CH626336A5 - Process for the preparation of cholecalciferol derivatives - Google Patents
Process for the preparation of cholecalciferol derivatives Download PDFInfo
- Publication number
- CH626336A5 CH626336A5 CH149077A CH149077A CH626336A5 CH 626336 A5 CH626336 A5 CH 626336A5 CH 149077 A CH149077 A CH 149077A CH 149077 A CH149077 A CH 149077A CH 626336 A5 CH626336 A5 CH 626336A5
- Authority
- CH
- Switzerland
- Prior art keywords
- methanol
- term
- examples
- acid
- formula
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C401/00—Irradiation products of cholesterol or its derivatives; Vitamin D derivatives, 9,10-seco cyclopenta[a]phenanthrene or analogues obtained by chemical preparation without irradiation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J17/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J53/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by condensation with a carbocyclic rings or by formation of an additional ring by means of a direct link between two ring carbon atoms, including carboxyclic rings fused to the cyclopenta(a)hydrophenanthrene skeleton are included in this class
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/14—All rings being cycloaliphatic
- C07C2602/24—All rings being cycloaliphatic the ring system containing nine carbon atoms, e.g. perhydroindane
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)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Die vorliegende Erfindung bezieht sich auf ein Verfahren zur Herstellung von 24R,25- und 24S,25-Dihydroxy-cholecal-ciferol und von 3-nieder-Alkanoylaten hiervon, d.h. von Verbindungen der Formel The present invention relates to a process for the preparation of 24R, 25- and 24S, 25-dihydroxy-cholecal-ciferol and 3-lower alkanoylates thereof, i.e. of compounds of the formula
R R
1 1
worin Rj Hydroxy oder niederes Alkanoyloxy darstellt und die absolute Konfiguration am C-24 R oder S ist. where Rj is hydroxy or lower alkanoyloxy and the absolute configuration at C-24 is R or S.
Dieses Verfahren ist dadurch gekennzeichnet, dass man eine Verbindung der Formel This method is characterized in that a compound of the formula
R R
626 336 626 336
4 4th
worin Ri obige Bedeutung hat, R2 und R3 unabhängig voneinander niederes Alkyl oder zusammen niederes Alkylen bedeuten und die absolute Konfiguration am C-24 R oder S ist, mit einer Säure und einem hydroxylischen Lösungsmittel umsetzt. wherein R 1 has the above meaning, R 2 and R 3 independently of one another denote lower alkyl or together lower alkylene and the absolute configuration at C-24 is R or S, with an acid and a hydroxylic solvent.
Die Deketalisierung einer Verbindung der Formel II wird zweckmässig dadurch durchgeführt, dass man eine solche Verbindung mit einem einen Überschuss an Säure enthaltenden Alkanol umsetzt. Geeignete Säuren sind anorganische Säuren, wie Chlorwasserstoffsäure, Bromwasserstoffsäure, Schwefelsäure oder Bortrifluorid; organische Säuren, wie p-Toluolsul-fonsäure oder Trifluoressigsäure: und kationische Austauscherharze in Wasserstofform, wie Bio-Rad AG 50 W-X 4, Bio-Rad AG 50 W, Dowex 50 W, Duolite C20, Amberlit IR, Zeocarb, Permutit Q oder Nalcite. Kationische Austauscherharze in Wasserstofform, insbesondere Bio-Rad AG 50 W-X 4; und organische Säuren, insbesondere p-Toluolsulfonsäure, sind bevorzugt. Geeignete Alkanole sind Methanol, Äthanol, 2-Propanol, 2-Butanol, 2-Pentanol und dergleichen. Als hy-droxylische Lösungsmittel können auch aliphatische Diole, wie Äthylenglykol oder Propylenglykol, verwendet werden. Alkanole, insbesondere Methanol, sind bevorzugt. Die Deketalisie-rungstemperatur ist nicht kritisch. Zweckmässig arbeitet man jedoch bei einer Temperatur zwischen —20 und +20 °C um die Bildung von Nebenprodukte zu vermeiden. Eine Deke-talisierungstemperatur von etwa -5 °C ist bevorzugt. The decetalation of a compound of formula II is conveniently carried out by reacting such a compound with an alkanol containing an excess of acid. Suitable acids are inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid or boron trifluoride; organic acids, such as p-toluenesulfonic acid or trifluoroacetic acid: and cationic exchange resins in hydrogen form, such as Bio-Rad AG 50 WX 4, Bio-Rad AG 50 W, Dowex 50 W, Duolite C20, Amberlit IR, Zeocarb, Permutit Q or Nalcite . Cationic exchange resins in hydrogen form, in particular Bio-Rad AG 50 W-X 4; and organic acids, especially p-toluenesulfonic acid, are preferred. Suitable alkanols are methanol, ethanol, 2-propanol, 2-butanol, 2-pentanol and the like. Aliphatic diols, such as ethylene glycol or propylene glycol, can also be used as hydroxyl solvents. Alkanols, especially methanol, are preferred. The decetalation temperature is not critical. However, it is advisable to work at a temperature between -20 and +20 ° C to avoid the formation of by-products. A decalization temperature of about -5 ° C is preferred.
