(2S,3R)-4-[bis[(2-methylpropan-2-yl)oxy]phosphoryl]-3-methyl-2-(phenylmethoxycarbonylamino)butanoic acid | 1403265-58-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S,3R)-4-[bis[(2-methylpropan-2-yl)oxy]phosphoryl]-3-methyl-2-(phenylmethoxycarbonylamino)butanoic acid
• CAS: 1403265-58-6
• 化学式: C₂₁H₃₄NO₇P
• 分子量: 443.477
• InChiKey: SLQVLCHQCCQILX-RDJZCZTQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  30
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S,3R)-4-[bis[(2-methylpropan-2-yl)oxy]phosphoryl]-3-methyl-2-(phenylmethoxycarbonylamino)butanoic acid 在 碳酸氢钠 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 ((((2R,3S)-4-(benzyloxy)-3-(((benzyloxy)carbonyl)amino)-2-methyl-4-oxobutyl)phosphoryl)bis(oxy))bis(methylene)bis(2,2-dimethylpropanoate)
  参考文献：
  名称：

  用于将磷酸苏氨酸模拟物 (2 S ,3 R )-2-氨基-3-甲基-4-膦酰丁酸 (Pmab) 固相掺入生物可逆膦酰-双-新戊酰氧基甲基肽中的试剂的设计和合成(POM) 前药形式

  摘要：

  本文报道了N- Fmoc-(2 S ,3 R )-2-氨基-3-甲基-4-膦酰丁酸双-新戊酰氧基甲基磷酸酯 [Fmoc-Pmab(POM) 2 - OH, 2 ] 作为磷酸酶稳定的磷酸苏氨酸 (pThr) 模拟物，具有正交保护，适用于合成具有膦酸部分生物可逆保护的含 Pmab 的肽。这代表了适用于简便固相肽合成形式的生物可逆保护 pThr 模拟物的第一份报告。

  DOI：

  10.1007/s00726-013-1567-0
• 作为产物：
  描述：

  (2S,3R)-4-[di-(tert-butyl)-oxyphosphinyl]-N-(phenylmethoxycarbonyl)-L-valine methyl ester 在 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 生成 (2S,3R)-4-[bis[(2-methylpropan-2-yl)oxy]phosphoryl]-3-methyl-2-(phenylmethoxycarbonylamino)butanoic acid
  参考文献：
  名称：

  用于将磷酸苏氨酸模拟物 (2 S ,3 R )-2-氨基-3-甲基-4-膦酰丁酸 (Pmab) 固相掺入生物可逆膦酰-双-新戊酰氧基甲基肽中的试剂的设计和合成(POM) 前药形式

  摘要：

  本文报道了N- Fmoc-(2 S ,3 R )-2-氨基-3-甲基-4-膦酰丁酸双-新戊酰氧基甲基磷酸酯 [Fmoc-Pmab(POM) 2 - OH, 2 ] 作为磷酸酶稳定的磷酸苏氨酸 (pThr) 模拟物，具有正交保护，适用于合成具有膦酸部分生物可逆保护的含 Pmab 的肽。这代表了适用于简便固相肽合成形式的生物可逆保护 pThr 模拟物的第一份报告。

  DOI：

  10.1007/s00726-013-1567-0

文献信息

• Peptide and peptide mimetic binding antagonists of polo-like kinase 1 polo box domain and methods of use
  申请人：The United States of America, as represented by the Secretary, Department of Health & Human Services

  公开号：US10905769B2

  公开（公告）日：2021-02-02

  The description provides novel compounds that may serve as anticancer therapeutics. The compounds of the description bind to polo-like kinases through the polo-box domain. The peptide derivatives of the description have achieved improved efficacy in biochemical assays against Plk1. Exemplary compounds of the description include macrocyclic peptidomimetics with high affinity and selectivity for polo-like kinases, which may provide the basis for a new genre of anticancer therapeutics. Other exemplary compounds of the description include bi-valent compounds with that bind to polo-like kinases through both kinase domain and polo-box domain simultaneously by incorporating additional moieties that target Plk1 kinase domain, which significantly enhances affinitity relative and may provide the basis for a new genre of anticancer therapeutics. The description also provides methods of use, methods of preparation, compositions, and kits thereof. Further, the description provides a novel method of design and/or synthesis of phosphoryl-derived peptide derivatives useful as therapeutic agents.

