5β-cholestane-3α,7α,25-triol | 38623-79-9

• 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: 5β-cholestane-3α,7α,25-triol
• 英文别名: Koprostan-3α,7α,25-triol；5beta-Cholestane-3alpha,7alpha,25-triol；(3R,5S,7R,8R,9S,10S,13R,14S,17R)-17-[(2R)-6-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-3,7-diol
• CAS: 38623-79-9
• 化学式: C₂₇H₄₈O₃
• 分子量: 420.676
• InChiKey: UROPIWALBBMYRP-JTKZRGNMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 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：

  5β-cholestane-3α,7α,25-triol 在 selenium(IV) oxide 、 silver carbonate 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 26.0h， 生成 7α,25-dihydroxy-4-cholesten-3-one
  参考文献：
  名称：

  Bile acids. LXXIII. Synthesis of analogs of 7α-hydroxy-4-cholesten-3-one as substrates for hepatic steroid 12α-hydroxylase

  摘要：

  Analogs of 7 alpha-hydroxy-4-cholesten-3-one were prepared to ascertain structural features necessary for maximal activity of hepatic microsomal 12 alpha-steroid hydroxylase. Methyl 3 alpha,7 alpha-dihydroxy-5 beta-cholane-24-carboxylate derived from chenodeoxycholic acid was oxidized at C-3 with silver carbonate/Celite. The product was hydrolyzed and dehydrogenated with SeO2 to provide 3-oxo-7 alpha-hydroxy-4-cholene-24-carboxylic acid. 5 beta-Cholestane-3 alpha,7 alpha,25-triol and 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol were similarly oxidized at C-3 and dehydrogenated to provide 7 alpha,25-dihydroxy-4-cholesten-3-one and 7 alpha,12 alpha,25-trihydroxy-4-cholesten-3-one, respectively. The products were characterized by thin-layer and gas chromatography, ultraviolet, infrared, proton resonance and mass spectrometry.

  DOI：

  10.1016/s0039-128x(84)80020-3
• 作为产物：
  描述：

  鹅去氧胆酸 以 乙醚 为溶剂， 反应 2.0h， 生成 5β-cholestane-3α,7α,25-triol
  参考文献：
  名称：

  Mehrwertige Alkohole aus Sterinen und Sterinderivaten，VI斯特雷德米特Strecturmerkmalen des Ecdysons und der Elatericine

  摘要：

  AUS Litho-，Desoxy- UNDChenodesoxycholsäure（1A - C ^）wurden黚死Homosäuren 5A - Ç模具叔-C 25 -Carbinole 7A - Ç dargestellt。位于Das Ecdyson-Analoge Produkt 18b umwandeln中的胆固醇。Hyodesoxy- UNDHomohyodesoxycholsäurewurden裸片Tetrole部33a，b übergeführt。Aus 34a – d沸腾的硬脂酸酯37a – d mit diosphenolischer Struktur gewonnen。

  DOI：

  10.1002/jlac.19727580109

文献信息

• New bile alcohols — synthesis of 5β-cholestane-3α, 7α, 25-triol and 5β-cholestane-3α, 7α, 25-24(14C)-triol1
  作者：Bertram I. Cohen、G.S. Tint、Taiju Kuramoto、Erwin H. Mosbach

  DOI：10.1016/0039-128x(75)90093-8

  日期：1975.3

  the diformoxy derivative (II) using formic acid. Reaction of II with thionyl chloride yielded the acid chloride which was treated with diazomethane (CH 2 N 2 or 14 CH 2 N 2 ) to produce 3ga, 7α-diformoxy-24-oxo-25-diazo-25-homocholane (III, A or B). 25-Homochenodeoxycholic acid (IV, A or B) was formed from III by means of the Wolff rearrangement of the Arndt-Eistert synthesis. The methyl ester of V (A

  摘要 5β-胆甾烷-3α, 7α, 25-三醇和5β-胆甾烷-3α, 7α, 25-24( 14 C)-三醇由3α, 7α-二羟基-5β-胆酸（鹅去氧胆酸）合成。鹅去氧胆酸使用甲酸转化为二甲氧基衍生物(II)。II 与亚硫酰氯反应生成酰氯，用重氮甲烷（CH 2 N 2 或 14 CH 2 N 2 ）处理生成 3ga, 7α-diformoxy-24-oxo-25-diazo-25-homocholane (III, A或 B)。25-高鹅脱氧胆酸（IV、A 或 B）是通过 Arndt-Eistert 合成的沃尔夫重排由 III 形成的。V(A或B)的甲酯在醚中用甲基碘化镁处理以提供所需的三醇VI(A和B)。三醇通过质谱和元素分析进行​​鉴定，并通过薄层色谱和气液色谱进行表征。3α、7α、
• Preparation and characterization of (24R and 24S)-5μ-cholestane-3α, 7α,24,25-tetrols and (24R and 24S)-5β-cholestane-3α, 24, 25-triols
  作者：A.K. Batta、B. Dayal、G.S. Tint、S. Shefer、V. Toome、G. Salen、E.H. Mosbach

