(S)-2-{(R)-2-tert-butoxycarbonylamino-3-[(R)-2-tert-butoxycarbonylamino-2-((S)-1-methoxycarbonyl-2-methyl-propionylcarbamoyl)-ethyldisulfanyl]-propionylamino}-3-methyl-butyric acid methyl ester | 139167-60-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-2-{(R)-2-tert-butoxycarbonylamino-3-[(R)-2-tert-butoxycarbonylamino-2-((S)-1-methoxycarbonyl-2-methyl-propionylcarbamoyl)-ethyldisulfanyl]-propionylamino}-3-methyl-butyric acid methyl ester
• 英文别名: (2S,2′S)-dimethyl 2,2′-[((2R,2′R)-3,3′-disulfanediylbis{2-[(tert-butoxycarbonyl)amino]propanoyl})bis(azanediyl)]bis(3-methylbutanoate)；(Boc-Cys-Val-OMe)₂；(L-Boc-Cys-Val-OMe)₂；Boc-Cys(1)-Val-OMe.Boc-Cys(1)-Val-OMe；methyl (2S)-2-[[(2R)-3-[[(2R)-3-[[(2S)-1-methoxy-3-methyl-1-oxobutan-2-yl]amino]-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-oxopropyl]disulfanyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]-3-methylbutanoate
• CAS: 139167-60-5
• 化学式: C₂₈H₅₀N₄O₁₀S₂
• 分子量: 666.858
• InChiKey: OPTNSSZVTLEILL-MUGJNUQGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  44
• 可旋转键数：
  21
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  238
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (S)-2-{(R)-2-tert-butoxycarbonylamino-3-[(R)-2-tert-butoxycarbonylamino-2-((S)-1-methoxycarbonyl-2-methyl-propionylcarbamoyl)-ethyldisulfanyl]-propionylamino}-3-methyl-butyric acid methyl ester 在 吡啶 、 溴 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以46%的产率得到(S)-methyl 2-{(R)-4-[(tert-butoxycarbonyl)-amino]-3-oxoisothiazolidin-2-yl}-3-methylbutanoate
  参考文献：
  名称：

  Selective Reduction of Peptide Isothiazolidin-3-ones

  摘要：

  Isothiazolidinones are a rare but potentially important chemical moiety in biochemistry. We report the identification of several thiol, phosphinate, and carbon nucleophiles that form covalent adducts by addition to the sulfenamide sulfur. This reduction is selective for isothiazolidinones over similar peptide disulfides. We synthesized a coumarin-based thioacid nucleophile which shows a marked fluorescence increase after addition to an isothiazolidinone sulfenamide bond.

  DOI：

  10.1021/ol062077j
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 (S)-2-{(R)-2-tert-butoxycarbonylamino-3-[(R)-2-tert-butoxycarbonylamino-2-((S)-1-methoxycarbonyl-2-methyl-propionylcarbamoyl)-ethyldisulfanyl]-propionylamino}-3-methyl-butyric acid methyl ester
  参考文献：
  名称：

  具有半胱氨酸二肽的高细胞毒性生物共轭金（I）配合物

  摘要：

  从半胱氨酸开始，通过偶联不同的氨基酸并使用几种正交保护，制备了几种含半胱氨酸二肽的金（I）配合物。第一步是胱氨酸与Boc 2 O的反应，其中的硫中心被保护为二硫键，以保护氨基，然后偶联氨基酸酯。最后用巯基乙醇将二硫键断裂，得到二肽衍生物。与[AuCl（PPh 3）]进一步反应，得到金-二肽-膦物质。从这些形式正式的具有通式[Au（SR）（PR 3）]引入了不同的结构修饰，例如氨基保护基类型的变化，膦的类型，每个分子的金（I）原子数或使用非蛋白构象受限的氨基酸酯为了评估它们对最终复合物生物学活性的影响。评价了这些复合物在体外对不同肿瘤人类细胞系（A549，MiaPaca2和Jurkat）的细胞毒活性。该复合物显示出优异的细胞毒性活性，其IC 50值在非常低的微摩尔范围内。来自复合物的结构-活性关系研究为设计更有效和更有前途的金（I）抗癌剂提供了可能性。

