妊娠烯醇酮-D4 | 61574-54-7

• 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: 妊娠烯醇酮-D4
• 中文别名: 孕烯醇酮-d4
• 英文名称: <17α,21-2H4>pregnenolone
• 英文别名: 17,21,21,21-d₄-pregnenolone；pregnenolone-17α,21,21,21-d₄；pregnenolone-d₄；(d4-17,21,21,21)-pregnenolone；17,21,21,21-tetradeuterio-3β-hydroxy-pregn-5-en-20-one；17,21,21,21-Tetradeuterio-3β-hydroxy-pregn-5-en-20-on；Pregnenolone-17alpha,21,21,21-D4；2,2,2-trideuterio-1-[(3S,8S,9S,10R,13S,14S,17S)-17-deuterio-3-hydroxy-10,13-dimethyl-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-yl]ethanone
• CAS: 61574-54-7
• 化学式: C₂₁H₃₂O₂
• 分子量: 320.452
• InChiKey: ORNBQBCIOKFOEO-QVFJSNPXSA-N

物化性质

• 熔点：
  >181°C (dec.)
• 溶解度：
  氯仿（少量溶解）、乙醇（少量，超声处理）、甲醇（少量，加热）

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  妊娠烯醇酮-D4 在 羟胺 作用下， 以 水 为溶剂， 反应 0.5h， 生成
  参考文献：
  名称：

  Disturbance in sex-steroid serum profiles of cattle in response to exogenous estradiol: A screening approach to detect forbidden treatments

  摘要：

  Estradiol benzoate (EB) has been one of the most widely used estrogenic agents in animal husbandry, as a way of exogenously introducing the natural hormone estradiol-17 beta into the animal organism. Estradiol was previously employed to induce anabolic effects or reproductive improvements in cattle. However, the employment of EB in European countries has been permanently forbidden by Directive 2008/97/EC to guarantee consumers' health. Despite this prohibition, the control of estradiol-17 beta and its esters continues to be a difficult task for residue-monitoring plans in European Communities because official analyses of natural thresholds for hormones in cattle have not yet been established, leading to a lack of confirmation for any exogenous administration of natural hormones. Several researchers have worked on excretion profiles of metabolites, variation in specific hormonal ratios and metabolomic fingerprints after hormonal treatments. This research focuses on the possible existence of disturbances in the serum profile of animals treated with EB in terms of steroid sex hormones (androgens, oestrogens and progestogens), by investigating the serum levels of several of these hormones. The serum samples were collected from three groups of cows: one treated with an intramuscular injection of EB, one treated with a combination of intravaginal EB and progesterone and a control (non-treated) group. The samples have been analysed by a validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method, and 17 natural hormones were identified and quantified. Subsequently, data from the serum profiles were submitted for statistic and multivariate analysis, and it was possible to observe a manifest variation between animal groups. The obtained results can help in the development of a viable screening tool for monitoring purposes in cattle. (C) 2010 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2010.12.005
• 作为产物：
  描述：

  孕烯醇酮 在 氘代甲醇 、 1-溴-3-甲基-2-丁烯 作用下， 反应 16.0h， 以96%的产率得到妊娠烯醇酮-D4
  参考文献：
  名称：

  异戊二烯基卤化物自发转化为酸：在温和条件下无金属制备氘代化合物中的应用

  摘要：

  在这里，我们揭示了一种简单的卤化氘 (DX) 生成方法，该方法由合成化学实验室中现成的普通且廉价的试剂制成，i . e . 在温和条件下，异戊二烯基、烯丙基和炔丙基卤化物。我们设想，原位生成酸卤化氘可用于酸催化反应，并可用于有机催化氘化。本工作报告了一种无金属氘标记方法，覆盖范围广泛的底物，包括酚类化合物（即. 类黄酮和芪）、吲哚、吡咯、羰基化合物和类固醇。该方法也适用于常用药物，如洛索洛芬、氟哌啶醇、甾烷酮、黄体酮、雄烯二酮、多奈哌齐、酮咯酸、肾上腺素、可的松、孕烯醇酮和地塞米松。这项工作证明了一些氘代化合物的克级无色谱合成。这项工作提供了一种简单、清洁且无副产物的位点选择性氘代，并且氘代产物无需色谱分离即可获得。当将这些引发剂用于其他酸催化反应时，DX 的氘同位素效应可能会提供不同于使用普通酸的反应所获得的产物。虽然异戊二烯卤化物自发转化为酸的机制尚不清楚，

