2-hydroxyphosphinoylmethyl-4-methyl-pentanoic acid ethyl ester | 865703-09-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 2-hydroxyphosphinoylmethyl-4-methyl-pentanoic acid ethyl ester
• 英文别名: 2-(ethoxycarbonyl)-4-methylamylphosphinic acid；2-(ethoxycarbonyl)-4-methylamylphosphonic acid
• CAS: 865703-09-9
• 化学式: C₉H₁₉O₄P
• 分子量: 222.221
• InChiKey: OTDWQVIUZHEVRF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.68
• 重原子数：
  14.0
• 可旋转键数：
  6.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  63.6
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2-hydroxyphosphinoylmethyl-4-methyl-pentanoic acid ethyl ester 在 sodium hydroxide 、 溶剂黄146 、 乙酰氯 作用下， 以 甲醇 、 水 为溶剂， 反应 6.0h， 生成 2-{[1-(9H-fluoren-9-ylmethoxycarbonylamino)-ethyl]-hydroxy-phosphinoylmethyl}-4-methyl-pentanoic acid
  参考文献：
  名称：

  Shortcut to Fmoc-Protected Phosphinic Pseudodipeptidic Blocks

  摘要：

  A three-component condensation reaction of Fmoc-carbamate, aldehydes, and alkylphosphinic acids provides a new, direct, and efficient method for synthesizing Fmoc-protected phosphinic pseudodipeptidic blocks, directly usable for solid-phase peptide synthesis.

  DOI：

  10.1021/ol051622y
• 作为产物：
  描述：

  [2-(ethoxycarbonyl)-4-methylpentyl]phosphonous acid bis(trimethylsilyl) ester 在 乙醇 作用下， 以 水 为溶剂， 生成 2-hydroxyphosphinoylmethyl-4-methyl-pentanoic acid ethyl ester
  参考文献：
  名称：

  Synthesis of phosphorus isosters of β-amyloid peptides fragments

  摘要：

  We have developed a synthetic route to pseudo dipeptides, analogs of certain fragments of beta-amyloid peptides (products of the APP protein hydrolysis). These compounds can be used for preparation of phosphinic acidic oligopeptides representing the peptide sequence of the beta-amyloid but containing the phosphorus isoster peptide fragment. Synthesis of pseudo ornityl-glutamate, pseudo arginyl-glutamate, pseudo glycyl-leucine, and pseudo isoleucyl-glycine via amino- and amidoalkylation of phosphonic acids containing the structural isoster of the corresponding amino acid is described.

  DOI：

  10.1134/s1070363215090121

文献信息

• Functional examination of novel kisspeptin phosphinic peptides
  作者：Xiaoyang Zhang、Magdalini Matziari、Yixin Xie、David Fernig、Rong Rong、Jia Meng、Zhi-Liang Lu

  DOI：10.1371/journal.pone.0195089

  日期：——

  Kisspeptins acting on their cognate G protein-coupled receptor, kisspeptin receptor, play important roles in the suppression of cancer cell metastasis and regulation of the reproductive system, and therefore are important for therapeutic intervention. All native functional human kisspeptins (kisspeptin-54, kisspsptin-14 and kisspeptin-13) share the 10 amino acids of kisspeptin-10 at their C-terminus (45–54). However, they are inactivated rapidly by matrix metalloproteinases (MMPs) through the cleavage of the peptide bond between glycine51 and leucine52, which limits their clinical applications. Development of MMP-resistant analogues of kisspeptins may provide better therapeutic outputs. In the present study, two kisspeptin phosphinic peptides were designed and synthesized, and their ability to induce phosphorylation of ERK1/2 through kisspeptin receptor and their inhibition on MMP-2 and MMP-9 whose activity correlates with cancer metastasis were assessed. The results showed that one analogue, phosphinic kisspeptin R isomer (PKPR), exhibited kisspeptin receptor-agonistic activity and also inhibitory activity on MMP-2, indicating that PKPR may serve as a lead for the further development of kisspeptin analogues for therapeutic purpose.

  吻肽作用于其同源的 G 蛋白偶联受体--吻肽受体，在抑制癌细胞转移和调节生殖系统方面发挥着重要作用，因此对治疗干预具有重要意义。所有原生功能性人类吻肽（吻肽素-54、吻肽素-14 和吻肽素-13）的 C 端（45-54）都含有吻肽素-10 的 10 个氨基酸。然而，它们会被基质金属蛋白酶（MMPs）通过裂解甘氨酸51 和亮氨酸52 之间的肽键而迅速失活，这限制了它们的临床应用。开发抗 MMP 的吻肽类似物可提供更好的治疗效果。本研究设计并合成了两种吻肽（kisspeptin phosphinic peptides），评估了它们通过吻肽（kisspeptin）受体诱导ERK1/2磷酸化的能力及其对与癌症转移相关的MMP-2和MMP-9的抑制作用。结果表明，其中一种类似物--膦酰基吻肽素 R 异构体（PKPR）不仅具有吻肽素受体拮抗活性，还具有抑制 MMP-2 的活性，这表明 PKPR 可作为进一步开发用于治疗的吻肽素类似物的先导。
• Synthesis of Phosphinic Analogue of Alanylleucine
  作者：S. R. Golovash、O. S. Grigorkevich、G. S. Tsebrikova、M. E. Dmitriev、V. V. Ragulin

  DOI：10.1134/s1070363220040313

  日期：2020.4

  AbstractThe amidoalkylation reactions of a phosphonous acid containing a structural isostere of leucine in acetyl chloride and(or) acetic anhydride were studied under conditions of acid catalysis. A two-component method for the synthesis of a phosphinic analogue of alanylleucine using ethylidenebis(benzylcarbamate) was proposed.

  摘要在酸催化条件下，研究了含有亮氨酸结构等位异构体的亚磷酸在乙酰氯和（或）乙酸酐中的酰胺烷基化反应。提出了使用亚乙基双（苄基氨基甲酸酯）合成丙氨酰亮氨酸的次膦酸酯类似物的两组分方法。