粪甾烷酸 | 547-96-6

• 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: 粪甾烷酸
• 英文名称: 5beta-cholestan-3alpha,7alpha,12alpha-triol
• 英文别名: 5β-cholestane-3α,7α,12α-triol；3α,7α,12α-trihydroxylcholestane；trihydroxycoprostan；THC；5β-Cholestan-3α,7α,12α-triol；5beta-Cholestane-3alpha,7alpha,12alpha-triol；(3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-3,7,12-triol
• CAS: 547-96-6
• 化学式: C₂₇H₄₈O₃
• 分子量: 420.676
• InChiKey: RIVQQZVHIVNQFH-XJZYBRFWSA-N

物化性质

• 熔点：
  180-181°C
• 沸点：
  535.5±50.0 °C(Predicted)
• 密度：
  1.051±0.06 g/cm3(Predicted)
• 溶解度：
  氯仿（微溶）、DMSO（微溶）、甲醇（微溶、超声处理）
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  60.7
• 氢给体数：
  3
• 氢受体数：
  3

ADMET

代谢

Trihydroxycoprostane有一个已知的人类代谢物，包括胆烷-3,7,12,25-四醇。

Trihydroxycoprostane has known human metabolites that include Cholestane-3,7,12,25-tetrol.

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  粪甾烷酸 在 chromium(VI) oxide 作用下， 生成 5β-cholestane-3,7,12-trione
  参考文献：
  名称：

  Seno, Proceedings of the Japan Academy, 1954, vol. 30, p. 887,889

  摘要：

  DOI：
• 作为产物：
  描述：

  (3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-17-((R)-1,5-Dimethyl-hex-4-enyl)-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthrene-3,7,12-triol 在 palladium on activated charcoal 甲酸铵 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以95%的产率得到粪甾烷酸
  参考文献：
  名称：

  Rapid hydrogenation of unsaturated sterols and bile alcohols using microwaves

  摘要：

  This paper describes an operationally simple, rapid hydrogenation of unsaturated sterols and bile alcohols in a domestic microwave oven. This has been achieved by the addition of catalytic amounts of Pd/C in methylene chloride/propylene glycol solvents in the presence of ammonium formate followed by microwave irradiation. It is suggested that this methodology will be helpful in the identification of saturated and unsaturated sterols with different side-chain structures in rare diseases: sitosterolemia, cerebrotendinous xanthomatosis (CTX), as well as atherosclerosis and diabetes mellitus. Sterols, such as cholesterol, campesterol, sitosterol, and bile alcohols with unsaturated side chains, were converted to their reduced congeners with high yield and purity. (C) 1997 by Elsevier Science Inc.

  DOI：

  10.1016/s0039-128x(97)00010-x

文献信息

• Facial amphiphiles and methods of use
  申请人：Zhang Qinghai

  公开号：US09085602B1

  公开（公告）日：2015-07-21

  The invention provides amphiphilic compounds with hydrophobic and hydrophilic faces. The compounds can be readily prepared from steroids such as cholic acid or deoxycholic acid, which provide hydrophobic skeletons with structures similar to that of the lipid cholesterol. The compounds of the invention can be used to aid the solubilization, isolation, purification, stabilization, crystallization, and/or structural determination of membrane proteins, and to prepare micelles for delivery of a bioactive agent, such as a drug or a gene, to a subject.

  该发明提供了具有疏水和亲水面的两性化合物。这些化合物可以从类固醇如胆酸或去氧胆酸中轻松制备，这些类固醇提供了与脂质胆固醇类似的具有疏水骨架的结构。该发明的化合物可用于辅助溶解、分离、纯化、稳定化、结晶和/或确定膜蛋白的结构，并制备微胶束以传递生物活性剂，如药物或基因，给受试者。
• 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。
• Activities of Recombinant Human Cytochrome P450c27 (CYP27) Which Produce Intermediates of Alternative Bile Acid Biosynthetic Pathways
  作者：Irina A. Pikuleva、Amir Babiker、Michael R. Waterman、Ingemar Björkhem

  DOI：10.1074/jbc.273.29.18153

  日期：1998.7

  its role in the degradation of the side chain of C27 steroids in the hepatic bile acid biosynthesis pathway, which begins with 7alpha-hydroxylation of cholesterol in liver. However, recognition that in humans P450c27 is a widely or ubiquitously expressed mitochondrial P450, and that there are alternative pathways of bile acid synthesis which begin with 27-hydroxylation of cholesterol catalyzed by P450c27

