CH317879A - Process for the isomerization of spirostanes to propionates of furosten- (20:22) -26-ols - Google Patents
Process for the isomerization of spirostanes to propionates of furosten- (20:22) -26-olsInfo
- Publication number
- CH317879A CH317879A CH317879DA CH317879A CH 317879 A CH317879 A CH 317879A CH 317879D A CH317879D A CH 317879DA CH 317879 A CH317879 A CH 317879A
- Authority
- CH
- Switzerland
- Prior art keywords
- isomerization
- dependent
- propionates
- spirostanes
- ols
- Prior art date
Links
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 title claims description 10
- 238000000034 method Methods 0.000 title claims description 10
- INLFWQCRAJUDCR-LYLBMTSKSA-N spirostane group Chemical class [C@@H]12C[C@@H]3O[C@]4(CC[C@@H](C)CO4)[C@@H](C)[C@@H]3[C@@]1(C)CC[C@H]1[C@H]2CCC2CCCC[C@]12C INLFWQCRAJUDCR-LYLBMTSKSA-N 0.000 title claims description 7
- 238000006317 isomerization reaction Methods 0.000 title claims description 6
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 claims description 7
- 238000010992 reflux Methods 0.000 claims description 4
- QVZULXNXCIFMTL-IXCVKQQLSA-N 4802-74-8 Chemical compound O([C@@H]1[C@@H]([C@]2(CC(=O)[C@@H]3[C@@]4(C)CC[C@H](O)C[C@@H]4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 QVZULXNXCIFMTL-IXCVKQQLSA-N 0.000 claims description 3
- 238000009835 boiling Methods 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- 235000019260 propionic acid Nutrition 0.000 claims description 3
- 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 claims description 3
- 239000007858 starting material Substances 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 2
- 230000001419 dependent effect Effects 0.000 claims 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 4
- WQLVFSAGQJTQCK-UHFFFAOYSA-N diosgenin Natural products CC1C(C2(CCC3C4(C)CCC(O)CC4=CCC3C2C2)C)C2OC11CCC(C)CO1 WQLVFSAGQJTQCK-UHFFFAOYSA-N 0.000 description 4
- INLFWQCRAJUDCR-IQVMEADQSA-N (1R,2S,4S,5'S,6R,7S,8R,9S,12S,13S)-5',7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.02,9.04,8.013,18]icosane-6,2'-oxane] Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CCCCC4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@H](C)CO1 INLFWQCRAJUDCR-IQVMEADQSA-N 0.000 description 3
- UVLDESQWQRMYKD-UHFFFAOYSA-N Neobotogenin Natural products CC1C(C2(C(=O)CC3C4(C)CCC(O)CC4=CCC3C2C2)C)C2OC11CCC(C)CO1 UVLDESQWQRMYKD-UHFFFAOYSA-N 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- QOLRLLFJMZLYQJ-LOBDNJQFSA-N Hecogenin Chemical compound O([C@@H]1[C@@H]([C@]2(C(=O)C[C@@H]3[C@@]4(C)CC[C@H](O)C[C@@H]4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 QOLRLLFJMZLYQJ-LOBDNJQFSA-N 0.000 description 2
- OXLGJTRVVNGJRK-UHFFFAOYSA-N Hecogenin Natural products CC1CCC2(CC3CC4C5CCC6CC(O)CCC6(C)C5CC(=O)C4(C)C3C2C)OC1 OXLGJTRVVNGJRK-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- PBLXVDNSLUFVHF-GENYONHHSA-N Manogenin Chemical compound O([C@@H]1[C@@H]([C@]2(C(=O)C[C@@H]3[C@@]4(C)C[C@@H](O)[C@H](O)C[C@@H]4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 PBLXVDNSLUFVHF-GENYONHHSA-N 0.000 description 2
- RTMWIZOXNKJHRE-UHFFFAOYSA-N Tigogenin Natural products CC1COC2CC(C)(OC12)C3CCC4C5CCC6CC(O)CCC6(C)C5CCC34C RTMWIZOXNKJHRE-UHFFFAOYSA-N 0.000 description 2
- DWCSNWXARWMZTG-UHFFFAOYSA-N Trigonegenin A Natural products CC1C(C2(CCC3C4(C)CCC(O)C=C4CCC3C2C2)C)C2OC11CCC(C)CO1 DWCSNWXARWMZTG-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 239000000155 melt Substances 0.000 description 2
- NWMIYTWHUDFRPL-UHFFFAOYSA-N sapogenin Natural products COC(=O)C1(CO)C(O)CCC2(C)C1CCC3(C)C2CC=C4C5C(C)(O)C(C)CCC5(CCC34C)C(=O)O NWMIYTWHUDFRPL-UHFFFAOYSA-N 0.000 description 2
