US2433848A - Procedure for preparation of progesterone - Google Patents

Procedure for preparation of progesterone Download PDF

Info

Publication number
US2433848A
US2433848A US521851A US52185144A US2433848A US 2433848 A US2433848 A US 2433848A US 521851 A US521851 A US 521851A US 52185144 A US52185144 A US 52185144A US 2433848 A US2433848 A US 2433848A
Authority
US
United States
Prior art keywords
progesterone
procedure
solution
carbinol
acid
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 - Lifetime
Application number
US521851A
Inventor
Percy L Julian
Cole John Wayne
Magnani Arthur
Harold E Conde
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.)
Akzo Nobel Paints LLC
Original Assignee
Glidden Co
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 Glidden Co filed Critical Glidden Co
Priority to US521851A priority Critical patent/US2433848A/en
Application granted granted Critical
Publication of US2433848A publication Critical patent/US2433848A/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • 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
    • C07J75/00—Processes for the preparation of steroids in general

Definitions

  • 'I 'he present invention relates to the degradationotbile acids and similar acids-obtained by the oxidation degradation of steroids, and more particularly relates to an improvement in the Barbier wieland processfor converting bisnorcholenic' acid to progesterone. v
  • Step 2. '-'Conversion of the methyl ester to 3-hydroxy'ternorcholenylediphenyl carbinol.
  • a further object is to provide a simplified process oi preparing progesterone from bisnorcholenic acid.
  • An additional object is to reduce greatly the number of steps involved in producing progesterone irom bisnorcholenic acid.
  • Another object is to provide a new process for decomposing ozonides of the type where R and R are hydrocarbon residues, and R is a cyclopentano hydrophenanthrene nucleus,
  • A..further object is to provide a new process for converting carbinols of the type Step 5 .'--.Conversion of pregnenolone acetate into its semiecarbazone for isolation and purification.
  • Step'6' Hydrolysis of, the semi-carbazone to Sept. "7..0ikidation of the 3'-hydroxy group of bility of Stigmasterol, made a commercial exploitationof the Fernholz-Butenandt procedure for the preparation of progesterone impractical.
  • a preferred mode of carrying out the process comprises treating the carbinol in glacial acetic acid with halogen, passing in ozone, adding an oxidizing agent such as chromic acid, then a dehalogenating agent-all carried out in one operation.
  • an oxidizing agent such as chromic acid
  • a dehalogenating agent-all carried out in one operation.
  • the carbinol is dissolved in glacial acetic acid and, after addition of the reagents indicated above, and progesterone is isolated from the solution.
  • Example I (recrystallized from chloroform) in 250 cc. gla-' cial acetic acid is added at a room temperature 4 tion is concentrated under the vacuum of a wate pump and at 80 to 90 C. until 500 to 600 cc.-of distillate have collected.
  • the reaction mixture is now diluted with 3 to 4 volumes of water and extracted four times with ether.
  • the ether extractions are washed successively with water, 10% sodium hydroxide solution, and water again.
  • the washed ether extracts are combined, concentrated and steam distilled.
  • the residue from the steam distillation is cooled, taken up in ether and the ether extract again washed successively with. water, dilute a solution of 2.7 cc. (8.4) grams of bromine in 150 cc. of glacial acetic acid.
  • the solution is warmed to 96100 F. and an ozone-oxygen mixture containing 3 to 4% of ozone by volume passed in for 30 minutes at a rate of flow of 3.5 liters per minute.
  • the dibromide of the carbinol usually crystallizes out ,of solution toward the end of the bromination time and the solution should be clear at the end of the ozonization. During the ozonization the temperature rises several degrees.
