[1E,3E]-4,8-dimethylnona-1,3,7-trienyl-diethylphosphonate | 171780-75-9

• 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: [1E,3E]-4,8-dimethylnona-1,3,7-trienyl-diethylphosphonate
• 英文别名: diethyl ((E,E)-4,8-dimethyl-1,3,7-nonatrienyl)phosphonate；diethyl (E,E)-4,8-dimethyl-1,3,7-nonatrienylphosphonate；(1E,3E)-1-diethoxyphosphoryl-4,8-dimethylnona-1,3,7-triene
• CAS: 171780-75-9
• 化学式: C₁₅H₂₇O₃P
• 分子量: 286.351
• InChiKey: CGALDTJFFJGXSW-OGGMOHOESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  19
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [1E,3E]-4,8-dimethylnona-1,3,7-trienyl-diethylphosphonate 在 吡啶 、 三正丁胺 、 三甲基溴硅烷 、 N,N-二丁基丁烷-1-胺,磷酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 20.5h， 生成 tetraammonium (E,E)-4,8-dimethylnona-1,3,7-trienyltriphosphonate
  参考文献：
  名称：

  Synthesis of Prenyl Pyrophosphonates as New Potent Phosphoantigens Inducing Selective Activation of Human Vγ9Vδ2 T Lymphocytes

  摘要：

  gamma9delta2T cells represent the most abundant population of human blood gammadeltaT lymphocytes. They produce and promote strong cytotoxic activity against many pathogens that are implicated in several human infectious diseases. Their activation requires their exposure to small phosphorus-containing antigens in the family of prenyl pyrophosphates and their related biosynthetic precursors such as isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are naturally occurring metabolites in mycobacteria and several other microbial pathogens. The broad specificity in the recognition of these molecules by the T-lymphocyte population expressing a Vgamma9Vdelta2 cell receptor might facilitate their manipulation by designing small potent synthetic agonist ligands. In this paper, we describe the synthesis and the biological evaluation of new pyrophosphonate compounds as new isosteric analogues of natural prenyl pyrophosphates. Several prenyl and alkenyl pyrophosphonate with different chain lengths and degrees of insaturation (24-28, 48-50, and 64-66) were tested as well as the alkoxymethylpyrophosphonic analogue of IPP (compound 76) as its closest isostere. Several of them appeared to be better activators of Vgamma9Vdelta2 T cell proliferation than IPP. These results open the perspective of a potential use of isoprenoides pyrophosphonates as specific immunoregulatory molecules.

  DOI：

  10.1021/jm049861z
• 作为产物：
  描述：

  香叶醇 在 重铬酸吡啶 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 5.25h， 生成 [1E,3E]-4,8-dimethylnona-1,3,7-trienyl-diethylphosphonate
  参考文献：
  名称：

  Synthesis of Prenyl Pyrophosphonates as New Potent Phosphoantigens Inducing Selective Activation of Human Vγ9Vδ2 T Lymphocytes

  摘要：

  gamma9delta2T cells represent the most abundant population of human blood gammadeltaT lymphocytes. They produce and promote strong cytotoxic activity against many pathogens that are implicated in several human infectious diseases. Their activation requires their exposure to small phosphorus-containing antigens in the family of prenyl pyrophosphates and their related biosynthetic precursors such as isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are naturally occurring metabolites in mycobacteria and several other microbial pathogens. The broad specificity in the recognition of these molecules by the T-lymphocyte population expressing a Vgamma9Vdelta2 cell receptor might facilitate their manipulation by designing small potent synthetic agonist ligands. In this paper, we describe the synthesis and the biological evaluation of new pyrophosphonate compounds as new isosteric analogues of natural prenyl pyrophosphates. Several prenyl and alkenyl pyrophosphonate with different chain lengths and degrees of insaturation (24-28, 48-50, and 64-66) were tested as well as the alkoxymethylpyrophosphonic analogue of IPP (compound 76) as its closest isostere. Several of them appeared to be better activators of Vgamma9Vdelta2 T cell proliferation than IPP. These results open the perspective of a potential use of isoprenoides pyrophosphonates as specific immunoregulatory molecules.

  DOI：

  10.1021/jm049861z

文献信息

• SYNTHESIS AND BIOLOGICAL ACTIVITY OF A RETINYL PHOSPHONIC ACID DERIVATIVE AN ANALOG OF RETINYL PHOSPHATE: HOMORETINYLPHOSPHONIC ACID
  作者：Mehrnaz Kamal、Jean-Yves Winum、Véronique Barragan、Alain Leydet、Jean-Louis Montero

  DOI：10.1080/10426509908031633

  日期：1999.9.1

  Abstract The synthesis of phosphonate isosteres or homologues of natural retinylphosphate was developed starting from carbonylated terpenes, through Abramov and Wittig-Horner reactions. Homoretinylphosphonic acid (HRP) was isolated and tested for its ability to be involved in the biosynthesis of membrane glycoconjugates.

