NO130190B - - Google Patents
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- NO130190B NO130190B NO466268A NO466268A NO130190B NO 130190 B NO130190 B NO 130190B NO 466268 A NO466268 A NO 466268A NO 466268 A NO466268 A NO 466268A NO 130190 B NO130190 B NO 130190B
- Authority
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- Norway
- Prior art keywords
- general formula
- activity
- furan
- stands
- reaction
- Prior art date
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- -1 aluminum compound Chemical class 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 229910052782 aluminium Inorganic materials 0.000 claims description 3
- 150000003431 steroids Chemical class 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 230000000694 effects Effects 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 4
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 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
- PDMMFKSKQVNJMI-BLQWBTBKSA-N Testosterone propionate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CC)[C@@]1(C)CC2 PDMMFKSKQVNJMI-BLQWBTBKSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000002280 anti-androgenic effect Effects 0.000 description 3
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 229960001712 testosterone propionate Drugs 0.000 description 3
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- NOTFZGFABLVTIG-UHFFFAOYSA-N Cyclohexylethyl acetate Chemical compound CC(=O)OCCC1CCCCC1 NOTFZGFABLVTIG-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000003098 androgen Substances 0.000 description 2
- 230000001974 anti-anabolic effect Effects 0.000 description 2
- 230000001833 anti-estrogenic effect Effects 0.000 description 2
- 239000000051 antiandrogen Substances 0.000 description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 229960003387 progesterone Drugs 0.000 description 2
- 239000000186 progesterone Substances 0.000 description 2
- 210000001625 seminal vesicle Anatomy 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 201000010653 vesiculitis Diseases 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 229940030486 androgens Drugs 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000003388 anti-hormonal effect Effects 0.000 description 1
- 230000002158 anti-implantation Effects 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000000939 contragestive effect Effects 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 230000001836 utereotrophic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J73/00—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms
- C07J73/001—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom
- C07J73/003—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom by oxygen as hetero atom
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)
Description
Analogifremgangsmåte for fremstilling Analogy method of manufacture
av nye, terapeutisk aktive A-furan- of new, therapeutically active A-furan-
steroider. steroids.
Den foreliggende oppfinnelse angår en analogifremgangsmåte for fremstilling av nye, terapeutisk aktive A-furan-steroider med den generelle formel I The present invention relates to an analogue process for the production of new, therapeutically active A-furan steroids of the general formula I
hvori står for hydrogen eller acetyl, og det særegne ved analogifremgangsmåten er at et steroid med den generelle formel II hvori R-^ har den ovennevnte betydning, reduseres med en aluminium-forbindelse med den generelle formel III in which stands for hydrogen or acetyl, and the peculiarity of the analogous procedure is that a steroid of the general formula II in which R-^ has the above-mentioned meaning is reduced with an aluminum compound of the general formula III
hvori M står for et alkalimetall og R står for et lavere alkylradikal eller et lavere alkoksyradikal, n er 0 eller 1, where M stands for an alkali metal and R stands for a lower alkyl radical or a lower alkoxy radical, n is 0 or 1,
og m er et helt tall fra 0-3 når n er 0, og m er et helt tall fra 0-4 når n er 1. Metoden er beskrevet i britisk patentskrift nr. 1.081.647 (Shionogi & Co.Ltd.). and m is an integer from 0-3 when n is 0, and m is an integer from 0-4 when n is 1. The method is described in British Patent No. 1,081,647 (Shionogi & Co.Ltd.).
Utgangsforbindelsen kan fremstilles ut fra det tilsvarende 19-nor-3-oxo-4-en-steroid ved oksydasjon og dekarboksylering for dannelse av 5-oxo-A-dinor-2,5-seco-19-norsteroid-2-karboksylsyre, som i rekkefolge underkastes Grignard reaksjon, dehydratisering og oksydasjon for dannelse av 5-oxo-A-dinor-2,5-seco-19-nor-steroid-2-karboksylsyre og deretter enol-laktoniseres for å gi den onskede utgangsforbindelse med formel II. The starting compound can be prepared from the corresponding 19-nor-3-oxo-4-ene-steroid by oxidation and decarboxylation to form 5-oxo-A-dinor-2,5-seco-19-norsteroid-2-carboxylic acid, which sequentially subjected to Grignard reaction, dehydration and oxidation to form 5-oxo-A-dinor-2,5-seco-19-nor-steroid-2-carboxylic acid and then enol-lactonized to give the desired starting compound of formula II.
