cis-N-[(2,2,2-trichloroethoxy)carbonyl]-2,6-diphenethyl piperidin-4-one | 1174132-07-0

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: cis-N-[(2,2,2-trichloroethoxy)carbonyl]-2,6-diphenethyl piperidin-4-one
• 英文别名: 2,2,2-trichloroethyl (2R,6S)-4-oxo-2,6-bis(2-phenylethyl)piperidine-1-carboxylate
• CAS: 1174132-07-0
• 化学式: C₂₄H₂₆Cl₃NO₃
• 分子量: 482.834
• InChiKey: FIWSFRDHVIULGW-OYRHEFFESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  磷酰基乙酸三乙酯 、 cis-N-[(2,2,2-trichloroethoxy)carbonyl]-2,6-diphenethyl piperidin-4-one 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 4.5h， 以95%的产率得到{cis-N-[(2,2,2-trichloroethoxy)carbonyl]-2,6-diphenethylpiperidin-4-ylidene}acetic acid ethyl ester
  参考文献：
  名称：

  Stereocontrolled Synthesis and Pharmacological Evaluation ofcis-2,6-Diphenethyl-1-azabicyclo[2.2.2]octanes as Lobelane Analogues

  摘要：

  An efficient and highly stereocontrolled approach for the synthesis of the quinuclidine incorporated lobelane analogues, endo,endo-and exo,exo-2,6-cis-diphenethyl-1-azabicyclo-[2.2.2]octane (2 and 3), has been developed. Analogue; 2 and 3 were designed to mimic the axial and equatorial geometry, respectively, of the vesicular monoamine transporter-2 (VMAT2) inhibitor, lobelane. The exo,exo analogue 2 had comparable affinity to lobelane and had greater affinity than the endo,endo analogue 3 at the tetrabenazine binding site on VMAT2, indicating that the preferred binding mode of lobelane is likely the extended conformation.

  DOI：

  10.1021/jo901082r
• 作为产物：
  描述：

  1-(2,2,2-trichloroethoxy)carbonyl-2-phenethyl-4-oxo-1,2,3,4-tetrahydropyridine 、 Phenethylmagnesium chloride 在 三甲基氯硅烷 、 copper(I) bromide dimethylsulfide complex 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 以90%的产率得到cis-N-[(2,2,2-trichloroethoxy)carbonyl]-2,6-diphenethyl piperidin-4-one
  参考文献：
  名称：

  Stereocontrolled Synthesis and Pharmacological Evaluation ofcis-2,6-Diphenethyl-1-azabicyclo[2.2.2]octanes as Lobelane Analogues

  摘要：

  An efficient and highly stereocontrolled approach for the synthesis of the quinuclidine incorporated lobelane analogues, endo,endo-and exo,exo-2,6-cis-diphenethyl-1-azabicyclo-[2.2.2]octane (2 and 3), has been developed. Analogue; 2 and 3 were designed to mimic the axial and equatorial geometry, respectively, of the vesicular monoamine transporter-2 (VMAT2) inhibitor, lobelane. The exo,exo analogue 2 had comparable affinity to lobelane and had greater affinity than the endo,endo analogue 3 at the tetrabenazine binding site on VMAT2, indicating that the preferred binding mode of lobelane is likely the extended conformation.

  DOI：

  10.1021/jo901082r

文献信息

• Stereocontrolled Synthesis and Pharmacological Evaluation of<i>cis</i>-2,6-Diphenethyl-1-azabicyclo[2.2.2]octanes as Lobelane Analogues
  作者：Guangrong Zheng、Linda P. Dwoskin、Agripina G. Deaciuc、Peter A. Crooks

  DOI：10.1021/jo901082r

  日期：2009.8.21

  An efficient and highly stereocontrolled approach for the synthesis of the quinuclidine incorporated lobelane analogues, endo,endo-and exo,exo-2,6-cis-diphenethyl-1-azabicyclo-[2.2.2]octane (2 and 3), has been developed. Analogue; 2 and 3 were designed to mimic the axial and equatorial geometry, respectively, of the vesicular monoamine transporter-2 (VMAT2) inhibitor, lobelane. The exo,exo analogue 2 had comparable affinity to lobelane and had greater affinity than the endo,endo analogue 3 at the tetrabenazine binding site on VMAT2, indicating that the preferred binding mode of lobelane is likely the extended conformation.