Ein 24R,25- oder 24S,25-Dihydroxycholecalciferol-3-alk-anoylat der Formel I kann zu einem 24R,25- bzw 24S,25-Di-hydroxycholecalciferol verseift werden. Die Verseifung kann in an sich bekannter Weise durchgeführt werden, z.B. indem man dass Alkanoylat der Formel Ia in einer alkoholischen Lösung eines Alkalimetallhydroxids auflöst und die Lösung bei einer Temperatur zwischen etwa -20 und +20 °C, vorzugsweise bei etwa 0 °C, stehen lässt. Vorzugsweise wird die Verseifung in einer inerten Atmosphäre, wie Stickstoff oder Helium, durchgeführt. Geeignete alkoholische Lösungsmittel sind Methanol, Äthanol oder 2-Propanol. Geeignete Alkalimetall-hydroxyde sind Natrium- und Kaliumhydroxyd. Methanol und Kaliumhydroxyd sind bevorzugt. A 24R, 25- or 24S, 25-dihydroxycholecalciferol-3-alk-anoylate of the formula I can be saponified to a 24R, 25- or 24S, 25-di-hydroxycholecalciferol. The saponification can be carried out in a manner known per se, e.g. by dissolving the alkanoylate of the formula Ia in an alcoholic solution of an alkali metal hydroxide and leaving the solution at a temperature between about -20 and +20 ° C, preferably at about 0 ° C. The saponification is preferably carried out in an inert atmosphere, such as nitrogen or helium. Suitable alcoholic solvents are methanol, ethanol or 2-propanol. Suitable alkali metal hydroxides are sodium and potassium hydroxide. Methanol and potassium hydroxide are preferred.
Eine Verbindung der Formel II kann in an sich bekannter Weise beispielsweise wie in der deutschen Offenlegungschrift 2 710 062 beschrieben, hergestellt werden. A compound of the formula II can be prepared in a manner known per se, for example as described in German Offenlegungsschrift 2,710,062.
Beispiel 1 example 1
24R,25-Dihydroxycholecalciferol-3-acetat Eine mit 0,500 g eines Kationenaustauscherharzes in Wasserstofform (Bio-Rad AG 50W-X4) versetzte Lösung von 0,200 g 24R,25-Dihydroxycholecalciferol-3-acetat-24,25-ace-tonid in 5 ml Methanol wird 44 Stunden bei —5 °C unter Argon gerührt. Das Reaktionsgemisch wird filtriert, das Austauscherharz mit 3mal 10 ml Methanol gewaschen und die vereinigten Methanolphasen unter Vakuum bei 25 °C eingedampft. Man erhält 0,173 g rohes Produkt in Form eines dicken Öls. 24R, 25-dihydroxycholecalciferol-3-acetate A solution of 0.200 g 24R, 25-dihydroxycholecalciferol-3-acetate-24,25-ace-tonide in 5 mixed with 0.500 g of a cation exchange resin in hydrogen form (Bio-Rad AG 50W-X4) ml of methanol is stirred at -5 ° C under argon for 44 hours. The reaction mixture is filtered, the exchange resin is washed 3 times with 10 ml of methanol and the combined methanol phases are evaporated under vacuum at 25 ° C. 0.173 g of crude product is obtained in the form of a thick oil.
