DE2144405A1 - Saponification of pregnane series esters - using silica gel - Google Patents
Saponification of pregnane series esters - using silica gelInfo
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- DE2144405A1 DE2144405A1 DE19712144405 DE2144405A DE2144405A1 DE 2144405 A1 DE2144405 A1 DE 2144405A1 DE 19712144405 DE19712144405 DE 19712144405 DE 2144405 A DE2144405 A DE 2144405A DE 2144405 A1 DE2144405 A1 DE 2144405A1
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- prednisolone
- trifluoroacetate
- acetate
- diacetate
- silica gel
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
Description
Verfahren zur Iterstellung von Estern der Pregnanreihe Die Erfindung betrifft ein Verfahren zur Herstellung von 17a-E:stern bzw. 17a,21-Diestern von llß,17a,21-Triolen der Pregnanreihe. Process for the preparation of esters of the pregnane series The invention relates to a process for the preparation of 17a-E: stern or 17a, 21-diesters of llß, 17a, 21 triplets of the Pregnan series.
Aus der US-Patentschrift 3 444 217 ist es bekannt, 17a,21-Diester von llß,17a,21-Triolen der Pregnanreihe herzustellen, indem man ein llß-Trihaloacetoxy-17a,21-diol-dialkanoat der Pregnanreihe mit einer Lösung eines Alkalimetall- oder Erdalkalimetallsalzes einer Säure mit einem pa zwischen etwa 2,3 und etwa 7,3 behandelt, wodurch die llß-Trihaloacetoxygruppe selektiv in eine freie Hydroxygruppe umgewandelt wird.From US Pat. No. 3,444,217 it is known to employ 17a, 21-diesters of 11ß, 17a, 21-triols of the pregnane series by adding a llß-trihaloacetoxy-17a, 21-diol dialkanoate the Pregnan series with a solution of an alkali metal or alkaline earth metal salt treated with an acid with a pa between about 2.3 and about 7.3, whereby the llß-trihaloacetoxy group is selectively converted to a free hydroxy group.
Es wurde nun gefunden, daß man die gleichen Ausgangsstoffe einfacher und vorteilhafter selektiv verseifen kann, indem man sie in einem inerten Lösungsmittel mit Kieselgel behandelt, Auf diese Weise lassen sich auch 17as-Monoester der Pregnanreihe erhalten, wenn man von einem llß, 2 l-Bis-(trihaloacetoxy)-17a-ol-17a-alkanoat ausgeht.It has now been found that the same starting materials can be used more easily and can more advantageously selectively saponify them by placing them in an inert solvent Treated with silica gel, 17as monoesters of the Pregnan series can also be obtained in this way obtained if one starts from a llß, 2 l-bis (trihaloacetoxy) -17a-ol-17a-alkanoate.
Gegenstand der Erfindung ist; ein Verfahren zur Herstellung von 17a-Estern bzw. 17a,21-Diestern von 17ß,17a,21-Triolen der Pregnanreihe, dadurch gekennzeichnet, daß man ein llß, 21-Bis-(trihaloacetoxy)-17α-ol-17α-alkanoat bzw, ein llß-Trihaloacetoxy-17a,21-diol-dialkanoat der Pregnanreifle mit Kieselgel in einem inerten Lösungsmittel behandelt.The subject of the invention is; a process for the preparation of 17a-esters and 17a, 21-diesters of 17β, 17a, 21-triplets, respectively the Pregnan series, thereby characterized in that one 11ß, 21-bis (trihaloacetoxy) -17α-ol-17α-alkanoate or, a llß-trihaloacetoxy-17a, 21-diol-dialkanoat of Pregnanreifle with silica gel treated in an inert solvent.
Die erfindungsgemäße, neuartige und überraschende Verseifungsmethode hat verschiedene Vorteile. Die Aufarbeitung des Realç tionsgemisches wird wesentlich vereinfacht. Die Ausbeuten sind gut. Nach der neuen Methode ist es ferner oft möglich, die selektive Verseifung und die chromatographische Aufreinigung der erhaltenen Produkte in einem Arbeitsgang durchzuführen.The novel and surprising saponification method according to the invention has several advantages. The work-up of the reaction mixture becomes essential simplified. The yields are good. According to the new method, it is also often possible the selective saponification and the chromatographic purification of the obtained To carry out products in one operation.