  细胞色素P450c27（CYP27）的主要生理意义与其在肝胆汁酸生物合成途径中C27类固醇侧链降解中的作用有关，该作用始于肝脏中胆固醇的7α-羟基化。但是，人们认识到P450c27是广泛或普遍表达的线粒体P450，并且存在胆汁酸合成的其他途径，其始于P450c27催化的胆固醇的27-羟基化反应，这表明需要重新评估该酶及其作用催化性能。人们认为27-羟基胆固醇是P450c27与胆固醇反应形成的唯一产物。然而，本研究表明重组人P450c27还能够进一步氧化27-羟基胆固醇，首先生成醛，然后生成3beta-羟基-5-胆甾烯酸。动力学数据表明，在重构的系统中，由胆固醇形成27-羟基胆固醇后，它会从P450中释放出来，然后与胆固醇竞争重新进入酶活性位点以进一步氧化。在亚饱和底物浓度下，人P450c27将27-羟基胆固醇和3β-羟基-5-胆固醇氧化为酸的效率大于将胆固醇羟基化为27-羟基胆固醇的效率，
• Putative Helix F Contributes to Regioselectivity of Hydroxylation in Mitochondrial Cytochrome P450 27A1
  作者：Irina A. Pikuleva、Andrei Puchkaev、Ingemar Björkhem

  DOI：10.1021/bi010193i

  日期：2001.6.1

  correctly oriented substrate to the P450 active site. The I211K and F215K mutations, for example, affected the regioselectivity of P450 27A1-dependent hydroxylation reactions and conferred the P450 capacity to cleave the C-C bond of the substrate during the catalytic cycle. Studies of P450 11A1 indicate that Phe-202 has functions similar to those of its counterpart in P450 27A1 (Phe-215). We propose that

  基于与结构特征性细胞色素P450（P450s）的比对，我们确定了线粒体P450s 27A1和11A的推定F和G螺旋。我们在P450 27A1的推定螺旋F中的Phe-207，Ile-211和Phe-215以及推定的螺旋G中的Trp-235和Tyr-238处引入了取代，并比较了野生型和突变体的催化活性，产物模式，底物结合，过氧化氢的形成以及与氧化还原伴侣的相互作用。结果表明，突变的残基对于正确定向的底物向P450活性位点的传递很重要。例如，I211K和F215K突变影响了P450 27A1依赖性羟基化反应的区域选择性，并赋予了P450在催化循环中裂解底物CC键的能力。对P450 11A1的研究表明，Phe-202具有与P450 27A1（Phe-215）对应功能相似的功能。我们提出推定的螺旋F和G形成底物访问通道的侧面，从而提供了控制线粒体P450s中羟基化区域选择性的附加机制。
• Oxidation of 5β-cholestane-3α,7α,12α-triol into 3α,7α,12α-trihydroxy-5β-cholestanoic acid by cytochrome P-45026 from rabbit liver mitochondria
  作者：Helena Dahlbäck、Ingrid Holmberg

  DOI：10.1016/0006-291x(90)92034-w

  日期：1990.3

  Addition of NAD+ to the incubation mixture did not increase the formation of the acid. Incubation with 5 beta-cholestane-3 alpha,7 alpha,12 alpha,26-tetrol, cytochrome P-450(26), ferredoxin, ferredoxin reductase and NADPH resulted in one major product, 3 alpha,7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid. The cytochrome P-450 required both ferredoxin, ferredoxin reductase and NADPH for activity

  线粒体细胞色素P-450（26）先前被证明可催化5β-胆甾烷3α，7α，12α-三醇的26-羟基化反应，也可将该底物转化为3α，7α，12α -三羟基-5β-胆甾酸。3 alpha，7 alpha，12 alpha-trihydroxy-5 beta-cholestanoic acid的形成随着孵育时间和酶浓度的增加而增加。将NAD +添加到孵育混合物中不会增加酸的形成。与5个β-胆甾烷3α，7α，12α，26-四醇，细胞色素P-450（26），铁氧还蛋白，铁氧还蛋白还原酶和NADPH一起孵育可产生一种主要产物，即3个α，7个α，12个三羟基-5β-胆甾酸。细胞色素P-450需要铁氧还蛋白，铁氧还蛋白还原酶和NADPH才能发挥活性。NADPH无法用NAD +或NADP +代替。