4-Nitroestratriene-3,17beta-diol | 6936-94-3

• 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: 4-Nitroestratriene-3,17beta-diol
• 英文别名: 13-methyl-2-nitro-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3,17-diol；4-nitro-17β-estradiol；4-nitroestradiol；2-nitroestradiol；4-nitro-estratriene-(1.3.5(10))-diol-(3.17β)；(8R)-4-Nitro-3.17c-dihydroxy-13c-methyl-(8rH.9tH.14tH)-7.8.9.11.12.13.14.15.16.17-decahydro-6H-cyclopenta[a]phenanthren；4-Nitroestra-1,3,5(10)-triene-3,17beta-diol；(8R,9S,13S,14S,17S)-13-methyl-4-nitro-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol
• CAS: 6936-94-3
• 化学式: C₁₈H₂₃NO₄
• 分子量: 317.385
• InChiKey: OMZSNIQSXZEIKB-ZHIYBZGJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  23
• 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：
  86.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-Nitroestratriene-3,17beta-diol 在 horseradish peroxidase EC 1.11.1.7 phosphate buffer 、 亚硝酸钠-15N 、 双氧水 作用下， 以 甲醇 、 水 为溶剂， 生成
  参考文献：
  名称：

  17β-Estradiol nitration by peroxidase/H2O2/NO2−: a chemical assessment

  摘要：

  Nitration of 17beta-estradiol by H2O2 and nitrite in the presence of various peroxidases, viz. horseradish peroxidase, lactoperoxidase, and peroxidase-containing homogenates from bovine uteri, was systematically investigated to assess on a chemical basis its potential relevance to the mechanisms of impairment of estrogen functions under oxidative/nitrosative stress conditions. In the presence of excess nitrite 17beta-estradiol reacted smoothly to give 2-nitroestradiol (1), 4-nitroestradiol (2), and 2,4-dinitroestradiol (3). With 10-300 muM estradiol, formation yields of 1-3 were 12-55%, but dropped to 1% or less at lower estrogen concentration, for example, 1 muM, or in plasma as the reaction medium. Time course analysis showed that 2 is the prevalent nitration product under conditions of slow generation of nitrating species, suggesting some regioselectivity for estradiol nitration at C-4, whereas 1 prevails with bolus addition of reagents, due to faster degradation of 2. Competition experiments carried out with (NO2-)-N-15 showed that 2 is about twice more susceptible to nitration than 1 as determined by N-15 NMR analysis of the resulting 3. The biological effects of 1 and 2 were preliminarily tested on in vitro bovine embryo cultures. When 1 and 2 were substituted to the standard 17beta-estradiol in the oocyte maturation, a significant decrease in both cleavage and blastocyst efficiency was observed in the case of 1 but not 2. Overall, these results suggest that estradiol nitration is a potential pathway of hormonal dysfunction and toxicity but would require elevated estrogen levels of questionable physiological relevance. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.03.036
• 作为产物：
  描述：

  雌二醇 在 bismuth nitrate pentahydrate montmorillonite KSF clay 作用下， 以 二氯甲烷 为溶剂， 以75%的产率得到4-Nitroestratriene-3,17beta-diol
  参考文献：
  名称：

  Bismuth nitrate-induced novel nitration of estradiol: An entry to new anticancer agents

  摘要：

  Direct nitration of estradiol was carried out using metal nitrates on solid surfaces under mild condition, and a combination of bismuth nitrate pentahydrate impregnated KSF clay was found to be the best reagent to synthesize 2- and 4-nitroestradiol effectively. Furthermore, various basic side chains were introduced, through O-linker at C-3, to these nitroestradiols. The ability of these derivatives to cause cytotoxicity in Estrogen Receptor (ER)-positive and ER-negative breast cancer cell lines, as well as cancer cell lines of other origins, was examined. Qualitative structure activity relationship (SAR) has also been studied. We found that a basic side chain containing either a piperidine or morpholine ring, when conjugated to 2-nitroestradiol, was particularly effective at causing cytotoxicity in each of the cancer cell lines examined. Surprisingly, this effective cytotoxicity was even seen in ER-negative breast cancer cells. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.06.010

文献信息

• Oxidative chemistry of 2-nitro and 4-nitroestradiol: Dichotomous behavior of radical intermediates and novel potential routes for oxyfunctionalization and B-ring fission of steroidal scaffolds
  作者：A PEZZELLA、P MANINI、A NAPOLITANO、O CRESCENZI、V BARONE、M DISCHIA

  DOI：10.1016/j.steroids.2005.01.006

  日期：2005.7

  9(11)-tetraene-3,12,17-triol (6). With higher concentrations of H(2)O(2), the novel secoestra-1(10),2,4-trien-9-one derivative 7 was obtained from 2. Theoretical calculations suggested that the peculiar behavior of 2 may be due to the generation of a relatively stable radical intermediate at C(9), which would then be converted to the reactive quinone methide 8. The chemistry described in this paper appears to be

  用过氧化物酶/ H（2）O（2）系统氧化4-硝基-17β-雌二醇（1）通过苯氧基自由基偶联得到对称的C（2）-连接的二聚体（3）。2-硝基17β-雌二醇（2）的相似氧化反应（其中硝基与芳环共面）产生9α-和9β-羟基-2-硝基-17β-雌二醇（4a，b）（17beta） -2-nitroestra-1（10），2,4,9（11）-丁烯-3,17-二醇（5）和（12alpha，17beta）-2-nitroestra-1（10），2,4， 9（11）-四烯-3,12,17-三醇（6）。随着更高浓度的H（2）O（2），新型secoestra-1（10），2,4-trien-9-one衍生物7从2获得。理论计算表明2的特殊行为可能是由于会在C（9）处生成相对稳定的自由基中间体，然后将其转化为反应性醌甲基化物8。
• Convenient large scale preparation of catechol estrogens
  作者：G. Stubenrauch、R. Knuppen

  DOI：10.1016/0039-128x(76)90010-6

  日期：1976.11

  2-Hydroxyestrone, 2-hydroxyestradiol-17beta, 2-hydroxy-17alpha-ethynylestradiol, 2-hydroxyestriol, 4-hydroxyestrone, 4-hydroxyestradiol-17beta, 4-hydroxy-17alpha-ethynylestradiol and 4-hydroxyestriol are prepared on a preparative scale from the corresponding aminophenols using a new inverse oxidation procedure. By the synthesis described both the 2- and 4-hydroxylated estrogens are available in high yields.
• Darstellung biochemisch interessanter Thioäther der Östrogene, II. 2-Methoxy-4-carboxymethylmercapto-östron-3-methyläther
  作者：FRIEDRICH MARKS、ELLEN KUBINYI、ERICH HECKER

  DOI：10.1515/bchm2.1968.349.2.1215

  日期：1968.1
• Nitrated estrogenic hormones
  申请人：NIEDERL JOSEPH B

  公开号：US02438819A1

  公开（公告）日：1948-03-30
• Notes: Synthesis of Nitroestradiols
  作者：Tad Patton

  DOI：10.1021/jo01093a611

  日期：1959.11