4-aminophenyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D-galactopyranoside

• 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: 4-aminophenyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D-galactopyranoside
• 英文别名: [(2R,3S,4S,5R,6S)-3,4,5-triacetyloxy-6-(4-aminophenyl)sulfanyloxan-2-yl]methyl acetate
• 化学式: C₂₀H₂₅NO₉S
• 分子量: 455.486
• InChiKey: KLSFMEJLNVDFAT-CXQPBAHBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  166
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  4-aminophenyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D-galactopyranoside 在 sodium azide 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 p-(δ-azidovalerylamido)phenyl 2,3,4,6-tetra-O-acetyl-β-D-thiogalactopyranoside
  参考文献：
  名称：

  Directing Drugs to Bugs: Antibiotic-Carbohydrate Conjugates Targeting Biofilm-Associated Lectins of Pseudomonas aeruginosa

  摘要：

  Chronic infections by Pseudomonas aeruginosa are characterized by biofilm formation, which effectively enhances resistance toward antibiotics. Biofilm-specific antibiotic delivery could locally increase drug concentration to break antimicrobial resistance and reduce the drug's peripheral side effects. Two extracellular P. aeruginosa lectins, LecA and LecB, are essential structural components for biofilm formation and thus render a possible anchor for biofilm-targeted drug delivery. The standard-of-care drug ciprofloxacin suffers from severe systemic side effects and was therefore chosen for this approach. We synthesized several ciprofloxacin-carbohydrate conjugates and established a structure-activity relationship. Conjugation of ciprofloxacin to lectin probes enabled biofilm accumulation in vitro, reduced the antibiotic's cytotoxicity, but also reduced its antibiotic activity against planktonic cells due to a reduced cell permeability and on target activity. This work defines the starting point for new biofilm/lectin-targeted drugs to modulate antibiotic properties and ultimately break antimicrobial resistance.

  DOI：

  10.1021/acs.jmedchem.0c00856
• 作为产物：
  描述：

  beta-D-半乳糖五乙酸酯 在 sodium metabisulfite 、 tin(II) chloride dihdyrate 、 水 、 氢溴酸 、 溶剂黄146 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 丙酮 、 乙腈 为溶剂， 反应 22.0h， 生成 4-aminophenyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D-galactopyranoside
  参考文献：
  名称：

  β-半乳糖苷酶光开关抑制剂的开发

  摘要：

  偶氮苯作为生物应用的光致变色支架尤为受关注，因为它们具有较高的抗疲劳性，在扩展的（反式）和弯曲的（顺式）异构体之间存在较大的几何变化，并且具有多种合成途径。尽管已广泛使用它们，但尚无报道对酶β-半乳糖苷酶的光致变色抑制剂进行研究，该酶在生物化学和单分子研究中起着重要作用。在这里，我们报告基于2-苯基乙基β- D-硫代半乳糖苷（PETG）和1-氨基-1-脱氧-β - D-半乳糖（β- D）的分子结构合成光致变色竞争性β-半乳糖苷酶抑制剂-半乳糖胺）。具有高度热稳定性的基于PETG的偶氮苯在极性溶剂中显示出出色的光致变色特性，并具有中等至高的光平稳态（PSS）。优化的化合物37是来自大肠杆菌的强竞争性β-半乳糖苷酶的抑制剂，并且在光照射下其抑制常数（K i）在60nM至290nM之间变化。额外的对接实验支持观察到的结构-活性关系。

  DOI：

  10.1039/c8ob02122h

文献信息

• Novel Uridine Glycoconjugates, Derivatives of 4-Aminophenyl 1-Thioglycosides, as Potential Antiviral Compounds
  作者：Ewelina Krol、Gabriela Pastuch-Gawolek、Binay Chaubey、Gabriela Brzuska、Karol Erfurt、Boguslaw Szewczyk

  DOI：10.3390/molecules23061435

  日期：——

  series of uridine glycoconjugates, derivatives of 4-aminophenyl 1-thioglycosides, was designed and synthesized. All compounds were evaluated in vitro for their antiviral activity against hepatitis C virus (HCV) and classical swine fever virus (CSFV), two important human and animal viral pathogens for which new or improved therapeutic options are needed. The antiviral activity of all synthesized compounds

  设计并合成了一系列新颖的尿苷糖缀合物，即4-氨基苯基1-硫代糖苷的衍生物。体外评估了所有化合物对丙型肝炎病毒（HCV）和经典猪瘟病毒（CSFV）的抗病毒活性，丙型肝炎病毒是两种重要的人和动物病毒病原体，需要新的或改良的治疗方法。使用假斑减少测定法证实了所有合成化合物的抗病毒活性，其中在这些化合物的存在下观察到了CSFV和HCV生长的明显停滞。两种合成的化合物9和12对HCV和CSFV传播表现出显着的抑制作用，HCV的IC50值分别为4.9和13.5 µM，CSFV的IC50值分别为4.2和4 µM，具有低细胞毒性。使用各种感染和复制模型，我们已经表明，这两种化合物均能够在低微摩尔范围内将IC50值显着降低高达90％的病毒基因组复制。合成化合物的结构活性分析表明，高抗病毒活性归因于糖缀合物的疏水性以及将能够协调金属离子的元素引入连接糖和尿苷部分的间隔基，这可用于开发新的未来的抗病毒化合物。
• [EN] GLYCOCLUSTERS AND THEIR PHARMACEUTICAL USE AS ANTIBACTERIALS<br/>[FR] GLYCOCLUSTERS ET LEUR UTILISATION PHARMACEUTIQUE COMME ANTIBACTÉRIENS
  申请人：CENTRE NAT RECH SCIENT

