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US 5,565,588 AGranted
9-alpha-hydroxy steroids, process for their preparation, process for the preparation of the corresponding 9(11)-dehydro derivatives and pharmaceutical preparations containing said steroids
AssigneeRoussel Uclaf
InventorsJacobus N. M. Batist, Arthur F. Marx, Willem J. Van Zoest, Jagdish C. Kapur
Life of this patent
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Abstract
New 9-alpha-hydroxy steroids are prepared by the introduction of substituents on the D-ring of 9-alpha-hydroxy-androst-4-ene-3,17-dione. The resulting compounds are useful intermediates in the synthesis of corticosteroids.
Claims24
Process for the preparation of 9-alpha-hydroxy steroids containing a D-ring according to formula:
- ##STR22## where R.sub.2 is ethynyl, haloethynyl, optionally protected hydroxy, cyano, 1'-(1-6C)alkoxy-ethenyl, 1'-(1-6C)alkylthio-ethenyl, 1'-aryloxy-ethenyl, 1'-arylthio-ethenyl, 1',1'-trimethylene-dithio-ethyl, and where
- R.sub.3 is hydrogen,
- R.sub.4 is hydrogen, hydroxy, alpha-methyl, beta-methyl or
- R.sub.3 and R.sub.4 together form methylene, or
- R.sub.2 and R.sub.3 together form a double bond,
- R.sub.5 is cyano, --COCHR.sub.1 R.sub.1 ', carbamoyl, hydroxy, ethynyl,
- haloethynyl, sulfonate, sulfite, trialkylsilyloxy, formyloxy,
- optionally halogenated (1-6C)carboxylic acyloxy,
- --C(.dbd.NR.sub.80)--CH.sub.3, --C(NHR.sub.82).dbd.CH.sub.2, --C(.dbd.NR.sub.80)--CH.sub.2 X, X is halogen
- R.sub.80 is hydrogen, --CO)--R.sub.81, trialkylsilyl,
- R.sub.81 is hydrogen, (1-6C)alkyl, phenyl, phenyl substituted with
- - 2chlorine atoms, methyl or nitro groups,
- R.sub.82 is --(CO)--R.sub.81, trialkylsilyl or
- R.sub.2 and R.sub.5 together are carbonyl (provided R.sub.4 is not H),
- provided that when R.sub.5 is --COCHR.sub.1 R.sub.1 ', R.sub.1 is hydrogen, hydroxy, optionally halogenated (1-6C)carboxylic acyloxy, halogen, optionally substituted benzoyloxy,
- R.sub.1 ' is hydrogen or halogen, comprising the step of using as starting compound asteroid in which the 9-alpha-hydroxyl group is already present.
13 more elements
Process for the preparation of 9-alpha-hydroxy steroids containing a D-ring according to formula:
- ##STR24## where R3 is hydrogen and R4 is hydrogen and R4 is hydroxy, alpha-methyl or beta-methyl or R3 and R4 together form methylene, comprising the step of using as starting compound asteroid in which the 9-alpha-hydroxyl group is already present.
Process for the preparation of 9-alpha-hydroxy steroids containing a D-ring according to formula:
- ##STR30## where R.sub.2 is optionally protected hydroxy, R.sub.3 is hydrogen, R.sub.4 is hydrogen, hydroxy, alpha-methyl, betamethyl or
- R.sub.3 and R.sub.4 together form methylene or
- R.sub.2 and R.sub.4 together form a double bond,
- comprising the step of using as starting compound asteroid in which the 9-alpha-hydroxyl group is already present.
1 more element
Process for the preparation of 9-alpha-hydroxy steroids containing a D-ring according to formula:
- where Y is hydrogen, chlorine, bromine or iodine,
- R.sub.2 is alpha or beta oriented and stands for optionally protected hydroxy (except beta-acetyloxy when R4 and Y both are hydrogen),
- R.sub.3 is hydrogen, R4 is hydrogen, hydroxy, alpha-methyl, beta-methyl, or
- R3 and R4 together from methylene, or
- R.sub.2 and R.sub.3 together form a double bond, with the provision that R.sub.2 also may be beta-acetyloxy, comprising the step of using as starting compound asteroid in which the 9-alpha-hydroxyl group is already present.
2 more elements
Process for the preparation of 9-alpha-hydroxy steroids containing a D-ring according to formula:
- ##STR36## where R.sub.2 is hydroxy,
- R.sub.6 is acetyl, 1'-(1-6C)alkoxy-ethenyl, 1'-(1-6C)alkylthio-ethenyl, 1'-aryloxy-ethenyl, 1'-arylthio-ethenyl, 1'-trimethylenedithio-ethyl,
- R.sub.3 is hydrogen and
- R.sub.4 is hydroxy, alpha-methyl or beta-methyl, or
- R.sub.3 and R.sub.4 together form methylene or,
- R.sub.2 and R.sub.3 together form a double bond comprising the step of using as starting compound asteroid in which the 9-alpha-hydroxyl group is already present.
3 more elements
Process for the preparation of 9-alpha-hydroxy pregnanes containing a D-ring according to formula:
- ##STR38## where R.sub.1 is hydrogen, halogen, optionally substituted benzoate, hydroxy, optionally halogenated (1-6C)carboxylic acyloxy, R.sub.1 ' is hydrogen or halogen, R.sub.2 is optionally protected hydroxy,
- Z is oxygen or .dbd.NR.sub.80, where R.sub.80 is hydrogen, --(CO)--R.sub.81 or trialkylsilyl and R.sub.81 is hydrogen, (1-6C)alkyl, phenyl, phenyl substituted with 0-2 chlorine atoms, methyl or nitro groups,
- R.sub.3 is hydrogen,
- R.sub.4 is hydrogen, hydroxy, alpha-methyl, beta-methyl, or
- R.sub.3 and R.sub.4 together form methylene, or
- R.sub.2 and R.sub.3 together form a double bond, comprising using as starting compound asteroid in which the 9-alpha-hydroxy group is already present.
3 more elements
Process for the preparation of 9-alpha-hydroxy pregnanes containing a D-ring according to formula:
- ##STR43## where A is hydroxy, bromine or iodine, optionally substituted benzoyloxy or optionally halogenated (1-6C)carboxylic acyloxy,
- R.sub.2 is optionally protected hydroxy,
- R.sub.3 is hydrogen, R.sub.4 is hydrogen, hydroxyl, alpha-methyl, beta-methyl or R.sub.3 and R.sub.4 together form methylene or R.sub.2 and R.sub.3 together form a double bond,
- comprising one or more of the following steps:
- (1) treating a 9-alpha-hydroxy pregnane containing a D-ring according to formula:
- ##STR44## where R.sub.2, R.sub.3 and R.sub.4 are as defined above with a C.sup.21 -brominating or -iodinating agent,
- (2) substituting the iodine atom with an optionally halogenated (1-6C)carboxylic acyloxy group or an optionally substituted benzoyloxy group,
- (3) hydrolyzing the ester group on C.sup.21,
- (4) dehydrating the product according to any one of the preceding steps resulting in the corresponding 16,17-dehydro steroid.
6 more elements
Dependencies are inferred from the claim text.