6-methylene-5α-androstane-3,17-dione | 4729-50-4

• 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: 6-methylene-5α-androstane-3,17-dione
• 英文别名: 6-methyleneandrostane-3,17-dione；6-methylene-5a-androstane-3b,17-dione；6-Methylen-5α-androstan-3,17-dion；(5R,8R,9S,10R,13S,14S)-10,13-dimethyl-6-methylidene-1,2,4,5,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthrene-3,17-dione
• CAS: 4729-50-4
• 化学式: C₂₀H₂₈O₂
• 分子量: 300.441
• InChiKey: QYRHBSKUWKINIQ-YDWUEFBCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-methylene-5α-androstane-3,17-dione 在 甲酸 作用下， 生成 6α-methylandrost-4-ene-3,17-dione
  参考文献：
  名称：

  修饰的类固醇激素—XLI：3β-乙酰氧基-4aα-羟基-5β-甲基-A-同型B-nor类固醇重排成6-亚甲基-5β-H系列正常类固醇

  摘要：

  描述了影响3β-乙酰氧基-4aα-羟基-5β-甲基-A-高-B-正甾族化合物的分子重排成6-亚甲基-5β-H系列相应的正常结构的方法。NMR光谱数据导致最初的类固醇A-homo-B-nor类型中存在的4a-羟基具有α-构型。

  DOI：

  10.1016/s0040-4020(01)96936-4
• 作为产物：
  描述：

  17β-hydroxy-6-methyleneandrosta-4-ene-3-one 在 potato dextrose broth medium 作用下， 以 乙醇 为溶剂， 反应 96.0h， 以10%的产率得到6-methylene-5α-androstane-3,17-dione
  参考文献：
  名称：

  Formation of 5α steroids by biotranformation involving the 5α-reductase activity of Penicillium decumbens

  摘要：

  The biotransformation of a series of Delta(4)-3-ketosteroids by the fungus Penicillium decumbens ATCC 10436 has been investigated. Conversion to the 5 alpha-dihydrosteroid was observed for several substrates of the androstene and pregnene series: the reaction is tolerant of non-polar subdituents (Cl and CH3) at C-4 of the substrate, but does not occur in the presence of a 4-hydroxyl group, or with additional unsaturation at the Delta(1) or Delta(6) positions. A-nor-, B-nor-, 3-deoxy-, and 3,5-cycloandrostanes are not reduced, but 6-methylenetestosterone is converted to a 6-methylene-5 alpha-dihydro derivative. Several biotransformations are reported which involve oxidoreductase activity at C-3 and/or C-17, either concomitant or independent of Delta(4) reduction: the substrate specificity of the oxidoreductase processes has been examined and defined by the use of 3 alpha-hydroxy, 3 beta-hydroxy, 3-keto, and 17 beta-hydroxy-17-keto substituted steroids. In this way, the existence in P. decumbens of 3 beta-hydroxy-3-keto and 17 beta-hydroxy-17-keto oxidoreductases has been demonstrated.

  DOI：

  10.1016/0039-128x(94)90020-5

文献信息

• Steroids as Molecular Photonic Wires. <i>Z </i>→ <i>E</i> Olefin Photoisomerization by Intramolecular Triplet−Triplet Energy Transfer with and without Intervening Olefinic Gates¹
  作者：Larry D. Timberlake、Harry Morrison

  DOI：10.1021/ja9808595

  日期：1999.4.1

  3β-((dimethylphenylsilyl)oxy)-17-(Z)-ethylidene-6-methylene-5α-androstane (3a), and 3α-((dimethylphenylsilyl)oxy)-17-(Z)-ethylidene-6-methylene-5α-androstane (3b) have been prepared. The triplet−triplet excited-state energy transfer (TTET) that occurs from the C3 aryl “donor” group to the C17 ethylidene “acceptor” has been studied in detail at 10 mM steroid concentration. Irradiation with 266 nm light results

  类固醇 3β-((二甲基苯基甲硅烷基)氧基)-17-(Z)-亚乙基-5α-雄甾烷 (1), 3β-((二甲基苯基甲硅烷基)氧基)-17-(Z)-亚乙基-5-雄甾烷 (2), 3β-((二甲基苯基甲硅烷基)氧基)-17-(Z)-亚乙基-6-亚甲基-5α-雄甾烷(3a)和3α-((二甲基苯基甲硅烷基)氧基)-17-(Z)-亚乙基-6-亚甲基- 5α-雄甾烷 (3b) 已制备。已经在 10 mM 类固醇浓度下详细研究了从 C3 芳基“供体”基团到 C17 亚乙基“受体”发生的三重态-三重态激发态能量转移 (TTET)。用 266 nm 光照射导致 C17 亚乙基的 Z → E 烯烃异构化，这是内部和内部 TTET 的结果。对于 1、2、3a 和 3b，ΦZ→E = 0.037、0.018、0.028 和 0.004。这些化合物和适当模型的详细动力学分析，添加和不添加烯烃猝灭剂，提供一组完整的速率常数，这些常数是相对于假定的
• Modified aromatase inhibitors having improved bioavailability
  申请人：Kneller W. Bruce

