N-(2-(2-(2-(prop-2-ynyloxy)ethoxy)ethoxy)ethyl)-5-(hexahydro-2-oxo-1H-thieno[3,4-d]imidazol-4-yl)pentanamide | 1421701-68-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 生物素及其衍生物
• 英文名称: N-(2-(2-(2-(prop-2-ynyloxy)ethoxy)ethoxy)ethyl)-5-(hexahydro-2-oxo-1H-thieno[3,4-d]imidazol-4-yl)pentanamide
• 英文别名: N-(2-{2-[2-(prop-2-yn-1-yloxy)ethoxy]ethoxy}ethyl)biotinamide；Biotin-PEG3-propargyl；5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[2-[2-(2-prop-2-ynoxyethoxy)ethoxy]ethyl]pentanamide
• CAS: 1421701-68-9
• 化学式: C₁₉H₃₁N₃O₅S
• 分子量: 413.538
• InChiKey: GHIQFERKSLOFCW-BQFCYCMXSA-N

物化性质

• 沸点：
  687.3±55.0 °C(Predicted)
• 密度：
  1.163±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  28
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  6

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  N-(2-(2-(2-(prop-2-ynyloxy)ethoxy)ethoxy)ethyl)-5-(hexahydro-2-oxo-1H-thieno[3,4-d]imidazol-4-yl)pentanamide 、 5-(azidomethyl)picolinaldehyde 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 以45%的产率得到N-(2-{2-[2-({1-[(2-formylpyridin-4-yl)methyl]-1H-1,2,3-triazol-4-yl}methoxy)ethoxy]ethoxy}ethyl)biotinamide
  参考文献：
  名称：

  通过仿生铜 (II) 介导的羟醛反应对蛋白质进行单步 N 端修饰

  摘要：

  在温和条件下铜 (II) 盐存在的情况下， 2-吡啶甲醛衍生物在肽和蛋白质的 N 末端发生独特的醛醇反应。肽和蛋白质很容易在一个步骤中用有用的官能团或反应性手柄进行修饰。

  DOI：

  10.1002/chem.202201677
• 作为产物：
  描述：

  [丙炔基-三聚乙二醇-氨基] 、 (+)生物素-N-琥珀酰亚胺基酯 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以95%的产率得到N-(2-(2-(2-(prop-2-ynyloxy)ethoxy)ethoxy)ethyl)-5-(hexahydro-2-oxo-1H-thieno[3,4-d]imidazol-4-yl)pentanamide
  参考文献：
  名称：

  走向生物素化硫酸软骨素类似物的图书馆：从合成到体内研究。

  摘要：

  硫酸软骨素-E（CS-E）寡糖类似物（二至六）是从乳糖制备的。在这些化合物中，2-乙酰氨基基团被羟基取代。这种修饰加快了合成的速度，从乳糖起源的嵌段开始，只需几步即可构建大寡糖。使用的保护基如下：用于羟基糖基化的Fmoc，用于端基位置保护的烯丙基和三氯乙酰亚氨酸酯离去基团用于制备至多八糖。我们利用烯丙基的存在通过点击转化为3-叠氮基-2-羟基丙基的两个步骤（环氧化和叠氮化钠环氧化物开口）来发展点击生物素化。生物素化剂是水溶性的炔丙基化和生物素化的三甘醇（PEG）。通过使用表面等离振子共振（SPR），表明二糖，四糖和六糖对HSF / GSF和CXCL12的结合亲和力和选择性与CS-E相似。一项平行研究证实了它们是天然化合物的模仿，基于六糖与Otx2的相互作用，Otx2是参与大脑成熟的同源结构域蛋白，因此验证了我们合成生物活性GAG的简化方法。

  DOI：

  10.1002/chem.201202173

文献信息

• Synthesis of Fucosylated Chondroitin Sulfate Nonasaccharide as a Novel Anticoagulant Targeting Intrinsic Factor Xase Complex
  作者：Xiao Zhang、Huiying Liu、Lisha Lin、Wang Yao、Jinhua Zhao、Mingyi Wu、Zhongjun Li

  DOI：10.1002/anie.201807546

  日期：2018.9.24

  Fucosylated chondroitin sulfate (FuCS) is a structurally distinct glycosaminoglycan, and its oligosaccharides exhibit excellent anticoagulant activity with lower risks of adverse effects and bleeding. Herein we report a facile approach to the synthesis of FuCS hexa‐ and nonasaccharides on the basis of the enzymatic degradation of chondroitin over 12 linear steps. As compared with a clinical low‐molecular‐weight

  岩藻糖基化硫酸软骨素（FuCS）是结构上独特的糖胺聚糖，其寡糖具有出色的抗凝活性，具有较低的不良反应和出血风险。在此，我们报告了一种基于软骨素在12个线性步骤上酶促降解的合成FuCS六糖和九糖的简便方法。与临床低分子量肝素药物（依诺肝素）相比，本研究中合成的九糖通过与高浓度因子IXa结合表现出相似的APTT活性和选择性内在因子Xase复合物抑制活性（（12.9±0.83）n m）。亲和力，因此为开发针对内在凝血途径的新型抗凝剂提供了希望。
• Semisynthesis of Chondroitin Sulfate Oligosaccharides Based on the Enzymatic Degradation of Chondroitin
  作者：Xiao Zhang、Huiying Liu、Wang Yao、Xiangbao Meng、Zhongjun Li

