2,2,5,5-tetramethylpyrrolidine-1-oxyl-3-carboxylic acid methyl ester | 2154-33-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 2,2,5,5-tetramethylpyrrolidine-1-oxyl-3-carboxylic acid methyl ester
• 英文别名: 1-Pyrrolidinyloxy, 3-(methoxycarbonyl)-2,2,5,5-tetramethyl-
• CAS: 2154-33-8
• 化学式: C₁₀H₂₀NO₃
• 分子量: 202.274
• InChiKey: MZCJOXPCRWIKNU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  30.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,2,5,5-tetramethylpyrrolidine-1-oxyl-3-carboxylic acid methyl ester 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 以83%的产率得到3-羧基-PROXYL
  参考文献：
  名称：

  Facile Synthesis of 3-Methoxycarbonyl-2,2,5,5-tetra-methylpyrrolidine-1-oxyl and Derivatives

  摘要：

  We have achieved an efficient alternative synthesis of blood-brain-barrier permeable nitroxyl radicals 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (1a) and 3-ethoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (1b), which affords la and 1b in 65% isolated yields by four steps from 2,2,6.6-tetramethyl-4-piperidone (2), respectively. This protocol is applicable to the synthesis of 3-isopropoxy-2,2,5,5-tetramethylpyrrolidine-1-oxyl (1c) and 3-carbonyl-2,2,5,5-tetramethylpyrro-lidine-1-oxyl (6).

  DOI：

  10.3987/com-09-11861
• 作为产物：
  描述：

  1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine 在 二乙烯三胺五醋酸 、 sodium chloride 、 xanthine oxidase 、 黄嘌呤 作用下， 生成 2,2,5,5-tetramethylpyrrolidine-1-oxyl-3-carboxylic acid methyl ester
  参考文献：
  名称：

  EPR detection of cellular and mitochondrial superoxide using cyclic hydroxylamines

  摘要：

  Superoxide (O(2)(center dot-)) has been implicated in the pathogenesis of many human diseases, but detection of the O(2)(center dot-) radicals in biological systems is limited due to inefficiency of O(2)(center dot-) spin trapping and lack of site-specific information. This work studied production of extracellular, intracellular and mitochondrial O(2)(center dot-) in neutrophils, cultured endothelial cells and isolated mitochondria using a new set of cationic, anionic and neutral hydroxylamine spin probes with various lipophilicity and cell permeability. Cyclic hydroxylamines rapidly react with O(2)(center dot-), producing stable nitroxides and allowing site-specific O(2)(center dot-) detection in intracellular, extracellular and mitochondrial compartments. Negatively charged 1-hydroxy-4-phosphono-oxy-2,2,6, 6-tetramethylpiperidine (PP-H) and positively charged 1-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl-trimethylammonium (CAT1-H) detected only extramitochondrial O(2)(center dot-). Inhibition of EPR signal by SOD2 over-expression showed that mitochondria targeted mitoTEMPO-H detected intramitochondrial O(2)(center dot-) both in isolated mitochondria and intact cells. Both 1-hydroxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine (CP-H) and 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CM-H) detected an increase in cytoplasm O(2)(center dot-) stimulated by PMA, but only CM-H and mitoTEMPO-H showed an increase in rotenone-induced mitochondrial O(2)(center dot-). These data show that a new set of hydroxylamine spin probes provide unique information about site-specific production of the O(2)(center dot-) radical in extracellular or intracellular compartments, cytoplasm or mitochondria.

  DOI：

  10.3109/10715762.2010.540242
• 作为试剂：
  描述：

  1-(4-氯苯基)乙醇 在 2,2,5,5-tetramethylpyrrolidine-1-oxyl-3-carboxylic acid methyl ester 作用下， 以95%的产率得到对氯苯乙酮
  参考文献：
  名称：

  PROCESSES FOR PRODUCING OXIDE WITH HIGHER OXIDATION THAN ALCOHOL

  摘要：

  公开号：

  EP1178026B1

文献信息

• Nitroxyl compound and diagnostic media based thereon useful for
  申请人：Schering Aktiengesellschaft

  公开号：US04845090A1

  公开（公告）日：1989-07-04

  Diagnostic media suitable for NMR diagnoses contain compounds of Formula I ##STR1## wherein is a single bond or a double bond, X is the grouping --(CH.sub.2).sub.n -- or, if is a single bond, also the grouping --NHCO(CH.sub.2).sub.n -- wherein n means 0 to 4, m means the numbers 0, 1, or 2, R.sub.1 is an alkyl residue substituted by hydroxy groups, acyloxy groups and/or alkylidenedioxy groups, R.sub.2 has the same meanings as R.sub.1 or is a hydrogen atom or an alkyl residue, R.sub.3 and R.sub.4 are alkyl residues, and R.sub.5 and R.sub.6 are alkyl residues optionally substituted by hydroxy groups.

