Патент USA US3098860код для вставки
lice 3,098,850 Patented July 23, 1963 2 testosterone propionate while the androgenic activity was about 25 percent that of testosterone propionate. The novel compounds of this invention, because of their ana bolic activity, are useful in increasing weight, muscle strength, and for increasing the sense of well-being and positive nitrogen balance in pituitary de?ciences. A 3,098,850 3-ENAM DERIVATIVES 0F Zea-METHYL Sa-ANDRGSTANES John C. Babcock, Portage Township, Kalamatoo County, ' J Allan Campbell, Kalamazoo Township, Kalamazoo County, and Raymond L. Pederson, ‘Kalamazoo, Mich, assignors to The Upjohn Company, Kalamazoo, Mich, favorable anabolic response can be achieved without a corporation of Michigan noticeable androgenic response owing to the high anabolic androgenic ratio. They can be prepared and administered 10 in a wide variety of oral or parenteral ‘dosage forms sing The present invention relates to novel steroid com ly, or in admixture with other coacting compounds. They pounds and is more particularly concerned with ‘20c can be associated with a pharmaceutical carrier which No Drawing. Filed Dec. 9, 1957, Ser. No. 701,347 3 Claims. (Cl. 260-4395) methyl - 3 - oxygenated _ 17 - oxygenated-5u-androstane can be a solid material or a liquid in which the compound compounds, to novel intermediates in the production thereof and to processes for the production of the novel compounds and novel intermediates. The novel compounds of the present invention can be represented by the following formula: tions can take the form of solutions, emulsions, sus pensions, syrups or elixirs. 20 The process of the instant invention comprises treat ing a 17-oxygenated-5a-androstan-3-one with a secondary CH3 , is dissolved, dispersed or suspended. The solid composi tions can take, the form of tablets, powders, capsules, pills, or the like, preferably in unit dosage forms for simple administration or precise dosages. The liquid composi R, cyclic alkylene amine to produce the 3-enamine of the corresponding starting material. The 3-enamine thus produced is then allowed to react with a methylating agent 25 to produce the 2a-methyl-3-enamine compounds which on hydrolytic removal of the enamine blocking group yield the corresponding Za-methyl-d7-oxygenated-5a (I) androstan-3-one compounds. wherein R is selected from the group consisting of Reduction of these ,com pounds with sodium borohydride produces the correspond 30 ing 3-hydroxy compounds which on acylation are produc H y tive of the 3-esters thereof. During the acylation step, a 17?-hydroxyl, when present, will also be acylated and H thereby be productive of the corresponding 3,17-diacylates. wherein Ac is the acyl radical of an organic carboxylic acid, preferably a hydrocarbon carboxylic acid contain 35 Similarly, acylation of the 2u-methyl-3-keto compounds (before reduction with sodium borohydride) wherein a ing from one to twelve carbon atoms, inclusive, and keto; l7-hydroxyl is present, is productive of the corresponding and wherein R’ is selected from the group consisting of 17-acylate. \’ H’ \q n’ 0113' wherein Ac is as above de?ned, H0 , Alternatively the compounds of the present invention \ 40 can be produced by reduction of the 4-double bond of the corresponding 2iz-methyl - 17.- oxygenated-4-andro sten~3-one U as more speci?cally illustrated by Examples 2 and 3. The saturated compounds thus produced can then be reduced with sodium borohydriderto produce the on,’ and keto. It is an object of the invention to provide the novel Zen-mBihYl - 3 - oxygenated - 17 - oxygenated-Sa-andro 45 corresponding 3_-hydroxy compounds. Acylation of the hydroxy groups as described above is productive of the corresponding 3- and l7-acylates and the 3,17-diacylates. The compounds of the present invention can be pre pared from l7l8-hydroxy 45a - androstan-3-one, 17,6-hy stane compounds, particularly the 2a-methyl-5a-andro 50 droxy - 17a - methyl-5a-androstan-3-one, and Stat-andro ‘stane compounds represented by Formula I wherein R stane-3,17,-dione, compounds well known in the art [see is a ketone or a