  • the solution after ozonization is cooled at once to 70 F. and the oxidizing mixture, cooled before using, and consisting of 10 grams chromic oxide, 1 cc. concentrated sulfuric acid, 15 cc. of water and 80 cc. glacial acetic acid, is added with stirring during several minutes, never allowing the temperature of the reaction mixture to rise above 80 F.
  • 20 cc. of methanol is added to the reaction mixture.
  • the reaction mixture is now diluted with 500 cc. of glacial acetic acid and the resulting solution cooled to 60 F.
  • 300 cc. of one molar chromous chloride solution prepared according to the procedure of Conant and Cutter, J. A. C. S-., 48 1023 (1926), is then added with shaking under an atmosphere of carbon dioxide. After standing for /2 hour (or the solution may stand as long as over night, if desired), the solusodium hydroxide and water.
  • Example II The procedure was identical with that in Ex-' ample I except that the chromous chloride was replaced by 300 cc. of a 1 molar solution of vanadous chloride prepared according to the method of Conant and Cutter, J. A. C. S., 48 1023 (1926), and the vanadous chloride was added to the mixture without dilution of the mixture prior to the addition of the debrominating agent.
  • the crude progesterone had a melting point of 117 to 124 C.
  • Example III The procedure was the same as in Example I except that 300 cc. of a commercial 20% solution of titanous chloride was used as the debrominating agent. and there was no dilution of the reaction mixture prior to the addition of thedebrominating agent.
  • the crude progesterone had a melting point of 117 to 124 C.
  • Example IV The procedure was the same as in Example III, except that the reaction mixture was heated on a steam cone for one hour for the debromination.
  • the crude progesterone had a melting point of 113 to 119 C.
  • oxidizing agents than chromic acid which are capable of converting the 3-.OI-I group to a keto group may be employed, such as chromates and permanganates.
  • the nuclear double bond may also be protected by the use of other known removable reagents such as hydrobromides, etc.
  • the method for decomposing ozonides and dehalogenation by the use of the chromous. vanadous and titanous salts which method is a significant feature of this invention, is also applicable where the 3-OH group is not oxidized to the 3-ket'o group.
  • the series of steps outlined above for the preparation of progesterone may be altered in that after bromination and ozonization the resulting ozonide is treated directly with the chromous, vanadous or titanous salts toyield pregene 5-3-ol-2Q-one. Obviously this procedure is applicable. where the starting material contains a 3-acyloxy group.
  • the process of the present invention may be The final ether I solution is concentrated to a volume of about 20 v employed with other carbinols than the diphenyl' carbinol.
  • any carbinol of the formula carbinols of the formula CH: /CII CHI IEC-C R R which upon dehydration forms ethylenes of the type in which R is hydrogen or a hydrocarbon radical may be used.
  • the process which comprises the steps of first treating S-hydroxy A-ternorcholenyl diphenyl carbinol with bromine, ozonizing the brominated material, convertin the 3-hydroxy group of the ozonization product toa keto group, treating the resulting 3-keto compound with a dehalogenating agent, all without isolation of intermediates, and recovering progesterone from the reaction mixture.
  • progesterone which comprises successively treating a solution 01' 3-hydroxy A-ter-norcholeny1 diphenyl carbinol in acetic acid with bromine, ozone, chromic acid, and chromous chloride, without isolation of intermediates, and recovering progesterone from the reaction mixture.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Steroid Compounds (AREA)

