CH206602A - Process for the preparation of 3-oxybisnorcholenic acid. - Google Patents
Process for the preparation of 3-oxybisnorcholenic acid.Info
- Publication number
- CH206602A CH206602A CH206602DA CH206602A CH 206602 A CH206602 A CH 206602A CH 206602D A CH206602D A CH 206602DA CH 206602 A CH206602 A CH 206602A
- Authority
- CH
- Switzerland
- Prior art keywords
- acid
- formula
- oxybisnorcholenic
- isolation
- oxidative degradation
- Prior art date
Links
- 239000002253 acid Substances 0.000 title claims description 14
- 238000000034 method Methods 0.000 title claims description 13
- 238000002360 preparation method Methods 0.000 title description 3
- 239000000203 mixture Substances 0.000 claims description 13
- 230000003647 oxidation Effects 0.000 claims description 8
- 238000007254 oxidation reaction Methods 0.000 claims description 8
- 238000002955 isolation Methods 0.000 claims description 7
- 230000007062 hydrolysis Effects 0.000 claims description 6
- 238000006460 hydrolysis reaction Methods 0.000 claims description 6
- 238000010525 oxidative degradation reaction Methods 0.000 claims description 6
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 5
- 238000007127 saponification reaction Methods 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 238000001640 fractional crystallisation Methods 0.000 claims description 3
- 238000004508 fractional distillation Methods 0.000 claims description 3
- 239000007800 oxidant agent Substances 0.000 claims description 3
- 239000007858 starting material Substances 0.000 claims description 3
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- HCXVJBMSMIARIN-PHZDYDNGSA-N stigmasterol Chemical class 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 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 239000000243 solution Substances 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 2
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- LDEKDFZOPHVUAB-UHFFFAOYSA-N acetic acid;dihydrobromide Chemical compound Br.Br.CC(O)=O LDEKDFZOPHVUAB-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
- 229910001863 barium hydroxide Inorganic materials 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J75/00—Processes for the preparation of steroids in general
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Description
Verfahren zur Darstellung von 3-Ogybisnor eholensäure. Vorliegende Erfindung betrifft ein Ver fahren zur Herstellung von 3-Oxybisrrorcholerr- säure, welches dadurch gekennzeichnet ist, daLS man aus einem Oxydationsgemisch,
wel ches durch oxydativen Abbau eines sterin- artigen Stoffes der Bruttoformel C21H38Rg und der Konstitutionsformel
EMI0001.0011
worin R einen durch Hydrolyse in die Hydro- xylgruppe überführbaren Substituenten und g einen beim oxydativen Abbau in die COOH-Gruppe übergehenden Rest bedeuten, mit Hilfe solcher Oxydationsmittel erhältlich ist,
die einfache Kohlenstoff-Kohlenstoffbin- dungen zu spalten vermögen, die Verbindung der Bruttoformel C21H32RCOOR und der Konstitutionsformel
EMI0001.0023
isoliert und mit einem hydrolysierenden Mit tel behandelt.
Die durch Hydrolyse in die Hydroxyl- gruppe umwandelbare Gruppe R kann eine Ester- oder Äthergruppe oder irgend eine andere durch Hydrolyse in die Hydroxyl- gruppe zurückverwandelbare Gruppe sein. Die in die COOH-Gruppe überführbare Gruppe g kann ebenfalls ein beliebiger Rest sein, zum Beispiel ein Kohlenwasserstoffrest der Zusammensetzung CSH15, in welchen Fällen es sich um ein Stigmasterinderivat handelt.
Die als Endprodukt des Verfahrens an fallende 3-Oxybisnorcliolensäure besitzt die allgemeine Zusammensetzung C:_Ha4Os und die Konstitutionsformel
EMI0002.0003
Die 3-Oxybisriorcholensäure ist bekannt; sie besitzt einen Schmelzpunkt von 295 bis <B>3020</B> C und kann als Zwischenprodukt für die Darstellung physiologisch wertvoller Ver bindungen Verwendung finden.
