5'-O-(N-(2-benzyloxybenzoyl)sulfamoyl)-3'-O-tert-butyldimethylsilyl-2'-deoxyadenosine 1,8-diazabicyclo[5.4.0]undec-7-ene salt

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 5'-O-(N-(2-benzyloxybenzoyl)sulfamoyl)-3'-O-tert-butyldimethylsilyl-2'-deoxyadenosine 1,8-diazabicyclo[5.4.0]undec-7-ene salt
• 英文别名: [(2R,3S,5R)-5-(6-aminopurin-9-yl)-3-[tert-butyl(dimethyl)silyl]oxyoxolan-2-yl]methyl N-(2-phenylmethoxybenzoyl)sulfamate;2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine
• 化学式: C₉H₁₆N₂*C₃₀H₃₈N₆O₇SSi
• 分子量: 807.059
• InChiKey: AMFBOFDOJBOLSG-UTXSYOJYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.02
• 重原子数：
  56
• 可旋转键数：
  12
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  194
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  5'-O-(N-(2-benzyloxybenzoyl)sulfamoyl)-3'-O-tert-butyldimethylsilyl-2'-deoxyadenosine 1,8-diazabicyclo[5.4.0]undec-7-ene salt 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 8.0h， 生成
  参考文献：
  名称：

  Antitubercular Nucleosides That Inhibit Siderophore Biosynthesis:  SAR of the Glycosyl Domain

  摘要：

  Tuberculosis is the leading cause of infectious disease mortality in the world by a bacterial pathogen. We previously demonstrated that a bisubstrate inhibitor of the adenylation enzyme MbtA, which is responsible for the second step of mycobactin biosynthesis, exhibited potent antitubercular activity. Here we systematically investigate the structure-activity relationships of the bisubstrate inhibitor glycosyl domain resulting in the identification of a carbocyclic analogue that possesses a K-I(app) value of 2.3 nM and MIC99 values of 1.56 mu M against M. tuberculosis H37Rv. The SAR data suggest the intriguing possibility that the bisubstrate inhibitors utilize a transporter for entry across the mycobacterial cell envelope. Additionally, we report improved conditions for the expression of MbtA and biochemical analysis, demonstrating that MbtA follows a random sequential enzyme mechanism for the adenylation half-reaction.

  DOI：

  10.1021/jm061068d
• 作为产物：
  描述：

  2'-脱氧腺苷 在 咪唑 、 4-二甲氨基吡啶 、 sodium hydride 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 35.77h， 生成 5'-O-(N-(2-benzyloxybenzoyl)sulfamoyl)-3'-O-tert-butyldimethylsilyl-2'-deoxyadenosine 1,8-diazabicyclo[5.4.0]undec-7-ene salt
  参考文献：
  名称：

  Antitubercular Nucleosides That Inhibit Siderophore Biosynthesis:  SAR of the Glycosyl Domain

  摘要：

  Tuberculosis is the leading cause of infectious disease mortality in the world by a bacterial pathogen. We previously demonstrated that a bisubstrate inhibitor of the adenylation enzyme MbtA, which is responsible for the second step of mycobactin biosynthesis, exhibited potent antitubercular activity. Here we systematically investigate the structure-activity relationships of the bisubstrate inhibitor glycosyl domain resulting in the identification of a carbocyclic analogue that possesses a K-I(app) value of 2.3 nM and MIC99 values of 1.56 mu M against M. tuberculosis H37Rv. The SAR data suggest the intriguing possibility that the bisubstrate inhibitors utilize a transporter for entry across the mycobacterial cell envelope. Additionally, we report improved conditions for the expression of MbtA and biochemical analysis, demonstrating that MbtA follows a random sequential enzyme mechanism for the adenylation half-reaction.

  DOI：

  10.1021/jm061068d

文献信息

• Antitubercular Nucleosides That Inhibit Siderophore Biosynthesis:  SAR of the Glycosyl Domain
  作者：Ravindranadh V. Somu、Daniel J. Wilson、Eric M. Bennett、Helena I. Boshoff、Laura Celia、Brian J. Beck、Clifton E. Barry、Courtney C. Aldrich

  DOI：10.1021/jm061068d

  日期：2006.12.1

  Tuberculosis is the leading cause of infectious disease mortality in the world by a bacterial pathogen. We previously demonstrated that a bisubstrate inhibitor of the adenylation enzyme MbtA, which is responsible for the second step of mycobactin biosynthesis, exhibited potent antitubercular activity. Here we systematically investigate the structure-activity relationships of the bisubstrate inhibitor glycosyl domain resulting in the identification of a carbocyclic analogue that possesses a K-I(app) value of 2.3 nM and MIC99 values of 1.56 mu M against M. tuberculosis H37Rv. The SAR data suggest the intriguing possibility that the bisubstrate inhibitors utilize a transporter for entry across the mycobacterial cell envelope. Additionally, we report improved conditions for the expression of MbtA and biochemical analysis, demonstrating that MbtA follows a random sequential enzyme mechanism for the adenylation half-reaction.