2,3,4-tri-O-acetyl-L-fucopyranosyl trichloroacetimidate | 197505-11-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,3,4-tri-O-acetyl-L-fucopyranosyl trichloroacetimidate
• 英文别名: [(2S,3R,4R,5S)-4,5-diacetyloxy-2-methyl-6-(2,2,2-trichloroethanimidoyl)oxyoxan-3-yl] acetate
• CAS: 197505-11-6
• 化学式: C₁₄H₁₈Cl₃NO₈
• 分子量: 434.658
• InChiKey: CBEDSVQSHODOKN-PFFKSSDRSA-N

物化性质

• 沸点：
  404.0±55.0 °C(Predicted)
• 密度：
  1.55±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2,3,4-tri-O-acetyl-L-fucopyranosyl trichloroacetimidate 在 三丁基膦 、 三氟化硼乙醚 、 sodium methylate 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 17.67h， 生成
  参考文献：
  名称：

  Development of Fluorogenic Substrates of α-l-Fucosidase Useful for Inhibitor Screening and Gene-expression Profiling

  摘要：

  Inhibitors of human alpha-L-fucosidases, tissue alpha-L-fucosidase (tFuc), and plasma alpha-L-fucosidase reportedly play roles in multiple diseases, suggesting their therapeutic potential for gastric disease associated with Helicobacter pylori and fucosidosis. Terminal fucose linkages on glycoproteins and glycolipids are a natural substrate for both enzymes; however, there are currently no fluorogenic substrates allowing their cellular evaluation. Here, we described the development of novel three-color fluorogenic substrates for lysosome-localized tFuc that exhibited excellent specificity and sensitivity in three human cell lines. Additionally, we developed a cell-based high throughput inhibitor screening system in a 96-well format and a cell-based inhibitory activity evaluation system in a 6-well format for tFuc inhibitors using this substrate, which allowed accurate quantification of the inhibition rate. Moreover, analysis of significant changes in gene expression resulting from 30% inhibition of tFuc in HeLa cells revealed potential roles in gastric disease.

  DOI：

  10.1021/acsmedchemlett.9b00259
• 作为产物：
  描述：

  6-deoxy-L-galactose 在 吡啶 、 碳酸氢铵 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 水 为溶剂， 反应 192.5h， 生成 2,3,4-tri-O-acetyl-L-fucopyranosyl trichloroacetimidate
  参考文献：
  名称：

  Development of Fluorogenic Substrates of α-l-Fucosidase Useful for Inhibitor Screening and Gene-expression Profiling

  摘要：

  Inhibitors of human alpha-L-fucosidases, tissue alpha-L-fucosidase (tFuc), and plasma alpha-L-fucosidase reportedly play roles in multiple diseases, suggesting their therapeutic potential for gastric disease associated with Helicobacter pylori and fucosidosis. Terminal fucose linkages on glycoproteins and glycolipids are a natural substrate for both enzymes; however, there are currently no fluorogenic substrates allowing their cellular evaluation. Here, we described the development of novel three-color fluorogenic substrates for lysosome-localized tFuc that exhibited excellent specificity and sensitivity in three human cell lines. Additionally, we developed a cell-based high throughput inhibitor screening system in a 96-well format and a cell-based inhibitory activity evaluation system in a 6-well format for tFuc inhibitors using this substrate, which allowed accurate quantification of the inhibition rate. Moreover, analysis of significant changes in gene expression resulting from 30% inhibition of tFuc in HeLa cells revealed potential roles in gastric disease.

  DOI：

  10.1021/acsmedchemlett.9b00259

文献信息

• Synthesis and evaluation of the bioactivity of simplified analogs of the seco-pseudopterosins; progress toward determining a pharmacophore
  作者：Virginia M. Tanis、Claudia Moya、R.S. Jacobs、R. Daniel Little

  DOI：10.1016/j.tet.2008.09.025

  日期：2008.11

  synthetic approach based upon the use of well-established reactions, which enabled us to develop routes that proved to be efficient, practical, and easy to implement. The results of several bioassays, including an assessment of the ability to inhibit phagocytosis and to competitively bind to the adenosine receptor A2A, demonstrate that greatly simplified structural analogs of the pseudopterosins and their

