(25R)-cholest-5-ene-3β,7α,26-triol | 144300-24-3

• 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: (25R)-cholest-5-ene-3β,7α,26-triol
• 英文别名: 7alpha,27-OHC；(25R)-cholest-5-ene-3beta,7alpha,26-triol；(3S,7S,8S,9S,10R,13R,14S,17R)-17-[(2R,6R)-7-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-3,7-diol
• CAS: 144300-24-3
• 化学式: C₂₇H₄₆O₃
• 分子量: 418.66
• InChiKey: RXMHNAKZMGJANZ-GNENNHQYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  60.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (25R)-cholest-5-ene-3β,7α,26-triol 在 TES buffer 、 catalase 、 cholesterol oxidase 作用下， 以 various solvent(s) 为溶剂， 以90%的产率得到(25R)-7α,26-dihydroxycholest-4-en-3-one
  参考文献：
  名称：

  甾醇合成。胆固醇氧化衍生物的氟化和氘代类似物的制备和表征。

  摘要：

  氧化的固醇，包括自氧化产物和固醇代谢产物，都具有许多重要的生物学活性。可靠标准品的提供大大简化了通过色谱和光谱法鉴定和定量氧固醇的方法，氘代和氟化类似物作为定量内标非常有价值。我们描述了43种含氧固醇的制备，纯化和表征，包括胆固醇及其类似物与25,26,26的4β-羟基，7α-羟基，7β-羟基，7-酮和19-羟基衍生物，26,27,27,27-七氟（F7）和26,26,26,27,27,27-六氘（d6）取代。还制备了（25R）-胆甾-5-烯-3β，26-二醇（1d）的7α-羟基，7β-羟基和7-酮衍生物及其16,16-二氘代子宫类似物。这些d2-26-羟基甾醇和[16,16-2H2]-（25R）-胆甾烯-5 -ene-3β，26-二醇（1e）是由[16,16-2H2]-（25R）-胆甾醇合成的可以由薯os皂苷元制备-5-烯-3β，26-二醇二乙酸酯（2e）。1e和2e中C-16处高度特异

  DOI：

  10.1016/s0009-3084(99)00005-5
• 作为产物：
  描述：

  (25R)-3β,26-diacetoxycholest-5-en-7-one 在 sodium hydroxide 、 L-Selectride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 (25R)-cholest-5-ene-3β,7α,26-triol
  参考文献：
  名称：

  甾醇合成。胆固醇氧化衍生物的氟化和氘代类似物的制备和表征。

  摘要：

  氧化的固醇，包括自氧化产物和固醇代谢产物，都具有许多重要的生物学活性。可靠标准品的提供大大简化了通过色谱和光谱法鉴定和定量氧固醇的方法，氘代和氟化类似物作为定量内标非常有价值。我们描述了43种含氧固醇的制备，纯化和表征，包括胆固醇及其类似物与25,26,26的4β-羟基，7α-羟基，7β-羟基，7-酮和19-羟基衍生物，26,27,27,27-七氟（F7）和26,26,26,27,27,27-六氘（d6）取代。还制备了（25R）-胆甾-5-烯-3β，26-二醇（1d）的7α-羟基，7β-羟基和7-酮衍生物及其16,16-二氘代子宫类似物。这些d2-26-羟基甾醇和[16,16-2H2]-（25R）-胆甾烯-5 -ene-3β，26-二醇（1e）是由[16,16-2H2]-（25R）-胆甾醇合成的可以由薯os皂苷元制备-5-烯-3β，26-二醇二乙酸酯（2e）。1e和2e中C-16处高度特异

  DOI：

  10.1016/s0009-3084(99)00005-5

文献信息

• Expression Cloning of an Oxysterol 7α-Hydroxylase Selective for 24-Hydroxycholesterol
  作者：Jia Li-Hawkins、Erik G. Lund、Amy D. Bronson、David W. Russell

  DOI：10.1074/jbc.m001810200

  日期：2000.6

  7alpha-hydroxylated bile acids from oxysterols requires an oxysterol 7alpha-hydroxylase encoded by the Cyp7b1 locus. As expected, mice deficient in this enzyme have elevated plasma and tissue levels of 25- and 27-hydroxycholesterol; however, levels of another major oxysterol, 24-hydroxycholesterol, are not increased in these mice, suggesting the presence of another oxysterol 7alpha-hydroxylase. Here, we describe

