(R)-(+)-2-carbomethoxy-3-tropinone | 85506-18-9

• 物质功能分类: 医药中间体
• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: (R)-(+)-2-carbomethoxy-3-tropinone
• 英文别名: Ecgonone methyl ester；methyl (1R,2R,5S)-8-methyl-3-oxo-8-azabicyclo[3.2.1]octane-2-carboxylate
• CAS: 85506-18-9
• 化学式: C₁₀H₁₅NO₃
• 分子量: 197.234
• InChiKey: WXEMSGQRTGSYOG-LKEWCRSYSA-N

物化性质

• 沸点：
  294.1±35.0 °C(Predicted)
• 密度：
  1.173±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-(+)-2-carbomethoxy-3-tropinone 在 吡啶 、 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 90.91h， 生成 脱水芽子碱甲基酯甲磺酸盐
  参考文献：
  名称：

  COMPOUNDS AND METHODS FOR PREVENTING OR TREATING SENSORY HAIR CELL DEATH

  摘要：

  本文揭示了一些化合物和包含这些化合物的药物组合物，用于预防或治疗听力损失。本文描述的化合物和药物组合物可以预防或治疗毛细胞死亡。此外，本文描述的化合物和药物组合物可以保护接受氨基糖苷类抗生素的个体免受肾脏损伤。还公开了使用这些化合物的方法，单独或与其他治疗剂联合使用。

  公开号：

  US20160229869A1
• 作为产物：
  描述：

  diisopropyl 8-benzyl-3-oxo-8-azabicyclo[3.2.1]-octane-2,4-dicarboxylate 在 palladium on activated charcoal porcine liver esterase 、 聚合甲醛 、 甲酸 、 phosphate buffer 、 氢气 、 sodium 作用下， 以 甲醇 、 水 为溶剂， 反应 26.0h， 生成 (R)-(+)-2-carbomethoxy-3-tropinone
  参考文献：
  名称：

  Novel asymmetric dealkoxycarbonylation of 3-oxo-8-azabicyclo[3.2.1]-octane-2,4-dicar☐ylates using porcine liver esterase: A new route to (−)-anhydroecgonine methyl ester

  摘要：

  The porcine liver esterase-catalyzed dealkoxycarbonylation of 8-benzyl-3-oxo-8-azabicyclo[3.2.1]octane-2,4-dicarboxylates (4) was found to give high enantiomeric excess of the desymmetrized keto ester (5). This novel dealkoxylcarbonylation opened a new route to the asymmetric synthesis of (1R)cocaine related radiopharmaceuticals such as (1R)-beta-CIT, for diagnosis of Parkinson's disease. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(99)00976-4

文献信息

• Chemical Targeting of Voltage Sensitive Dyes to Specific Cells and Molecules in the Brain
  作者：Tomas Fiala、Jihang Wang、Matthew Dunn、Peter Šebej、Se Joon Choi、Ekeoma C. Nwadibia、Eva Fialova、Diana M. Martinez、Claire E. Cheetham、Keri J. Fogle、Michael J. Palladino、Zachary Freyberg、David Sulzer、Dalibor Sames

  DOI：10.1021/jacs.0c00861

  日期：2020.5.20

  dense dopaminergic axons in the mouse striatum and sparse noradrenergic axons in the mouse cortex in acute brain slices. PFQX in conjunction with ligand-directed acyl imidazole chemistry enables covalent labeling of AMPA-type glutamate receptors in the same brain regions. Probe variants bearing either a classical electrochromic ANEP dye or state-of-the-art VoltageFluor-type dye respond to membrane potential

  电压敏感荧光染料 (VSD) 是探测神经元和其他可兴奋细胞中信号转导的重要工具。然而，由于在脑组织或活体动物中缺乏细胞特异性靶向方法，这些高度亲脂性传感器的影响受到限制。我们通过引入非遗传分子平台来解决这一关键挑战，用于大脑中合成 VSD 的细胞和分子特异性靶向。我们采用葡聚糖聚合物颗粒，通过动态封装和高亲和力配体克服 VSD 固有的亲脂性，仅在生理表达水平上利用神经传递机制的天然成分将构建体靶向特定神经元细胞。二氯烷，一种单胺转运蛋白配体，能够靶向小鼠纹状体中密集的多巴胺能轴突和急性脑切片中小鼠皮层中稀疏的去甲肾上腺素能轴突。PFQX 与配体导向的酰基咪唑化学相结合，能够在相同的大脑区域中对 AMPA 型谷氨酸受体进行共价标记。带有经典电致变色 ANEP 染料或最先进的电压氟型染料的探针变体以与母体染料类似的方式响应膜电位变化，如全细胞贴片记录所示。我们用单光子和双光子荧光显微镜证明了用
• Design and synthesis of a cocaine-diamide hapten for vaccine development
  作者：Mitsuya Sakurai、Peter Wirsching、Kim D. Janda

