雌酮-2,4,16,16-d4 | 53866-34-5

• 物质功能分类: 化学试剂 - 氘代试剂
• 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: 雌酮-2,4,16,16-d4
• 中文别名: 雌酚酮-2,4,16,16-d4；氘代雌酮；雌激素酮-d4
• 英文名称: [2,4,16,16-2H4]estrone
• 英文别名: [2,4,16,16-D4]-estrone；Estrone-2,4,16,16-d4；(8R,9S,13S,14S)-2,4,16,16-tetradeuterio-3-hydroxy-13-methyl-6,7,8,9,11,12,14,15-octahydrocyclopenta[a]phenanthren-17-one
• CAS: 53866-34-5
• 化学式: C₁₈H₂₂O₂
• 分子量: 274.34
• InChiKey: DNXHEGUUPJUMQT-QSPUTOQOSA-N

物化性质

• 熔点：
  258-260 °C(lit.)
• 溶解度：
  氯仿（微溶，加热），DMSO（少量溶解），乙醇（微溶，超声处理）
• 稳定性/保质期：
  遵照规定使用和储存，则不会发生分解。

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

安全信息

• 危险品标志：
  T
• 安全说明：
  S22,S36/37/39,S45,S53
• 危险类别码：
  R60,R61
• WGK Germany：
  3
• 海关编码：
  28459000
• 储存条件：
  保持贮藏器密封，并将其放入一个紧密封装的容器中。储存时，请选择阴凉、干燥的地方。

制备方法与用途

雌酮-d4（E1-d4）是一种氘标记的雌酮。雌酮（E1）是一种天然产生的雌激素，主要由多种组织生成，尤其是脂肪组织。在脂肪细胞中，雄烯二酮经过芳构化过程转化为雌酮[1][2]。

反应信息

• 作为反应物：
  描述：

  雌酮-2,4,16,16-d4 在 4-二甲氨基吡啶 、 lithium aluminium deuteride 作用下， 以 四氢呋喃 、 吡啶 为溶剂， 反应 3.0h， 生成 2,4,16,16,17α-D5-estradiol-3,17-dipalmitate
  参考文献：
  名称：

  Microwave-assisted synthesis of deuterium labeled estrogen fatty acid esters

  摘要：

  Deuterated analogs of estrogen fatty acid esters are needed as internal standards for isotope dilution GC/MS analyses. We have developed a rapid and efficient synthesis for 2,4,16,16-D-4-estrone palmitate, stearate, oleate, linoleate, and linolenate and the corresponding 2,4,16,16,17(alpha-D-5-estradiol fatty acid 17-mono and 3,17-diesters using analogous fatty acid chlorides or fatty acid anhydrides and 4-(dimethylamino)pyridine under microwave irradiation. Chemoselective hydrolysis of fatty acid diesters was carried out by KOH in t-BuOH. (c) 2005 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2005.08.001
• 作为产物：
  描述：

  雌酚酮 在 氘代三氟乙酸 、 乙醇 作用下， 反应 0.17h， 以95%的产率得到雌酮-2,4,16,16-d4
  参考文献：
  名称：

  Expedient microwave deuteration of estrone in CF3COOD

  摘要：

  A rapid and efficient deuteration procedure was developed for estrone. Irradiation of estrone in CF3COOD in a microwave oven gave [2,4,16,16-H-2(4)]-estrone in 95% yield. Ultrasound and CF3COOD reflux deuterations of estrone were also studied. (C) 2002 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4039(02)00509-9

文献信息

• Profiling Endogenous Serum Estrogen and Estrogen-Glucuronides by Liquid Chromatography−Tandem Mass Spectrometry
  作者：Patrick Caron、Etienne Audet-Walsh、Johanie Lépine、Alain Bélanger、Chantal Guillemette

