7-oxo-cholest-5-ene-3β,25-diol | 64907-23-9

• 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: 7-oxo-cholest-5-ene-3β,25-diol
• 英文别名: 25-hydroxy-7-ketocholesterol；7-keto,25-hydroxycholesterol；7-keto-25-hydroxycholesterol；3β-25-Dihydroxycholest-5-en-7-on；(3beta)-3,25-Dihydroxycholest-5-en-7-one；(3S,8S,9S,10R,13R,14S,17R)-3-hydroxy-17-[(2R)-6-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-1,2,3,4,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-7-one
• CAS: 64907-23-9
• 化学式: C₂₇H₄₄O₃
• 分子量: 416.645
• InChiKey: NQBVGGWSAXBLBE-BYJKJZODSA-N

物化性质

• 熔点：
  169-173°C
• 沸点：
  550.2±33.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-oxo-cholest-5-ene-3β,25-diol 在 11β-hydroxysteroid dehydrogenase type 1 作用下， 生成 胆固醇杂质35
  参考文献：
  名称：

  11β-羟基类固醇脱氢酶1和2对氧固醇7β，25-二羟基胆固醇和7-酮，25-羟基胆固醇的酶促转化。

  摘要：

  氧固醇是通过自氧化或酶促过程衍生的胆固醇代谢产物。它们由大量的生物活性脂质组成，这些脂质与多种疾病的进展有关。为了阐明涉及氧固醇的（病理）生理机制，阐明氧固醇的潜在形成和降解至关重要。已经报道了11β-羟基类固醇脱氢酶（11β-HSDs）通过催化7-酮胆固醇（7kC）和7β-羟基胆固醇（7βOHC）的相互转化而在氧固醇代谢中的作用。本研究解决了11β-HSD1在从7-酮，25-羟基胆固醇（7k25OHC）酶促生成7β，25-二羟基胆固醇（7β25OHC）中的功能，并测试了11β-HSD2是否能够催化逆反应。第一次使用重组酶，可以证明胆固醇25-羟化酶（CH25H）从7kC形成7k25OHC，以及人和小鼠11β-HSD1进一步立体定向氧化还原成7β25OHC。另外，使用人11β-HSD2的实验显示7β25OHC氧化为7k25OHC。分子建模为7β25OHC和7k25OHC的立体定向互变提供了

  DOI：

  10.1016/j.jsbmb.2019.03.011
• 作为产物：
  描述：

  25-羟基胆甾醇 在 叔丁基过氧化氢 、 N-羟基邻苯二甲酰亚胺 、 cobalt(II) acetate 作用下， 以 丙酮 为溶剂， 反应 12.0h， 以59.9%的产率得到7-oxo-cholest-5-ene-3β,25-diol
  参考文献：
  名称：

  N-羟基邻苯二甲酰亚胺催化类固醇与叔丁基氢过氧化物的烯丙基氧化

  摘要：

  开发了一种在温和条件下在催化量的 N-羟基邻苯二甲酰亚胺 (NHPI) 存在下用叔丁基过氧化氢对 Δ(5)-类固醇进行烯丙基氧化的优化新方法，显示出优异的区域选择性和化学选择性（官能团兼容性） . 发现 Co(OAc)2 可以增强 NHPI 的催化能力，从而提高产率和缩短反应时间。还研究了与各种Δ(5)-甾体底物的反应机理和反应范围。

  DOI：

  10.1016/j.steroids.2014.12.004

文献信息

• Oxysterols direct immune cell migration via EBI2
  作者：Sébastien Hannedouche、Juan Zhang、Tangsheng Yi、Weijun Shen、Deborah Nguyen、João P. Pereira、Danilo Guerini、Birgit U. Baumgarten、Silvio Roggo、Ben Wen、Richard Knochenmuss、Sophie Noël、Francois Gessier、Lisa M. Kelly、Mirka Vanek、Stephane Laurent、Inga Preuss、Charlotte Miault、Isabelle Christen、Ratna Karuna、Wei Li、Dong-In Koo、Thomas Suply、Christian Schmedt、Eric C. Peters、Rocco Falchetto、Andreas Katopodis、Carsten Spanka、Marie-Odile Roy、Michel Detheux、Yu Alice Chen、Peter G. Schultz、Charles Y. Cho、Klaus Seuwen、Jason G. Cyster、Andreas W. Sailer

