(1R,3aS,7aR)-1-[(R)-6-triethylsilanyloxy-6-methylheptan-2-yl]-7a-methylhexahydro-1H-inden-4(2H)-one | 1101133-55-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (1R,3aS,7aR)-1-[(R)-6-triethylsilanyloxy-6-methylheptan-2-yl]-7a-methylhexahydro-1H-inden-4(2H)-one
• 英文别名: (1R,3aS,7aR)-7a-methyl-1-[(2R)-6-methyl-6-triethylsilyloxyheptan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-one
• CAS: 1101133-55-4
• 化学式: C₂₄H₄₆O₂Si
• 分子量: 394.714
• InChiKey: SSBPDZGZFAVZPC-GECPAALWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.38
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1R,3aS,7aR)-1-[(R)-6-triethylsilanyloxy-6-methylheptan-2-yl]-7a-methylhexahydro-1H-inden-4(2H)-one 在 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 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 2.5h， 生成 14-epi-2α-methyl-1α,25(OH)2-6,7-dehydro-19-norvitamin D3
  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：

  (1R,3aR,7aR)-1-[(1R)-1,5-二甲基-5-[(三乙基硅烷基)氧基]己基]八氢-7a-甲基-4H-茚-4-酮 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以80%的产率得到(1R,3aS,7aR)-1-[(R)-6-triethylsilanyloxy-6-methylheptan-2-yl]-7a-methylhexahydro-1H-inden-4(2H)-one
  参考文献：
  名称：

  2α-和2β-取代的14-表位维生素原D 3的合成及其基因组活性

  摘要：

  14-表位-维生素D 3三烯在80°C下热异构化后，合成并分离了14-表位-维生素D 3的2α和2β取代类似物。在HOS细胞骨钙蛋白启动子的VDR结合亲和力和反式激活活性进行了测试，并且2α甲基取代的类似物被发现具有更大的基因组活性比14-外延-previtamin d 3。我们发现，在修改的C2位置塞科-steroidal骨架提供了对前维生素d形式的生物基因组活动以及天然维生素d形式有趣的效果。

  DOI：

  10.1016/j.tet.2010.05.028

文献信息

• Revisiting the 7,8-cis-vitamin D3 derivatives: synthesis, evaluating the biological activity, and study of the binding configuration
  作者：Daisuke Sawada、Shinji Kakuda、Midori Kamimura-Takimoto、Akiko Takeuchi、Yotaro Matsumoto、Atsushi Kittaka

  DOI：10.1016/j.tet.2016.03.081

  日期：2016.6

  disclosed that 14-epi-19-nortachysterol showed the unprecedented binding configuration in human vitamin D receptor (hVDR), that is, 5,6- and 7,8-s-trans configuration. However, this configuration is variable because of the rotation at the single bond between C7 and C8. For the precise discussion of the 7,8-s-trans configuration, we designed and synthesized the 7,8-cis-locked skeleton of vitamin D3 derivatives

  四-7,8-顺式-1α，25-二羟基维生素d 3个衍生物，7,8-顺-和7,8-顺式-14-外延1α，25-二羟基-19-去甲维生素d 3以及7,8合成了-顺式和7,8-顺式-14 - epi -1α，25-二羟基维生素D 3，并对其化学稳定性进行了表征。在我们以前的工作中，我们透露，14-外延-19-nortachysterol显示，人体维生素d受体（hVDR），也就是5,6-和7,8-前所未有的绑定配置小号-反式组态。但是，由于在C7和C8之间的单键处旋转，因此此配置可变。对于-7,8-的精确讨论小号-反式构型，我们设计并合成的7,8-顺式维生素d -locked骨架3层的衍生物。在四个类似物中，19-nor衍生物在环境温度下稳定，并研究了它们的hVDR结合亲和力和hVDR复合物的共晶体分析。具有三烯系统的其他衍生物被异构化为相应的维生素原D 3和维生素D 3。
• Synthesis and Biological Evaluation of 4-Substituted Vitamin D and 14-Epi-Previtamin D Analogs
  作者：Daisuke Sawada、Yuya Tsukuda、Hiroshi Saito、Ken-ichiro Takagi、Kyouhei Horie、Eiji Ochiai、Kazuya Takenouchi、Atsushi Kittaka