  公开号：US20050203074A1

  公开（公告）日：2005-09-15

  The present invention relates to the modification of 3-beta-hydroxyandrost-4-ene-6,17-dione (“3-OHAT”) and its metabolites/derivatives at either the 3 rd or 17 th carbon or 3 rd and 17 th carbons with various ethers and/or esters and to the modification of 3-beta-hydroxyandrost-4-ene-6,17-dione (“3-OHAT”) and its metabolites/derivatives at carbon 6 with a methyl, methoxy, methylene, hydroxymethylene or acetoxy functional group to improve and increase the oral bioavailability and/or plasma half life and/or efficacy in mammals.

  本发明涉及对 3-beta-羟基雄甾-4-烯-6,17-二酮（"3-OHAT"）及其代谢物/衍生物在第 3 或 或 碳或 碳或 3 第 和第 17 碳 3-OHAT"）及其代谢物/衍生物的第 6 碳上的甲基、甲氧基、亚甲基、羟甲基或乙酰氧基官能团，以改善和提高哺乳动物的口服生物利用度和/或血浆半衰期和/或药效。
• Novel analogues of Istaroxime, a potent inhibitor of Na+,K+-ATPase: Synthesis, structure–activity relationship and 3D-quantitative structure–activity relationship of derivatives at position 6 on the androstane scaffold
  作者：Mauro Gobbini、Silvia Armaroli、Leonardo Banfi、Alessandra Benicchio、Giulio Carzana、Patrizia Ferrari、Giuseppe Giacalone、Giuseppe Marazzi、Barbara Moro、Rosella Micheletti

  DOI：10.1016/j.bmc.2010.04.095

  日期：2010.6.15

  We report the synthesis and biological properties of novel analogues of Istaroxime acting as positive inotropic compounds through the inhibition of the Na+, K+-ATPase. We explored the chemical space around the position 6 of the steroidal scaffold by changing the functional groups at that position and maintaining a basic oximic chain in position 3. Some compounds showed inhibitory potencies of the Na+, K+-ATPase higher than Istaroxime and many of the compounds tested in vivo were safer than digoxin, the classic digitalis compound currently used for the treatment of congestive heart failure as inotropic agent. The 3D-QSAR analyses using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods have been successfully applied to a set of 63 androstane derivatives as Na+,K+-ATPase inhibitors. The contour plots provide many useful insights into relationships between structural features and inhibitory potency. (C) 2010 Elsevier Ltd. All rights reserved.
• Formation of 5α steroids by biotranformation involving the 5α-reductase activity of Penicillium decumbens
  作者：Herbert L. Holland、Sophia Dore、Xu Weili、Frances M. Brown

  DOI：10.1016/0039-128x(94)90020-5

  日期：1994.11

  The biotransformation of a series of Delta(4)-3-ketosteroids by the fungus Penicillium decumbens ATCC 10436 has been investigated. Conversion to the 5 alpha-dihydrosteroid was observed for several substrates of the androstene and pregnene series: the reaction is tolerant of non-polar subdituents (Cl and CH3) at C-4 of the substrate, but does not occur in the presence of a 4-hydroxyl group, or with additional unsaturation at the Delta(1) or Delta(6) positions. A-nor-, B-nor-, 3-deoxy-, and 3,5-cycloandrostanes are not reduced, but 6-methylenetestosterone is converted to a 6-methylene-5 alpha-dihydro derivative. Several biotransformations are reported which involve oxidoreductase activity at C-3 and/or C-17, either concomitant or independent of Delta(4) reduction: the substrate specificity of the oxidoreductase processes has been examined and defined by the use of 3 alpha-hydroxy, 3 beta-hydroxy, 3-keto, and 17 beta-hydroxy-17-keto substituted steroids. In this way, the existence in P. decumbens of 3 beta-hydroxy-3-keto and 17 beta-hydroxy-17-keto oxidoreductases has been demonstrated.
• Modified steroid hormones—XLI
  作者：M.T. Davies、B. Ellis、D.N. Kirk、V. Petrow

  DOI：10.1016/s0040-4020(01)96936-4

  日期：1965.1

  Methods are described for effecting the molecular rearrangement of 3β-acetoxy-4aα-hydroxy-5β-methyl-A-homo-B-nor steroids into corresponding normal structures of the 6-methylene-5β-H series. NMR spectral data lead to the assignment of the α-configuration to the 4a-hydroxyl group present in the initial steroidal A-homo-B-nor types.

  描述了影响3β-乙酰氧基-4aα-羟基-5β-甲基-A-高-B-正甾族化合物的分子重排成6-亚甲基-5β-H系列相应的正常结构的方法。NMR光谱数据导致最初的类固醇A-homo-B-nor类型中存在的4a-羟基具有α-构型。