Als Trihaloacetoxygruppen eignen sich Trifluor-, Trichlor-, Tribrom- und Trijodacetoxygruppen oder auch gemischte Trihaloacetoxy-Gruppierungen, wie z.B. Fluordichloracetoxy, Dichlorfluoracetoxy, Fluordibromacetoxy, Trifluoracetylester sind besonders bevorzugt. Der Ausdruck Alkanoat umfaßt geradkettige oder verzweigte Alkanoyloxygruppen mit vorzugsweise 1 - 18, insbesondere 1 - 8, C-Atomen. Typische Alkanoyloxygrup pen sind z.B. Acetoxy, Propionyloxy, Butyryloxy, Isobutyryloxy, Valeryloxy, Isovaleryloxy, Capronyloxy, Heptanoyloxy, Octanoyloxy, ferner Nonanoyloxy, Decanoyloxy, Dodecanoyloxy, Tetradecanoyloxy, Hexadecanoyloxy und Octadecanoyloxy.Suitable trihaloacetoxy groups are trifluoro, trichloro, tribromo and triiodoacetoxy groups or mixed trihaloacetoxy groups, e.g. Fluorodichloroacetoxy, dichlorofluoroacetoxy, fluorodibromoacetoxy, trifluoroacetyl ester are particularly preferred. The term alkanoate includes straight-chain or branched ones Alkanoyloxy groups with preferably 1 to 18, in particular 1 to 8, carbon atoms. Typical Alkanoyloxy groups are e.g. acetoxy, propionyloxy, butyryloxy, isobutyryloxy, Valeryloxy, isovaleryloxy, capronyloxy, heptanoyloxy, octanoyloxy, also nonanoyloxy, Decanoyloxy, dodecanoyloxy, tetradecanoyloxy, hexadecanoyloxy and octadecanoyloxy.
Das erfindungsgemäße Verfahren ist grundsätzlich auf alle llß,21-Bis-(trihaloacetoxy)-l7a-alkanoyloxy-pregnane bzw.The method according to the invention is basically applicable to all 11ß, 21-bis (trihaloacetoxy) -17a-alkanoyloxy-pregnanes respectively.
llß-Trihaloacetoxy-17a,21-dialkanoyloxy-pregnane sowie die Dehydroderivate dieser Verbindungen anwendbar Funktionelle Gruppen in anderen Stellungen des Steroidkcrns hindern die Reaktion nicht und werden ihrerseits durch das Reagenz auch nicht angegriffen, Das Steroid kann zusätzliche Substituenten wie Hydroxy, Keto, Halogen, Alkyl und Alkoxy enthalten, vorzugsweise in 1-, 2-, 3-, 4-, 6-, 7-, 9-, 16- und/oder 20-Stellung. Auch weitere Estergruppen können anwesend sein.llß-Trihaloacetoxy-17a, 21-dialkanoyloxy-pregnane and the dehydro derivatives of these compounds are applicable Functional groups in other positions of the steroid do not hinder the reaction and are in turn affected by the reagent also not attacked, the steroid can have additional substituents such as hydroxy, Contain keto, halogen, alkyl and alkoxy, preferably in 1-, 2-, 3-, 4-, 6-, 7-, 9, 16 and / or 20 position. Other ester groups can also be present.
Die Ausgangsverbindungen können gesättigt sein oder eine oder mehrere Doppelbindungen, z.B in 1(2)-, 3(4)-, 4(5)-, 5(6)-und/oder 6(7)-Stellung, enthalten. -Ferner können Doppelbindungen in Seitenketten vorliegen, etwa in Form von Methylengruppen, z.B.The starting compounds can be saturated or one or more Double bonds, e.g. in 1 (2), 3 (4), 4 (5), 5 (6) and / or 6 (7) positions. -Furthermore, there can be double bonds in side chains, for example in the form of methylene groups, e.g.
einer 16-Methylengruppe.a 16-methylene group.