  DOI：

  10.1039/d1ob01275d

文献信息

• THE PREPARATION OF SOME STEROIDS CONTAINING DEUTERIUM
  作者：B. Nolin、R. Norman Jones

  DOI：10.1139/v52-087

  日期：1952.10.1

  The preparation of several deuterated steroids is described, viz.,(i) the trideuteroacetates of the following alcohols: Δ^5,7,9-estratrienol-17β;Δ^1,5:10estrienol-3-one-17 (estrone); androstanol-3a; androstanol-3β; an-drostanol-17β; pregnanol-20a; Δ⁵-pregnenol-3β -one-20; Δ⁵-pregnenol-3β -one-20-d₄-17,21; Δ⁵-cholestenol-3β; Δ-cholestadienol-3β; ergostanol-3 β; Δ¹⁴-ergostenol-3β; Δ²²-5-isoergostenol-3a.(ii) Δ⁵-pregnenol-3 β -one-20-d₃-21 acetate; Δ -pregnenol-3 β -one-20-d₄-17,21.(iii) androstanone-3-d₄,-2,4; cholestanone-3-d₄-2,4; Δ^8:14-ergostenone-3-d₄-2,4; cholestanone- 7-d₂-6; androstanone-17-d₂-16.From difficulties encountered in the preparation of cholestanone-7-d₂-6, it is inferred that 7-ketones enolize less readily than 3-, 17-, or 20-ketones.

  描述了几种氘代类固醇的制备，即：(i) 以下醇的三氘代醋酸酯：Δ^5,7,9-雌三烯醇-17β；Δ^1,5:10雌甾二烯醇-3-酮-17（雌酮）；雄甾醇-3α；雄甾醇-3β；雄甾醇-17β；孕醇-20α；Δ⁵-孕酮-3β-酮-20；Δ⁵-孕酮-3β-酮-20-二氘代-17,21；Δ⁵-胆甾醇-3β；Δ-胆甾二烯醇-3β；麦角甾醇-3β；Δ¹⁴-麦角甾醇-3β；Δ²²-5-异麦角甾醇-3α。(ii) Δ⁵-孕酮-3β-酮-20-二氘代-21 醋酸酯；Δ-孕酮-3β-酮-20-二氘代-17,21。(iii) 雄甾酮-3-二氘代,-2,4；胆甾酮-3-二氘代-2,4；Δ^8:14-麦角甾酮-3-二氘代-2,4；胆甾酮-7-二氘代-6；雄甾酮-17-二氘代-16。从制备胆甾酮-7-二氘代-6时遇到的困难推断出，7-酮不像3-、17-或20-酮那样容易发生烯醇化。
• Isotope-Labeling Studies Support the Electrophilic Compound I Iron Active Species, FeO³⁺, for the Carbon–Carbon Bond Cleavage Reaction of the Cholesterol Side-Chain Cleavage Enzyme, Cytochrome P450 11A1
  作者：Francis K. Yoshimoto、I-Ji Jung、Sandeep Goyal、Eric Gonzalez、F. Peter Guengerich

  DOI：10.1021/jacs.6b04437

  日期：2016.9.21

  hormones. Various reaction mechanisms are possible for the carbon-carbon bond cleavage step of P450 11A1, and most current proposals involve the oxoferryl active species, Compound I (FeO(3+)). Compound I can either (i) abstract an O-H hydrogen atom or (ii) be attacked by a nucleophilic hydroxy group of its substrate, 20R,22R-dihydroxycholesterol. The mechanism of this carbon-carbon bond cleavage step was tested

