3,5-bis-[(tert-butyldimethylsilyl)oxy]-4-[(tert-butyldimethylsilyl)oxyethylidene]cyclohexanol | 681433-92-1

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: 3,5-bis-[(tert-butyldimethylsilyl)oxy]-4-[(tert-butyldimethylsilyl)oxyethylidene]cyclohexanol
• 英文别名: [3,5-bis-[(t-butyldimethylsilyl)oxy]-4-[(t-butyldimethylsilyl)oxy]-ethylidene]-cyclohexanone
• CAS: 681433-92-1
• 化学式: C₂₆H₅₄O₄Si₃
• 分子量: 514.969
• InChiKey: QIPOMEGWJANYLJ-DHIUTWEWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.08
• 重原子数：
  33.0
• 可旋转键数：
  7.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  44.76
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3,5-bis-[(tert-butyldimethylsilyl)oxy]-4-[(tert-butyldimethylsilyl)oxyethylidene]cyclohexanol 在 二异丁基氢化铝 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 、 甲苯 为溶剂， 反应 2.0h， 生成 (3R,5R)-[3,5-bis-[(tert-butyldimethylsilyl)oxy]-4-[2-(tert-butyldimethylsilyl)oxyethyl]cyclohexylidene]ethanol
  参考文献：
  名称：

  Synthesis and biological activities of new 1α,25-dihydroxy-19-norvitamin D3 analogs with modifications in both the A-ring and the side chain

  摘要：

  In a series of studies on structure-activity relationships of 2-substituted 19-norvitamin D analogs, we found that 1 alpha,25-dihydroxy-19-norvitamin D-3 analogs with 2 beta-hydroxyethoxy or 2E-hydroxyethylidene moieties show strong binding affinity for the vitamin D receptor (VDR) as well as marked transcriptional activity. To further examine the effects of side chain structure on the activity of 2-substituted 19-norvitamin D analogs, we have synthesized new 19-norvitamin D3 analogs with modifications in both the A-ring at the C(2) position and the side chain. The side chains of these analogs contained a double bond between C(22) and C(23) or an oxygen atom at C(22). The biological activity of the analogs was evaluated in vitro. All the side chain-modified analogs were less active than 1 alpha,25-dihydroxyvitamin D-3 1e and the parent compounds 3-6e possessing a natural 20R-configuration in binding to the VDR, but, except for the (20R)-22-oxa analogs 3-6d, were significantly more potent in transcriptional activity. Of the side-chain-modified analogs 4 and 5, the 2 beta-hydroxyethoxy- and 2E-hydroxyethylidene-22,24-diene-24a,26a,27a-trihorno analogs showed markedly higher transcriptional activity (25- and 17.5-fold, respectively) compared with le. Elongation of the side chain at the C-24, C-26, and C-27 positions and introduction of a 22,24-diene moiety strongly increased transcriptional activity, as seen in the 20-epi analogs 3-6f. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.01.061
• 作为产物：
  描述：

  3,5-bis-[(tert-butyldimethylsilyl)oxy]-4-[(trimethylsilyl)oxy]cyclohexanol 在 palladium on activated charcoal 咪唑 、 sodium tetrahydroborate 、 正丁基锂 、 草酰氯 、 氢气 、 sodium hydride 、 二异丁基氢化铝 、 溶剂黄146 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 36.0h， 生成 3,5-bis-[(tert-butyldimethylsilyl)oxy]-4-[(tert-butyldimethylsilyl)oxyethylidene]cyclohexanol
  参考文献：
  名称：

  Synthesis and biological activities of new 1α,25-dihydroxy-19-norvitamin D3 analogs with modifications in both the A-ring and the side chain

  摘要：

  In a series of studies on structure-activity relationships of 2-substituted 19-norvitamin D analogs, we found that 1 alpha,25-dihydroxy-19-norvitamin D-3 analogs with 2 beta-hydroxyethoxy or 2E-hydroxyethylidene moieties show strong binding affinity for the vitamin D receptor (VDR) as well as marked transcriptional activity. To further examine the effects of side chain structure on the activity of 2-substituted 19-norvitamin D analogs, we have synthesized new 19-norvitamin D3 analogs with modifications in both the A-ring at the C(2) position and the side chain. The side chains of these analogs contained a double bond between C(22) and C(23) or an oxygen atom at C(22). The biological activity of the analogs was evaluated in vitro. All the side chain-modified analogs were less active than 1 alpha,25-dihydroxyvitamin D-3 1e and the parent compounds 3-6e possessing a natural 20R-configuration in binding to the VDR, but, except for the (20R)-22-oxa analogs 3-6d, were significantly more potent in transcriptional activity. Of the side-chain-modified analogs 4 and 5, the 2 beta-hydroxyethoxy- and 2E-hydroxyethylidene-22,24-diene-24a,26a,27a-trihorno analogs showed markedly higher transcriptional activity (25- and 17.5-fold, respectively) compared with le. Elongation of the side chain at the C-24, C-26, and C-27 positions and introduction of a 22,24-diene moiety strongly increased transcriptional activity, as seen in the 20-epi analogs 3-6f. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.01.061

文献信息

• EP1559708
  申请人：——

  公开号：——

  公开（公告）日：——
• Crystal Structures of Hereditary Vitamin D-Resistant Rickets-Associated Vitamin D Receptor Mutants R270L and W282R Bound to 1,25-Dihydroxyvitamin D₃ and Synthetic Ligands
  作者：Makoto Nakabayashi、Yoshito Tsukahara、Yukiko Iwasaki-Miyamoto、Mika Mihori-Shimazaki、Sachiko Yamada、Satomi Inaba、Masayuki Oda、Masato Shimizu、Makoto Makishima、Hiroaki Tokiwa、Teikichi Ikura、Nobutoshi Ito

  DOI：10.1021/jm400537h

  日期：2013.9.12

  The vitamin D receptor (VDR), a member of the nuclear receptor superfamily, functions as a ligand-dependent transcription factor for various genes. Hereditary vitamin D-resistant rickets (HVDRR), an autosomal recessive disease, is caused by mutations in the VDR In particular, the missense mutations R274L and W286R in the ligand-binding domain of the VDR can severely reduce or even eliminate natural hormone responsiveness. Here, we report a crystal structure analysis of the R270L and W282R mutants of rat VDR (human R274L and W286R, respectively) in complex with the natural hormone and synthetic ligands. We also studied the folding properties of the mutant proteins by using circular dichroism spectra. Our study indicates that these mutations result in only local structural modifications. We discuss why these mutations disrupt the VDR function and provide clues to develop effective ligands for the treatment of HVDRR