Acetic acid (1R,2R)-2-acetoxy-2-benzyloxycarbamoyl-1-(bis-benzyloxy-phosphoryloxymethyl)-ethyl ester | 717920-99-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Acetic acid (1R,2R)-2-acetoxy-2-benzyloxycarbamoyl-1-(bis-benzyloxy-phosphoryloxymethyl)-ethyl ester
• 英文别名: [(2R,3R)-3-acetyloxy-1-bis(phenylmethoxy)phosphoryloxy-4-oxo-4-(phenylmethoxyamino)butan-2-yl] acetate
• CAS: 717920-99-5
• 化学式: C₂₉H₃₂NO₁₀P
• 分子量: 585.548
• InChiKey: MXFCPVGCMIYRFV-VSGBNLITSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  41
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  136
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  Acetic acid (1R,2R)-2-acetoxy-2-benzyloxycarbamoyl-1-(bis-benzyloxy-phosphoryloxymethyl)-ethyl ester 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 2.5h， 以88%的产率得到Acetic acid (1R,2R)-2-acetoxy-1-hydroxycarbamoyl-3-phosphonooxy-propyl ester
  参考文献：
  名称：

  Selective Inhibition of Trypanosoma brucei 6-Phosphogluconate Dehydrogenase by High-Energy Intermediate and Transition-State Analogues

  摘要：

  Two series of compounds were designed to mimic the transition state and high-energy intermediates (HEI) of the enzymatic reaction of 6-phosphogluconate dehydrogenase (6PGDH). Sulfoxide analogues (7-11) were designed to mimic the transition state during the oxidation of the substrate to 3-keto-6-phosphogluconate, an enzyme-bound intermediate of the enzyme. Hydroxamate and amide derivatives Of D-erythronic acid were designed to mimic the 1,2-cis-enediol HEI of the 6PGDH reaction. These two series of compounds were assayed as competitive inhibitors of the Trypanosoma brucei and sheep liver enzymes, and their selectivity value (ratio sheep/parasite) was calculated. The sulfoxide transition-state analogues showed weak and selective inhibition of the T. brucei enzyme. The hydroxamic derivatives showed potent and selective inhibition of the T brucei 6PGDH with a K-i in the nanomolar range.

  DOI：

  10.1021/jm031066i
• 作为产物：
  描述：

  (4R,5R)-5-(hydroxymethyl)-2,2-dimethyl-N-(phenylmethoxy)-1,3-dioxolane-4-carboxamide 在 吡啶 、 4-二甲氨基吡啶 、 Dowex 50wx8-200 resin 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 49.5h， 生成 Acetic acid (1R,2R)-2-acetoxy-2-benzyloxycarbamoyl-1-(bis-benzyloxy-phosphoryloxymethyl)-ethyl ester
  参考文献：
  名称：

  Selective Inhibition of Trypanosoma brucei 6-Phosphogluconate Dehydrogenase by High-Energy Intermediate and Transition-State Analogues

  摘要：

  Two series of compounds were designed to mimic the transition state and high-energy intermediates (HEI) of the enzymatic reaction of 6-phosphogluconate dehydrogenase (6PGDH). Sulfoxide analogues (7-11) were designed to mimic the transition state during the oxidation of the substrate to 3-keto-6-phosphogluconate, an enzyme-bound intermediate of the enzyme. Hydroxamate and amide derivatives Of D-erythronic acid were designed to mimic the 1,2-cis-enediol HEI of the 6PGDH reaction. These two series of compounds were assayed as competitive inhibitors of the Trypanosoma brucei and sheep liver enzymes, and their selectivity value (ratio sheep/parasite) was calculated. The sulfoxide transition-state analogues showed weak and selective inhibition of the T. brucei enzyme. The hydroxamic derivatives showed potent and selective inhibition of the T brucei 6PGDH with a K-i in the nanomolar range.

  DOI：

  10.1021/jm031066i

文献信息

• Selective Inhibition of <i>Trypanosoma brucei</i> 6-Phosphogluconate Dehydrogenase by High-Energy Intermediate and Transition-State Analogues
  作者：Christophe Dardonville、Eliana Rinaldi、Michael P. Barrett、Reto Brun、Ian H. Gilbert、Stefania Hanau

  DOI：10.1021/jm031066i

  日期：2004.6.1

  Two series of compounds were designed to mimic the transition state and high-energy intermediates (HEI) of the enzymatic reaction of 6-phosphogluconate dehydrogenase (6PGDH). Sulfoxide analogues (7-11) were designed to mimic the transition state during the oxidation of the substrate to 3-keto-6-phosphogluconate, an enzyme-bound intermediate of the enzyme. Hydroxamate and amide derivatives Of D-erythronic acid were designed to mimic the 1,2-cis-enediol HEI of the 6PGDH reaction. These two series of compounds were assayed as competitive inhibitors of the Trypanosoma brucei and sheep liver enzymes, and their selectivity value (ratio sheep/parasite) was calculated. The sulfoxide transition-state analogues showed weak and selective inhibition of the T. brucei enzyme. The hydroxamic derivatives showed potent and selective inhibition of the T brucei 6PGDH with a K-i in the nanomolar range.