tert-butyldimethyl(((R,E)-5-(2-((1R,3aS,7aR,E)-7a-methyl-1-((S)-6-methyl-6-((triethylsilyl)oxy)heptan-2-yl)octahydro-4H-inden-4-ylidene)ethylidene)-2-methylenecyclohexyl)oxy)silane | 1279708-94-9

• 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: tert-butyldimethyl(((R,E)-5-(2-((1R,3aS,7aR,E)-7a-methyl-1-((S)-6-methyl-6-((triethylsilyl)oxy)heptan-2-yl)octahydro-4H-inden-4-ylidene)ethylidene)-2-methylenecyclohexyl)oxy)silane
• CAS: 1279708-94-9
• 化学式: C₃₉H₇₂O₂Si₂
• 分子量: 629.17
• InChiKey: DALNZIRPMVMUPL-WUIGNODISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.79
• 重原子数：
  43.0
• 可旋转键数：
  13.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  18.46
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  tert-butyldimethyl(((R,E)-5-(2-((1R,3aS,7aR,E)-7a-methyl-1-((S)-6-methyl-6-((triethylsilyl)oxy)heptan-2-yl)octahydro-4H-inden-4-ylidene)ethylidene)-2-methylenecyclohexyl)oxy)silane 在 软骨素硫酸钠盐 作用下， 以 甲醇 为溶剂， 生成 (20S)-25-hydroxy-2-methylene-19-nor-vitamin D3
  参考文献：
  名称：

  1-Desoxy analog of 2MD: Synthesis and biological activity of (20S)-25-hydroxy-2-methylene-19-norvitamin D3

  摘要：

  During our ongoing structure-activity studies in the vitamin D area, we obtained (20S)-1 alpha,25-dihydroxy-2-methylene-19-norvitamin D-3 (5). This analog, designated 2MD, is characterized by a significantly enhanced calcemic activity and is currently evaluated as a potential drug for osteoporosis. Therefore, it was of interest to synthesize also its 1-desoxy analog and to evaluate its biological action. These studies were aimed at solving an intriguing problem: can such a vitamin also be hydroxylated in vivo at the allylic C-1 position despite lack of the exomethylene moiety at C-10? The Wittig-Horner coupling of the known protected (20S)-25-hydroxy Grundmann ketone 17 and the phosphine oxides 16 and 33, differing in their hydroxyls protection, provided the target 1-desoxy-2MD (6) after removal of the silyl protecting groups. Two synthetic paths have been elaborated leading to the desired A-ring synthons and starting from commercially available compounds:1,4-cyclohexanedione monoethylene acetal (7) and (-)-quinic acid (19). The biological activity in vitro of the synthesized 1-desoxy-2MD (6) was evaluated and this analog was found to have an affinity for the vitamin D receptor (VDR) similar as its parent compound 2MD (5) while being much less active in the transcriptional assay. The results of the biological tests in vivo are also discussed. (C) 2010 Published by Elsevier Ltd.

  DOI：

  10.1016/j.jsbmb.2010.03.063
• 作为产物：
  描述：

  (E)-2-[(R)-3'-[(tert-butyldimethylsilyl)oxy]-4'-methylene-cyclohexylidene]ethanol 在 正丁基锂 、 双氧水 、 苯基锂 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 生成 tert-butyldimethyl(((R,E)-5-(2-((1R,3aS,7aR,E)-7a-methyl-1-((S)-6-methyl-6-((triethylsilyl)oxy)heptan-2-yl)octahydro-4H-inden-4-ylidene)ethylidene)-2-methylenecyclohexyl)oxy)silane
  参考文献：
  名称：

  1-Desoxy analog of 2MD: Synthesis and biological activity of (20S)-25-hydroxy-2-methylene-19-norvitamin D3

  摘要：

  During our ongoing structure-activity studies in the vitamin D area, we obtained (20S)-1 alpha,25-dihydroxy-2-methylene-19-norvitamin D-3 (5). This analog, designated 2MD, is characterized by a significantly enhanced calcemic activity and is currently evaluated as a potential drug for osteoporosis. Therefore, it was of interest to synthesize also its 1-desoxy analog and to evaluate its biological action. These studies were aimed at solving an intriguing problem: can such a vitamin also be hydroxylated in vivo at the allylic C-1 position despite lack of the exomethylene moiety at C-10? The Wittig-Horner coupling of the known protected (20S)-25-hydroxy Grundmann ketone 17 and the phosphine oxides 16 and 33, differing in their hydroxyls protection, provided the target 1-desoxy-2MD (6) after removal of the silyl protecting groups. Two synthetic paths have been elaborated leading to the desired A-ring synthons and starting from commercially available compounds:1,4-cyclohexanedione monoethylene acetal (7) and (-)-quinic acid (19). The biological activity in vitro of the synthesized 1-desoxy-2MD (6) was evaluated and this analog was found to have an affinity for the vitamin D receptor (VDR) similar as its parent compound 2MD (5) while being much less active in the transcriptional assay. The results of the biological tests in vivo are also discussed. (C) 2010 Published by Elsevier Ltd.

  DOI：

  10.1016/j.jsbmb.2010.03.063