benzyl N²-((benzyloxy)carbonyl)-N⁶-(tert-butoxycarbonyl)-L-lysinate | 128972-27-0

• 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: benzyl N²-((benzyloxy)carbonyl)-N⁶-(tert-butoxycarbonyl)-L-lysinate
• 英文别名: Nalpha-CBZ-Nepsilon-(tert-butoxycarbonyl)-L-lysine benzyl ester；benzyl (2S)-6-[(2-methylpropan-2-yl)oxycarbonylamino]-2-(phenylmethoxycarbonylamino)hexanoate
• CAS: 128972-27-0
• 化学式: C₂₆H₃₄N₂O₆
• 分子量: 470.566
• InChiKey: GTQCBZHWLOVRHD-QFIPXVFZSA-N

物化性质

• 熔点：
  76-79 °C(Solv: ethyl ether (60-29-7); hexane (110-54-3))
• 沸点：
  625.6±55.0 °C(Predicted)
• 密度：
  1.149±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  34
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  benzyl N²-((benzyloxy)carbonyl)-N⁶-(tert-butoxycarbonyl)-L-lysinate 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 benzyl (2S)-6-[[(2S)-2-[[(3S,4S)-5-cyclohexyl-3-hydroxy-4-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]amino]-4-methylpentanoyl]amino]-2-(phenylmethoxycarbonylamino)hexanoate
  参考文献：
  名称：

  1,2,4-Triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity. 1. Synthesis and biological properties of alkyl alcohol and statine derivatives

  摘要：

  A series of 1,2,4-triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity, which incorporate (1S,2S)-2-amino-1,3-dicyclohexyl-1-hydroxypropane, statine (Sta), and (3S,4S)-4-amino-5-cyclohexyl-3-hydroxy-pentanoic acid (ACHPA) transition-state mimetics, have been prepared. Structure-activity relationships for renin inhibitory activity in the series are consistent with the 2-[8-isobutyl-6-phenyl-1,2,4-triazolo[4,3-a]pyrazin-3-yl]-3-(3 pyridyl)propionic acid moiety 10b acting as a non-peptidic replacement for the P4-P2 (Pro-Phe-His) residues of the natural substrate angiotensinogen. Compounds 12m, 12o and 12q were potent inhibitors of partially purified human renin (IC50 values 1.7, 6.8, and 3.7 nM, respectively), and also effectively lowered blood pressure in anesthetized, sodium depleted marmosets following intravenous administration. On oral administration however, no blood pressure lowering activity could be detected, and absorption studies in bile duct cannulated rats indicate that this may be due primarily to poor oral absorption, rather than rapid biliary excretion. The reason for the observed poor oral activity is not clear, but it seems unlikely that poor aqueous solubility or metabolic instability to gut enzymes are rate-determining, and other factors such as high molecular weight may also be very important.

  DOI：

  10.1021/jm00171a005
• 作为产物：
  描述：

  N-alpha-Cbz-L-赖氨酸 在 sodium hydroxide 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 benzyl N²-((benzyloxy)carbonyl)-N⁶-(tert-butoxycarbonyl)-L-lysinate
  参考文献：
  名称：

  Synthesis and evaluation of peptidic maleimides as transglutaminase inhibitors

  摘要：

  A series of novel transglutaminase inhibitors was prepared, based on the scaffold of a commonly used peptide substrate and bearing an electrophilic maleimide group. These compounds were evaluated in vitro and shown to lead to irreversible inactivation of tissue transglutaminase. Comparison with inhibitors studied previously provides insight into the steric environment of the enzyme active site. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.10.061

文献信息

• Synthesis and Spectroscopic Properties of Fluorinated Coumarin Lysine Derivatives
  作者：Lakshmi Shukla、Lindon W. K. Moodie、Tomas Kindahl、Christian Hedberg

  DOI：10.1021/acs.joc.7b03214

  日期：2018.4.20

  protein reporters. For successful application, a robust and scalable, yet flexible, route to non-natural amino acids is required. This work describes an improved synthesis of coumarin-conjugated lysine derivatives where fluorinated variants are accessed. These analogues can be utilized at low pH and should find application probing biological processes that operate under acidic conditions.

  荧光氨基酸向蛋白质中的位点选择性掺入已经成为可表达的蛋白质报道分子的有价值的替代物。为了成功应用，需要一种稳健，可扩展但灵活的途径来合成非天然氨基酸。这项工作描述了香豆素共轭赖氨酸衍生物的改进的合成方法，其中有氟化的变体。这些类似物可在低pH值下使用，应用于探测在酸性条件下运行的生物过程。
• Solid-Phase Synthesis of DOTA–Peptides
  作者：Luis M. De León-Rodriguez、Zoltan Kovacs、Gregg R. Dieckmann、A. Dean Sherry

  DOI：10.1002/chem.200305389

  日期：2004.3.5

  DOTA-linked N-Fmoc amino acids (DOTA-F and DOTA-K) is described that allows insertion of DOTA at any endo-position within a peptide sequence. Three model pentapeptides were prepared to test the general utility of these derivatives in solid-phase peptide synthesis. Both DOTA derivatives reacted smoothly by means of standard HBTU activation chemistry to the point of insertion of the DOTA amino acid, but extension

