(5Z,7E,20R)-1α,3β-bis(tert-butyldimethylsilyloxy)-20-cyanomethyl-9,10-seco-5,7,10(19)-pregnatriene | 151919-93-6

• 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: (5Z,7E,20R)-1α,3β-bis(tert-butyldimethylsilyloxy)-20-cyanomethyl-9,10-seco-5,7,10(19)-pregnatriene
• 英文别名: 1α,3β-bis-(tert-butyldimethylsilyloxy)-20(R)-cyanomethyl-9,10-secopregna-5(Z),7(E),10(19)-triene；(3R)-3-[(1R,3aS,4E,7aR)-4-[(2Z)-2-[(3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylidenecyclohexylidene]ethylidene]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]butanenitrile
• CAS: 151919-93-6
• 化学式: C₃₅H₆₁NO₂Si₂
• 分子量: 584.046
• InChiKey: PJHLYIYZGNDINY-GSFYQCCGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.74
• 重原子数：
  40
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  42.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (5Z,7E,20R)-1α,3β-bis(tert-butyldimethylsilyloxy)-20-cyanomethyl-9,10-seco-5,7,10(19)-pregnatriene 在 二异丁基氢化铝 、 三乙胺 作用下， 以 正己烷 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 (R,Z)-3-((1R,3aS,7aR,E)-4-((Z)-2-((3S,5R)-3,5-bis((tert-butyldimethylsilyl)oxy)-2-methylenecyclohexylidene)ethylidene)-7a-methyloctahydro-1H-inden-1-yl)-N-isopropylbutan-1-imine oxide
  参考文献：
  名称：

  Practical Synthesis and Evaluation of the Biological Activities of 1α,25-dihydroxyvitamin D₃ Antagonists, 1α,25-dihydroxyvitamin D₃-26,23-lactams. Designed on the Basis of the Helix 12-Folding Inhibition Hypothesis

  摘要：

  A practical synthetic route to novel vitamin D antagonists of DLAM (1 alpha.,25-dihydroxyvitamin D-3-26,23lactam) was developed from vitamin D-2 via the 1,3-dipolar cycloaddition reaction as a key step. Six DLAM derivatives (24 compounds) with a variety of nitrogen substituents and stereochemistries at C23 and C25 were synthesized. Among these new derivatives, (23S,25S)-DLAM isomers bound effectively to VDRs and showed antagonistic activity in the HL-60 cell differentiation inhibition assay. The importance of the substituent on the nitrogen of DLAMs for antagonistic activity was also suggested by computational docking studies.

  DOI：

  10.1021/jm050738x
• 作为产物：
  描述：

  (5Z,7E)-(1S,3R,20S)-1,3-bis<(tert-butyldimethylsilyl)oxy>-9,10-seco-22,23-dinor-5,7,10(19)-cholatrien-24-ol 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 5.0h， 生成 (5Z,7E,20R)-1α,3β-bis(tert-butyldimethylsilyloxy)-20-cyanomethyl-9,10-seco-5,7,10(19)-pregnatriene
  参考文献：
  名称：

  Practical Synthesis and Evaluation of the Biological Activities of 1α,25-dihydroxyvitamin D₃ Antagonists, 1α,25-dihydroxyvitamin D₃-26,23-lactams. Designed on the Basis of the Helix 12-Folding Inhibition Hypothesis

  摘要：

  A practical synthetic route to novel vitamin D antagonists of DLAM (1 alpha.,25-dihydroxyvitamin D-3-26,23lactam) was developed from vitamin D-2 via the 1,3-dipolar cycloaddition reaction as a key step. Six DLAM derivatives (24 compounds) with a variety of nitrogen substituents and stereochemistries at C23 and C25 were synthesized. Among these new derivatives, (23S,25S)-DLAM isomers bound effectively to VDRs and showed antagonistic activity in the HL-60 cell differentiation inhibition assay. The importance of the substituent on the nitrogen of DLAMs for antagonistic activity was also suggested by computational docking studies.

  DOI：

  10.1021/jm050738x

文献信息

• An Improved Synthesis of 24,24-Difluoro-1.ALPHA.,25-dihydroxyvitamin D3 from Readily Available Vitamin D2.
  作者：Kaori ANDO、Fumiaki KOIKE、Fumihiro KONDO、Hiroaki TAKAYAMA

  DOI：10.1248/cpb.43.189

  日期：——

  An improved synthesis of a highly potent vitamin D3 analog, 24, 24-difluoro-1α, 25-dihydroxyvitamin D3 (1b)has been accomplished via vitamin D2-SO2 adducts. The introduction of fluorine atoms was performed by treating the α-keto ester (11) with diethylaminosulfur trifluoride. The total yield was 12.5% from inexpensive vitamin D2 in 11 steps. This sequence is sufficiently straightforward to be conducted on a gram scale.

  通过维生素D2-SO2加合物，完成了一种高效能维生素D3类似物24, 24-二氟-1α, 25-二羟基维生素D3 (1b) 的改进合成。引入氟原子的过程是通过用二乙胺硫三氟化物处理α-酮酯（11）来实现的。该方法从廉价的维生素D2中在11个步骤中获得了12.5%的总产率。这一序列简单明了，足以在克级规模上进行。
• VITAMIN D3 LACTONE DERIVATIVE
  申请人：Teijin Pharma Limited

  公开号：EP1589009B1

  公开（公告）日：2014-10-08
• EP1477483
  申请人：——

  公开号：——

  公开（公告）日：——