2-benzyl-3-hydroxyphosphinoyl-propionic acid | 865703-11-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 2-benzyl-3-hydroxyphosphinoyl-propionic acid
• 英文别名: 2-benzyl-3-(hydroxyhydrophosphoryl)propanoic acid；2-Benzyl-3-[hydroxy(oxido)phosphaniumyl]propanoic acid
• CAS: 865703-11-3
• 化学式: C₁₀H₁₃O₄P
• 分子量: 228.185
• InChiKey: AOFWGYYTJFNMQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  80.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-benzyl-3-hydroxyphosphinoyl-propionic acid 在 magnesium 、 溶剂黄146 、 三乙胺 、 乙酰氯 、 三氟乙酸 、 silver(l) oxide 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.0h， 生成 3-((1-adamantyloxy){1-[(9H-fluoren-9-ylmethoxy)carbonyl]-2-azepanyl}phosphoryl)-2-benzylpropanoic acid
  参考文献：
  名称：

  A Versatile Annulation Protocol toward Novel Constrained Phosphinic Peptidomimetics

  摘要：

  [GRAPHICS]The development of a novel 3-center 2-component annulation reaction between alpha,omega-carbamoylaldehydes and suitably monoalkylated phosphinic acids is reported. Depending on the starting alpha,omega-carbamoylaldehyde, diverse phosphinic scaffolds varying in the size of their rigidity element, the nature and stereochernistry of substituents, and the participation of heteroatoms in the azacyclic ring system can be obtained in one synthetic step and in high yield. In addition, this methodology allows the synthesis of Fmoc-protected constrained aminophosphinic acids that can be easily converted to suitable pseudodipeptide building blocks compatible with the requirements of peptide synthesis on the solid phase. Finally, the careful choice of both substituents and protecting groups can provide functionally diverse, orthogonally protected constrained scaffolds for extended derivatization of the target phosphinic peptidomimetic structrures.

  DOI：

  10.1021/jo071081l
• 作为产物：
  描述：

  在 甲醇 、 sodium hydroxide 作用下， 生成 2-benzyl-3-hydroxyphosphinoyl-propionic acid
  参考文献：
  名称：

  A Versatile Annulation Protocol toward Novel Constrained Phosphinic Peptidomimetics

  摘要：

  [GRAPHICS]The development of a novel 3-center 2-component annulation reaction between alpha,omega-carbamoylaldehydes and suitably monoalkylated phosphinic acids is reported. Depending on the starting alpha,omega-carbamoylaldehyde, diverse phosphinic scaffolds varying in the size of their rigidity element, the nature and stereochernistry of substituents, and the participation of heteroatoms in the azacyclic ring system can be obtained in one synthetic step and in high yield. In addition, this methodology allows the synthesis of Fmoc-protected constrained aminophosphinic acids that can be easily converted to suitable pseudodipeptide building blocks compatible with the requirements of peptide synthesis on the solid phase. Finally, the careful choice of both substituents and protecting groups can provide functionally diverse, orthogonally protected constrained scaffolds for extended derivatization of the target phosphinic peptidomimetic structrures.

  DOI：

  10.1021/jo071081l

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。
• Structure-Guided, Single-Point Modifications in the Phosphinic Dipeptide Structure Yield Highly Potent and Selective Inhibitors of Neutral Aminopeptidases
  作者：Stamatia Vassiliou、Ewelina Węglarz-Tomczak、Łukasz Berlicki、Małgorzata Pawełczak、Bogusław Nocek、Rory Mulligan、Andrzej Joachimiak、Artur Mucha

  DOI：10.1021/jm501071f

  日期：2014.10.9

  The constitution of P1′-extended structures was rationally designed and the lead, phosphinic dipeptide hPhePψ[CH2]Phe, was modified in a single position. Introducing a heteroatom/heteroatom-based fragment to either the P1 or P1′ residue required new synthetic pathways. The compounds in the refined structure were low nanomolar and subnanomolar inhibitors of N. meningitides, porcine and human APNs,

  来自脑膜炎奈瑟菌（脑膜炎的病原体，Nm）的丙氨酰氨肽酶的七种晶体结构与有机磷化合物复合的 APN) 被解析以确定最佳抑制剂 - 酶相互作用。Leu 和 hPhe 的对映体膦酸类似物对应于加工良好的底物的 P1 氨基酸残基，用于评估绝对构型的影响以及氨基膦酸酯极性头与活性位点之间形成的立体定向氢键网络结合亲和力上的残基。对于 hPhe 类似物，可以通过加入适当的 P1 侧链来克服不完美的立体化学互补性。P1'-延伸结构的结构设计合理，铅、次膦酸二肽hPhePψ[CH 2] Phe，在一个位置进行了修改。将基于杂原子/杂原子的片段引入 P1 或 P1' 残基需要新的合成途径。精制结构中的化合物是脑膜炎奈瑟菌、猪和人 APN 的低纳摩尔和亚纳摩尔抑制剂，以及参考亮氨酸氨肽酶 (LAP)。非天然次膦酸二肽类似物对单锌 APNs 表现出高亲和力，与二锌 LAP 相比具有合理的选择性。另一组包含Nm APN
• Shortcut to Fmoc-Protected Phosphinic Pseudodipeptidic Blocks
  作者：Magdalini Matziari、Athanasios Yiotakis

  DOI：10.1021/ol051622y

  日期：2005.9.1

  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.