Besonders wertvolle 17α-Monoester bzw. 17α,21-Diester, die nach dem neuen Verfahren erhältlich sind, haben eine Doppelbindung in 4(5)- oder zwei Doppelbindungen in 1(2)- und 4(5)-Stellung; Ketogruppen in 3- und/oder 20»Stellung; Halogen-, insbesondere Fluoratome in 6- und/oder 9-Stellung; Methylgruppen in 6- und/oder 16-Stellung; eine Methylen-, Fluormethylen- oder Chlormethylengruppe in 16-Stellung. Typische l7a-Monoester bzw. 17a,21-Dies3ter leiten sich ab z.B. von antiinflammatorisch wirksamen Steroiden wie Hydrocortison, Prednisolon, 6a-Methyl-prednisolon, Betamethason, Dexamethason, Triamcinolon, 6a-Fluor-triamcinolon, Flumethason, Paramethason, 16-Methylen-prednisolon, 9α-Fluor-16-methylen-prednisolon, 16-Fluormethylen-prednisolon, Sd-Fluor-16-fluormethylenprednisolon.Particularly valuable 17α-monoesters or 17α, 21-diesters, obtainable by the new process have a double bond in 4 (5) - or two double bonds in 1 (2) and 4 (5) positions; Keto groups in 3- and / or 20 »position; Halogen, especially fluorine, atoms in the 6- and / or 9-position; Methyl groups in the 6- and / or 16-position; a methylene, fluoromethylene or chloromethylene group in 16 position. Typical 17a monoesters or 17a, 21 dies are derived from e.g. of anti-inflammatory steroids such as hydrocortisone, prednisolone, 6a-methyl-prednisolone, Betamethasone, dexamethasone, triamcinolone, 6a-fluoro-triamcinolone, flumethasone, paramethasone, 16-methylene-prednisolone, 9α-fluoro-16-methylen-prednisolone, 16-fluoromethylene-prednisolone, Sd-fluoro-16-fluoromethylene prednisolone.
Die herstellung der als Ausgangsstoffe verwendbaren llß-Trihaloacetoxy-17α,21-diol-dialkanoate ist in der Literatur beschrieben.The preparation of the IIß-trihaloacetoxy-17α, 21-diol-dialkanoates which can be used as starting materials is described in the literature.
Die 11ß,21-Bis-(trihaloacetoxy)-17α-alkanoyloxy-pregnan-derivate sind z0B. erhältlich durch Umsetzung des zugrundeliegenden llß,17a, 21-Triols mit einem Trihaloacetanhydrid in Pyridin zum entsprechen den llß,21-Bis-trihaloacetat und nachfolgende Veresterung der 17a-Hydroxygruppe mit Alkansäureanhydrid/p-Toluolsulfonsäure.The 11β, 21-bis (trihaloacetoxy) -17α-alkanoyloxy-pregnane derivatives are z0B. obtainable by reacting the underlying llß, 17a, 21-triol with a trihaloacetic anhydride in pyridine to correspond to the llß, 21-bis-trihaloacetate and subsequent esterification of the 17a-hydroxy group with alkanoic anhydride / p-toluenesulfonic acid.
Die Auswahl des für die selektive Verseifung verwendbaren Kieselgels ist nicht kritisch. Z,B. sind handelsübliche für die Säulenchromatographie vorgesehene Sorten geeignet, wie Kieselgel 0,05-0,2 mm (70-325 mesh ASTM), Als inerte Lösungsmittel eignen sich grundsätzlich alle, in denen das Ausgangssteroid löslich ist. Je polarer das Lösungsmittel ist, um so geringer ist jedoch die Adsorption des Steroids durch das Kieselgel. Zvzeckmäßig verwendet man als Lösungsmittel chlorierte Kohlenwasserstoffe wie Chloroform, Methylenchlorid, Trichloräthylen, 1, 2-Dichloräthan; ferner auch Kohlenwasserstoffe wie Benzol, Toluol; Alkohole wie Methanol, Aethänol, Isopropanol; Aether wie Diäthyläther, Tetrahydrofuran, Dioxan; sowie Gemische dieser ;ösungsmittel untereinander. Die Verwendung von Chloroform ist besonders bevorzugt.The selection of the silica gel that can be used for selective saponification is not critical. Z, B. are commercially available ones intended for column chromatography Grades suitable, such as silica gel 0.05-0.2 mm (70-325 mesh ASTM), as inert solvents basically all those in which the starting steroid is soluble are suitable. The more polar However, the less the adsorption of the steroid is by the solvent the silica gel. Chlorinated hydrocarbons are usually used as solvents such as chloroform, methylene chloride, trichlorethylene, 1,2-dichloroethane; furthermore also Hydrocarbons such as benzene, toluene; Alcohols such as methanol, ethanol, isopropanol; Ethers such as diethyl ether, tetrahydrofuran, dioxane; and mixtures of these solvents among themselves. The use of chloroform is particularly preferred.
