GB929272A - Steroids and their production - Google Patents

Steroids and their production

Info

Publication number
GB929272A
GB929272A GB1202659A GB1202659A GB929272A GB 929272 A GB929272 A GB 929272A GB 1202659 A GB1202659 A GB 1202659A GB 1202659 A GB1202659 A GB 1202659A GB 929272 A GB929272 A GB 929272A
Authority
GB
United Kingdom
Prior art keywords
hydroxy
group
methyl
steroids
hydrogen
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
GB1202659A
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Koninklijke Philips NV
Original Assignee
Philips Gloeilampenfabrieken NV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Philips Gloeilampenfabrieken NV filed Critical Philips Gloeilampenfabrieken NV
Publication of GB929272A publication Critical patent/GB929272A/en
Expired legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
    • A61K31/5685—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone having an oxo group in position 17, e.g. androsterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
    • A61K31/569—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone substituted in position 17 alpha, e.g. ethisterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J13/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J15/00—Stereochemically pure steroids containing carbon, hydrogen, halogen or oxygen having a partially or totally inverted skeleton, e.g. retrosteroids, L-isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J75/00—Processes for the preparation of steroids in general
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Steroid Compounds (AREA)

Abstract

The invention comprises 10a -methyl-9a -steroids of the general formula I shown in the figure wherein R1 represents a hydrogen atom or a methyl group, R2 represents no double bonds or one or more double bonds at one or more of positions 1, 2, 3, 4, 5, 6, 15 and 16 in the steroid nucleus, R3 represents a hydrogen or halogen atom, or a methyl, ethyl, hydroxy, etherified hydroxy or esterified hydroxy group, R4 represents a keto, hydroxy, etherified hydroxy or esterified hydroxy group, R5 represents a hydrogen or halogen atom, R6 represents a hydrogen or halogen atom or a methyl, hydroxy, etherified hydroxy or esterified hydroxy group, R7 represents a hydrogen or halogen atom, R8 represents a hydrogen atom or a hydroxy or keto group, R9 represents a hydrogen atom or a saturated or unsaturated hydrocarbon group containing from 1 to 6 carbon atoms or such group in which one or more hydrogen atoms is or are replaced by one or more hydroxy, etherified hydroxy or esterified hydroxy groups, and/or double bonded oxygen atoms, R10 represents a hydrogen atom or a hydroxy, etherified hydroxy or esterified hydroxy group (R9 and R10 being <FORM:0929272/IV(a)/1> <FORM:0929272/IV(a)/2> <FORM:0929272/IV(a)/3> <FORM:0929272/IV(a)/4> <FORM:0929272/IV(a)/5> <FORM:0929272/IV(a)/6> <FORM:0929272/IV(a)/7> <FORM:0929272/IV(a)/8> <FORM:0929272/IV(a)/9> not both hydrogen) or R9 and R10 together represent a keto group, and R11 represents a hydrogen atom or a methyl, hydroxy, etherified hydroxy or esterified hydroxy group; and the preparation of 10a -methyl-9a -steroids of the general formula VII shown in the Figure wherein R4 represents a keto, hydroxy, etherified hydroxy or esterified hydroxy group and R2 represents no double bonds or one or more double bonds at one or more of positions 1, 3, 4, 5 and 6 by oxidising 10a -methyl-9a -steroids of the general formula VI shown in the Figure wherein QVI represents a methyl group, and QVII represents an aldehyde group or a cyanhydric or bisulphite addition group derived therefrom or an O-acyl group derived from an aliphatic carboxylic acid having from 1 to 6 carbon atoms or an aromatic carboxylic acid, or QVI represents hydrogen and QVII represents a -COOR group wherein R represents an alkyl group having from 1 to 6 carbon atoms; the preparation of 10a -methyl-9a -steroids of the general formula V shown in the Figure wherein R2 and R4 have the above significance by oxidising 10a -methyl-9a -steroids of the general formula IV shown in the Figure wherein R2 and R2 have the above significance, QIV represents a secondary amine residue (including cyclic amine), or an O-acyl, alkyl or phenyl group and QV represents hydrogen, or both QIV and QV each represent a phenyl group or an aliphatic hydrocarbon group having from 1 to 6 carbon atoms; the preparation of 10a -methyl-9a -steroids of the general formula VIII shown in the Figure, wherein R2 and R4 have the above significance, R9 represents a hydrogen atom and R10 represents a hydroxy group, by reducing 10a -methyl-9a -steroids of the general formula VII with a reducing agent capable of reducing ketones to secondary alcohols (a 3-keto group converted to a 3-hydroxy group by this reduction step may be oxidised to a 3-keto group, for example, by means of manganese dioxide); the preparation of 10a -methyl-9a -steroids of the general formula VIII shown in the Figure wherein R9 represents a saturated or unsaturated hydrocarbon group containing from 1 to 6 carbon atoms or such radical containing one or more hydroxy or esterified hydroxy groups and/or double bonded oxygen atoms, and R10 represents a hydroxy or esterified hydroxy group, by reacting a 10a -methyl-9a -steroid of the formula VII with a Grignard compound or equivalent organo-metallic reagent of a saturated or unsaturated aliphatic halide having 1 to 6 carbon atoms or with an alkali metal acetylide having from 1 to 6 carbon atoms (in the latter case the process may include an additional step of partly or completely hydrogenating the unsaturated R9 group containing a triple bond) (a keto group present at the 3-position should be protected by converting to a 3-ether, enamine or glycol acetal to prevent attack by the organo-metal reagent and subsequently regenerating the 3-keto group). The oxidation processes referred to above may be carried out with chromium trioxide, sodium, potassium or ammonium dichromate or potassium permanganate in an acidic or alkaline medium or with ozone in which case it is necessary to decompose the intermediate ozonide with oxidising agents such as hydrogen peroxide or alkaline permanganate or with reducing agents such as aldehydes, zinc dust and acetic acid, or iron powder and sulphuric acid. It is preferable to protect a double bond at the 4,5-position when using the above oxidation methods such as by conversion to a 4,5-dibromide and then splitting off the bromine atoms, for example, by means of zinc dust in glacial acetic acid, or by conversion to a 4,5-epoxide and then decomposing the epoxide with a reducing agent, for example, a reducing agent referred to above, or with a solution of potassium iodide in acetic acid. Hydroxy groups present at the 3- and/or 17-positions in the products of the above process may be esterified as required. All the above processes may be modified in that the initial reactants are prepared by processes described in Specifications 929,273, 929,274 and 929,275. In addition, the above processes or modified processes may be adapted to prepare any of the 10a -methyl-9a -steroids of the general formula I shown in the Figure and referred to above. In the examples the compounds of formulae XXIII, XXIV and XXV shown in the Figure are prepared. Therapeutic compositions contain as the active ingredients 10a -methyl-9a -steroids of the general formula I shown in the Figure, wherein R1 to R11 have the above significance, mixed with or dissolved or dispersed in a solid or liquid excipient. The compositions may be administered orally or by injection, and have progestative, anabolic, antiinflammatory and anti-hormonal (such as anti-estrogenic or anti-androgenic) activities.
GB1202659A 1958-04-12 1959-04-12 Steroids and their production Expired GB929272A (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
NL226774 1958-04-12
NL232312 1958-10-15
NL236884 1959-03-07
NL237103 1959-03-13