Beispiel 2 24R,25-Dihydroxycholecalciferol Eine mit 0,500 g eines Kationenaustauscherharzes in Wasserstofform (Bio-Rad AG 50W-X4) versetzte Lösung von 0,200 g 24R,25-Dihydroxycholecalciferol-24,25-acetonid in 5 ml Methanol wird unter Argon 40 Stunden bei -5 °C gerührt. Das Reaktionsgemisch wird filtriert, das Austauscherharz mit 3mal 10 ml Methanol gewaschen und die vereinigten Methanolphasen unter Vakuum bei 25 °C eingedampft. Der Rückstand wird mit einem Waters Associates Flüssigchromatographen Modell 202 mit einem 1:1-Gemisch von n-Hex- Example 2 24R, 25-dihydroxycholecalciferol A solution of 0.200 g of 24R, 25-dihydroxycholecalciferol-24,25-acetonide in 5 ml of methanol mixed with 0.500 g of a cation exchange resin in hydrogen form (Bio-Rad AG 50W-X4) is added under argon for 40 hours -5 ° C stirred. The reaction mixture is filtered, the exchange resin is washed 3 times with 10 ml of methanol and the combined methanol phases are evaporated under vacuum at 25 ° C. The residue is washed on a Waters Associates model 202 liquid chromatograph with a 1: 1 mixture of n-hex.
an/Äthylacetat als Eluierungsmittel gereinigt. Man erhält 0,127 g (70%) Produkt. Nach Kristallisation aus Methylformat erhält man 0,094 g (40%) Produkt in Form von weissen Kristallen, Schmelzpunkt 136-137 °C; [«]D25 +113,0° (c0,33, EtOH). on / ethyl acetate as eluent. 0.127 g (70%) of product is obtained. After crystallization from methyl format, 0.094 g (40%) of product is obtained in the form of white crystals, melting point 136-137 ° C .; [«] D25 + 113.0 ° (c0.33, EtOH).
Beispiel 3 Example 3
24S,25-Dihydroxycholecalciferol-3-acetat Eine mit 0,500 g eines Kationenaustauscherharzes in Was-stofform (Bio-Rad AG 50W-X4) versetzte Lösung von 0,200 g 24S,25-Dihydroxycholecalciferol-3-acetat-24,25-ace-tonid in 5 ml Methanol wird 40 Stunden unter Argon bei —5 °C gerührt. Das Reaktionsgemisch wird filtriert, das Austauscherharz mit 3mal 10 ml Metahnol gewaschen und die vereinigten Methanolphasen unter Vakuum bei 25 °C eingedampft. Man erhält 0,68 g rohes Produkt in Form eines dicken Öls. 24S, 25-dihydroxycholecalciferol-3-acetate A solution of 0.200 g 24S, 25-dihydroxycholecalciferol-3-acetate-24,25-ace-tonide mixed with 0.500 g of a cation exchange resin in the form of hydrogen (Bio-Rad AG 50W-X4) in 5 ml of methanol is stirred for 40 hours under argon at -5 ° C. The reaction mixture is filtered, the exchange resin is washed with 3 times 10 ml of methanol and the combined methanol phases are evaporated under vacuum at 25 ° C. 0.68 g of crude product is obtained in the form of a thick oil.
