(R)-4-[(3S,8S,9S,10R,13R,14S,17R)-3-(tert-Butyl-dimethyl-silanyloxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-pentanoic acid | 897364-87-3

• 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: (R)-4-[(3S,8S,9S,10R,13R,14S,17R)-3-(tert-Butyl-dimethyl-silanyloxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-pentanoic acid
• 英文别名: (4R)-4-[(3S,8S,9S,10R,13R,14S,17R)-3-[tert-butyl(dimethyl)silyl]oxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid
• CAS: 897364-87-3
• 化学式: C₃₀H₅₂O₃Si
• 分子量: 488.827
• InChiKey: IGJFVZMWNOWLGG-RFWRZFGQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.46
• 重原子数：
  34
• 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：

  (R)-4-[(3S,8S,9S,10R,13R,14S,17R)-3-(tert-Butyl-dimethyl-silanyloxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-pentanoic acid 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 17.0h， 以3.561 g的产率得到(3beta)-3-O-叔-丁基二甲基硅烷基-胆甾-5-烯-3,24-二醇
  参考文献：
  名称：

  (25S)-Cholesten-26-oic Acids - 秀丽隐杆线虫 DAF-12 受体的有效配体的合成和激素活性

  摘要：

  使用高度立体选择性的 Evans aldol 反应在 C-25 处引入立体中心，我们描述了正交双保护 (25S)-26-羟基胆固醇 11 的有效合成。在几个合成步骤中，这个关键的中间体 11 已被转化进入四种 (25S)-cholesten-26-oic 酸 1-4，基于市售的 3β-hydroxychol-5-en-24-oic 酸，它们分 12-15 个步骤获得，总产率为 19-53%（ 5）。我们对化合物 1-4 的生物学研究表明，(25S)-Δ7-dafachronic 酸 (1) 代表了秀丽隐杆线虫中激素受体 DAF-12 的最活跃的甾体配体。此外，饱和的 (25S)-dafachronic 酸 (3) 代表该受体的新配体，并且 (25S)-甾体酸与其相应的 (25R)-对应物相比更具活性。

  DOI：

  10.1002/ejoc.200900443
• 作为产物：
  描述：

  3B-羟基-D5-胆烯酸 在 咪唑 、 4-二甲氨基吡啶 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (R)-4-[(3S,8S,9S,10R,13R,14S,17R)-3-(tert-Butyl-dimethyl-silanyloxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-pentanoic acid
  参考文献：
  名称：

  On the importance of the pore inner cavity for the ionophoric activity of 1,3-alternate calix[4]arene/steroid conjugates

  摘要：

  1,3-Alternate calix[4]arenes, decorated with four nonpolar 'all-trans' tetracyclic nuclei and cation-stabilizing beta-methoxyethoxy appendages, were synthesized from commercially available starting materials and through straightforward functional groups transformations/couplings. Their Na+-transport activities, when compared with those exerted by the known conformationally-rigidified 1,3-alternate calix[4]-arene AB/cis cholic acid conjugates, suggest that the cation conductance is related to the morphology of the pendant steroids. (c) 2006 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tet.2006.04.028

文献信息

• Side-chain deuterated cholesterol as a molecular probe to determine membrane order and cholesterol partitioning
  作者：Shinya Hanashima、Yuki Ibata、Hirofumi Watanabe、Tomokazu Yasuda、Hiroshi Tsuchikawa、Michio Murata

  DOI：10.1039/c9ob01342c

  日期：——

  original membrane properties, was synthesized by a stereoselective introduction of 2H into the side chain of cholesterol. A deuterium label at the side-chain more sensitively reflects membrane fluidity than the conventional labeling at the 3 position of a sterol core (3-d-cholesterol), thus providing 24-d-cholesterol with desirable properties to report membrane ordering. Solid state 2H NMR of 24-d-cholesterol

  胆固醇是哺乳动物细胞膜中必不可少的成分。但是，它的分布和与磷脂的相互作用通常难以捉摸，部分原因是用于制备胆固醇探针的化学修饰常常会引起其膜行为的显着扰动。为了克服这些问题，通过将2H立体选择性地引入胆固醇的侧链，合成了2H标记的探针（24-d-胆固醇），该探针完全保留了原始的膜特性。与在固醇核心（3-d-胆固醇）的3位上的常规标记相比，侧链上的氘标记更敏感地反映了膜的流动性，因此为24-d-胆固醇提供了报告膜有序性所需的特性。双层膜中24-d-胆固醇与鞘磷脂（SM）和不饱和磷脂酰胆碱的固态2H NMR清楚地显示了筏状液有序（Lo）相和基于与胆固醇相互作用的无序液相中胆固醇的分配比例每个阶段都围绕脂质。结果证明该探针优于广泛使用的3-d-胆固醇。例如，24-d-胆固醇清楚地显示了棕榈酰-SM和硬脂酰-SM之间胆固醇的Lo分布比存在10 mol％的差异。在固态2H NMR中24-d-胆固醇的全
• Asymmetric isopropylation of steroidal 24-aldehydes for the synthesis of 24(R)-hydroxycholesterol
  作者：Makoto Okamoto、Masayasu Tabe、Takao Fujii、Toshio Tanaka