  摘要 从羰基化萜烯开始，通过 Abramov 和 Wittig-Horner 反应，合成了天然磷酸视黄酯的等排体或同系物。高锡基膦酸 (HRP) 被分离出来并测试其参与膜糖缀合物生物合成的能力。
• Phosphonate and bisphosphonate analogues of farnesyl pyrophosphate as potential inhibitors of farnesyl protein transferase
  作者：Sarah A Holstein、Diana M Cermak、David F Wiemer、Kriste Lewis、Raymond J Hohl

  DOI：10.1016/s0968-0896(98)00034-0

  日期：1998.6

  Several phosphonate and bisphosphonate analogues of farnesyl pyrophosphate have been prepared for an examination of their ability to inhibit farnesyl protein transferase (FPTase). A Horner-Wadsworth-Emmons condensation of farnesal or geranial with tetraethyl methylenediphosphonate gave the desired vinyl phosphonates, while alkylation of the dimethyl methylphosphonate anion with a terpenoid bromide

  制备了法呢基焦磷酸的几种膦酸酯和双膦酸酯类似物，以检查其抑制法呢基蛋白转移酶（FPTase）的能力。法呢醛或香叶醛与亚甲基二膦酸四乙酯的霍纳-沃兹沃思-埃蒙斯缩合反应得到所需的乙烯基膦酸酯，而甲基膦酸二甲酯阴离子与萜类溴化物烷基化得到相应的饱和膦酸酯。亚甲基二膦酸四乙酯与法呢基溴的烷基化反应得到预期的双膦酸烷基酯，其通过制备亚硒酸苯基酯，氧化为亚硒酸酯并消除而转化为其α，β-不饱和衍生物。以类似的方式，通过与法呢基溴反应，将膦酰基乙酸三乙酯转化为法呢基焦磷酸酯类似物。制备相应的酸后，测试每种化合物对FPTase的抑制作用，浓度最高可达10 microM。这些化合物对FPTase活性的影响变化很大，范围从抑制到令人惊讶地增强。
• Phosphonates useful as modulators of T-gamma-9-delta-2 activity
  申请人：Montero Jean-Louis

  公开号：US20100204184A1

  公开（公告）日：2010-08-12

  The invention concerns novel phosphonate derivatives, preparation method, use thereof as ligands modulating T γ9δ2 lymphocyte activity and pharmaceutical compositions comprising them.

  这项发明涉及新型膦酸盐衍生物、其制备方法，以及将其用作调节T γ9δ2淋巴细胞活性的配体和包含它们的制药组合物。
• US8017596B2
  申请人：——

  公开号：US8017596B2

  公开（公告）日：2011-09-13
• Synthesis of Prenyl Pyrophosphonates as New Potent Phosphoantigens Inducing Selective Activation of Human Vγ9Vδ2 T Lymphocytes
  作者：Ibrahim Zgani、Chantal Menut、Michel Seman、Valerie Gallois、Virginie Laffont、Jeanine Liautard、Jean-Pierre Liautard、Marc Criton、Jean-Louis Montero

  DOI：10.1021/jm049861z

  日期：2004.8.1

  gamma9delta2T cells represent the most abundant population of human blood gammadeltaT lymphocytes. They produce and promote strong cytotoxic activity against many pathogens that are implicated in several human infectious diseases. Their activation requires their exposure to small phosphorus-containing antigens in the family of prenyl pyrophosphates and their related biosynthetic precursors such as isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are naturally occurring metabolites in mycobacteria and several other microbial pathogens. The broad specificity in the recognition of these molecules by the T-lymphocyte population expressing a Vgamma9Vdelta2 cell receptor might facilitate their manipulation by designing small potent synthetic agonist ligands. In this paper, we describe the synthesis and the biological evaluation of new pyrophosphonate compounds as new isosteric analogues of natural prenyl pyrophosphates. Several prenyl and alkenyl pyrophosphonate with different chain lengths and degrees of insaturation (24-28, 48-50, and 64-66) were tested as well as the alkoxymethylpyrophosphonic analogue of IPP (compound 76) as its closest isostere. Several of them appeared to be better activators of Vgamma9Vdelta2 T cell proliferation than IPP. These results open the perspective of a potential use of isoprenoides pyrophosphonates as specific immunoregulatory molecules.