[19-2H]-androst-4-ene-17,19-dione | 885039-33-8

• 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: [19-2H]-androst-4-ene-17,19-dione
• 英文别名: (8R,9S,10S,13S,14S)-10-deuteriocarbonyl-13-methyl-1,2,3,6,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one
• CAS: 885039-33-8
• 化学式: C₁₉H₂₆O₂
• 分子量: 287.406
• InChiKey: GQLNTJMNGYMPRV-YZHGWTAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.79
• 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：

  [19-2H]-androst-4-ene-17,19-dione 在 硼氘化钠 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以35%的产率得到[19,19-2H2]19-hydroxyandrost-4-en-17-one
  参考文献：
  名称：

  Gas chromatography–mass spectrometric analysis of oxidative reactions of [19,19-2H2]19-hydroxy-3-deoxy androgens by placental aromatase

  摘要：

  Aromatase is a cytochrome P-450 enzyme complex that catalyzes the conversion of androst-4-ene-3,17-dione (AD) to estrone through three sequential oxidations of the 19-methyl group. 3-DeoxyAD (1) and its 5-ene isomer 4 are potent and good competitive aromatase inhibitors, which are converted by aromatase to the aldehyde derivatives 3 and 6, respectively, through 19-hydroxy intermediates 2 and 5, respectively. To study the deuterium isotope effect on the conversions of 19-ols 2 and 5 into the corresponding 19-als 3 and 6, we initially synthesized [19,19-H-2(2)]19-ols 2 and 5 starting from the corresponding non-labeled 19-als 3 and 6 through (NaBH4)-H-2 reduction of the 19-aldehyde group, followed by oxidation with pyridinium dichromate, and a subsequent NaB2H4 reduction. Approximately 1:1 mixtures of non-labeled (d(0)) and deuterated (d(2)) 19-ols 2 and 5 were separately incubated with human placental microsomes in the presence of NADPH under an air atmosphere, and deuterium contents of the recovered substrates and the 19-aldehyde products were determined by gas chromatography-mass spectrometry. In each experiment, the ratio of d(0) to d(2) of the recovered substrate along with that of do to all of the product were identical to the d(0) to d(2) ratio of the employed substrate irrespective of the incubation time, indicating that the 19-oxygenations of the 3-deoxy steroids 2 and 5 proceeded without a detectable isotope effect, as seen in the aromatization sequence of the natural substrate AD. (c) 2005 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2005.04.009
• 作为产物：
  描述：

  17-oxoandrost-4-en-19-al 在 硼氘化钠 、 chromium(VI) oxide 、 硫酸 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 2.77h， 生成 [19-2H]-androst-4-ene-17,19-dione
  参考文献：
  名称：

  NaBH4还原3个脱氧雄激素的19个羰基的立体化学。具有19-羟基的[19S-3H]-和[19R-3H]标记的芳香化酶抑制剂的合成。

  摘要：

  为了研究androst-4-en-17-one（1）及其5-烯异构体4的芳香化酶反应的立体化学方面，芳香化酶的竞争性抑制剂[19S-（3）H]-和[19R-（通过NaB（3）H（4）还原相应的19-醛3和6作为关键反应合成3）H]-标记的19-羟基衍生物2和5。NaB（3）H（4）还原的迄今未知的立体化学是基于氘标记的NaB（2）H（4）建立的。19-als 3和6的NaB（2）H（4）还原产物的（1）H-NMR光谱与相应的真实甾类化合物的（1）H-NMR光谱比较显示，19S-（2）H与19R-的比率对于4-烯类固醇2，（2）H分别为90:10和对于5-烯异构体5为70:30。[19S-（2）H] 19-ols的琼斯氧化，然后是未标记的NaBH（4）还原，得到相应的[19R-（2）H] 19-醇2和5（对于类固醇2为R-（2）H：S-（2）H = 90：10，对于类固醇5为70:30）。在

  DOI：

  10.1248/cpb.52.722

文献信息

• Stereochemistry of NaBH4 Reduction of a 19-Carbonyl Group of 3-Deoxy Androgens. Synthesis of [19S-3H]- and [19R-3H]-Labeled Aromatase Inhibitors Having a 19-Hydroxy Group
  作者：Mitsuteru Numazawa、Norishige Sohtome、Masao Nagaoka

  DOI：10.1248/cpb.52.722

  日期：——

  aromatase, the [19S-(3)H]- and [19R-(3)H]-labeled 19-hydroxy derivatives 2 and 5, were synthesized through NaB(3)H(4) reduction of the corresponding 19-aldehydes 3 and 6 as a key reaction. The hitherto unknown stereochemistry of the NaB(3)H(4) reduction was established based on the deuterium-labeling experiments with NaB(2)H(4). A comparison of (1)H-NMR spectra of the NaB(2)H(4) reduction products of 19-als

  为了研究androst-4-en-17-one（1）及其5-烯异构体4的芳香化酶反应的立体化学方面，芳香化酶的竞争性抑制剂[19S-（3）H]-和[19R-（通过NaB（3）H（4）还原相应的19-醛3和6作为关键反应合成3）H]-标记的19-羟基衍生物2和5。NaB（3）H（4）还原的迄今未知的立体化学是基于氘标记的NaB（2）H（4）建立的。19-als 3和6的NaB（2）H（4）还原产物的（1）H-NMR光谱与相应的真实甾类化合物的（1）H-NMR光谱比较显示，19S-（2）H与19R-的比率对于4-烯类固醇2，（2）H分别为90:10和对于5-烯异构体5为70:30。[19S-（2）H] 19-ols的琼斯氧化，然后是未标记的NaBH（4）还原，得到相应的[19R-（2）H] 19-醇2和5（对于类固醇2为R-（2）H：S-（2）H = 90：10，对于类固醇5为70:30）。在
• Gas chromatography–mass spectrometric analysis of oxidative reactions of [19,19-2H2]19-hydroxy-3-deoxy androgens by placental aromatase
  作者：Masao Nagaoka、Mitsuteru Numazawa

  DOI：10.1016/j.steroids.2005.04.009

  日期：2005.11

  Aromatase is a cytochrome P-450 enzyme complex that catalyzes the conversion of androst-4-ene-3,17-dione (AD) to estrone through three sequential oxidations of the 19-methyl group. 3-DeoxyAD (1) and its 5-ene isomer 4 are potent and good competitive aromatase inhibitors, which are converted by aromatase to the aldehyde derivatives 3 and 6, respectively, through 19-hydroxy intermediates 2 and 5, respectively. To study the deuterium isotope effect on the conversions of 19-ols 2 and 5 into the corresponding 19-als 3 and 6, we initially synthesized [19,19-H-2(2)]19-ols 2 and 5 starting from the corresponding non-labeled 19-als 3 and 6 through (NaBH4)-H-2 reduction of the 19-aldehyde group, followed by oxidation with pyridinium dichromate, and a subsequent NaB2H4 reduction. Approximately 1:1 mixtures of non-labeled (d(0)) and deuterated (d(2)) 19-ols 2 and 5 were separately incubated with human placental microsomes in the presence of NADPH under an air atmosphere, and deuterium contents of the recovered substrates and the 19-aldehyde products were determined by gas chromatography-mass spectrometry. In each experiment, the ratio of d(0) to d(2) of the recovered substrate along with that of do to all of the product were identical to the d(0) to d(2) ratio of the employed substrate irrespective of the incubation time, indicating that the 19-oxygenations of the 3-deoxy steroids 2 and 5 proceeded without a detectable isotope effect, as seen in the aromatization sequence of the natural substrate AD. (c) 2005 Elsevier Inc. All rights reserved.