Som reduksjonsmiddel anvendes en aktiv aluminiumforbindelse An active aluminum compound is used as a reducing agent
med den generelle formel III. En omsetning i henhold til oppfinnelsen kan utfores innen et bredt temperaturområde, endog ved -80°C, avhengig av den benyttede forbindelse for å gi de onskede A-furan-steroidforbindelser med formel I. with the general formula III. A reaction according to the invention can be carried out within a wide temperature range, even at -80°C, depending on the compound used to give the desired A-furan-steroid compounds of formula I.
Omsetningen mellom utgangsforbindelsene og det aktive reduksjonsmiddel kan utfores i et inert løsningsmiddel, f.eks. et flytende hydrokarbon som petroleter, petrolbensin, ligroin, benzen eller toluen, eller en eter som f.eks. dietyleter, dipropyleter, dibutyleter, diglym (dietylenglykoldimetyleter), tetrahydrofuran, tetrahydropyran og dioksan. Selv om fremgangsmåten kan gjennomfores innen et bredt temperaturområde foretrekkes det å utfore omsetningen mellom -50°C og 0°C når reduksjonsmidlet er dialkylaluminiumhydrid eller litiumaluminiumhydrid. The reaction between the starting compounds and the active reducing agent can be carried out in an inert solvent, e.g. a liquid hydrocarbon such as petroleum ether, benzine, naphtha, benzene or toluene, or an ether such as e.g. diethyl ether, dipropyl ether, dibutyl ether, diglyme (diethylene glycol dimethyl ether), tetrahydrofuran, tetrahydropyran and dioxane. Although the method can be carried out within a wide temperature range, it is preferred to carry out the reaction between -50°C and 0°C when the reducing agent is dialkyl aluminum hydride or lithium aluminum hydride.
Omroring og erstatning av luft med en inert gass som f.eks. nitrogen eller argon anvendes fortrinnsvis under omsetningen. Agitation and replacement of air with an inert gas such as e.g. nitrogen or argon is preferably used during the reaction.
I mange tilfelle kan den onskede furanforbindelse fremstilles ved hjelp av disse reduksjonsmidler i nesten kvantitativt utbytte. Etter omsetningen blandes reaksjonsblandingen med vann eller en organisk eller uorganisk syre som f.eks. saltsyre, bromhydrogensyre, svovelsyre, benzensulfonsyre eller eddiksyre for å spalte adduktet og overskudd av reduksjonsmiddel. In many cases the desired furan compound can be prepared using these reducing agents in almost quantitative yield. After the reaction, the reaction mixture is mixed with water or an organic or inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, benzenesulfonic acid or acetic acid to cleave the adduct and excess reducing agent.
Deretter ekstraheres med et passende losningsmiddel for å isolere de onskede A-furan-steroidforbindelser. It is then extracted with a suitable solvent to isolate the desired A-furan-steroid compounds.
De foreliggende A-furan-steroidforbindelser har nyttige farmakologiske egenskaper og kan anvendes som midler for regulering av de fysiologiske funksjoner. Spesielt viser A-furanoostran-17(3 -ol-derivatene antideciduomatogen aktivitet, antiuterotropin aktivitet, antianabolsk aktivitet, antiandrogen aktivitet, uterotrop aktivitet, antiostrogen aktivitet, contragestiv aktivitet og lipidomsettende aktivitet. Det skal bemerkes at nesten alle disse virkningene er antihormonal aktivitet. Når disse nye forbindelser, 3-oksa-A-norostra-l,5(10)-dien-173 -ol og acetatet derav, tilfores subkutant så gir de fullstendig blokade av den desiduale vekst som induseres av progesteron. Subkutan tilforsel av 3-oksa-A-norostra-l, 5 (10) -dien-17 (3 -ol forhindret vekst av seminalblære og levator ani-muskelen frembragt av testosteronpropionat i en utstrekning på 10 til 30%. The present A-furan-steroid compounds have useful pharmacological properties and can be used as agents for regulating the physiological functions. In particular, the A-furanoostran-17(3-ol) derivatives show antideciduomatogenic activity, antiuterotropin activity, antianabolic activity, antiandrogen activity, uterotropic activity, antiestrogenic activity, contragestive activity and lipid-converting activity. It should be noted that almost all of these effects are antihormonal activity. When these new compounds, 3-oxa-A-norostra-1,5(10)-dien-173-ol and its acetate, are administered subcutaneously and they completely block progesterone-induced decidual growth Subcutaneous administration of 3-oxa -A-norostra-1,5(10)-dien-17(3)ol prevented the growth of the seminal vesicle and the levator ani muscle produced by testosterone propionate to an extent of 10 to 30%.
