美替诺龙醋酸酯的合成

Synthesis of Methenolone Acetate

目的 由 17β 乙酰氧基 5α雄甾 1 烯 3 酮 (1)经 5步反应合成蛋白同化激素美替诺龙醋酸酯 (17β 乙酰氧基 1 甲基 5α雄甾 1 烯 3 酮 ,6 )。方法 17β 乙酰氧基 5α雄甾 1 烯 3 酮 (1)在酸的存在下与NBS反应 ,得2 β 溴 1α ,17β 二羟基 5α 雄甾烷 3 酮 17 醋酸酯 (2 ) ,化合物 (2 )用H2 /活性镍催化氢解 ,得 1α ,17β 二羟基 5α 雄甾烷 3 酮 17 醋酸酯 (3) ,然后在对甲苯磺酸的催化下化合物 (3)与甲醇作用 ,得 3,3 二甲氧基 5α 雄甾烷 1α ,17β 二醇 17 醋酸酯 (4 )。化合物 (4 )经铬酐 硫酸氧化 ,得 17β 乙酰氧基 3,3 二甲氧基 5α 雄甾烷 1 酮 (5 ) ,再经格氏反应和乙酰化反应 ,制得 17β 乙酰氧基 1 甲基 5α 雄甾 1 烯 3 酮 (美替诺龙醋酸酯 ,6 )。由化合物 1到 6的总收率为 48.7%。结果 此法以较高收率合成了美替诺龙醋酸酯。

Purpose: To prepare methenolone acetate (17β-acetoxy-1-methyl-5α -androst-1-en-3-one,6) in five steps from 17β-Acetoxy-5α -androst-1-en-3-one(1). Methods: 17β-Acetoxy-5α-androst-1-en-3-one(1) was reacted with NBS in the presence of acid to give 2β-bromo-1α, 17β-dihydroxy-5α-androstan-3-one 17ace-tate(2). And (2) was debrominated by H2/Raney Ni to give 1α, 17β -dihydroxy-5α-androstan-3-one 17ace-tate(3), which was treated with methanol in the presence of ptoluenesulfonic acid to give 3,3-dimethyloxy-5α-androstan-1α, 17β-diol 17-acetate(4). (4) was oxidized with chromium trioxide-sulfuric acid to yield 17β -acetxoy-3,3-dimethyloxy-5α-androst-1-one (5). (5) was treated by Grignard reagent, sulfuric acid and then acetylated to yield 17β-Acetoxy-1-methyl-5α-androst-1-ene-3-one (6,methenolone acetate). Total yield of 6 from 1 is 48.7%. Results: Methenolone acetate was prepared in high yield. Conclusions: This method is applicable to industrial production.