methyl 2-oxotricyclo[3.3.1.1^3,7]decane-1-carboxylate | 40933-58-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 2-oxotricyclo[3.3.1.1^3,7]decane-1-carboxylate
• 英文别名: methyl 2-oxoadamantane-1-carboxylate；2-Keto-1-adamantancarbonsaeuremethylester；2-Oxoadamantan-1-carbonsaeure-methylester；Methyl-2-oxoadamantan-1-carboxylat；2-Oxoadamantane-1-carboxylic acid, methyl ester
• CAS: 40933-58-2
• 化学式: C₁₂H₁₆O₃
• 分子量: 208.257
• InChiKey: QAZFHGFVYPQQSU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 2-oxotricyclo[3.3.1.1^3,7]decane-1-carboxylate 在 盐酸羟胺 、 sodium acetate trihydrate 、 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 11.5h， 以72%的产率得到2-(hydroxyimino)adamantane-1-carboxylic acid
  参考文献：
  名称：

  邻苯二甲酰亚胺活化的金刚烷氨基酸的光脱羧

  摘要：

  合成了由邻苯二甲酰亚胺（即 3-6）活化的金刚烷 α-、β-和 δ-氨基酸，并研究了它们的光化学反应性。氨基酸衍生物 3-6 经历了光诱导电子转移 (PET) 和脱羧反应序列，最有可能是通过三重激发态。β-氨基酸衍生物的脱羧通过环化反应成功，提供了具有潜在生物学意义的复杂多环分子。光诱导脱羧产生的金刚烷基自由基可以被烯烃或氧捕获，分别传递加合物或醇。在丙酮敏化条件下（量子产率，Φ = 0.02-0.5），光脱羧过程比直接激发更有效，并且反应性取决于衍生物的电子供体（羧酸盐）和受体（三重激发态的邻苯二甲酰亚胺）之间的链长（分子内距离）。不同自由基的形成，即 1- 或 2-金刚烷基中间体，可能不会影响脱羧的整体速率本报告提供了对光脱羧的更好理解和分子系统的合理设计以进行光诱导脱羧和环化反应。

  DOI：

  10.1002/ejoc.201600491
• 作为产物：
  描述：

  4-(epoxymethylene)protoadamantane 在 Jones reagent 、 氯化亚砜 、 硫酸 作用下， 以 水 为溶剂， 反应 3.0h， 生成 methyl 2-oxotricyclo[3.3.1.1^3,7]decane-1-carboxylate
  参考文献：
  名称：

  Anti-allodynic effect of 2-(aminomethyl)adamantane-1-carboxylic acid in a rat model of neuropathic pain: A mechanism dependent on CaV2.2 channel inhibition

  摘要：

  Neuropathic pain is a serious physical disabling condition resulting from lesion or dysfunction of the peripheral sensory nervous system. Despite the fact that the mechanisms underlying neuropathic pain are poorly understood, the involvement of voltage-gated calcium (Ca-V) channels in its pathophysiology has justified the use of drugs that bind the Ca-V channel alpha(2)delta auxiliary subunit, such as gabapentin (GBP), to attain analgesic and anti-allodynic effects in models involving neuronal sensitization and nerve injury. GBP binding to alpha(2)delta inhibits nerve injury-induced trafficking of the alpha(1) pore forming subunits of Ca-V channels, particularly of the N-type, from the cytoplasm to the plasma membrane of pre-synaptic terminals in dorsal root ganglion neurons and dorsal horn spinal neurons. In the search for alternative forms of treatment, in this study we describe the synthesis and pharmacological profile of a GABA derivative, 2-aminoadamantane-1-carboxylic acid (GZ4), which displays a close structure-activity relationship with GBP. Behavioral assessment using von Frey filament stimuli showed that GZ4 treatment reverted mechanical allodynia/hyperalgesia in an animal model of spinal nerve ligation-induced neuropathic pain. In addition, using the patch clamp technique we show that GZ4 treatment significantly decreased whole-cell currents through N-type Ca-V channels heterologously expressed in HEK-293 cells. Interestingly, the behavioral and electrophysiological time course of GZ4 actions reflects that its mechanism of action is similar but not identical to that of GBP. While GBP actions require at least 24 h and imply uptake of the drug, which suggests that the drug acts mainly intracellularly affecting channels trafficking to the plasma membrane, the faster time course (1-3 h) of GZ4 effects suggests also a direct inhibition of Ca2+ currents acting on cell surface channels. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.02.006

文献信息

• 3,7-disubstituted bicyclo[3.3.1]nonanes—III
  作者：J.A. Peters、J.M. Van Der Toorn、H. Van Bekkum

