SYNTHESIS OF 16α-BROMOACETOXY ANDROGENS AND 17β-BROMOACETYLAMINO-4-ANDROSTEN-3-ONE: POTENTIAL AFFINITY LABELS OF HUMAN PLACENTAL ARMATASE.

Article abstract of DOI:10.1016/0039-128X(81)90029-5

A novel synthesis of 16α-hydroxy-4-androstene-3,17-dione (3), 16α-hydroxy-4-androstene-3,6,17-trione (4), 17β-amino-5-androsten-3β-ol (10) and 17β-amino-4-androsten-3-one (14) is described. 16α-Bromoacetoxy-4-androstene-3,17-dione (5), 16α-bromoacetoxy-4-androstene-3,6,17-trione (6) and 17β-bromoacetylamino-4-androsten-3-one (15) were synthesized as potentially selective irreversible inhibitors of androgen aromatases. 16α-Bromo-4-androstene-3,17-dione (1) and 16α-bromo-4-androstene-3,6,17-trione (2) were converted to compounds 3 and 4 in 80-90percent yield by controlled stereospecific hydrolysis using sodium hydroxide in aqueous pyridine.Reductive amination of 3β-hydroxy-5-androsten-17-one and 3-methoxy-3,5-androstadien-17-one (11) using ammonium acetate and sodium cyanohydridoborate (NaBH3CN) and a subsequent treatment with acid gave the amines 10 and 14, respectively, as a salt.The corresponding 17-imino compounds 9 and 13 were also isolated from the reaction mixtures when methanol was used as a solvent for the reaction.The 16α-hydroxyl compounds 3 and 4 and the 17β-amino compound 14 were converted to the corresponding bromoacetyl derivatives, 5, 6, and 15, with bromoacetic acid and N,N'-dicyclohexylcarbodiimide.