(1R,3aS,7aR)-1-[(2R)-6-triethylsilyloxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,6,7,7a-hexahydro-1H-inden-4-yl trifluoromethanesulfonate | 1227058-11-8

• 英文名称: (1R,3aS,7aR)-1-[(2R)-6-triethylsilyloxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,6,7,7a-hexahydro-1H-inden-4-yl trifluoromethanesulfonate
• CAS: 1227058-11-8
• 化学式: C₂₅H₄₅F₃O₄SSi
• 分子量: 526.777
• InChiKey: AMIODILFRZDIIO-GECPAALWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.17
• 重原子数：
  34.0
• 可旋转键数：
  12.0
• 环数：
  2.0
• 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：

  (1R,3aS,7aR)-1-[(2R)-6-triethylsilyloxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,6,7,7a-hexahydro-1H-inden-4-yl trifluoromethanesulfonate 在 喹啉 、 盐酸 、 copper(l) iodide 、 Wilkinson's catalyst 、 二乙酰二(三苯基膦)钯 、 四丁基氟化铵 、 氢气 、 二乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 2.75h， 生成 14-epi-2α-methyl-1α,25-dihydroxy-19-nortachysterol
  参考文献：
  名称：

  Development of 14-epi-19-Nortachysterol and Its Unprecedented Binding Configuration for the Human Vitamin D Receptor

  摘要：

  In the study of the synthesis of 14-epi-19-norprevitamin D-3, we found 14-epi-19-nortachysterol derivatives through C6,7-cis/trans isomerization. We also succeeded in their chemical synthesis and revealed their marked stability and potent VDR binding affinity. To the best of our knowledge, this is the first isolation of stable tachysterol analogues. Surprisingly, 14-epi-19-nortachysterol derivatives exhibited an unprecedented binding configurations for the ligand binding pocket in hVDR, C5,6-s-trans and C7,8-s-trans triene configurations, which were opposite the natural C7,8-ene-configuration of 1 alpha,25(OH)(2)D-3.

  DOI：

  10.1021/ja201481j
• 作为产物：
  描述：

  N-苯基双(三氟甲烷磺酰)亚胺 、 (1R,3aS,7aR)-1-[(R)-6-triethylsilanyloxy-6-methylheptan-2-yl]-7a-methylhexahydro-1H-inden-4(2H)-one 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 以82%的产率得到(1R,3aS,7aR)-1-[(2R)-6-triethylsilyloxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,6,7,7a-hexahydro-1H-inden-4-yl trifluoromethanesulfonate
  参考文献：
  名称：

  Development of 14-epi-19-Nortachysterol and Its Unprecedented Binding Configuration for the Human Vitamin D Receptor

  摘要：

  In the study of the synthesis of 14-epi-19-norprevitamin D-3, we found 14-epi-19-nortachysterol derivatives through C6,7-cis/trans isomerization. We also succeeded in their chemical synthesis and revealed their marked stability and potent VDR binding affinity. To the best of our knowledge, this is the first isolation of stable tachysterol analogues. Surprisingly, 14-epi-19-nortachysterol derivatives exhibited an unprecedented binding configurations for the ligand binding pocket in hVDR, C5,6-s-trans and C7,8-s-trans triene configurations, which were opposite the natural C7,8-ene-configuration of 1 alpha,25(OH)(2)D-3.

  DOI：

  10.1021/ja201481j

文献信息

• Effects of 2-substitution on 14-<i>epi</i>-19-nortachysterol-mediated biological events: based on synthesis and X-ray co-crystallographic analysis with the human vitamin D receptor
  作者：Daisuke Sawada、Shinji Kakuda、Akiko Takeuchi、Fumihiro Kawagoe、Midori Takimoto-Kamimura、Atsushi Kittaka

  DOI：10.1039/c8ob00158h

  日期：——

  Both 2α- and 2β-hydroxypropyl substituted 14-epi-1α,25-dihydroxy-19-nortachysterols were synthesized to study the human vitamin D receptor (hVDR) binding affinity, binding configurations, and interactions with amino acid residues in the ligand binding domain of hVDR by X-ray co-crystallographic analysis. In conjunction with our previous results on 14-epi-19-nortachysterol, 2-methylidene-, 2α-methyl-

  合成2α-和2β-羟丙基取代的14- Epi -1α，25-二羟基-19-北甾醇，以研究人类维生素D受体（hVDR）的结合亲和力，结合构型以及与配体结合域中氨基酸残基的相互作用X射线共晶体分析hVDR。结合我们先前对14- epi -19-nortachysterol，2-甲叉基-，2α-甲基-，2β-甲基和2α-羟基丙氧基-14- epi -19-nortachysterol的研究结果，我们提出了多种取代作用在14- Epi -19-nortachysterol骨架中的C2位置具有生物活性。