(3aR,4R,5R,7S,8S,9R,9aS,12R)-8-hydroxy-4,7,9,12-tetramethyl-3-oxo-7-vinyldecahydro-4,9a-propanocyclopenta[8]annulen-5-yl (4-((bis(benzyloxy)phosphoryl)oxy)benzoyl)carbamate | 1188391-13-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (3aR,4R,5R,7S,8S,9R,9aS,12R)-8-hydroxy-4,7,9,12-tetramethyl-3-oxo-7-vinyldecahydro-4,9a-propanocyclopenta[8]annulen-5-yl (4-((bis(benzyloxy)phosphoryl)oxy)benzoyl)carbamate
• CAS: 1188391-13-0
• 化学式: C₄₂H₅₀NO₉P
• 分子量: 743.834
• InChiKey: GXPGGBTZPJLUDW-JQDLRBNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.84
• 重原子数：
  53.0
• 可旋转键数：
  11.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  137.46
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  (3aR,4R,5R,7S,8S,9R,9aS,12R)-8-hydroxy-4,7,9,12-tetramethyl-3-oxo-7-vinyldecahydro-4,9a-propanocyclopenta[8]annulen-5-yl (4-((bis(benzyloxy)phosphoryl)oxy)benzoyl)carbamate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、275.8 kPa 条件下， 反应 8.0h， 生成 [(1S,2R,3S,4R,6R,7R,8R,14R)-4-ethyl-3-hydroxy-2,4,7,14-tetramethyl-9-oxo-6-tricyclo[5.4.3.01,8]tetradecanyl] N-(4-phosphonooxybenzoyl)carbamate
  参考文献：
  名称：

  Water-soluble phosphate prodrugs of pleuromutilin analogues with potent in vivo antibacterial activity against Gram-positive pathogens

  摘要：

  A phosphate prodrug strategy was investigated to address the problem of poor aqueous solubility of pleuromutilin analogues. Water-soluble phosphate prodrugs 6a, 6b and 6c of pleuromutilin analogues were designed and synthesized. Three compounds all exhibited excellent aqueous solubility (>50 mg/mL) at near-neutral pH and sufficient stability in buffer solution. In particular, the phenol pleuromutilin prodrug 6c displayed favourable pharmacokinetic profiles and comparable potency with vancomycin against MSSA and MRSA strains in vivo. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.07.115
• 作为产物：
  描述：

  SB-222734 、 亚磷酸二苄酯 在 四氯化碳 、 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 3.17h， 以81.8%的产率得到(3aR,4R,5R,7S,8S,9R,9aS,12R)-8-hydroxy-4,7,9,12-tetramethyl-3-oxo-7-vinyldecahydro-4,9a-propanocyclopenta[8]annulen-5-yl (4-((bis(benzyloxy)phosphoryl)oxy)benzoyl)carbamate
  参考文献：
  名称：

  Water-soluble phosphate prodrugs of pleuromutilin analogues with potent in vivo antibacterial activity against Gram-positive pathogens

  摘要：

  A phosphate prodrug strategy was investigated to address the problem of poor aqueous solubility of pleuromutilin analogues. Water-soluble phosphate prodrugs 6a, 6b and 6c of pleuromutilin analogues were designed and synthesized. Three compounds all exhibited excellent aqueous solubility (>50 mg/mL) at near-neutral pH and sufficient stability in buffer solution. In particular, the phenol pleuromutilin prodrug 6c displayed favourable pharmacokinetic profiles and comparable potency with vancomycin against MSSA and MRSA strains in vivo. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.07.115