benzyl 4-[2-fluoro-4-[(5R)-5-(methylsulfonyloxymethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl]piperazine-1-carboxylate | 903594-02-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: benzyl 4-[2-fluoro-4-[(5R)-5-(methylsulfonyloxymethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl]piperazine-1-carboxylate
• CAS: 903594-02-5
• 化学式: C₂₃H₂₆FN₃O₇S
• 分子量: 507.54
• InChiKey: QSRQMUGHRUGZIL-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  114
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  benzyl 4-[2-fluoro-4-[(5R)-5-(methylsulfonyloxymethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl]piperazine-1-carboxylate 在 palladium on activated charcoal 吡啶 、 二氯甲烷 、 氢气 、 三乙胺 、 甲胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 59.0h， 生成 N-[[(5S)-3-[3-氟-4-[4-(2-羟基乙酰基)-1-哌嗪基]苯基]-2-氧代-5-噁唑烷基]甲基]-乙酰胺
  参考文献：
  名称：

  Synthesis and Antibacterial Activity of U-100592 and U-100766, Two Oxazolidinone Antibacterial Agents for the Potential Treatment of Multidrug-Resistant Gram-Positive Bacterial Infections

  摘要：

  Bacterial resistance development has become a very serious clinical problem for many classes of antibiotics. The 3-aryl-2-oxazolidinones are a relatively new class of synthetic antibacterial agents, having a new mechanism of action which involves very early inhibition of bacterial protein synthesis. We have prepared two potent, synthetic oxazolidinones, U-100592 and U-100766, which are currently in clinical development for the treatment of serious multidrug-resistant Gram-positive bacterial infections caused by strains of staphylococci, streptococci, and enterococci. The in vitro and in vivo (po and iv) activities of U-100592 and U-100766 against representative strains are similar to those of vancomycin. U-100592 and U-100766 demonstrate potent in vitro activity against Mycobacterium tuberculosis. A novel and practical asymmetric synthesis of (5S)-(acetamidomethyl)-2-oxazolidinones has been developed and is employed for the synthesis of U-100592 and U-100766. This involves the reaction of N-lithioarylcarbamates with (R)-glycidyl butyrate, resulting in excellent yields and high enantiomeric purity of the intermediate (R)-5-(hydroxymethyl)-2-oxazolidinones,

  DOI：

  10.1021/jm9509556
• 作为产物：
  描述：

  N-[[(5S)-3-[3-氟-4-[4-(2-羟基乙酰基)-1-哌嗪基]苯基]-2-氧代-5-噁唑烷基]甲基]-乙酰胺 在 草酰氯 、 sodium hydride 、 碳酸氢钠 、 sodium carbonate 、 二甲基亚砜 、 三乙胺 、 亚硝基苯 、 D-脯氨酸 、 sodium iodide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 反应 28.0h， 生成 benzyl 4-[2-fluoro-4-[(5R)-5-(methylsulfonyloxymethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl]piperazine-1-carboxylate
  参考文献：
  名称：

  Short and practical enantioselective synthesis of linezolid and eperezolid via proline-catalyzed asymmetric α-aminooxylation

  摘要：

  An efficient enantioselective synthesis of the antibacterials, linezolid (U-100766), and eperezolid (U-100592) using D-proline-catalyzed asymmetric alpha-aminooxylation of aldehydes as the key step is described here. This is the first report on the enantioselective synthesis of linezolid and eperezolid using asymmetric catalysis. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2006.07.065

文献信息

• A short synthesis of oxazolidinone derivatives linezolid and eperezolid: A new class of antibacterials
  作者：Braj B. Lohray、Sundarababu Baskaran、B. Srinivasa Rao、B. Yadi Reddy、I. Nageswara Rao

  DOI：10.1016/s0040-4039(99)00893-x

  日期：1999.6

  Oxazolidinone derivatives such as Linezolid and Eperazolid, which are a new class of antibacterials, have been synthesized from 1,2,5,6-dianhydro-3,4-isopropylidine-D-mannitol in good yield.