  描述了到两个DOTA连接的N-Fmoc氨基酸（DOTA-F和DOTA-K）的一般合成途径，其允许将DOTA插入肽序列内的任何内位。制备了三种模型五肽以测试这些衍生物在固相肽合成中的通用性。两种DOTA衍生物均通过标准的HBTU活化化学反应平稳地反应到DOTA氨基酸的插入点，但是肽链的延伸超出DOTA-氨基酸的插入要求使用预活化的C-五氟苯基酯N-alpha -Fmoc氨基酸。然后使用此方法通过将DOTA置于N末端或两个不同内部位置之一的方式制备三个Gal-80结合肽（12-mers）;将所得GdDOTA-12-mers与Gal-80的结合进行了分析比较的。此处描述的方法允许将DOTA进行多种控制导入肽序列内的任何位置。这提供了筛选DOTA连接的肽文库以获得最佳靶向特性的潜在方法。
• Convenient Synthesis of Nε-(Carboxymethyl)lysine, a Key Advanced Glycation Endproduct Biomarker
  作者：John Nielsen、Jeanette Andersen、Thomas Hjelmgaard、Lars Dragsted

  DOI：10.1055/s-0031-1290348

  日期：2012.3

  Advanced glycation endproducts (AGEs) are formed when sugars react with peptides and proteins without the help of enzymes and by thermal processing of food such as baking and frying. AGEs and especially N ε-(carboxymethyl)lysine (CML) has been used as general key biomarkers for oxidative stress and a number of diseases associated with poor lifestyle. Herein we present the first synthetic pathway to the free zwitter ion of CML via a protected intermediate.

  高级糖化终产物（AGEs）是糖在没有酶的帮助下与肽和蛋白质发生反应时，以及在烘烤和油炸等食品热加工过程中形成的。AGEs 尤其是 N δµ-（羧甲基）赖氨酸（CML）已被用作氧化应激和与不良生活方式相关的多种疾病的一般关键生物标志物。在此，我们首次提出了通过受保护中间体合成 CML 自由齐聚物离子的途径。
• Controlled Synthesis of <i>O</i>-Glycopolypeptide Polymers and Their Molecular Recognition by Lectins
  作者：Debasis Pati、Ashif Y. Shaikh、Soumen Das、Pavan Kumar Nareddy、Musti J Swamy、Srinivas Hotha、Sayam Sen Gupta

  DOI：10.1021/bm201813s

  日期：2012.5.14

  The facile synthesis of high molecular weight water-soluble O-glycopolypeptide polymers by the ring-opening polymerization of their corresponding N-carboxyanhydride (NCA) in very high yield (overall yield > 70%) is reported. The per-acetylated-O-glycosylated lysine-NCA monomers, synthesized using stable glycosyl donors and a commercially available protected amino acid in very high yield, was polymerized

  据报道，通过其相应的N-羧基酐（NCA）的开环聚合，可以非常高的收率（总收率＞ 70％）容易地合成高分子量的水溶性O-糖基多肽聚合物。过乙酰化的O使用稳定的糖基供体和可商购的受保护氨基酸以非常高的产率合成的β-糖基化的赖氨酸-NCA单体，使用可商购的胺引发剂进行聚合。发现合成的水溶性糖多肽在水溶液中为α-螺旋。但是，我们能够通过聚合外消旋氨基酸糖NCAs来控制糖多肽的二级构象（α螺旋结构与非螺旋结构）。我们还研究了糖多肽聚（α-甘露聚糖-O-lys）与凝集素Con-A一起使用沉淀和血凝试验以及等温滴定量热法（ITC）。ITC结果清楚地表明，α-螺旋结构和非螺旋结构的结合过程都是由焓驱动的，具有负的熵贡献。与采用α-螺旋结构的相应多肽相比，具有非螺旋结构的糖多肽聚（α-甘露聚糖-O -lys ）的结合化学计量稍高。
• Spontaneous Orthogonal Protein Crosslinking via a Genetically Encoded 2‐Carboxy‐4‐Aryl‐1,2,3‐Triazole
  作者：Yali Xu、Abdur Rahim、Qing Lin

  DOI：10.1002/anie.202202657

  日期：2022.5.23

  A genetically encoded N2-carboxy-4-aryl-1,2,3-triazole-lysine (CATK) permits a spontaneous, quantitative, site-specific inter-strand crosslinking with a proximal Tyr in a small antibody-mimetic protein, generating a novel protein topology accompanied by improved cellular uptake and enhanced proteolytic resistance.

  基因编码的N 2 -羧基-4-芳基-1,2,3-三唑-赖氨酸 (CATK) 允许与小型抗体模拟蛋白中的近端 Tyr 自发、定量、位点特异性链间交联，产生一种新颖的蛋白质拓扑结构，伴随着改善的细胞摄取和增强的蛋白水解抗性。