5-androsten-7,17-dione-3β-ol ethylene ketal tert-butyldimethylsilyl ether | 202415-77-8

• 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: 5-androsten-7,17-dione-3β-ol ethylene ketal tert-butyldimethylsilyl ether
• 英文别名: 3β-(t-butyldimethylsilyloxy)-17,17-ethylenedioxyandrost-5-en-7-one；(3'S,8'R,9'S,10'R,13'S,14'S)-3'-[tert-butyl(dimethyl)silyl]oxy-10',13'-dimethylspiro[1,3-dioxolane-2,17'-2,3,4,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene]-7'-one
• CAS: 202415-77-8
• 化学式: C₂₇H₄₄O₄Si
• 分子量: 460.729
• InChiKey: KWXKCOWEWNAXMJ-CRJBWFSKSA-N

物化性质

• 熔点：
  224-226 °C
• 沸点：
  520.1±50.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.26
• 重原子数：
  32
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-androsten-7,17-dione-3β-ol ethylene ketal tert-butyldimethylsilyl ether 在 盐酸 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 7-酮基去氢表雄酮
  参考文献：
  名称：

  Anti-proliferative action of endogenous dehydroepiandrosterone metabolites on human cancer cell lines

  摘要：

  Dehydroepiandrosterone (DHEA) is a naturally occurring steroid synthesized in the adrenal cortex, gonads, brain, and gastrointestinal tract, and it is known to have chemopreventive and anti-proliferative actions on tumors. These effects are considered to be induced by the inhibition of glucose-6-phosphate dehydrogenase (G6PD) and/or HMG-CoA reductase (HMGR) activities. The present study was undertaken to investigate whether endogenous DHEA metabolites, i.e. DHEA-sulfate, 7-oxygenated DHEA derivatives, androsterone, epiandrosterone, and etiocholanolone, have anti-proliferative effects on cancer cells and to clarify which enzyme, G6PD or HMGR, is responsible for growth inhibition. Growth of Hep G2, Caco-2, and HT-29 cells, evaluated by 3-[4,5-dimethylthiazol]-2yl-2,5-diphenyl tetrazolium bromide (MTT) and bromodeoxyuridine incorporation assays, was time- and dose-dependently inhibited by addition of all DHEA-related steroids we tested. In particular, the growth inhibition due to etiocholanolone was considerably greater than that caused by DHEA in all cell lines. The suppression of growth of the incubated steroids was not correlated with the inhibition of G6PD (r = -0.031, n = 9, NS) or HMGR (r = 0.219, n = 9, NS) activities. The addition of deoxyribonucleosides or mevalonolactone to the medium did not overcome the inhibition of growth induced by DHEA or etiocholanolone, while growth suppression by DHEA was partially prevented by the addition of ribonucleosides. These results demonstrate that endogenous DHEA metabolites also have an anti-proliferative action that is not induced by inhibiting G6PD or HMGR activity alone. These non-androgenic DHEA metabolites may serve as chemopreventive or anti-proliferative therapies. (C) 2002 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(02)00117-4
• 作为产物：
  描述：

  去氢表雄酮 在 咪唑 、 叔丁基过氧化氢 、 ruthenium(III) chloride trihydrate 、 对甲苯磺酸 作用下， 以 二氯甲烷 、 环己烷 、 水 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 66.0h， 生成 5-androsten-7,17-dione-3β-ol ethylene ketal tert-butyldimethylsilyl ether
  参考文献：
  名称：

  Synthetic studies on the indane SHIP1 agonist AQX-1125

  摘要：

  开发了一种新的基于茚烷的SHIP1激动剂AQX-1125的合成方法。测试AQX-1125和一些类似物提供了有关药效团和生物活性的信息。

  DOI：

  10.1039/d2ob00555g

文献信息

• SYNTHESIS OF A SUBSTITUTED INDENE DERIVATIVE
  申请人：AQUINOX PHARMACEUTICALS (CANADA) INC.

  公开号：US20170204048A1

  公开（公告）日：2017-07-20

  This invention is directed to methods of preparing AQX-1125 having the formula: This invention is also directed to intermediates utilized in the methods of preparing AQX-1125.

  这项发明涉及制备具有分子式AQX-1125的方法。该发明还涉及用于制备AQX-1125的中间体。
• Efficient Synthesis of IPL576,092:  A Novel Anti-Asthma Agent
  作者：Yaping Shen、David L. Burgoyne

  DOI：10.1021/jo0108717

  日期：2002.5.1

  of the novel anti-asthma agent IRL576,092 (2) is described. The synthetic route developed involves stereoselective 1,2-reduction of the enone carbonyl functionality of 6 and subsequent hydroboration as the key steps. Starting from the commercially available 5-androsten-3beta-ol-17-one 3, this approach affords IPL576,092 (2) in nine steps with overall yields of 25%, employing a limited number of chromatographic

