23-oxo-24-nor-5β-cholane-3α,7α-diyl diacetate | 202462-10-0

• 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: 23-oxo-24-nor-5β-cholane-3α,7α-diyl diacetate
• 英文别名: [(3R,5S,7R,8R,9S,10S,13R,14S,17R)-7-acetyloxy-10,13-dimethyl-17-[(2R)-4-oxobutan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl] acetate
• CAS: 202462-10-0
• 化学式: C₂₇H₄₂O₅
• 分子量: 446.627
• InChiKey: ORUSBHZXADMUHE-RAXQWLNNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  69.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  23-oxo-24-nor-5β-cholane-3α,7α-diyl diacetate 在 lithium aluminium tetrahydride 、 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.5h， 生成 (3R,5R,7R,8R,9S,10S,13R,14S,17R)-17-((Z)-(1R,5R)-6-Benzyloxy-1,5-dimethyl-hex-3-enyl)-3-(tert-butyl-diphenyl-silanyloxy)-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-7-ol
  参考文献：
  名称：

  Synthesis of pavoninin-1, a shark repellent substance, and its structural analogues toward mechanistic studies on their membrane perturbation

  摘要：

  Pavoninin-1 (1), which was isolated from a defense secretion of the sole Pardachirus spp. as an ichthyotoxic and a shark repellent principle, and its structural analogue 2 were synthesized, where glycosylation using an 2-azidoglycosyl sulfoxide (10) afforded the corresponding beta-glycoside exclusively in high yield. Introduction of the alpha,beta-unsaturated ketone system in the ring A of 1 was achieved by phenylselenenylation of dihydropavoninin-1 (3) and subsequent oxidative elimination without protection of the hydroxyl groups in the sugar portion. The mode of action of these glycosides was evaluated for their perturbation on phosphatidylcholine liposomal membrane, using the fluorescent dye leakage method. The results revealed that membrane affinity does not parallel membrane perturbation but rather compensates it, and the spatial arrangement of hydrophobic and hydrophilic regions within a molecule is likely to reflect on the difference in potency of action among them. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(97)00170-3
• 作为产物：
  描述：

  3α,7α-diacetoxy-5β-cholan-24-ol 在 pyridinium chlorochromate 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 23-oxo-24-nor-5β-cholane-3α,7α-diyl diacetate
  参考文献：
  名称：

  犀鸟中的两种主要胆汁酸，（24R，25S）-3alpha，7alpha，24-三羟基-5beta-胆甾烷-27-牛磺酸和其12alpha-羟基衍生物。

  摘要：

  从鸟类犀牛科的Bucerotidae科的两种犀鸟的胆囊胆汁中分离出两种主要胆汁酸。确定其结构为3α，7α，24-二羟基-5β-胆甾醇-27-oic酸及其12α-羟基衍生物，3α，7α，12α，24-四羟基-5β-胆甾醇-27-oic酸（戊酸，VA），两者均以胆汁中的牛磺酸酰胺化物形式存在于胆汁中。合成了四种钒酸的非对映异构体，并通过X射线晶体学分析确定了它们的指定结构。发现VA及其12-脱氧衍生物具有（24R，25S）构型。还通过HPLC分析了另外13种犀鸟物种，它们显示出与双歧双歧杆菌和帕尼尼假单胞菌相似的胆汁酸模式。

  DOI：

  10.1007/s11745-016-4150-0

文献信息

• Bile Acid Derivatives as Ligands of the Farnesoid X Receptor. Synthesis, Evaluation, and Structure−Activity Relationship of a Series of Body and Side Chain Modified Analogues of Chenodeoxycholic Acid
  作者：Roberto Pellicciari、Gabriele Costantino、Emidio Camaioni、Bahman M. Sadeghpour、Antonio Entrena、Timothy M. Willson、Stefano Fiorucci、Carlo Clerici、Antimo Gioiello

  DOI：10.1021/jm049904b

  日期：2004.8.1

  The farnesoid X receptor (FXR) is activated by endogenous bile acids (BAs) and plays a variety of physiological roles related to modulation of gene transcription. In particular, FXR positively regulates the cholesterol catabolism while feedback inhibits the BA synthesis by repressing the expression of the CYP7A and CYP8B genes. We have previously shown that 6alpha-ethyl-CDCA (6ECDCA) is a potent and selective FXR agonist. In this paper we report an extensive structure-activity relationship for a series of synthetic bile acids. Our results indicate that the 6alpha position plays a fundamental role in determining affinity and that the side chain of BA is amenable to a variety of chemical modification. Although none of the new derivatives is more potent than 6ECDCA, we show here that a wide variability in efficacy, from full agonists to partial antagonists, can be obtained.