  说明提供了可用作抗癌疗法的新型化合物。所述化合物通过 polo-box 结构域与 polo-like 激酶结合。描述中的肽衍生物在生化试验中对 Plk1 的疗效有所提高。本发明的示例化合物包括对polo-like激酶具有高亲和力和选择性的大环肽拟化物，可为新型抗癌疗法奠定基础。本发明的其他示例化合物包括双价化合物，它们通过加入靶向 Plk1 激酶结构域的附加分子，同时通过激酶结构域和 polo-box 结构域与 polo-like 激酶结合，从而显著增强了亲和性，并可为新型抗癌疗法奠定基础。说明还提供了使用方法、制备方法、组合物及其试剂盒。此外，该描述还提供了一种设计和/或合成可用作治疗剂的磷酸衍生肽衍生物的新方法。
• Preparation of orthogonally protected (2S,3R)-2-amino-3-methyl-4-phosphonobutyric acid (Pmab) as a phosphatase-stable phosphothreonine mimetic and its use in the synthesis of polo-box domain-binding peptides
  作者：Fa Liu、Jung-Eun Park、Kyung S. Lee、Terrence R. Burke

  DOI：10.1016/j.tet.2009.09.093

  日期：2009.11

  Reported herein is the first stereoselective synthesis of (2S,3R)-4-[bis-(tert-butyloxy)phosphinyl]-2-[(9H-fluoren-9-ylmethoxy)carbonyl]amino-3-methylbutanoic acid [(N-Fmoc, O,O-(bis-(tert-butyl))-Pmab), 4] as a hydrolytically-stable phosphothreonine mimetic bearing orthogonal protection compatible with standard solid-phase protocols. The synthetic approach used employs Evans' oxazolidinone for chiral induction. Also presented is the application of 4 in the solid-phase synthesis of polo-like kinase 1 (Plk1) polo box domain (PBD)-binding peptides. These Pmab-containing pepticles retain PBD binding efficacy similar to a parent pThr containing peptide. Reagent 4 should be a highly useful reagent for the preparation of signal transduction-directed pepticles. Published by Elsevier Ltd.
• PEPTIDE AND PEPTIDE MIMETIC BINDING ANTAGONISTS OF POLO-LIKE KINASE 1 POLO BOX DOMAIN AND METHODS OF USE
  申请人：The United States of America, as represented by theSecretary, Department of Health &Human Services

  公开号：US20180296686A1

  公开（公告）日：2018-10-18

  The description provides novel compounds that may serve as anticancer therapeutics. The compounds of the description bind to polo-like kinases through the polo-box domain. The peptide derivatives of the description have achieved improved efficacy in biochemical assays against Plk1. Exemplary compounds of the description include macrocyclic peptidomimetics with high affinity and selectivity for polo-like kinases, which may provide the basis for a new genre of anticancer therapeutics. Other exemplary compounds of the description include bi-valent compounds with that bind to polo-like kinases through both kinase domain and polo-box domain simultaneously by incorporating additional moieties that target Plk1 kinase domain, which significantly enhances affinitity relative and may provide the basis for a new genre of anticancer therapeutics. The description also provides methods of use, methods of preparation, compositions, and kits thereof. Further, the description provides a novel method of design and/or synthesis of phosphoryl-derived peptide derivatives useful as therapeutic agents.
• [EN] PEPTIDE MIMETIC LIGANDS OF POLO-LIKE KINASE 1 POLO BOX DOMAIN AND METHODS OF USE<br/>[FR] LIGANDS MIMÉTIQUES PEPTIDIQUES DU DOMAINE POLO-BOX DES KINASES POLO-LIKE 1 ET LEURS PROCÉDÉS D'UTILISATION
  申请人：US GOV HEALTH & HUMAN SERV

  公开号：WO2012142245A2

  公开（公告）日：2012-10-18

  Novel compounds are provided that bind to polo-like kinases through the polo-box domain. In certain embodiments, the novel compounds are PEGylated peptides. The PEGylated peptides in accordance with the invention demonstrate high PBD-binding affinity. In certain embodiments, the PEGylated peptides have also achieved activities in whole cell systems. The invention also provides compounds that bind polo-like kinases through the polo-box domain and possess reduced anionic charge. Further provided are methods of design and/or synthesis of the PEGylated peptides and methods of use thereof. The invention provides methods of use of the compounds and methods of synthesis of the compounds.
• [EN] PEPTIDE AND PEPTIDE MIMETIC BINDING ANTAGONISTS OF POLO-LIKE KINASE 1 POLO BOX DOMAIN AND METHODS OF USE<br/>[FR] PEPTIDES ET PEPTIDES MIMÉTIQUES ANTAGONISTES DE LIAISON DE DOMAINE POLO-BOX DE KINASE 1 DE TYPE POLO ET PROCÉDÉ D'UTILISATION
  申请人：THE US SECRETARY DEPT OF HEALTH & HUMAN SERVICES

  公开号：WO2017082924A1

  公开（公告）日：2017-05-18

  The description provides novel compounds that may serve as anticancer therapeutics. The compounds of the description bind to polo-like kinases through the polo-box domain. The peptide derivatives of the description have achieved improved efficacy in biochemical assays against Plk1. The description also provides methods of use, methods of preparation, compositions, and kits thereof. Further, the description provides a novel method of design and/or synthesis of phosphoryl-derived peptide derivatives useful as therapeutic agents.