雌酚酮-D2 | 56588-58-0

• 物质功能分类: 原料药 - 激素及调节内分泌功能类药 - 雌激素及孕激素类药
• 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: 雌酚酮-D2
• 中文别名: 雌酮-D2
• 英文名称: <16,16-(2)H2>estrone
• 英文别名: 16,16-di-deuterium-estra-1,3,5(10)-triene-17-one；(16,16²H2)-Oestron；16,16-dideuterio-3-hydroxy-estra-1,3,5(10)-trien-17-one；Estrone-16,16-D2；(8R,9S,13S,14S)-16,16-dideuterio-3-hydroxy-13-methyl-6,7,8,9,11,12,14,15-octahydrocyclopenta[a]phenanthren-17-one
• CAS: 56588-58-0
• 化学式: C₁₈H₂₂O₂
• 分子量: 272.356
• InChiKey: DNXHEGUUPJUMQT-XIMAIENTSA-N

物化性质

• 熔点：
  247 - 250°C (dec.)
• 溶解度：
  可溶于DMSO（少量）、甲醇（少量）

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 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：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

制备方法与用途

雌酮最初用于治疗绝经期症状、原发性闭经和激素缺乏情况。它在1950年代通过油剂注射或口服给药，当时也可以用其他雌激素类药物替代。

雌酮口服的效果较弱，因为其被吸收后会在肝脏经历首过效应，转化为雌三醇，并进一步与葡萄糖醛酸或硫酸结合形成失活的醚类化合物而排出体外。雌酮-D2则是雌酮的一种氘代化合物。

反应信息

• 作为反应物：
  描述：

  雌酚酮-D2 在 sodium tetrahydroborate 作用下， 反应 0.5h， 生成 17B-雌二醇-D2
  参考文献：
  名称：

  Mass spectrometric studies on 17β-estradiol-17-fatty acid esters: Evidence for the formation of anion-dipole intermediates

  摘要：

  AbstractThe behaviour towards low collision energy processes (eV range) of [M  H]− prepared under negative ion chemical ionization (NICI) ammonia conditions from 17β‐estradiol‐17‐fatty acid esters has been investigated. From such bifunctional compounds containing two acidic sites (i.e. phenol and ester groups), two isomeric forms (i.e. phenoxide and enolate forms) characterize the [M  H]− ion structures, whose distribution depends on the ion preparation mode. Here NICI (ammonia) provides both phenoxide and enolate forms as the [M  H]− species. This behaviour contrasts with the regioselectivity observed for proton abstraction from phenol under NICI (N2O) and fast atom bombardment conditions. Production of both phenoxide and enolate forms in NICI (ammonia) is demonstrated under NICI (ND3) conditions in which DO‐labelled [Md  H]− enolate ions are produced in a similar yield to unlabelled [Md  D]− phenoxide ions. Collisionally activated dissociation (CAD) spectra of both isomeric deprotonated molecules differ strongly by the presence of two different pairs of complementary daughter ions, suggesting that these ionic species are unconvertible. This is due to a steric hindrance effect on the long‐distance proton transfer. A mechanistic investigation on the formation of fragment ion pairs produced under CAD was performed with various deuterium‐labelled molecules. From these experiments, evidence is provided for molecular isomerizations into ion‐dipole complexes (prior to dissociation) which are structurally dependent on the initial charge location. Direct dissociation of these intermediates competes with the occurrence of exothermic proton transfer(s) yielding the formation of other isomeric intermediate forms. The orientation of these proton transfers is dictated by the relative acidities of both moieties of the complex.

  DOI：

  10.1002/oms.1210270612
• 作为产物：
  描述：

  雌酚酮 在 sodium hydroxide 作用下， 以 氘代甲醇-d 、 重水 为溶剂， 反应 24.0h， 以99%的产率得到雌酚酮-D2
  参考文献：
  名称：

  [EN] 16- AND 17- DEUTERATED ESTROGEN-3-SULFAMATES AS ESTROGENIC AGENTS
  [FR] 3-SULFAMATES D'ŒSTROGÈNES 16- ET 17-DEUTÉRÉS À TITRE D'AGENTS ŒSTROGÉNIQUES

