androst-5-ene-17,19-dione | 157022-97-4

• 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: androst-5-ene-17,19-dione
• 英文别名: (8R,9S,10S,13S,14S)-13-methyl-17-oxo-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthrene-10-carbaldehyde
• CAS: 157022-97-4
• 化学式: C₁₉H₂₆O₂
• 分子量: 286.414
• InChiKey: DVDSCBZPGQBFFD-BGJMDTOESA-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：

  androst-5-ene-17,19-dione 在 硼氘化钠 作用下， 以 甲醇 为溶剂， 反应 9.0h， 以90%的产率得到[17α,19S-2H2]-androst-5-ene-17β,19-diol
  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：

  5-androsten-17-one 在 lead(IV) acetate 、 重铬酸吡啶 、 高氯酸 、 碘 、 calcium carbonate 、 锌 、 N-溴代乙酰胺 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 环己烷 为溶剂， 反应 5.5h， 生成 androst-5-ene-17,19-dione
  参考文献：
  名称：

  Reaction of androst-5-en-17-one with hypobromous acid and its use for synthesis of 19-oxygenated 5-ene and 4-en-6-one steroids

  摘要：

  Reaction of androst-5-en-17-one (1) with hypobromous acid using a short reaction rime (30 min) along with a careful isolation procedure gave, for the first time, the addition 5 alpha-bromo-6 beta-hydroxyandrostan-17-one (3), in 43% yield. This bromohydrin was much more reactive than 5 alpha-brormo-3 beta-acetoxy-6 beta-hydroxyandrostan-17-one (4) towards KHCO3 and HClO4. The high reactivity of compound 3 was found ro be a principal reason for the difficulty in isolating this compound the addition reaction so far. 19-Hydroxyandrost-5-en-17-one (16) and androst-5-ene-17,19-dione (18), ns well ns 19-hydroxyandrost-4-ene-6,17-dione (28) and androst-4-ene-6,17,19-trione (29), were synthesised through hypoiodite reaction of the bromohydrin 3 as a key reaction. (C) 1998 by Elsevier Science Inc.

  DOI：

  10.1016/s0039-128x(97)00136-0

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
• Synthesis of Androst-5-en-7-ones and Androsta-3,5-dien-7-ones and Their Related 7-Deoxy Analogs as Conformational and Catalytic Probes for the Active Site of Aromatase
  作者：Mitsuteru Numazawa、Ayako Mutsumi、Mii Tachibana、Kumiko Hoshi

  DOI：10.1021/jm00040a012

  日期：1994.7

  A series of androst-5-en-7-ones and androsta-3,5-dien-7-ones and their 7-deoxy derivatives, respectively, were synthesized and tested for their abilities to inhibit aromatase in human placental microsomes. All the steroids inhibited the enzyme in a competitive manner with K-i's ranging from 0.058 to 45 mu M. The inhibitory activities of 17-oxo compounds were much more potent than those of the corresponding 17 beta-alcohols in each series. Steroids having an oxygen function (hydroxy or carbonyl) at C-19 were less potent inhibitors than the corresponding parent compounds having a 19-methyl group. 3,5-Dien-7-one 24 and its 19-hydroxy and 19-oxo derivatives (12 and 13) as well as 19-oxo-5-en-7-one 3 caused a time-dependent inactivation of aromatase only in the presence of NADPH in which the k(inact) values of 19-als 3 and 13 (0.143 and 0.189 min(-1), respectively) were larger than those of the corresponding 19-methyl (23 and 24) and 19-hydroxy (1 and 12) steroids, respectively. 19-Nor-5-en-7-one 4 but not its 3,5-diene derivative 14 also inactivated the enzyme in a time-dependent manner. In contrast, 7-deoxy steroids 21 and 27, having a 19-methyl group, did not cause it. The inactivations were prevented by the substrate androstenedione, and no significant effects of L-cysteine on the inactivations were observed in each case. The results suggest that oxygenation at C-19 would be at least in part involved in the inactivations caused by the inhibitors 23 and 24. The conjugated enone structures should play a critical role in the inactivation sequences.
• Reaction of androst-5-en-17-one with hypobromous acid and its use for synthesis of 19-oxygenated 5-ene and 4-en-6-one steroids
  作者：Mitsuteru Numazawa、Keiko Yamada

  DOI：10.1016/s0039-128x(97)00136-0

  日期：1998.2

  Reaction of androst-5-en-17-one (1) with hypobromous acid using a short reaction rime (30 min) along with a careful isolation procedure gave, for the first time, the addition 5 alpha-bromo-6 beta-hydroxyandrostan-17-one (3), in 43% yield. This bromohydrin was much more reactive than 5 alpha-brormo-3 beta-acetoxy-6 beta-hydroxyandrostan-17-one (4) towards KHCO3 and HClO4. The high reactivity of compound 3 was found ro be a principal reason for the difficulty in isolating this compound the addition reaction so far. 19-Hydroxyandrost-5-en-17-one (16) and androst-5-ene-17,19-dione (18), ns well ns 19-hydroxyandrost-4-ene-6,17-dione (28) and androst-4-ene-6,17,19-trione (29), were synthesised through hypoiodite reaction of the bromohydrin 3 as a key reaction. (C) 1998 by Elsevier Science Inc.
• 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.