(8R.9S.10R.13S.14S)-10.13-二甲基-7.8.9.11.12.13.15.16-八氢-10H-环戊并[a]菲-3.6.17(14H)-三酮 | 72648-46-5

• 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
• 中文名称: (8R.9S.10R.13S.14S)-10.13-二甲基-7.8.9.11.12.13.15.16-八氢-10H-环戊并[a]菲-3.6.17(14H)-三酮
• 中文别名: (8R,9S,10R,13S,14S)-10,13-二甲基-7,8,9,11,12,13,15,16-八氢-10H-环戊并[A]菲-3,6,17(14H)-三酮
• 英文名称: androsta-1,4-dien-3,6,17-trione
• 英文别名: Androsta-1,4-dien-3,6,17-trion；androst-1,4-diene-3,17-one；6-Oxo-androsta-1,4-dien-3,17-dion；Androsta-1,4-diene-3,6,17-trion；Androsta-1,4-diene-3,6,17-trione；(8R,9S,10R,13S,14S)-10,13-dimethyl-7,8,9,11,12,14,15,16-octahydrocyclopenta[a]phenanthrene-3,6,17-trione
• CAS: 72648-46-5
• 化学式: C₁₉H₂₂O₃
• 分子量: 298.382
• InChiKey: BXPQXTJWPDQYMP-IEVKOWOJSA-N

物化性质

• 熔点：
  >196°C (dec.)
• 溶解度：
  可溶于氯仿（轻微）、甲醇（非常轻微，加热）

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  51.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  雄甾-1,4-二烯-3,17-二酮 在 air 、 potassium tert-butylate 作用下， 以 叔丁醇 为溶剂， 反应 8.0h， 以15%的产率得到(8R.9S.10R.13S.14S)-10.13-二甲基-7.8.9.11.12.13.15.16-八氢-10H-环戊并[a]菲-3.6.17(14H)-三酮
  参考文献：
  名称：

  Synthesis and aromatase inhibition by potential metabolites of exemestane (6-methylenandrosta-1,4-diene-3,17-dione)

  摘要：

  Exemestane (6-methylenandrosta-1,4-diene-3,17-dione; FCE 24304) is an orally active irreversible aromatase inhibitor which is in phase II clinical evaluation for the potential therapy of postmenopausal breast cancer. A series of exemestane analogs, with modifications at the 6-methylene group and with additional reduction at the 17-keto group, were synthesized as potential metabolites and tested in vitro for their effect on human placental aromatase. All these new analogs were found to be less potent in inhibiting aromatase than exemestane. The most effective compound was the 17beta-hydroxy-derivative (compound 2), which is 2.6-fold less potent than exemestane [50% inhibitory concentration (IC50) 69 and 27 nM, respectively]. The various C-6 modified derivatives of the 17-oxo series were found to inhibit the aromatase enzyme in the following descending order: 6-methylene (exemestane) > 6-spirooxirane (6) > 6beta-hydroxymethyl (11) > 6-hydroxymethyl (7) > 6beta-carboxy (13), showing IC50 values of 27, 206, 295, 2,300, and 7,200 nM, respectively. The 17beta-hydroxy analogs of some of the above mentioned compounds were also synthesized (3, 4, 12) and found to be 3-8-fold less potent than the corresponding 17-keto analogs.

  DOI：

  10.1016/0039-128x(93)90029-m

文献信息

• Photoexcited nitroarenes for the oxidative cleavage of alkenes
  作者：Alessandro Ruffoni、Charlotte Hampton、Marco Simonetti、Daniele Leonori

  DOI：10.1038/s41586-022-05211-0

  日期：2022.10.6

  The oxidative cleavage of alkenes is an integral process that converts feedstock materials into high-value synthetic intermediates1,2,3. The most viable method to achieve this in one chemical step is with ozone4,5,6,7, which however poses technical and safety challenges owing to the explosive nature of ozonolysis products8,9. Herein, we disclose an alternative approach to achieve oxidative cleavage

  烯烃的氧化裂解是将原料转化为高价值合成中间体的完整过程1,2,3。在一个化学步骤中实现这一目标的最可行的方法是使用臭氧4,5,6,7，然而，由于臭氧分解产物的爆炸性8,9 ，这带来了技术和安全挑战。在此，我们公开了一种使用硝基芳烃和紫光照射实现烯烃氧化裂解的替代方法。我们证明光激发硝基芳烃是有效的臭氧替代物，可以轻松地与烯烃发生自由基[3+2]环加成反应。由此产生的“ N“掺杂”臭氧化物可以安全处理，并在温和水解条件下产生相应的羰基产物。这些特征使得能够在存在广泛的常用有机官能团的情况下控制所有类型的烯烃的裂解。此外，通过利用电子、空间和介导的极性效应，硝基芳烃的结构和功能多样性提供了一个模块化平台，可以在含有一种以上烯烃的底物中获得位点选择性。
• Synthesis and aromatase inhibition by potential metabolites of exemestane (6-methylenandrosta-1,4-diene-3,17-dione)
  作者：Franco Buzzetti、Enrico Di Salle、Antonio Longo、Gabriella Briatico

  DOI：10.1016/0039-128x(93)90029-m

  日期：1993.11

  Exemestane (6-methylenandrosta-1,4-diene-3,17-dione; FCE 24304) is an orally active irreversible aromatase inhibitor which is in phase II clinical evaluation for the potential therapy of postmenopausal breast cancer. A series of exemestane analogs, with modifications at the 6-methylene group and with additional reduction at the 17-keto group, were synthesized as potential metabolites and tested in vitro for their effect on human placental aromatase. All these new analogs were found to be less potent in inhibiting aromatase than exemestane. The most effective compound was the 17beta-hydroxy-derivative (compound 2), which is 2.6-fold less potent than exemestane [50% inhibitory concentration (IC50) 69 and 27 nM, respectively]. The various C-6 modified derivatives of the 17-oxo series were found to inhibit the aromatase enzyme in the following descending order: 6-methylene (exemestane) > 6-spirooxirane (6) > 6beta-hydroxymethyl (11) > 6-hydroxymethyl (7) > 6beta-carboxy (13), showing IC50 values of 27, 206, 295, 2,300, and 7,200 nM, respectively. The 17beta-hydroxy analogs of some of the above mentioned compounds were also synthesized (3, 4, 12) and found to be 3-8-fold less potent than the corresponding 17-keto analogs.
• Nangia, Ashwini; Anthony, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1997, vol. 36, # 12, p. 1113 - 1118
  作者：Nangia, Ashwini、Anthony

  DOI：——

  日期：——
• Metabolism of 1-dehydroand rostanes in man
  作者：Ferdinando Galletti、Rinaldo Gardi

  DOI：10.1016/s0039-128x(71)80169-1

  日期：1971.7
• Goelitzer; Bonnekessel; Jones, Pharmazie, 2006, vol. 61, # 7, p. 575 - 581
  作者：Goelitzer、Bonnekessel、Jones、Palusczak、Hartmann

  DOI：——

  日期：——