rac-(1S,2R,5S,6S,7S)-(3-benzyl-2-phenyl-7-pyrrolidin-1-yl-3-azabicyclo[3.2.0]hept-6-yl)methanol

• 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: rac-(1S,2R,5S,6S,7S)-(3-benzyl-2-phenyl-7-pyrrolidin-1-yl-3-azabicyclo[3.2.0]hept-6-yl)methanol
• 英文别名: (3-benzyl-2-exo-phenyl-7-exo-pyrrolidin-1-yl-3-azabicyclo[3.2.0]hept-6-endo-yl)methanol；[(1S,2R,5R,6R,7R)-3-benzyl-2-phenyl-7-pyrrolidin-1-yl-3-azabicyclo[3.2.0]heptan-6-yl]methanol
• 化学式: C₂₄H₃₀N₂O
• 分子量: 362.515
• InChiKey: RSLYNHHGHMPLKL-JTKSJCOOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  26.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  rac-(1S,2R,5S,6S,7S)-(3-benzyl-2-phenyl-7-pyrrolidin-1-yl-3-azabicyclo[3.2.0]hept-6-yl)methanol 、 乙酸乙酯 在 immobilized lipase B from Candida antarctica (Novozym 435) 作用下， 反应 5.0h， 以92.2%的产率得到
  参考文献：
  名称：

  Diastereoselective Multicomponent Cascade Reaction Leading to [3.2.0]-Heterobicyclic Compounds

  摘要：

  A general three-component triple cascade reaction through an iminium-enamine-iminium sequential activation initiated by a hetero-Michael addition to alpha,beta-unsaturated aldehydes affords [3.2.0]heterobicycles in high diastereoselectivity. The rate and diastereoselectivity of the reaction depended on the (E)-4-heterocrotonate and size of the secondary amine. The enantiomers of the major diastereoisomer of oxa- and azabicyclo[3.2.0]heptane derivatives were separated by enzymatic kinetic resolution with immobilized Candida antarctica Lipase B (CALB), with E values up to 153. The absolute configuration of the nonacylated enantiomer of oxabicyclo[3.2.0]heptane was determined by single crystal X-ray analysis.

  DOI：

  10.1021/jo3019413
• 作为产物：
  描述：

  反式肉桂醛 在 lithium aluminium tetrahydride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 6.0h， 生成 rac-(1S,2R,5S,6S,7S)-(3-benzyl-2-phenyl-7-pyrrolidin-1-yl-3-azabicyclo[3.2.0]hept-6-yl)methanol
  参考文献：
  名称：

  Chemoenzymatic synthesis and evaluation of 3-azabicyclo[3.2.0]heptane derivatives as dopaminergic ligands

  摘要：

  New 3-azabicyclo[3.2.0]heptane derivatives were synthesized using a multicomponent reaction. Racemic compounds were efficiently resolved by kinetic resolution with immobilized lipase B of Candida antarctica (Novozym 435). The obtained compounds demonstrated greater binding affinity at D-2L and D-3 dopamine receptors compared to D-1 binding sites, and individual enantiomers of the same compound possessed distinct affinities. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.07.025

文献信息

• A Novel Diastereoselective Multicomponent Cascade Reaction
  作者：Kadri Kriis、Kerti Ausmees、Tõnis Pehk、Margus Lopp、Tõnis Kanger

  DOI：10.1021/ol1005714

  日期：2010.5.21

  A novel multicomponent cascade reaction led to the formation of a strained 3-azabicyclo[3.2.0]heptane derivative 4. The unstable ester 4 was reduced in a one-pot procedure to a stable alcohol 6. The formation of the bicyclic product is highly diastereoselective, predominantly affording one diastereoisomer. The obtained azabicycloheptanes are important pharmacophores.

  一种新型的多组分级联反应导致形成应变的3-氮杂双环[3.2.0]庚烷衍生物4。通过一锅法将不稳定的酯4还原为稳定的醇6。双环产物的形成是高度非对映选择性的，主要提供一种非对映异构体。所获得的氮杂双环庚烷是重要的药效团。
• Diastereoselective Multicomponent Cascade Reaction Leading to [3.2.0]-Heterobicyclic Compounds
  作者：Kerti Ausmees、Kadri Kriis、Tõnis Pehk、Franz Werner、Ivar Järving、Margus Lopp、Tõnis Kanger

  DOI：10.1021/jo3019413

  日期：2012.12.7

  A general three-component triple cascade reaction through an iminium-enamine-iminium sequential activation initiated by a hetero-Michael addition to alpha,beta-unsaturated aldehydes affords [3.2.0]heterobicycles in high diastereoselectivity. The rate and diastereoselectivity of the reaction depended on the (E)-4-heterocrotonate and size of the secondary amine. The enantiomers of the major diastereoisomer of oxa- and azabicyclo[3.2.0]heptane derivatives were separated by enzymatic kinetic resolution with immobilized Candida antarctica Lipase B (CALB), with E values up to 153. The absolute configuration of the nonacylated enantiomer of oxabicyclo[3.2.0]heptane was determined by single crystal X-ray analysis.
• Chemoenzymatic synthesis and evaluation of 3-azabicyclo[3.2.0]heptane derivatives as dopaminergic ligands
  作者：Reet Reinart-Okugbeni、Kerti Ausmees、Kadri Kriis、Franz Werner、Ago Rinken、Tõnis Kanger

  DOI：10.1016/j.ejmech.2012.07.025

  日期：2012.9

  New 3-azabicyclo[3.2.0]heptane derivatives were synthesized using a multicomponent reaction. Racemic compounds were efficiently resolved by kinetic resolution with immobilized lipase B of Candida antarctica (Novozym 435). The obtained compounds demonstrated greater binding affinity at D-2L and D-3 dopamine receptors compared to D-1 binding sites, and individual enantiomers of the same compound possessed distinct affinities. (C) 2012 Elsevier Masson SAS. All rights reserved.