  拟蝶呤是一种海洋天然产物，具有显着的抗炎和伤口愈合特性。我们描述了seco-pseudopterosin样核心的六个结构类似物的合成，除了在天然产物的碳环核心中发现的立体中心之一外，其他所有结构都缺乏。选择我们的靶标是为了尝试鉴定拟蝶呤及其山梨类似物的最小药效团。在建立良好的反应的基础上，我们努力利用保守的合成方法，这使我们能够开发出被证明是有效，实用且易于实施的途径。几种生物测定的结果，包括评估抑制吞噬作用和竞争性结合腺苷受体A 2A的能力证明了拟蝶呤和它们的山高形式的大大简化的结构类似物能够维持几种表征天然产物的重要生物活性，并且具有相当的功效。那些带有两个而不是一个直接连接在芳环上的氧原子的体系是更有效的结合剂。该观察结果可提供有关最小药效团的关键结构特征的重要线索。
• Synthesis of the Shimofuridin Nucleoside Disaccharide
  作者：Spencer Knapp、Vijay K. Gore

  DOI：10.1021/jo960727z

  日期：1996.1.1
• Brønsted Acid-Promoted Glycosylations of Disaccharide Glycal Substructures of the Saccharomicins
  作者：Bradley R. Balthaser、Frank E. McDonald

  DOI：10.1021/ol901923x

  日期：2009.11.5

  An acid-promoted glycosylation and alkynol cycloisomerization sequence provided direct access to the 2-deoxytrisaccharide corresponding to the fucose-saccharosamine-digitoxose substructure of saccharomicin B. In the course of this work, the absolute stereochemistry of the repeating fucose-saccharosamine disaccharide of saccharomicins was also confirmed.
• Synthesis of the Saccharomicin Fucose−Aglycon Conjugate and Determination of Absolute Configuration
  作者：Joseph M. Pletcher、Frank E. McDonald

  DOI：10.1021/ol051971s

  日期：2005.10.1

  Schmidt glycosylation of the appropriately protected 3,4-dihydroxycinnamate methyl ester with 2,3,4-triacetoxyfucopyranosyltrichloroacetimidate gives aryl glycoside in high yield and diastereoselectivity. 2-Sulfation of fucose, installation of taurine, and global deprotection of the remaining protecting groups affords the fucose-aglycon conjugate of saccharomicin. This synthesis which arises from L-fucose also establishes the absolute configuration of the reducing terminus of the saccharomicin oligosaccharide.
• Preparation and characterization of 6I,6n-di-O-(l-fucopyranosyl)-β-cyclodextrin (n=II–IV) and investigation of their functions
  作者：Yuki Nishi、Naoe Yamane、Toshiko Tanimoto

  DOI：10.1016/j.carres.2007.06.016

  日期：2007.11

  Three positional isomers of 6(I),6(n)-di-O-(beta-L-fucopyranosyl)-cyclomaltoheptaose [61,6(n)-di-O-(beta-L-Fuc)-beta-cyclodextrin, -beta CD, n = II-IV] were chemically synthesized using the corresponding authentic compounds, 6(I),6(n)-di-O-(tert-butyidimethylsilyl)-beta CD (n = II-IV), as the fucosyl acceptors, and 2,3,4-tri-O-acetyl-L-fucopyranosyl trichloroacetimidate as the fucosyl donor. Their structures were analyzed by HPLC, MS, and NMR spectroscopy. The hemolytic activities of L-Fuc-beta CDs were lower than that of beta CD, while the solubilities of these branched CDs in water were much higher than that of beta CD. The molecular interaction between these compounds and the fucose-binding lectin Aleuria aurantia lectin (AAL) was investigated using an optical biosensor based on a surface plasmon resonance (SPR) technique. The order of binding affinity, as a function of the fucose-binding position, was 6(I),6(IV)- 6(I),6(III)- > 6(I),6(II)-di-O-(beta-L-Fuc)-beta CD > 6-O-(beta-L-Fuc)-beta CD. (C) 2007 Elsevier Ltd. All rights reserved.