(3R,5R)-[3,5-bis-[(tert-butyldimethylsilyl)oxy]-4-[2-(tert-butyldimethylsilyl)oxyethyl]cyclohexylidene]ethyldiphenylphoshine oxide | 681433-95-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (3R,5R)-[3,5-bis-[(tert-butyldimethylsilyl)oxy]-4-[2-(tert-butyldimethylsilyl)oxyethyl]cyclohexylidene]ethyldiphenylphoshine oxide
• CAS: 681433-95-4
• 化学式: C₄₀H₆₇O₄PSi₃
• 分子量: 727.2
• InChiKey: ZMKUNTAABJTFNR-ZLMHQGOISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.45
• 重原子数：
  48.0
• 可旋转键数：
  11.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 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：

  (1R,3aR,7aR)-1-((2E,4E)-(R)-6-Ethyl-1-methyl-6-triethylsilanyloxy-octa-2,4-dienyl)-7a-methyl-octahydro-inden-4-one 、 (3R,5R)-[3,5-bis-[(tert-butyldimethylsilyl)oxy]-4-[2-(tert-butyldimethylsilyl)oxyethyl]cyclohexylidene]ethyldiphenylphoshine oxide 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 2.0h， 生成 (Z)-24a,26a,27a-trihomo-1α-[(tert-butyldimethylsilyl)oxy]-2-[2-((tert-butyldimethylsilyl)oxy)ethylidene]-22,24-diene-25-[(triethylsilyl)oxy]-19-norvitamin D₃ tert-butyldimethylsilyl ether 、 (E)-24a,26a,27a-trihomo-1α-[(tert-butyldimethylsilyl)oxy]-2-[2-((tert-butyldimethylsilyl)oxy)ethylidene]-22,24-diene-25-[(triethylsilyl)oxy]-19-norvitamin D₃ tert-butyldimethylsilyl ether
  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：

  (2R,6R)-2,6-bis-[(tert-butyldimethylsilyl)oxy]-4-(benzyloxy)cyclohexanone 在 palladium on activated charcoal 咪唑 、 sodium tetrahydroborate 、 正丁基锂 、 草酰氯 、 氢气 、 双氧水 、 二异丁基氢化铝 、 二甲基亚砜 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 11.58h， 生成 (3R,5R)-[3,5-bis-[(tert-butyldimethylsilyl)oxy]-4-[2-(tert-butyldimethylsilyl)oxyethyl]cyclohexylidene]ethyldiphenylphoshine oxide
  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