17β-Estradiol-3,4-quinone | 144082-88-2

• 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: 17β-Estradiol-3,4-quinone
• 英文别名: 17β-estradiol 3,4-quinone；estradiol-3,4-quinone；(8R,9S,13S,14S,17S)-17-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,4-dione
• CAS: 144082-88-2
• 化学式: C₁₈H₂₂O₃
• 分子量: 286.371
• InChiKey: XVPUMLOTNZVTSL-ZHIYBZGJSA-N

物化性质

• 沸点：
  472.2±45.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  17β-Estradiol-3,4-quinone 在 碳酸氢钠 作用下， 以 phosphate buffer 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 4-OHE₂-1-N7Gua-dipyrene adduct
  参考文献：
  名称：

  荧光标记儿茶酚雌激素3,4-醌衍生的N7鸟嘌呤加合物的光谱表征及其在大鼠乳腺组织中的鉴定。

  摘要：

  雌酮（E1）和雌二醇（E2）的致癌性4-羟基邻苯二酚雌激素（CE）氧化为儿茶酚雌激素3,4-醌（CE-3,4-Q）导致亲电子中间体与DNA共价结合形成去嘌呤加合物[Cavalieri等。（1997年）过程。Natl。学院 科学 USA 94，10937]。这些DNA加合物4-OHE1-1-N7Gua和4-OHE2-1-N7Gua不发荧光。为了利用激光激发的荧光方法，用荧光标记物标记儿茶酚雌激素衍生的代谢产物和加合物。4-OHEi-1-N7Gua加合物标准品（i = 1、2）和4-OHEi代谢物已用1-苯磺酸磺酰氯衍生化，并通过低温光谱法在非缩窄和缩窄条件下进行了研究。分子建模研究有助于解释荧光光谱；4-OHE2-1-N7Gua-dipyrene加合物和4-OHE2-dipyrene代谢物的高能效结构揭示了独特的构象，与荧光数据相符，表明labels标记与鸟嘌呤和/或芳香族化合物具有显着的p

  DOI：

  10.1021/tx980119+
• 作为产物：
  描述：

  4-羟雌二醇 在 manganese(IV) oxide 作用下， 以 乙腈 为溶剂， 反应 0.17h， 生成 17β-Estradiol-3,4-quinone
  参考文献：
  名称：

  儿茶酚雌激素与核苷的加成

  摘要：

  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

  DOI：

  10.1016/s0039-128x(02)00070-3

文献信息

• 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.
• Synthesis and Structure Elucidation of Estrogen Quinones Conjugated with Cysteine, <i>N</i>-Acetylcysteine, and Glutathione
  作者：Kai Cao、Douglas E. Stack、Ragulan Ramanathan、Michael L. Gross、Eleanor G. Rogan、Ercole L. Cavalieri

  DOI：10.1021/tx9702291

  日期：1998.8.1

  Catechol estrogen quinones (CE-Q) have been implicated as ultimate carcinogenic metabolites in estrogen-induced carcinogenesis. CE-Q may covalently bind to DNA to initiate cancer. These quinones can also be conjugated with glutathione, a reaction that prevents damage to DNA by CE-Q. The glutathione conjugates are then catabolized through mercapturic acid biosynthesis to cysteine and N-acetylcysteine conjugates. This may be the most important detoxification pathway of CE-Q. The chemical synthesis and characterization of these conjugates are the first essential steps to better understand their function in biological systems. Eighteen conjugates were synthesized by reaction of estrone-3,4-quinone (E-1-3,4-Q), estradiol-3,4-quinone (E-2-3,4-Q), estrone-2,3-quinone (E-1-2,3-Q), or estradiol-2,3-quinone (E-2-2,3-Q) with various sulfur: nucleophiles, RSH, in which R is the cysteine, N-acetylcysteine, or glutathione moiety. Reactions of E-1-3,4-Q and E-2-3,4-Q produce regiospecifically 4-OHE1-2-SR and 4-OHE2-2-SR, respectively, in almost quantitative yield. E-1-2,3-Q and E-2-2,3-Q react regioselectively and quantitatively to form S-OHE1(E-2)-1-SR and 8-OHE1(E-2)-4-SR, in which the l-isomers are always the major products. The ratio between 1 and 4 isomers is 3.5 for cysteine, 2.7 for N-acetylcysteine, and 2.5 for glutathione. The synthesized conjugates will be used as standards in the identification of these compounds formed in biological systems.
• Molecular Characteristics of Catechol Estrogen Quinones in Reactions with Deoxyribonucleosides
  作者：Douglas E. Stack、Jaeman Byun、Michael L. Gross、Eleanor G. Rogan、Ercole L. Cavalieri