Ytterligere forsoksdata: Additional trial data:
Anti- deciduomatoaen virkning: Fullstendig blokkering av desidual vekst, fremkalt av progesteron, ved en dose på 0.8 mg som tilfores subkutant til mus i 9 dager. Anti-deciduomatoa effect: Complete blocking of decidual growth, induced by progesterone, at a dose of 0.8 mg administered subcutaneously to mice for 9 days.
Anti- implantering: Virkning lik 20% ved en dose på 1 mg som tilfores subkutant til mus i 6 dager. Anti-implantation: Efficacy equal to 20% at a dose of 1 mg administered subcutaneously to mice for 6 days.
Anti- anabolsk; Virkning lik 78% av testosteron-propionat med Anti-anabolic; Effect equal to 78% of testosterone propionate with
en dose på 1 mg, som tilfores subkutant til mus i 10 dager. a dose of 1 mg, which is administered subcutaneously to mice for 10 days.
Anti- ostrogen; Virkning lik 44% av Ostradiol tilfort i en dose Anti-estrogen; Effect equal to 44% of Ostradiol added in one dose
på 0.3 mg, som tilfores subkutant til mus, når musene undersokes ved vaginal TTC-reduksjon. of 0.3 mg, which is administered subcutaneously to mice, when the mice are examined by vaginal TTC reduction.
Anti- åndrogen: Virkning lik 39% okning av sedblære-vekt fremkalt Ved testosteron-propionat med en dose på 1 mg, som tilfores subkutant i 10 dager. Anti-androgen: Effect equal to 39% increase in seminal vesicle weight induced by testosterone propionate with a dose of 1 mg, which is administered subcutaneously for 10 days.
Fra "Journal of the Medicinal Chemistry" er det kjent A-mettede 19-mety1-steroider, som er analoge til androgenene og som således skiller seg fra de foreliggende A-aromatiske steroider, som er analoge til østrogenene. From the "Journal of the Medicinal Chemistry" there are known A-saturated 19-methyl steroids, which are analogous to the androgens and which thus differ from the present A-aromatic steroids, which are analogous to the estrogens.
De nevnte 19-metyl-steroider har videre bare en svak androgen The aforementioned 19-methyl steroids also have only a weak androgen
og anti-androgen virkning. and anti-androgenic effect.
De. folgende eksempler illustrerer oppfinnelsen ytterligere: The. the following examples further illustrate the invention:
Eksempel 1 Example 1
Til en losning av 517 mg 17 (3 -acetyloksy-3-oksa-A-norostra - 1(10)-en-2-on i 14 ml tetrahydrofuran, avkjolt til -20°C til To a solution of 517 mg of 17 (3-acetyloxy-3-oxa-A-norostra-1(10)-en-2-one in 14 ml of tetrahydrofuran, cooled to -20°C to
-25°C, tilsettes dråpevis en losning av 0.8 g diisobutylaluminiumhydrid i 4.7 ml tetrahydrofuran. Den resulterende blanding omrores i 20 min.-ved samme temperatur og overskudd av diisobutylaluminiumhydrid spaltes ved tilsetning av noen få dråper 10% svovelsyre, "vann tilsettes til reaksjonsblandingen og det foretas ekstraksjon med metylenklorid. Ekstrakten vaskes med vann, torres og inndampes. Omkrystallisering av råproduktet fra en blanding av aceton og heksan gir 294 mg -25°C, a solution of 0.8 g diisobutylaluminum hydride in 4.7 ml tetrahydrofuran is added dropwise. The resulting mixture is stirred for 20 min at the same temperature and excess diisobutylaluminum hydride is decomposed by adding a few drops of 10% sulfuric acid, water is added to the reaction mixture and extraction is carried out with methylene chloride. The extract is washed with water, dried and evaporated. Recrystallization of the crude product from a mixture of acetone and hexane yields 294 mg
3-oksa-A-norostra-l, 5 (10 )-dien-17[3-ol med smeltepunkt 137.5 3-oxa-A-norostra-1, 5 (10 )-dien-17[3-ol with melting point 137.5
til 139.5°C. IR:V <C>^<1>4 3628, 1505, 902 cm<-1>. Tynnsjikt-kromatografering: Rf 0.52 (silikagel: cykloheksanetylacetat (1:1)). to 139.5°C. IR: V <C>^<1>4 3628, 1505, 902 cm<-1>. Thin layer chromatography: Rf 0.52 (silica gel: cyclohexane ethyl acetate (1:1)).
