CH236759A - Process for the preparation of a lactone of the cyclopentanopolyhydrophenanthrene series. - Google Patents
Process for the preparation of a lactone of the cyclopentanopolyhydrophenanthrene series.Info
- Publication number
- CH236759A CH236759A CH236759DA CH236759A CH 236759 A CH236759 A CH 236759A CH 236759D A CH236759D A CH 236759DA CH 236759 A CH236759 A CH 236759A
- Authority
- CH
- Switzerland
- Prior art keywords
- lactone
- lactonization
- agents
- preparation
- action
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 8
- 150000002596 lactones Chemical class 0.000 title claims description 3
- 238000002360 preparation method Methods 0.000 title claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 238000007273 lactonization reaction Methods 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- 239000007795 chemical reaction product Substances 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 230000000911 decarboxylating effect Effects 0.000 claims description 3
- 230000003301 hydrolyzing effect Effects 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 239000013078 crystal Substances 0.000 claims description 2
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- 150000003901 oxalic acid esters Chemical class 0.000 claims description 2
- 239000000047 product Substances 0.000 claims description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 claims 1
- 230000001419 dependent effect Effects 0.000 claims 1
- 239000007858 starting material Substances 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 239000002574 poison Substances 0.000 description 2
- 231100000614 poison Toxicity 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- -1 their alcoholates Chemical class 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 229930183217 Genin Natural products 0.000 description 1
- 241000233780 Scilla Species 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 125000000422 delta-lactone group Chemical group 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 150000008131 glucosides Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J19/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 by a lactone ring
-
- 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)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung eines Laetons der Cyelopentanopolyhydrophenanthren-Reihe. Die Genine -der -S-cilla-Glucoside und der Krötengifte sind Derivate der Cyclopentano- polyhydrop@henanthren-Reihe,
die als eharak- teristisches Merkmal in der Seitenkette eine einfach oder doppelt ungesättigte 8-Lacton- Gruppe aufweisen. Synthetische Verfahren zur Herstellung solchem Stoffe sind bis jetzt nicht bekannt .geworden.
Es wurde nun gefunden, dass man zu einem Lacton der Cyclo#pentano#polyhydro- phenanthren-Reihe gelangen kann, wenn man eine Verbindung ,der Formel
EMI0001.0024
worin X eine veresterte Carboxylgruppe und R einen durch Hydrolyse in eine Hydroxyl- gruppe überführbaren Rest bedeuten, mit einem Oxalsäureester kondensiert,
das Reak- tionsprodukt der Einwirkung -von Mitteln unterwirft, die eine Lactonisierung herbei führen, und anschliessend mit @decarboxy- lierenden und hydrolysierenden Mitteln be handelt.
Die Kündensation wird zweckmässig in Gegenwart von Kondensationsmitteln, wie Alkalimetallen, ihren Alkoholaten, Amiden und ähnlich wirkenden Stoffen vorgenom men, wobei auch Lösungs- und Verdünnungs mittel zugegen sein können.
Die Lactonisierung des Kondensations- produktes kann beispielsweise durch Einwir- kunig von Säuren geschehen oder mit Hilfe von umesternden Mitteln erfolgen. Nach der Lactonisierung werden sodann decarboxylie- rende und .hydrolysiemende Mittel einwirken gelassen.
Das neue Verfahrensprodukt, das 45,6;20,22 3-Ogy-21-o.xymethylen-nor-fcho@ladiensäure- lacton, bildet fairblose Kristalle. Es stellt ein ö-Lacton dar, das mit,
den Geninen der Scilla- Gluüoside und der Krötengifte verwandt und deshalb von grossem Interesse für die Thera- pie ist. Es soll therapeutische Verwendung finden oder als Zwischenprodukt zur Herstel lung therapeutisch verwendbarer Verbindun gendienen.
<I>Beispiel:</I> <B>5,0</B> ,g 45,6;20,22-3-Acetoxy-nor-eho-Iadien- säure-methylester und 1,5 g Oxalester werden in abs. Äther gelöst und mit 1,4 g frischem Kalium-methylat versetzt.. Die Reaktions mischung färbt ,sich langsam dunkel. Man überlässt sie während 24 Stunden sich selbst und zersetzt dann mit verdünntem Eisessig. Die Reaktionsprodukte werden in Äther auf- genammen, getrocknet, und der Äther wird verdampft.
