trehalose-6-sulfate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: trehalose-6-sulfate
• 英文别名: alpha-D-Glucopyranosyl 6-O-sulfo-alpha-D-glucopyranoside；[(2R,3S,4S,5R,6R)-3,4,5-trihydroxy-6-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]methyl hydrogen sulfate
• 化学式: C₁₂H₂₂O₁₄S
• 分子量: 422.364
• InChiKey: AJWOGPXMZBTABG-LIZSDCNHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.1
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  241
• 氢给体数：
  8
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  2,2',3,3',4,4',6-hepta-O-benzyl-α-D-trehalose 在 吡啶 、 10 wt% Pd(OH)2 on carbon 、 三氧化硫吡啶 作用下， 以 甲醇 、 水 为溶剂， 生成 trehalose-6-sulfate
  参考文献：
  名称：

  Rational design of first generation inhibitors for trehalose 6-phosphate phosphatases

  摘要：

  In this study, trehalose 6-phosphate phosphatase (T6PP) was targeted for inhibitor development. T6PP catalyzes the hydrolysis of trehalose-6-phosphate to form trehalose and inorganic phosphate, a reaction essential to important fungal, bacterial, and nematodal pathogens. At the current time, there are no specific inhibitors of T6PP available to serve as tools for interrogating its structure and function nor as leads for pharmaceutical applications. Herein, we describe the synthesis of non-hydrolysable mimics of trehalose-6-phosphate, which incorporate 6-sulfate (1),-phosphonate (2),-fluorophosphonate (3) and boronate (4) groups in place of the 6-phosphate moiety of the substrate. The inhibitory efficacies of these adducts were evaluated against trehalose 6-phosphatephosphatases selected from evolutionarily distant pathogenic bacteria and nematodes. Phosphonates 2 and 3 were found to display good inhibitory activities against the T6PPs, while the sulfate analog, trehalose-6-sulfate, proved to be a particularly effective broad-spectrum inhibitor of these phosphatases and an ideal prototype for optimization. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2017.01.041

文献信息

• Rational design of first generation inhibitors for trehalose 6-phosphate phosphatases
  作者：Chunliang Liu、Debra Dunaway-Mariano、Patrick S. Mariano

  DOI：10.1016/j.tet.2017.01.041

  日期：2017.3

  In this study, trehalose 6-phosphate phosphatase (T6PP) was targeted for inhibitor development. T6PP catalyzes the hydrolysis of trehalose-6-phosphate to form trehalose and inorganic phosphate, a reaction essential to important fungal, bacterial, and nematodal pathogens. At the current time, there are no specific inhibitors of T6PP available to serve as tools for interrogating its structure and function nor as leads for pharmaceutical applications. Herein, we describe the synthesis of non-hydrolysable mimics of trehalose-6-phosphate, which incorporate 6-sulfate (1),-phosphonate (2),-fluorophosphonate (3) and boronate (4) groups in place of the 6-phosphate moiety of the substrate. The inhibitory efficacies of these adducts were evaluated against trehalose 6-phosphatephosphatases selected from evolutionarily distant pathogenic bacteria and nematodes. Phosphonates 2 and 3 were found to display good inhibitory activities against the T6PPs, while the sulfate analog, trehalose-6-sulfate, proved to be a particularly effective broad-spectrum inhibitor of these phosphatases and an ideal prototype for optimization. (C) 2017 Elsevier Ltd. All rights reserved.