Man führt die selektive Verseifung durch, indem man die Ausgangsstoffe bei Temperaturen zwischen 0° und Siedetemperatur, vorzugsweise zwischen 20 und 45°, rührt oder stehenläßt. Die Reaktionszeiten liegen etwa zwischen 1/2 und 48 Stunden. Eine bevorzugte Reaktionsweise besteht darin, daß man eine Suspension des Kieselgels in einer Chloroform-Lösung des Ausgangs-Steroids unter vermindertem Druck bei etwa 20 - 450 eindampft und anschließend das Endprodukt mit einem geeigneten Lösungsmittel (vorzugsweise mit einem Gemisch aus einem Alkohol und einem halogenierten Kohlenwasserstoff, z.B Chloroform/Methanol) herauslöst. Die weitere Aufreinigung kann nach üblichen Methoden der Säulen- oder Dickschichtchromatographie und/oder Kristallisation erfolgen. In manchen Fällen ist es zweckmäßig, das erhaltene trockene mit dem Endprodukt beladene Kieselgel direkt auf eine Kieselgelsäule aufzubringen und die chromatographische Reinigung anzuschließen. Bevorzugte Endprodukte sind solche der allgemeinen Formel I: worin R6 H, F oder CH3, R9 11 oder F, R16 (H,H), (ßH,«OAlkanoyl mit 1 - 8 C-Atomen), (αH,ßCH3), (ßH,aCH3), (=CH2), (=ClIF) oder (=CHCl), R17 Alkanoyl mit 1 - 8 C-Atomen und R21 H oder Alkanoyl mit 1 - 8 C-Atomen bedeuten sowie deren 1(2)-Dehydroderivate.The selective saponification is carried out by stirring or allowing the starting materials to stand at temperatures between 0 ° and the boiling point, preferably between 20 and 45 °. The reaction times are approximately between 1/2 and 48 hours. A preferred mode of reaction consists in evaporating a suspension of the silica gel in a chloroform solution of the starting steroid under reduced pressure at about 20-450 and then evaporating the end product with a suitable solvent (preferably with a mixture of an alcohol and a halogenated hydrocarbon , e.g. chloroform / methanol) dissolves. The further purification can be carried out by customary methods of column or thick layer chromatography and / or crystallization. In some cases it is expedient to apply the dry silica gel obtained, which is loaded with the end product, directly to a silica gel column and to follow up with the chromatographic purification. Preferred end products are those of the general formula I: where R6 H, F or CH3, R9 11 or F, R16 (H, H), (ßH, «OAlkanoyl with 1 - 8 carbon atoms), (αH, ßCH3), (ßH, aCH3), (= CH2) , (= ClIF) or (= CHCl), R17 denotes alkanoyl with 1 - 8 carbon atoms and R21 denotes H or alkanoyl with 1 - 8 carbon atoms and their 1 (2) -dehydro derivatives.
Die Endprodukte des neuen Verfahrens sind physiologisch wirksame Substanzen und können als Arzneimittel verwendet werden. Insbesondere zeigen sie Corticoid-Wirkungen, z.B. antiphlogistische und antiproliferative Eigenschaften. Insbesondere sind sie bei topischer Anwendung wertvoll.The end products of the new process are physiologically active substances and can be used as a medicine. In particular, they show corticoid effects, e.g. anti-inflammatory and anti-proliferative properties. In particular, they are valuable when applied topically.
In den nachstehenden Beispielen sind die Temperaturen in Celsiusgraden angegeben. Die Verhältniszahlen der Lösungsmittel beziehen sich auf Volumen-Teile.In the examples below, the temperatures are in degrees Celsius specified. The solvent ratios relate to parts by volume.