free or esteri?ed hydroxyl and wherein Fieser and Fieser, Natural Products Related to Phenan R’ is a ketone or a hydroxyl or a hydroxyl and methyl threne, Reinhold Publishing Corp., New York (‘1949), group, the hydroxyls being either free or esteri?ed. It page 375]. is a further object of this invention to provide the novel 55 According to the process of the present invention, the intermediates and methods for the production of the ketone group at the 3-position of the above starting ma novel compounds of this invention. Other objects of the terial is converted to the corresponding 3-enamine deriva present invention will be apparent to those skilled in tive by reaction with a secondary cyclic alkylene amine. the art to which this invention pertains. The enamine formation can be carried out in accordance The compounds of the present invention, compounds 60 with the disclosure of US. Patent 2,781,342.‘ Amines represented by Formula I, are valuable therapeutic agents. which can be used are cyclic amines such as pyrrolidine, ‘WT, They exhibit anabolic-androgenic, progestational, and gonadotropin inhibiting properties. They are especially piperidine, C-alkyl substituted piperidines, e.g., 2,4-di methylpyrrolidine, 3-isopropylpyrrolidine, 3,3-dirnethyl useful as anabolic-androgenic agents and are of particular pyrrolidine and the like. The preferred secondary amine advantage in cases where selective anabolic activity is 65 is usually pyrrolidine. Although large molar equivalent required because of their favorable anabolic-androgenic excesses of the cyclic amine can be employed in the re ratio. For example, 2u,17a-dimethyl - 175 - hydroxy-Sa androstan-3-one was found to have an oral anabolic ac tivity of over twice that of methyltestosterone and an action, the preferred proportion of amine to starting steroid is usually from about 1.1}to about seven moles of amine per mole of steroid and especially from about 1.1 androgenic activity of less than methyltestosterone. Like 70 to two. Moisture in the reaction is detrimental to the wise the anabolic activity of Zea-methyl-17?-l1ydroxy-5a procurement of high yields of product, and preferred androstan-B-oue was found to be about equal to that of reaction conditions therefore include removal of the water 3,098,850 pounds is preferred. Any suitable temperature between The reaction is preferably conducted above room tem— about zero and 100 degrees centigrade may be employed, with room temperature being satisfactory. Hydrogenation perature, i.e., above about 25 degrees centigrade, e.g., between about 25 and 150 degrees centigrade. Reaction is continued until approximately one molar equivalent of hydrogen has been absorbed. The catalyst is then sep arated from the solution by ?ltration and the hydrogenated times can vary between about a'few minutes to several days, depending in part upon the reaction solvent or solvents, ratio of reactants, selected amine, water removal and temperature. Reaction solvents employed are organic solvents inert to the reaction such as benzene, toluene, xylene, chlorobenzene, pentane, hexane, methylene chlo~ ride, carbon tetrachloride, methanol, ethanol, tertiary butyl alcohol, tetrahydrofuran, dioxane, and the like. 4 or more is operative, a pressure of from about ten to 25 formed during the enamine formation by known methods. products separated by conventional separation or extrac tion procedures. When reduction is accomplished with a metal such as, 10 The 3-enarnine of the corresponding starting material thus produced is then methylated in a preferably dry inert organic polar solvent such as ethanol, methanol, isopropanol, butanol, dimethylformamide, and the like, for example, lithium, sodium, potassium, and the like, with lithium being prefered, the reaction is conducted in , liquid ammonia for a period of a few minutes to about four hours. A solvent such as, for example, ether, tetra hydrofuran, methylene chloride and the like may be employed if desired. On completion of the reaction, the with an excess of methylating agent such as a methyl ammonia is allowed to evaporate and the product is ' halide