11β,21-二羟基-5β-孕甾-3,20-二酮 | 566-01-8

• 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: 11β,21-二羟基-5β-孕甾-3,20-二酮
• 中文别名: 5Β-孕甾-11Β,21-二醇-3,20-二酮
• 英文名称: 5β-dihydrocorticosterone
• 英文别名: 5beta-Dihydrocorticosterone；(5R,8S,9S,10S,11S,13S,14S,17S)-11-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-1,2,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-one
• CAS: 566-01-8
• 化学式: C₂₁H₃₂O₄
• 分子量: 348.483
• InChiKey: CTTOFMJLOGMZRN-BBWLNIHDSA-N

物化性质

• 熔点：
  127 - 134°C
• 溶解度：
  氯仿（微溶）、二氯甲烷（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  11β,21-二羟基-5β-孕甾-3,20-二酮 在 potassium phosphate 、 rabbit aldose reductase-like protein AKR₁B₁₉ 、 烟酰胺腺嘌呤双核苷酸磷酸盐 作用下， 以 甲醇 为溶剂， 生成 孕烷-20-酮,3,11,21-三羟基-,(3b,5b,11b)-
  参考文献：
  名称：

  Characterization of rabbit aldose reductase-like protein with 3β-hydroxysteroid dehydrogenase activity

  摘要：

  In this study, we isolated the cDNA for a rabbit aldose reductase-like protein that shared an 86% sequence identity to human aldo-keto reductase (AKR)(1) 1B10 and has been assigned as AKR1B19 in the AKR superfamily. The purified recombinant AKR1B19 was similar to AKR1B10 and rabbit aldose reductase (AKR1B2) in the substrate specificity for various aldehydes and alpha-dicarbonyl compounds. In contrast to AKR1B10 and AKR1B2, AKR1B19 efficiently reduced 3-keto-5 alpha/beta-dihydro-C19/C21/C24-steroids into the corresponding 3 beta-hydroxysteroids, showing K-m of 1.3-9.1 mu M and k(cat) of 1.1-7.6 min(-1). The stereospecific reduction was also observed in the metabolism of 5 alpha- and 5 beta-dihydrotestosterones in AKR1B19-overexpressing cells. The mRNA for AKR1B19 was ubiquitously expressed in rabbit tissues, and the enzyme was co-purified with 3 beta-hydroxysteroid dehydrogenase activity from the lung. Thus, AKR1B19 may function as a 3-ketoreductase, as well as a defense system against cytotoxic carbonyl compounds in rabbit tissues. The molecular determinants for the unique 3-ketoreductase activity were investigated by replacement of Phe303 and Met304 in AKR1B19 with Gln and Ser, respectively, in AKR1B10. Single and double mutations (F303Q, M304S and F303Q/M304S) significantly impaired this activity, suggesting the two residues play critical roles in recognition of the steroidal substrate. (C) 2012 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.abb.2012.07.012
• 作为产物：
  描述：

  肾上腺酮 、 氢(+1)阳离子 、 NADPH(4-) 生成 11β,21-二羟基-5β-孕甾-3,20-二酮 、 NADP⁺
  参考文献：
  名称：

  人类固醇 5β-还原酶 (AKR1D1) 的底物特异性和抑制剂分析

  摘要：

  人类类固醇 5β-还原酶（醛酮还原酶 1D1）催化 Δ(4)-酮类固醇的 C4-C5 双键的立体特异性 NADPH 依赖性还原，以产生 A/B 顺式环连接。这种顺式构型对于胆汁酸生物合成至关重要，并且在类固醇代谢中起着重要作用。该酶的生化特性尚未得到彻底研究，并且报告了相互矛盾的数据，部分原因是缺乏高度均一的蛋白质。在本研究中，我们使用 C18、C19、C21 和 C27 Δ(4)-酮类固醇系统地确定了同源人重组 AKR1D1 的底物特异性，并评估了酶的 pH 速率依赖性。我们的结果表明 AKR1D1 能有效减少在生理 pH 值下测试的所有类固醇，这表明 AKR1D1 是人类存在的所有 5β-类固醇代谢物所必需的唯一酶。如果 C11 位置未被取代，则使用 C18 至 C21 类固醇观察到底物抑制。这种结构活性关系可以通过 AKR1D1 晶体结构揭示的一个小的替代底物结合口袋的存在来解释。作为相关

  DOI：

  10.1016/j.steroids.2011.01.003

文献信息

• METHODS FOR THE PURIFICATION OF DEOXYCHOLIC ACID
  申请人：Moriarty Robert M.

  公开号：US20130137884A1

  公开（公告）日：2013-05-30

  Synthetic methods for preparing deoxycholic acid and intermediates thereof, high purity synthetic deoxycholic acid, compositions and methods of use are provided. Also, provided are processes for the synthesis of 12-keto or 12-α-hydroxy-steroids from Δ-9,11-ene, 11-keto or 11-hydroxy-β-steroids. This invention is also directed to novel compounds prepared during the synthesis. This invention is also directed to the synthesis of deoxycholic acid starting from hydrocortisone.

  提供了用于制备去氧胆酸及其中间体的合成方法，高纯度合成去氧胆酸，以及使用的组合物和方法。还提供了从 Δ-9,11-烯基，11-酮基或11-羟基-β-类固醇合成12-酮基或12-α-羟基类固醇的方法。本发明还涉及在合成过程中制备的新化合物。本发明还涉及从氢化可的松开始合成去氧胆酸的方法。
• 5 alpha reduced glucocorticoid metabolites for the treatment of inflammation
  申请人：THE UNIVERSITY OF EDINBURGH

  公开号：EP1808176A2

  公开（公告）日：2007-07-18

  The present invention relates to the modulation of glucocorticoid metabolism. In particular, the invention relates to the modulation of the functional activity of the glucocorticoid receptor by 5α reduced metabolic breakdown products of glucocorticoids.

  本发明涉及糖皮质激素代谢的调节。特别是，本发明涉及通过 5α 还原糖皮质激素的代谢分解产物来调节糖皮质激素受体的功能活性。
• Metabolite
  申请人：Walker Robert Brian

  公开号：US20050130946A1

  公开（公告）日：2005-06-16

  The present invention relates to the modulation of glucocorticoid metabolism. In particular the invention relates to the modulation of the functional activity of the glucocorticoid receptor by 5α reduced metabolic breakdown products of glucocorticoids.

  本发明涉及糖皮质激素代谢的调节。特别是本发明涉及通过 5α 还原糖皮质激素的代谢分解产物来调节糖皮质激素受体的功能活性。
• MODULATION OF ACTIVATION OF GLUCOCORTICOID RECEPTORS BY BREAKDOWN PRODUCTS OF GLUCOCORTICOIDS
  申请人：THE UNIVERSITY OF EDINBURGH

  公开号：EP1515718A2

  公开（公告）日：2005-03-23
• Metabolomics-Based Identification of Disease-Causing Agents
  申请人：Skolnick Jeffrey

  公开号：US20110246081A1

  公开（公告）日：2011-10-06

  A method, computer-readable medium, and system for identifying one or more metabolites associated with a disease, comprising: comparing gene expression data from diseased cells to gene expression data from control cells in order to deduce genes that are differentially-regulated in the diseased cells relative to the control cells; based on enzyme function and pathway data for all human metabolites that utilize the genes that are differentially-regulated in the disease cells, identifying one or more metabolites whose intracellular levels are higher or lower in diseased cells than in control cells, and thereby associating the one or more metabolites with the disease.