3α,4α-dihydroxy-5α-androstan-17-one

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 3α,4α-dihydroxy-5α-androstan-17-one
• 英文别名: (3R,4S,5R,8R,9S,10R,13S,14S)-3,4-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-17-one
• 化学式: C₁₉H₃₀O₃
• 分子量: 306.445
• InChiKey: RFMKWBMPDNCUNR-CWBKUMBBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3α,4α-dihydroxy-5α-androstan-17-one 在 sodium tetrahydroborate 作用下， 以 甲醇 、 水 为溶剂， 反应 1.0h， 生成 5α-androstane-3α,4α,17β-triol
  参考文献：
  名称：

  Metabolism of 4-hydroxyandrostenedione and 4-hydroxytestosterone: Mass spectrometric identification of urinary metabolites

  摘要：

  4-Hydroxyandrost-4-ene-3,17-dione is a second generation, irreversible aromatase inhibitor and commonly used as anti breast cancer medication for postmenopausal women. 4-Hydroxytestosterone is advertised as anabolic steroid and does not have any therapeutic indication. Both substances are prohibited in sports by the World Anti-Doping Agency, and, due to a considerable increase of structurally related steroids with anabolic effects offered via the internet, the metabolism of two representative candidates was investigated.Excretion studies were conducted with oral applications of 100mg of 4-hydroxyandro-stenedione or 200mg of 4-hydroxytestosterone to healthy male volunteers. Urine samples were analyzed for metabolic products using conventional gas chromatography-mass spectrometry approaches, and the identification of urinary metabolites was based on reference substances, which were synthesized and structurally characterized by nuclear magnetic resonance spectroscopy and high resolution/high accuracy mass spectrometry.Identified phase-I as well as phase-II metabolites were identical for both substances. Regarding phase-I metabolism 4-hydroxyandrostenedione (1) and its reduction products 3 beta-hydroxy-5 alpha-androstane-4,17-dione (2) and 3 alpha-hydroxy-5 beta-androstane-4,17-dione (3) were detected. Further reductive conversion led to all possible isomers of 3 xi,4 xi-dihydroxy,-5 xi-androstan-17-one (4, 6-11) except 3 alpha,4 alpha-dihydroxy-5 beta-androstan-17-one (5).Out of the 17 beta-hydroxylated analogs 4-hydroxytestosterone (18), 3 beta,17 beta-dihydroxy-alpha-androstan-4-one (19),3 alpha,17 beta-dihydroxy-5 beta-androstan-4-one (20), 5 alpha-androstane-3 beta,4 beta,17 beta-triol (21), 5 alpha-androstane-3 alpha,4 beta,17 beta-triol (26) and 5 alpha-androstane-3 alpha,4 alpha,17 beta-triol (28) were identified in the post administration urine specimens. Furthermore 4-hydroxyandrosta-4,6-diene-3,17-dione (29) and 4-hydroxyandrosta-1,4-diene-3,17-dione (30) were determined as oxidation products. Conjugation was diverse and included glucuronidation and sulfatation. (c) 2006 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2006.11.018
• 作为产物：
  描述：

  5-雄甾-3-烯-17-酮 在 四氧化锇 、 sodium hydrogensulfite 作用下， 以 吡啶 、 水 为溶剂， 反应 2.08h， 以58%的产率得到3α,4α-dihydroxy-5α-androstan-17-one
  参考文献：
  名称：

  Metabolism of 4-hydroxyandrostenedione and 4-hydroxytestosterone: Mass spectrometric identification of urinary metabolites