Beispiel 1 2 g rohes 9a-Fluor-16-methylen-prednisolon-llß-trifluoracetat-17a-önanthat-21-acetat (erhältlich durch Reaktion von 9a-Fluor-16-methylen-prednisolon-21-acetat mit Trifluoressigsäurea-nllydrid/ Pyridin bei 0°C zu 9α-Fluor-16-methylen-prednisolon-11ß-trifluorace tat-21-acetat (F. 250°) und anschließende Umsetzung mit Önanthsäure/Trifluoressigsäureanhydrid bei 800) werden in 200 ml Chloroform gelöst. Man gibt 200 g Kieselgel zu und dampft bei 30 - 400 unter vermindertem Druck ein. Nach Aufbewahren über Nacht extrahiert man das Produkt mit Chloroform/lIethanol (1:1).Example 1 2 g of crude 9a-fluoro-16-methylene-prednisolone-11ß-trifluoroacetate-17a-enanthate-21-acetate (obtainable by reaction of 9a-fluoro-16-methylene-prednisolone-21-acetate with trifluoroacetic acid a-nllydride / Pyridine at 0 ° C to 9α-fluoro-16-methylene-prednisolone-11β-trifluoroacetate-21-acetate (F. 250 °) and subsequent reaction with enanthic acid / trifluoroacetic anhydride at 800) are dissolved in 200 ml of chloroform. 200 g of silica gel are added and the mixture is evaporated at 30-400 under reduced pressure. Extracted after storing overnight the product with chloroform / lethanol (1: 1).
Der Extrakt wird eingedampft und chromatographisch (Kieselgel, Benzol/Chloroform 3:1, dann Benzol/Chloroform 1:1) gereinigt.The extract is evaporated and chromatographed (silica gel, benzene / chloroform 3: 1, then benzene / chloroform 1: 1).
Man erhält 9α-Fluor-16-methylen-prednisolon-17α-önanthat-21 acetat, F. 159-160° (aus Aether).9α-Fluoro-16-methylene-prednisolone-17α-enanthate-21 is obtained acetate, mp 159-160 ° (from ether).
Analog erhält man aus Hydrocortison-llß-trifluoracetat-17a,21-diacetat Prednisolon-11ß-trifluoroacetat-17α,21-diacetat sa-Methyl-prednisolon-llß-trifluoracetat-17a,21-diacetat Betamethason-llß-trifluoracetat-17a,21-diacetat Dexamethason-llß-trifluoracetat-17a,21-diacetat Triamcinolon-llß-trifluoracetat-16a,17a,21-triacetat 6a-Fluortriamcinolon-llß-trifluoracetat-16a,17a,21-triacetat Flumethason-11ß-trifluoracetat-17α,21-diacetat Paramethason-llß-trifluoracetat-17a,21-diacetat 16-Methylen-prednisolon-11ß-trifluoroacetat-17α,21-diacetat 9α-Fluor-16-methylen-prednisolon-17α,21-diacetat 16-Fluormethylen-prednisolon-17α,21-diacetat 16-Chlormethylen-prednisolon-17α,21-diacetat 9α-Fluor-16-fluormethylen-prednisolon-17α,21-diacetat , Betamethason-llß-trifluoracetat-17a-valerat-2l-acetat Betamethason-llß-trifluoracetat-17a,21-diptopionat Dexamethason-llß-trifluoracetat-17a,21-dibutyrat Flumethason-llß-trifluoracetat-17a-octanoat-2l-acetat Paramethason-llß-trifluoracetat-17a-propionat-21-butyrat Prednisolon-11ß-trichloracetat-17α,21-dipropionat Triamcinolon-11ß-trifluoroacetat-17α,21-dipropionat-17α-valerat 9α-Fluor-16-methylen-prednisolon-11ß-trifluoracetat-17α,21-diönanthat durch Behandeln mit Kieselgel in Chloroform Hydrocortison-17a,21-diacetat Prednisolon-17a,21-diacetat 6α-Methyl-prednisolon-17α,21-diacetat Betamethason-17a,21-diacetat Dexamethason-17e,2-1-diacetat Triamcinolon-16α,17α,21-triacetat 6α-Fluortriamcinolon-16α,17α,21-triacetat Flumethason-l7a,2l-diacetat Paramethason-17a,21-diacetat 16-Methylen-prednisolon-17α,21-diacetat 9α-Fluor-16-methylen-prednisolon-17α,21-diacetat, F. 219-226° 16-Fluormethylen-prednisolon-17α,21-diacetat 16-Chlormethylen-prednisolon-17α,21-diacetat 