GB948545A - C-nor-steroids - Google Patents

C-nor-steroids

Info

Publication number
GB948545A
GB948545A GB5162A GB5162A GB948545A GB 948545 A GB948545 A GB 948545A GB 5162 A GB5162 A GB 5162A GB 5162 A GB5162 A GB 5162A GB 948545 A GB948545 A GB 948545A
Authority
GB
United Kingdom
Prior art keywords
diketo
hydroxy
allopregnane
acetate
keto
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
GB5162A
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.)
Organon Laboratories Ltd
Original Assignee
Organon Laboratories Ltd
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 Organon Laboratories Ltd filed Critical Organon Laboratories Ltd
Publication of GB948545A publication Critical patent/GB948545A/en
Expired legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J61/00Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by contraction of only one ring by one or two atoms
    • 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 (1) a process for the preparation of C-nor-steroids oxygenated in the 11-position wherein an 11, 12- diketo-steroid is treated with a strong base and the thus obtained 11-carboxy-11-hydroxy-C-nor-steroid is oxidized in an acid medium to give an 11-keto-C-nor-steroid; (2) compounds of the formula: <FORM:0948545/C2/1> wherein Y is H(b OH) or =O; R1 is H, OH or O acyl; R2 is H, OH or O acyl; and C1-C2 is saturated or unsaturated; and (3) compounds of the formula: <FORM:0948545/C2/2> wherein X is a halogen atom; Y is H(b OH) or =O; R1 is OH or O acyl; R2 is OH; and C1-C2 is saturated or unsaturated. The starting material in process (1) may be, for example, 11, 12-diketo-tigogenin which is converted to 11-keto-C-nor-tigogenin. In this product the spirostan side-chain may be degraded, for example, by reaction with a mixture of acetic anhydride, pyridine and methylamine hydrochloride (giving 11-keto-C-nor-pseudo-tigogenin), followed by oxidation with chromic acid to give 3b ,16b -dihydroxy-11,20-diketo-C-nor-allopregnane 3-acetate 16 - (gamma - methyl - delta - acetoxy) - valerate, boiling with methanolic sodium acetate to give D 16-11, 20-diketo -3b -acetoxy-C-nor-allopregnane and reducing this to 3b -acetoxy-11, 20-diketo -C-nor-allopregnane. This may then be enol-acylated to give D 17-3,20-diacetoxy-11-keto -C-nor-allopregnane, this oxidized with an organic per-acid to 3b , 20-diacetoxy-11-keto-17, 20-oxido-C-nor-allopregnane, and this hydrolysed to 3b , 17a -dihydroxy-11, 20-diketo-C-nor-allopregnane. This may then be iodated or brominated to give the 21-halo compound which on reaction with, for example, sodium acetate gives 3b , 17a , 21-trihydroxy-11, 20-diketo-C-nor-allopregnane 21-acetate which on hydrolysis gives the 21-ol. The acetate may be oxidized to the 3-ketone, and this may be reduced, by halogenation and dehydrohalogenation or by means of selenium dioxide, to give D 1,4-3, 11, 20-triketo -17a , 21-dihydroxy-C-nor-pregnadiene-21-acetate which on hydrolysis gives the 21-ol. A halogen atom can be introduced into the 9-position by reduction of the 11-keto group and dehydration to the D 9(11)-compound which by reaction with for example, N-bromo-acetamide, followed by treatment with, for example, potassium acetate gives the 9, 11-oxido-compound which is subsequently converted to the desired 11b -hydroxy -9-halogen compound by reaction with hydrochloric or hydrofluoric acid. On oxidation this compound gives the 11-keto-9a -halogen compound. The thus prepared compounds can be esterified at the 17a - and 21-positions