p-nitrophenyl 1-thio-β-D-lactoside | 27894-82-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: p-nitrophenyl 1-thio-β-D-lactoside
• 英文别名: (2S,3R,4S,5R,6R)-2-[(2R,3S,4R,5R,6S)-4,5-dihydroxy-2-(hydroxymethyl)-6-(4-nitrophenyl)sulfanyloxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol
• CAS: 27894-82-2
• 化学式: C₁₈H₂₅NO₁₂S
• 分子量: 479.462
• InChiKey: KFIHZCBTAOSIEH-XZILNXCWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  240
• 氢给体数：
  7
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  p-nitrophenyl 1-thio-β-D-lactoside 在 吡啶 、 N-氯代丁二酰亚胺 、 四丁基碘化铵 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 23.0h， 生成 (2S,3R,4S,5R,6R)-6-(acetoxymethyl)-5-(((2S,3R,4S,5S,6R)-3,5-diacetoxy-6-(acetoxymethyl)-4-((3-phenylisoxazol-5-yl)methoxy)tetrahydro-2H-pyran-2-yl)oxy)-2-((4-nitrophenyl)thio)tetrahydro-2H-pyran-3,4-diyl diacetate
  参考文献：
  名称：

  Synthesis and screening of a small glycomimetic library for inhibitory activity on medically relevant galactoside-specific lectins in assays of increasing biorelevance

  摘要：

  在碳水化合物配体中合成引入琼脂取代物，是鉴定医学相关凝集素强效抑制剂的一种方法。我们测试了 27 种半乳糖苷/乳糖苷衍生物，这些衍生物含有不同的琼脂酮分子和一些 O-3/O-3′ 功能，可与一种具有生物危害性的植物毒素和四种人类粘附/生长调节半凝集素结合。通过使用固相分析法进行系统评估，发现了凝集素结合的不同敏感性特征，以及相对于半乳糖/乳糖活性增加的情况。甚至还能检测到同源人类蛋白质之间的数量差异。研究表明，取代的乳糖与半乳糖-1 和半乳糖-3 的结合是由热驱动的。为了确定取代的苷类化合物保护细胞免受有害凝集素结合的潜力，进行了与人类肿瘤细胞的结合试验。与未取代的母糖相比，经鉴定的化合物总是具有更强的效力。不过，琼脂取代物被证明能够传递细胞毒性。本报告引导人们进一步关注研究半乳糖核心的其他 2′-和 3′-取代，以及配体在糖团中的呈递潜力，以提高亲和性和选择性，并继续使用本报告中应用的便捷生化测试系统与生物测定的战略结合。

  DOI：

  10.1039/c0nj00277a
• 作为产物：
  描述：

  2,2',3,3',4',6,6'-七-O-乙酰基-alpha-D-乳糖基溴化物 在 甲醇 、 sodium methylate 、 四丁基硫酸氢铵 、 sodium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 p-nitrophenyl 1-thio-β-D-lactoside
  参考文献：
  名称：

  Aryl O- and S-galactosides and lactosides as specific inhibitors of human galectins-1 and -3: Role of electrostatic potential at O-3

  摘要：

  Phase transfer catalyzed reaction was used for the high yielding synthesis of aryl 1-thio-beta-D-galacto- and lacto-pyranosides carrying a panel of substituents on the phenyl groups. Best galectin-1 inhibitors were simple p-nitrophenyl thiogalactoside 5a for the monosaccharide and o-nitrophenyl thiolactoside 6f or napthylsulfonyl lactoside 8c, both being 20 times better relative to natural ligands. Relative inhibitory properties as low as 2500 and 40 mu M were observed, respectively. The electronic effects of the lactoside aglycons directly influenced the electrostatic potential at O-3, which was associated with the inhibitory potencies against galectin-1. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.12.010

文献信息

• Synthesis of glycopolymers containing GM3-saccharide
  作者：Suoding Cao、René Roy

  DOI：10.1016/0040-4039(96)00584-9

  日期：1996.5

  GM3-trisaccharide [Neu5Acα-(2→3)-Galβ-(1→4)-Glcβ-(1→OR)] was synthesized using our “active-latent” thioglycosylation strategy. The trisaccharide was prepared with a p-acrylamidophenyl aglycon for copolymerization with acrylamide. The resulting water-soluble sialyl α-(2→3)-lactoside copolyacrylamide with different carbohydrate incorporation was shown to possess antigenic properties.

