-11-10 CH CH1371977A patent/CH618446A5/de not_active IP Right Cessation
-
1979
- 1979-06-25 NO NO792125A patent/NO143503C/no unknown
-
1980
- 1980-07-07 KE KE3062A patent/KE3062A/xx unknown
- 1980-08-07 HK HK405/80A patent/HK40580A/xx unknown
-
1981
- 1981-12-30 MY MY137/81A patent/MY8100137A/xx unknown
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