10-<(1S)-1-hydroxyethyl>estr-4-ene-3,17-dione | 111582-35-5

• 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
• 英文名称: 10-<(1S)-1-hydroxyethyl>estr-4-ene-3,17-dione
• 英文别名: [19S]-19-methyl-19-hydroxyandrost-4-en-3,17-dione
• CAS: 111582-35-5
• 化学式: C₂₀H₂₈O₃
• 分子量: 316.441
• InChiKey: NHSZUAANZQSIMY-NYJPLASDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.45
• 重原子数：
  23.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  54.37
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  10-<(1S)-1-hydroxyethyl>estr-4-ene-3,17-dione 生成 10-acetylestr-4-ene-3,17-dione
  参考文献：
  名称：

  Metabolism of 19-methyl substituted steroids and a proposal for the third aromatase monooxygenation

  摘要：

  The article summarizes the results of recent studies on the metabolism of 10-ethylestr-4-ene-3,17-dione, 10-[(1R)-1-hydroxyethyl]-, and 10-[(1S)-1-hydroxyethyl]estr-4-ene-3,17-dione, in placenta. These compounds are the 19-methyl analogs of androstenedione, 19-hydroxyandrostenedione, and 19-oxoandrostenedione, respectively. No conversion of 10-ethylestr-4-ene-3,17-dione to either estrogens or oxygenated metabolites was detected. Both 10-[(1R)-1-hydroxyethyl]- and 10-[(1S)-1-hydroxyethyl]estr-4-ene-3,17-dione were oxygenated to 10-(1,1-dihydroxyethyl)estr-4-ene-3,17-dione and isolated following in situ dehydration as 10-acetylestr-4-ene-3,17-dione. Evidence for the involvement of aromatase in these conversions is discussed. No conversion of 10-acetylestr-4-ene-3,17-dione to either estrogens or other oxygenated products was detected. These results lead us to propose a new mechanism for the third aromatase monooxygenation. We propose that the third oxygenation is initiated by 1 beta-hydrogen abstraction at C1 of 19,19-dihydroxyandrostenedione, followed by homolytic cleavage of the C10-C19 bond with concurrent formation of a delta 1(10),4-3-ketosteroid and a C19 carbon radical, and terminated by oxygen rebound at C19.

  DOI：

  10.1016/0039-128x(87)90025-0
• 作为产物：
  描述：

  19-methylandrost-4-en-3,17-dione 生成 10-<(1S)-1-hydroxyethyl>estr-4-ene-3,17-dione
  参考文献：
  名称：

  Metabolism of 19-methyl substituted steroids and a proposal for the third aromatase monooxygenation

  摘要：

  The article summarizes the results of recent studies on the metabolism of 10-ethylestr-4-ene-3,17-dione, 10-[(1R)-1-hydroxyethyl]-, and 10-[(1S)-1-hydroxyethyl]estr-4-ene-3,17-dione, in placenta. These compounds are the 19-methyl analogs of androstenedione, 19-hydroxyandrostenedione, and 19-oxoandrostenedione, respectively. No conversion of 10-ethylestr-4-ene-3,17-dione to either estrogens or oxygenated metabolites was detected. Both 10-[(1R)-1-hydroxyethyl]- and 10-[(1S)-1-hydroxyethyl]estr-4-ene-3,17-dione were oxygenated to 10-(1,1-dihydroxyethyl)estr-4-ene-3,17-dione and isolated following in situ dehydration as 10-acetylestr-4-ene-3,17-dione. Evidence for the involvement of aromatase in these conversions is discussed. No conversion of 10-acetylestr-4-ene-3,17-dione to either estrogens or other oxygenated products was detected. These results lead us to propose a new mechanism for the third aromatase monooxygenation. We propose that the third oxygenation is initiated by 1 beta-hydrogen abstraction at C1 of 19,19-dihydroxyandrostenedione, followed by homolytic cleavage of the C10-C19 bond with concurrent formation of a delta 1(10),4-3-ketosteroid and a C19 carbon radical, and terminated by oxygen rebound at C19.

  DOI：

  10.1016/0039-128x(87)90025-0

文献信息

• Gas Chromatography-Mass Spectrometric Study of 19-Oxygenation of the Aromatase Inhibitor 19-Methylandrostenedione with Human Placental Microsomes
  作者：Mitsuteru Numazawa、Masao Nagaoka、Wakako Handa、Akane Yamada

  DOI：10.1248/bpb.29.1242

  日期：——

  To gain insight into the catalytic function of aromatase, we studied 19-oxygenation of 19-methyl-substituted derivative of the natural substrate androstenedione (AD), compound 1, with human placental aromatase by use of gas chromatography-mass spectrometry (GC-MS). Incubation of the 19-methyl derivative 1 with human placental microsomes in the presence of NADPH under an aerobic condition did not yield a detectable amount of [19S]19-hydroxy product 2 or its [19R]-isomer 3 when the product was analyzed as the bis-methoxime-trimethylsilyl (TMS) derivative by GC-MS; moreover, the production of estrogen was not detected as the bis-TMS derivative of estradiol (detection limit: about 3 ng and 10 pg per injection for the 19-ol and estradiol, respectively). The results reveal that the 19-methyl steroid 1 does not serve as a substrate of aromatase, although it does serve as a powerful inhibitor of the enzyme.

  为了深入了解芳香化酶的催化功能，我们利用气相色谱-质谱法（GC-MS）研究了天然底物雄烯二酮（AD）的 19-甲基取代衍生物化合物 1 与人胎盘芳香化酶的 19-氧合反应。在有氧条件下，在 NADPH 存在下，将 19-甲基衍生物 1 与人胎盘微粒体进行孵育，当以双甲氧基-三甲基硅烷基（TMS）衍生物的形式进行气相色谱-质谱分析时，没有检测到[19S]19-羟基产物 2 或其[19R]-异构体 3；此外，也没有检测到以雌二醇的双 TMS 衍生物形式产生的雌激素（检测限：约 3 纳克和 10 皮克）：19-醇和雌二醇的检测限分别为每次注射约 3 毫微克和 10 皮克）。结果表明，19-甲基类固醇 1 不能作为芳香化酶的底物，但它确实是该酶的强力抑制剂。