  由氧固醇合成7α-羟基化胆汁酸需要由Cyp7b1基因座编码的氧固醇7α-羟化酶。如预期的那样，缺乏这种酶的小鼠血浆和组织中的25-和27-羟基胆固醇水平升高；但是，在这些小鼠中另一种主要的氧固醇24羟胆固醇的水平并未增加，这表明存在另一种氧固醇7α-羟化酶。在这里，我们描述了鼠类和人类cDNA和编码第二个氧固醇7α-羟化酶的基因的克隆和表征。这些基因包含12个外显子，位于人的6号染色体（CYP39A1基因座）和小鼠的17号染色​​体的同义位置（Cyp39a1基因座）。CYP39A1是一种微粒体细胞色素P450酶，对24-羟基胆固醇具有优先性，并在肝脏中表达。肝脏CYP39A1 mRNA的水平不响应饮食中的胆固醇，胆汁酸或胆汁酸结合树脂而改变，这与编码其他固醇7α-羟化酶的那些不同。肝中CYP39A1的表达具有两性性（女性>男性），与CYP7B1的表达相反（男性>女性）。我们得出结论，在小鼠
• The Enzymes, Regulation, and Genetics of Bile Acid Synthesis
  作者：David W. Russell

  DOI：10.1146/annurev.biochem.72.121801.161712

  日期：2003.6

  ▪ Abstract  The synthesis and excretion of bile acids comprise the major pathway of cholesterol catabolism in mammals. Synthesis provides a direct means of converting cholesterol, which is both hydrophobic and insoluble, into a water-soluble and readily excreted molecule, the bile acid. The biosynthetic steps that accomplish this transformation also confer detergent properties to the bile acid, which are exploited by the body to facilitate the secretion of cholesterol from the liver. This role in the elimination of cholesterol is counterbalanced by the ability of bile acids to solubilize dietary cholesterol and essential nutrients and to promote their delivery to the liver. The synthesis of a full complement of bile acids requires 17 enzymes. The expression of selected enzymes in the pathway is tightly regulated by nuclear hormone receptors and other transcription factors, which ensure a constant supply of bile acids in an ever changing metabolic environment. Inherited mutations that impair bile acid synthesis cause a spectrum of human disease; this ranges from liver failure in early childhood to progressive neuropathy in adults.

  ▪ 摘要：在哺乳动物体内，胆汁酸的合成和排泄构成了胆固醇分解的主要途径。合成提供了一种将既疏水又不溶于水的胆固醇直接转化为水溶性且容易排泄的分子——胆汁酸的直接方法。完成这种转化的生物合成步骤也赋予了胆汁酸的清洁剂特性，这些特性被机体利用来促进从肝脏排泄胆固醇。这种在胆固醇排泄中的作用被胆汁酸溶解膳食胆固醇和必需营养素以及促进它们传递到肝脏的能力所平衡。合成完整的胆汁酸需要17种酶。途径中的选择性酶的表达受到核激素受体和其他转录因子的严格调控，这些因子确保在不断变化的代谢环境中始终有足够的胆汁酸供应。遗传突变会影响胆汁酸的合成，导致一系列人类疾病，从儿童早期的肝衰竭到成年人的渐进性神经病变。
• Human steroid and oxysterol 7α-hydroxylase CYP7B1: substrate specificity, azole binding and misfolding of clinically relevant mutants
  作者：Aleksei V. Yantsevich、Yaroslav V. Dichenko、Farrell MacKenzie、Dmitry V. Mukha、Alexander V. Baranovsky、Andrei A. Gilep、Sergey A. Usanov、Natallia V. Strushkevich

  DOI：10.1111/febs.12733

  日期：2014.3

  experiments with purified enzyme, the requirements for CYP7B1 hydroxylation of steroid molecules are as follows: C5 hydrogen in the α‐configuration (or double bond at C5), a polar group at C17, a hydroxyl group at C3, and the absence of the hydroxyl group at C20–C24 in the C27‐sterol side chain. 21‐hydroxy‐pregnenolone was identified as a new substrate, and overall low activity toward pregnanes could be related