- LIKMAJRDDDTEIG-UHFFFAOYSA-N 1-hexene Chemical compound CCCCC=C LIKMAJRDDDTEIG-UHFFFAOYSA-N 0.000 description 1
- BQNMOLSYHYSCMS-UHFFFAOYSA-N 12-Epirockogenin Natural products CC1C(C2(C(O)CC3C4(C)CCC(O)CC4CCC3C2C2)C)C2OC11CCC(C)CO1 BQNMOLSYHYSCMS-UHFFFAOYSA-N 0.000 description 1
- GMBQZIIUCVWOCD-UQHLGXRBSA-N Isosarsasapogenin Natural products O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CC[C@H](O)C[C@H]4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 GMBQZIIUCVWOCD-UQHLGXRBSA-N 0.000 description 1
- PBLXVDNSLUFVHF-UHFFFAOYSA-N Neomanogenin Natural products CC1C(C2(C(=O)CC3C4(C)CC(O)C(O)CC4CCC3C2C2)C)C2OC11CCC(C)CO1 PBLXVDNSLUFVHF-UHFFFAOYSA-N 0.000 description 1
- YHGXHXTZNBXLKF-UHFFFAOYSA-N Pseudohecogenin Natural products C1CC2CC(O)CCC2(C)C(CC(=O)C23C)C1C3CC1C2C(C)=C(CCC(CO)C)O1 YHGXHXTZNBXLKF-UHFFFAOYSA-N 0.000 description 1
- BQNMOLSYHYSCMS-TUUYSWIFSA-N Rockogenin Chemical compound O([C@@H]1[C@@H]([C@]2([C@H](O)C[C@@H]3[C@@]4(C)CC[C@H](O)C[C@@H]4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 BQNMOLSYHYSCMS-TUUYSWIFSA-N 0.000 description 1
- GMBQZIIUCVWOCD-WWASVFFGSA-N Sarsapogenine Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CC[C@H](O)C[C@H]4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@H](C)CO1 GMBQZIIUCVWOCD-WWASVFFGSA-N 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- UVLDESQWQRMYKD-MOAZMYQBSA-N gentrogenin Chemical compound O([C@@H]1[C@@H]([C@]2(C(=O)C[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 UVLDESQWQRMYKD-MOAZMYQBSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229950002323 smilagenin Drugs 0.000 description 1
- -1 steroid sapogenins Chemical class 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- YHGXHXTZNBXLKF-RVKDJADKSA-N tribufuroside C Chemical compound C([C@@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H](CC(=O)[C@]13C)[C@@H]2[C@@H]3C[C@H]2[C@@H]1C(C)=C(CC[C@H](CO)C)O2 YHGXHXTZNBXLKF-RVKDJADKSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero 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)
- Steroid Compounds (AREA)
Description
<B>Verfahren</B> zur Isomerisierung <B>von</B> Spirostanen <B>zu</B> Propionaten <B>von</B> Furosten-(20: 22)-26-olen Gegenstand der vorliegenden Erfindung ist ein. Verfahren zur Isomeriserung von Ver bindungen der Spirostanreihe, wie von Ste- roid-Sapogeninen, beispielsweise des Sarsar Sapogenins,
wobei Propionate der entspre chenden Furosten-(20:22)-26-ole, wie zum Beispiel der Pseudosapogenine, entstehen.
Es ist bekannt, zur Isomexisierung von Steroid=Sapogeninen diese mit Essigsäure- oder Propionsäureanhydrid in geschlossenem Gefäss auf etwa 200 zu erhitzen.
Ein solches Arbeiten unter hohem Druck ist besonders bei technischer Durchführung sehr vorteilhaft. Auch hat sich gezeigt, dass es nicht möglich ist, diese Reaktion in einem Druckgefäss aus Eisen durchzuführen. Es ist zwar auch be kannt, die .Steroid-#Sapogenine zur Issomerisie- rung zum Beispiel mit Buttersäureanhydrid unter Rückfluss, das heisst bei einer Tempera tur von etwa 200",
zu erhitzen. Das Arbeiten mit Buttersäure zeigt jedoch verschiedene Nachteile, so dass für die genannte Isomeri- sierung das Verfahren mit Acetanhydrid im Druckgefäss vorgezogen wurde.
Das besondere Merkmal der vorliegenden Erfindung besteht nun darin, dass man Ver bindungen der ;Spirostanreihe mit Propion- säureanhydrid -unter Atmosphärendruck er hitzt.
Vorteilhaft wird die Reaktion bei einer Temperatur im Bereiche des Siedepunktes des Reaktionsgemisches durchgeführt, so zum Bei spiel unterRückfluss. Man destilliert dabei vor zugsweise die gebildete Propionsäure ab, und zwar kontinuierlich oder von Zeit zu Zeit.