  DOI：10.1021/ac9019126

  日期：2009.12.15

  Estrogens, namely, 17β-estradiol (E2), are conjugated to glucuronides (G), and this metabolic conversion is part of their tissular-concentration control-mechanism. This inactivation process has been observed, in addition to the liver, in several estrogen-dependent tissues and the resulting polar metabolites are detected in circulation. We developed and validated a highly sensitive and specific mass spectrometry-based method to directly measure estrogen-G serum levels. The method uses deuterated standards but does not involve enzymatic hydrolysis, a major improvement over previous techniques. Estrone (E1), E1-sulfate, E2, the 3-G of E1, E2, 2-methoxy-E1 (2-MeOE1) and 2-methoxy-E2 (2-MeOE2), and the 17-G of E2 were measured in serum of 19 premenopausal and 10 postmenopausal healthy women. Two extractions, solid-phase and liquid−liquid, were performed to isolate the estrogens. Estrogens were then quantified by mass spectrometry in the negative MRM ion mode using an API3200 spectrometer with a turbo ionspray source. The method selectively measured estrogen glucuronides with sensitivity ≥5 pg/mL, accuracy 90−111%, and reproducibility (CV = 1.4−13.3%). The method is applicable between 5 and 1000 pg/mL. For the ovarian follicular phase, the major metabolite found was E1-3G, with E2-3G and 2-MeOE1-3G found in lesser amounts (54, 10.4, and 7.8 pg/mL, respectively) These concentrations are 2.6- to 3-fold greater than found for luteal-phase estrogens. The concentrations of E2-17G and 2-MeOE2-3G were usually less than the limit of quantification. In serum of postmenopausal women, E1-3G was the most abundant estrogen found (30.9 pg/mL). Our method profiles estrogens and estrogen-glucuronides and may represent a new tool to identify biomarkers in hormone-dependent diseases.

  雌激素，即 17β-estradiol (E2)，会与葡萄糖醛酸（G）共轭，这种代谢转换是其组织浓度控制机制的一部分。除肝脏外，在一些依赖雌激素的组织中也观察到了这种灭活过程，并在血液循环中检测到了由此产生的极性代谢物。我们开发并验证了一种基于质谱的高灵敏度和特异性方法，可直接测量血清中的雌激素-G 水平。该方法使用氚代标准，但不涉及酶水解，是对以往技术的重大改进。对 19 名绝经前和 10 名绝经后健康女性血清中的雌酮（E1）、E1-硫酸盐、E2、E1 的 3-G、E2、2-甲氧基-E1（2-MeOE1）和 2-甲氧基-E2（2-MeOE2）以及 E2 的 17-G进行了测定。通过固相和液相两种提取方法分离出雌激素。然后使用配备涡轮离子源的 API3200 光谱仪，在负 MRM 离子模式下对雌激素进行质谱定量。该方法可选择性地测定雌激素葡糖醛酸苷，灵敏度≥5 pg/mL，准确度为 90-111%，重现性良好（CV = 1.4-13.3%）。该方法适用于 5 至 1000 pg/mL。在卵巢卵泡期，发现的主要代谢物是 E1-3G，E2-3G 和 2-MeOE1-3G 的含量较少（分别为 54、10.4 和 7.8 pg/mL），这些浓度是黄体期雌激素的 2.6 至 3 倍。E2-17G 和 2-MeOE2-3G 的浓度通常低于定量限。在绝经后妇女的血清中，E1-3G 是含量最高的雌激素（30.9 pg/mL）。我们的方法能分析雌激素和雌激素-葡萄糖醛酸苷，可能是确定激素依赖性疾病生物标志物的一种新工具。
• Synthesis of estromustine, estramustine and estramustine phosphate labelled with deuterium
  作者：Danilo Giribone、Erminia Fontana

  DOI：10.1002/jlcr.809

  日期：2004.2

  The preparation of estromustine (EoM), estramustine (EaM) and estramustine phosphate (EMP) specifically labelled with deuterium is reported. A two-step, one-pot procedure based on the reaction of N,N-bis(2-chloroethyl)carbamoyl chloride with the commercially available [2,4,16,16-2H4]estrone (1) or [2,4,16,16,17-2H5]estradiol (2) afforded [2,4,16,16-2H4]estromustine (3) and [2,4,16,16,17-2H5]estramustine (4), respectively. The phosphorylation of 4 followed by hydrolysis gave [2,4,16,16,17-2H5]estramustine phosphate (5) in 65% chemical yield from 2. Copyright © 2004 John Wiley & Sons, Ltd.