9a-Fluor-16-£1uormethylen-prednisolon-17a,21-diacetat Betamethason-17α-valerat-21-acetat Betamethason-17a,21-dipropionat Dexamethason-17a,21-dibutyrat Flumethason-17α-octanoat-21-acetat Paramethason-17a-propionat-21-butyrat Prednisolon-l7a,2l-dipropionat Triamcinolon-16α,21-dipropionat-17α-valerat 9a-Fluor-16-methylen-prednisolon-17a,21-diönanthat, F. 95-970 Beispiel 2 Man löst 1 g 9α-Fluor-16-methylen-prednisolon-11ß,21-bis-(trifluoracetat)-17a-önanthat in 100 ml Methylenchlorid, versetzt mit 100 g Kieselgel und kocht 8 Stunden. Dann dampft man ein, gibt den Rückstand auf eine Kieselgelsäule, eluiert mit Benzol-Chloroform und erhält 9α-Fluor-16-methylenprednisolon-17α-önanthat, F. 164-166° (aus Aether).Similarly, from hydrocortisone-11ß-trifluoroacetate-17a, 21-diacetate is obtained Prednisolone 11β-trifluoroacetate-17α, 21-diacetate sa-methyl-prednisolone-11β-trifluoroacetate-17a, 21-diacetate Betamethasone-11ß-trifluoroacetate-17a, 21-diacetate Dexamethasone-11ß-trifluoroacetate-17a, 21-diacetate Triamcinolone-IIβ-trifluoroacetate-16a, 17a, 21-triacetate 6a-fluorotriamcinolone-IIβ-trifluoroacetate-16a, 17a, 21-triacetate Flumethasone-11β-trifluoroacetate-17α, 21-diacetate Paramethasone-IIβ-trifluoroacetate-17a, 21-diacetate 16-methylene-prednisolone-11β-trifluoroacetate-17α, 21-diacetate 9α-fluoro-16-methylene-prednisolone-17α, 21-diacetate 16-fluoromethylene-prednisolone-17α, 21-diacetate 16-chloromethylene-prednisolone-17α, 21-diacetate 9α-fluoro-16-fluoromethylene-prednisolone-17α, 21-diacetate, Betamethasone-llß-trifluoroacetate-17a-valerate-2l-acetate Betamethasone-11ß-trifluoroacetate-17a, 21-diptopionate, dexamethasone-llß-trifluoroacetate-17a, 21-dibutyrate Flumethasone-11ß-trifluoroacetate-17a-octanoate-2l-acetate Paramethason-llß-trifluoroacetate-17a-propionate-21-butyrate Prednisolone-11ß-trichloroacetate-17α, 21-dipropionate triamcinolone-11ß-trifluoroacetate-17α, 21-dipropionate-17α-valerate 9α-Fluoro-16-methylene-prednisolone-11β-trifluoroacetate-17α, 21-dionanthate by treating with silica gel in chloroform, hydrocortisone-17a, 21-diacetate, prednisolone-17a, 21-diacetate 6α-methyl-prednisolone-17α, 21-diacetate betamethasone-17a, 21-diacetate dexamethasone-17e, 2-1-diacetate Triamcinolone-16α, 17α, 21-triacetate 6α-fluorotriamcinolone-16α, 17α, 21-triacetate Flumethasone-17a, 2l-diacetate Paramethasone-17a, 21-diacetate 16-methylene-prednisolone-17α, 21-diacetate 9α-fluoro-16-methylene-prednisolone-17α, 21-diacetate, m.p. 219-226 ° 16-fluoromethylene-prednisolone-17α, 21-diacetate 16-chloromethylene-prednisolone-17a, 21-diacetate, 9a-fluoro-16- £ 1uormethylene-prednisolone-17a, 21-diacetate Betamethasone-17α-valerate-21-acetate betamethasone-17a, 21-dipropionate dexamethasone-17a, 21-dibutyrate Flumethasone 17α-octanoate-21-acetate Paramethasone-17a-propionate-21-butyrate Prednisolone-17a, 2l-dipropionate Triamcinolone-16α, 21-dipropionate-17α-valerate 9a-fluoro-16-methylene-prednisolone-17a, 21-diönanthate, F. 95-970 EXAMPLE 2 1 g of 9α-fluoro-16-methylene-prednisolone-11β, 21-bis (trifluoroacetate) -17a-enanthate is dissolved in 100 ml of methylene chloride, mixed with 100 g of silica gel and boiled for 8 hours. then it is evaporated, the residue is placed on a silica gel column, eluted with benzene-chloroform and receives 9α-fluoro-16-methylenprednisolon-17α-oenanthate, mp 164-166 ° (from ether).