  使用我们的“活性潜伏”硫糖基化策略合成了GM 3-三糖[Neu5Acα-（2→3）-Galβ-（1→4）-Glcβ-（1→OR）]。用对-丙烯酰胺基苯基糖苷配基制备三糖以与丙烯酰胺共聚。所得到的具有不同碳水化合物掺入的水溶性唾液酸α-（2→3）-乳糖苷共聚丙烯酰胺具有抗原性。
• Aryl O- and S-galactosides and lactosides as specific inhibitors of human galectins-1 and -3: Role of electrostatic potential at O-3
  作者：Denis Giguère、Sachiko Sato、Christian St-Pierre、Suzanne Sirois、René Roy

  DOI：10.1016/j.bmcl.2005.12.010

  日期：2006.3

  Phase transfer catalyzed reaction was used for the high yielding synthesis of aryl 1-thio-beta-D-galacto- and lacto-pyranosides carrying a panel of substituents on the phenyl groups. Best galectin-1 inhibitors were simple p-nitrophenyl thiogalactoside 5a for the monosaccharide and o-nitrophenyl thiolactoside 6f or napthylsulfonyl lactoside 8c, both being 20 times better relative to natural ligands. Relative inhibitory properties as low as 2500 and 40 mu M were observed, respectively. The electronic effects of the lactoside aglycons directly influenced the electrostatic potential at O-3, which was associated with the inhibitory potencies against galectin-1. (C) 2006 Elsevier Ltd. All rights reserved.
• Synthesis and screening of a small glycomimetic library for inhibitory activity on medically relevant galactoside-specific lectins in assays of increasing biorelevance
  作者：Sabine André、Denis Giguère、Tarun K. Dam、Fred Brewer、Hans-Joachim Gabius、René Roy

  DOI：10.1039/c0nj00277a

  日期：——

  Synthetic introduction of aglyconic substitutions into carbohydrate ligands is an approach toward identifying potent inhibitors of medically relevant lectins. We tested a panel of 27 galactoside/lactoside derivatives harboring varying aglycone moieties together with some O-3/O-3′ functionality toward a biohazardous plant toxin and four human adhesion/growth-regulatory galectins. Differential sensitivity profiles of lectin binding with cases showing activity increase relative to galactose/lactose were revealed by systematic assessments using a solid-phase assay. Quantitative differences between the homologous human proteins could even be detected. Binding of substituted lactosides to galectins-1 and -3 was shown to be enthalpically driven. To determine the potential of substituted glycosides to protect cells from harmful lectin association, binding assays with human tumor cells were performed. Invariably, compounds were identified with increased potency relative to the unsubstituted parent sugars. However, aglyconic substitutions were shown to be able to convey cytotoxicity. This report directs further attention to examining additional 2′- and 3′-substitutions of the galactose core and the potential of ligand presentation in glycoclusters to enhance avidity and selectivity, continuing to use the herein applied strategic combination of a convenient biochemical test system with bioassays.

  在碳水化合物配体中合成引入琼脂取代物，是鉴定医学相关凝集素强效抑制剂的一种方法。我们测试了 27 种半乳糖苷/乳糖苷衍生物，这些衍生物含有不同的琼脂酮分子和一些 O-3/O-3′ 功能，可与一种具有生物危害性的植物毒素和四种人类粘附/生长调节半凝集素结合。通过使用固相分析法进行系统评估，发现了凝集素结合的不同敏感性特征，以及相对于半乳糖/乳糖活性增加的情况。甚至还能检测到同源人类蛋白质之间的数量差异。研究表明，取代的乳糖与半乳糖-1 和半乳糖-3 的结合是由热驱动的。为了确定取代的苷类化合物保护细胞免受有害凝集素结合的潜力，进行了与人类肿瘤细胞的结合试验。与未取代的母糖相比，经鉴定的化合物总是具有更强的效力。不过，琼脂取代物被证明能够传递细胞毒性。本报告引导人们进一步关注研究半乳糖核心的其他 2′-和 3′-取代，以及配体在糖团中的呈递潜力，以提高亲和性和选择性，并继续使用本报告中应用的便捷生化测试系统与生物测定的战略结合。