  氧固醇和神经固醇是细胞色素P450家族单加氧酶产生的重要信号分子，通过核受体实现其作用。CYP7B1催化类固醇和氧固醇的6或7羟基化反应，因此分别参与神经类固醇的代谢和胆汁酸的合成。CYP7B1的双重生理作用是由酶功能异常引起的不同疾病，肝衰竭和进行性神经病证明的。在这里，我们在分子水平上介绍CYP7B1的生化特征，以了解底物特异性和对唑类药物的敏感性。根据我们使用纯化酶进行的实验，对类固醇分子的CYP7B1羟基化的要求如下：C5氢为α-构型（或C5为双键），C17为极性基团，在C3的羟基上有一个羟基，而在C27-甾醇侧链的C20-C24上没有羟基。21-羟基孕烯醇酮被认为是一种新的底物，而对孕激素的总体低活性可能与CYP7B1产生的7-羟基衍生物的效力增加有关。CYP7B1在重构系统中的氧固醇的代谢转化（失活）是通过两个连续的羟基化进行的。在疾病患者中发现的两个突变Gly57Arg和Ph
• Synthesis of 7α-hydroxy derivatives of regulatory oxysterols
  作者：Dansu Li、Thomas A Spencer

  DOI：10.1016/s0039-128x(00)00131-8

  日期：2000.9

  7 alpha-Hydroxy derivatives of oxysterols are of considerable interest because of their possible involvement in regulation of cholesterol metabolism This paper describes stereoselective syntheses and complete characterization of the 7 alpha-hydroxy derivatives of four key oxysterols: 25-hydroxycholesterol, 27-hydroxycholesterol, 24(S)-hydroxycholesterol, and 24(S),25-epoxycholesterol. (C) 2000 Elsevier Science Inc. All rights reserved.
• 7alpha Hydroxylation of 25-Hydroxycholesterol in Liver Microsomes. Evidence that the Enzyme Involved is Different from Cholesterol 7alpha-Hydroxylase
  作者：Anders Toll、Kjell Wikvall、Elly Sudjana-Sugiaman、Kazu-Hiro Kondo、Ingemar Bjorkhem

  DOI：10.1111/j.1432-1033.1994.00309.x

  日期：1994.9

  Rat, pig and human liver microsomes were found to catalyze 7α‐hydroxylation of 25‐hydroxycholesterol. In contrast to cholesterol 7α‐hydroxylase activity, the 7α‐hydroxylase activity towards 25‐hydroxycholesterol in rat liver was not stimulated by cholestyramine treatment. After transfection with cDNA for human cholesterol 7α‐hydroxylase, COS cells showed a significant activity towards cholesterol but not towards 25‐hydroxycholesterol. During purification of cholesterol 7α‐hydroxylase from pig liver microsomes, about 99% of the 7α‐hydroxylase activity towards 25‐hydroxycholesterol and 27‐hydroxycholesterol was clearly separated from 7α‐hydroxylase activity for cholesterol. The small amount of 25‐hydroxycholesterol 7α‐hydroxylase activity retained in a partially purified preparation of cholesterol 7α‐hydroxylase was not inhibited by addition of cholesterol, indicating that the oxysterol binding site is different from the cholesterol binding site, presumely due to the presence of two different enzymes. It is concluded that different enzymes are involved in 7α‐hydroxylation of cholesterol and 7α hydroxylation of side‐chain‐oxidized cholesterol in rat, pig and human liver.Inhibition experiments with a partially purified fraction of the oxysterol 7α‐hydroxylase from pig liver gave results consistent with the contention that the same enzyme is responsible for 7α hydroxylation of both 25‐hydroxycholesterol and 27‐hydroxycholesterol.It has been suggested that cholesterol 7α‐hydroxylase can preferentially use oxysterols, in particular 25‐hydroxycholesterol, as substrates and by this means inactivate important physiological regulators of cholesterol homeostasis. Such a mechanism would explain the unique property of the liver to resist down‐regulation of the low‐density‐lipoprotein receptor [Dueland, S., Trawick, J. D., & Davies, R. A. (1993) J. Biol. Chem. 267, 22695–22698]. The present results do not support the contention that the important coupling between cholesterol 7α‐hydroxylase activity, the low‐density‐lipoprotein receptor activity and hydroxymethylglutaryl coenzyme A reductase activity in liver cells is due to inactivation of 25‐hydroxycholesterol or 27‐hydroxycholesterol by the action of cholesterol 7α‐hydroxylase.