2,3-雌酮 O-苯醌 | 40551-33-5

• 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: 2,3-雌酮 O-苯醌
• 中文别名: 2,3-雌酮O-苯醌
• 英文名称: 2,3-estrogen o-quinone
• 英文别名: Estrone-2,3-quinone；estrone 2,3-quinone；Estra-1(10),4-diene-2,3,17-trione；(8R,9S,13S,14S)-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-2,3,17-trione
• CAS: 40551-33-5
• 化学式: C₁₈H₂₀O₃
• 分子量: 284.355
• InChiKey: WFPLOQDPWXNOST-JPVZDGGYSA-N

物化性质

• 沸点：
  483.4±45.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 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：

  2,3-雌酮 O-苯醌 以 乙腈 为溶剂， 生成 estron quinone methide
  参考文献：
  名称：

  Molecular Characteristics of Catechol Estrogen Quinones in Reactions with Deoxyribonucleosides

  摘要：

  Estrogens can have two roles in the induction of cancer: stimulating proliferation of cells by receptor-mediated processes, and generating electrophilic species that can covalently bind to DNA. The latter role is thought to proceed through catechol estrogen metabolites, which can be oxidized to o-quinones that bind to DNA. Four estrogen-deoxyribonucleoside adducts were synthesized by reaction of estrone 3,4-quinone (E(1)-3,4-Q), 17 beta-estradiol 3,4-quinone (E(2)-3,4-Q), or estrone 2,3-quinone (E(1)-2,3-Q) with deoxyguanosine (dG) or deoxyadenosine (dA) in CH3CO2H/H2O (1:1). Reaction of E(1)-3,4-Q or E(2)-3,4-Q with dG produced specifically 7-[4-hydroxyestradiol-1(alpha,beta)-yl]guanine (4-OHE(1)-1(alpha,beta)-N7Gua) or 7-[4-hydroxyestradiol-1(alpha,beta)-yl]-guanine (4-OHE(2)-1(alpha,beta)-N7Gua), respectively, in 40% yield, with loss of deoxyribose. These two quinones did not react with dA, deoxycytidine, or thymidine. When E(1)-2,3-Q was reacted with dG or dA, N-2-(2 -hydroxyestron-6-yl)deoxyguanosine (2-OHE(1)-6-N(2)dG, 10% yield) and N-6-(2-hydroxyestron-6-yl)deoxyadenosine (2-OHE(1)-6-N(6)dA, 80% yield), respectively, were formed. These adducts provide insight into the type of DNA damage that can be caused by o-quinones of the catechol estrogens. The estrogen 3,4-quinones are expected to produce depurinating guanine adducts that are lost from DNA, generating apurinic sites, whereas the 2,3-quinones would form stable adducts that remain in DNA, unless repaired. The adducts reported here will be used as references in studies to elucidate the structure of estrogen adducts in biological systems.

  DOI：

  10.1021/tx960002q
• 作为产物：
  描述：

  2-羟基雌酚酮 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 乙腈 为溶剂， 反应 0.17h， 生成 2,3-雌酮 O-苯醌
  参考文献：
  名称：

  大鼠肝脏微粒体中雌酮及其邻苯二酚代谢物对醌-谷胱甘肽偶联物的生物激活。

  摘要：

  尽管雌激素的致癌作用主要归因于激素特性，但是人们对雌激素通过与细胞大分子结合而起化学致癌作用感兴趣。在本研究中，我们探讨了影响P450催化由2-羟基雌酮（2-OHE）和4-羟基雌酮（4 -OHE）以及大鼠肝微粒体中的雌酮。捕获最初形成的邻醌作为它们的GSH偶联物，将其分离并通过HPLC和电喷雾MS检测进行表征。从2-OHE-o-醌中观察到两个单-GSH缀合物，以及其中GSH已经两次添加到产生二-GSH缀合物的分子中的缀合物。4-OHE-邻醌仅产生一个单-GSH加合物以及一个双-GSH加合物。2-OHE和4-OHE都是P450的优良底物，它们分别以雌酮的生成率94和40倍生成邻醌GSH加合物。在异常低的浓度（P450 / mL为0.2 nmol）下，2-OHE而不是4-OHE饱和的P450可能是由于在酶的活性位点形成的邻醌的稳定性不同。初步数据表明2-OHE和4-OHE的邻醌都可以异构化为醌甲基化物（4-烷基-2

