4β-acetoxycholest-5-en-3β-ol

• 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: 4β-acetoxycholest-5-en-3β-ol
• 英文别名: 4β-Acetoxycholesterin；Hydroxy-3β-acetoxy-4β-cholesten-5；acetic acid-(3β-hydroxy-cholesten-(5)-yl-(4β)-ester)；Essigsaeure-(3β-hydroxy-cholesten-(5)-yl-(4β)-ester)；(10R)-3c-Hydroxy-4c-acetoxy-10r.13c-dimethyl-17c-((R)-1.5-dimethyl-hexyl)-(8cH.9tH.14tH)-Δ⁵-tetradecahydro-1H-cyclopenta[a]phenanthren；4β-Acetoxy-cholesten-(5)-ol-(3β)；[(3S,4R,8S,9S,10R,13R,14S,17R)-3-hydroxy-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-4-yl] acetate
• 化学式: C₂₉H₄₈O₃
• 分子量: 444.698
• InChiKey: CPAJTVKFJMIGFR-UOVLKSFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4β-acetoxycholest-5-en-3β-ol 在 吡啶 、 氯化亚砜 、 乙醚 作用下， 生成 bis-(4β-acetoxy-cholesten-(5)-yl-(3β))-sulfite
  参考文献：
  名称：

  Polyglucosan body disease in a mixed-breed dog

  摘要：

  AIM: To describe the histopathology of a previously unrecorded canine disease and deduce the cause of the lesions.METHODS: Formalin-fixed tissues were processed into paraffin wax and epoxy resin for light and electron microscopy of variously stained sections of liver, brain, heart muscle and kidney.RESULTS: Periodic acid Schiff (PAS)-positive bodies in liver and myocardium were typical of a polyglucosan body disease. Neurons contained coarse granular material that stained similarly to the polyglucosan bodies.CONCLUSION: The nature, distribution and histochemistry of lesions observed are consistent with a putative diagnosis of Glycogen storage disease type IV, an inherited metabolic defect associated with a deficiency of glycogen-branching enzyme not previously reported in dogs.

  DOI：

  10.1080/00480169.2002.36247
• 作为产物：
  描述：

  6β-chloro-5-hydroxy-5α-cholestan-3β-yl acetate 在 1,4-二氧六环 、 吡啶 、 氯化亚砜 、 溶剂黄146 作用下， 生成 4β-acetoxycholest-5-en-3β-ol
  参考文献：
  名称：

  Polyglucosan body disease in a mixed-breed dog

  摘要：

  AIM: To describe the histopathology of a previously unrecorded canine disease and deduce the cause of the lesions.METHODS: Formalin-fixed tissues were processed into paraffin wax and epoxy resin for light and electron microscopy of variously stained sections of liver, brain, heart muscle and kidney.RESULTS: Periodic acid Schiff (PAS)-positive bodies in liver and myocardium were typical of a polyglucosan body disease. Neurons contained coarse granular material that stained similarly to the polyglucosan bodies.CONCLUSION: The nature, distribution and histochemistry of lesions observed are consistent with a putative diagnosis of Glycogen storage disease type IV, an inherited metabolic defect associated with a deficiency of glycogen-branching enzyme not previously reported in dogs.

  DOI：

  10.1080/00480169.2002.36247

文献信息

• Cholesterol and the Adrenal Cortical Hormone
  作者：O. ROSENHEIM、H. KING

  DOI：10.1038/1391015a0

  日期：1937.6

  oxygen, leading to the formation of cis Δ5:6-cholestene-3 : 4-diol, suggested that this reactive primary oxidation product may play an important role in the metabolism of cholesterol and the sexual hormones. Experimental confirmation of this view was obtained by feeding experiments, which showed that the diol, as well as its intermediate dehydration product cholestenone, were converted into coprosterol

  发现胆固醇分子的碳原子 C4 是氧的第一个攻击点，导致形成顺式 Δ5:6-cholestene-3:4-二醇，表明这种反应性初级氧化产物可能在胆固醇和性激素的代谢。这一观点的实验证实是通过饲养实验获得的，该实验表明二醇及其中间脱水产物胆甾酮被动物有机体转化为粪甾醇1。我们现在已经通过顺式二醇的 3 单乙酸酯（或 3-苯甲酸酯）的轻度氧化获得了可能是 4-酮胆甾醇 3-乙酸酯（或 3-苯甲酸酯）的氧化物。这些化合物在水解时产生高活性物质 C27H42O2 (I)，它具有典型的二酚（布楚樟脑）（II）组 -C = COH-CO-。
• Synthesis of [D4]- and [D7]-4β-hydroxycholesterols for use in a novel drug-drug interaction assay
  作者：Wesley A. Turley、Richard C. Burrell、Samuel J. Bonacorsi、Angela K. Goodenough、Joelle M. Onorato

