17a-Methyl-17/3-hydroxy-5a-androstan

In addition to the protective effect of 17a-alkylation, methyl substitution in positions 1,2, and 6 and the position of unsaturation in ring A also have an important influence on the relative activity of 17/3-hydroxy-dehydrogenase [5]. The relative activities of 17/3-hydroxy-5a-androstan-... 

The 11-keto group is relatively difficult to attack, due to steric hindrance. However, reaction of 3/ -hydroxy-5a-androstane-l 1,17-dione (37) with methylmagnesium bromide at 25° unexpectedly gives a 30% yield of 1 la,17a-dimethyl-5a-androstane-3/ , 11 j3,17/ -triol (38) in addition to the 17-mono-methyl product (39). 

Pregnene-17a,21-diol-3,20-dione, 38B, 539 39B, 386 Aldosterone monohydrate, 38B, 540, 17/3-Bromoacetoxy-5a-androstan-3-one, 44B, 482, 2/3-Bromo-3a-hydroxy-5a-pregnane-l 1, 20-dione, 46B, 528, 2a-Bromo-17p-acetoxy-9-methyl-5a,9P,1Oa-estran-3-one,... 

An example is the preparation of 18-trideuterio 5a-steroids bearing a side chain at C-17. Labeling of this position with three deuteriums was accomplished by utilizing the Johnson procedure for steroid total synthesis. This synthesis involves, in part, introduction of the 18-angular methyl group by methylation of the D-homo-17a-keto-17-furfurylidene intermediate (243). By substituting d3-methyl iodide in this step, the C/D cis- and ra/J5-18,18,18-d3 labeled ketones [(244) and (245)] are obtained. Conversion of the C/D tra 5-methylation product (245) into 18,18,18-d3-d /-3)8-hydroxy-5a-androstan-17-one (246) provides an intermediate which can be converted into a wide variety of C-18 labeled compounds of high (98%) isotopic... 

An ethereal solution approximately 2.5 molar in methyllithium is prepared from 17 ml of methyl iodide and 4 g of lithium metal in 200 ml of anhydrous ether. A mixture consisting of 150 ml anhydrous ether, 3 g (10 mmoles) of 3jS-hydroxy-5a-androstane-ll,17-dione and 60 ml (0.15 moles) of the above methyllithium solution are stirred at room temperature for 40 hr. The reaction mixture is diluted with 100 ml of water and the ether is removed by distillation. Filtration of the chilled aqueous phase yields 2.6 g (77%) of 1 la,17a-dimethyl-5a-androstane-3a,l l/ ,17j5-triol mp 149-154°. Recrystallization from acetone-hexane yields pure material mp 164-166° [a] —5° (CHCI3). 

An aqueous slurry of 6 parts of 17/3-hydroxy-17a -methyl-1-oxo-1,2-seco-A-nor-5a -androstan-2-oic acid in 200 parts of water is made alkaline to pH 10 by the addition of dilute aqueous sodium hydroxide, then is treated with 6 parts of sodium borohydride. This mixture is allowed to react at room temperature for about 3 hours. Benzene is added and the resulting mixture is acidified carefully with dilute hydrochloric acid. The benzene layer is separated, and the aqueous layer is further extracted with benzene. The combined benzene extracts are washed successively with aqueous potassium bicarbonate and water, dried over anhydrous sodium sulfate, then evaporated to dryness in vacuo. The resulting residue is triturated with ether to afford pure 17/3-hydroxy-17a -methyl-2-oxa-5a -androstan-3-one,... 

A mixture of 2.0 grams of 2,3-dihydroxyimino-17a-methyl-5ca-androstan-17p-ol, 5 ml of piperidine and 10 ml of ethylene glycol was heated at a temperature between 180° and 190°C for 30 minutes. After the resulting product was cooled, water was added thereto, and the separated product was filtered, washed with water and dried. The product was dissolved in benzene and passed through a column of alumina. The column was washed with ether, and the eluted fractions were collected and condensed. Subsequently, the residue was recrystallized from ether or aqueous methanol to produce 1.53 grams of 17 3-hydroxy-17a-methyl-5a-androstano[2,3-c]furazan which has a melting point of 152°C. 

This mixture is then diluted with water, washed with ethyl acetate, acidified with dilute sulfuric acid, and finally extracted with benzene. The benzene extract is washed with water, dried over anhydrous sodium sulfate, and evaporated to dryness at reduced pressure to produce crude 17 3-hydroxy-17a-methyl-l-oxo-l,2-seco-A-nor-5a-androstan-2-oic acid, which after recrystallization from aqueous isopropyl alcohol melts at about 166° to 173°C (decomposition). 

C(3)-carbonyl group. A close approach to ideal boat geometry is observed in ring B of 3-methoxy-7a,8a-methyleneoestra-l,3,5(10)-trien-17)8-yl bromoacetate. Crystal and molecular structures are also reported for 16/8,17)8-dibromo-5a-androstane, 2a-bromo-17a-methyl-5a,14/S-androstan-3a-ol, esters of 3a,5a-cyclocholestan-6/3-ol, 4a,6,7a-trichloro-17a,21-dihydroxypregn-5-ene-3,l 1,20-trione 21 -acetate," 6a-bromo-17/8-hydroxy-17a-methyl-4-oxa-5a-androstan-3-... 

In 1965, Neumann and Wiechert [100] published the results of their investigations of some 150 steroids. They studied the androgenic and anabolic activity of steroids substituted in the C-1 and/or the C-2 position. Five parent compounds were chosen 1. 5a-androstan-17]3-ol 2. testosterone 3. 5a-dihydrotestosterone 4. A -5a-androsten-17j8-ol 3-one and 5. A -5a-androsten-17/3-ol. The parent compounds were further classified according to the substitution in the 17-position, i.e., l7j8-hydroxy, 17a-methyl 17j8-hydroxy, or 17/3-acetoxy compounds. 

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