Analog erhält man aus Hydrocortison-llß,21-bis-(trifluoracetat)-17a-acetat Prednisolon-11ß,21-bis-(trifluoracetat)-17ß-acetat 6a-Methyl-prednisolon-llß,21-bis-(trifluoracetat)-lr-acetat Betamethason-llß,21-bis-(trifluoracetat)-17a-acetat Dexamethason-llß,21-bis-(trifluoracetat)-17a-acetat Triamcinolon-llß,21-bis-(trifluoracetat)-16a,17a-diacetat 6α-Fluortriamcinolon-11ß,21-bis-(trifluoracetat)-16α,17α-diacetat Flumethason-11ß,21-bis-(trifluoracetat)-17α-acetat Paramethason-llß,21-bis-(trifluoracetat)-17a-acetat 16-Methylen-prednisolon-llß,21-bis-(trifluorat::etatH7a-æcetat 9a-Fluor-16-methylen-prednisolon-llß,21-bis-(trifluoracetat) 17a-acetat 16-Fluormethylen-prednisolon-11ß,21-bis-(trifluoracetat)-17α-acetat 16-Chlormethylen-prednisolon-11ß,21-bis-(trifluoracetat)-17α acetat 9α-Fluor-16-fluormethylen-prednisolon-11ß,21-bis-(trifluoracetat)-17a-acetat durch Behandeln mit Kieselgel in Methylenchlorid Hydrocortison-17a-acetat Prednisolon- 17a-acetat 6a-Methyl-prednisolon-17a-acetat Betamethason-17a-acetat Dexamethason-17a-acetat Triamcinolon-16α,17α-diacetat 6α-Fluortriamcinolon-16α,17α-diacetat Flumethason-17a-acetat Paramethason-17a-acetat 16-Methylen-prednisolon-17α-acetat 9α-Fluor-16-methylen-prednisolon-17α-acetat 16-Fluormethylen-prednisolon-17α-acetat 16-Chlormethylen-prednisolon-17α-acetat 9α-Fluor-16-fluormethylen-prednisolon-17α-aceSimilarly, 21-bis (trifluoroacetate) -17a-acetate is obtained from hydrocortisone-11ß Prednisolone-11ß, 21-bis- (trifluoroacetate) -17ß-acetate 6a-methyl-prednisolone-11ß, 21-bis- (trifluoroacetate) -lr-acetate Betamethasone-llß, 21-bis- (trifluoroacetate) -17a-acetate, dexamethasone-llß, 21-bis- (trifluoroacetate) -17a-acetate Triamcinolone-11β, 21-bis- (trifluoroacetate) -16a, 17a-diacetate 6α-fluorotriamcinolone-11β, 21-bis- (trifluoroacetate) -16α, 17α-diacetate Flumethason-11ß, 21-bis- (trifluoroacetate) -17α-acetate Paramethason-11ß, 21-bis- (trifluoroacetate) -17a-acetate 16-methylene-prednisolone-llß, 21-bis- (trifluorate :: etatH7a-æcetat 9a-fluoro-16-methylen-prednisolone-llß, 21-bis- (trifluoroacetate) 17a-acetate 16-fluoromethylene-prednisolone-11ß, 21-bis- (trifluoroacetate) -17α-acetate 16-chloromethylene-prednisolone-11ß, 21-bis- (trifluoroacetate) -17a-acetate 9α-fluoro-16-fluoromethylene-prednisolone-11ß, 21-bis- (trifluoroacetate) -17a-acetate by Treat with silica gel in methylene chloride Hydrocortisone 17a acetate Prednisolone 17a-acetate 6a-methyl-prednisolone-17a-acetate betamethasone-17a-acetate dexamethasone-17a-acetate Triamcinolone-16α, 17α-diacetate 6α-fluorotriamcinolone-16α, 17α-diacetate Flumethasone-17a-acetate Paramethasone-17a-acetate 16-methylene-prednisolone-17α-acetate 9α-fluoro-16-methylene-prednisolone-17α-acetate 16-fluoromethylene-prednisolone-17α-acetate 16-chloromethylene-prednisolone-17α-acetate 9α-fluoro-16-fluoromethylene-prednisolone-17α-ace
