5'-(tert-butyldimethylsilyl)-3'-(1-aminoethyl phosphonyl)-2'-deoxyadenosine | 1162655-71-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 5'-(tert-butyldimethylsilyl)-3'-(1-aminoethyl phosphonyl)-2'-deoxyadenosine
• 英文别名: [(2R,3S,5R)-5-(6-aminopurin-9-yl)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-3-yl]oxy-(1-azaniumylethyl)phosphinate
• CAS: 1162655-71-1
• 化学式: C₁₈H₃₃N₆O₅PSi
• 分子量: 472.556
• InChiKey: MVOITUILPRJUDV-CKISJDIXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.59
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  161
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  N6-benzoyl-5'-(tert-butyldimethylsilyl)-3'-(1-(benzyloxycarbonylamino)ethyl phosphonyl)-2'-deoxyadenosine triethylammonium salt 在 ammonium hydroxide 、 5%-palladium/activated carbon 、 氢气 作用下， 以 甲醇 、 水 为溶剂， 反应 18.0h， 以99%的产率得到5'-(tert-butyldimethylsilyl)-3'-(1-aminoethyl phosphonyl)-2'-deoxyadenosine
  参考文献：
  名称：

  Inhibition of tRNA-dependent ligase MurM from Streptococcus pneumoniae by phosphonate and sulfonamide inhibitors

  摘要：

  Ligase MurM catalyses the addition of Ala from alanyl-tRNA(Ala), or Ser from seryl-tRNA(Ser), to lipid intermediate II in peptidoglycan biosynthesis in Streptococcus pneumoniae, and is a determinant of high-level penicillin resistance. Phosphorus-based transition state analogues were designed as inhibitors of the MurM-catalysed reaction. Phosphonamide analogues mimicking the attack of a lysine nucleophile upon Ala-tRNA(Ala) showed no inhibition of MurM, but adenosine 3'-phosphonate analogues showed inhibition of MurM, the most active being a 2'-deoxyadenosine analogue (IC50 100 mu M). Structure/function studies upon this analogue established that modi. cation of the amino group of the aminoalkylphosphonate resulted in loss of potency, and modi. cation of the adenosine 5'-hydroxyl group with either a t-butyl dimethyl silyl or a carbamate functional group resulted in loss of activity. A library of 48 aryl sulfonamides was also screened against MurM using a radiochemical assay, and two compounds showed sub-millimolar inhibition. These compounds are the first small molecule inhibitors of the Fem ligase family of peptidyltransferases found in Gram-positive bacteria. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.03.028

文献信息

• Inhibition of tRNA-dependent ligase MurM from Streptococcus pneumoniae by phosphonate and sulfonamide inhibitors
  作者：Elena Cressina、Adrian J. Lloyd、Gianfranco De Pascale、B. James Mok、Stephen Caddick、David I. Roper、Christopher G. Dowson、Timothy D.H. Bugg

  DOI：10.1016/j.bmc.2009.03.028

  日期：2009.5

  Ligase MurM catalyses the addition of Ala from alanyl-tRNA(Ala), or Ser from seryl-tRNA(Ser), to lipid intermediate II in peptidoglycan biosynthesis in Streptococcus pneumoniae, and is a determinant of high-level penicillin resistance. Phosphorus-based transition state analogues were designed as inhibitors of the MurM-catalysed reaction. Phosphonamide analogues mimicking the attack of a lysine nucleophile upon Ala-tRNA(Ala) showed no inhibition of MurM, but adenosine 3'-phosphonate analogues showed inhibition of MurM, the most active being a 2'-deoxyadenosine analogue (IC50 100 mu M). Structure/function studies upon this analogue established that modi. cation of the amino group of the aminoalkylphosphonate resulted in loss of potency, and modi. cation of the adenosine 5'-hydroxyl group with either a t-butyl dimethyl silyl or a carbamate functional group resulted in loss of activity. A library of 48 aryl sulfonamides was also screened against MurM using a radiochemical assay, and two compounds showed sub-millimolar inhibition. These compounds are the first small molecule inhibitors of the Fem ligase family of peptidyltransferases found in Gram-positive bacteria. (C) 2009 Elsevier Ltd. All rights reserved.