methyl 8-benzyl-2-hydroxy-8-azabicyclo[3.2.1]oct-2-ene-3-carboxylate | 208037-75-6

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: methyl 8-benzyl-2-hydroxy-8-azabicyclo[3.2.1]oct-2-ene-3-carboxylate
• 英文别名: methyl (1R,5S)-8-benzyl-2-hydroxy-8-azabicyclo[3.2.1]oct-2-ene-3-carboxylate
• CAS: 208037-75-6
• 化学式: C₁₆H₁₉NO₃
• 分子量: 273.332
• InChiKey: JSIAVLBZENQBLN-GXTWGEPZSA-N

物化性质

• 沸点：
  408.2±45.0 °C(Predicted)
• 密度：
  1.264±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 8-benzyl-2-hydroxy-8-azabicyclo[3.2.1]oct-2-ene-3-carboxylate 在 palladium on activated charcoal 氢气 、 sodium hydride 、 sodium carbonate 、 sodium iodide 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 水 、 甲苯 为溶剂， 反应 36.5h， 生成 11-O-tert-butyl 3-O-ethyl (1R,2S,6S,8S)-5-oxa-4,11-diazatricyclo[6.2.1.02,6]undec-3-ene-3,11-dicarboxylate
  参考文献：
  名称：

  Enantiospecific Synthesis of Natural (−)-Cocaine and Unnatural (+)-Cocaine from d- and l-Glutamic Acid

  摘要：

  Natural (-)-cocaine and unnatural (+)-cocaine have been synthesized enantiospecifically from D- and L-glutamic acid, respectively. The axial-equatorial substitutents were introduced by a stereo- and regiospecific dipolar cycloaddition to the corresponding (LR,5S)- and (1S,5R)-N-BOC-nortropenes with (ethoxycarbonyl)formonitrile N-oxide. A sequence of subsequent stereochemically controlled transformations converted the fused isoxazoline to the requisite P-hydroxy ester. Synthesis of the key intermediate N-BOC-nortropenes involved construction of the 8-azabicyclo[3.2.1]octane framework by Dieckmann condensation of cis-5-substituted D-and L-proline esters. For comparison, (1R,SS)-N-BOC-nortropene also was derived by degradation from natural cocaine. The cis-5-substituted D-and L-proline esters were obtained by sulfide contraction and subsequent catalytic hydrogenation to induce stereospecifically the C-5 stereochemistry from D-and L-thiopyroglutamate, which in turn were prepared from D-and L-glutamic acids, respectively.

  DOI：

  10.1021/jo980153t
• 作为产物：
  描述：

  3-[(2S,5R)-5-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidin-2-yl]propanoic acid 在 双(三甲基硅烷基)氨基钾 、 potassium carbonate 、 乙酰氯 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 29.0h， 生成 methyl 8-benzyl-2-hydroxy-8-azabicyclo[3.2.1]oct-2-ene-3-carboxylate
  参考文献：
  名称：

  Enantiospecific Synthesis of Natural (−)-Cocaine and Unnatural (+)-Cocaine from d- and l-Glutamic Acid

  摘要：

  Natural (-)-cocaine and unnatural (+)-cocaine have been synthesized enantiospecifically from D- and L-glutamic acid, respectively. The axial-equatorial substitutents were introduced by a stereo- and regiospecific dipolar cycloaddition to the corresponding (LR,5S)- and (1S,5R)-N-BOC-nortropenes with (ethoxycarbonyl)formonitrile N-oxide. A sequence of subsequent stereochemically controlled transformations converted the fused isoxazoline to the requisite P-hydroxy ester. Synthesis of the key intermediate N-BOC-nortropenes involved construction of the 8-azabicyclo[3.2.1]octane framework by Dieckmann condensation of cis-5-substituted D-and L-proline esters. For comparison, (1R,SS)-N-BOC-nortropene also was derived by degradation from natural cocaine. The cis-5-substituted D-and L-proline esters were obtained by sulfide contraction and subsequent catalytic hydrogenation to induce stereospecifically the C-5 stereochemistry from D-and L-thiopyroglutamate, which in turn were prepared from D-and L-glutamic acids, respectively.

  DOI：

  10.1021/jo980153t

文献信息

• [EN] DIAMINOCYCLOHEXANE COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS DE DIAMINOCYCLOHEXANE ET LEURS UTILISATIONS
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2013012827A1

  公开（公告）日：2013-01-24

  The present invention provides compounds of Formula (I), or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein all of the variables are as defined herein. These compounds are agonists, partial agonists and modulators of the NPY Y4 receptor and may be used for the treatment and prophylaxis of various diseases and conditions.

  本发明提供了化合物的结构式（I），或其立体异构体，或其药学上可接受的盐，其中所有变量均如本文所定义。这些化合物是NPY Y4受体的激动剂、部分激动剂和调节剂，可用于治疗和预防各种疾病和病况。