  DOI：10.1248/cpb.57.1431

  日期：——

  We synthesized the 4-hydroxy and 4-methoxy analogs of active vitamin D3 (1α,25(OH)2D3, 1) and its C14-epimer with the previtamin D3 form of 14-epi-1α,25(OH)2preD3 (14-epi-pre1). Their vitamin D receptor (VDR) binding affinity and osteocalcin promoter transactivation activity in HOS cells were evaluated, and had lower activity than the natural hormone (1) and 14-epi-pre1, respectively.

  我们合成了活性维生素D3（1α,25(OH)2D3, 1）的4-羟基和4-甲氧基类似物及其C14-表异构体，以及维生素D3前体14-epi-1α,25(OH)2preD3 (14-epi-pre1)的C14-表异构体。我们评估了它们与维生素D受体（VDR）的结合亲和力以及在HOS细胞中的骨钙素启动子转激活活性，结果发现它们分别比天然激素（1）和14-epi-pre1的活性低。
• Synthesis of 2α-substituted-14-epi-previtamin D3 and its genomic activity
  作者：Daisuke Sawada、Tomoyuki Katayama、Yuya Tsukuda、Nozomi Saito、Masashi Takano、Hiroshi Saito、Ken-ichiro Takagi、Eiji Ochiai、Seiichi Ishizuka、Kazuya Takenouchi、Atsushi Kittaka

  DOI：10.1016/j.bmcl.2009.07.112

  日期：2009.9

  We synthesized and isolated 2 alpha-substituted analogs of 14-epi-previtamin D-3 after thermal isomerization at 80 degrees C for the first time. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the 2 alpha-methyl-substituted analog was found to have greater genomic activity than 14-epi-previtamin D-3. (C) 2009 Elsevier Ltd. All rights reserved.
• Synthesis of 2α- and 2β-substituted-14-epi-previtamin D3 and their genomic activity
  作者：Daisuke Sawada、Tomoyuki Katayama、Yuya Tsukuda、Nozomi Saito、Hiroshi Saito、Ken-ichiro Takagi、Eiji Ochiai、Seiichi Ishizuka、Kazuya Takenouchi、Atsushi Kittaka

  DOI：10.1016/j.tet.2010.05.028

  日期：2010.7

  and 2β-Substituted analogs of 14-epi-previtamin D3 were synthesized and isolated after thermal isomerization of 14-epi-vitamin D3 triene at 80 °C. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were tested, and the 2α-methyl-substituted analog was found to have greater genomic activity than 14-epi-previtamin D3. We found that modification at the C2 position

  14-表位-维生素D 3三烯在80°C下热异构化后，合成并分离了14-表位-维生素D 3的2α和2β取代类似物。在HOS细胞骨钙蛋白启动子的VDR结合亲和力和反式激活活性进行了测试，并且2α甲基取代的类似物被发现具有更大的基因组活性比14-外延-previtamin d 3。我们发现，在修改的C2位置塞科-steroidal骨架提供了对前维生素d形式的生物基因组活动以及天然维生素d形式有趣的效果。
• Development of 14-<i>epi</i>-19-Nortachysterol and Its Unprecedented Binding Configuration for the Human Vitamin D Receptor
  作者：Daisuke Sawada、Yuya Tsukuda、Hiroshi Saito、Shinji Kakuda、Midori Takimoto-Kamimura、Eiji Ochiai、Kazuya Takenouchi、Atsushi Kittaka

  DOI：10.1021/ja201481j

  日期：2011.5.11

  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.