(4R,5R,6S)-6-((R)-1-Hydroxy-ethyl)-4-methyl-7-oxo-3-trifluoromethanesulfonyloxy-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester | 154428-43-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: (4R,5R,6S)-6-((R)-1-Hydroxy-ethyl)-4-methyl-7-oxo-3-trifluoromethanesulfonyloxy-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester
• 英文别名: (4-nitrophenyl)methyl (4R,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-(trifluoromethylsulfonyloxy)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
• CAS: 154428-43-0
• 化学式: C₁₈H₁₇F₃N₂O₉S
• 分子量: 494.402
• InChiKey: IWRZEHCVPRPEPY-NRMKKVEVSA-N

物化性质

• 沸点：
  628.0±55.0 °C(Predicted)
• 密度：
  1?+-.0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  164
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (4R,5R,6S)-6-((R)-1-Hydroxy-ethyl)-4-methyl-7-oxo-3-trifluoromethanesulfonyloxy-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester 在 三乙胺 作用下， 反应 1.0h， 生成 [4S-(4α,5β,6β(S*))]-1-(2-amino-2-oxoethyl)-({6-[6-(1-hydroxyethyl)-4-methyl-2-({[(4-nitrophenyl)methyl]oxy}carbonyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]-9-oxo-9H-fluoren-2-yl}methyl)-1,4-diazaniabicyclo[2.2.2]octane 1-propanesulfonate trifluo...
  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
• 作为产物：
  描述：

  三氟甲磺酸酐 、 4-nitrobenzyl (4R,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3,7-dioxo-1-azabicyclo[3.2.0]-heptane-2-carboxylate 在 三乙胺 作用下， 反应 0.5h， 生成 (4R,5R,6S)-6-((R)-1-Hydroxy-ethyl)-4-methyl-7-oxo-3-trifluoromethanesulfonyloxy-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester
  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

• Synthesis and biological properties of a new series of anti-MRSA β-lactams; 2-(thiazol-2-ylthio)carbapenems
  作者：Hisatoshi Shinagawa、Hiroshi Yamaga、Hitoshi Houchigai、Yoshihiro Sumita、Makoto Sunagawa

  DOI：10.1016/s0968-0896(96)00273-8

  日期：1997.3

  A series of 1 beta-methylcarbapenems containing variously C-2 substituted thiazol-2-ylthio groups were synthesized, and their in vitro anti-MRSA activity was examined. Among them, 1 beta-methyl-2-(4-arylthiazol-2-ylthio) carbapenems exhibited superior anti-MRSA activity. Introduction of a cationic moiety in the C-2 side chain not only reduced the binding to HSA but also increased the stability against DHP-I, without affecting the anti-MRSA, activity. It was also found that the distance between the cationic moiety and the carbapenem skeleton was related to the strength of HSA binding and the stability against DHP-I. (C) 1997 Elsevier Science Ltd.
• Synthesis of novel di- and tricationic carbapenems with potent anti-MRSA activity
  作者：Takahisa Maruyama、Yasuo Yamamoto、Yuko Kano、Mizuyo Kurazono、Eiki Shitara、Katsuyoshi Iwamatsu、Kunio Atsumi

  DOI：10.1016/j.bmcl.2008.11.039

  日期：2009.1

  A new series of 1 beta-methyl carbapenems possessing a 6,7-disubstituted imidazo[5,1-b]thiazol-2-yl group directly attached to the C-2 position of the carbapenem nucleus was prepared, and their activities against methicillin-resistant Staphylococcus aureus (MRSA) were evaluated. First, a benzyl moiety was introduced at the C-6 position of imidazo[5,1-b]thiazole attached to the carbapenem. These benzylated molecules showed potent anti-MRSA activity, but poor water solubility. In order to overcome this drawback, we designed and synthesized di- and tricationic carbapenems and finally discovered a novel carbapenem (15i), which exhibited excellent anti-MRSA activity and good water solubility. (C) 2008 Elsevier Ltd. All rights reserved.
• 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.