Den Rückstand behandelt man in der Wärme mit Bromwasserstoff-Eisessig, dem etwas Acetanhydrid beigemischt ist. Das Reaktionsprodukt wird durch Verdünnen mit MTasser ausgefällt, mit viel Wasser nach ,gewaschen und und im Hochvakuum sublimiert, wobei Decarboxylierung stattfindet. Das Sublimat wird chromatographisch durch Ad- sorption an Aluminiumoxyd .gereinigt.
Man erhält das d5.6; 20,22-3- Aeetoxy-2'1-oxy methy - Ien-nor-cho@adensäure-lacton, welches insbe sondere mit sauren Mitteln, zum d5,6:20,?2-3 Oxy-21-oxymethylen-nor-choladiensäure-lac.- ton verseift wird.
Process for the preparation of a laeton of the cyelopentanopolyhydrophenanthrene series. The genins - the -S-cilla-glucosides and the toad poisons are derivatives of the cyclopentano- polyhydrop @ henanthrene series,
which have a mono- or doubly unsaturated 8-lactone group as a characteristic feature in the side chain. Synthetic processes for the production of such substances are not yet known .get.
It has now been found that a lactone of the cyclo # pentano # polyhydrophenanthrene series can be obtained if a compound of the formula
EMI0001.0024
where X is an esterified carboxyl group and R is a radical which can be converted into a hydroxyl group by hydrolysis, condensed with an oxalic acid ester,
the reaction product is subjected to the action of agents which bring about lactonization, and then treated with @decarboxy- lating and hydrolyzing agents.
The termination is expediently carried out in the presence of condensation agents such as alkali metals, their alcoholates, amides and similarly acting substances, it being possible for solvents and diluents to be present.
The lactonization of the condensation product can take place, for example, through the action of acids or with the aid of interesterifying agents. After the lactonization, decarboxylating and hydrolyzing agents are allowed to act.
The new process product, 45.6; 20.22 3-Ogy-21-o.xymethylene- nor-fcho@ladienoic acid-lactone, forms fairbless crystals. It is an δ-lactone that is
related to the genines of the Scilla glucosides and the toad poisons and is therefore of great interest for therapy. It is intended to be used therapeutically or as an intermediate for the manufacture of therapeutically usable compounds.
<I> Example: </I> <B> 5.0 </B>, g 45.6; 20.22-3-acetoxy-nor-eho-iadienoic acid methyl ester and 1.5 g oxal ester are in Section. Dissolved ether and mixed with 1.4 g of fresh potassium methylate. The reaction mixture turns dark slowly. They are left to their own devices for 24 hours and then decomposed with diluted glacial acetic acid. The reaction products are taken up in ether, dried, and the ether is evaporated.
The residue is treated warm with hydrogen bromide-glacial acetic acid, to which a little acetic anhydride has been added. The reaction product is precipitated by dilution with M water, washed with plenty of water and sublimed in a high vacuum, decarboxylation taking place. The sublimate is purified by chromatography by adsorption onto aluminum oxide.
You get the d5.6; 20,22-3- Aeetoxy-2'1-oxy methy - Ien-nor-cho @ adenic acid-lactone, which in particular with acidic agents, for the d5,6: 20,? 2-3 Oxy-21-oxymethylene-nor -choladienoic acid-lac.- clay is saponified.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH236759T | 1941-06-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH236759A true CH236759A (en) | 1945-03-15 |
Family
ID=4459597
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH236759D CH236759A (en) | 1941-06-14 | 1941-06-14 | Process for the preparation of a lactone of the cyclopentanopolyhydrophenanthrene series. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH236759A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2002540A1 (en) * | 1968-02-23 | 1969-10-17 | Hoechst Ag |
-
1941
- 1941-06-14 CH CH236759D patent/CH236759A/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2002540A1 (en) * | 1968-02-23 | 1969-10-17 | Hoechst Ag |
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