Numazawa M, Osawa Y
Steroids. 1981 Aug;38(2):149-59. doi: 10.1016/0039-128x(81)90029-5.
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.
描述了16α-羟基-4-雄烯-3,17-二酮（3）、16α-羟基-4-雄烯-3,6,17-三酮（4）、17β-氨基-5-雄烯-3β-醇（10）和17β-氨基-4-雄烯-3-酮（14）的一种新合成方法。合成了16α-溴乙酰氧基-4-雄烯-3,17-二酮（5）、16α-溴乙酰氧基-4-雄烯-3,6,17-三酮（6）和17β-溴乙酰氨基-4-雄烯-3-酮（15），作为雄激素芳香化酶潜在的选择性不可逆抑制剂。16α-溴-4-雄烯-3,17-二酮（1）和16α-溴-4-雄烯-3,6,17-三酮（2）通过在吡啶水溶液中用氢氧化钠进行可控的立体定向水解，以80 - 90%的产率转化为化合物3和4。使用醋酸铵和氰基硼氢化钠（NaBH3CN）对3β-羟基-5-雄烯-17-酮和3-甲氧基-3,5-雄二烯-17-酮（11）进行还原胺化，随后用酸处理，分别得到盐形式的胺10和14。当使用甲醇作为反应溶剂时，还从反应混合物中分离出了相应的17-亚氨基化合物9和13。16α-羟基化合物3和4以及17β-氨基化合物14用溴乙酸和N,N'-二环己基碳二亚胺转化为相应的溴乙酰衍生物5、6和15。