  摘要：

  本发明涉及雌二醇的新颖衍生物，特别是雌二醇磺酸酯的氘代衍生物。本发明还涉及包含这些新颖衍生物的组合物，以及这些新颖衍生物和包含这些衍生物的组合物的用途。

  公开号：

  WO2014122480A1

文献信息

• Female sex hormone degrading bacteria and use thereof
  申请人：EBARA CORPORATION

  公开号：EP1454980A2

  公开（公告）日：2004-09-08

  The present invention provides female sex hormone degrading bacteria belonging to the genus Novosphingobium, Sphingomonas or Ochrobactrum and having at least one of the property (a) the ability to degrade at least ethynylestradiol; the property (b) the ability to degrade at least 17β-estradiol and/or estrone, and having a degradation rate constant k1 for 17β-estradiol and/or estrone of 0.05 or more; and the property (c) the ability to degrade at least 17β-estradiol and/or estrone, and having the ability to decrease the concentration of 17β-estradiol and/or estrone, contained in wastewater, to less than 10 ng/L. These bacteria can efficiently degrade various female sex hormones, including recalcitrant synthetic female sex hormones, to such very low concentrations as not to affect the environment, and can easily be cultured and proliferated.

  本发明提供属于Novosphingobium属、Sphingomonas属或Ochrobactrum属的雌性激素降解细菌，该细菌至少具有以下特性之一：(a)降解至少乙炔雌二醇的能力；(b)降解至少17β-雌二醇和/或雌酮的能力，且17β-雌二醇和/或雌酮的降解速率常数k1为0.(c) 至少能降解 17β-estradiol 和/或雌酮，并能将废水中 17β-estradiol 和/或雌酮的浓度降至 10 纳克/升以下。这些细菌能有效地降解各种雌性激素，包括难降解的合成雌性激素，降解浓度极低，不会对环境造成影响，而且易于培养和增殖。
• Estrone and estradiol metabolism in vivo in human breast cysts☆
  作者：Uma Raju、Daniel W. Sepkovic、William R. Miller、J.Michael Dixon、H.Leon Bradlow、Mortimer Levitz

  DOI：10.1016/s0039-128x(00)00184-7

  日期：2000.12

  Fibrocystic disease of the breast manifesting palpable cysts express breast cyst fluids frequently containing estrogen sulfates at concentrations far exceeding those found in sera of the patient. The study explored the potential of the breast cyst to synthesize some of these estrogen sulfates. Deuterated estrone and estradiol were synthesized and either (estradiol, 4 cases or estrone, 2 cases) was injected into a cyst. The cyst was aspirated at approximately 0, 4 and 8 h, the target being 1 ml, 50% and complete aspiration respectively. Metabolites were purified sequentially by ether extraction, enzymatic hydrolysis of estrogen conjugates, chromatography on Sephadex LH 20 and identified by gas chromatography linked to mass spectrometry. The unconjugated fraction isolated from the ether extract was subjected to the same purification and detection scheme. Among the conjugates, deuterated estrone sulfate was the major metabolite of either precursor in all studies, while estradiol sulfate was not detected in any of the 6 experiments. The sulfate fractions also yielded traces of 16 alpha -hydroxyestrone (2 studies), 4-hydroxyestrone (4 studies) and 2-hydroxyestrone (1 study). in the unconjugated fraction, one study with deuterated estradiol, 4-hydroxyestrone was obtained. In one study with deuterated estrone, traces of 2-hydroxyestrone and 16 alpha -hydroxyestrone were obtained. These novel data are significant because patients with fibrocystic disease are at slightly elevated risk for developing breast cancer and 16 alpha -hydroxyestrone and 4-hydroxyestrone are reported carcinogens. (C) 2000 Elsevier Science Inc. All rights reserved.
• Ranjith, H.; Dharmaratne, W.; Kilgore, James L., Journal of the Chemical Society. Perkin transactions I, 1993, # 13, p. 1529 - 1536
  作者：Ranjith, H.、Dharmaratne, W.、Kilgore, James L.、Roitman, Esther、Shackleton, Cedric、Caspi, Eliahu

  DOI：——

  日期：——
• 16- AND 17- DEUTERATED ESTROGEN-3-SULFAMATES AS ESTROGENIC AGENTS
  申请人：UNIVERSITY OF BATH

  公开号：US20160039866A1

  公开（公告）日：2016-02-11

  The present invention relates to novel derivatives of estradiol, in particular to deuterated derivatives of estradiol sulfamates. The present invention also relates to compositions comprising said novel derivatives, as well as to uses of said novel derivatives and compositions comprising said derivatives.