(4R,5R)-5-(hydroxymethyl)-2,2-dimethyl-N-(phenylmethoxy)-1,3-dioxolane-4-carboxamide | 717920-96-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (4R,5R)-5-(hydroxymethyl)-2,2-dimethyl-N-(phenylmethoxy)-1,3-dioxolane-4-carboxamide
• 英文别名: (4R,5R)-5-(hydroxymethyl)-2,2-dimethyl-N-phenylmethoxy-1,3-dioxolane-4-carboxamide
• CAS: 717920-96-2
• 化学式: C₁₄H₁₉NO₅
• 分子量: 281.309
• InChiKey: XRQTZHXBTJFUNY-VXGBXAGGSA-N

物化性质

• 熔点：
  111-112 °C
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  77
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4R,5R)-5-(hydroxymethyl)-2,2-dimethyl-N-(phenylmethoxy)-1,3-dioxolane-4-carboxamide 在 四氮唑 、 叔丁基过氧化氢 作用下， 以 水 、 乙腈 为溶剂， 反应 4.5h， 生成 Phosphoric acid dibenzyl ester (4R,5R)-5-benzyloxycarbamoyl-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester
  参考文献：
  名称：

  乙二醇模拟作为杜氏弗朗西斯菌的d-阿拉伯糖5-磷酸异构酶（KdsD）的抑制剂

  摘要：

  我们探索了来自弗朗西斯菌tularensis的d-阿拉伯糖5-磷酸异构酶（KdsD，EC 5.3.1.13），它是一种高度感染性的革兰氏阴性病原体，已引起人们的关注，将其作为潜在的生物武器，作为开发新型化学疗法的目标。从合成基因在大肠杆菌中表达土拉弗雷特氏菌KdsD，对其进行纯化和鉴定。制备了一组拟模拟酶催化机理中假定的烯二醇中间体的异羟肟酸酯，并测试了它们是否为图拉菌（F. tularensis） KdsD的抑制剂。IC 50为7μM的最佳抑制剂是迄今为止报道的最有效的KdsD抑制剂。

  DOI：

  10.1016/j.bmcl.2010.12.066
• 作为产物：
  描述：

  D-erythronolactone acetonide 、 苄氧基胺盐酸盐 在 sodium methylate 、 三甲基铝 作用下， 以 甲醇 、 二氯甲烷 、 正己烷 为溶剂， 反应 3.0h， 以56%的产率得到(4R,5R)-5-(hydroxymethyl)-2,2-dimethyl-N-(phenylmethoxy)-1,3-dioxolane-4-carboxamide
  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.
• Enediol mimics as inhibitors of the d-arabinose 5-phosphate isomerase (KdsD) from Francisella tularensis
  作者：Alejandra Yep、Roderick J. Sorenson、Michael R. Wilson、H.D. Hollis Showalter、Scott D. Larsen、Paul R. Keller、Ronald W. Woodard

  DOI：10.1016/j.bmcl.2010.12.066

  日期：2011.5

  development of novel chemotherapeutics. F. tularensis KdsD was expressed in Escherichia coli from a synthetic gene, purified, and characterized. A group of hydroxamates designed to be mimics of the putative enediol intermediate in the enzyme’s catalytic mechanism were prepared and tested as inhibitors of F. tularensis KdsD. The best inhibitor, which has an IC50 of 7 μM, is the most potent KdsD inhibitor reported

  我们探索了来自弗朗西斯菌tularensis的d-阿拉伯糖5-磷酸异构酶（KdsD，EC 5.3.1.13），它是一种高度感染性的革兰氏阴性病原体，已引起人们的关注，将其作为潜在的生物武器，作为开发新型化学疗法的目标。从合成基因在大肠杆菌中表达土拉弗雷特氏菌KdsD，对其进行纯化和鉴定。制备了一组拟模拟酶催化机理中假定的烯二醇中间体的异羟肟酸酯，并测试了它们是否为图拉菌（F. tularensis） KdsD的抑制剂。IC 50为7μM的最佳抑制剂是迄今为止报道的最有效的KdsD抑制剂。