GB963482A - New steroids and new processes for the preparation of steroids - Google Patents

New steroids and new processes for the preparation of steroids

Info

Publication number
GB963482A
GB963482A GB36664/59A GB3666459A GB963482A GB 963482 A GB963482 A GB 963482A GB 36664/59 A GB36664/59 A GB 36664/59A GB 3666459 A GB3666459 A GB 3666459A GB 963482 A GB963482 A GB 963482A
Authority
GB
United Kingdom
Prior art keywords
methyl
hydroxy
pregn
ene
acetate
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
GB36664/59A
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.)
Individual
Original Assignee
Individual
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 Individual filed Critical Individual
Priority to GB36664/59A priority Critical patent/GB963482A/en
Priority to US130358A priority patent/US3134769A/en
Publication of GB963482A publication Critical patent/GB963482A/en
Expired legal-status Critical Current

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J71/00Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
    • 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Steroid Compounds (AREA)

Abstract

The invention comprises 1-methyl-steroids and 1-methylene-steroids which are the 1-methyl compounds of the pregnane series having a double bond in the 4(5) or 5(6) position which conform to the general formula <FORM:0963482/C1/1> wherein the rings marked A and B represent the A and B rings of the steroid nucleus, Y represents -H, -OH or -OCOCH3 or D 1 and X represents =O or (-H)-OH or (-H)-OCOCH3, the said double bond being in the 4(5) position when Y represents D 1, and the 1-methyl-genins of the general formulae: <FORM:0963482/C1/2> <FORM:0963482/C1/3> <FORM:0963482/C1/4> and the 1-methylene genins conforming to the general formulae: <FORM:0963482/C1/5> <FORM:0963482/C1/6> wherein X1 represents (-H)-OH or (-H)-OCOCH3 and Y1 represents -H or -OH; the preparation of the 1-methyl -1- hydroxy steroids of the first four general formulae above by subjecting the corresponding 1,3-dihydroxy-steroids to oxidation at the 1-position and reacting the resulting 1-keto-steroid with a methyl magnesium halide (the selective oxidation may be carried out using a pyridine-chromium trioxide complex or an aqueous solution of a mixture of chromic and sulphuric acids and the oxidation may be preceded by a selective acetylation at the 3-position with an acetic acid-acetic anhydride mixture to form a 1-hydroxy -3- acetoxy-steroid ; the preparation of steroids of the last two general formulae above or a 1-methyl-genin free from a hydroxyl group in the 1-position and conforming to any of the second, third and fourth general formulae above by acetylating in the 3-position the corresponding 1-methyl-1, 3-dihydroxy-genin, dehydrating in the 1-position the resulting 1-methyl -1- hydroxy -3- acetoxy-genin and, if desired, hydrogenating in the presence of palladium on charcoal the 1-methylene -3- acetoxy-genin thus obtained (the optional hydrogenation step may be preceded by a saponification step to form a 1-methylene -3- hydroxy-genin); the preparation of 1-methyl-1, 3, 20-trihydroxy-pregn -5- ene by reducing 1, 3-diacetoxy-pregn -5- ene -20- one with lithium aluminium hydride and acetylating in the 3- and 20-positions the resultant 1, 3, 20-trihydroxy-pregn -5- ene with an acetic acid-acetic anhydride mixture to form 1-hydroxy-3, 20-diacetoxy-pregn -5- ene, oxidising this compound in the 1-position by treatment with a pyridine-chromium trioxide complex or with an aqueous solution of a mixture of chromic and sulphuric acids and reacting the resulting 1-keto-3, 20-diacetoxy-pregn -5- ene with a methyl magnesium halide and, if required, oxidising as before to form 1-methyl -1- hydroxy-3, 20-diketo-pregn -5- ene; the preparation of 1-methyl -D 1,4-3, 20-diketo-pregnadiene by dehydrating 1-methyl -1- hydroxy-3, 20-diketo, pregn -5- ene by treatment with an acid or alkali; the preparation of 1-methyl -1- acetoxy -3- hydroxy-16a , 17a -epoxy-pregn -5- ene -20- one by epoxidising 1-methyl -1- acetoxy -3- hydroxy -D 5,16-pregnadien -20- one with alkaline hydrogen peroxide; the preparation of 1-methyl-1, 3-diacetoxy -16b - bromo -17a - hydroxy-pregn -5- ene -20- one by acetylating in the 3-position 1-methyl -1- acetoxy -3- hydroxy -16a , 17a -epoxy-pregn -5- ene -20- one with an acetic acid-acetic anhydride mixture and reacting the resulting 1, 3-diacetoxy compound with hydrobromic acid and, if required, removing the 16b -bromine atom by hydrogenating in the presence of palladium on charcoal to form 1-methyl-1, 3-diacetoxy -17a - hydroxy-pregn -5- ene -20- one and, if required, acylating this compound with an acid chloride or anhydride of a carboxylic acid containing not more than 9 carbon atoms, saponifying in the 3-position the