  适用于核磁共振诊断的诊断介质包含Formula I的化合物，其中是单键或双键，X是基团--(CH.sub.2).sub.n --或者，如果是单键，也是基团--NHCO(CH.sub.2).sub.n --其中n表示0到4，m表示数字0、1或2，R.sub.1是被羟基、酰氧基和/或烷基二氧基基团取代的烷基残基，R.sub.2具有与R.sub.1相同的含义，或者是氢原子或烷基残基，R.sub.3和R.sub.4是烷基残基，R.sub.5和R.sub.6是烷基残基，可以选择地被羟基取代。
• A Short Way to Esters of 1-Oxyl-2,2,5,5-Tetramethylpyrrolidine-3-carboxylic Acid by Favorski Rearrangement
  作者：Gašper Marc、Slavko Pečar

  DOI：10.1080/00397919508012662

  日期：1995.4

  Abstract The reaction of 3-bromo-4-oxo-l-oxyl-2,2,6,6-tetramethylpiperidine (1) with a solid sodium, alkoxide of primary or secondary alcohol provides a short way to prepare ester of 3-carboxy-1-oxyl-2,2,5,5-tetramethylpyrrolidine where the ring contraction from six (1) to five (6a-f) in a Favorski rearrangement occurs.

  摘要 3-bromo-4-oxo-l-oxyl-2,2,6,6-四甲基哌啶 (1) 与固体伯醇或仲醇钠、醇盐的反应为制备 3-羧基酯提供了一条捷径。 -1-oxyl-2,2,5,5-四甲基吡咯烷，在 Favorski 重排中环从六 (1) 收缩到五 (6a-f)。
• Acyl-Protected Hydroxylamines as Spin Label Generators for EPR Brain Imaging
  作者：Alexander T. Yordanov、Ken-ichi Yamada、Murali C. Krishna、Angelo Russo、John Yoo、Sean English、James B. Mitchell、Martin W. Brechbiel

  DOI：10.1021/jm0105169

  日期：2002.5.1

  In a search for novel electron paramagnetic resonance (EPR) brain imaging agents, we have designed and synthesized the acyl-protected hydroxylamines 1-acetoxy-4-methoxycarbonyl-2,2,6,6-tetramethylpiperidine (AMCPe), 1-acetoxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (AMCPy), and 1-acetoxy-3-(acetoxymethoxy)carbonyl-2,2,5,5-tetramethylpyrrolidine (DACPy), in which both the ring size and the number of ester functions were varied. In all of them, the nitroxide was first reduced and the resultant hydroxylamine was then protected with an acetyl group. These compounds are lipophilic, which is a major prerequisite for blood-brain barrier penetration. Once in the brain, esterases and oxidants quickly convert these derivatives into ionic, water-soluble radicals and thus EPR detectable species that then reside in the central nervous system for periods of time sufficient for detection and imaging. The biological relevancy of these new compounds in mice has been assessed, and their biodistribution patterns have been compared. The five-membered ring derivative AMCPy emerged as a potent EPR brain imaging agent while the other two derivatives, AMCPe and DACPy, were quite ineffective.
• Facile Synthesis of 3-Methoxycarbonyl-2,2,5,5-tetra-methylpyrrolidine-1-oxyl and Derivatives
  作者：Bunpei Hatano、Hiroki Araya、Yutaka Yoshimura、Haruna Sato、Tomohiro Ito、Tateaki Ogata、Tatsuro Kijima

  DOI：10.3987/com-09-11861

  日期：——

  We have achieved an efficient alternative synthesis of blood-brain-barrier permeable nitroxyl radicals 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (1a) and 3-ethoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (1b), which affords la and 1b in 65% isolated yields by four steps from 2,2,6.6-tetramethyl-4-piperidone (2), respectively. This protocol is applicable to the synthesis of 3-isopropoxy-2,2,5,5-tetramethylpyrrolidine-1-oxyl (1c) and 3-carbonyl-2,2,5,5-tetramethylpyrro-lidine-1-oxyl (6).
• EPR detection of cellular and mitochondrial superoxide using cyclic hydroxylamines
  作者：Sergey I. Dikalov、Igor A. Kirilyuk、Maxim Voinov、Igor A. Grigor'ev

  DOI：10.3109/10715762.2010.540242

  日期：2011.4

  Superoxide (O(2)(center dot-)) has been implicated in the pathogenesis of many human diseases, but detection of the O(2)(center dot-) radicals in biological systems is limited due to inefficiency of O(2)(center dot-) spin trapping and lack of site-specific information. This work studied production of extracellular, intracellular and mitochondrial O(2)(center dot-) in neutrophils, cultured endothelial cells and isolated mitochondria using a new set of cationic, anionic and neutral hydroxylamine spin probes with various lipophilicity and cell permeability. Cyclic hydroxylamines rapidly react with O(2)(center dot-), producing stable nitroxides and allowing site-specific O(2)(center dot-) detection in intracellular, extracellular and mitochondrial compartments. Negatively charged 1-hydroxy-4-phosphono-oxy-2,2,6, 6-tetramethylpiperidine (PP-H) and positively charged 1-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl-trimethylammonium (CAT1-H) detected only extramitochondrial O(2)(center dot-). Inhibition of EPR signal by SOD2 over-expression showed that mitochondria targeted mitoTEMPO-H detected intramitochondrial O(2)(center dot-) both in isolated mitochondria and intact cells. Both 1-hydroxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine (CP-H) and 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CM-H) detected an increase in cytoplasm O(2)(center dot-) stimulated by PMA, but only CM-H and mitoTEMPO-H showed an increase in rotenone-induced mitochondrial O(2)(center dot-). These data show that a new set of hydroxylamine spin probes provide unique information about site-specific production of the O(2)(center dot-) radical in extracellular or intracellular compartments, cytoplasm or mitochondria.