Synthesis of 16 alpha-bromoacetoxy androgens and 17 beta-bromoacetylamino-4-androsten-3-one: potential affinity labels of human placental aromatase.
A novel synthesis of 16 alpha-hydroxy-4-androstene-3,17-dione (3), 16 alpha-hydroxy-4-androstene-3,6,17-trione (4), 17 beta-amino-5-androsten-3 beta-o1 (10) and 17 beta-amino-4-androsten-3-one (14) is described. 16 alpha-Bromoacetoxy-4-androstene-3,17-dione (5), 16 alpha-bromoacetoxy-4-androstene-3,6,17-trione (6) and 17 beta-bromoacetylamino-4-androsten-3-one (15) were synthesized as potentially selective irreversible inhibitors of androgen aromatases. 16 alpha-Bromo-4-androstene-3,17-dione (1) and 16 alpha-bromo-4-androstene-3,6,17-trione (2) were converted to compounds 3 and 4 in 80-90% yield by controlled stereospecific hydrolysis using sodium hydroxide in aqueous pyridine. Reductive amination of 3 beta-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 16 alpha-hydroxyl compounds 3 and 4 and the 17 beta-amino compound 14 were converted to the corresponding bromoacetyl derivatives, 5, 6, and 15, with bromoacetic acid and N,N'-dicyclohexylcarbodiimide.
D000345:Affinity Labels / Q000138:chemical synthesis*; D000736:Androstenes / Q000138:chemical synthesis*; D001141:Aromatase / Q000378:metabolism*; D005260:Female; D006801:Humans; D010088:Oxidoreductases / Q000378:metabolism*; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D013379:Substrate Specificity
D000345:Affinity Labels; D000736:Androstenes; C032362:17 beta-bromoacetylamino-4-androsten-3-one; D010088:Oxidoreductases; D001141:Aromatase