  公开号：WO2015040209A1

  公开（公告）日：2015-03-26

  A molecule responding to formula (I)of the glycocluster type with galactose residues at their extremities. Simple and efficient methods for the preparation of these compounds. Medical use of compounds (I) as inhibitors of infections by Pseudomonas aeruginosa, more specifically as inhibitors of Pseudomonas aeruginosa's virulence.

  一种分子对具有半乳糖残基的糖团型式（I）做出响应。这些化合物的制备有简单高效的方法。将化合物（I）用作铜绿假单胞菌感染的抑制剂，更具体地说是铜绿假单胞菌毒力的抑制剂。
• Development of photoswitchable inhibitors for β-galactosidase
  作者：Karin Rustler、Matthias J. Mickert、Julian Nazet、Rainer Merkl、Hans H. Gorris、Burkhard König

  DOI：10.1039/c8ob02122h

  日期：——

  biochemistry and single molecule studies. Herein, we report the synthesis of photochromic competitive β-galactosidase inhibitors based on the molecular structure of 2-phenylethyl β-D-thiogalactoside (PETG) and 1-amino-1-deoxy-β-D-galactose (β-D-galactosylamine). The thermally highly stable PETG-based azobenzenes show excellent photochromic properties in polar solvents and moderate to high photostationary states

  偶氮苯作为生物应用的光致变色支架尤为受关注，因为它们具有较高的抗疲劳性，在扩展的（反式）和弯曲的（顺式）异构体之间存在较大的几何变化，并且具有多种合成途径。尽管已广泛使用它们，但尚无报道对酶β-半乳糖苷酶的光致变色抑制剂进行研究，该酶在生物化学和单分子研究中起着重要作用。在这里，我们报告基于2-苯基乙基β- D-硫代半乳糖苷（PETG）和1-氨基-1-脱氧-β - D-半乳糖（β- D）的分子结构合成光致变色竞争性β-半乳糖苷酶抑制剂-半乳糖胺）。具有高度热稳定性的基于PETG的偶氮苯在极性溶剂中显示出出色的光致变色特性，并具有中等至高的光平稳态（PSS）。优化的化合物37是来自大肠杆菌的强竞争性β-半乳糖苷酶的抑制剂，并且在光照射下其抑制常数（K i）在60nM至290nM之间变化。额外的对接实验支持观察到的结构-活性关系。
• Copper(I)-Catalyzed Sandmeyer-Type <i>S</i>-Arylation of 1-Thiosugars with Aryldiazonium Salts under Mild Conditions
  作者：Rapelly Venkatesh、Varsha Tiwari、Jeyakumar Kandasamy

  DOI：10.1021/acs.joc.2c00930

  日期：2022.9.2

  Preparation of S-aryl thioglycosides from 1-thiosugars via S-arylation was demonstrated under mild reaction conditions. A wide range of protected and unprotected 1-thiosugars derived from glucose, glucosamine, galactose, mannose, ribose, maltose, and lactose underwent cross-coupling reactions with functionalized aryldiazonium salts in the presence of copper(I) chloride and DBU. The desired products

  在温和的反应条件下证明了通过S-芳基化从 1-硫糖制备S-芳基硫糖苷。在氯化铜 (I) 和 DBU 存在下，衍生自葡萄糖、氨基葡萄糖、半乳糖、甘露糖、核糖、麦芽糖和乳糖的多种受保护和未受保护的 1-硫糖与官能化芳基重氮盐发生交叉偶联反应。在 5 分钟内以 55-88% 的收率获得所需的产品。在标准反应条件下可以耐受各种官能团，包括卤素。证明了生物学相关的抗糖尿病药 dapagliflozin S -类似物和熊果苷S -类似物（酪氨酸酶抑制剂）的合成。
• Small molecule glycoconjugates with anticancer activity
  作者：Gabriela Pastuch-Gawołek、Katarzyna Malarz、Anna Mrozek-Wilczkiewicz、Marta Musioł、Maciej Serda、Barbara Czaplinska、Robert Musiol

  DOI：10.1016/j.ejmech.2016.01.061

  日期：2016.4

  Glycoconjugates are combinations of sugar moieties with organic compounds. Due to their biological resemblance, such structures often have properties that are desirable for drugs. In this study we designed and synthesised several glycoconjugates from small molecular quinolines and substituted gluco- and galactopyranosyl amines. Although the parent quinoline compounds were inactive in affordable concentrations, the glycoconjugates that were obtained appeared to be cytotoxic against cancer cells at the micromolar level. When combined with copper ions, their activity increased even further. Their mechanism of action is connected to the formation of reactive oxygen species and the intercalation of DNA. (C) 2016 Elsevier Masson SAS. All rights reserved.