(8R,9S,10R,13S,14S)-10,13-二甲基-1,2,3,8,9,11,12,14,15,16-十氢环戊烯并[a]菲-4,7,17-三酮 | 184435-18-5

• 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-1,2,3,8,9,11,12,14,15,16-十氢环戊烯并[a]菲-4,7,17-三酮
• 英文名称: androst-5-ene-4,7,17-trione
• 英文别名: Androst-5-en-4,7,17-trione；(8R,9S,10R,13S,14S)-10,13-dimethyl-1,2,3,8,9,11,12,14,15,16-decahydrocyclopenta[a]phenanthrene-4,7,17-trione
• CAS: 184435-18-5
• 化学式: C₁₉H₂₄O₃
• 分子量: 300.398
• InChiKey: OAOOSQMVGGCQGG-XDQNADNFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  51.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (8R,9S,10R,13S,14S)-10,13-二甲基-1,2,3,8,9,11,12,14,15,16-十氢环戊烯并[a]菲-4,7,17-三酮 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 甲苯 为溶剂， 反应 40.0h， 以40 mg的产率得到androst-2,5-diene-4,7,17-trione
  参考文献：
  名称：

  Hanson, James R.; Kiran, Ismail; Masarwah, Natheer F., Journal of Chemical Research, Miniprint, 1998, # 9, p. 2420 - 2434

  摘要：

  DOI：
• 作为产物：
  描述：

  17β-acetoxyandrosta-4,6-diene 在 chromium(VI) oxide 、 氢氧化钾 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 2.17h， 生成 (8R,9S,10R,13S,14S)-10,13-二甲基-1,2,3,8,9,11,12,14,15,16-十氢环戊烯并[a]菲-4,7,17-三酮
  参考文献：
  名称：

  Hanson, James R.; Kiran, Ismail; Masarwah, Natheer F., Journal of Chemical Research, Miniprint, 1998, # 9, p. 2420 - 2434

  摘要：

  DOI：

文献信息

• Aromatase Inactivation by a Suicide Substrate, Androst-5-ene-4,7,17-trione: The 5.BETA.,6.BETA.-Epoxy-19-oxo Derivative, as a Possible Reactive Electrophile Irreversibly Binding to the Active Site.
  作者：Mitsuteru NUMAZAWA、Mii TACHIBANA

  DOI：10.1248/bpb.20.490

  日期：——

  In order to understand the mechanism involved in the aromatase inactivation by androst-5-ene, 4, 7, 17-trione (4), a suicide substrate of aromatase, 5β, 6β-epoxyandrosta-4, 7, 17, 19-tetraone (6) was synthesized as a candidate for a reactive electrophile involved in irreversible binding to the active site of aromatase upon treatment of 19-oxo-5-ene steroid 5 with hydrogen peroxide in the presence of NaHCO3. The epoxide 6 was a competitive inhibitor of human placental aromatase (K1=34 μM); moreover, it inactivated the enzyme in an active-site-directed manner in the absence of NADPH (K1=36 μM, a rate constant for inactivation (kinact)=0.027 min-1). NADPH stimulated the inactivation rate, but the substrate androst-4-ene-3, 17-dione blocked the inactivation. A nucleophile, L-cysteine, did not cause a significant change in the inactivation. When both the epoxide 6 and its 19-methyl analog 7 were subjected separately to a reaction with N-acetyl-L-cycteine in the presence of NaHCO3, the 19-oxo compound 6 disappeared from the reaction mixture more rapidly (t/1/2=6.0 min) than the 19-methyl analog 7 (t1/2=16 min). On the basis of these results, it is suggested that the 5β, 6β-epoxy-19-oxo steroid 6 may be the reactive electrophile that alkylates a nucleophilic residue of the amino acid of the active site.

  为了了解雄甾-5-烯-3,17-二酮（4）这种芳香化酶自杀底物对芳香化酶失活的作用机理，在NaHCO3存在下，将5β,6β-环氧雄甾-4,7,17,19-四酮（6）作为反应性亲电试剂的候选物进行合成，该试剂在19-氧代-5-烯类固醇5与过氧化氢反应时，会与芳香化酶的活性位点发生不可逆的结合。环氧物6是人体胎盘芳香化酶的竞争性抑制剂（K1=34 μM）；此外，它会在没有NADPH的情况下以活性位点定向的方式使酶失活（K1=36 μM，失活速率常数（kinact）=0.027 min-1）。NADPH会刺激失活速率，但底物雄甾-4-烯-3,17-二酮会阻止失活。亲核试剂L-半胱氨酸不会导致失活发生明显变化。当环氧物6及其19-甲基类似物7在NaHCO3存在下分别与N-乙酰-L-半胱氨酸发生反应时，19-氧代化合物6从反应混合物中消失的速度（t/1/2=6.0 min）比