diethyl ((E)-4-methyl-1,3-pentadienyl)phosphonate | 67221-19-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: diethyl ((E)-4-methyl-1,3-pentadienyl)phosphonate
• 英文别名: diethyl (E)-4-methylpenta-1,3-dienylphosphonate；(1E)-1-diethoxyphosphoryl-4-methylpenta-1,3-diene
• CAS: 67221-19-6
• 化学式: C₁₀H₁₉O₃P
• 分子量: 218.233
• InChiKey: MOJVBBAFCDNIMT-VQHVLOKHSA-N

物化性质

• 沸点：
  96-98 °C(Press: 0.01 Torr)
• 密度：
  1.003±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  14
• 可旋转键数：
  6
• 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：

  diethyl ((E)-4-methyl-1,3-pentadienyl)phosphonate 在 吡啶 、 三甲基溴硅烷 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以99%的产率得到(E)-4-methylpenta-1,3-dienylphosphonic acid
  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：

  异戊烯醇 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 diethyl ((E)-4-methyl-1,3-pentadienyl)phosphonate
  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

• Phosphonates useful as modulators of t $g(g)9$g(d)2 lymphocyte activity
  申请人：Montero Jean-Louis

  公开号：US20060241087A1

  公开（公告）日：2006-10-26

  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酯衍生物，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药物组合物。
• Synthesis and Metabolism of BTN3A1 Ligands: Studies on Diene Modifications to the Phosphoantigen Scaffold
  作者：Nyema M. Harmon、Michael M. Poe、Xueting Huang、Rohit Singh、Benjamin J. Foust、Chia-Hung Christine Hsiao、David F. Wiemer、Andrew J. Wiemer

  DOI：10.1021/acsmedchemlett.1c00408

  日期：2022.2.10

  Phosphoantigens (pAgs) are small organophosphorus compounds such as (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP) that trigger an immune response. These molecules bind to butyrophilin 3A1 (part of the HMBPP receptor) and activate Vγ9Vδ2 T cells. To explore the structure–activity relationships underlying this process, we evaluated a series of novel diene analogs of HMBPP. Here we report that

  磷酸抗原 (pAg) 是触发免疫反应的小型有机磷化合物，例如 ( E )-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP)。这些分子与嗜乳蛋白 3A1（HMBPP 受体的一部分）结合并激活 Vγ9Vδ2 T 细胞。为了探索该过程背后的构效关系，我们评估了一系列 HMBPP 的新型二烯类似物。在这里，我们报告 [(1 E)-4-methylpenta-1,3-dien-1-yl] 膦酸缺乏 HMBPP 的烯丙醇，而是含有二烯支架，对 Vγ9Vδ2 T 细胞的激活表现出中纳摩尔级的效力。这些化合物还会在暴露于负载的 K562 细胞时触发 T 细胞干扰素 γ 的产生。尽管烯丙醇和二烯支架都能增强 pAg 活性，但两者的结合会降低活性并导致谷胱甘肽结合。总之，这些数据表明二烯支架产生中间 pAg，这可能对调节 HMBPP 受体的机制有影响。
• 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。
• XU YUAN-YAO; JIN XIAO-LI; HUANG GUO-HUA; WANG QI-WEN, ACTA CHIM. SIN. ENGL. ED.,(1985) N 3, 273-284
  作者：XU YUAN-YAO、 JIN XIAO-LI、 HUANG GUO-HUA、 WANG QI-WEN

  DOI：——

  日期：——
• STURTZ G.; DAMIN B.; CLEMENT J.-C., J. CHEM. RES. SYNOP., 1978, NO 3, 89 (M 1209-1228)
  作者：STURTZ G.、 DAMIN B.、 CLEMENT J.-C.

  DOI：——

  日期：——