  DOI：10.1038/nature10280

  日期：2011.7

  The EBI2 receptor (Epstein–Barr virus-induced gene 2, also known as GPR183) was recently shown to be linked to autoimmune disease, and is a critical regulator of the humoral immune response. It is a G-protein-coupled receptor, and its natural ligand has been unknown. Two groups now bring an end to the 'orphan' status of this receptor with identification of specific oxysterols as its natural ligands. The most potent ligand and activator is 7a,25-dihydroxycholesterol, and the EBI2–oxysterol signalling pathway has an important role in the adaptive immune response. Epstein–Barr virus-induced gene 2 (EBI2, also known as GPR183) is a G-protein-coupled receptor that is required for humoral immune responses; polymorphisms in the receptor have been associated with inflammatory autoimmune diseases1,2,3. The natural ligand for EBI2 has been unknown. Here we describe the identification of 7α,25-dihydroxycholesterol (also called 7α,25-OHC or 5-cholesten-3β,7α,25-triol) as a potent and selective agonist of EBI2. Functional activation of human EBI2 by 7α,25-OHC and closely related oxysterols was verified by monitoring second messenger readouts and saturable, high-affinity radioligand binding. Furthermore, we find that 7α,25-OHC and closely related oxysterols act as chemoattractants for immune cells expressing EBI2 by directing cell migration in vitro and in vivo. A critical enzyme required for the generation of 7α,25-OHC is cholesterol 25-hydroxylase (CH25H)4. Similar to EBI2 receptor knockout mice, mice deficient in CH25H fail to position activated B cells within the spleen to the outer follicle and mount a reduced plasma cell response after an immune challenge. This demonstrates that CH25H generates EBI2 biological activity in vivo and indicates that the EBI2–oxysterol signalling pathway has an important role in the adaptive immune response.

  EBI2 受体（EpsteinâBarr 病毒诱导基因 2，又称 GPR183）最近被证明与自身免疫性疾病有关，是体液免疫反应的关键调节因子。它是一种 G 蛋白偶联受体，其天然配体一直不为人知。现在，两个研究小组通过鉴定特定的氧基甾醇作为其天然配体，结束了该受体的 "孤儿 "地位。最有效的配体和激活剂是 7a,25-二羟基胆固醇，EBI2âoxysterol 信号通路在适应性免疫反应中起着重要作用。爱泼斯坦巴氏病毒诱导基因 2（EBI2，又称 GPR183）是一种 G 蛋白偶联受体，是体液免疫反应所必需的；该受体的多态性与炎症性自身免疫疾病有关1,2,3。EBI2 的天然配体一直未知。在这里，我们描述了 7δ±,25-二羟基胆固醇（又称 7δ±,25-OHC或 5-胆甾烯-3δ²,7δ±,25-三醇）作为 EBI2 的强效选择性激动剂的鉴定结果。通过监测第二信使读数和可饱和的高亲和力放射性配体结合，我们验证了 7δ±,25-OHC 和密切相关的氧基甾醇对人类 EBI2 的功能性激活。此外，我们还发现 7δ±，25-OHC 和密切相关的氧杂环醇通过引导细胞在体外和体内迁移，对表达 EBI2 的免疫细胞起着趋化吸引作用。生成 7δ±,25-OHC 所需的一个关键酶是胆固醇 25- 羟化酶（CH25H）4。 与 EBI2 受体基因敲除小鼠类似，缺乏 CH25H 的小鼠无法将脾脏内的活化 B 细胞定位到外滤泡，并且在免疫挑战后浆细胞反应减弱。这表明 CH25H 能在体内产生 EBI2 生物活性，并表明 EBI2âoxysterol 信号通路在适应性免疫反应中起着重要作用。
• Oxysterols direct B-cell migration through EBI2
  作者：Changlu Liu、Xia V. Yang、Jiejun Wu、Chester Kuei、Neelakandha S. Mani、Li Zhang、Jingxue Yu、Steven W. Sutton、Ning Qin、Homayon Banie、Lars Karlsson、Siquan Sun、Timothy W. Lovenberg

  DOI：10.1038/nature10226

  日期：2011.7

  The EBI2 receptor (Epstein–Barr virus-induced gene 2, also known as GPR183) was recently shown to be linked to autoimmune disease, and is a critical regulator of the humoral immune response. It is a G-protein-coupled receptor, and its natural ligand has been unknown. Two groups now bring an end to the 'orphan' status of this receptor with identification of specific oxysterols as its natural ligands. The most potent ligand and activator is 7a,25-dihydroxycholesterol, and the EBI2–oxysterol signalling pathway has an important role in the adaptive immune response. EBI2 (also called GPR183) is an orphan G-protein-coupled receptor that is highly expressed in spleen and upregulated upon Epstein–Barr-virus infection1. Recent studies indicated that this receptor controls follicular B-cell migration and T-cell-dependent antibody production2,3,4,5,6. Oxysterols elicit profound effects on immune and inflammatory responses as well as on cholesterol metabolism7,8,9. The biological effects of oxysterols have largely been credited to the activation of nuclear hormone receptors10,11. Here we isolate oxysterols from porcine spleen extracts and show that they are endogenous ligands for EBI2. The most potent ligand and activator is 7α,25-dihydroxycholesterol (OHC), with a dissociation constant of 450 pM for EBI2. In vitro, 7α,25-OHC stimulated the migration of EBI2-expressing mouse B and T cells with half-maximum effective concentration values around 500 pM, but had no effect on EBI2-deficient cells. In vivo, EBI2-deficient B cells or normal B cells desensitized by 7α,25-OHC pre-treatment showed reduced homing to follicular areas of the spleen. Blocking the synthesis of 7α,25-OHC in vivo with clotrimazole, a CYP7B1 inhibitor, reduced the content of 7α,25-OHC in the mouse spleen and promoted the migration of adoptively transferred pre-activated B cells to the T/B boundary (the boundary between the T-zone and B-zone in the spleen follicle), mimicking the phenotype of pre-activated B cells from EBI2-deficient mice. Our results show an unexpected causal link between EBI2, an orphan G-protein-coupled receptor controlling B-cell migration, and the known immunological effects of certain oxysterols, thus uncovering a previously unknown role for this class of molecules.