  DOI：

  10.1021/tx950178c

文献信息

• Synthesis of N-acetylcysteine conjugates of catechol estrogens
  作者：Emako Suzuki、Ryo Iwasaki、Junichi Goto、Yasuhiko Matsuki、Toshio Nambara

  DOI：10.1016/0039-128x(95)00232-f

  日期：1996.5

  The synthesis of N-acetylcysteine conjugates of 2-hydroxyestrone (2-OHE1) and 4-hydroxyestrone (4-OHE1) is described. The reaction of estrone 2,3-quinone with N-acetylcysteine provided 2-OHE1 and its C-4 and C-1 thioether conjugates in a ratio of 1:1, while estrone 3,4-quinone with N-acetylcysteine gave 4-OHE1 and its C-2 thioether conjugate as a sole product. Their structures were characterized by

  描述了2-羟基雌酮（2-OHE1）和4-羟基雌酮（4-OHE1）的N-乙酰半胱氨酸缀合物的合成。雌酮2,3-醌与N-乙酰半胱氨酸的反应提供了2-OHE1及其C-4和C-1硫醚共轭物，比例为1：1，而雌酮3,4-醌与N-乙酰半胱氨酸的比例为4- OHE1及其C-2硫醚共轭物是唯一产品。通过检查NMR光谱，化学衍生化（甲基化和乙酰化），并与4-溴雌酮2,3-醌或2-溴雌酮3,4-醌对N-乙酰半胱氨酸的反应性进行比较来表征它们的结构。
• Oxidative Transformation of 2-Hydroxyestrone. Stability and Reactivity of 2,3-Estrone Quinone and Its Relationship to Estrogen Carcinogenicity
  作者：Katmerka Tabakovic、William B. Gleason、William H. Ojala、Yusuf J. Abul-Hajj

  DOI：10.1021/tx950205z

  日期：1996.1.1

  (thiol, imidazole, amino, phenolate, and acetoxy) to give Michael addition products. These results support the possible involvement of 3,4-catechol/quinone estrogens in estrogen's carcinogenicity. To explain the decreased carcinogenicity of 2-hydroxyestrogens, the reactions of 2,3-estrone quinone (2,3-EQ) with nucleophiles were investigated. Reactions of 4-methylimidazole with 2,3-EQ gave a complex mixture

  雌激素在啮齿动物和人类中的致癌性归因于细胞大分子的烷基化和/或氧化还原循环，活性自由基的产生以及DNA损伤。导致形成儿茶酚雌激素的雌二醇的代谢活化被认为是其遗传毒性作用的先决条件。4-羟基雌二醇，虽然不是2-羟基雌二醇，但是是仓鼠肿瘤的有效诱导剂。先前的研究表明3,4-雌酮醌可以进行氧化还原循环，并能够诱导MCF-7乳腺癌细胞中的单链DNA断裂，并且可以与各种亲核试剂（硫醇，咪唑，氨基，酚盐和乙酰氧基）制得迈克尔加成产物。这些结果支持3，4-邻苯二酚/醌雌激素可能与雌激素的致癌性有关。为了解释2-羟基雌激素降低的致癌性，研究了2,3-雌酮醌（2,3-EQ）与亲核试剂的反应。4-甲基咪唑与2,3-EQ的反应产生了复杂的产物混合物，导致形成儿茶酚，CO二聚产物和被确定为1-（4-甲基咪唑）-2的1,6-Michael加成产物-羟基雌酮。2,3-EQ在弱碱性条件下与酚酸乙酯或乙酸酯的反应生成了几
• Adduction of catechol estrogens to nucleosides
  作者：Isabelle Jouanin、Laurent Debrauwer、Gwénola Fauglas、Alain Paris、Estelle Rathahao

  DOI：10.1016/s0039-128x(02)00070-3

  日期：2002.12

  adducts and deglycosylated adducts are formed, and therefore formation of stable adducts on DNA as well as the loss of purines from the DNA strands could be possible. MS(2) and MS(3) experiments prove to be relevant for further structural determinations, enabling in some cases the elucidation of the regiochemistry of adduction on the A and B rings of the steroid moiety.

