((4,5-dihydroxy-6-(2-(phosphonooxy)ethyl)pyridin-3-yl)methyl)phosphonic acid | 1361310-29-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ((4,5-dihydroxy-6-(2-(phosphonooxy)ethyl)pyridin-3-yl)methyl)phosphonic acid
• CAS: 1361310-29-3
• 化学式: C₈H₁₃NO₉P₂
• 分子量: 329.14
• InChiKey: XCTIFEUBNDYGAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.18
• 重原子数：
  20.0
• 可旋转键数：
  6.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  177.64
• 氢给体数：
  6.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  吡哆醛 在 咪唑 、 四氮唑 、 palladium on activated charcoal 、 四丁基氟化铵 、 氢气 、 双氧水 、 碘 、 间氯过氧苯甲酸 、 potassium hydroxide 、 sodium hydroxide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 ((4,5-dihydroxy-6-(2-(phosphonooxy)ethyl)pyridin-3-yl)methyl)phosphonic acid
  参考文献：
  名称：

  Rational design, synthesis and evaluation of first generation inhibitors of the Giardia lamblia fructose-1,6-biphosphate aldolase

  摘要：

  Inhibitors of the Giardia lamblia fructose 1,6-bisphosphate aldolase (GlFBPA), which transforms fructose 1,6-bisphosphate (FBP) to dihydroxyacetone phosphate and glyceraldehyde 3-phosphate, were designed based on 3-hydroxy-2-pyridone and 1,2-dihydroxypyridine scaffolds that position two negatively charged tetrahedral groups for interaction with substrate phosphate binding residues, a hydrogen bond donor to the catalytic Asp83, and a Zn2+ binding group. The inhibition activities for the GlFBPA catalyzed reaction of FBP of the prepared alkyl phosphonate/phosphate substituted 3-hydroxy-2-pyridinones and a dihydroxypyridine were determined. The 3-hydroxy-2-pyridone inhibitor 8 was found to bind to GlFBPA with an affinity (K-i = 14 mu M) that is comparable to that of FBP (K-m = 2 mu m) or its inert analog TBP (K-i = 1 mu M). The X-ray structure of the GlFBPA-inhibitor 8 complex (2.3 angstrom) shows that 8 binds to the active site in the manner predicted by in silico docking with the exception of coordination with Zn2+. The observed distances and orientation of the pyridone ring O=C-C-OH relative to Zn2+ are not consistent with a strong interaction. To determine if Zn2+ coordination occurs in the GIFBPA-inhibitor 8 complex in solution, EXAFS spectra were measured. A four coordinate geometry comprised of the three enzyme histidine ligands and an oxygen atom from the pyridone ring O=C-C-OH was indicated. Analysis of the Zn2+ coordination geometries in recently reported structures of class II FBPAs suggests that strong Zn2+ coordination is reserved for the enediolate-like transition state, accounting for minimal contribution of Zn2+ coordination to binding of 8 to GlFBPA. (C) 2010 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.jinorgbio.2010.12.012