(2R,4S,5S)-methyl 3-acetyl-2-azidopropyl-5-[(1R,2R,3R,4R)-2,3-di-tert-butyldimethylsilyloxy-4-(uracil-1-yl)]tetrahydrofuryl-(1,3)-oxazolidine-4-carboxylate | 1223564-04-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R,4S,5S)-methyl 3-acetyl-2-azidopropyl-5-[(1R,2R,3R,4R)-2,3-di-tert-butyldimethylsilyloxy-4-(uracil-1-yl)]tetrahydrofuryl-(1,3)-oxazolidine-4-carboxylate
• 英文别名: methyl (2R,4S,5S)-3-acetyl-2-(3-azidopropyl)-5-[(2R,3R,4R,5R)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-(2,4-dioxopyrimidin-1-yl)oxolan-2-yl]-1,3-oxazolidine-4-carboxylate
• CAS: 1223564-04-2
• 化学式: C₃₀H₅₂N₆O₉Si₂
• 分子量: 696.949
• InChiKey: BNAHERCAYZXPDA-DXGZOGIFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.42
• 重原子数：
  47
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  147
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (2R,4S,5S)-methyl 3-acetyl-2-azidopropyl-5-[(1R,2R,3R,4R)-2,3-di-tert-butyldimethylsilyloxy-4-(uracil-1-yl)]tetrahydrofuryl-(1,3)-oxazolidine-4-carboxylate 在 lithium iodide 作用下， 以 乙酸乙酯 为溶剂， 反应 5.0h， 以81%的产率得到(2R,4S,5S)-3-acetyl-2-azidopropyl-5-[(1R,2R,3R,4R)-2,3-di-tert-butyldimethylsilyloxy-4-(uracil-1-yl)]tetrahydrofuryl-(1,3)-oxazolidine-4-carboxylic acid
  参考文献：
  名称：

  Function-Oriented Synthesis of Simplified Caprazamycins: Discovery of Oxazolidine-Containing Uridine Derivatives as Antibacterial Agents against Drug-Resistant Bacteria

  摘要：

  The rational simplification of the caprazamycin (CPZ) class of nucleoside natural products was carried out to address their molecular complexity. First, analogues 6-8, where the diazepanone ring of the CPZ was removed and a lipophilic side chain was attached to either the C-7' or N(6') atom, were used to investigate the conformation activity relationship. On the basis of this relationship, we designed the oxazolidine-containing uridine derivatives 18-21 by restricting the conformation of 6-8. As a result, the 'Bu ester derivatives 20 were found to be the most active against a range of bacterial strains containing VRE with a potency similar to that of the parent CPZs. This study provides a novel strategy for the development of a new type of antibacterial agent effective against drug-resistant bacteria.

  DOI：

  10.1021/jm100243n
• 作为产物：
  描述：

  methyl (4S,5S)-2-(3-azidopropyl)-5-[(2R,3R,4R,5R)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-(2,4-dioxopyrimidin-1-yl)oxolan-2-yl]-1,3-oxazolidine-4-carboxylate 、 乙酰氯 在 三乙胺 作用下， 反应 12.0h， 以265 mg的产率得到(2R,4S,5S)-methyl 3-acetyl-2-azidopropyl-5-[(1R,2R,3R,4R)-2,3-di-tert-butyldimethylsilyloxy-4-(uracil-1-yl)]tetrahydrofuryl-(1,3)-oxazolidine-4-carboxylate
  参考文献：
  名称：

  Function-Oriented Synthesis of Simplified Caprazamycins: Discovery of Oxazolidine-Containing Uridine Derivatives as Antibacterial Agents against Drug-Resistant Bacteria

  摘要：

  The rational simplification of the caprazamycin (CPZ) class of nucleoside natural products was carried out to address their molecular complexity. First, analogues 6-8, where the diazepanone ring of the CPZ was removed and a lipophilic side chain was attached to either the C-7' or N(6') atom, were used to investigate the conformation activity relationship. On the basis of this relationship, we designed the oxazolidine-containing uridine derivatives 18-21 by restricting the conformation of 6-8. As a result, the 'Bu ester derivatives 20 were found to be the most active against a range of bacterial strains containing VRE with a potency similar to that of the parent CPZs. This study provides a novel strategy for the development of a new type of antibacterial agent effective against drug-resistant bacteria.

  DOI：

  10.1021/jm100243n

文献信息

• Function-Oriented Synthesis of Simplified Caprazamycins: Discovery of Oxazolidine-Containing Uridine Derivatives as Antibacterial Agents against Drug-Resistant Bacteria
  作者：Kensuke Ii、Satoshi Ichikawa、Bayan Al-Dabbagh、Ahmed Bouhss、Akira Matsuda

  DOI：10.1021/jm100243n

  日期：2010.5.13

  The rational simplification of the caprazamycin (CPZ) class of nucleoside natural products was carried out to address their molecular complexity. First, analogues 6-8, where the diazepanone ring of the CPZ was removed and a lipophilic side chain was attached to either the C-7' or N(6') atom, were used to investigate the conformation activity relationship. On the basis of this relationship, we designed the oxazolidine-containing uridine derivatives 18-21 by restricting the conformation of 6-8. As a result, the 'Bu ester derivatives 20 were found to be the most active against a range of bacterial strains containing VRE with a potency similar to that of the parent CPZs. This study provides a novel strategy for the development of a new type of antibacterial agent effective against drug-resistant bacteria.