to produce the 2a-methyl-3~enamine of the corre isolated ‘by conventional procedures such as ?ltration or extraction with an organic solvent. sponding starting material. Methyl halides thus employed The thus-produced Za-methyl-l7-oxygenated-5a-andro are those wherein the halogen is chlorine, bromine or 20 iodine with bromine and iodine generally preferred. A preferred method is to treat the isolated and dried 3 enamine with an excess of methyl iodide in dry methanol stan-3-one compounds are reduced at the 3-position with a chemical carbonyl reducing agent in an organic solvent, e.g., ethanol, methanol, isopropyl alcohol, and tetrahydro furan, to produce the corresponding 3-hydroxy com and re?ux until the reaction is complete. At the end of the re?ux period, the excess methyl iodide is removed by 25 pounds, i.e., Za-methyl-Soc-androstane-3,17,8+diol, 2a,17cx distillation. The S-enamine, preferably the 3-pyrrolidyl enamine, of Zea-methyl-17f3-hydroxy-5a-androstran-3-one, dimethyl-5a-androstane-3,l7B-diol, and 2a-methyl-3-hy 2u,17a-dimethyl-17B-hydroxy-5a-androstran - 3 - one, and alkali metal borohydride or an alkali metal aluminum droxy-5a-androstan-17-one. Reducing agents such as an hydride, e.g., sodium borohydride, lithium aluminum hy-. 2a-methyl-5u-androstrane-3,17-dione thus produced can then be hydrolyzed with water, aqueous acid or base, 30 dride, lithium borohydride, and the like, are operative. The temperature of the reaction mixture is usually main alkanols or alkanol water mixtures. This treatment re tained between about zero and about 100 degrees centi moves the 3-enamine group and results in regeneration of grade with temperatures between about room temperature the A4-3-keto group in the steroid nucleus, with produc and the re?ux temperature of the reaction mixture being tion of the Zea-methyl compounds of the corresponding starting material. A preferred method for the hydrolysis 35 preferred for a period varying from a few minutes to several hours. After the completion of the reaction, the of the S-enamine group is in la methanol and ten percent reaction mixture is preferably mixed with water or an aqueous sodium hydroxide solution. The alkaline solu tion is heated under re?ux for a few minutes and then concentrated by distillation to remove most of the acid to decompose any excess reducing agent and organo metal complexes. The product is isolated by known meth methanol present and cause precipitation of the product. 40 ods such as, for example, ?ltration or extraction with an organic solvent. If the product is not solid the hydrolysis mixture is diluted with water and extracted with a water-immiscible solvent The compounds of this invention, represented by For such as methylene chloride, benzene, toluene, hexane, or mula I, may be utilized either as the free alcohols or as distillation giving the Zea-methyl compounds, i.e., Za-meth at those positions, is accomplished by allowing the hy the esters. Acylation of the hydroxyl groups either at the the like. The combined solvent extractions are then dried over a drying agent and the solvent removed by 45 3- or 17-positions when such hydroxyl groups are present droxy compounds to react with the anhydride of an organic carboxylic acid, preferably a hydrocarbon car boxylic acid containing from one to twelve canbon atoms, An alternate method for the preparation of the 20: 50 inclusive, for example, a saturated straight-chain aliphatic yl-l7/8-hydroxy - 5a - androstan - 3 - one, 20:,170: - dimeth yl-17?