  DOI：10.1016/0039-128x(78)90022-3

  日期：1978.1

  (24R and 24S)-5beta-cholestane-3alpha,7alpha,24,25-tetrols were prepared by osmium tetroxide oxidation of 5beta-cholest-24-ene-3alpha,7alpha-diol. The resulting diastereomeric tetrols were separated by thin-layer chromatography, their purity ascertained by melting point, gas-liquid chromatography and mass spectra and their structural configurations were assigned by molecular rotation measurement and circular dichroism studies. In a similar fashion, the (24R and 24S)-5beta-cholestane-3alpha,24,25-triols were prepared and their structures identified.

  （24R和24S）-5β-胆甾烷-3α,7α,24,25-四醇是通过5β-胆甾-24-烯-3α,7α-二醇用四氧化锇进行氧化反应制备的。所得的二色异构体四醇通过薄层色谱法分离，其纯度通过熔点、气液色谱和质谱测定，结构配置通过分子旋转测量和圆二色性研究确定。以类似的方式，制备了（24R和24S）-5β-胆甾烷-3α,24,25-三醇，并确定了它们的结构。
• Purification and characterization of a vitamin D3 25-hydroxylase from pig liver microsomes
  作者：E Axén、T Bergman、K Wikvall

  DOI：10.1042/bj2870725

  日期：1992.11.1

  A cytochrome P-450 which catalyses 25-hydroxylation of vitamin D3 has been purified to apparent homogeneity from pig liver microsomes. The specific content of cytochrome P-450 was 12 nmol.mg of protein-1, and the preparation showed a single band with an apparent M(r) of 50,500 upon SDS/PAGE. A monoclonal antibody raised against the vitamin D3 25-hydroxylase reacted strongly with the purified 25-hydroxylating cytochrome P-450 from pig kidney microsomes [Bergman & Postlind (1990) Biochem. J. 270, 345-350]. The liver enzyme showed structural and functional properties very similar to those of the kidney enzyme. The two enzymes differed with respect to only one of the first 16 N-terminal amino acids. The vitamin D3 25-hydroxylase in pig liver microsomes exhibited a turnover and an apparent Km for 25-hydroxylation of vitamin D3 which were of the same order of magnitude as those of a well-characterized male-specific 25-hydroxylating cytochrome P-450 in rat liver microsomes. The two enzymes differed structurally. The pig liver enzyme was, in contrast to the rat liver enzyme, not sex-specific, and did not catalyse 16 alpha-hydroxylation of testosterone. These properties of the 25-hydroxylase in rat liver microsomes have led to questions on the role of microsomal 25-hydroxylation of vitamin D3. It is concluded that studies on microsomal 25-hydroxylation with the rat may be misleading. The results of the present study show that the pig appears to be a representative species for evaluation of vitamin D3 hydroxylases in other mammals, including man.

  一种细胞色素P-450酶催化维生素D3的25-羟化已经从猪肝微粒体中纯化到表观同质性。细胞色素P-450的特异性含量为12 nmol.mg蛋白质^-1，该制备在SDS/PAGE上显示一个明显的M(r)为50,500的单一条带。一种针对维生素D3 25-羟化酶制备的单克隆抗体与从猪肾微粒体中纯化的25-羟化细胞色素P-450强烈反应[Bergman & Postlind（1990）Biochem. J. 270, 345-350]。肝酶显示出与肾酶非常相似的结构和功能特性。这两种酶仅在前16个N末端氨基酸中的一个方面不同。猪肝微粒体中的维生素D3 25-羟化酶表现出与大鼠肝微粒体中一个经过充分表征的男性特异性25-羟化细胞色素P-450相同数量级的25-羟化维生素D3的周转和表观Km。这两种酶在结构上有所不同。与大鼠肝酶相比，猪肝酶不是性别特异性的，也不催化睾酮的16α-羟化。大鼠肝微粒体中25-羟化维生素D3的这些特性引发了对微粒体25-羟化在维生素D3代谢中作用的质疑。结论是，在大鼠上进行的微粒体25-羟化研究可能是误导性的。本研究的结果表明，猪似乎是其他哺乳动物，包括人类，评估维生素D3羟化酶的代表性物种。
• Characterization of pig kidney microsomal cytochrome <i>P</i>-450 catalysing 25-hydroxylation of vitamin D3 and C27 steroids
  作者：T Bergman、H Postlind