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19712144405 DE2144405A1 (en) | 1971-09-04 | 1971-09-04 | Saponification of pregnane series esters - using silica gel |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19712144405 DE2144405A1 (en) | 1971-09-04 | 1971-09-04 | Saponification of pregnane series esters - using silica gel |
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| Publication Number | Publication Date |
|---|---|
| DE2144405A1 true DE2144405A1 (en) | 1973-03-08 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19712144405 Pending DE2144405A1 (en) | 1971-09-04 | 1971-09-04 | Saponification of pregnane series esters - using silica gel |
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| Country | Link |
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| DE (1) | DE2144405A1 (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2421180A1 (en) * | 1978-03-29 | 1979-10-26 | Taisho Pharmaceutical Co Ltd | HYDROCORTISONE 17-BUTYRATE 21-PROPIONATE AND ITS USE IN PARTICULAR AS AN ANTI-INFLAMMATORY AGENT |
| FR2428649A1 (en) * | 1978-06-15 | 1980-01-11 | Beiersdorf Ag | DIESTERS IN 17,21 OF HYDROCORTISONE AND MEDICINAL PRODUCTS CONTAINING SAME |
| EP0072547A1 (en) * | 1981-08-18 | 1983-02-23 | Schering Aktiengesellschaft | 6-Alpha-methyl-prednisolone derivatives, their preparation and utilization |
| EP0095894A2 (en) * | 1982-05-31 | 1983-12-07 | Ohta Seiyaku Kabushiki Kaisha. | 6 Alpha-methylprednisolone derivatives |
| EP0030615B1 (en) * | 1979-11-16 | 1984-08-29 | STEROSYNT Ltd. | 6-alpha-9-alpha-difluoro-16-beta-methyl-prednisolone-17,21 diesters and pharmaceutical compositions containing them |
-
1971
- 1971-09-04 DE DE19712144405 patent/DE2144405A1/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2421180A1 (en) * | 1978-03-29 | 1979-10-26 | Taisho Pharmaceutical Co Ltd | HYDROCORTISONE 17-BUTYRATE 21-PROPIONATE AND ITS USE IN PARTICULAR AS AN ANTI-INFLAMMATORY AGENT |
| FR2428649A1 (en) * | 1978-06-15 | 1980-01-11 | Beiersdorf Ag | DIESTERS IN 17,21 OF HYDROCORTISONE AND MEDICINAL PRODUCTS CONTAINING SAME |
| EP0030615B1 (en) * | 1979-11-16 | 1984-08-29 | STEROSYNT Ltd. | 6-alpha-9-alpha-difluoro-16-beta-methyl-prednisolone-17,21 diesters and pharmaceutical compositions containing them |
| EP0072547A1 (en) * | 1981-08-18 | 1983-02-23 | Schering Aktiengesellschaft | 6-Alpha-methyl-prednisolone derivatives, their preparation and utilization |
| US4587236A (en) * | 1981-08-18 | 1986-05-06 | Schering Aktiengesellschaft | Novel 6α-methylprednisolone derivatives, their preparation, and their use |
| EP0095894A2 (en) * | 1982-05-31 | 1983-12-07 | Ohta Seiyaku Kabushiki Kaisha. | 6 Alpha-methylprednisolone derivatives |
| EP0095894A3 (en) * | 1982-05-31 | 1985-01-02 | Ohta Seiyaku Kabushiki Kaisha. | 6 alpha-methylprednisolone derivatives |
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