Description

' pure pregnenolone.
Patented Jam 6 1948 znaaue; v PROCEDURE FOR PREPARATION OF 1 raoaas'ranonn Percy L. JulianpMaywood, John Wayne Cole,
Chicago, vArthur Magnani,
Wilmette, and
.- Harold E. Conde, Chicago, 111., aaslgnors to The leveland, Ohio, at corpora- Game; Company,
tibn ofOhio no Drawing.-
'I 'he present invention relates to the degradationotbile acids and similar acids-obtained by the oxidation degradation of steroids, and more particularly relates to an improvement in the Barbier wieland processfor converting bisnorcholenic' acid to progesterone. v
With his discovery of 3-hydroxy bisnorcholenic acid from'the plant sterol, Stigmasterol, Ann. 507 128 (1933), Fernholz immediately realized that a Barbier-Wieland' degradation ,off this acid, Gilman; Organic Chem., vol. II, page'1357 (1943),
followed by oxidation of the -3-hydroxy group, would lead toprogesterone, 'Ber. 67 1855, 2027 (1934). Almost simultaneouslyButenandt,whose brilliant work on the isolation of the corpus luteum hormone from natural'sources had corroborated-theearlier work of Allen and his coworkers,.likewise saw the significance of Fernholzs discovery, Ber; 6'] 1611, 1901, 2085 (1934). Both of 'thes'eworkers almost simultaneously applied the 'Barbier-Wieland technique toFernholzs acid, Butenandt apparently finishing and publishinghis-experiments. a short time before those oi Fernhola came into print. I
Neither 10f these; workers, however, departed essentially. from the traditional Barbier-Wieland procedure nor'jdid they improve upon this procedure in the case'of the substances they were working with. Thus a total of at least-seven distinct steps wasinvolve'd in going from 3-acetoxy bisnorcholenicacid to progesterone. These steps may be outlined as follows:
Step -1.Conversion of the acid ester '(viadiazo-methane). Q
Step 2.'-'Conversion of the methyl ester to 3-hydroxy'ternorcholenylediphenyl carbinol.
into its methyl Step. 3.-' Acetylation of the 'ternorcholenyl-di I phenyl-carbinol and dehydration to the corresponding' diph'enyl ethylene. r
Step 4.'Ozon izatlon of the diphenyl-ethylene to pregnenol'one acetate. Y
Application February '10. 1944, Serial No. 521,851
serum. (or. zoo-c973) z tion to provide an improved process for producing progesterone.
A further object is to provide a simplified process oi preparing progesterone from bisnorcholenic acid.
An additional object is to reduce greatly the number of steps involved in producing progesterone irom bisnorcholenic acid. I
Another object is to provide a new process for decomposing ozonides of the type where R and R are hydrocarbon residues, and R is a cyclopentano hydrophenanthrene nucleus,
to the corresponding ketones;
A..further object is to provide a new process for converting carbinols of the type Step 5 .'--.Conversion of pregnenolone acetate into its semiecarbazone for isolation and purification. n Y, I. J I
Step'6'. Hydrolysis of, the semi-carbazone to Sept. "7..0ikidation of the 3'-hydroxy group of bility of Stigmasterol, made a commercial exploitationof the Fernholz-Butenandt procedure for the preparation of progesterone impractical.
It'is'accordingly an object of the present inven-' Other objects will be apparent to those skilled in the art from the following description. In United States Patents Nos. 2,218,971, 2,273,045 and 2,273,046 there are disclosed pro- .cedures which make Stigmasterol readily accessible. In United States Patent No. 2,304,100 there Barbier-Wieland procedure outlined above was eliminated, whereby the acid can be converted directly into the-carbinol of Step 2 without going through the commercially difficult step of esterification with explosive diazo-methane.
1 In the present invention further improvements in the procedure leading to the preparation of progesterone are obtained, and the process involves the complete elimination of Step 3 above,
- and the replacement of the remaining four steps by one operative procedure.
Thus the seven steps of the above procedure now become a twostep operation of great simplicity which yields a hormone or a high degree of purity and in greatly enhanced yields. v