  DOI：10.1002/jlcr.1952

  日期：2012.2

  Cytochrome P450 3A (CYP3A) enzymes are involved in the metabolism of over half of today's prescription drugs. As a result, drugs metabolized by CYP3A have a risk of drug–drug interactions (DDIs). Recent studies have shown the potential to use 4β-hydroxycholesterol as an endogenous biomarker of CYP3A activity and predictor of potential DDIs. Bristol–Myers Squibb has developed a liquid chromatography-electron ionization-tandem mass spectrometry method that accurately measures 4β-hydroxycholesterol levels in clinical plasma samples following treatment with a CYP3A inducer or inhibitor. Stable isotope labeled (SIL) [D4]- and [D7]-4β-hydroxycholesterols were synthesized to assist in the development of this new quantification method. The SIL analogs were prepared from the appropriate [D4]- or [D7]-cholesterol starting material in two steps. The labeled cholesterols were oxidized with bromine and silver acetate in pyridine to give an acetate protected hydroxy group at C4. Hydrolysis of the acetate protecting group provided [D4]- and [D7]-4β-hydroxycholesterols in 15%–28% overall yield. 4α-Hydroxycholesterol was also required during method development and was prepared in four steps from cholesteryl benzoate in 1% overall yield.

  细胞色素 P450 3A (CYP3A) 酶参与了当今一半以上处方药的代谢。因此，经 CYP3A 代谢的药物有发生药物间相互作用 (DDI) 的风险。最近的研究表明，4β-羟基胆固醇有可能被用作 CYP3A 活性的内源性生物标记物和潜在 DDIs 的预测因子。百时美施贵宝公司已开发出一种液相色谱-电离-串联质谱方法，可准确测量临床血浆样本中使用 CYP3A 诱导剂或抑制剂治疗后的 4β- 羟基胆固醇水平。为了帮助开发这种新的定量方法，我们合成了稳定同位素标记（SIL）[D4]- 和 [D7]-4β-羟基胆固醇。SIL 类似物由适当的[D4]-或[D7]-胆固醇起始材料分两步制备而成。标记的胆固醇在吡啶中被溴和乙酸银氧化，从而在 C4 处产生一个受乙酸酯保护的羟基。水解乙酸酯保护基团可得到[D4]-和[D7]-4β-羟基胆固醇，总产率为 15%-28%。4α- 羟基胆固醇也是在方法开发过程中需要的，由胆固醇苯甲酸酯分四步制备，总收率为 1%。
• Synthesis and evaluation of new 6-hydroximinosteroid analogs as cytotoxic agents
  作者：Javier Poza、Miriam Rega、Vanessa Paz、Beatriz Alonso、Jaime Rodríguez、Nélida Salvador、Antonio Fernández、Carlos Jiménez

  DOI：10.1016/j.bmc.2007.05.003

  日期：2007.7

  Taking into account the structural requirements for cytotoxicity, several new hydroximinosteroid derivatives have been prepared and evaluated for their cytotoxic activity against A-549, HI 16, PSN1, and T98G cultured tumor cell lines in order to obtain further information on the potential pharmacophoric core of this type of compound. The influence of the oxygenated position in the A ring, the presence of an additional oxygenated position at C-7 and C-16, and a fluorinated position at C-5 were considered in order to study the structure-activity relationships. The results reveal the importance of oxygenated positions in the A ring (e.g., 4,5-epoxide showed an IC50 value against HCT-116 under micromolar level) for an increase in cytotoxic activity in this type of compound. Furthermore, they showed an important selectivity toward colon tumor line (HCT-116). (c) 2007 Elsevier Ltd. All rights reserved.
• 79. The action of selenium dioxide on sterols and bile acids. Part III. Cholesterol
  作者：O. Rosenheim、W. W. Starling

  DOI：10.1039/jr9370000377

  日期：——
• 118. Acyl migrations in the sterol series
  作者：M. F. C. Paige

  DOI：10.1039/jr9430000437

  日期：——