(5β,12α)-12-(benzoyloxy)-3-oxocholan-24-oic acid methyl ester | 473462-08-7

• 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,12α)-12-(benzoyloxy)-3-oxocholan-24-oic acid methyl ester
• 英文别名: methyl 12α-(benzoyloxy)-3-oxo-5β-cholan-24-oate；[(5R,8R,9S,10S,12S,13R,14S,17R)-17-[(2R)-5-methoxy-5-oxopentan-2-yl]-10,13-dimethyl-3-oxo-1,2,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-12-yl] benzoate
• CAS: 473462-08-7
• 化学式: C₃₂H₄₄O₅
• 分子量: 508.698
• InChiKey: XVZWWWVBBJHTJM-SDPUYNCSSA-N

物化性质

• 沸点：
  587.6±35.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.72
• 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：

  (5β,12α)-12-(benzoyloxy)-3-oxocholan-24-oic acid methyl ester 在 溴 、 lithium carbonate 、 溶剂黄146 、 lithium bromide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.67h， 生成 (12α)-12-(benzoyloxy)-3-oxochol-4-en-24-oic acid
  参考文献：
  名称：

  Synthesis of [3,4-¹³C₂]-Enriched Bile Salts as NMR Probes of Protein−Ligand Interactions

  摘要：

  Synthetic methodology that allows for incorporation of isotopic carbon at the C-3 and C-4 positions of bile salts is reported. Three [3,4-C-13(2)]-enriched bile salts were synthesized from either deoxycholic or lithocholic acid. The steroid 3alpha-OH group was oxidized and the A-ring was converted into the Delta(4)-3-ketone. The C-24 carboxylic acid was next converted into the carbonate group and selectively reduced to the alcohol in the presence of the A-ring enone. Following protection of the 24-OH group, the Delta(4)-3-ketone was converted into the A-ring enol lactone. Condensation of the enol lactone with [1,2-C-13(2)]-enriched acetyl chloride and subsequent Robinson annulation afforded a [3,4-C-13(2)]-enriched Delta(4)-3-ketone that was subsequently converted back into a 3alpha-hydroxy-5beta-reduced bile steroid. C-7 hydroxylation, when necessary, was achieved via conversion of the Delta(4)-3-ketone into the corresponding Delta(4,6)-dien-3-one, epoxidation of the Delta(6)- double bond, and hydrogenolysis/hydrogenation of the 5,6-epoxy enone system. The [3,4-C-13(2)]-enriched bile salts were subsequently complexed to human ileal bile acid binding protein (I-BABP), and H-1-C-13 HSQC spectra were recorded to show the utility of the compounds for investigating the interactions of bile acids with I-BABP.

  DOI：

  10.1021/jo0259109
• 作为产物：
  描述：

  去氧胆酸 在 吡啶 、 盐酸 作用下， 以 水 、 甲苯 为溶剂， 反应 78.0h， 生成 (5β,12α)-12-(benzoyloxy)-3-oxocholan-24-oic acid methyl ester
  参考文献：
  名称：

  脱氧胆酸衍生物作为 P-糖蛋白介导的多药外排抑制剂

  摘要：

  脱氧胆酸衍生物被设计为 P-糖蛋白 (Pgp, ABCB1) 抑制剂。因此，已报道了甲基脱氧胆酸衍生物 5-10 及其醚类似物 15-20 的合成和生物活性。这些化合物调节 Pgp 介导的 MDR 的效力是通过柔红霉素积累和多柔比星在过度表达 Pgp 的 K562/R7 多药耐药细胞中的细胞毒性增强来评估的。同时，它们对 K562 敏感细胞的内在毒性受到赞赏。Methyl 12α-[(2R or 2S) tetrahydro-2H-pyran-2-yloxy]-3-oxo-5β-cholan-24-oate 9b 已显示出作为 Pgp 抑制剂的良好效率和低内在毒性。因此，该衍生物构成了一种新的先导化合物，可用作改进无毒 Pgp 调节剂设计的起点。

  DOI：

  10.1016/j.steroids.2016.09.017

文献信息

• Synthesis of [3,4-¹³C₂]-Enriched Bile Salts as NMR Probes of Protein−Ligand Interactions
  作者：Gregory P. Tochtrop、Gregory T. DeKoster、David P. Cistola、Douglas F. Covey

  DOI：10.1021/jo0259109

  日期：2002.9.1

  Synthetic methodology that allows for incorporation of isotopic carbon at the C-3 and C-4 positions of bile salts is reported. Three [3,4-C-13(2)]-enriched bile salts were synthesized from either deoxycholic or lithocholic acid. The steroid 3alpha-OH group was oxidized and the A-ring was converted into the Delta(4)-3-ketone. The C-24 carboxylic acid was next converted into the carbonate group and selectively reduced to the alcohol in the presence of the A-ring enone. Following protection of the 24-OH group, the Delta(4)-3-ketone was converted into the A-ring enol lactone. Condensation of the enol lactone with [1,2-C-13(2)]-enriched acetyl chloride and subsequent Robinson annulation afforded a [3,4-C-13(2)]-enriched Delta(4)-3-ketone that was subsequently converted back into a 3alpha-hydroxy-5beta-reduced bile steroid. C-7 hydroxylation, when necessary, was achieved via conversion of the Delta(4)-3-ketone into the corresponding Delta(4,6)-dien-3-one, epoxidation of the Delta(6)- double bond, and hydrogenolysis/hydrogenation of the 5,6-epoxy enone system. The [3,4-C-13(2)]-enriched bile salts were subsequently complexed to human ileal bile acid binding protein (I-BABP), and H-1-C-13 HSQC spectra were recorded to show the utility of the compounds for investigating the interactions of bile acids with I-BABP.
• Deoxycholic acid derivatives as inhibitors of P-glycoprotein-mediated multidrug efflux
  作者：Luc Rocheblave、Marc Rolland de Ravel、Elodie Monniot、Jeremy Tavenard、Claude-Yves Cuilleron、Catherine Grenot、Sylvie Radix、Eva-Laure Matera、Charles Dumontet、Nadia Walchshofer

  DOI：10.1016/j.steroids.2016.09.017

  日期：2016.12

  Deoxycholic acid derivatives were designed as P-glycoprotein (Pgp, ABCB1) inhibitors. Thus the synthesis and the biological activity of methyl deoxycholate derivatives 5-10 and their ether analogs 15-20 have been reported. The potency of these compounds to modulate Pgp-mediated MDR was evaluated through daunorubicin accumulation and potentiation of doxorubicin cytotoxicity in K562/R7 multidrug resistant

  脱氧胆酸衍生物被设计为 P-糖蛋白 (Pgp, ABCB1) 抑制剂。因此，已报道了甲基脱氧胆酸衍生物 5-10 及其醚类似物 15-20 的合成和生物活性。这些化合物调节 Pgp 介导的 MDR 的效力是通过柔红霉素积累和多柔比星在过度表达 Pgp 的 K562/R7 多药耐药细胞中的细胞毒性增强来评估的。同时，它们对 K562 敏感细胞的内在毒性受到赞赏。Methyl 12α-[(2R or 2S) tetrahydro-2H-pyran-2-yloxy]-3-oxo-5β-cholan-24-oate 9b 已显示出作为 Pgp 抑制剂的良好效率和低内在毒性。因此，该衍生物构成了一种新的先导化合物，可用作改进无毒 Pgp 调节剂设计的起点。