' Briefly outlined a preferred mode of carrying out the process comprises treating the carbinol in glacial acetic acid with halogen, passing in ozone, adding an oxidizing agent such as chromic acid, then a dehalogenating agent-all carried out in one operation. In short the carbinol is dissolved in glacial acetic acid and, after addition of the reagents indicated above, and progesterone is isolated from the solution.
To efiect this very simplified and time-saving procedure, certain novel chemical reactions had v to be introduced. Thus vigorous ozonization oi the free carbinol gave better yields of an ozonide than those obtained by ozonization of the diphenyl-ethylene such as is described in Step 4 above. To our knowledge this is the first time that a carbinol has been so directly converted into the ozonide of its corresponding ethylene and the invention comprises, interalia, this method ;of treating tertiary carbinols of the type herein contemplated.
After addition of sufllcient chromic-acid to the ozonide to convert the B-hydroxy group into the 3-keto group, a solution of chromous chloride is added. Instead of chromous chloride we have also been able to use quite successfully vanadous chloride or a 20% commercial solution of titanous chloride. Our yields are greatly enhanced by the smooth action of such highly reducing agents as chromous chloride in effecting clean cleavage of the ozonide as well as complete and smooth dehalogenation. This novel method of dehalogenating has in this case as well as in others proved to be a most useful tool and may be used-for treating compounds of the general type contemplated herein.
Following the treatment of an acetic acid solution of 3-hydroxy ternor-cholenyl-carbinol by bromine, ozone, chromic acid, and chromous chloride, all in direct succession in the same reaction vessel, it is very easy to separate from the solution progesterone of a high degree of purity.
The following examples serve to illustrate the invention:
Example I (recrystallized from chloroform) in 250 cc. gla-' cial acetic acid is added at a room temperature 4 tion is concentrated under the vacuum of a wate pump and at 80 to 90 C. until 500 to 600 cc.-of distillate have collected.
The reaction mixture is now diluted with 3 to 4 volumes of water and extracted four times with ether. The ether extractions are washed successively with water, 10% sodium hydroxide solution, and water again. The washed ether extracts are combined, concentrated and steam distilled. The residue from the steam distillation is cooled, taken up in ether and the ether extract again washed successively with. water, dilute a solution of 2.7 cc. (8.4) grams of bromine in 150 cc. of glacial acetic acid. The solution is warmed to 96100 F. and an ozone-oxygen mixture containing 3 to 4% of ozone by volume passed in for 30 minutes at a rate of flow of 3.5 liters per minute. The dibromide of the carbinol usually crystallizes out ,of solution toward the end of the bromination time and the solution should be clear at the end of the ozonization. During the ozonization the temperature rises several degrees.
The solution after ozonization is cooled at once to 70 F. and the oxidizing mixture, cooled before using, and consisting of 10 grams chromic oxide, 1 cc. concentrated sulfuric acid, 15 cc. of water and 80 cc. glacial acetic acid, is added with stirring during several minutes, never allowing the temperature of the reaction mixture to rise above 80 F. After standing for 1 hour at room temperature, 20 cc. of methanol is added to the reaction mixture. The reaction mixture is now diluted with 500 cc. of glacial acetic acid and the resulting solution cooled to 60 F. 300 cc. of one molar chromous chloride solution, prepared according to the procedure of Conant and Cutter, J. A. C. S-., 48 1023 (1926), is then added with shaking under an atmosphere of carbon dioxide. After standing for /2 hour (or the solution may stand as long as over night, if desired), the solusodium hydroxide and water.
Example II The procedure was identical with that in Ex-' ample I except that the chromous chloride was replaced by 300 cc. of a 1 molar solution of vanadous chloride prepared according to the method of Conant and Cutter, J. A. C. S., 48 1023 (1926), and the vanadous chloride was added to the mixture without dilution of the mixture prior to the addition of the debrominating agent. The crude progesterone had a melting point of 117 to 124 C.