  DOI：10.1021/acs.joc.9b00112

  日期：2019.6.7

  Chondroitin sulfate (CS) is a structurally complex polyanionic glycosaminoglycan that plays essential roles in physiological processes. Here we report a facile approach to a library of CS tetra- and hexasaccharides based on the enzymatic degradation of chondroitin over 10 or 11 steps, which is the shortest synthetic route toward size-defined CS oligosaccharides reported to date. Subsequent biotinylation

  硫酸软骨素（CS）是一种结构复杂的聚阴离子糖胺聚糖，在生理过程中起着至关重要的作用。在这里，我们报告了一种基于软骨素在10或11步以上的酶促降解的CS四糖和六糖文库的简便方法，这是迄今为止迄今为止报道的针对尺寸确定的CS寡糖的最短合成途径。随后的生物素化使得能够研究它们与生长因子的相互作用，填补了现有研究的空白，并为进一步探索CS的生物学功能提供了探针。
• In vivo programming of endogenous antibodies via oral administration of adaptor ligands
  作者：Masanobu Nagano、Nancy Carrillo、Nobumasa Otsubo、Wataru Hakamata、Hitoshi Ban、Roberta P. Fuller、Nasir K. Bashiruddin、Carlos F. Barbas

  DOI：10.1016/j.bmc.2017.09.010

  日期：2017.11

  Vaccination is a reliable method of prophylaxis and a crucial measure for public health. However, the majority of vaccines cannot be administered orally due to their degradation in the harsh gut environment or inability to cross the GI tract. In this study, we report the first proof-of-concept study of orally producible chemically programmed antibodies via specific conjugation of adaptor ligands to endogenous antibodies, in vivo. Pre-immuniztion with 2,4-dinitrophenyl (DNP), or the reactive hapten, 1,3-diketone (DK), or a novel reactive hapten, vinyl sulfone (VS) in mice, followed by oral administration of adaptor ligands composed of the hapten and biotin to the pre-immunized mice resulted in successful in vivo formation of the biotin-hapten-antibody complexes within 2 h. Pharmacokinetic evaluations revealed that apparent serum concentrations of programmed antibodies were up to 144 nM and that the serum half-lives reached up to 34.4 h. These findings show promise for the future development of orally bioavailable drug-hapten-antibody complexes as a strategy to quickly and easily modulate immune targets for aggressive pathogens as well as cancer. (C) 2017 Elsevier Ltd. All rights reserved.
• Design, Synthesis, and Functional Activity of Labeled CD1d Glycolipid Agonists
  作者：Peter J. Jervis、Paolo Polzella、Justyna Wojno、John-Paul Jukes、Hemza Ghadbane、Yoel R. Garcia Diaz、Gurdyal S. Besra、Vincenzo Cerundolo、Liam R. Cox

  DOI：10.1021/bc300556e

  日期：2013.4.17

  Invariant natural killer T cells (iNKT cells) are restricted by CD1d molecules and activated upon CD1d-mediated presentation of glycolipids to T cell receptors (TCRs) located on the surface of the cell. Because the cytokine response profile is governed by the structure of the glycolipid, we sought a method for labeling various glycolipids to study their in vivo behavior. The prototypical CD1d agonist, alpha-galactosyl ceramide (alpha-GalCer) 1, instigates a powerful immune response and the generation of a wide range of cytokines when it is presented to iNKT cell TCRs by CD1d molecules. Analysis of crystal structures of the TCR-alpha-GalCer-CD1d ternary complex identified the alpha-methylene unit in the fatty acid side chain, and more specifically the pro-S hydrogen at this position, as a site for incorporating a label. We postulated that modifying the glycolipid in this way would exert a minimal impact on the TCR-glycolipid-CD1d ternary complex, allowing the labeled molecule to function as a good mimic for the CD1d agonist under investigation. To test this hypothesis, the synthesis of a biotinylated version of the CD1d agonist threitol ceramide (ThrCer) was targeted. Both diastereoisomers, epimeric at the label tethering site, were prepared, and functional experiments confirmed the importance of substituting the pro-S, and not the pro-R, hydrogen with the label for optimal activity. Significantly, functional experiments revealed that biotinylated ThrCer (S)-10 displayed behavior comparable to that of ThrCer 5 itself and also confirmed that the biotin residue is available for streptavidin and antibiotin antibody recognition. A second CD1d agonist, namely alpha-GalCer C20:2 4, was modified in a similar way, this time with a fluorescent label. The labeled alpha-GalCer C20:2 analogue (11) again displayed functional behavior comparable to that of its unlabeled substrate, supporting the notion that the alpha-methylene unit in the fatty acid amide chain should be a suitable site for attaching a label to a range of CD1d agonists. The flexibility of the synthetic strategy, and late-stage incorporation of the label, opens up the possibility of using this labeling approach to study the in vivo behavior of a wide range of CD1d agonists.