GB886861A - Steroid compounds - Google Patents

Steroid compounds

Info

Publication number
GB886861A
GB886861A GB28456/58A GB2845658A GB886861A GB 886861 A GB886861 A GB 886861A GB 28456/58 A GB28456/58 A GB 28456/58A GB 2845658 A GB2845658 A GB 2845658A GB 886861 A GB886861 A GB 886861A
Authority
GB
United Kingdom
Prior art keywords
keto
group
dimethyl
hydroxy
bismethylenedioxy
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
GB28456/58A
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.)
Merck and Co Inc
Original Assignee
Merck and Co Inc
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 Merck and Co Inc filed Critical Merck and Co Inc
Publication of GB886861A publication Critical patent/GB886861A/en
Expired legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J5/00Normal 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J75/00Processes 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)

Abstract

The invention comprises steroid compounds of the general formulae <FORM:0886861/IV (b)/1> <FORM:0886861/IV (b)/2> <FORM:0886861/IV (b)/3> wherein X represents hydrogen, fluorine, chlorine or bromine, R represents hydrogen or an acyl group, including a phosphate group, Y represents a keto or hydroxy group, Z represents a group convertible to a keto group by acid hydrolysis, and the dotted line in the 1 (2) position represents the presence of an optional double bond, and a process that comprises reacting 16a -methylcortisone with formaldehyde under acidic conditions to form 17a ,20,20,21-bismethylenedioxy-16a -methyl-3,11-diketo-4-pregnene, protecting the 3-keto group of this compound by converting it to a group convertible to a keto group by acid hydrolysis, epoxidising the 3-protected keto compound to form a 3-(protected keto)-17a ,20,20, 21 - bismethylenedioxy - 5, 6 - epoxy - 16a - methyl - 11-keto-pregnane, reacting this compound with formic acid to produce a mixture of 17a ,20,20,20-bismethylenedioxy - 17a - methyl - 6a - formlyoxy - 5-hydroxy-3,11-diketo-pregnane and 17a ,20,20,21-bismethylenedioxy - 16a - methyl - 5 - formyloxy - 6a -hydroxy-3,11-diketo-pregnane, treating this mixture with a base such as aqueous alkali metal hydroxide, to form 17a ,20,20,21-bismethylenedioxy - 16a - methyl - 3, 6, 11 - triketo - allo - pregnane, protecting the 3-keto group of this compound by converting it to a group convertible to a keto group by acid hydrolysis to form a 3-protected keto-a 17,20,20,21-bismethylenedioxy-16a -methyl-6, 11-diketo-allopregnane, reacting this compound with a methyl Grignard reagent to for a 3-protected keto-17a ,20,20,21-bismethylenedioxy - 6a , 16a - dimethyl - 6b - hydroxy - 11 - keto allopregnane, and reacting this compound with a dehydrating agent such as thionyl chloride in pyridine, to form a 3-protected keto-17a ,20,20, 21 - bismethylenedioxy - 6, 16a - dimethyl - 11 - keto-5-pregnene, with the optional further step of reducing the 11-keto group to an 11b -hydroxy group, e.g. with lithium aluminium hydride, to form a 3-protected keto-17a ,20,20,21-bismethylenedioxy - 6, 16a - dimethyl - 11b - hydroxy - 5 - pregnene, with the optional further step of subjecting the 3-protected keto-17a ,20,20,21-bismethylenedioxy-6,16a -dimethyl-11-(keto or b -hydroxy)-5-pregnene to acid hydrolysis, e.g. with p-toluenesulphonic monohydric in anhydrous acetone, to form 3-keto-17a ,20,20,21-bismethylenedioxy-6a ,16a -dimethyl-11-(keto or b -hydroxy)-4-pregnene, with the optional further step of hydrolysing the last mentioned compound with aqueous organic acid to produce 6a ,16a -dimethyl - cortisone or 6a , 16a - dimethyl - hydro - cortisone, with the optional further steps of acylating the 6a ,16a -dimethyl-hydrocortisone to form the corresponding 21-acylate, reacting the 21-acylate with a dehydrating agent, e.g. phosphorus oxychloride or methane sulphonyl chloride, to produce a 6a ,16a -dimethyl-17a -hydroxy-21 - acyloxy - 3, 20 - diketo - 4, 9 (11) - pregnadiene, and brominating this compound to form 9a - bromo - 6a , 16a - dimethyl - 11b , 17a - di - hydroxy - 21 - acyloxy - 3, 20 - diketo - 4 - preg - nene, with the optional further steps of reacting the 9a -bromo compound with anhydrous potassium acetate in ethanol to form a 6a ,16a -dimethyl-9,11 - epoxy - 17a - hydroxy - 3, 20 - diketo - 21 - acyloxy-4-pregnene and treating the 9,11-epoxy compound with hydrogen fluoride to form a 6a , 16a - dimethyl - 9a - fluoro - hydrocortisone 21-acylate which may be hydrolysed to the corresponding 21-hydroxy compound, and with the optional further step of oxidising the 6a ,16a -dimethyl-9a -fluoro-hydrocortisone or the 21-acylate thereof with chromium trioxide in pyridine to form 6a ,16a -dimethyl-9a -fluoro-cortisone or its 21-acylate. The invention also includes processes for the preparation of 21-hydroxy-1,4-pregnadienes of the above general formula by reducing the corresponding 4-pregnene compounds or 21-acylates thereof with the dehydrogenating activity produced by growing Schizomycetes or Bacillus sphaericus micro-organisms, and for the preparation of the 21-hydroxy- and 21-acylate-1,4-pregnadiene compounds of the above general formula by reducing the corresponding 4-pregnene compounds with selenium dioxide. The group at the 3-position which is convertible to keto by acid hydrolysis may be a cyclic ketal group such as an ethylenedioxy, ethylenedithioketal or ethylene hemithioketal group, a cyclic amine group, a pair of univalent groups such as a non-cyclic grouping-particularly dimethylketal or dimethylthioketal, or a single univalent group such as an enol ether group in which case there is an additional double bond in the 3-position. Detailed examples are given. Specification 877,085 is referred to.
GB28456/58A 1957-09-16 1958-09-04 Steroid compounds Expired GB886861A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US886861XA 1957-09-16 1957-09-16

Publications (1)

Publication Number Publication Date
GB886861A true GB886861A (en) 1962-01-10

Family

ID=22212822

Family Applications (1)

Application Number Title Priority Date Filing Date
GB28456/58A Expired GB886861A (en) 1957-09-16 1958-09-04 Steroid compounds

Country Status (1)

Country Link
GB (1) GB886861A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116196907A (en) * 2022-12-29 2023-06-02 中国核动力研究设计院 Solid phase extractant and preparation method and application thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116196907A (en) * 2022-12-29 2023-06-02 中国核动力研究设计院 Solid phase extractant and preparation method and application thereof

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