Example III The procedure was the same as in Example I except that 300 cc. of a commercial 20% solution of titanous chloride was used as the debrominating agent. and there was no dilution of the reaction mixture prior to the addition of thedebrominating agent. The crude progesterone had a melting point of 117 to 124 C.
Example IV The procedure was the same as in Example III, except that the reaction mixture was heated on a steam cone for one hour for the debromination. The crude progesterone had a melting point of 113 to 119 C.
Other oxidizing agents than chromic acid which are capable of converting the 3-.OI-I group to a keto group may be employed, such as chromates and permanganates. In certain phases of the invention the nuclear double bond may also be protected by the use of other known removable reagents such as hydrobromides, etc.
The method for decomposing ozonides and dehalogenation by the use of the chromous. vanadous and titanous salts, which method is a significant feature of this invention, is also applicable where the 3-OH group is not oxidized to the 3-ket'o group. Thus the series of steps outlined above for the preparation of progesterone may be altered in that after bromination and ozonization the resulting ozonide is treated directly with the chromous, vanadous or titanous salts toyield pregene 5-3-ol-2Q-one. Obviously this procedure is applicable. where the starting material contains a 3-acyloxy group. H
The process of the present invention may be The final ether I solution is concentrated to a volume of about 20 v employed with other carbinols than the diphenyl' carbinol. In general any carbinol of the formula carbinols of the formula CH: /CII CHI IEC-C R R which upon dehydration forms ethylenes of the type in which R is hydrogen or a hydrocarbon radical ma be used.
Reference is made to copending application Serial No. 521,850 filed concurrently herewith, now Patent No. 2,374,683. I
Having described the invention what is claimed 1. The process which comprises the steps of first treating S-hydroxy A-ternorcholenyl diphenyl carbinol with bromine, ozonizing the brominated material, convertin the 3-hydroxy group of the ozonization product toa keto group, treating the resulting 3-keto compound with a dehalogenating agent, all without isolation of intermediates, and recovering progesterone from the reaction mixture.
2. The process or claim 1 in which the dehalo- 'genating agent is chromous chloride.
3. The process of claim 1 in which the dehalogenating agent is vanadous chloride.
4. The process 01 claim 1 in which the dehalogenating agent is titanous chloride.
5. The process of producing progesterone which comprises successively treating a solution 01' 3-hydroxy A-ter-norcholeny1 diphenyl carbinol in acetic acid with bromine, ozone, chromic acid, and chromous chloride, without isolation of intermediates, and recovering progesterone from the reaction mixture.
6. The method of converting ter-nor-cholenyl on. on c-c-n wherein R represents phenyl radicals, and R is an etio-chlolenyl radical, into ketones of the formula which comprises subjecting said carbinols to the action of first bromine and then ozone, and decomposing the ozonide with a reducing agent.
7. The process which comprises successively treating 3-hydroxy A ternorcholenyl diphenyl carbinol with bromine and then treating the bromination product with ozone.
8. The process of producing progesterone whichcomprises successively treating a solution of 3- hydroxy A ternorcholenyl diphenyl carbinol with bromine, ozone, chromic acid, and a debrominating agent, without isolation of intermediates and recovering progesterone from the reaction mixture. Y
PERCY L. JULIAN. JOHN WAYNE COLE. ARTHUR MAGNANI. HAROLD E. CONDE.
REFERENCES CITED The following references are of record in the file of this patent:
UNITED STATES PATENTS Number Name Date 2,232,438 Butenandt Feb. 18, 1941 2,304,100 Julian Dec. 8, 1942
US521851A 1944-02-10 1944-02-10 Procedure for preparation of progesterone Expired - Lifetime US2433848A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US521851A US2433848A (en) 1944-02-10 1944-02-10 Procedure for preparation of progesterone

