(4S)-3-{(2S,3S)-2-(biphenyl-4-ylmethoxy)-3-{5-[(tert-butyldimethylsilyloxy)methyl]isoxazol-3-yl}-3-hydroxy-2-methylpropanoyl}-5,5-dimethyl-4-phenyl-1,3-oxazolidin-2-one | 1219005-01-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4S)-3-{(2S,3S)-2-(biphenyl-4-ylmethoxy)-3-{5-[(tert-butyldimethylsilyloxy)methyl]isoxazol-3-yl}-3-hydroxy-2-methylpropanoyl}-5,5-dimethyl-4-phenyl-1,3-oxazolidin-2-one
• 英文别名: (4S)-3-[(2S,3S)-3-[5-[[tert-butyl(dimethyl)silyl]oxymethyl]-1,2-oxazol-3-yl]-3-hydroxy-2-methyl-2-[(4-phenylphenyl)methoxy]propanoyl]-5,5-dimethyl-4-phenyl-1,3-oxazolidin-2-one
• CAS: 1219005-01-2
• 化学式: C₃₈H₄₆N₂O₇Si
• 分子量: 670.878
• InChiKey: XBVOEXREKIXMHW-VRCSSVMSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.37
• 重原子数：
  48
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (4S)-3-{(2S,3S)-2-(biphenyl-4-ylmethoxy)-3-{5-[(tert-butyldimethylsilyloxy)methyl]isoxazol-3-yl}-3-hydroxy-2-methylpropanoyl}-5,5-dimethyl-4-phenyl-1,3-oxazolidin-2-one 在 盐酸羟胺 、 lithium methanolate 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以38%的产率得到(2S,3S)-2-(biphenyl-4-ylmethoxy)-3-{5-[(tert-butyldimethylsilyloxy)methyl]isoxazol-3-yl}-N,3-dihydroxy-2-methylpropanamide
  参考文献：
  名称：

  Structure based design of an in vivo active hydroxamic acid inhibitor of P. aeruginosa LpxC

  摘要：

  Lipid A is an essential component of the Gram negative outer membrane, which protects the bacterium from attack of many antibiotics. The Lipid A biosynthesis pathway is essential for Gram negative bacterial growth and is unique to these bacteria. The first committed step in Lipid A biosynthesis is catalysis by LpxC, a zinc dependent deacetylase. We show the design of an LpxC inhibitor utilizing a robust model which directed efficient design of picomolar inhibitors. Analysis of physiochemical properties drove design to focus on an optimal lipophilicity profile. Further structure based design took advantage of a conserved water network over the active site, and with the optimal lipophilicity profile, led to an improved LpxC inhibitor with in vivo activity against wild type Pseudomonas aeruginosa. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.140
• 作为产物：
  描述：

  4-溴甲基联苯 在 正丁基锂 、 氯化亚砜 、 水 、 sodium hydride 、 lithium hydroxide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 、 正庚烷 、 乙基苯 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 28.5h， 生成 (4S)-3-{(2S,3S)-2-(biphenyl-4-ylmethoxy)-3-{5-[(tert-butyldimethylsilyloxy)methyl]isoxazol-3-yl}-3-hydroxy-2-methylpropanoyl}-5,5-dimethyl-4-phenyl-1,3-oxazolidin-2-one
  参考文献：
  名称：

  Structure based design of an in vivo active hydroxamic acid inhibitor of P. aeruginosa LpxC

  摘要：

  Lipid A is an essential component of the Gram negative outer membrane, which protects the bacterium from attack of many antibiotics. The Lipid A biosynthesis pathway is essential for Gram negative bacterial growth and is unique to these bacteria. The first committed step in Lipid A biosynthesis is catalysis by LpxC, a zinc dependent deacetylase. We show the design of an LpxC inhibitor utilizing a robust model which directed efficient design of picomolar inhibitors. Analysis of physiochemical properties drove design to focus on an optimal lipophilicity profile. Further structure based design took advantage of a conserved water network over the active site, and with the optimal lipophilicity profile, led to an improved LpxC inhibitor with in vivo activity against wild type Pseudomonas aeruginosa. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.140