  DOI：10.1016/0040-4039(96)01170-7

  日期：1996.7

  A cocaine-diamide hapten was designed in an effort to obtain a potent, long-lasting anti-cocaine immune response for the treatment of cocaine abuse. The analogue incorporated an amido linker functionality in place of the carbomethoxy group at C-2 and a benzoylamino replacement of the benzoyloxy group at C-3 of the cocaine framework. Compound 3 was synthesized in 6 chemical steps starting from (+)-

  设计可卡因-二酰胺半抗原的目的是为了获得有效，持久的抗可卡因免疫反应，以治疗可卡因滥用。该类似物在C-2的可卡因骨架中并入了酰胺基连接基官能团，取代了C-2处的碳甲氧基，并取代了C-3处的苯甲酰氧基的苯甲酰氨基取代。化合物3是从（+）-2-羰甲氧基-3-肌注酮开始的6个化学步骤合成的。
• A Second-Generation ^99mTechnetium Single Photon Emission Computed Tomography Agent That Provides in Vivo Images of the Dopamine Transporter in Primate Brain
  作者：Peter C. Meltzer、Paul Blundell、Thomas Zona、Lihua Yang、Hong Huang、Ali A. Bonab、Eli Livni、Alan Fischman、Bertha K. Madras

  DOI：10.1021/jm0301484

  日期：2003.7.1

  The dopamine transporter (DAT), located presynaptically on dopamine neurons, provides a marker for Parkinson's disease (Pd) and attention deficit hyperactivity disorder (ADHD). In ADHD, DAT density levels are elevated, while in Pd these levels are depleted. The depletion of DAT levels also corresponds with the loss of dopamine. We now describe the design, synthesis, biology, and SPECT imaging in nonhuman primates of second-generation (99m)technetium-based tropane ligands that bind potently and selectively to the DAT. We demonstrate that improved selectivity and biological stability allows sufficient agent to enter the brain and label the DAT in vivo to provide a quantitative measure of DAT density in nonhuman primates. We introduce FLUORATEC (N-[(2-((3'-N-propyl-(1"R)-3"alpha-(4-fluorophenyl)tropane-2"beta-1-propanoyl)(2-mercaptoethyl)amino)acetyl)-2-aminoethanethiolato]technetium(V) oxide), a DAT imaging agent that has emerged from these studies and is now in phase 1 clinical trials in the U.S.
• Synthesis and Monoamine Transporter Binding Properties of 2,3-Diaryltropanes
  作者：Sharadsrikar V. Kotturi、Songchun Jiang、An-Chih Chang、Philip Abraham、Hernán A. Navarro、Michael J. Kuhar、F. Ivy Carroll

  DOI：10.1021/jm0582423

  日期：2005.11.1

  Synthetic procedures were developed for the synthesis of 2 beta,3 beta- and 2 alpha,3 alpha-diaryltropanes. These compounds are analogues of the 3-aryltropane-2 beta-carboxylic acid methyl ester class of monoamine uptake inhibitors, where the 2 beta-carbomethoxy group has been replaced by an aryl group. The compounds were evaluated for inhibition of radioligand binding at the dopamine, norepinephrine, and serotonin transporters (DAT, NET, and 5-HTT, respectively). The results showed that the replacement of the 2 beta-carbomethoxy group in the 3-aryltropane class with a 2 beta-aryl group led to compounds possessing very similar monoamine transporter binding properties. However, the 2 beta,3 beta-diaryltropanes tended to be more potent at the DAT and more selective for the DAT relative to the NET and 5-HTT. One of the most interesting compounds was 3 beta-(4-methylphenyl)-2 beta-(4-methylphenyl)tropane (3d), which showed an IC50 of 1.23 nM at the DAT with 289- and 185-fold selectivity for the DAT relative to the NET and 5-HTT. The 2 alpha,3 alpha-diaryltropanes were much less potent at all three transporters than 2 beta,3 beta-diaryltropanes.
• Synthesis of the 2β,3α- and 2β,3β-isomers of 3-(p-substituted phenyl)tropane-2-carboxylic acid methyl esters
  作者：Kathryn I. Keverline、Philip Abraham、Anita H. Lewin、F.Ivy Carroll

  DOI：10.1016/0040-4039(95)00477-t

  日期：1995.5

  The synthesis of 3-(p-substituted phenyl)trop-2-ene-2-carboxylic acid methyl ester 8 and its reduction with samarium iodide provide a new synthesis of 3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acid methyl ester (2) and, in addition, give the first synthesis of the 2 beta,3 alpha-diastereoisomer 4.