  本报告介绍了用氘特异标记的雌莫司汀（EoM）、雌莫司汀（EaM）和磷酸雌莫司汀（EMP）的制备方法。在 N,N-双（2-氯乙基）氨基甲酰氯与市售 [2,4,16,16-2H4]estrone (1) 或 [2,4,16,16,17-2H5]estradiol (2) 反应的基础上，采用两步一步法分别制备出 [2,4,16,16-2H4]estromustine (3) 和 [2,4,16,16,17-2H5]estramustine (4)。4 经过磷酸化和水解后，从 2 中得到[2,4,16,16,17-2H5]雌莫司汀磷酸酯（5），化学收率为 65%。 Copyright © 2004 John Wiley & Sons, Ltd. All Rights Reserved.
• Liquid chromatography–mass spectrometry (LC–MS) of steroid hormone metabolites and its applications
  作者：Trevor M. Penning、Seon-Hwa Lee、Yi Jin、Alejandro Gutierrez、Ian A. Blair

  DOI：10.1016/j.jsbmb.2010.01.005

  日期：2010.8

  Advances in liquid chromatography-mass spectrometry (LC-MS) can be used to measure steroid hormone metabolites in vitro and in vivo. We find that LC-electrospray ionization (ESI)-MS using a LCQ ion trap mass spectrometer in the negative ion mode can be used to monitor the product profile that results from 5 alpha-dihydrotestosterone (DHT)-17 beta-glucuronide, DHT-17 beta-sulfate, and tibolone-17 beta-sulfate reduction catalyzed by human members of the aldo-keto reductase (AKR) 1C subfamily and assign kinetic constants to these reactions. We also developed a stable isotope dilution LC-electron capture atmospheric pressure chemical ionization (ECAPCI)-MS method for the quantitative analysis of estrone (El)) and its metabolites as pentafluorobenzyl (PFB) derivatives in human plasma in the attomole range. The limit of detection for E1-PFB was 740 attomole on column. Separations can be performed using normal-phase LC because ionization takes place in the gas phase rather than in solution. This permits efficient separation of the regioisomeric 2- and 4-methoxy-E1. The method was validated for the simultaneous analysis of plasma E2 and its metabolites: 2-methoxy-E2, 4-methoxy-E2, 16 alpha-hydroxy-E2, estrone (E1), 2-methoxy-E1, 4-methoxy-E1, and 16 alpha-hydroxy-E1 from 5 pg/mL to 2000 pg/mL. Our LC-MS methods have sufficient sensitivity to detect steroid hormone levels in prostate and breast tumors and should aid their molecular diagnosis and treatment. (C) 2010 Elsevier Ltd. All rights reserved.
• 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.
• Regioselective deuterium labeling of estrone and catechol estrogen metabolites
  作者：Douglas E. Stack、Justin Ritonya、Scott Jakopovic、Brittney Maloley-Lewis

  DOI：10.1016/j.steroids.2014.08.018

  日期：2014.12

  Increased exposure to estrogens and estrogen metabolites is linked with increased rates of breast, ovarian and other human cancers. Metabolism of estrogen can led to formation of electrophilic o-quinones capable of binding to DNA In order to gain insight into the mechanism of estrogen-induced DNA damage, estrone and catechol estrogens derived from estrone, have been regioselectively labeled with deuterium at the 1-position. Estrone-1-d, estrone-1,2,4-d(3), 4-hydroxyestrone-1-d and 2-hydroxyestrone-1-d have been synthesized with or without deuteriums at the 16-position. The key labeling step involves deuterated trifluoroacetic acid exchange catalyzed by t-butyl alcohol. This economical, straightforward labeling technique makes available a range of estrone compounds containing deuterium at the 1-position. (C) 2014 Elsevier Inc. All rights reserved.