2-benzyloxy-3-(methoxymethoxy)pyridine-4-carboxaldehyde | 1246560-71-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-benzyloxy-3-(methoxymethoxy)pyridine-4-carboxaldehyde
• 英文别名: 2-(Benzyloxy)-3-(methoxymethoxy)isonicotinaldehyde；3-(methoxymethoxy)-2-phenylmethoxypyridine-4-carbaldehyde
• CAS: 1246560-71-3
• 化学式: C₁₅H₁₅NO₄
• 分子量: 273.288
• InChiKey: YNDJJHVEXQEFNZ-UHFFFAOYSA-N

物化性质

• 熔点：
  <25 °C
• 沸点：
  424.2±45.0 °C(Predicted)
• 密度：
  1.209±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.46
• 重原子数：
  20.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  57.65
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2-benzyloxy-3-(methoxymethoxy)pyridine-4-carboxaldehyde 在 sodium tetrahydroborate 作用下， 以94%的产率得到(2-(benzyloxy)-3-(methoxymethoxy)pyridin-4-yl)methanol
  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
• 作为产物：
  描述：

  苯甲醇 在 正丁基锂 、 sodium hydride 作用下， 以 乙醚 为溶剂， 生成 2-benzyloxy-3-(methoxymethoxy)pyridine-4-carboxaldehyde
  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

文献信息

• Connection of Metallamacrocycles via Dynamic Covalent Chemistry: A Versatile Method for the Synthesis of Molecular Cages
  作者：Anton Granzhan、Clément Schouwey、Thomas Riis-Johannessen、Rosario Scopelliti、Kay Severin

  DOI：10.1021/ja200580x

  日期：2011.5.11

  A modular approach for the synthesis of cage structures is described. Reactions of [(arene)RuCl(2)](2) [arene = p-cymene, 1,3,5-C(6)H(3)Me(3), 1,3,5-C(6)H(3)(i-Pr)(3)] with formyl-substituted 3-hydroxy-2-pyridone ligands provide trinuclear metallamacrocycles with pendant aldehyde groups. Subsequent condensation reactions with di- and triamines give molecular cages with 3, 6, or 12 Ru centers in a diastereoselective

  描述了一种用于合成笼结构的模块化方法。[(芳烃)RuCl(2)](2) [芳烃 = 对伞花烃, 1,3,5-C(6)H(3)Me(3), 1,3,5-C(6) 的反应H(3)(i-Pr)(3)] 与甲酰基取代的 3-羟基-2-吡啶酮配体提供带有醛基侧基的三核金属大环。随后与二胺和三胺的缩合反应以非对映选择性和化学选择性（自分类）方式产生具有 3、6 或 12 个 Ru 中心的分子笼。一些笼子也可以在一锅反应中制备，方法是在碱存在下将 [(芳烃)RuCl(2)](2) 与吡啶酮配体和胺混合。通过X射线晶体学对笼进行综合分析。最大的十二核复合体的直径为~3 nm；腔尺寸范围从 290 到 740 Å(3)。
• Combining Metallasupramolecular Chemistry with Dynamic Covalent Chemistry: Synthesis of Large Molecular Cages
  作者：Anton Granzhan、Thomas Riis-Johannessen、Rosario Scopelliti、Kay Severin

  DOI：10.1002/anie.201002748

  日期：——

  Ru‐built cube: By combining metallasupramolecular chemistry with dynamic covalent chemistry, complex nanostructures can be formed. Large cages are synthesized by reaction of trinuclear metallamacrocycles containing pendant aldehyde groups (see picture; Ru blue, aldehyde linkers green) with triamines (red).

  Ru-built立方：通过将金属超分子化学与动态共价化学结合起来，可以形成复杂的纳米结构。大型笼子是通过含有侧基醛基的三核金属环（见图片； Ru蓝色，醛接头绿色）与三胺（红色）反应合成的。
• An Imine-Based Molecular Cage with Distinct Binding Sites for Small and Large Alkali Metal Cations
  作者：Clément Schouwey、Rosario Scopelliti、Kay Severin

  DOI：10.1002/chem.201300098

  日期：2013.5.10

  The synthesis of a cylindrical, imine‐based cage composed of two trimeric metallamacrocycles is described. The cage acts as a heterotopic receptor for alkali metal cations. The small cations Li+, Na+, and K+ bind to the outside of the cage with good selectivity for Li+, whereas the larger cations Rb+ and Cs+ are bound inside the cage to form unusual π complexes with a good selectivity for Cs+. Negative

  描述了由两个三聚金属lamcrocrocycles组成的圆柱形，基于亚胺的笼子的合成。笼子充当碱金属阳离子的异位受体。小阳离子Li +，Na +和K +以对Li +的良好选择性结合到笼子的外部，而较大的阳离子Rb +和Cs +则以笼罩在笼子内部的方式形成非寻常的π络合物，具有对Li +的良好选择性。 Cs +。观察到两个结合位点之间的异位协同作用。Cs +的复杂化与颜色变化相关，这使笼子可用作Cs +的特定传感器。