  DOI：10.1016/0040-4020(75)80226-2

  日期：1975.1

  The conformation of bicyclo[3.3.1]nonane-3α,7α-dicarboxylic acid and its dimethyl ester has been studied by comparing 1H NMR and 13C NMR spectra of these compounds with those of some model 3,7-disubstituted bicyclo[3.3.1]nonanes, fixed in a single conformation by the use of adamantane as an integrated holding group or by means of suitable substitution. It is shown that the dicarboxylic acid and its

  通过比较这些化合物的1 H NMR和13 C NMR谱图与某些模型的3,7-二取代双环[3.3]谱图，研究了双环[3.3.1]壬烷-3α，7α-二羧酸及其二甲酯的构象。.1]壬烷，通过使用金刚烷作为一个整体的保留基团或通过适当的取代固定在一个构象中。结果表明，二羧酸及其二甲基酯主要以两个快速相互转化（相同）的椅形结构存在，并且环明显扁平。双人船构型的人口似乎很少。
• Design and synthesis of 1,2-annulated adamantane piperidines with anti-influenza virus activity
  作者：Grigoris Zoidis、Nicolas Kolocouris、Lieve Naesens、Erik De Clercq

  DOI：10.1016/j.bmc.2009.01.009

  日期：2009.2

  1-2 Annulated adamantane piperidines 4, 6, 16, 17, 19, 23 and 25 were synthesized and evaluated for anti-influenza A virus activity. The stereoelectronic requirements for optimal antiviral potency were investigated. Piperidine 23 proved to be the most active of the compounds tested against influenza A virus, being 3.5-fold more active than amantadine, equipotent to rimantadine and 15-fold more potent than ribavirin. It is noteworthy that piperidine 23 displayed one of the highest selectivity indexes (SI>732) among aminoadamantanes or other cage structure amines tested till now. (c) 2009 Elsevier Ltd. All rights reserved.
• MOISEEV I. K.; MRATXUZINA T. A.; BELYAEV P. G.; NAFIKOV G. F.; TKACHEVA E+, ZH. ORGAN. XIMII, 1979, 15, HO 11, 2341-2344
  作者：MOISEEV I. K.、 MRATXUZINA T. A.、 BELYAEV P. G.、 NAFIKOV G. F.、 TKACHEVA E+

  DOI：——

  日期：——
• STETTER H.; LOEHR V.; SIMOS A., J. LIEBIGS ANN. CHEM. <JLAC-BF>, 1977, NO 6, 999-1004
  作者：STETTER H.、 LOEHR V.、 SIMOS A.

  DOI：——

  日期：——
• Anti-allodynic effect of 2-(aminomethyl)adamantane-1-carboxylic acid in a rat model of neuropathic pain: A mechanism dependent on CaV2.2 channel inhibition
  作者：Grigoris Zoidis、Alejandro Sandoval、Jorge Baruch Pineda-Farias、Vinicio Granados-Soto、Ricardo Felix

  DOI：10.1016/j.bmc.2014.02.006

  日期：2014.3

  Neuropathic pain is a serious physical disabling condition resulting from lesion or dysfunction of the peripheral sensory nervous system. Despite the fact that the mechanisms underlying neuropathic pain are poorly understood, the involvement of voltage-gated calcium (Ca-V) channels in its pathophysiology has justified the use of drugs that bind the Ca-V channel alpha(2)delta auxiliary subunit, such as gabapentin (GBP), to attain analgesic and anti-allodynic effects in models involving neuronal sensitization and nerve injury. GBP binding to alpha(2)delta inhibits nerve injury-induced trafficking of the alpha(1) pore forming subunits of Ca-V channels, particularly of the N-type, from the cytoplasm to the plasma membrane of pre-synaptic terminals in dorsal root ganglion neurons and dorsal horn spinal neurons. In the search for alternative forms of treatment, in this study we describe the synthesis and pharmacological profile of a GABA derivative, 2-aminoadamantane-1-carboxylic acid (GZ4), which displays a close structure-activity relationship with GBP. Behavioral assessment using von Frey filament stimuli showed that GZ4 treatment reverted mechanical allodynia/hyperalgesia in an animal model of spinal nerve ligation-induced neuropathic pain. In addition, using the patch clamp technique we show that GZ4 treatment significantly decreased whole-cell currents through N-type Ca-V channels heterologously expressed in HEK-293 cells. Interestingly, the behavioral and electrophysiological time course of GZ4 actions reflects that its mechanism of action is similar but not identical to that of GBP. While GBP actions require at least 24 h and imply uptake of the drug, which suggests that the drug acts mainly intracellularly affecting channels trafficking to the plasma membrane, the faster time course (1-3 h) of GZ4 effects suggests also a direct inhibition of Ca2+ currents acting on cell surface channels. (C) 2014 Elsevier Ltd. All rights reserved.