  DOI：

  10.1002/chem.201501458

文献信息

• Copper‐Promoted O‐Arylation of the Phenol Side Chain of Tyrosine Using Triarylbismuthines
  作者：Adrien Le Roch、Martin Hébert、Alexandre Gagnon

  DOI：10.1002/ejoc.202000790

  日期：2020.9.7

  for the O‐arylation of the side chain of tyrosine using triarylbismuth reagents is reported. The reaction is performed in dichloromethane under oxygen at 50 °C in the presence of pyridine, is promoted by copper diacetate, shows excellent scope and functional group tolerance, and retains the integrity of the chiral center. The reactivity of other amino acids possessing a nucleophilic side chain under these

  报道了使用三芳基铋试剂对酪氨酸侧链进行O-芳基化的方法。该反应在吡啶存在下于氧气中于50°C的氧气中于二氯甲烷中进行，由二乙酸铜促进，显示出极好的范围和官能团耐受性，并保留了手性中心的完整性。研究了在这些条件下具有亲核侧链的其他氨基酸的反应性。可以实现含酪氨酸的二肽和三肽的O-酰化。
• Thiirancarboxamides as Inhibitors of Papain
  作者：Gemma Bruno、Tanja Schirmeister

  DOI：10.1002/ardp.200300820

  日期：2004.2

  Derivatives of the thiirancarboxylic acid building‐block containing a peptide bond were synthesised and screened against the model cysteine protease papain. The most active of the series showed a second‐order rate constant of inactivation comparable to that of the parent compound. The insertion of a peptide moiety seems to compensate the lack of a free carboxylate interacting with the histidinium ion

  合成含有肽键的硫茚甲酸结构单元的衍生物，并针对模型半胱氨酸蛋白酶木瓜蛋白酶进行筛选。该系列中最活跃的表现出与母体化合物相当的二阶失活速率常数。肽部分的插入似乎弥补了在酶活性位点与组氨酸鎓离子相互作用的游离羧酸盐的缺乏。
• Chemistry of isoprenylated cysteinyl containing peptides. [2,3]. Sigmatropic rearrangement of S-farnesylcysteinyl sulfoxides. Studies toward a mild method of deprenylating lipopeptides.
  作者：Eric M. Gordon、Jelka Pluscec

  DOI：10.1021/ja00030a081

  日期：1992.2
• Reactions of 1,3-Diketones with a Dipeptide Isothiazolidin-3-one: Toward Agents That Covalently Capture Oxidized Protein Tyrosine Phosphatase 1B
  作者：Kasi Viswanatharaju Ruddraraju、Zachary D. Parsons、Elizabeth M. Llufrio、Natasha L. Frost、Kent S. Gates

  DOI：10.1021/acs.joc.5b01949

  日期：2015.12.18

  Protein tyrosine phosphatase 1B (PTP1B) is a validated therapeutic target for the treatment of type 2 diabetes; however, the enzyme has been classified by some as an "undruggable target". Here we describe studies directed toward the development of agents that covalently capture the sulfenyl amide "oxoform" of PTP1B generated during insulin signaling events. The sulfenyl amide residue found in oxidized PTP1B presents a unique electrophilic sulfur center that may be exploited in drug and probe design. Covalent capture of oxidized PTP1B could permanently disable the intracellular pool of enzyme involved in regulation of insulin signaling. Here, we employed a dipeptide model of oxidized PTP1B to investigate the nucleophilic capture of the sulfenyl amide residue by structurally diverse 1,3-diketones. All of the 1,3-diketones examined here reacted readily with the electrophilic sulfur center in the sulfenyl amide residue to generate stable covalent attachments. Several different types of products were observed, depending upon the substituents present on the 1,3-diketone. The results provide a chemical foundation for the development of agents that covalently capture the oxidized form of PTP1B generated in cells during insulin signaling events.