17-Methyltestosterone Oxidation

The orally effective androgen 17a-methyltestosterone (51) is prepared from 3jS-hydroxyandrost-5-en-17-one (49) by treatment with methylmagnesium iodide to give the 17a-methyl compound (50) which is then oxidized to yield... 

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. 

The prototypical 17-alkylandrogen, 17- methyltestosterone, is prepared from dehydroepiandrosterone (DHEA 1-5) in two steps. Reaction of DHEA with an excess of methylmagnesium bromide gives the corresponding 17-methyl derivative (13-1) (Scheme 5.13). Oppenauer oxidation then converts the hydroxyl at C3 to a carbonyl group the olefin shifts into conjugation in the process to give mestanolone (13-2). 

Two papers report the synthesis of novel androstane derivatives methylated at C-8a. In the first" (Scheme 8). treatment of the tosylhydrazone of (143) with lithium hydride furnished the diene (144). Reaction with diborane. followed by alkaline hydrogen peroxide, gave the allylic alcohol (145), which was submitted to Simmons-Smith reaction and oxidized to the a-cyclopropyl ketone (146). Cleavage of the 7a.8a-methylene bridge with lithium in liquid ammonia afforded the 8a-methyl derivative (147). This was then converted into 17a-ethynyl-8a-methyltestosterone (148a) by a classical sequence of reactions. ... 

In the second synthesis, 8a-methyltestosterone (I48b) was prepared from the previously reported 8a-methyl-5a-pregn-9(l l)-ene-3)3.20-diol (149). Catalytic hydrogenation of (149) gave the saturated diol, which was successively oxidized to the diketone, selectively protected as the C-3 dimethyl ketal, reduced at C-20, and hydrolysed to the hydroxy-ketone (150). This in turn was transformed into the 8 -methylprogesterone (151), 8a-methyltestosterone (I48b), and 8a-methyl-oestradiol (152) analogues by conventional methods. ... 

Allylic oxidation of 17-methyltestosterone by Gibberella saubinetti gives the corresponding 6P hydroxy product (Scheme 16). 

---