[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(3R)-3-hydroxy-2,2-dimethyl-4-[[3-[2-(methyldisulfanyl)ethylamino]-3-oxopropyl]amino]-4-oxobutyl] hydrogen phosphate | 59212-62-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子
• 英文名称: [[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(3R)-3-hydroxy-2,2-dimethyl-4-[[3-[2-(methyldisulfanyl)ethylamino]-3-oxopropyl]amino]-4-oxobutyl] hydrogen phosphate
• CAS: 59212-62-3
• 化学式: C₂₂H₃₈N₇O₁₆P₃S₂
• 分子量: 813.634
• InChiKey: FFKBJBIVDRSJLG-GORZOVPNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.4
• 重原子数：
  50
• 可旋转键数：
  20
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  397
• 氢给体数：
  9
• 氢受体数：
  22

反应信息

• 作为产物：
  描述：

  coenzyme A trilithium salt 、 甲基硫代磺酸甲酯 以 甲醇 为溶剂， 反应 0.5h， 以30%的产率得到[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(3R)-3-hydroxy-2,2-dimethyl-4-[[3-[2-(methyldisulfanyl)ethylamino]-3-oxopropyl]amino]-4-oxobutyl] hydrogen phosphate
  参考文献：
  名称：

  N-thiolated β-lactams: Studies on the mode of action and identification of a primary cellular target in Staphylococcus aureus

  摘要：

  This study focuses on the mechanism of action of N-alkylthio beta-lactains, a new family of antibacterial compounds that show promising activity against Staphylococcus and Bacillus microbes. Previous investigations have determined that these compounds are highly selective towards these bacteria, and possess completely unprecedented structure-activity profiles for a beta-lactam antibiotic. Unlike penicillin, which inhibits cell wall crosslinking proteins and affords a broad spectrum of bacteriocidal activity, these N-thiolated lactams are bacteriostatic in their behavior and act through a different mechanistic mode. Our current findings indicate that the compounds react rapidly within the bacterial cell with coenzyme A (CoA) through in vivo transfer of the N-thio group to produce an alkyl-CoA mixed disulfide species, which then interferes with fatty acid biosynthesis. Our studies on coenzyme A disulfide reductase show that the CoA thiol-redox buffer is not perturbed by these compounds; however, the lactams appear to act as prodrugs. The experimental evidence that these beta-lactams inhibit fatty acid biosynthesis in bacteria, and the elucidation of coenzyme A as a primary cellular target, offers opportunities for the discovery of other small organic compounds that can be developed as therapeutics for MRSA and anthrax infections. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.12.027