  DOI：10.1021/tx960002q

  日期：1996.1.1

  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.
• Slow loss of deoxyribose from the N7deoxyguanosine adducts of estradiol-3,4-quinone and hexestrol-3′,4′-quinone.
  作者：Muhammad Saeed、Muhammad Zahid、Sandra J. Gunselman、Eleanor Rogan、Ercole Cavalieri

  DOI：10.1016/j.steroids.2004.09.011

  日期：2005.1

  A variety of evidence has been obtained that estrogens are weak tumor initiators. A major step in the multi-stage process leading to tumor initiation involves metabolic formation of 4-catechol estrogens from estradiol (E,) and/or estrone and further oxidation of the catechol estrogens to the corresponding catechol estrogen quinones. The electrophilic catechol quinones react with DNA mostly at the N-3 of adenine (Ade) and N-7 of guanine (Gua) by 1,4-Michael addition to form depurinating adducts. The N3Ade adducts depurinate instantaneously, whereas the N7Gua adducts depurinate with a half-life of several hours. Only the apurinic sites generated in the DNA by the rapidly depurinatingN3Ade adducts appear to produce mutations by error-prone repair. Analogously to the catechol estrogen-3.4-quinones, the synthetic nonsteroidal estrogen hexestrol- 3',4'-quinone (HES-3',4'-Q) reacts with DNA at the N-3 of Ade and N-7 of Gua to form deputinating adducts. We report here an additional similarity between the natural estrogen E-2 and the synthetic estrogen HES, namely, the slow loss of deoxyribose from the N7deoxyguanosine (N7dG) adducts formed by reaction of E-2-3.4-Q or HES-3'.4'-Q with dG. The half-life of the loss of deoxyribose from the N7dG adducts to form the corresponding 4-OHE2-I-N7Gua and 3'-OH-HES-6'-N7Gua is 6 or 8 h, respectively. The slow cleavage of this glycosyl bond in DNA seems to limit the ability of these adducts to induce mutations. (C) 2004 Elsevier Inc. All rights reserved.
• Spectral Characterization of Fluorescently Labeled Catechol Estrogen 3,4-Quinone-Derived N7 Guanine Adducts and Their Identification in Rat Mammary Gland Tissue
  作者：Ryszard Jankowiak、Dan Zamzow、Douglas E. Stack、Rosa Todorovic、Ercole L. Cavalieri、Gerald J. Small

  DOI：10.1021/tx980119+

  日期：1998.11.1

  Molecular modeling studies assisted in interpretation of the fluorescence spectra; energetically favored structures of the 4-OHE2-1-N7Gua-dipyrene adduct and 4-OHE2-dipyrene metabolite reveal unique conformations which, in agreement with fluorescence data, show a significant pi-pi interaction of pyrene labels with guanine and/or the aromatic ring of catechol estrogen. The conformation obtained for the

  雌酮（E1）和雌二醇（E2）的致癌性4-羟基邻苯二酚雌激素（CE）氧化为儿茶酚雌激素3,4-醌（CE-3,4-Q）导致亲电子中间体与DNA共价结合形成去嘌呤加合物[Cavalieri等。（1997年）过程。Natl。学院 科学 USA 94，10937]。这些DNA加合物4-OHE1-1-N7Gua和4-OHE2-1-N7Gua不发荧光。为了利用激光激发的荧光方法，用荧光标记物标记儿茶酚雌激素衍生的代谢产物和加合物。4-OHEi-1-N7Gua加合物标准品（i = 1、2）和4-OHEi代谢物已用1-苯磺酸磺酰氯衍生化，并通过低温光谱法在非缩窄和缩窄条件下进行了研究。分子建模研究有助于解释荧光光谱；4-OHE2-1-N7Gua-dipyrene加合物和4-OHE2-dipyrene代谢物的高能效结构揭示了独特的构象，与荧光数据相符，表明labels标记与鸟嘌呤和/或芳香族化合物具有显着的p