  DOI：10.1016/0957-4166(95)00073-x

  日期：1995.3

  The chiral beta-amino alcohols-catalyzed addition of diisopropylzinc to steroidal 24-aldehydes successfully provided 24(R)-hydroxycholesterols in good yields with high diastereoselectivities, which are synthetic intermediates of 1 alpha,24(R)-dihydroxyvitamin D-3 (1). alpha,beta-Unsaturated steroidal aldehydes were found to give the corresponding isopropylated adducts in much higher yields (up to 91%) than those of saturated steroidal aldehydes.
• The Effect of Small Molecules on Sterol Homeostasis: Measuring 7-Dehydrocholesterol in Dhcr7-Deficient Neuro2a Cells and Human Fibroblasts
  作者：Zeljka Korade、Hye-Young H. Kim、Keri A. Tallman、Wei Liu、Katalin Koczok、Istvan Balogh、Libin Xu、Karoly Mirnics、Ned A. Porter

  DOI：10.1021/acs.jmedchem.5b01696

  日期：2016.2.11

  Well-established cell culture models were combined with new analytical methods to assess the effects of small molecules on the cholesterol biosynthesis pathway. The analytical protocol, which is based on sterol derivation with the dienolphile PTAD, was found to be reliable for the analysis of 7-DHC and desmosterol. The PTAD method was applied to the screening of a small library of pharmacologically active substances, and the effect of compounds on the cholesterol pathway was determined. Of some 727 compounds, over 30 compounds decreased 7-DHC in Dhcr7-deficient Neuro2a cells. The examination of chemical structures of active molecules in the screen grouped the compounds into distinct categories. In addition to statins, our screen found that SERMs, antifungals, and several antipsychotic medications reduced levels of 7-DHC. The activities of selected compounds were verified in human fibroblasts derived from Smith Lemli Opitz syndrome (SLOS) patients and linked to specific transformations in the cholesterol biosynthesis pathway.
• Pharmacophore Analysis of the Nuclear Oxysterol Receptor LXRα
  作者：Thomas A. Spencer、Dansu Li、Jonathon S. Russel、Jon L. Collins、Randy K. Bledsoe、Thomas G. Consler、Linda B. Moore、Cristin M. Galardi、David D. McKee、John T. Moore、Michael A. Watson、Derek J. Parks、Millard H. Lambert、Timothy M. Willson

  DOI：10.1021/jm0004749

  日期：2001.3.1

  A cell-free assay was developed for the orphan nuclear receptor LXR alpha that measures the ligand-dependent recruitment of a peptide from the steroid receptor coactivator 1 (SRC1) to the nuclear receptor. Using this ligand-sensing assay (LiSA), the structural requirements for activation of the receptor by oxysterols and related compounds were studied. The minimal pharmacophore for receptor activation was shown to be a sterol with a hydrogen bond acceptor at C24. 24(S),25-Epoxycholesterol (1), which meets this criterion, is among the most efficacious of the oxysterols and is an attractive candidate as the LXR alpha natural hormone. Cholenic acid dimethylamide (14) showed increased efficacy compared to 1, whereas the unnatural oxysterol 22(S)-hydroxycholesterol (4) was shown to be an antagonist of 1 in the LiSA. The structural requirements for SRC1 recruitment in the LiSA correlated with the transcriptional activity of compounds in a cell-based reporter assay employing LXR alpha -GAL4 chimeric receptors. Site-directed mutagenesis identified Trp(443) as an amino acid critical for activation of LXR alpha by oxysterol ligands. This information was combined with the structure-activity relationship developed from the LiSA to develop a 3D homology model of LXR alpha. This model may aid the design of synthetic drugs targeted at this transcriptional regulator of cholesterol homeostasis.
• Synthesis and biological activity of (24E)- and (24Z)-26-hydroxydesmosterol
  作者：Ratni Saini、Olga Kataeva、Arndt W. Schmidt、Yuqin Wang、Anna Meljon、William J. Griffiths、Hans-Joachim Knölker

  DOI：10.1016/j.bmc.2013.07.015

  日期：2013.9

  Using 3 beta-hydroxychol-5-en-24-oic acid (4) as starting material, the diastereoisomeric allylic alcohols (24E)-26-hydroxydesmosterol (2) and (24Z)-26-hydroxydesmosterol (3) have been synthesised in six steps with 67% and 12% overall yield, respectively. Both of these isomers are found in newborn mouse brain where sterol synthesis is high. Unlike desmosterol (1), neither of these isomers is a ligand to the liver x receptors and thus represents a novel biological deactivation mechanism avoiding cholesterol synthesis. (C) 2013 Elsevier Ltd. All rights reserved.