  描述了新型抗哮喘药IRL576,092（2）的对映体合成。所开发的合成途径涉及关键步骤，即立体选择性地还原6的烯酮羰基官能团，然后进行硼氢化。从市售的5-androsten-3beta-ol-17-one 3开始，采用有限数量的色谱步骤，该方法分9个步骤提供IPL576,092（2），总产率为25％。
• Simultaneous determination of dehydroepiandrosterone and its 7-oxygenated metabolites in human serum by high-resolution gas chromatography–mass spectrometry
  作者：Yasushi Matsuzaki、Shigemasa Yoshida、Akira Honda、Teruo Miyazaki、Naomi Tanaka、Aya Takagiwa、Yoshinori Fujimoto、Hiroshi Miyazaki

  DOI：10.1016/j.steroids.2004.08.003

  日期：2004.12

  A highly sensitive and specific method has been developed for the simultaneous measurement of free (unconjugated) or sulfate-conjugated forms of dehydroepiandrosterome (DHEA), 7alpha-hydroxy-DHEA (7alpha-OH-DHEA), 7beta-hydroxy-DHEA (7beta-OH-DHEA), and 7-oxo-DHEA (7-oxo-DHEA) in human serum. This method is based upon a stable isotope-dilution technique by gas chromatography-selected-ion monitormg mass spectrometry. Free steroids were extracted from serum with an organic solvent and the sulfate-conjugated steroids remained in aqueous phase. Free steroids were purified by solid-phase extraction, while sulfate-conjugated steroids were hydrolyzed by sulfatase and deconjugated steroids were purified by solid-phase extractions. The extracts were treated with O-methylhydroxylamine hydrochloride and were subsequently dimethylisopropylsilylated. The resulting methyloxime-dimethylisopropylsilyl (MO-DMIPS) ether derivatives were quantified by gas chromatography-selected-ion monitoring mass spectrometry in a high-resolution mode. The detection limits of MO-DMIPS ether derivatives of DHEA, 7alpha-OH-DHEA, 7beta-OH-DHEA and 7-oxo-DHEA were 1.0, 0.5, 0.5 and 2.0pg, respectively. Coefficients of variation between samples ranged from 10.6 to 22.9% for free 7-oxygenated DHEA to less than 10% for DHEA and sulfate-conjugated 7-oxygenated DHEA. The concentrations of these steroids were measured in 18 sera samples from healthy volunteers (9 males and 9 females; aged 23-78 years). Free DHEA, 7alpha-OH-DHEA, 7beta-OH-DHEA and 7-oxo-DHEA levels ranged between 0.21-3.55, 0.001-0.194, 0.003-0.481, and 0.000-0.077 ng/ml, respectively, and the sulfate-conjugated steroid levels of these metabolites ranged between 253-4681, 0.082-3.001, 0.008-0.903, and 0.107-0.803 ng/ml, respectively. The free DHEA-related steroid concentrations were much lower than those previously measured by RIA and low-resolution GC-MS. The present method made it possible to determine simultaneously serum DHEA-related steroid levels with sufficient sensitivity and accuracy. (C) 2004 Elsevier Inc. All rights reserved.
• J. Org. Chem. 2002, 67, 3908-3910
  作者：

  DOI：——

  日期：——
• Anti-proliferative action of endogenous dehydroepiandrosterone metabolites on human cancer cell lines
  作者：Shigemasa Yoshida、Akira Honda、Yasushi Matsuzaki、Sugano Fukushima、Naomi Tanaka、Aya Takagiwa、Yoshinori Fujimoto、Hiroshi Miyazaki、Gerald Salen

  DOI：10.1016/s0039-128x(02)00117-4

  日期：2003.1

  Dehydroepiandrosterone (DHEA) is a naturally occurring steroid synthesized in the adrenal cortex, gonads, brain, and gastrointestinal tract, and it is known to have chemopreventive and anti-proliferative actions on tumors. These effects are considered to be induced by the inhibition of glucose-6-phosphate dehydrogenase (G6PD) and/or HMG-CoA reductase (HMGR) activities. The present study was undertaken to investigate whether endogenous DHEA metabolites, i.e. DHEA-sulfate, 7-oxygenated DHEA derivatives, androsterone, epiandrosterone, and etiocholanolone, have anti-proliferative effects on cancer cells and to clarify which enzyme, G6PD or HMGR, is responsible for growth inhibition. Growth of Hep G2, Caco-2, and HT-29 cells, evaluated by 3-[4,5-dimethylthiazol]-2yl-2,5-diphenyl tetrazolium bromide (MTT) and bromodeoxyuridine incorporation assays, was time- and dose-dependently inhibited by addition of all DHEA-related steroids we tested. In particular, the growth inhibition due to etiocholanolone was considerably greater than that caused by DHEA in all cell lines. The suppression of growth of the incubated steroids was not correlated with the inhibition of G6PD (r = -0.031, n = 9, NS) or HMGR (r = 0.219, n = 9, NS) activities. The addition of deoxyribonucleosides or mevalonolactone to the medium did not overcome the inhibition of growth induced by DHEA or etiocholanolone, while growth suppression by DHEA was partially prevented by the addition of ribonucleosides. These results demonstrate that endogenous DHEA metabolites also have an anti-proliferative action that is not induced by inhibiting G6PD or HMGR activity alone. These non-androgenic DHEA metabolites may serve as chemopreventive or anti-proliferative therapies. (C) 2002 Elsevier Science Inc. All rights reserved.