1-[(3aR,4R,6R,6aR)-6-[[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxymethyl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]pyrimidine-2,4-dione | 215183-75-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[(3aR,4R,6R,6aR)-6-[[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxymethyl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]pyrimidine-2,4-dione
• CAS: 215183-75-8
• 化学式: C₁₇H₂₄N₂O₁₀
• 分子量: 416.385
• InChiKey: RLEBFPFKBYZLNN-OUQNRHAVSA-N

物化性质

• 密度：
  1.58±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  156
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1-[(3aR,4R,6R,6aR)-6-[[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxymethyl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]pyrimidine-2,4-dione 在 sodium azide 、 水 、 对甲苯磺酸 、 三乙胺 、 三苯基膦 、 丙酮 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 1-[(3aR,4R,6R,6aR)-6-[[(3aR,4R,6R,6aR)-6-(aminomethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]oxymethyl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]pyrimidine-2,4-dione
  参考文献：
  名称：

  Synthesis of the Nucleoside Moiety of Liposidomycins: Elucidation of the Pharmacophore of this Family of MraY Inhibitors

  摘要：

  Tunicamycins (TCMs) and liposidomycins (LPMs) are naturally occurring inhibitors of the bacterial translocase (MraY). Based on structure-activity relationship (SAR) studies, a molecular model has been proposed for their inhibitory mechanism. This study points out the importance of the nucleoside moiety of liposidomycins in the inhibition of MraY. A simplified molecule (I) based on the liposidomycin core structure has been synthesised and tested on MraY. The compound displayed a moderate inhibitory activity (IC50-50 mu M). The validation of the molecular model was then performed by synthesising higher homologues of I, containing an additional stereocentre in the 5' position (XIV and XV). In agreement with the prediction, only the (S) isomer XV showed significant activity against MraY (IC50=5 mu M). (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00349-8
• 作为产物：
  描述：

  四乙酰核糖 在 甲醇 、 氯化亚砜 、 氨 、 氰化汞 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 144.0h， 生成 1-[(3aR,4R,6R,6aR)-6-[[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxymethyl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]pyrimidine-2,4-dione
  参考文献：
  名称：

  Synthesis of the Nucleoside Moiety of Liposidomycins: Elucidation of the Pharmacophore of this Family of MraY Inhibitors

  摘要：

  Tunicamycins (TCMs) and liposidomycins (LPMs) are naturally occurring inhibitors of the bacterial translocase (MraY). Based on structure-activity relationship (SAR) studies, a molecular model has been proposed for their inhibitory mechanism. This study points out the importance of the nucleoside moiety of liposidomycins in the inhibition of MraY. A simplified molecule (I) based on the liposidomycin core structure has been synthesised and tested on MraY. The compound displayed a moderate inhibitory activity (IC50-50 mu M). The validation of the molecular model was then performed by synthesising higher homologues of I, containing an additional stereocentre in the 5' position (XIV and XV). In agreement with the prediction, only the (S) isomer XV showed significant activity against MraY (IC50=5 mu M). (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00349-8

文献信息

• Synthesis of analogues of the O-β-d-Ribofuranosyl nucleoside moiety of liposidomycins. Part 2: role of the hydroxyl groups upon the inhibition of MraY
  作者：C. Dini、N. Drochon、J.C. Guillot、P. Mauvais、P. Walter、J. Aszodi

  DOI：10.1016/s0960-894x(00)00714-9

  日期：2001.2

  O-beta -D-Ribofuranosyl nucleoside I is the minimal structural entity of liposidomycins that maintains enzyme inhibitory activity on MraY. A set of compounds with hydroxyl patterns different from I has been synthesized. The presence of a hydroxyl group in the 3 " position is essential for the activity. The 3'-deoxy derivative (IV), however, shows a 5-fold improved potency. (C) 2001 Elsevier Science Ltd. All rights reserved.