with carboxylic acids or inorganic acids such as phosphoric. Examples describe the above-detailed process for the preparation of C-nor-prednisone and in further examples (1) 3a -hydroxy-11,12-diketo-cholanic acid methyl ester 3-formate gives 3a ,11-dihydroxy-11-carboxy-C-nor-cholanic acid and then the 11-keto compound, this with phenyl magnesium bromide gives D 23-3a -hydroxy -11- keto-24, 24-diphenyl-C-nor-cholene, this with N-bromo-succinimide gives D 23-3a -hydroxy-11-keto-22-bromo-24, 24-diphenyl-C-nor-cholene and this on oxidation gives 3a -hydroxy-11, 20-diketo-C-nor-pregnane; (2) 3b , 12b -diacetoxy-11, 20-diketo-allopregnane (prepared by hydrogenation of the D 16-compound) is converted to its 20-ethylene ketal, this is hydrolysed to the 3b , 12b -diol, this is oxidized to the corresponding 11, 12-diketo-allopregnane compound and this by the process of the invention gives 3b -hydroxy-11,20-diketo-C-nor-allopregnane; (3) the acetate of the last-named product is hydrolysed to that product and this by the process outlined above is converted into D 1,4-3,11,20-triketo-C-nor-pregnadiene; (4) D 1,4-3,11, 20-triketo-17a -hydroxy-C-nor-pregnadiene, prepared similarly, is converted to the 17-acetate and other esters; (5) the product of (1) is oxidized to the 3-ketone, this is brominated to 4-bromo-3,11,20-triketo-C-nor-pregnane, this is converted to D 4-3, 11, 20-triketo-C-nor-pregnane, this is ketalized at the 3- and 20-positions, the diketal reduced to the 11-ol, and the keto groups again liberated, and the thus obtained 11-keto and 11-hydroxy compounds are converted into the corresponding 17a -hydroxy and 17a , 21-dihydroxy compounds, to obtain 11-keto-17a -hydroxy-C-nor-progesterone, 11-hydroxy -17a - hydroxy -C-nor-progesterone, C-nor-cortisone and C-nor-cortisol, which may then be esterified; (6) 3, 11, 20-triketo -17a , 21-dihydroxy-C-nor-allopregnane-21-acetate is converted to the 3, 20-disemicarbazone, this is reduced and hydrolysed to 3, 20-diketo-11b , 17a , 21-trihydroxy -C-nor-allopregnane -21-acetate, this is dehydrated to the corresponding D 9(11)-compound, this is converted via the 9a -bromo-11 b -hydroxy compound and the 9, 11-oxido-compound to 3, 20-diketo-11 b , 17a , 21-trihydroxy -9a - fluoro -C-nor-allopregnane -21-acetate, this is reduced to 9a -fluoro-C-nor-prednisolone -21- acetate, this is oxidized to the corresponding prednisone compound, and this is hydrolysed and converted to various other 21-esters; and (7) 3, 11, 20-triketo-17a , 21-dihydroxy -C-nor-pregnane -21- acetate is similarly converted to 9a -fluoro-C-nor-cortisone and -hydrocortisone and 21-esters thereof.
GB5162A 1961-01-13 1962-01-01 C-nor-steroids Expired GB948545A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
NL260043 1961-01-13

Publications (1)

Publication Number Publication Date
GB948545A true GB948545A (en) 1964-02-05

Family

ID=19752807

Family Applications (1)

Application Number Title Priority Date Filing Date
GB5162A Expired GB948545A (en) 1961-01-13 1962-01-01 C-nor-steroids

Country Status (4)

Country Link
BE (1) BE612592A (en)
BR (1) BR6235608D0 (en)
CH (1) CH425775A (en)
GB (1) GB948545A (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110964077A (en) * 2018-09-30 2020-04-07 天津药业研究院有限公司 Oxidation synthesis method of steroid 11-keto compound

Also Published As

Publication number Publication date
BR6235608D0 (en) 1973-07-10
BE612592A (en) 1962-07-12
CH425775A (en) 1966-12-15

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