methyl 3β-formyloxy-5β-cholan-24-oate | 71837-93-9

• 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: methyl 3β-formyloxy-5β-cholan-24-oate
• 英文别名: methyl-3β-formyloxy-5β-cholanate；methyl 3β-formyloxycholanoate；3β-lithocholic acid；3β-formyloxy-5β-cholan-24-oic acid methyl ester；3β-Formyloxy-5β-cholan-24-saeure-methylester
• CAS: 71837-93-9
• 化学式: C₂₆H₄₂O₄
• 分子量: 418.617
• InChiKey: GUZAGPGVQJJYRZ-GFZGZXGPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.78
• 重原子数：
  30.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  52.6
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  methyl 3β-formyloxy-5β-cholan-24-oate 在 Zn(N3)2-2 pyr 、 水 、 sodium methylate 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 48.0h， 生成 3α-amino-5β-colanato di metile
  参考文献：
  名称：

  类固醇环肽，腔体的合成和形状

  摘要：

  从石胆酸和（S）-苯丙氨酸合成了环-[3α-（苯丙氨酰氨基）-5β-胆酸盐] 2 2。该合成需要三个转化：i）3α-羟基向3α-氨基的立体选择性转化；ii）制备线性甾体肽；iii）环二聚。NMR测量和MM3计算支持亲脂性空腔为2的构象。

  DOI：

  10.1016/s0040-4039(00)75839-4
• 作为产物：
  描述：

  石胆酸 在 硫酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 生成 methyl 3β-formyloxy-5β-cholan-24-oate
  参考文献：
  名称：

  Comparison of epimeric methyl lithocholate and methyl iso-lithocholate molecules: single crystal X-ray structure of methyl lithocholate, ab initio HF/6-31G* optimized structures and experimental and calculated DFT/B3LYP 13C NMR chemical shifts

  摘要：

  C-13 NMR chemical shifts have been measured and assigned for epimeric methyl 3alpha/beta-hydroxy-5beta-cholan-24-oates (methyl lithocholate [3alpha-OH epimer] and methyl iso-lithocholate [3beta-OH epimer]). Their molecular dynamics simulations suggest that for both epimers there exists two predominant gas phase conformations, which have been further forwarded for ab initio/HF optimizations and DFT/GIAO based C-13 NMR chemical shift calculations. Excellent linear relationships have been observed between experimental and calculated C-13 NMR chemical shifts for both epimers. For methyl lithocholate (MeLC), the other minimum energy conformation equates very well with the single crystal X-ray structure (orthorhombic, space group P2(1)2(1)2(1), unit cell a = 7.14710(10) Angstrom, b = 11.9912(2) Angstrom. c = 26.4368(5) Angstrom). The crystalline packing of MeLC consists of continuous parallel intermolecular hydrogen bonded [3alpha-(OHO)-O-...=C24] head-to-tail polymeric chains, which are further cross-linked by many simultaneous weak C(sp(3))(HO)-O-...-type of interactions. (C) 2002 Elsevier Science B.V. All rights reserved.

  DOI：

  10.1016/s0022-2860(02)00476-3

文献信息

• Synthesis of Lithocholic Acid Derivatives as Proteasome Regulators
  作者：Zhao Dang、Kathy Jung、Keduo Qian、Kuo-Hsiung Lee、Li Huang、Chin-Ho Chen

  DOI：10.1021/ml3001962

  日期：2012.11.8

  derivatives 3α-O-pimeloyl-lithocholic acid methyl ester (2) and its isosteric isomer (6) were found to activate the chymotrypsin-like activity of the proteasome at an EC50 of 7.8 and 4.3 μM, respectively. Replacing the C24 methyl ester in 2 with methylamide resulted in a complete devoid of proteasome activating activity. Epimerizing the C3 substituent from an α to β orientation transformed the activator

  由于蛋白酶体活性降低，异常蛋白质聚集体的积累，例如淀粉样蛋白 β 肽 (Aβ)，可能会导致阿尔茨海默病的神经变性。在这项研究中，发现石胆酸衍生物3α- O-庚二酰-石胆酸甲酯 ( 2 ) 及其等排异构体 ( 6 ) 分别以7.8 和 4.3 μM的 EC 50激活蛋白酶体的糜蛋白酶样活性. 在更换C24甲基酯2与甲酰胺导致完全没有蛋白酶体激活活性。将 C3 取代基从 α 到 β 方向差向异构化将激活剂转化为蛋白酶体抑制剂。与细胞蛋白酶体激活剂 PA28 不同，被2激活的蛋白酶体不受 Aβ 抑制。此外，2有效地拮抗 Aβ 对蛋白酶体的抑制作用。总之，化合物2代表了一类新的小分子，不仅可以激活蛋白酶体，还可以拮抗Aβ对蛋白酶体的抑制作用。
• Development of novel lithocholic acid derivatives as vitamin D receptor agonists
  作者：Hiroyuki Masuno、Yuko Kazui、Aya Tanatani、Shinya Fujii、Emiko Kawachi、Teikichi Ikura、Nobutoshi Ito、Keiko Yamamoto、Hiroyuki Kagechika

  DOI：10.1016/j.bmc.2019.07.003

  日期：2019.8

  more potent lithocholic acid derivatives, we synthesized several derivatives bearing a 3-sulfonate/carbonate or 3-amino/amide substituent, and examined their differentiation-inducing activity toward human promyelocytic leukemia HL-60 cells. Introduction of a nitrogen atom at the 3-position of lithocholic acid (2) decreased the activity, but compound 6 bearing a 3-methylsulfonate group showed more potent

  尽管与维生素D3的活性代谢产物1α，25-二羟基维生素相比，胆酸（2）与维生素D受体（VDR）的第二种内源性配体与维生素D3的活性代谢产物的结合亲和力和维生素D活性非常弱D3（1）。据报道，作为VDR激动剂，3-酰化的石胆酸比石胆酸（2）的效力稍强。在这里，为了开发更有效的石胆酸衍生物，我们合成了带有3-磺酸盐/碳酸盐或3-氨基/酰胺取代基的几种衍生物，并研究了它们对人早幼粒细胞白血病HL-60细胞的诱导分化活性。在石胆酸（2）的3位引入一个氮原子会降低活性，但是带有3-甲基磺酸盐基团的化合物6的活性比硫代胆酸（2）或它的酰化衍生物要强。通过竞争性结合测定和X射线晶体学分析VDR配体结合域（LBD）与6的复合物，证实了6与VDR的结合。
• ACYL AMIDES AS EPIMERIZATION REAGENTS^1,2
  作者：Frederic C. Chang、Robert T. Blickenstaff

  DOI：10.1021/ja01544a081

  日期：1958.6
• SYNTHESES OF α- AND β-DIMERS OF LITHOCHOLIC ACID ESTERS
  作者：Yuexian Li、Jerry Ray Dias

  DOI：10.1080/00304949609356522

  日期：1996.4
• Solid state structural studies of five bile acid derivatives
  作者：Arto Valkonen、Manu Lahtinen、Jari Tamminen、Erkki Kolehmainen

  DOI：10.1016/j.molstruc.2007.11.018

  日期：2008.8

  Five synthetically important bile acid derivatives have been characterized by C-13 CP-MAS, X-ray diffraction (both single crystal and powder), FTIR, and thermoanalytical (DSC and TG) methods. The crystallinity of all these derivatives is high, which can be deducted from the C-13 CP-MAS and powder X-ray diffraction data. Two of the compounds showed polymorphism, and one polymorph was structurally elucidated for both by comparing single crystal and powder X-ray diffraction data. (C) 2007 Elsevier B.V. All rights reserved.