Beispiel 4 24S,25-Dihydroxycholecalciferol Eine mit 0,500 g eines Kationenaustauscherharzes in Wasserstofform (Bio-Rad 50W-X4) versetzte Lösung von 0,170 g 24S,25-Dihydroxycholecalciferol-24,25-acetonid in 5 ml Methanol wird 40 Stunden bei —5 °C unter Argon gerührt. Das Reaktionsgemisch wird filtriert, das Austauscherharz mit 3mal 10 ml Methanol gewaschen und die vereinigten Methanolphasen unter Vakuum bei 25 °C eingedampft. Der Rückstand wird mit einem Waters Associates Flüssigchromatographen Modell 202 mit einem 1:1-Gemisch von n-Hexan/Äthylacetat als Eluierungsmittel gereinigt. Man erhält 0,086 g (60%) Produkt. Nach Kristallisation aus Methylformat erhält man 0,045 g (29%) Produkt in Form von weissen Kristallen, Schmelzpunkt 111-112 "C; [a]D25 +93,7° (c0,3, EtOH). Example 4 24S, 25-Dihydroxycholecalciferol A solution of 0.170 g of 24S, 25-dihydroxycholecalciferol-24.25-acetonide in 5 ml of methanol, mixed with 0.500 g of a cation exchange resin in hydrogen form (Bio-Rad 50W-X4), is stirred at -5 ° for 40 hours C stirred under argon. The reaction mixture is filtered, the exchange resin is washed 3 times with 10 ml of methanol and the combined methanol phases are evaporated under vacuum at 25 ° C. The residue is purified on a Waters Associates Model 202 liquid chromatograph with a 1: 1 mixture of n-hexane / ethyl acetate as the eluent. 0.086 g (60%) of product is obtained. After crystallization from methyl format, 0.045 g (29%) of product is obtained in the form of white crystals, melting point 111-112 "C; [a] D25 + 93.7 ° (c0.3, EtOH).
Beispiel 5 24R,25-Dihydroxycholecalciferol Eine Lösung von 0,173 g rohem 24R,25-Dihydroxychole-calciferol-3-acetat (siehe Beispiel 1) und 0,200 g Kaliumhydroxyd in 5 ml Methanol wird 6 Stunden unter Argon bei 0 °C gerührt. Das Methanol wird dann unter Vakuum abgedampft und der Rückstand mit 30 ml Wasser vermischt und mit 3mal 50 ml Methylenchlorid extrahiert. Die vereinigten organischen Phasen werden mit 3mal 30 ml gesättigter Natriumchloridlösung gewaschen, über Natriumsulfat getrocknet, filtriert und unter Vakuum bei 25 °C eingedampft. Der Rückstand wird mit einem Waters Associates Flüssigchromatographen Modell 202 mit einem 1:1-Gemisch von n-Hexan/Äthylacetat als Eluierungsmittel gereinigt. Man erhält 0,132 g (84%) Produkt. Nach Kristallisation aus Methylformat erhält man 0,098 g Produkt in Form von weissen Kristallen, Schmelzpunkt 136-137 °C. Example 5 24R, 25-dihydroxycholecalciferol A solution of 0.173 g of crude 24R, 25-dihydroxychole-calciferol-3-acetate (see Example 1) and 0.200 g of potassium hydroxide in 5 ml of methanol is stirred at 0 ° C. for 6 hours under argon. The methanol is then evaporated under vacuum and the residue is mixed with 30 ml of water and extracted with 3 times 50 ml of methylene chloride. The combined organic phases are washed with 3 times 30 ml of saturated sodium chloride solution, dried over sodium sulfate, filtered and evaporated under vacuum at 25 ° C. The residue is purified on a Waters Associates Model 202 liquid chromatograph with a 1: 1 mixture of n-hexane / ethyl acetate as the eluent. 0.132 g (84%) of product is obtained. After crystallization from methyl format, 0.098 g of product is obtained in the form of white crystals, melting point 136-137 ° C.
Beispiel 6 24S,25-Dihydroxycholecalciferol Eine Lösung von 0,168 g rohem 24S,25-Dihydroxychole-calciferol-3-acetat (siehe Beispiel 3) und 0,200 g Kaliumhydroxyd in 5 ml Methanol wird 6 Stunden unter Argon bei 0 °C gerührt. Das Methanol wird unter Vakuum abgedampft und der Rückstand mit 30 ml Wasser vermischt und mit 3mal 50 ml Methylenchlorid extrahiert. Die vereinigten organischen Phasen werden mit 3mal 30 ml gesättigter Natriumchloridlösung gewaschen, über Natriumsulfat getrocknet, filtriert und unter Vakuum bei 25 °C eingedampft. Der Rückstand wird mit einem Waters Associates Flüssigchromatographen Modell 202 mit einem 1:1-Gemisch von n-Hexan/Äthylacetat als Eluierungsmittel gereinigt. Man erhält 0,126 g (82%) Produkt. Nach Kristallisation aus Methylformat erhält man 0,085 g Produkt in Form von weissen Kristallen, Schmelzpunkt 111-112 °C. Example 6 24S, 25-dihydroxycholecalciferol A solution of 0.168 g of crude 24S, 25-dihydroxychole-calciferol-3-acetate (see Example 3) and 0.200 g of potassium hydroxide in 5 ml of methanol is stirred at 0 ° C. for 6 hours under argon. The methanol is evaporated off under vacuum and the residue is mixed with 30 ml of water and extracted with 3 times 50 ml of methylene chloride. The combined organic phases are washed with 3 times 30 ml of saturated sodium chloride solution, dried over sodium sulfate, filtered and evaporated under vacuum at 25 ° C. The residue is purified on a Waters Associates Model 202 liquid chromatograph with a 1: 1 mixture of n-hexane / ethyl acetate as the eluent. 0.126 g (82%) of product is obtained. After crystallization from methyl format, 0.085 g of product is obtained in the form of white crystals, melting point 111-112 ° C.
