A -Methyltestosterone

Estriol, hydrocortisone, estradiol, estrone, testosterone, 17-a-methyltestosterone, 4-pregnen-20a-ol-3 -one, progesterone Zorbax ODS, 1.8 pm Acetonitrile-0.8 vaM sodium tetraborate, 5 mM SDS (80 20) 320 mm x 50 pm i.d. 240 mm packed length... 

In Anlehnimg an Arbeiten auf dem Corticoid-Gebiet wurde in ent-sprechende Androsten-Derivate ein Fluoratom eingefiihrt. Das 9 a-Fluor-11 B-hydroxy-17 a-methyltestosteron = Fluoxymesteron... 

Smith, R. J. F., 1974, Effects of 17 a-methyltestosterone on the dorsal pad and tubercles of fathead minnows (Pimephales promelas Rafinesque), Can. J. Zool., 52 1031-1038. 

Testosterone (T.) derivatives for clinical use. T. esters for im. depot injection are T. propionate and T. heptanoate (or enanthate). These are given in oily solution by deep intramuscular injection. Upon diffusion of the ester from the depot, esterases quickly split off the acyl residue, to yield free T. With increasing lipophilicity, esters will tend to remain in the depot, and the duration of action therefore lengthens. A T. ester for oral use is the undecanoate. Owing to the fatty acid nature of undecanoic acid, this ester is absorbed into the lymph, enabling it to bypass the liver and enter, via the thoracic duct, the general circulation. 17-0 Methyltestosterone is effective by the oral route due to its increased metabolic stability, but because of the hepatotoxicity of Cl 7-alkylated androgens (cholestasis, tumors) its use should be avoided. Orally active mesterolone is 1 a-methyl-dihydrotestosterone. Trans-dermal delivery systems for T. are also available. 

Treatment of 4-methyltestosterone under the same conditions affords 17 -hydroxy-4,4-dimethyl-5a-androstan-3 One in about 60% yield while 17jS-hydroxyandrosta-4,6-dien-3-one gives only a low yield of 17 -hydroxy-4,4-dimethylandrost-5-en-3-one. ... 

Alternatively, as described in U.S. Patent 3,341,557, 6-dehydro-17-methyltestosterone may be used as the starting material. A mixture of 0.4 g of cuprous chloride, 20 ml of 4 M methylmagnesium bromide in ether and 60 ml of redistilled tetrahydrofuran was stirred and cooled in an ice bath during the addition of a mixture of 2.0 g of 6-dehydro-l 7-methyl-testosterone, 60 ml of redistilled tetrahydrofuran and 0.2 g of cuprous chloride. The ice bath was removed and stirring was continued for four hours. Ice and water were then carefully added, the solution acidified with 3N hydrochloric acid and extracted several times with ether. The combined ether extracts were washed with a brine-sodium carbonate solution, brine and then dried over anhydrous magnesium sulfate, filtered and then poured over a 75-g column of magnesium silicate (Florisil) packed wet with hexanes (Skellysolve B). The column was eluted with 250 ml of hexanes, 0.5 liter of 2% acetone, two liters of 4% acetone and 3.5 liters of 6% acetone in hexanes. 

Testosterone, when administered by mouth, is rapidly absorbed. However, it is largely converted to inactive metabolites, and only about one sixth of the dose administered is available in active form. Testosterone can be administered parenterally, but it has a more prolonged absorption time and greater activity in the propionate, enanthate, undecanoate, or cypionate ester forms. These derivatives are hydrolyzed to release free testosterone at the site of injection. Testosterone derivatives alkylated at the 17 position, eg, methyltestosterone and fluoxymesterone, are active when given by mouth. 

An enzyme reactor with immobilized 3 -hydroxysteroid dehydrogenase has been successfully used for the analysis of residues of 17 -methyltestosterone in trout by high-performance liquid chromatography (HPLC) (269). Following their separation by reversed-phase chromatography, the major tissue metabolites of 17 -methyltestosterone, namely 5 -androstane-17 -methyl-3, 17 -diol, and 5 -androstane-17 -methyl-3, 17 -diol, were enzymatically modified in the presence of a coreactant, nicotinamide-adenine dinucleotide (NAD), to the corresponding ketone. The position at 3 was enzymatically oxidized, and NADH, the reduced form of NAD, was produced as a coproduct and subjected to fluorescence detection. Reoxidation of NADH to NAD provides the possibility for electrochemical detection. 

---