Das als Ausgangsmaterial für das erfin dungsgemässe Verfahren dienende Oxydations gemisch, wie es aus sterinartigen Stoffen der allgemeinen Formel CgiH82RX erhältlich ist, kann in beliebiger Weise erhalten worden sein, zum Beispiel durch Behandlung von sterinartigen Stoffen der Zusammensetzung C81H3=Rg mit Ozon bezw. Oxydationsmitteln, die fähig sind, einfache Kohlenstoff-Kohlen- stoffbindungen zu spalten,
wobei die Doppel bindung im Ringsystem der sterinartigen Stoffe durch Anlagerung von Halogen oder Halogenwasserstoff vor dem Angriff des Oxy- datiosmittels intermediär geschützt worden sein kann.
Die Isolierung der Derivate der 3-Oxy- bisnorcholensäure aus dem Oxydationsge misch und ihre Hydrolyse kann in verschie dener Weise erfolgen, wie dies dem Fach mann von andern Isolierungs- und Hy droly- sierungsverfahren bekannt ist.
Die Isolierung des 3-Oxybisnorcholensäui-edei-ivates der For mel C2iH32RC00H oder der 3-Oxybisnor- cholensäure selbst aus der Verseifungslösung wird zweckmässigerweise durch fraktionierte Kristallisation oder Destillation bewirkt.
<I>Beispiel 1:</I> Das bei der Oxydation von Stigmasterin- acetatdibromid mit Chromsäure anfallende Oxydationsgemisch wird mit Zinkstaub in Eisessiglösung entbronit. Hierauf wird das Reaktionsgemisch filtriert und das Filtrat nach Zusatz von Wasser mit Äther extra liiert. Die ätherische Lösung wird mit 2-n- Kalilauge geschüttelt und der dabei gebil dete Niederschlag abfiltriert und in Äther aufgenommen. Die ätherische Lösung wird mit verdünnter Schwefelsäure angesäuert, mit Wasser ausgewaschen und zur Troehne ver dampft.
Der Rückstand wird mit 5 o/oiger methylalkoholischer Kalilauge verseift. Das Verseifungsgemisch wird angesäuert, mit Äther extrahiert und die ätherische Lösung zur Trockne verdampft. Der Rückstand lie fert beim Enikristallisieren aus AIetliylalkohol die 3-Oxybisnorcliolensäure vom Sehmelz- punkt zirka 295-302o <B>C.</B>
Beispiel <I>?:</I> Das Reaktionsgemisch,das bei derOxydation von Pliytostei-inacetatdibroniid mittels Chrom säure in Eises"ig erhalten ist, wird mit Zinkstaub entbroint; der überschüssige Zink staub wird abfiltriert und das Filtrat in Wasser gegossen.
Die wässrige Lösung wird dann mit Äther extrahiert und die ätherische Lösung mit 2-n-Natrorilauge geschüttelt. Der dabei ge bildete Niederschhig wird abfiltriert, in Äther aufgenommen und die ätherische Lösung mit Schwefelsäure angesäuert. Diese wird hier auf zur Trockne eingedampft, wonach man den Rückstand mit niethylalkoholischer Kali lauge verseift. Nach Ansäuern des Versei fungsgemisches iuid Extraktion desselben mit Äther wird die ätherische Lösung zur Trockne verdampft.
Der Rückstand wird in heissem Methanol gelöst und zu dieser Lösung eine heisse Methanollösung von Bariumhydroxyd zugegeben. Nachdem das Gemisch auf Zim- inertemperatur abgekühlt ist, wird der Nieder schlag abfiltriert.
Das Filtrat wird in Wasser gegossen, mit Salzsäure angesäuert und mit Äther extrahiert. Die ätherische Lösung wird mit Wasser ausgewaschen und zur Trockne ver dampft. Der Rückstand wird aus Eisessig unikristallisiert, wobei die freie 3-Oxybisnor- cholensäure vom Schmelzpunkt 295-3Ö2 C anfällt.
