5β-androst-3-en-17-one | 146829-71-2

• 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: 5β-androst-3-en-17-one
• 英文别名: (5R,8R,9S,10S,13S,14S)-10,13-dimethyl-1,2,5,6,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one
• CAS: 146829-71-2
• 化学式: C₁₉H₂₈O
• 分子量: 272.431
• InChiKey: RJWNCDOWHNLVPF-USOAJAOKSA-N

物化性质

• 沸点：
  371.6±42.0 °C(Predicted)
• 密度：
  1.032±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  5β-androst-3-en-17-one 在 sodium tetrahydroborate 、 四氧化锇 作用下， 以 吡啶 、 甲醇 、 水 为溶剂， 反应 3.08h， 生成 5β-androstan-3β,4β,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：

  雄烯二酮 在 溶剂黄146 、 锌 作用下， 反应 0.17h， 以34%的产率得到5-雄甾-3-烯-17-酮
  参考文献：
  名称：

  Significant steroids: effective and general synthesis of 4α- and 4β-amino-5α-androstanes

  摘要：

  采用K2CO3作为活化剂，通过2α-溴酮的取代反应合成了4α-氨基甾体；在ZnCl2-H2O催化剂的作用下，通过甾体3,4α-环氧化物的区域选择性和反式立体特异性环开裂反应，以优异的产率合成了4β-氨基甾体。

  DOI：

  10.1039/b817910g

文献信息

• Synthesis of Fluorinated Steroids Using a Novel Fluorinating Reagent Tetrabutylammonium Difluorodimethylphenylsilicate (TAMPS)
  作者：Pavel Herrmann、Jaroslav Kvíčala、Vladimír Pouzar、Hana Chodounská

  DOI：10.1135/cccc20081825

  日期：——

  Steroidal 3-fluoroderivatives were prepared from corresponding tosylates using tetrabutylammonium difluorodimethylphenylsilicate as fluorinating agent. The reaction was tested on all four possible C-3 and C-5 stereoisomers of cholestane and 17-oxoandrostane skeletons. In this reaction only one isomer was always formed with opposite configuration at C-3 to starting tosylate. The reaction is accompanied by elimination which affords a mixture of corresponding olefines.

  使用四丁基铵二氟二甲基苯基硅酸酯作为氟化试剂，从相应的tosylates制备了类固醇3-氟衍生物。该反应在胆甾烷和17-氧基雄甾烷骨架的所有四个可能的C-3和C-5立体异构体上进行了测试。在这个反应中，只形成了一个异构体，其C-3位置的构型与起始的tosylate相反。该反应伴随着消除作用，产生相应的烯烃混合物。
• Structure−Activity Relationships of New A,D-Ring Modified Steroids as Aromatase Inhibitors:  Design, Synthesis, and Biological Activity Evaluation
  作者：Margarida M. D. S. Cepa、Elisiário J. Tavares da Silva、Georgina Correia-da-Silva、Fernanda M. F. Roleira、Natércia A. A. Teixeira

  DOI：10.1021/jm050129p

  日期：2005.10.1

  3-deoxy steroidal olefin 3a and its epoxide derivative 4a proved to be strong competitive aromatase inhibitors (K(i) = 50 and 38 nM and IC50 = 225 and 145 nM, respectively). According to our findings, the C-3 carbonyl group is not essential for anti-aromatase activity, but 5alpha-stereochemistry and some planarity in the steroidal framework is required. Furthermore, modification of the steroidal cyclopentanone

  抑制芳香酶是预防和治疗乳腺癌的有效方法。设计并合成了新的A，D环修饰的福尔马斯坦和睾丸内酯类固醇类似物，并在体外研究了它们的生化活性，以寻找新的芳香酶抑制剂并深入了解其结构活性关系（SAR）。所有测试的化合物都没有福尔马坦活性。然而，事实证明3-脱氧甾体烯烃3a及其环氧化物衍生物4a是强竞争性芳香酶抑制剂（K（i）分别为50和38 nM，IC50 = 225和145 nM）。根据我们的发现，C-3羰基对于抗芳香化酶活性不是必不可少的，但是5α-立体化学和甾体骨架中的某些平面性是必需的。此外，通过构建δ-内酯六元环对甾体环戊酮D环的修饰降低了抑制效力。根据获得的结果，可以得出结论，芳香化酶活性位点的结合袋需要在类固醇A，B环和D环结构的平面中对于结合至关重要。
• A photochemical approach to 18-nor-17β-hydroxymethyl-17α-methylandrost-13-ene steroids
  作者：Marharyta V. Laktsevich-Iskryk、Anton S. Rudovich、Vladimir N. Zhabinskii、Vladimir A. Khripach、Alaksiej L. Hurski

  DOI：10.1016/j.steroids.2020.108652

  日期：2020.7

  A photochemical approach to 18-nor-17 beta-hydroxymethyl-17 alpha-methylandrost-13-ene unit of the long-term metabolites of 17-methylated androgenic anabolic steroids (AAS) is reported. It is based on a visible light-promoted radical decarboxylative alkynylation of steroidal redox-active ester. The developed method was used in synthesis of the long-term metabolite of AAS oxymesterone.
• Significant steroids: effective and general synthesis of 4α- and 4β-amino-5α-androstanes
  作者：Xianbing Ke、Hao Hu、Keda Zhang、Wenjin Xu、Qifeng Zhu、Lamei Wu、Xianming Hu

  DOI：10.1039/b817910g

  日期：——

  4α-Aminosteroids were synthesized by the substitution of a 2α-bromo ketone using K2CO3 as an activator; 4β-aminosteroids were synthesized in excellent yields by a highly regioselective and trans-stereospecific ring opening of a steroidal 3,4α-epoxide using ZnCl2–H2O as a catalyst.

  采用K2CO3作为活化剂，通过2α-溴酮的取代反应合成了4α-氨基甾体；在ZnCl2-H2O催化剂的作用下，通过甾体3,4α-环氧化物的区域选择性和反式立体特异性环开裂反应，以优异的产率合成了4β-氨基甾体。
• 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.