5 5
10 10th
15 15
20 20th
25 25th
30 30th
35 35
40 40
45 45
50 50
55 55
60 60
65 65
S S
Claims (4)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US05/664,848 US4026882A (en) | 1976-03-08 | 1976-03-08 | Syntheses of 3,24R,25- and 3,24S,25-trihydroxy-5,7-cholestadiene 24,25-ketals and alkanoyl derivatives thereof |
US05/664,833 US4028349A (en) | 1976-03-08 | 1976-03-08 | Syntheses of 24R,25- and 24S,25-dihydroxycholesterol 24,25-ketals and alkanoyl derivatives thereof |
US05/664,799 US4021423A (en) | 1976-03-08 | 1976-03-08 | Syntheses of 24R,25- and 24S,25-dihydroxycholecalciferol |
Publications (1)
Publication Number | Publication Date |
---|---|
CH626336A5 true CH626336A5 (en) | 1981-11-13 |
Family
ID=27418118
Family Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CH149077A CH626336A5 (en) | 1976-03-08 | 1977-02-08 | Process for the preparation of cholecalciferol derivatives |
CH202281A CH627192A5 (en) | 1976-03-08 | 1981-03-25 | Process for preparing novel cholesterol derivatives |
CH202181A CH627764A5 (en) | 1976-03-08 | 1981-03-25 | Process for the preparation of cholestadiene derivatives |
CH202081A CH627159A5 (en) | 1976-03-08 | 1981-03-25 | Process for the preparation of novel cholesterol derivatives |
Family Applications After (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CH202281A CH627192A5 (en) | 1976-03-08 | 1981-03-25 | Process for preparing novel cholesterol derivatives |
CH202181A CH627764A5 (en) | 1976-03-08 | 1981-03-25 | Process for the preparation of cholestadiene derivatives |
CH202081A CH627159A5 (en) | 1976-03-08 | 1981-03-25 | Process for the preparation of novel cholesterol derivatives |
Country Status (7)
Country | Link |
---|---|
JP (1) | JPS52108960A (en) |
CH (4) | CH626336A5 (en) |
DE (1) | DE2710062A1 (en) |
FR (1) | FR2343727A1 (en) |
GB (1) | GB1572952A (en) |
IT (1) | IT1078064B (en) |
NL (1) | NL7702484A (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5735599A (en) * | 1980-08-05 | 1982-02-26 | Chugai Pharmaceut Co Ltd | 24,25-dihydroxycholestane and its preparation |
DE3265509D1 (en) * | 1981-04-29 | 1985-09-26 | Hoffmann La Roche | Process for the preparation of cholesterol derivatives, and intermediate derivatives therefor |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1178427B (en) * | 1961-01-26 | 1964-09-24 | Olin Mathieson | Process for the preparation of 16ª ‡, 17ª ‡ -dihydroxysteroids of the pregnan series |
US3715374A (en) * | 1972-05-05 | 1973-02-06 | Wisconsin Alumni Res Found | 24,25-dihydroxycholecalciferol |
US3901928A (en) * | 1973-01-10 | 1975-08-26 | Robert Henry Hesse | 1' ,3' -dihydroxy steroid-5-enes method of preparing same and their use for preparing 1' -hydroxy-25-hydrogen vitamin d compounds |
JPS51128417A (en) * | 1975-04-28 | 1976-11-09 | Teijin Ltd | A method for stabilizing active vitamin d3 derivatives |
-
1977
- 1977-02-08 CH CH149077A patent/CH626336A5/en not_active IP Right Cessation
- 1977-02-28 IT IT20765/77A patent/IT1078064B/en active
- 1977-03-04 FR FR7706407A patent/FR2343727A1/en active Granted
- 1977-03-04 JP JP2291477A patent/JPS52108960A/en active Pending