Process for the preparation of 3-ogybisnor eholenic acid. The present invention relates to a process for the production of 3-oxybisrrorcholerric acid, which is characterized in that one from an oxidation mixture,
which by oxidative degradation of a sterol-like substance of the gross formula C21H38Rg and the constitutional formula
EMI0001.0011
in which R is a substituent which can be converted into the hydroxyl group by hydrolysis and g is a radical which is converted into the COOH group during oxidative degradation, can be obtained with the aid of such oxidizing agents,
capable of cleaving simple carbon-carbon bonds, the combination of the gross formula C21H32RCOOR and the constitutional formula
EMI0001.0023
isolated and treated with a hydrolyzing agent.
The group R which can be converted into the hydroxyl group by hydrolysis can be an ester or ether group or any other group which can be converted back into the hydroxyl group by hydrolysis. The group g which can be converted into the COOH group can likewise be any desired radical, for example a hydrocarbon radical of the composition CSH15, in which cases it is a stigmasterine derivative.
The 3-oxybisnorcliolenoic acid obtained as the end product of the process has the general composition C: _Ha4Os and the constitutional formula
EMI0002.0003
3-Oxybisriorcholenic acid is known; it has a melting point of 295 to 3020 C and can be used as an intermediate for the preparation of physiologically valuable compounds.
The starting material for the process according to the invention serving oxidation mixture, as it is obtainable from sterol-like substances of the general formula CgiH82RX, can have been obtained in any way, for example by treating sterol-like substances of the composition C81H3 = Rg with ozone respectively. Oxidizing agents capable of breaking simple carbon-carbon bonds,
where the double bond in the ring system of the sterol-like substances may have been protected as an intermediate from attack by the oxy-dative agent by addition of halogen or hydrogen halide.
The isolation of the derivatives of 3-oxybisnorcholenic acid from the Oxydationsge and their hydrolysis can take place in various ways, as is known to those skilled in the art from other isolation and hydrolysis processes.
The isolation of the 3-oxybisnorcholensäui-edei-ivates of the formula C2iH32RC00H or the 3-oxybisnorcholenic acid itself from the saponification solution is expediently effected by fractional crystallization or distillation.
<I> Example 1: </I> The oxidation mixture obtained during the oxidation of stigmasterine acetate dibromide with chromic acid is debronite with zinc dust in glacial acetic acid solution. The reaction mixture is then filtered and the filtrate is extracted with ether after adding water. The ethereal solution is shaken with 2N potassium hydroxide solution and the precipitate formed is filtered off and taken up in ether. The ethereal solution is acidified with dilute sulfuric acid, washed out with water and evaporated to dryness.
The residue is saponified with 5% methyl alcoholic potassium hydroxide solution. The saponification mixture is acidified, extracted with ether and the ethereal solution evaporated to dryness. During enicrystallization from acetyl alcohol, the residue yields 3-oxybisnorcliolenoic acid with a melting point of about 295-302 ° C
Example <I>?: </I> The reaction mixture that is obtained from the oxidation of Pliytostei-inacetatdibroniid by means of chromic acid in ice "ig is deboned with zinc dust; the excess zinc dust is filtered off and the filtrate is poured into water.
The aqueous solution is then extracted with ether and the ethereal solution is shaken with 2N sodium hydroxide solution. The precipitate formed is filtered off, taken up in ether and the ethereal solution acidified with sulfuric acid. This is here evaporated to dryness, after which the residue is saponified with niethyl alcoholic potassium hydroxide solution. After acidifying the saponification mixture iuid extraction of the same with ether, the ethereal solution is evaporated to dryness.
The residue is dissolved in hot methanol and a hot methanol solution of barium hydroxide is added to this solution. After the mixture has cooled to the inert temperature, the precipitate is filtered off.
The filtrate is poured into water, acidified with hydrochloric acid and extracted with ether. The ethereal solution is washed out with water and evaporated to dryness. The residue is unicrystallized from glacial acetic acid, the free 3-oxybisnorcholenic acid with a melting point of 295-3Ö2 C being obtained.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE206602X | 1935-03-09 | ||
| CH194755T | 1936-03-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH206602A true CH206602A (en) | 1939-08-15 |
Family
ID=25722700
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH206602D CH206602A (en) | 1935-03-09 | 1936-03-07 | Process for the preparation of 3-oxybisnorcholenic acid. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH206602A (en) |
-
1936
- 1936-03-07 CH CH206602D patent/CH206602A/en unknown
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