Metabolism of anabolic steroids in humans: Synthesis of 6β-hydroxy metabolites of 4-chloro-1,2-dehydro-17α-methyltestosterone, fluoxymesterone, and metandienone

Article abstract of DOI:10.1016/0039-128X(95)00008-E

Hydroxylation at position 6β of testosterone I (17β-hydroxyandrost-4- en-3-one) and the anabolic steroids 17α-methyltestosterone II (17β-hydroxy- 17α-methylandrost-4-en-3-one), metandienone III (17β-hydroxy-17α- methylandrosta-1,4-dien-3-one), 4-chloro-1,2-dehydro-17α-methyltestosterone IV (4-chloro-17β-hydroxy-17α-methylandrosta-1,4-dien-3-one), and fluoxymesterone V (9-fluoro-11β, 17β-dihydroxy-17a-methylandrost-4-en-3- one) was achieved via light-induced autooxidation of the corresponding trimethylsilyl 3,5-dienol ethers dissolved in isopropanol or ethanol. The reaction further yielded the 6α-hydroxy isomer in low amounts. The 6β- hydroxy isomers of I-V and the 6α-hydroxy isomers of I, III, and IV were isolated and characterized by ¹H and ¹³C NMR, high-performance liquid chromatography, gas chromatography, and mass spectrometry. Human excretion studies with single administered doses of boldenone (17β-hydroxyandrosta- 1,4-dien-3-one), 4-chloro-1,2-dehydro-17α-methyltestosterone, fluoxymesterone, metandienone, 17α-methyltestosterone, and [16,16,17- ²H₃]testosterone showed that 6β-hydroxylation is the major metabolic pathway in the metabolism of 4-chloro-1,2-dehydro-17α-methyltestosterone, fluoxymesterone, and metandienone, whereas for boldenone, 17α- methyltestosterone, and testosterone, 6β hydroxylation is negligable.