  摘要：

  4-Hydroxyandrost-4-ene-3,17-dione is a second generation, irreversible aromatase inhibitor and commonly used as anti breast cancer medication for postmenopausal women. 4-Hydroxytestosterone is advertised as anabolic steroid and does not have any therapeutic indication. Both substances are prohibited in sports by the World Anti-Doping Agency, and, due to a considerable increase of structurally related steroids with anabolic effects offered via the internet, the metabolism of two representative candidates was investigated.Excretion studies were conducted with oral applications of 100mg of 4-hydroxyandro-stenedione or 200mg of 4-hydroxytestosterone to healthy male volunteers. Urine samples were analyzed for metabolic products using conventional gas chromatography-mass spectrometry approaches, and the identification of urinary metabolites was based on reference substances, which were synthesized and structurally characterized by nuclear magnetic resonance spectroscopy and high resolution/high accuracy mass spectrometry.Identified phase-I as well as phase-II metabolites were identical for both substances. Regarding phase-I metabolism 4-hydroxyandrostenedione (1) and its reduction products 3 beta-hydroxy-5 alpha-androstane-4,17-dione (2) and 3 alpha-hydroxy-5 beta-androstane-4,17-dione (3) were detected. Further reductive conversion led to all possible isomers of 3 xi,4 xi-dihydroxy,-5 xi-androstan-17-one (4, 6-11) except 3 alpha,4 alpha-dihydroxy-5 beta-androstan-17-one (5).Out of the 17 beta-hydroxylated analogs 4-hydroxytestosterone (18), 3 beta,17 beta-dihydroxy-alpha-androstan-4-one (19),3 alpha,17 beta-dihydroxy-5 beta-androstan-4-one (20), 5 alpha-androstane-3 beta,4 beta,17 beta-triol (21), 5 alpha-androstane-3 alpha,4 beta,17 beta-triol (26) and 5 alpha-androstane-3 alpha,4 alpha,17 beta-triol (28) were identified in the post administration urine specimens. Furthermore 4-hydroxyandrosta-4,6-diene-3,17-dione (29) and 4-hydroxyandrosta-1,4-diene-3,17-dione (30) were determined as oxidation products. Conjugation was diverse and included glucuronidation and sulfatation. (c) 2006 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2006.11.018

文献信息

• Metabolism of 4-hydroxyandrostenedione and 4-hydroxytestosterone: Mass spectrometric identification of urinary metabolites
  作者：Maxie Kohler、Maria K. Parr、Georg Opfermann、Mario Thevis、Nils Schlörer、Franz-Josef Marner、Wilhelm Schänzer

  DOI：10.1016/j.steroids.2006.11.018

  日期：2007.3

  4-Hydroxyandrost-4-ene-3,17-dione is a second generation, irreversible aromatase inhibitor and commonly used as anti breast cancer medication for postmenopausal women. 4-Hydroxytestosterone is advertised as anabolic steroid and does not have any therapeutic indication. Both substances are prohibited in sports by the World Anti-Doping Agency, and, due to a considerable increase of structurally related steroids with anabolic effects offered via the internet, the metabolism of two representative candidates was investigated.Excretion studies were conducted with oral applications of 100mg of 4-hydroxyandro-stenedione or 200mg of 4-hydroxytestosterone to healthy male volunteers. Urine samples were analyzed for metabolic products using conventional gas chromatography-mass spectrometry approaches, and the identification of urinary metabolites was based on reference substances, which were synthesized and structurally characterized by nuclear magnetic resonance spectroscopy and high resolution/high accuracy mass spectrometry.Identified phase-I as well as phase-II metabolites were identical for both substances. Regarding phase-I metabolism 4-hydroxyandrostenedione (1) and its reduction products 3 beta-hydroxy-5 alpha-androstane-4,17-dione (2) and 3 alpha-hydroxy-5 beta-androstane-4,17-dione (3) were detected. Further reductive conversion led to all possible isomers of 3 xi,4 xi-dihydroxy,-5 xi-androstan-17-one (4, 6-11) except 3 alpha,4 alpha-dihydroxy-5 beta-androstan-17-one (5).Out of the 17 beta-hydroxylated analogs 4-hydroxytestosterone (18), 3 beta,17 beta-dihydroxy-alpha-androstan-4-one (19),3 alpha,17 beta-dihydroxy-5 beta-androstan-4-one (20), 5 alpha-androstane-3 beta,4 beta,17 beta-triol (21), 5 alpha-androstane-3 alpha,4 beta,17 beta-triol (26) and 5 alpha-androstane-3 alpha,4 alpha,17 beta-triol (28) were identified in the post administration urine specimens. Furthermore 4-hydroxyandrosta-4,6-diene-3,17-dione (29) and 4-hydroxyandrosta-1,4-diene-3,17-dione (30) were determined as oxidation products. Conjugation was diverse and included glucuronidation and sulfatation. (c) 2006 Elsevier Inc. All rights reserved.