methyl (4R)-4-[(3R,5S,7S,8R,9S,10S,13R,14S,17R)-7-formyloxy-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoate | 1364279-29-7

• 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: methyl (4R)-4-[(3R,5S,7S,8R,9S,10S,13R,14S,17R)-7-formyloxy-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoate
• CAS: 1364279-29-7
• 化学式: C₂₆H₄₂O₅
• 分子量: 434.616
• InChiKey: GJPDYNDIBVNASK-LBSADWJPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (4R)-4-[(3R,5S,7S,8R,9S,10S,13R,14S,17R)-7-formyloxy-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoate 在 sodium azide 、 三乙胺 作用下， 以 N,N-二甲基丙烯基脲 、 二氯甲烷 为溶剂， 反应 192.33h， 生成 24-methyl 3β-azido-7β-formyloxy-5β-cholanoate
  参考文献：
  名称：

  New fluorescent bile acids: Synthesis, chemical characterization, and disastereoselective uptake by Caco-2 cells of 3-deoxy 3-NBD-amino deoxycholic and ursodeoxycholic acid

  摘要：

  Deoxycholic acid (DCA), a secondary bile acid (BA), and ursodeoxycholic acid (UDCA), a tertiary BA, cause opposing effects in vivo and in cell suspensions. Fluorescent analogues of DCA and UDCA could help investigate important questions about their cellular interactions and distribution.We have prepared a set of isomeric 3 alpha- and 3 beta-amino analogues of UDCA and DCA and derivatised these with the discrete fluorophore, 4-nitrobenzo-2-oxa-1,3-diazol (NBD), forming the corresponding four fluorescent adducts. These absorb in the range 465-470 nm and fluoresce at approx. 535 nm.In order to determine the ability of the new fluorescent bile acids to mimic the parents, their uptake was studied using monolayers of Caco-2 cells, which are known to express multiple proteins of the organic anion-transporting peptide (OATP) subfamily of transporters. Cellular uptake was monitored over time at 4 and 37 degrees C to distinguish between passive and active transport.All four BA analogues were taken up but in a strikingly stereo-and structure-specific manner, suggesting highly discriminatory interactions with transporter protein(s). The alpha-analogues of DCA and to a lesser extent UDCA were actively transported, whereas the beta-analogues were not. The active transport process was saturable, with Michaelis-Menten constants for 3 alpha-NBD DCA (5) being K-m = 42.27 +/- 12.98 mu M and V-max = 2.8 +/- 0.4 nmol/(mg protein*min) and for 3 alpha-NBD UDCA (3) K-m = 28.20 +/- 7.45 mu M and V-max = 1.8 +/- 0.2 nmol/(mg protein(*)min). These fluorescent bile acids are promising agents for investigating questions of bile acid biology and for detection of bile acids and related organic anion transport processes. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.01.002
• 作为产物：
  描述：

  在 氨 作用下， 以 甲醇 为溶剂， 反应 0.08h， 生成 methyl (4R)-4-[(3R,5S,7S,8R,9S,10S,13R,14S,17R)-7-formyloxy-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoate
  参考文献：
  名称：

  Chemical synthesis of 3β-sulfooxy-7β-hydroxy-24-nor-5-cholenoic acid: An internal standard for mass spectrometric analysis of the abnormal Δ5-bile acids occurring in Niemann-Pick disease

  摘要：

  In Niemann-Pick disease, type C1, increased amounts of 3 beta,7 beta-dihydroxy-5-cholenoic acid are reported to be present in urinary bile acids. The compound occurs as a tri-conjugate, sulfated at C-3, N-acetylglucosamidated at C-7, and N-acylamidated with taurine or glycine at C-24. For sensitive LC-MS/MS analysis of this bile acid, a suitable internal standard is needed. We report here the synthesis of a satisfactory internal standard, 3 beta-sulfooxy-7 beta-hydroxy-24-nor-5-cholenoic acid (as the disodium salt). The key reactions involved were (1) the so-called "second order" Beckmann rearrangement (one-carbon degradation at C-24) of hyodeoxycholic acid (HDCA) 3,6-diformate with sodium nitrite in a mixture of trifluoroacetic anhydride and trifluoroacetic acid, (2) simultaneous inversion at C-3 and elimination at C-6 of the ditosylate derivatives of the resulting 3 alpha,6 alpha-dihydroxy-24-nor-5 beta-cholanoic acid with potassium acetate in aqueous N,N-dimethylformamide, and (3) regioselective sulfation at C-3 of an intermediary 3 beta,7 beta-dihydroxy-24-nor-Delta(5) derivative using sulfur trioxide-trimethylamine complex. Overall yield of the desired compound was 1.8% in 12 steps from HDCA. (C) 2009 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2009.04.007

文献信息

• THERAPEUTIC COMPOUNDS AND METHODS OF USE THEREOF
  申请人：REGENTS OF THE UNIVERSITY OF MINNESOTA

  公开号：US20200376007A1

  公开（公告）日：2020-12-03

  The invention provides a compound of formula (I): or a salt thereof, wherein R 1 , R 2 , R 3 , R 4 and R 6 have any of the values described in the specification, as well as compositions comprising a compound of formula (I). The compounds are agonists of the TGR5 receptor.

  该发明提供了一个化合物的结构式(I)：或其盐，其中R1、R2、R3、R4和R6可以取得规范中描述的任何值，以及包含结构式(I)化合物的组合物。这些化合物是TGR5受体的激动剂。
• A fluorescent analogue of tauroursodeoxycholic acid reduces ER stress and is cytoprotective
  作者：Jason Gavin、Fran Quilty、Ferenc Majer、Georgina Gilsenan、Anne Marie Byrne、Aideen Long、Gabor Radics、John F. Gilmer

  DOI：10.1016/j.bmcl.2016.06.059

  日期：2016.11

  Tauroursodeoxycholic acid (TUDCA) is a cytoprotective ER stress inhibitor and chemical chaperone. It has therapeutic potential in a wide array of diseases but a specific macromolecular target or molecular mechanism of action remains obscure. This Letter describes an effective new synthetic approach to taurine conjugation of bile acids which we used to prepare 3 alpha-dansyl TUDCA (4) as a probe for TUDCA actions.As a model of ER stress we used the hepatocarcinoma cell line HUH7 and stimulation with either deoxycholic acid (DCA, 200 mu M) or tunicamycin (5 mu g/ml) and measured levels of Bip/GRP78, ATF4, CHOP and XBP1s/XBP1u. Compound 4 was more effective than UDCA at inhibiting ER stress markers and had similar effects to TUDCA. In a model of cholestasis using the cytotoxic DCA to induce apoptosis, pretreatment with 4 prevented cell death similarly to TUDCA whereas the unconjugated clinically used UDCA had no effect.3 alpha-Dansyl TUDCA (4) appears to be a suitable reporter for TUDCA effects on ER stress and related cytoprotective activity. (C) 2016 Elsevier Ltd. All rights reserved.