2-benzyl-3-hydroxyphosphinoyl-propionic acid ethyl ester | 865703-08-8

• 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-benzyl-3-hydroxyphosphinoyl-propionic acid ethyl ester
• CAS: 865703-08-8
• 化学式: C₁₂H₁₇O₄P
• 分子量: 256.238
• InChiKey: OGZBNDUUISTXFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.88
• 重原子数：
  17.0
• 可旋转键数：
  6.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 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-benzyl-3-hydroxyphosphinoyl-propionic 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-benzyl-3-{[(9H-fluoren-9-ylmethoxycarbonylamino)-phenyl-methyl]-hydroxy-phosphinoyl}-propionic 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：

  苄基丙二酸二乙酯 在 四氢吡咯 、 聚合甲醛 、 次磷酸铵 、 六甲基二硅氮烷 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 32.5h， 生成 2-benzyl-3-hydroxyphosphinoyl-propionic acid ethyl ester
  参考文献：
  名称：

  Neuromodulation by selective angiotensin-converting enzyme 2 inhibitors

  摘要：

  DOI：

  10.1016/j.neuroscience.2022.07.003

文献信息

• A Carbodiimide-Mediated P–C Bond-Forming Reaction: Mild Amidoalkylation of <i>P</i>-Nucleophiles by Boc-Aminals
  作者：Paraskevi Kokkala、Thayalan Rajeshkumar、Anastasia Mpakali、Efstratios Stratikos、Konstantinos D. Vogiatzis、Dimitris Georgiadis

  DOI：10.1021/acs.orglett.1c00155

  日期：2021.3.5

  carbodiimide-mediated P–C bond-forming reaction is described. The reaction involves activation of β-carboxyethylphosphinic acids and subsequent reaction with Boc-aminals using acid-catalysis. Mechanistic experiments using 31P NMR spectroscopy and DFT calculations support the contribution of unusually reactive cyclic phosphinic/carboxylic mixed anhydrides in a reaction pathway involving ion-pair “swapping”

  描述了碳二亚胺介导的 P-C 键形成反应的第一个例子。该反应涉及 β-羧乙基次膦酸的活化以及随后使用酸催化与 Boc-胺类反应。使用31 P NMR 光谱和 DFT 计算的机械实验支持异常反应性环状次膦酸/羧酸混合酸酐在涉及离子对“交换”的反应途径中的贡献。该协议的效用通过直接合成 Boc 保护的次膦酸二肽，作为强效锌氨基肽酶抑制剂的前体而突出。
• Development of Potent and Selective Phosphinic Peptide Inhibitors of Angiotensin-Converting Enzyme 2
  作者：Andreas Mores、Magdalini Matziari、Fabrice Beau、Philippe Cuniasse、Athanasios Yiotakis、Vincent Dive

  DOI：10.1021/jm701275z

  日期：2008.4.1

  Arimotensin-converting enzyme 2 (ACE2), a recently identified human homologue of angiotensin-converting enzyme, is a zinc metallocarboxypeptidase which may play a unique role in cardiovascular and renal function. Here we report the discovery of potent and selective inhibitors of ACE2, which have been identified by evaluating a series of phosphinic di- and tripeptides of the general formula: Z-Xaa(PO2-CH2)YaaOH and Ac-Zaa-Xaa(PO2-CH2)YaaOH. The most potent inhibitor in this series is a tripeptide that displays a K-i value of 0.4 nM toward ACE2 and is 3 orders of magnitude less potent toward carboxypeptidase A. Phosphinic tripeptides exhibit high potency exclusively when the Xaa position is occupied by a pseudoproline. A model of interaction between one inhibitor of this series and ACE2 suggests that the critical role played by a proline in inhibitors, but also for substrates hydrolysis, may rely on the presence of Tyr(510) in the ACE2 active site.