Eksempel 2 Example 2
Til en losning av 10 mg 17(3-acetyloksy-3-oksa-A-nor6stra-1(10)-en-2-on i 10 ml tetrahydrofuran, avkjolt til -20° til -25°C, tilsettes dråpevis en losning av 15 mg diisobutyl-aluminium-hydrid i 1 ml tetrahydrofuran. Den dannede blanding omrores i 10 minutter ved samme temperatur og overskudd av reaksjonskomponenten dekomponeres ved tilsetning av noen få dråper 10% svovelsyre. Reaksjonsblåndingen fortynnes med vann og ekstraheres med metylenklorid. Den ekstraherte losning vaskes med vann, torkes og inndampes. Tynnskikts-kromatografering gir 3-oksa-A-norostra-l, 5 (10 )-dien-17(3-ol med smp. 139°C, og acetatet derav med IR:^ max 1740' 1502' 1243 cm •' Tynnskikts-kromatogram Rf 0.80 (silikagel: cykloheksan-etylacetat (1:1)). Acetatet er identisk med acetylerings-produktet av 17(3-ol forbindelsen, som er identisk med produktet fra eksempel 1. To a solution of 10 mg of 17(3-acetyloxy-3-oxa-A-nor6stra-1(10)-en-2-one in 10 ml of tetrahydrofuran, cooled to -20° to -25°C, is added dropwise a solution of 15 mg of diisobutyl aluminum hydride in 1 ml of tetrahydrofuran. The resulting mixture is stirred for 10 minutes at the same temperature and the excess of the reaction component is decomposed by adding a few drops of 10% sulfuric acid. The reaction mixture is diluted with water and extracted with methylene chloride. The extracted solution washed with water, dried and evaporated. Thin-layer chromatography gives 3-oxa-A-norostra-1, 5 (10 )-dien-17(3-ol with m.p. 139°C, and the acetate thereof with IR:^ max 1740 ' 1502' 1243 cm •' Thin-layer chromatogram Rf 0.80 (silica gel: cyclohexane-ethyl acetate (1:1)). The acetate is identical to the acetylation product of the 17(3-ol compound, which is identical to the product from example 1.
(utbyttet av 17|3-ol forbindelsen og acetatet derav var omtrent (the yield of the 17|3-ol compound and its acetate was approx
2 mg og 1 mg). 2 mg and 1 mg).
Claims (1)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB5306367A GB1200640A (en) | 1967-11-22 | 1967-11-22 | A-furan oxasteroids and their preparation |
Publications (1)
Publication Number | Publication Date |
---|---|
NO130190B true NO130190B (en) | 1974-07-22 |
Family
ID=10466492
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO466268A NO130190B (en) | 1967-11-22 | 1968-11-22 |
Country Status (8)
Country | Link |
---|---|
CH (1) | CH560187A5 (en) |
DE (1) | DE1810477A1 (en) |
DK (1) | DK123531B (en) |
FR (1) | FR1602555A (en) |
GB (1) | GB1200640A (en) |
NL (1) | NL6816764A (en) |
NO (1) | NO130190B (en) |
SE (1) | SE346784B (en) |
-
1967
- 1967-11-22 GB GB5306367A patent/GB1200640A/en not_active Expired
-
1968
- 1968-11-18 DK DK560168A patent/DK123531B/en unknown
- 1968-11-21 FR FR1602555D patent/FR1602555A/en not_active Expired
- 1968-11-21 SE SE1585568A patent/SE346784B/xx unknown
- 1968-11-22 NL NL6816764A patent/NL6816764A/xx unknown
- 1968-11-22 DE DE19681810477 patent/DE1810477A1/en active Pending
- 1968-11-22 NO NO466268A patent/NO130190B/no unknown
- 1968-11-22 CH CH1743968A patent/CH560187A5/xx not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
DK123531B (en) | 1972-07-03 |
CH560187A5 (en) | 1975-03-27 |
GB1200640A (en) | 1970-07-29 |
NL6816764A (en) | 1969-05-27 |
SE346784B (en) | 1972-07-17 |
DE1810477A1 (en) | 1969-08-14 |
FR1602555A (en) | 1970-12-28 |
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