[(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 | 1188441-16-8

• 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: [(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
• CAS: 1188441-16-8
• 化学式: C₂₈H₄₀NO₉P
• 分子量: 565.601
• InChiKey: XZOIWYWMRSFQGT-PNUOTMQBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.61
• 重原子数：
  39.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  159.46
• 氢给体数：
  4.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  [(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 在 sodium carbonate 作用下， 以 甲醇 、 水 为溶剂， 反应 2.17h， 以82.3%的产率得到FU-23
  参考文献：
  名称：

  First Scale-Up Synthesis of FU-23, a Novel Water-Soluble Pleuromutilin-Derived Antibiotic

  摘要：

  A first scale-up synthesis of FU-23 (1), a potent and effective water-soluble pleuromutilin-derived antibiotic, is described. The original synthesis from the medicinal chemistry group provided 1 in seven steps and 10.9% overall yield, required four chromatographies and employed expensive reagents such as AgOCN and 4-acetyl-salicoyl chloride. The optimized synthetic route for the preparation of phosphate salt 1 consists of seven linear steps with a 42.8% overall yield. Significant cost reduction and more robust reaction conditions have been developed with no chromatography required at any stage.

  DOI：

  10.1021/op100063h
• 作为产物：
  描述：

  (3R)-3-deoxo-11-deoxy-3-methoxy-11-oxo-4-epi-mutilin 在 盐酸 、 4-二甲氨基吡啶 、 5% Pd(II)/C(eggshell) 、 palladium 10% on activated carbon 、 氢气 、 N,N-二异丙基乙胺 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 四氯化碳 、 二氯甲烷 、 水 、 乙腈 为溶剂， -25.0~25.0 ℃ 、300.01 kPa 条件下， 反应 14.5h， 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：

  First Scale-Up Synthesis of FU-23, a Novel Water-Soluble Pleuromutilin-Derived Antibiotic

  摘要：

  A first scale-up synthesis of FU-23 (1), a potent and effective water-soluble pleuromutilin-derived antibiotic, is described. The original synthesis from the medicinal chemistry group provided 1 in seven steps and 10.9% overall yield, required four chromatographies and employed expensive reagents such as AgOCN and 4-acetyl-salicoyl chloride. The optimized synthetic route for the preparation of phosphate salt 1 consists of seven linear steps with a 42.8% overall yield. Significant cost reduction and more robust reaction conditions have been developed with no chromatography required at any stage.

  DOI：

  10.1021/op100063h

文献信息

• Water-soluble phosphate prodrugs of pleuromutilin analogues with potent in vivo antibacterial activity against Gram-positive pathogens
  作者：Liqiang Fu、Zhiteng Jiang、Zhan cai、Xin Liu、Huili He、Yushe Yang

  DOI：10.1016/j.bmcl.2009.07.115

  日期：2009.9

  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.