Als Ausgangsstoffe lassen sich ,Spirostane beliebi ger sterischer Konfiguration, also normal; oder iso - iSpirostane der normal- oder allo- Steroidreihe verwenden, die im Cyclopentano- polyliydrophenanthrenring gesättigt oder<B>in</B> -t- gesättigt sind und auch beliebige Substituen- ten aufweisen können,
zum Beispiel in 3-, 11- oder 12-Stellung freie oder funktionell abge wandelte Oxy- oder OxogTuppen, wie Saasa.- Sapogenin, Diosgenin, Tigogenin, d4 Tigo- genon, 11-Ketotigogenin, @Smilagenin,
Heco- genin, Rockogenin, Botogenin und Manogenin bzw. deren Derivate.
Die Erfindung wird in den nachstehenden Beispielen näher beschrieben. Zwischen. Ge wichtsteil und Volumteil besteht die gleiche Beziehung wie zwischen ,Gramm und Kubik zentimeter. D.ie Tiemperaturen sind in Celsius graden angegeben.
Beispiel <I>1</I> 0,457 Gewichtsteile Diosgenin löst man in 2:,2i5 Volumteilen Propionsäureanhydrid und erhitzt '24 Stunden zum ':Sieden unter Rück fluss.
Dann wird die entstandene Propion- säure mit einem Fraktionieraufsatz langsam bis 160 abdestilliert (etwa 0,4 Volumteile) und der Rückstand nochmals 24 -Stunden ge kocht.
Nach anschliessendem Abdestillieren des Propionsäureanhydrids im Vakuum hin terbleibt ein nur langsam erstarrendes brau nes ä1, das beinahe reines Pseudo-diosgenin- dipropionat darstellt. Aus Methanol umkri stallisiert, schmilzt es bei 791 bis 80 .
Beispiel <I>2</I> 10 Gewichtsteile Hecogenin werden mit 50 Volumteilen Propionsäure-anhydrid auf ähn liche Weise umgesetzt wie in Beispiel 1 an gegeben ist.
Das nach dem Abdestillieren des Anhydrids mirückbleibende gelbe Öl kristalli- siert. Durch Umlösen aus Methanol oder Hexen werden daraus mindestens S 'Gewichts teile Pseudohecogenin-di-propionat vom F. _ 99 bis 100,0 erhalten.
<I>Beispiel 3</I> 10 Gewichtsteile 11-Keto-tigogenin in ähn licher Weise mit 50 Volumteilen'Propionsäure- anhydrid inngesetzt, liefern ebenfalls in sehr guter Ausbeute das T1-Keto-pseudo-tigogenin- dipropionat, das, aus Methanol umgelöst, bei 108 bis 109 schmilzt.
<B> Process </B> for isomerization <B> of </B> spirostanes <B> to </B> propionates <B> of </B> furosten- (20:22) -26-ols are the subject of the present invention Invention is a. Process for the isomerization of compounds of the spirostane series, such as steroid sapogenins, for example Sarsar sapogenin,
where propionates of the corresponding furosten- (20:22) -26-ole, such as the pseudosapogenins, arise.
It is known that steroid = sapogenins can be isomexized by heating them with acetic or propionic anhydride to around 200 in a closed vessel.
Working in this way under high pressure is particularly advantageous when it is carried out industrially. It has also been shown that it is not possible to carry out this reaction in a pressure vessel made of iron. It is also known to use the steroid sapogenins for isomerization, for example with butyric anhydride under reflux, that is to say at a temperature of about 200 ",
to heat. However, working with butyric acid shows various disadvantages, so that the process with acetic anhydride in the pressure vessel was preferred for the isomerization mentioned.
The special feature of the present invention consists in the fact that compounds of the spirostane series with propionic acid anhydride are heated under atmospheric pressure.
The reaction is advantageously carried out at a temperature in the range of the boiling point of the reaction mixture, for example under reflux. The propionic acid formed is preferably distilled off, continuously or from time to time.
As starting materials, Spirostane can be any steric configuration, ie normal; or iso - iSpirostane of the normal or allo- steroid series, which are saturated in the cyclopentanopolyhydrophenanthrene ring or <B> in </B> -t- and can also have any substituents,
For example, in the 3-, 11- or 12-position free or functionally modified oxy or oxog groups, such as Saasa.- sapogenin, diosgenin, tigogenin, d4 tigogenon, 11-ketotigogenin, @Smilagenin,
Hecogenin, rockogenin, botogenin and manogenin or their derivatives.
The invention is described in more detail in the examples below. Between. Part of weight and part by volume have the same relationship as between, grams and cubic centimeters. The temperatures are given in degrees Celsius.
Example <I> 1 </I> 0.457 parts by weight of diosgenin is dissolved in 2:, 2i5 parts by volume of propionic anhydride and heated for '24 hours to ': boiling under reflux.
