tetramethyl (E)-4,8-dimethylnona-3,7-diene-1,1-diyldiphosphonate | 855793-00-9

• 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: tetramethyl (E)-4,8-dimethylnona-3,7-diene-1,1-diyldiphosphonate
• 英文别名: tetramethyl 4,8-dimethyl-3,7-nonadienyl-1,1-bisphosphonate；tetramethyl (E)-4,8-dimethyl-nona-3,7-dienyl-1,1-bisphosphonate
• CAS: 855793-00-9
• 化学式: C₁₅H₃₀O₆P₂
• 分子量: 368.347
• InChiKey: BGYAGCPXRWLCLD-SDNWHVSQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.37
• 重原子数：
  23.0
• 可旋转键数：
  11.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  71.06
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  tetramethyl (E)-4,8-dimethylnona-3,7-diene-1,1-diyldiphosphonate 在 2,4,6-三甲基吡啶 、 三甲基溴硅烷 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 3.0h， 以50%的产率得到tetrasodium (E)-4,8-dimethylnona-3,7-diene-1,1-diyldiphosphonate
  参考文献：
  名称：

  Mono- and dialkyl isoprenoid bisphosphonates as geranylgeranyl diphosphate synthase inhibitors

  摘要：

  Nitrogenous bisphosphonates are used clinically to reduce bone resorption associated with osteoporosis or metastatic bone disease, and are recognized as inhibitors of farnesyl diphosphate synthase. Inhibition of this enzyme decreases cellular levels of both farnesyl diphosphate and geranylgeranyl diphosphate which results in a variety of downstream biological effects including inhibition of protein geranylgeranylation. Our lab recently has prepared several isoprenoid bisphosphonates that inhibit protein geranylgeranylation and showed that one selectively inhibits geranylgeranyl diphosphate synthase. This results in depletion of intracellular geranylgeranyl diphosphate and impacts protein geranylgeranylation but does not affect protein farnesylation. To clarify the structural features of isoprenoid bisphosphonates that account for their geranylgeranyl diphosphate synthase inhibition, we have prepared a new group of isoprenoid bisphosphonates. The complete set of compounds has been tested for in vitro inhibition of human recombinant geranylgeranyl diphosphate synthase and cellular inhibition of protein geranylgeranylation. These results show some surprising relationships between in vitro and cellular activity, and will guide development of clinical agents directed at geranylgeranyl diphosphate synthase. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.09.029
• 作为产物：
  描述：

  香叶基溴 、 四甲基亚甲基二磷酸酯 在 15-冠醚-5 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.17h， 以45%的产率得到tetramethyl (E)-4,8-dimethylnona-3,7-diene-1,1-diyldiphosphonate
  参考文献：
  名称：

  铜介导的双膦酸酯模板上的烯丙基THP醚置换

  摘要：

  已在包含双膦酸酯双键的系统中检查了格氏试剂在铜介导的烯丙基THP醚置换中的作用。使用衍生自几种芳族卤化物或苄基溴的格氏试剂，置换的产率很高，但与烷基卤的反应得到的混合结果更多。除了其作为亲核试剂的作用外，格氏试剂还似乎使双膦酸酯去质子化以生成阴离子中间体。这种阴离子的形成似乎限制了膦酸酯基团的竞争性亲核进攻，并提供了一种中间体，该中间体可以通过与亲电试剂（如甲基碘）反应而被捕获，以进入更取代的系统。

  DOI：

  10.1016/j.jorganchem.2004.10.013

文献信息

• Geranylgeranyl pyrophosphate synthase inhibitors
  申请人：Wiemer F. David

  公开号：US20060052347A1

  公开（公告）日：2006-03-09

  The invention provides novel pyrophosphate synthase inhibitors of formula I as well as compositions comprising such inhibitors and methods for their use.

  这项发明提供了一种新型的焦磷酸合酶抑制剂，其化学式为I，以及包含这种抑制剂的组合物和使用它们的方法。
• Mono- and dialkyl isoprenoid bisphosphonates as geranylgeranyl diphosphate synthase inhibitors
  作者：Andrew J. Wiemer、Jose S. Yu、Kimberly M. Lamb、Raymond J. Hohl、David F. Wiemer

  DOI：10.1016/j.bmc.2007.09.029

  日期：2008.1

  Nitrogenous bisphosphonates are used clinically to reduce bone resorption associated with osteoporosis or metastatic bone disease, and are recognized as inhibitors of farnesyl diphosphate synthase. Inhibition of this enzyme decreases cellular levels of both farnesyl diphosphate and geranylgeranyl diphosphate which results in a variety of downstream biological effects including inhibition of protein geranylgeranylation. Our lab recently has prepared several isoprenoid bisphosphonates that inhibit protein geranylgeranylation and showed that one selectively inhibits geranylgeranyl diphosphate synthase. This results in depletion of intracellular geranylgeranyl diphosphate and impacts protein geranylgeranylation but does not affect protein farnesylation. To clarify the structural features of isoprenoid bisphosphonates that account for their geranylgeranyl diphosphate synthase inhibition, we have prepared a new group of isoprenoid bisphosphonates. The complete set of compounds has been tested for in vitro inhibition of human recombinant geranylgeranyl diphosphate synthase and cellular inhibition of protein geranylgeranylation. These results show some surprising relationships between in vitro and cellular activity, and will guide development of clinical agents directed at geranylgeranyl diphosphate synthase. (c) 2007 Elsevier Ltd. All rights reserved.
• Copper-mediated displacements of allylic THP ethers on a bisphosphonate template
  作者：Larry W. Shull、David F. Wiemer

  DOI：10.1016/j.jorganchem.2004.10.013

  日期：2005.5

  The copper-mediated displacement of allylic THP ethers by Grignard reagents has been examined in a system that contains a geminal bisphosphonate ester. With Grignard reagents derived from several aromatic halides or benzyl bromide the displacement proceeds in attractive yields, but more mixed results were obtained from reactions with alkyl halides. In addition to its role as a nucleophile, the Grignard

  已在包含双膦酸酯双键的系统中检查了格氏试剂在铜介导的烯丙基THP醚置换中的作用。使用衍生自几种芳族卤化物或苄基溴的格氏试剂，置换的产率很高，但与烷基卤的反应得到的混合结果更多。除了其作为亲核试剂的作用外，格氏试剂还似乎使双膦酸酯去质子化以生成阴离子中间体。这种阴离子的形成似乎限制了膦酸酯基团的竞争性亲核进攻，并提供了一种中间体，该中间体可以通过与亲电试剂（如甲基碘）反应而被捕获，以进入更取代的系统。