(4-nitrophenyl)methyl (4S,5R,6S)-3-[7-(hydroxymethyl)-9-oxofluoren-3-yl]-4-methyl-7-oxo-6-[(1R)-1-triethylsilyloxyethyl]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | 157743-80-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (4-nitrophenyl)methyl (4S,5R,6S)-3-[7-(hydroxymethyl)-9-oxofluoren-3-yl]-4-methyl-7-oxo-6-[(1R)-1-triethylsilyloxyethyl]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
• CAS: 157743-80-1
• 化学式: C₃₇H₄₀N₂O₈Si
• 分子量: 668.819
• InChiKey: AZAZUBAQJYKROX-LXTHUPMRSA-N

物化性质

• 沸点：
  812.4±65.0 °C(predicted)
• 密度：
  1.32±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.64
• 重原子数：
  48
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  139
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (4-nitrophenyl)methyl (4S,5R,6S)-3-[7-(hydroxymethyl)-9-oxofluoren-3-yl]-4-methyl-7-oxo-6-[(1R)-1-triethylsilyloxyethyl]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate 在 Rh on carbon 盐酸 、 氢气 、 三乙胺 、 sodium iodide 作用下， 以 四氢呋喃 、 二氯甲烷 、 丙酮 、 乙腈 为溶剂， -20.0 ℃ 、101.33 kPa 条件下， 生成 (4S,5R,6S)-3-[7-[[4-[2-(3-carbamoylanilino)-2-oxoethyl]-1,4-diazoniabicyclo[2.2.2]octan-1-yl]methyl]-9-oxofluoren-3-yl]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate;chloride
  参考文献：
  名称：

  Dicationic 2-fluorenonylcarbapenems: Potent anti-MRS agents with improved solubility and pharmacokinetic properties

  摘要：

  The synthesis and biological evaluation of a series of dicationic-substituted 2-fluorenonylcarbapenems is described. This class of compounds showed enhanced water solubility while maintaining potent activity against MRS. Introduction of a beta 1--methyl substituent was found to improve pharmacokinetics. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00567-3
• 作为产物：
  描述：

  6-Bromo-2-(methoxymethyl)fluoren-9-one 在 硫酸 作用下， 以 甲醇 为溶剂， 反应 1.5h， 生成 (4-nitrophenyl)methyl (4S,5R,6S)-3-[7-(hydroxymethyl)-9-oxofluoren-3-yl]-4-methyl-7-oxo-6-[(1R)-1-triethylsilyloxyethyl]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
  参考文献：
  名称：

  Practical Synthesis of Anti-Methicillin-Resistant Staphylococcus Aureus (MRSA) Carbapenem L-742,728

  摘要：

  Ani-MRSA carbapenem, L-742,728, has been prepared in large quantity using, the Suzuki-Miyaura cross-coupling as the key reaction. Three approaches have been examined by varying the coupling reaction between carbapenem nucleus A and side chains B, BC, and BCD, wherein BCD represents the fully elaborated side chain. The coupling of A with BCD offers the advantage of convergence and requires fewer chemical steps after installation of the thermally unstable carbapenem skeleton. This key reaction highlights the versatility and efficiency of the Suzuki-Miyaura reaction. This approach offers a general method for the preparation of the 3-aryl carbapenems, which possess strong antibacterial activity against resistant strains.

  DOI：

  10.1021/jo980381n

文献信息

• Practical Synthesis of Anti-Methicillin-Resistant <i>Staphylococcus</i> <i>Aureus</i> (MRSA) Carbapenem L-742,728
  作者：Nobuyoshi Yasuda、Mark A. Huffman、Guo-Jie Ho、Lyndon C. Xavier、Chunhua Yang、Khateeta M. Emerson、Fuh-Rong Tsay、Yulan Li、Michael H. Kress、Dale L. Rieger、Sandor Karady、Paul Sohar、Newton L. Abramson、Ann E. DeCamp、David J. Mathre、Alan W. Douglas、Ulf-H. Dolling、Edward J. J. Grabowski、Paul J. Reider

  DOI：10.1021/jo980381n

  日期：1998.8.1

  Ani-MRSA carbapenem, L-742,728, has been prepared in large quantity using, the Suzuki-Miyaura cross-coupling as the key reaction. Three approaches have been examined by varying the coupling reaction between carbapenem nucleus A and side chains B, BC, and BCD, wherein BCD represents the fully elaborated side chain. The coupling of A with BCD offers the advantage of convergence and requires fewer chemical steps after installation of the thermally unstable carbapenem skeleton. This key reaction highlights the versatility and efficiency of the Suzuki-Miyaura reaction. This approach offers a general method for the preparation of the 3-aryl carbapenems, which possess strong antibacterial activity against resistant strains.
• Dicationic 2-fluorenonylcarbapenems: Potent anti-MRS agents with improved solubility and pharmacokinetic properties
  作者：Mark L. Greenlee、Joanne B. Laub、Gregory P. Rouen、Frank DiNinno、Milton L. Hammond、Joann L. Huber、Jon G. Sundelof、Gail G. Hammond

  DOI：10.1016/s0960-894x(99)00567-3

  日期：1999.11

  The synthesis and biological evaluation of a series of dicationic-substituted 2-fluorenonylcarbapenems is described. This class of compounds showed enhanced water solubility while maintaining potent activity against MRS. Introduction of a beta 1--methyl substituent was found to improve pharmacokinetics. (C) 1999 Elsevier Science Ltd. All rights reserved.