  DOI：10.1042/bj2700345

  日期：1990.9.1

  The cytochrome P-450 enzyme which catalyses 25-hydroxylation of vitamin D3 (cytochrome P-450(25] from pig kidney microsomes [Postlind & Wikvall (1988) Biochem. J. 253, 549-552] has been further purified. The specific content of cytochrome P-450 was 15.0 nmol.mg of protein-1, and the protein showed a single spot with an apparent isoelectric point of 7.4 and an Mr of 50,500 upon two-dimensional isoelectric-focusing/SDS/PAGE. The 25-hydroxylase activity towards vitamin D3 was 124 pmol.min-1.nmol of cytochrome P-450-1 and towards 1 alpha-hydroxyvitamin D3 it was 1375 pmol.min-1.nmol-1. The preparation also catalysed the 25-hydroxylation of 5 beta-cholestane-3 alpha,7 alpha-diol at a rate of 1000 pmol.min-1.nmol of cytochrome P-450-1 and omega-1 hydroxylation of lauric acid at a rate of 200 pmol.min-1.nmol of cytochrome P-450-1. A monoclonal antibody raised against the 25-hydroxylating cytochrome P-450, designated mAb 25E5, was prepared. After coupling to Sepharose, the antibody was able to bind to cytochrome P-450(25) from kidney as well as from pig liver microsomes, and to immunoprecipitate the activity for 25-hydroxylation of vitamin D3 and 5 beta-cholestane-3 alpha,7 alpha-diol when assayed in a reconstituted system. The hydroxylase activity towards lauric acid was not inhibited by the antibody. By SDS/PAGE and immunoblotting with mAb 25E5, cytochrome P-450(25) was detected in both pig kidney and pig liver microsomes. These results indicate a similar or the same species of cytochrome P-450 in pig kidney and liver microsomes catalysing 25-hydroxylation of vitamin D3 and C27 steroids. The N-terminal amino acid sequence of the purified cytochrome P-450(25) from pig kidney microsomes differed from those of hitherto isolated mammalian cytochromes P-450.

  细胞色素P-450酶催化维生素D3的25-羟化（来自猪肾微粒体的细胞色素P-450（25）[Postlind＆Wikvall（1988）Biochem.J.253,549-552]已被进一步纯化。细胞色素P-450的特异含量为15.0 nmol.mg-1蛋白质，并且该蛋白质在二维等电聚焦/SDS/PAGE上显示出一个明显的等电点为7.4，分子量为50,500的单一斑点。对于维生素D3的25-羟化酶活性为124 pmol.min-1.nmol细胞色素P-450-1，对于1α-羟基维生素D3的酶活性为1375 pmol.min-1.nmol-1。该制剂还催化了5β-胆甾烷-3α,7α-二醇的25-羟化，速率为1000 pmol.min-1.nmol细胞色素P-450-1，以及月桂酸的ω-1羟化，速率为200 pmol.min-1.nmol细胞色素P-450-1。制备了一种针对25-羟化细胞色素P-450的单克隆抗体，称为mAb 25E5。将抗体偶联到Sepharose后，抗体能够结合到肾脏以及猪肝微粒体的细胞色素P-450（25），并在重构系统中免疫沉淀维生素D3和5β-胆甾烷-3α,7α-二醇的25-羟化活性。抗体未抑制对月桂酸的羟化活性。通过SDS/PAGE和mAb 25E5的免疫印迹，检测到细胞色素P-450（25）存在于猪肾和猪肝微粒体中。这些结果表明，在猪肾和肝微粒体中存在相似或相同的细胞色素P-450物种，可催化维生素D3和C27类固醇的25-羟化。从猪肾微粒体中纯化的细胞色素P-450（25）的N末端氨基酸序列与迄今为止分离的哺乳动物细胞色素P-450的氨基酸序列不同。
• Meiosis regulating compounds
  申请人：NOVO NORDISK A/S

  公开号：EP0946584B1

  公开（公告）日：2003-04-23