  细胞色素 P450 11A1 酶裂解胆固醇的 C20-C22 碳-碳键，形成孕烯醇酮，这是所有类固醇激素的第一个 21-碳前体。P450 11A1 的碳-碳键裂解步骤可能有多种反应机制，目前大多数提案都涉及 oxoferryl 活性物质，即化合物 I (FeO(3+))。化合物 I 可以 (i) 提取 OH 氢原子或 (ii) 被其底物 20R,22R-二羟基胆固醇的亲核羟基攻击。使用 (18) O 标记的分子氧和纯化的 P450 11A1 测试了该碳-碳键裂解步骤的机制。在分子氧 ((18)O2) 存在下，将 P450 11A1 与 20R,22R-二羟基胆固醇一起温育，并使用偶联分析来捕获酶产物中的不稳定 (18)O 原子（即，异己醛和孕烯醇酮）。对所得产物进行衍生化，并通过高分辨率质谱法分析 (18) O 含量。P450 11A1 显示没有将 (18)O 原子并入其碳-碳键裂解产物孕
• Akhtar, Muhammad; Corina, David L.; Miller, Sharon L., Journal of the Chemical Society. Perkin transactions I, 1994, # 3, p. 263 - 268
  作者：Akhtar, Muhammad、Corina, David L.、Miller, Sharon L.、Shyadehi, Akbar Z.、Wright, J. Neville

  DOI：——

  日期：——
• Simultaneous quantification of GABAergic 3α,5α/3α,5β neuroactive steroids in human and rat serum
  作者：Patrizia Porcu、Todd K. O’Buckley、Sarah E. Alward、Christine E. Marx、Lawrence J. Shampine、Susan S. Girdler、A. Leslie Morrow

  DOI：10.1016/j.steroids.2008.12.015

  日期：2009.4

  The 3 alpha,5 alpha- and 3 alpha,5 beta-reduced derivatives of progesterone, deoxycorticosterone, dehydroepiandrosterone and testosterone enhance GABAergic neurotransmission and produce inhibitory neurobehavioral and anti-inflammatory effects. Despite Substantial information oil the progesterone derivative (3 alpha,5 alpha)-3-hydroxypregnan-20-one (3 alpha,5 alpha-THP, allopregnanolone), the physiological significance of the other endogenous GABAergic neuroactive steroids has remained elusive. Here, we describe the validation of a method using gas chromatography-mass spectrometry to simultaneously identify serum levels of the eight 3 alpha,5 alpha- and 3 alpha,5 beta-reduced derivatives of progesterone, deoxycorticosterone, dehydroepiandrosterone and testosterone. The method shows specificity. sensitivity and enhanced throughput compared to other methods already available for neuroactive steroid quantification. Administration of pregnenolone to rats and progesterone to women produced selective effects on the 3 alpha,5 alpha- and 3 alpha,5 beta-reduced neuroactive steroids, indicating differential regulation of their biosynthetic pathways. Pregnenolone administration increased serum levels of 3 alpha,5 alpha-THP (+1488%, p<0.001), (3 alpha,5 alpha)-3,21-dihydroxypregnan-20-one (3 alpha,5 alpha-THDOC, +205%, p<0.01), (3 alpha,5 alpha)-3-hydroxyandrostan-17-one (3 alpha,5 alpha-A, +216%, p<0.001), (3 alpha,5 alpha,17 beta)-androstane-3,17-diol (3 alpha,5 alpha-A-diol, +190%, p<0.01). (3 alpha,5 beta)-3-hydroxypregnan-20-one (3 alpha,5 beta-THP) and (3 alpha,5 beta)-3-hydroxyandrostan-17-one (3 alpha,5 beta-A) were not altered, while (3 alpha,5 beta)-3,21-dihydroxypregnan-20-one (3 alpha,5 beta-THDOC) and (3 alpha,5 beta,17 beta)-androstane-3,17-diol (3 alpha,5 beta-A-diol) were increased from undetectable levels to 271 +/- 100 and 2.4 +/- 0.9 pg +/- SEM, respectively (5/8 rats). Progesterone administration increased serum levels of 3 alpha,5 beta-THP (+1806%, p<0.0001), 3 alpha,5 beta-THP (+575%, p<0.001), 3 alpha,5 beta-THDOC (+309%, p<0.001). 3 alpha,5 beta-THDOC levels were increased by 307%, although this increase was not significant because this steroid was detected only in 3/16 control Subjects. Levels of 3 alpha,5 alpha-A, 3 alpha,5 beta-A and pregnenolone were not altered. This method can be used to investigate the physiological and pathological role of neuroactive steroids and to develop bioinarkers and new therapeutics for neurological and psychiatric disorders. (C) 2009 Elsevier Inc. All rights reserved.