  克霉唑，可阻止体内7α，25-二羟基胆固醇的合成。
• 25-羟基-7-酮基胆固醇合成方法
  申请人：浙江工业大学

  公开号：CN105017366B

  公开（公告）日：2018-02-27

  本发明涉及一种25‑羟基‑7‑酮基胆固醇的合成方法，该方法为：在有机溶剂中，以25‑羟基胆固醇衍生物为原料，在N‑羟基催化剂存在下，通过引发剂引发，通空气或氧气于0℃～150℃温度下反应1～40小时，反应完全后于‑20℃～100℃下加入脱水剂进行脱水反应1～20小时，再在50～80℃水解反应1～2小时，反应液分离处理得到25‑羟基‑7‑酮基胆固醇。本发明所用的原料及试剂易得，且对环境友好，本发明避免了使用对环境污染严重的如金属Cr、氧化剂PCC等的使用；反应选择性好，收率高、成本低，其后处理简单，三废少，产品易分离且纯度高。
• Novel class of sterol ligands and their uses in regulation of cholesterol and gene expression
  申请人：Javitt B. Norman

  公开号：US20060121024A1

  公开（公告）日：2006-06-08

  This invention relates to oxysteroids and oxysteroid hormones which have been identified. These oxysteroids are C27 modified sterols, particularly derivatives of intermediates in cholesterol synthesis, including lanosterol, zymosterol and desmosterol, including C27 diol and C27 acid derivatives, as well as related compounds and analogs thereof. The oxysteroids are capable of binding to or otherwise interacting with orphan nuclear receptors to result in modulation of gene expression. The invention further relates to methods of modulating the rate of cholesterol synthesis in a mammal. More specifically, the invention relates to treatment of cholesterol-related conditions which are improved or ameliorated by modulating the rate of cholesterol synthesis or cholesterol metabolism in a human in need thereof by administration of these oxysteroids, analogs or antagonists thereof. The invention includes methods for ameliorating, treating or preventing macular degeneration in a mammal comprising administering to said mammal an agent which stimulates or enhances the expression or activity of steroid sulphotransferase (SLUT2), particularly SLUT2B1b, or which stimulates or enhances the expression or activity of CYP27A1 or sterol 27-hydroxylase or otherwise increasing the sulfonation or 27-hydroxylation of cholesterol intermediates, including 7-ketocholesterol. Assays for identification of analogs, antagonists or modulators of these oxysteroids or of sterol 27-hydroxylase are also provided.

  本发明涉及已经鉴定的氧化甾体和氧化甾体激素。这些氧化甾体是C27修饰类固醇，特别是胆固醇合成中间体的衍生物，包括鲸蜡醇、酵母蜡醇和脱酸酶醇，包括C27二醇和C27酸衍生物，以及相关化合物和类似物。这些氧化甾体能够与孤儿核受体结合或以其他方式相互作用，从而调节基因表达。本发明进一步涉及在哺乳动物中调节胆固醇合成速率的方法。更具体地，本发明涉及通过给予这些氧化甾体、类似物或其拮抗剂来改善或缓解需要调节胆固醇合成或胆固醇代谢速率的人类的与胆固醇相关的疾病的治疗。本发明包括治疗、改善或预防哺乳动物黄斑退化的方法，包括给予一种刺激或增强类固醇硫酸转移酶（SLUT2），特别是SLUT2B1b，表达或活性的药物，或者刺激或增强CYP27A1或类固醇27-羟化酶的表达或活性，或以其他方式增加胆固醇中间体的磺酸化或27-羟化，包括7-酮胆固醇。还提供了用于鉴定这些氧化甾体或类固醇27-羟化酶的类似物、拮抗剂或调节剂的测定方法。
• Utilisation de la 5-cholesten-3 béta,25-diol-7-one pour le traitement des peaux sèches ou du cuir chevelu sec
  申请人：L'OREAL

  公开号：EP1413291A1

  公开（公告）日：2004-04-28

  La présente invention concerne un procédé cosmétique de traitement des peaux sèches ou du cuir chevelu sec, comprenant l'application topique sur la peau ou le cuir chevelu d'une composition renfermant, dans un milieu physiologiquement acceptable, au moins un oxystérol choisi parmi : la 5-cholesten-3β,25-diol-7-one et ses esters et éthers.

  本发明涉及一种用于治疗皮肤干燥或头皮干燥的化妆品工艺，包括在生理上可接受的介质中，向皮肤或头皮局部施用一种组合物，该组合物含有至少一种氧甾醇，这些氧甾醇选自：5-胆甾烯-3β,25-二醇-7-酮及其酯类和醚类。