S-(-)-9-fluoro-2,3-dihydro-3-methyl-10-<1-(4-formylpiperazinyl)>-7-oxo-7H-pyrido-<1,2,3-de><1,4>benzoxazine-6-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: S-(-)-9-fluoro-2,3-dihydro-3-methyl-10-<1-(4-formylpiperazinyl)>-7-oxo-7H-pyrido-<1,2,3-de><1,4>benzoxazine-6-carboxylic acid
• 英文别名: (2S)-7-fluoro-6-(4-formylpiperazin-1-yl)-2-methyl-10-oxo-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5(13),6,8,11-tetraene-11-carboxylic acid
• 化学式: C₁₈H₁₈FN₃O₅
• 分子量: 375.356
• InChiKey: CXHQIMOGKMERDN-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  90.4
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  左氧氟沙星 在 copper(l) iodide 、 2,2,6,6-四甲基哌啶氧化物 、 氧气 作用下， 以 二甲基亚砜 为溶剂， 反应 16.0h， 以8%的产率得到S-(-)-9-fluoro-2,3-dihydro-3-methyl-10-<1-(4-formylpiperazinyl)>-7-oxo-7H-pyrido-<1,2,3-de><1,4>benzoxazine-6-carboxylic acid
  参考文献：
  名称：

  Complementation of Biotransformations with Chemical C–H Oxidation: Copper-Catalyzed Oxidation of Tertiary Amines in Complex Pharmaceuticals

  摘要：

  The isolation, quantitation, and characterization of drug metabolites in biological fluids remain challenging. Rapid access to oxidized drugs could facilitate metabolite identification and enable early pharmacology and toxicity studies. Herein, we compared biotransformations to classical and new chemical C-H oxidation methods using oxcarbazepine, naproxen, and an early compound hit (phthalazine 1). These studies illustrated the low preparative efficacy of biotransformations and the inability of chemical methods to oxidize complex pharmaceuticals. We also disclose an aerobic catalytic protocole (CuI/air) to oxidize tertiary amines and benzylic CH's in drugs. The reaction tolerates a broad range of functionalities and displays a high level of chemoselectivity, which is not generally explained by the strength of the C-H bonds but by the individual structural chemotype. This study represents a first step toward establishing a chemical toolkit (chemotransformations) that can selectively oxidize C-H bonds in complex pharmaceuticals and rapidly deliver drug metabolites.

  DOI：

  10.1021/ja405471h

文献信息

• Complementation of Biotransformations with Chemical C–H Oxidation: Copper-Catalyzed Oxidation of Tertiary Amines in Complex Pharmaceuticals
  作者：Julien Genovino、Stephan Lütz、Dalibor Sames、B. Barry Touré

  DOI：10.1021/ja405471h

  日期：2013.8.21

  The isolation, quantitation, and characterization of drug metabolites in biological fluids remain challenging. Rapid access to oxidized drugs could facilitate metabolite identification and enable early pharmacology and toxicity studies. Herein, we compared biotransformations to classical and new chemical C-H oxidation methods using oxcarbazepine, naproxen, and an early compound hit (phthalazine 1). These studies illustrated the low preparative efficacy of biotransformations and the inability of chemical methods to oxidize complex pharmaceuticals. We also disclose an aerobic catalytic protocole (CuI/air) to oxidize tertiary amines and benzylic CH's in drugs. The reaction tolerates a broad range of functionalities and displays a high level of chemoselectivity, which is not generally explained by the strength of the C-H bonds but by the individual structural chemotype. This study represents a first step toward establishing a chemical toolkit (chemotransformations) that can selectively oxidize C-H bonds in complex pharmaceuticals and rapidly deliver drug metabolites.