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US521851A US2433848A (en) 1944-02-10 1944-02-10 Procedure for preparation of progesterone

Publications (1)

Publication Number Publication Date
US2433848A true US2433848A (en) 1948-01-06

Family

ID=24078408

Family Applications (1)

Application Number Title Priority Date Filing Date
US521851A Expired - Lifetime US2433848A (en) 1944-02-10 1944-02-10 Procedure for preparation of progesterone

Country Status (1)

Country Link
US (1) US2433848A (en)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2601287A (en) * 1949-08-18 1952-06-24 Upjohn Co Partial synthesis of progesterone
US2620337A (en) * 1949-08-18 1952-12-02 Upjohn Co Adducts of bisnorcholatrienic-22-aldehydes
DE919046C (en) * 1950-01-04 1954-10-11 Hoechst Ag Process for the preparation of 3-acyloxy-bisnor-5-cholenic acid
US2752369A (en) * 1954-02-25 1956-06-26 Upjohn Co Oxidation of steroid-enamines
US2769020A (en) * 1952-03-11 1956-10-30 Schering Corp Process for the isolation of 11, 20-diketo pregnanes and products obtained thereby
US2854459A (en) * 1954-04-15 1958-09-30 Monsanto Chemicals Synthesis of steroids

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2232438A (en) * 1934-08-04 1941-02-18 Schering Corp Unsaturated pregnanolones and pregnandiones and a method of producing the same
US2304100A (en) * 1941-04-16 1942-12-08 Glidden Co Preparation of tertiary carbinols of the cyclopentanophenanthrene series

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2232438A (en) * 1934-08-04 1941-02-18 Schering Corp Unsaturated pregnanolones and pregnandiones and a method of producing the same
US2304100A (en) * 1941-04-16 1942-12-08 Glidden Co Preparation of tertiary carbinols of the cyclopentanophenanthrene series

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2601287A (en) * 1949-08-18 1952-06-24 Upjohn Co Partial synthesis of progesterone
US2620337A (en) * 1949-08-18 1952-12-02 Upjohn Co Adducts of bisnorcholatrienic-22-aldehydes
DE919046C (en) * 1950-01-04 1954-10-11 Hoechst Ag Process for the preparation of 3-acyloxy-bisnor-5-cholenic acid
US2769020A (en) * 1952-03-11 1956-10-30 Schering Corp Process for the isolation of 11, 20-diketo pregnanes and products obtained thereby
US2752369A (en) * 1954-02-25 1956-06-26 Upjohn Co Oxidation of steroid-enamines
US2854459A (en) * 1954-04-15 1958-09-30 Monsanto Chemicals Synthesis of steroids

Similar Documents

Publication Publication Date Title
US3104246A (en) Process of preparation of beta-methasone
US2767199A (en) Ring a halogenated allopregnanes
US2433848A (en) Procedure for preparation of progesterone
US2752366A (en) Carbonyloxysteroids
US2768189A (en) Method of producing alpha-brominated keto steroid compounds
Djerassi et al. Steroidal Sapogenins. XXII. 1 Steroids. XXXIV. 2 Degradation of 11-Oxygenated Sapogenins. Synthesis of Allopregnane-3β, 11β-diol-20-one and Allopregnane-3β, 11α-diol-20-one
US3876633A (en) Processes and intermediates for 16-substituted corticoid synthesis
Pappas et al. Norsteroids. II. Application of the Favorskii rearrangement to the preparation of A-norpregnanes
US2648663A (en) Preparation of 17alpha-hydroxy steroids
US3849402A (en) 19-oxygenated and 19-nor delta8(14)-steroid compounds
DUSZA et al. 20-Methylpregnane and Derivatives1, 2
US3637770A (en) Process for the production of 16alpha 17alpha-dihydroxy-19-nor-progesterone
US2773060A (en) Steroid ketals
US2296284A (en) Method for preparing material having the physiological activity of the corpus luteumhormone
US3024271A (en) 3, 11, 17-trioxygenated-18-nor-d-homo-13alpha-steroids and processes for their preparation
US3149102A (en) Process for the preparation of iminopregnadienes, novel steroid intermediates and novel 3-keto-delta4-18, 20-oxygenated steroid derivatives
US3214427A (en) Process for preparing 19-norsteroids of the androstane, pregnane and cholestane series and 10-cyano-19-nor-intermediates therein
US3336302A (en) Novel 19-oxygenated-b-nor-androstanes
US3040035A (en) 17alpha-acyloxy-6alpha-methyl-16-methylenepregn-4-ene-3, 20-diones and process and intermediates for the preparation thereof
US2601168A (en) delta 4-17alpha-methyl-3, 20-dioxo-pregnene compounds
US2562030A (en) Production of 17-hydroxy 20-keto steroid compounds
Rosen et al. 15-Oxa steroids
Maitra et al. Conversion of the cholesterol sidechain to a 17-acetyl group by remote chlorination reactions
US2894000A (en) 2, 4b-dimethyl-1-acetaldehydo-2-(beta-ketopropyl)-1, 2, 3, 4, 4a, 4b, 5, 6, 7, 9, 10, 10a- dodecahydrophenanthrene-4, 7-dione and methods of preparing the same
US2779774A (en) 3beta-oxy-delta16-allopregnenedione-11, 20 and process