Publications (1)

Publication Number Publication Date
GB929272A true GB929272A (en) 1963-06-19

Family

ID=27483655

Family Applications (4)

Application Number Title Priority Date Filing Date
GB4841359A Expired GB929275A (en) 1958-04-12 1959-04-09 Steroids and their production
GB4814262A Expired GB929274A (en) 1958-04-12 1959-04-12 Steroids and their production
GB4814162A Expired GB929273A (en) 1958-04-12 1959-04-12 Steroids and their production
GB1202659A Expired GB929272A (en) 1958-04-12 1959-04-12 Steroids and their production

Family Applications Before (3)

Application Number Title Priority Date Filing Date
GB4841359A Expired GB929275A (en) 1958-04-12 1959-04-09 Steroids and their production
GB4814262A Expired GB929274A (en) 1958-04-12 1959-04-12 Steroids and their production
GB4814162A Expired GB929273A (en) 1958-04-12 1959-04-12 Steroids and their production

Country Status (2)

Country Link
CH (3) CH396894A (en)
GB (4) GB929275A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014020577A1 (en) * 2012-08-03 2014-02-06 Centre National De La Recherche Scientifique Novel compounds which activate sirt1 enzymatic activity and pharmaceutical or cosmetic compositions comprising same

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014020577A1 (en) * 2012-08-03 2014-02-06 Centre National De La Recherche Scientifique Novel compounds which activate sirt1 enzymatic activity and pharmaceutical or cosmetic compositions comprising same
FR2994092A1 (en) * 2012-08-03 2014-02-07 Centre Nat Rech Scient NOVEL ENZYMA ACTIVITY COMPOUNDS OF SIRT1 AND PHARMACEUTICAL OR COSMETIC COMPOSITIONS COMPRISING THE SAME

Also Published As

Publication number Publication date
CH396894A (en) 1965-08-15
GB929275A (en) 1963-06-19
CH398576A (en) 1966-03-15
GB929274A (en) 1963-06-19
GB929273A (en) 1963-06-19
CH452517A (en) 1968-03-15

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