-hydroxy-5e-androstan-3tone, and Za-methyl-Sa androstane-3,l7-dione. methyl-17-oxygenated-5a-androstan-3-one compounds of acid, e.g., acetic, propionic, butyric, valeric, hexanoic, the present invention involves reduction of the 4-double laun'c, a saturated branched~chain aliphatic acid, e.g., testosterone and 17a-methyltestosterone according to the and p-toluic, a saturated dibasic acid (which can be con trimethylacetic, isobutyric, isovaleric, a cycloaliphatic bond of the appropriate Z-methylated starting materials saturated acid, e.g., cyclohexane-carboxylic acid, an al such as, for example, 2wrrnethyltestosterone, 2a,17a-di methyltestosterone, and the like, which are prepared from 55 karyl acid, e.g., phenylacetic, Z-phenylpropionic, 0-, m-, verted into water-soluble, e.g., sodium salts), e.g., succinic, adipic, a monobasic unsaturated acid, e.g., acrylic, cro~ Chem., 21, 1333 (1956). The reduction can be accom tonic, undecylenic, propiolic, cinnamic, a dibasic un plished either by hydrogenation with hydrogen in the presence of a catalyst such as palladium supported on 60 saturated acid (which can be converted into water-soluble, e.g., sodium salts), e.g., maleic and citraconic. Illus charcoal, barium sulfate, zinc oxide, calcium carbonate, trative of the esters thus produced are the 3-monoacylatcs and the like, or by a metal such as, for example, lithium such as, for example, 2a-methyl-3-hydroxy-5a-androstan in liquid ammonia. 17-one 3-acetate, 2u-methyl-3~hydroxy-i5aaandrostan-l7 The hydrogenation is usually conducted in a solvent 65 one 3-propionate, 2a-methyl-3-hydroxy-5a-androstan-17 medium. Alkanols, hexane, acetone, methyl ethyl ketone, one 3-hemisuccinate, 2oz-methyl-3~hydroxy-5a-androstan dioxane, acetic acid, ethyl acetate, or like organic solvents 17-one S-phenylacetate; the 17-monoacylates such as, for may be advantageously employed, with tertiary butyl al example, Za-methyl-l7,8-hydnoxy-ia-androstan-3-one l7 cohol being preferred. The catalyst can be reduced prior acetate, 2cz-methyl-l7?-hydroxy-5a-androstan-3-one 17 to the introduction of the 2-methyl-A4-steroid or prefer 70 isovalerate, Za-methyI-l7l8-hydroxy-5a-androstan - 3 - one ably the steroid, catalyst and supporting media can be 17 - propionate, Zea-methyl-17?-hydroxy-5a-androstan-3 contacted together in a solvent medium prior to introduc~ one 17-maleate; the 3,17-diacylates such as, for example, procedures given by Ringold and Rosenkranz in J. Org. tion of the hydrogen. It is not necessary to conduct the reaction under pressure, although, when pressure is utilized, a hydrogen pressure of about one to 100 pounds 75 2a,17a-dimethyl-5u-audrostane-3,l7/8-diol 3,17-diacetate, 2a,17u~dimethyl-5u-androstane-3,17B-diol 3,17-dipropio nate, 2a,17u-dimethyl-5oc-androstane-3,l7?-tdiol 3,17-di— 3,098,850 6 crotonate, 2a,17a-dimethyl-5a-androstane-3,17,8-dio1 3,17 concentrated to dryness and the residue was chromato-i dipropiolate, and the like. graphed over 110 grams of synthetic magnesium silicate. The following examples are illustrative of the process and products of the present invention, but are not to be The column was eluated with ninety milliliter fractions of three percent acetone in Skellysolve B :hexanes. Fractions construed as limiting. ' 26 to 36, inclusive, were combined and recrystallized from acetone to give 129 milligrams of ZDL-II‘lBlIhYl-17?-l1YdI‘OXY Example 1 .—2 a-Methyl-I 7?-Hydroxy-5a-Androstam 5‘oz-androstan-3-one identical to that obtained by the proce~ 3-One dure of Example 1. A solution of four grams of 17?-hydroxy-5wandrostan Example 3 .—2 0b,] 7a-Dimethy l-1 75-Hydr0xy-5 Ot 3-one in ?fty milliliters of benzene was concentrated by 10 Andr0stan-3-One heating to 35 milliliters in order to remove any water To 250 milliliters of liquid ammonia, which had been present. Two milliliters of pyrrolidine was then added dried with traces of lithium until a blue color remained, and the solution was re?uxed, under nitrogen for one was added 400 milligrams of lithium followed by a solu and one~half hours, using a water trap to remove any water formed in the reaction. After the re?ux period 15 tion of 2a,17a-dirnethyltestosterone in 48 milliliters of anhydrous ether and four milliliters of tetrahydrofuran. the reaction mixture was concentrated to dryness under Addition of the 2a,17a-dimethyltestosterone solution was reduced pressure to give 4.5 grams of the 3-pyrrolidy1 done dropwise over a period of thirty minutes. After enamine of 17B-hydroxy-5a~androstan-3-one as a crude stirring for an additional twenty minutes the mixture was white solid having a melting point of 201 to 206 degrees centigrade and a rotation of [oc]D plus 34 degrees (chloro 20 acidi?ed with the addition of ?ve grams of solid am monium chloride and the ammonia was allowed to evapo~ rate oif. The residue was diluted with water and extracted form). A suspension of 3.9 grams of the enamine in twenty ‘milliliters of absolute methanol and ?ve milliliters of with ether. methyl iodide (dried ‘and vfreshly distilled) was re?uxed dried, and evaponated to dryness to give 1.13 grams of The ether extract was washed with water, under nitrogen for three hours. The solid went into solu 25 solid 2a,17a-dimethyl-17?