  由1,2,5,6-二脱水-3,4-异丙基吡啶-D-甘露糖醇合成的新型抗菌剂恶唑烷酮衍生物（如Linezolid和Eperazolid）是高收率的。
• Discovery of a novel nitroimidazolyl–oxazolidinone hybrid with potent anti Gram-positive activity: Synthesis and antibacterial evaluation
  作者：Ali Khalaj、Maryam Nakhjiri、Amir Soheil Negahbani、Marjaneh Samadizadeh、Loghman Firoozpour、Saeed Rajabalian、Nasrin Samadi、Mohammad Ali Faramarzi、Neda Adibpour、Abbas Shafiee、Alireza Foroumadi

  DOI：10.1016/j.ejmech.2010.10.015

  日期：2011.1

  A number of linezolid analogues containing a nitroaryl-1,3,4-thiadiazole moiety, were prepared and evaluated as antibacterial agents against a panel of Gram-positive and Gram-negative bacteria. Among synthesized compounds, nitrofuran analogue 1b exhibited more potent inhibitory activity, with respect to other synthesized compounds and reference drug linezolid. The target compounds were also assessed for their cytotoxic activity against normal mouse fibroblast (NIH/3T3) cells using MTT assay. The results indicated that compound 1c exhibit potent antibacterial activity against Gram-positive bacteria at non-cytotoxic concentrations. (C) 2010 Elsevier Masson SAS. All rights reserved.
• Synthesis and Antibacterial Activity of U-100592 and U-100766, Two Oxazolidinone Antibacterial Agents for the Potential Treatment of Multidrug-Resistant Gram-Positive Bacterial Infections
  作者：Steven J. Brickner、Douglas K. Hutchinson、Michael R. Barbachyn、Peter R. Manninen、Debra A. Ulanowicz、Stuart A. Garmon、Kevin C. Grega、Susan K. Hendges、Dana S. Toops、Charles W. Ford、Gary E. Zurenko

  DOI：10.1021/jm9509556

  日期：1996.1.1

  Bacterial resistance development has become a very serious clinical problem for many classes of antibiotics. The 3-aryl-2-oxazolidinones are a relatively new class of synthetic antibacterial agents, having a new mechanism of action which involves very early inhibition of bacterial protein synthesis. We have prepared two potent, synthetic oxazolidinones, U-100592 and U-100766, which are currently in clinical development for the treatment of serious multidrug-resistant Gram-positive bacterial infections caused by strains of staphylococci, streptococci, and enterococci. The in vitro and in vivo (po and iv) activities of U-100592 and U-100766 against representative strains are similar to those of vancomycin. U-100592 and U-100766 demonstrate potent in vitro activity against Mycobacterium tuberculosis. A novel and practical asymmetric synthesis of (5S)-(acetamidomethyl)-2-oxazolidinones has been developed and is employed for the synthesis of U-100592 and U-100766. This involves the reaction of N-lithioarylcarbamates with (R)-glycidyl butyrate, resulting in excellent yields and high enantiomeric purity of the intermediate (R)-5-(hydroxymethyl)-2-oxazolidinones,
• Short and practical enantioselective synthesis of linezolid and eperezolid via proline-catalyzed asymmetric α-aminooxylation
  作者：Srinivasarao V. Narina、Arumugam Sudalai

  DOI：10.1016/j.tetlet.2006.07.065

  日期：2006.9

  An efficient enantioselective synthesis of the antibacterials, linezolid (U-100766), and eperezolid (U-100592) using D-proline-catalyzed asymmetric alpha-aminooxylation of aldehydes as the key step is described here. This is the first report on the enantioselective synthesis of linezolid and eperezolid using asymmetric catalysis. (c) 2006 Elsevier Ltd. All rights reserved.