  我们报告了由脱氧核苷（脱氧腺苷、脱氧鸟苷、脱氧胞苷和 5-甲基脱氧胞苷）与雌酮、雌二醇-17beta 和雌二醇-17 α 的儿茶酚雌激素 (CE) 加成而产生的产物的形成、检测、定量和结构表征。通过将儿茶酚氧化成醌并随后在酸性介质中与脱氧核苷进行迈克尔型反应，在一锅合成中获得粗产物。在所有实验中，在 HPLC 分离 (LC/ESI/MS(n)) 后，通过电喷雾电离质谱分析检测加合物。两种嘧啶脱氧胞苷和 5-甲基脱氧胞苷仅产生脱氧核苷的 CE 加合物，这对应于 DNA 上的稳定加合物。对于嘌呤，结果取决于使用的 CE（2,3- 或 3,4-儿茶酚），碳 17（雌酮的酮，雌二醇的 α 和β 异构体的醇）和嘌呤本身（脱氧腺苷或脱氧鸟苷）的功能和构型。稳定加合物和去糖基化加合物都形成，因此在 DNA 上形成稳定加合物以及从 DNA 链中丢失嘌呤是可能的。MS(2) 和 MS(3) 实验证明与进一步
• Assay of labile estrogen o-quinones, potent carcinogenic molecular species, by high performance liquid chromatography–electrospray ionization tandem mass spectrometry with phenazine derivatization
  作者：Kouwa Yamashita、Akina Masuda、Yuka Hoshino、Sachiko Komatsu、Mitsuteru Numazawa

  DOI：10.1016/j.jsbmb.2010.02.016

  日期：2010.4

  A sensitive and selective assay method for labile estrogen o-quinones, estrone (E-1)-2,3-quinone (Q), E-1-3,4-Q, estrachol (E-2)-2,3-Q and E-2-3,4-Q based on the use of phenazine (Phz) derivatization with o-phenylenediamine and high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was described The Phz derivatives of four estrogen o-quinones were purified by solid phase extraction and analyzed by HPLC-ESI-MS/MS The protonated molecule was observed as a base peak for all Phz derivatives in their ESI-mass spectra (positive mode) In multiple reaction monitoring, the transition from [M+H](+) to m/z 231 was chosen for quantification Calibration curves for the o-quinones were obtained using standard catechol estrogens after sodium metaperiodate treatment and Phz derivatization Using this method, these four estrogen o-quinones were analyzed with the limit of quantification of 5 ng/ml in acetonitrile (MeCN)-blank matrix (1 4, v/v), respectively, on a basis of the weight of catechol estrogens Assay accuracy and precision for four estrogen o-quinones were 896-113 0% and 3 1-12.6% (5, 125 and 2000 ng/ml in MeCN-blank matrix) Applications of this method enabled to determine the catalytic activities on hydroxylation and subsequent oxidation of E-1 and E2 of Mushroom tyrosinase and rat liver microsomal fraction It was confirmed by this method that tyrosinase exhibited 2- and 4-hydroxylation and further oxidation activities for catechols in the ring-A of estrogens. Whereas rat liver microsomal fraction possessed only 2- and 4-hydroxylation activities, and further oxidation activity for catechol estrogens was low (C) 2010 Elsevier Ltd All rights reserved.
• Zhang, Qiang; Tu, Tingting; D'Avignon, D. Andrea, Journal of the American Chemical Society, 2009, vol. 131, p. 1067 - 1076
  作者：Zhang, Qiang、Tu, Tingting、D'Avignon, D. Andrea、Gross, Michael L.

  DOI：——

  日期：——