-hydroxy-5a-androstan - 3 - one identical to that-obtained by the procedure of Example 1. tion after ?fteen minutes of re?ux. The reaction mixture An analytical sample melted at 134 to 136 degrees centi containing the 3-pyrrolidyl enarnine of 2a-methyl-tl7l3 grade and had a rotation of [ab plus one (chloroform). hydnOXy-Sa-andrOstan-S-Qne was then ‘concentrated to Analysis.—Calculated for C21H34O2: C, 79.19; H. 10.76. near dryness and was diluted with twenty milliliters of Found: C, 7-8.63;H, 10.58. ten percent sodium hydroxide solution and enough methanol to make a total volume of sixty milliliters. Example 4 .—2 a,] 7 a-DimeIhyI-S cc-A ndr0stane-3J 718-Di0l (The resulting solution was heated under re?ux‘ for 25 A solution containing 1.66 grams of sodium borohy -minutes and was then concentrated until a solid precipi dride in seventeen milliliters of 0.1 N sodium hydroxide tate formed. The solid was separated by ?ltration and 'was chromatographed over 100 grams of synthetic mag 35 was added to ‘a solution of 3.2 grams of 2oc,17a-dimethyl 17B-hydroxy-5a-androstan-3-one in 85 milliliters ,of nesium silicate. The column was eluted with 250 milli ethanol. After twenty minutes of stirring, the mixture liter petroleum ether-acetone fractions as follows: was diluted with 250 milliliters of water and Was acidi?ed Fractions 1—3-—-two percent acetone in petroleum ether to pH 6 by drop-wise addition of thirty percent acetic acid. Fractions 4-15‘—three percent acetone in petroleum ether 40 The resulting solid precipitate Was collected by ?ltration, Fractions 16-17——four percent acetone in petroleum ether washed, and dried to give three grams of 212,17 a-dimethyl Fractions 1'8-19--?ve percent acetone in petroleum ether 5a-androstrane-3,17-diol. Two recrystallizations from acetone gave 0.70 gram of puri?ed product having a Fractions 10 to 15, inclusive, were combined and evap melting point of 176 to 178 degrees centigrade and a rota orated to dryness to give 0.5 gram of 2a-methyl-17B hydroxy-5a-androstan-3-one which on recrystallization 45 tion of [1x1]; minus 24 degrees (pyridine). Analysis.——Calculated for C21H36O2: C, 78.69; H, 11.32. Found: C, 78.48; H, 11.48. Following the procedure above but substituting 2a methyl-17/i-hydroxy-5a-androstan-3-one of Examples 1 from ether-Skellysolve B hexanes gave needle-like crystals which melted at 151 to 153 degrees centigrade and had a rotation of [a]D plus 29 degrees (chloroform). Found: AnalysiS.—Calculated C, 78.93; H, 10.14. for (320113202: C, H, 50 and 2 as starting material therein is productive of 20a methyl-5u-androstane-3,17B-diol. Fractions 8 and 9 were combined and recrystallized from ether-Skellysolve B hexanes to give dense prism-like crystals which melted at 174 to 176 degrees centigrade. Example 5 .—Za-Methyl-3-Hydroxy-S a-A ndrostan-l 7-One Following the procedure of Example 4, reduction of Infrared analysis showed this material to be a different crystalline form of 2a~methyl-17/3-hydroxy-5oc-androstan 55 2a-methyl-5a-androstane-3,17-dione of Example 1 with one equivalent of sodium borohydride gave a reduction mixture which was chromatographed over synthetic mag 3-one. Following the procedure above but substituting 5on androstane-3,17,dione or 17,8-hydroxy-;17a-methyl-5oc-an nesium silicate using Skellysolve B hexanes plus acetone for elution of the column. The fraction which by in drostan-3-one as starting material therein is productive frared analysis showed the absence of a six membered ring ketone was recrystallized from acetone to give a of 2a-methyl-5a-androstane-3,17-dione and 2a,17a-di methyl - 17,8 - hydroxy - 5a - androstan - 3 - one, respec tively. 