3β-hydroxy-5α-cholestan-6α-yl acetate | 1973-42-8

• 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: 3β-hydroxy-5α-cholestan-6α-yl acetate
• 英文别名: 6α-acetyloxy-5α-cholestan-3β-ol
• CAS: 1973-42-8
• 化学式: C₂₉H₅₀O₃
• 分子量: 446.714
• InChiKey: HSTARSFCWAPQER-NRDPMAAJSA-N

物化性质

• 熔点：
  90-95 °C
• 沸点：
  516.1±33.0 °C(Predicted)
• 密度：
  1.02±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.01
• 重原子数：
  32.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  46.53
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  3β-hydroxy-5α-cholestan-6α-yl acetate 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 29.0h， 生成 (3R,5S,6S,8S,9S,10R,13R,17R)-17-((R)-1,5-Dimethyl-hexyl)-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthrene-3,6-diol
  参考文献：
  名称：

  First total synthesis of xestobergsterol A and active structural analogues of the xestobergsterols

  摘要：

  The novel pentacyclic polyhydroxylated sterol, xestobergsterol A la, a strong inhibitor of histamine release from rat mast cells induced by anti-IgE, has been synthesized in 24 steps and good overall yield From stigmasterol 7. The Breslow remote functionalization process has been extended to several more highly functionalized steroid derivatives, especially those with oxygen functionality in the B-ring. The key steps of the synthesis of xestobergsterol A la and its analogues, 7-deoxyxestobergsterol A Id and 16,23-seco-23-deoxyxestobergsterol A 73, are the Breslow remote functionalization of oxygenated steroids and for compounds la and Id, a novel base-catalyzed epimerization-aldol condensation of a dione to give the desired CD-cis ring structure of the xestobergsterols. Thus the known alcohol 75, prepared from stigmasterol 7, was taken to the tetraacetate 107 which was then converted via a Breslow remote functionalization into the alkene aldehyde 114 which was transformed in 5 steps to xestobergsterol A la. Testing of the synthetic materials showed that the two analogues, 7-deoxyxestobergsterol A Ib and 16,23-seco-23-deoxyxestobergsterol A 73, are also potent inhibitors of histamine release with ICS, values (IC50 500 nM and 750 nM, respectively) being only 1015 times less than that of xestobergsterol A itself (50 nM). (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(00)01086-3
• 作为产物：
  描述：

  3β-(2-tetrahydropyranyloxy)-5α-cholestan-6α-yl acetate 在 盐酸 、 水 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 1.33h， 以89%的产率得到3β-hydroxy-5α-cholestan-6α-yl acetate
  参考文献：
  名称：

  Synthesis of the sulfates derived from 5α-cholestane-3β, 6α-diol

  摘要：

  Three new steroid sulfates-3-beta-hydroxy-5-alpha-cholestan-6-alpha-yl sulfate, 6-alpha-hydroxy-5-alpha-cholestan-3-beta-yl sulfate, and 5-alpha-cholestan-3-beta,6-alpha-diyl disulfate-were synthesized. For the syntheses of the key intermediates, 3-beta-hydroxy-5-alpha-cholestan-6-alpha-yl acetate and 6-alpha-hydroxy-5-alpha-cholestan-3-beta-yl acetate, selective protection of hydroxy groups in 5-alpha-cholestane-3-beta,6-alpha-diol was necessary. This problem was solved by using a combination of acetyl, tetrahydropyranyl, and methoxymethyl protective groups, which represents a new approach leading to these hydroxy acetates. Sulfated derivatives of 5-alpha-cholestane-3-beta,6-alpha-diol are present in marine invertebrates and were synthesized for the purposes of biologic testing.

  DOI：

  10.1016/0039-128x(92)90107-k

文献信息

• Structure–activity relationship studies of Niemann-Pick type C1-like 1 (NPC1L1) ligands identified by screening assay monitoring pharmacological chaperone effect
  作者：Fumika Karaki、Kenji Ohgane、Kosuke Dodo、Yuichi Hashimoto

  DOI：10.1016/j.bmc.2013.06.022

  日期：2013.9

  A number of hereditary diseases are caused by defective protein trafficking due to a folding defect resulting from point mutations in proteins. Ligands that bind to the folding intermediates of such mutant proteins and rescue their trafficking defects, known as pharmacological chaperones, have promise for the treatment of certain genetic diseases, including Fabry disease, cystic fibrosis, and Niemann-Pick disease type C. Here we show that this pharmacological chaperone effect can be used for ligand screening, that is, binding of candidate ligands can be detected by monitoring the ligand-mediated correction of a localization defect caused by artificially introduced point mutations of the protein of interest. Using this method, we discovered novel steroidal ligands of Niemann-Pick type C1-like 1 (NPC1L1), an intestinal cholesterol transporter that is the target of the cholesterol absorption inhibitor ezetimibe, and conducted structure-activity relationship studies. We also present data indicating that the binding site of the new ligands is distinct from both the N-terminal sterol-binding domain and the ezetimibe-binding site. (C) 2013 Elsevier Ltd. All rights reserved.