The propionic acid formed is then slowly distilled off up to 160 (about 0.4 parts by volume) with a fractionation attachment and the residue is boiled for a further 24 hours.
After the propionic anhydride has subsequently been distilled off in vacuo, a brown oil remains that solidifies only slowly and is almost pure pseudo-diosgene-dipropionate. Umkri crystallized from methanol, it melts at 791 to 80.
Example <I> 2 </I> 10 parts by weight of hecogenin are reacted with 50 parts by volume of propionic anhydride in a manner similar to that given in Example 1.
The yellow oil remaining after the anhydride has been distilled off crystallizes. By redissolving from methanol or hexene, at least S 'parts by weight of pseudohecogenin di-propionate from F. _ 99 to 100.0 are obtained therefrom.
<I> Example 3 </I> 10 parts by weight of 11-keto-tigogenin mixed in a similar way with 50 parts by volume of propionic anhydride also provide the T1-keto-pseudo-tigogenin-dipropionate, which, from methanol, in very good yield redissolved, melts at 108 to 109.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH317879T | 1952-12-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH317879A true CH317879A (en) | 1956-12-15 |
Family
ID=4496991
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH317879D CH317879A (en) | 1952-12-15 | 1952-12-15 | Process for the isomerization of spirostanes to propionates of furosten- (20:22) -26-ols |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH317879A (en) |
-
1952
- 1952-12-15 CH CH317879D patent/CH317879A/en unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE946801C (en) | Process for the preparation of pregnan-11 ª‡ -ol-3,20-dione and allopregnan-11 ª‡-ol-3,20-dione | |
| CH505802A (en) | 17alpha-esters of pregnane series | |
| DE946898C (en) | Process for the production of steroid pseudosapogenins | |
| CH620451A5 (en) | ||
| DE957481C (en) | Process for the production of steroid pseudosapogenins from steroid sapogenins or their esters | |
| DE1643022C3 (en) | Process for the preparation of 21-esters of the 11a, 21-dihydroxysteroids with a branched-chain ester residue in the 21-position as well as the corresponding 6α-fluoro-11α-hydroxy-21-acyloxy-16α-methyl-1,4pregnadiene-3.20- dione intermediates | |
| AT250575B (en) | Process for the production of new, therapeutically valuable carboxylic acid esters of 17 α-ethynyl-19-nortestosterone | |
| DE1568499C3 (en) | Process for the production of unsaturated lactones of the steroid series | |
| AT229497B (en) | Process for the preparation of 9-halo-1, 4-pregnadien-11-ols | |
| AT239967B (en) | Process for the preparation of 18,20 oxidosteroids | |
| DE960818C (en) | Process for the preparation of 3ª ‰ -oxy-5 (6) -cholenic acid | |
| DEC0008597MA (en) | ||
| DE1643055C3 (en) | Process for the production of cardenolides | |
| CH553759A (en) | PROCESS FOR THE PREPARATION OF NEW 4-CHLORO-1,2 (ALPHA) -METHYLENE (DELTA) 4,6-PREGNADIEN-17 (ALPHA) -OL-3,20-Dione, OR ITS 17ESTER. | |
| DE1907804C3 (en) | 4-chloro-1alpha, 2alpha; 6alpha, 7alphadimethylene-3-keto-4-pregnene, processes for their preparation and agents containing them | |
| AT339514B (en) | METHOD FOR MANUFACTURING NEW 15ALFA, 16ALFA-METHYLENE-4-OSTRENE-17BETA-OLEN | |
| AT209007B (en) | Process for the preparation of 9 α-halo-4-pregnen-16 α, 17 α, 21-triol-3, 11, 20-triones and their esters | |
| AT316765B (en) | Process for the preparation of new esters of cardiac active steroids or steroid glycosides | |
| DE1643055B2 (en) | METHOD FOR MANUFACTURING CARDENOLIDS | |
| DE1019302B (en) | Process for the preparation of new derivatives of 1, 4-androstadien-3, 11, 17-trione [1 (2) -dehydroadrenosterone] | |
| DE1146878B (en) | Process for the preparation of new hydroxycarboxylic acid esters of the Pregnan range | |
| DE1040025B (en) | Process for the production of AEtioprecalciferol and AEtiocalciferol | |
| DE1140570B (en) | Process for the production of 2-halogen steroids of the pregnane and androstane series | |
| DE1075604B (en) | Rmgold and Dr George Rosenkranz, Mexico (Mexico) I Process for the production of la methyl-dihydrotestosterone and 2a - methyl - 17a - low - alkyldihydro testosterone and their 17 esters | |
| DE1070632B (en) | Process for the preparation of 2-alkyl and 2-aralkylide derivatives of 17ec-lower-alkyl-z! 4-androstene-17 /? Ol-3-ones and 17a-lower alkyl-androstane (or testane) -17 ^ -01-3-ones |