氧甲氢龙合成中伴生副产物2-(2-羟基乙氧基)-17β-羟基-2,17α-二甲基-A-失碳-5α-雄甾烷的鉴定与合成  

Synthesis and identification of 2-(2-hydroxyethoxy)-17β-hydroxy-2,17α-dimethyl-A-nor-5α-androstane,a by-product of oxandrolone during its synthesis

作　　者：屈洁[1] 饶志威[2] 左文果[1] 赵徐波 李宗桃[1] 

机构地区：[1]武汉大学药学院,湖北武汉430071 [2]南华大学药物药理研究所,湖南衡阳422101 [3]武汉志邦化学技术有限公司,湖北武汉430072

出　　处：《中国药物化学杂志》2012年第3期216-219,共4页Chinese Journal of Medicinal Chemistry

摘　　要：目的为改进氧甲氢龙的合成工艺及提高产率提供实验依据。方法通过柱色谱、重结晶等方法分离纯化合成氧甲氢龙过程中发现的副产物,经IR、1H-NMR、13C-NMR、MS、元素分析、X-单晶衍射实验等分析手段确证副产物的化学结构;推测副产物的形成机制并按此机制合成该副产物。结果与结论鉴定副产物为2-(2-羟基乙氧基)-17β-羟基-2,17α-二甲基-A-失碳-5α-雄甾烷,其形成机制可能是格氏试剂形成的甲基负离子在进攻中间体(7)17位的羰基碳的同时,一部分的甲基负离子从甾体平面结构的下方进攻了2位的乙缩酮的碳原子进而生成该副产物。准确分析出副产物的化学结构及形成机制。Oxandrolone is an anabolic hormone drug and has strong anabolic effect with no obvious androgenic effect.In synthesizing 2,2-ethandiyldioxy-17α-methyl-A-nor-5α-androstan-17β-ol which is one of the important intermediate of oxandrolone,a by-product was separated by column chromatography.The chemical structure of this by-product was confirmed as 2-（2-hydroxyethoxy）-17β-hydroxy-2,17α-dimethyl-A-nor-5α-androstane by melting point,IR,1H-NMR,13C-NMR,MS,and elemental analysis.Then the by-product was synthesized in order to study its possible formation mechanism.The result showed that the ketal structure is cleavaged in the presence of excessive methylmagnesium iodide that attacked 2-carbon when the methylmagnesium iodide attacked 17-carbon.

关 键 词：氧甲氢龙 2-(2-羟基乙氧基)-17β-羟基-2 17α-二甲基-A-失碳-5α-雄甾烷 合成 副产物 

分 类 号：R914.5[医药卫生—药物化学]