resultant 1, 3, 17-triacyloxy compound by boiling with aqueous potassium bicarbonate and oxidising in the 3-position the resulting 3-hydroxy-1, 17-diacyloxy compound with an aqueous solution of a mixture of chromic and sulphuric acids; the preparation of 1-methyl-3, 20-diketo -17a - acyloxy -D 1,4-pregnadiene by treating 1-methyl -1- acetoxy-3, 20-diketo -17a - acyloxy-pregn -5- ene either with an acid or with alkali and acylating the resulting 1-methyl-3, 20-diketo -17a - hydroxy -D 1,4-pregnadiene with a carboxylic acid chloride or anhydride as defined above, and the preparation of 1-methyl-16a , 17a -epoxy -D 1,4- pregnadiene-3, 20-dione by oxidising 1-methyl -1- acetoxy -3- hydroxy-16a , 17a -epoxy-pregn -5- ene -20- one with an aqueous solution of a mixture of sulphuric and chromic acids and then with an alkali. In reactions using a methyl magnesium halide it is necessary to block a 20-keto group such as by forming a 20-cyclic ketal group. The preferred compounds are 1-methyl -1- hydroxy-diosgenin, 1-methyl -1- hydroxy-D 2 5(27)-dehydrodiosgenin, 1-methyl -D 5- pregn-1, 3b , 20b -triol, 1-methyl-progesterone, 1-methyl -D 1- dehydroprogesterone, 1-methyl -17a - hydroxy-D 1-dehydroprogesterone and its esters, and 1-methyl -1- hydroxyprogesterone and its esters 1-Keto-diosgenin is prepared by oxidising ruscogenin with a chromium trioxide-pyridine complex or with chromic acid. Ruscogenin -3- acetate is prepared by acetylating ruscogenin with acetic acid and acetic anhydride. Neoruscogenin -3- acetate is prepared by a similar method. 1-Keto-diosgenin -3- acetate is prepared either by acetylating 1-keto-diosgenin or by oxidising ruscogenin -3- acetate with chromic acid. 1-Keto -D 25(27)- dehydrodiosgenin -3- acetate is prepared by oxidising neoruscogenin -3- acetate with chromic acid. D 5-Pregnen-1b , 3b -diol -20- one-1, 3-diacetate is prepared by acetylating the hydroxy groups in the 1- and 3-positions of ruscogenin or neoruscogenin, degrading the resulting 1-,3 diacetate and hydrogenating with palladium on charcoal. 1-Methyl -D 5,16- pregnadiene-1, 3b -diol -20- one-1-acetate is prepared by treating 1-methyl -1- hydroxy-diosgenin or the corresponding 3-acetate or 1-methyl -1- hydroxy -D 2 5(27)-dehydrodiosgenin -3- acetate with monomethylamine hydrochloride, pyridine and acetic anhydride at an elevated temperature and oxidising the resulting oil with chromium trioxide in acetic acid. 1-Methyl -1- acetoxy -3b - hydroxy -20- oxo-pregn -5- ene is prepared by hydrogenating the corresponding D 5,16-pregnadiene in the presence of palladium or on charcoal. 1-Methyl -3b - hydroxy -D 5- pregnen -20- one is prepared by treating 1-methyl-yamogenin -3- acetate or 1-methyl-diosgenin -3- acetate with methylamine hydrochloride, pyridine and acetic anhydride at an elevated temperature and then oxidising with chromium trioxide in acetic acid and hydrogenating the resulting 1-methyl -3b -hydroxy -D 5,16- pregnadien -20- one (which may be purified by condensation with Girards reagent T) in the presence of palladium on charcoal. The Provisional Specification refers to similar compounds and processes in which the acetoxy group at the 1-, 3- and/or 20-positions may be any acyloxy group derived from a lower fatty acid. Therapeutic compositions having progestational, androgenic and anti-inflammatory activity comprise one or more steroids of the above general formulae and a pharmaceutical carrier. The carrier may be a solid or liquid to form compositions in the form of tablets, powders or capsules for oral ingestion, or solutions for parenteral use.
GB36664/59A 1959-10-28 1959-10-28 New steroids and new processes for the preparation of steroids Expired GB963482A (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
GB36664/59A GB963482A (en) 1959-10-28 1959-10-28 New steroids and new processes for the preparation of steroids
US130358A US3134769A (en) 1959-10-28 1961-08-09 1-methyl-diosgenins

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB36664/59A GB963482A (en) 1959-10-28 1959-10-28 New steroids and new processes for the preparation of steroids

Publications (1)

Publication Number Publication Date
GB963482A true GB963482A (en) 1964-07-08

Family

ID=10390154

Family Applications (1)

Application Number Title Priority Date Filing Date
GB36664/59A Expired GB963482A (en) 1959-10-28 1959-10-28 New steroids and new processes for the preparation of steroids

Country Status (2)

Country Link
US (1) US3134769A (en)
GB (1) GB963482A (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3501504A (en) * 1968-02-23 1970-03-17 Searle & Co 1-methylen-5alpha-androstan-17-one and derivatives thereof

Also Published As

Publication number Publication date
US3134769A (en) 1964-05-26

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