2a-methyl-3dhydroxy-5a-androstan-17-one. The intermediate 3-pyrrolidyl enamine of 204 methyl-Sa-andrQStane-B,17-dione and 3-pyrrolidyl enamine of 2a,17a~dimethyl-17B-hydroxy-5oc-androstan-3-one are produced by the reaction. Example 2.—2oc-Mez’hy l-1 7/3-Hydr0xy-5a-Androsz‘an 65 Example 6 .—2 0a,] 7a-Dimethyl-5a-Andr0stane-3,1 7B-Di0l 3,17-Diacetate One gram of 2a,17a-dimethyl-5a-androstane-3,17/8-diol grams of ?ve percent palladium on charcoal catalyst was was dissolved in 22 milliliters of acetic anhydride and the solution was heated under re?ux for one-half hour. The excess acetic anhydride was then removed by distil lation under reduced pressure and the resulting residue was crystallized from methanol to give 2a,17a-dimethyl hydrogenated with hydrogen at atmospheric pressure. 5a-androstane-3,17p-diol 3,17-diacetate. 3-One A mixture containing 0.91 gram of Za-rnethyItestQs-ter one, forty milliliters of t-butyl alcohol and ninety milli Similarly, by allowing 2a,17a-dimethyl-5a-androstane After 32 minutes when the theoretical amount of hy drogen was taken up, the hydrogenation was stopped and 3,,l7?-diol to react with the appropriate hydrocarbon the catalyst was removed by ?ltration. The ?ltrate was 75 carboxylic acid anhydride, for example, at temperatures 3,098,850 2a,17wdimethy1-5u-androstane-3,17/3-diol 3,17-dicinna between 100 and 150 degrees centigrade, there are pro duced other 3,17-diacylates such as, for example, mate, 2oz,17uédirnethyl-5ot~androstane-3,175-diol 3,17-dimaleate, 2a,17a-dimethyl-5a-androstane-3,17/3-dio1 3,17-dipropio nate, and 2a,17a-dimethy1-5ot-androstane-Zi,17[3-diol 3,17-dicit 2a,17a-dimethyl-5u-androstane-3,17/3-dio1 3,17-dibutyrate, 2a,17ot-dimethyl-5a-androstane-S,17/3-di01 3,17-diva1erate, raconate. 2a, 170L-dlII1ethYl-5 0t-8l1dI'OStE1I16-3, 17,8-dio1 3,17-dihexan0 diol, 2a-methy1-17,6-hydroxy-5u-androstan-S-one, 20:,1711 Similarly, acylation of 2a-methyl-5a-androstane-3,17 ate, 2a,17u-dimethy1-5a-androstane-3,17B-dio1 3,17-di1aurate, 2a,17a-dimethy1-5ot-androstane-3,17B-dio1 3,17-di-(tri dirnethyl-17/3-hydroxy-5ot-androstan-3~one, and Zen-meth 10 yl-3-hydroxy-5a-androstan-17-one with the appropriate hydrocarbon carboxylic acid anhydride is productive of the corresponding 3,17-diacylates, 17-acylates, and 3-acyl methylacetate) , 2a,17a-dimethyl-5a-androstane-3,17,8-dio1 3,17-diisobutyr ates, respectively. The preferred acylates are those cor ate, 2a,17a-dimethyl-5oc-androstane-3,17?-diol 3,17-diisova1er ate, responding to the acylates described above for 2oc,17oc 15 It is to be understood that the invention is not to be limited to the exact details of operation or exact com 2a,17a-dirnethyl-5a-androstane-3,17/3-di0l 3,17-dicyclo hexane carboxylate, 2a,17a-dimethyl-5ot-androstane-3 ,17B-diol 3,17-dibenzo ate, 2a,17ot-dimethyl-5a-androstane-3,17,8-diol 3,17-diphenyl acetate, 20c, 17a-dimethy1-5 a-androstane-3, 17 ?-diol 3,17-di-(,B phenyl ) -propionate, pounds shown and described, as obvious modi?cations and equivalents will be apparent to one skilled in the art, 20 and the invention is therefore to be limited only by the scope of the appended claims. We claim: 1. The 3-pyrro1idyl enamine of 2ot-methyl-175-hydroxy I 2a,17u-dimethyl-5a-androstane-3,17,8-dio1 3,17-di-(o-, m-, p-toluate), 2a,17a-dimethyl-Sa-androstane-3,17,B-diol, 3,17-diherni 5a-androstan-3-one. 25 3. The 3-pyrrolidy1 enarnine of Zu-methyI-Sa-andm stane-3,17-dione. 2a,17a-dimethy1-5a-androstane—3,17B-dio1 3,17-dihemi adipate, . 30 References‘Cited in the ?le of this patent Conf. on Metabolic Aspects of Convalescence, Trans. ate, 2a,17a-dimethyl-Sa-androstane-E!,IZB-diol 3,17-diundec ylenate, 2a,17u-dimethy1-5a-androstane-3,17p-dio1 3,17-dipropio late, 2. The 3-pyrrolidyl enamine of 20¢,17oc-diII16tl1Yl-l7? hydroxy-5a-androstan-3-one. succinate, 2a,17a-dimethyl-5a-androstane-3,17(3-dio1 3,17-diacrylate, 2a,17u-dirnethy1-5a-androstane-B,17?-dio1 3,17-dicroton dimet-hyl-S a-androstane-3, 17,8-dio1. vol. 13, page 111 (1946), by Woodley et al., C.A., vol. 43, page 7124(g). 35 Fieser: Natural Products Related to Phenanthrene, pages 423, 424, and 427 (1949).