N6-benzoyl-5'-(tert-butyldimethylsilyl)-3'-(1-(benzyloxycarbonylamino)ethyl phosphonyl)-2'-deoxyadenosine triethylammonium salt | 1162655-66-4

• 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: N6-benzoyl-5'-(tert-butyldimethylsilyl)-3'-(1-(benzyloxycarbonylamino)ethyl phosphonyl)-2'-deoxyadenosine triethylammonium salt
• CAS: 1162655-66-4
• 化学式: C₆H₁₅N*C₃₃H₄₃N₆O₈PSi
• 分子量: 811.991
• InChiKey: LSJDBHITFNAPMX-CNUFZEEPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.58
• 重原子数：
  56.0
• 可旋转键数：
  15.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  179.26
• 氢给体数：
  3.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  N-benzyloxycarbonyl-1-aminoethanephosphonic acid methyl monoester 、 N-苯甲酰基-5’-O-叔丁基二甲基硅烷基-2’-脱氧腺苷 、 三乙胺 在 吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 144.0h， 以54%的产率得到N6-benzoyl-5'-(tert-butyldimethylsilyl)-3'-(1-(benzyloxycarbonylamino)ethyl phosphonyl)-2'-deoxyadenosine triethylammonium salt
  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