- 1977-03-07 GB GB9480/77A patent/GB1572952A/en not_active Expired
- 1977-03-08 NL NL7702484A patent/NL7702484A/en not_active Application Discontinuation
- 1977-03-08 DE DE19772710062 patent/DE2710062A1/en not_active Ceased
-
1981
- 1981-03-25 CH CH202281A patent/CH627192A5/en not_active IP Right Cessation
- 1981-03-25 CH CH202181A patent/CH627764A5/en not_active IP Right Cessation
- 1981-03-25 CH CH202081A patent/CH627159A5/en not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
NL7702484A (en) | 1977-09-12 |
CH627192A5 (en) | 1981-12-31 |
FR2343727A1 (en) | 1977-10-07 |
GB1572952A (en) | 1980-08-06 |
FR2343727B1 (en) | 1984-01-13 |
JPS52108960A (en) | 1977-09-12 |
CH627159A5 (en) | 1981-12-31 |
CH627764A5 (en) | 1982-01-29 |
DE2710062A1 (en) | 1977-09-15 |
IT1078064B (en) | 1985-05-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0000533B1 (en) | N-substituted 9,10-dihydrolysergic acid esters and a method for their preparation | |
CH509297A (en) | Progestational and deciduogenic 17alpha-substituted-11 | |
DE1962757C3 (en) | Evomonoside derivatives, processes for their production and pharmaceuticals containing them | |
CH626336A5 (en) | Process for the preparation of cholecalciferol derivatives | |
DE2155578B2 (en) | Process for the preparation of 8,9-didehydro-10-alkoxy-ergolenic derivatives | |
DE69707860T2 (en) | METHOD FOR PRODUCING TETRAHYDROINDOLIZINES | |
CH494219A (en) | 17alpha-3-hydroxypropyl-4-androstene-3beta 17beta-diol | |
DE2241680C2 (en) | 17-Hydroxy-7-alkoxycarbonyl-3-oxo-17α-prepregn-4-ene-21-carboxylic acid-γ-lactones and processes and intermediates for their preparation | |
EP0722946A1 (en) | Process for the separation of 3-formyl-cephem derivatives | |
DE2305078A1 (en) | NEW OXABICYCLOOCTANES AND THE PROCESS FOR THEIR PRODUCTION | |
DE69915965T2 (en) | Stereoselective process for the preparation of the 22R epimer of budesonide | |
CH628639A5 (en) | Process for the preparation of furanose derivatives | |
EP0502392B1 (en) | Process for the preparation of D-(+)-biotin and intermediates in this process | |
DE3325976C2 (en) | ||
DE2256866C3 (en) | Process for the preparation of 17 alpha- or 17beta-hydroxy compounds of the 20-ketopregnane or -17alpha-pregnane series | |
DE3012888C2 (en) | ||
EP0023663B1 (en) | Method for the preparation of new heterocycles that contain oxygen | |
DE2560493C2 (en) | 2,9-Dioxatricyclo [4,3,1,0 → 3 → →, → → 7 →] decane | |
DE944853C (en) | Process for the preparation of steroid-21-carboxylic acids unsaturated in the 17 (20) position or their salts and esters | |
DE1001679C2 (en) | Process for the preparation of 2,3-epoxy-12-oxy- (or keto) -22-isoallospirostane | |
DE938371C (en) | Process for the production of new 3,4-cyclopentano- and -hexano-hydronaphthalene compounds | |
JPS56108743A (en) | 3-nitro-2-hydroxy-4-phenylbutyric acid derivative, its ester and preparation thereof | |
CH620454A5 (en) | ||
DE2137557C3 (en) | Process for the production of Acyloxy Delta 4 androstenen or ostrenen | |
DE1643013C3 (en) | Process for the preparation of butenolides |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PL | Patent ceased |