(4R,4aS,7R,7aR,12bS)-7-(benzyl(methyl)amino)-3-(cyclopropylmethyl)-1,2,3,4,5,6,7,7a-octahydro-4aH-4,12-methanobenzofuro[3,2-e]isoquinolin-4a-ol | 1393735-89-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: (4R,4aS,7R,7aR,12bS)-7-(benzyl(methyl)amino)-3-(cyclopropylmethyl)-1,2,3,4,5,6,7,7a-octahydro-4aH-4,12-methanobenzofuro[3,2-e]isoquinolin-4a-ol
• CAS: 1393735-89-1
• 化学式: C₂₈H₃₄N₂O₂
• 分子量: 430.59
• InChiKey: DMYJKDRUPRVELG-YMLQGTIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.75
• 重原子数：
  32.0
• 可旋转键数：
  5.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  35.94
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (4R,4aS,7R,7aR,12bS)-7-(benzyl(methyl)amino)-3-(cyclopropylmethyl)-1,2,3,4,5,6,7,7a-octahydro-4aH-4,12-methanobenzofuro[3,2-e]isoquinolin-4a-ol 在 palladium on activated charcoal 、 氢气 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 (E)-N-[(4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a-hydroxy-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]-3-(furan-3-yl)-N-methylacrylamide
  参考文献：
  名称：

  Essential structure of opioid κ receptor agonist nalfurafine for binding to the κ receptor 2: Synthesis of decahydro(iminoethano)phenanthrene derivatives and their pharmacologies

  摘要：

  To clarify the essential structures of an opioid kappa receptor selective agonist, nalfurafine, for binding to the kappa receptor, we designed and synthesized some nalfurafine derivatives and the decahydro(iminoethano)phenanthrene derivatives with a cyclohexene moiety as a surrogate for the phenol ring. In addition to the 6-amide side chain and the 17-nitrogen substituted by a cyclopropylmethyl group, the 4,5-epoxy ring, phenolic hydroxy group, and angular hydroxy group played important roles in eliciting the binding properties of nalfurafine but these three moieties were not indispensable for binding to the kappa receptor. Moreover, the phenol ring was also not essential for the binding to the kappa receptor, and the cyclohexene moiety would play an important role in fixing the conformation of decahydro(iminoethano) phenanthrene derivatives to effectively raise the amide side chain, rendering a conformation that resembled the active one of nalfurafine. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.122
• 作为产物：
  描述：

  纳曲酮 在 palladium on activated charcoal 、 氢气 、 potassium carbonate 、 对甲苯磺酸 、 溶剂黄146 、 苯甲酸 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 生成 (4R,4aS,7R,7aR,12bS)-7-(benzyl(methyl)amino)-3-(cyclopropylmethyl)-1,2,3,4,5,6,7,7a-octahydro-4aH-4,12-methanobenzofuro[3,2-e]isoquinolin-4a-ol
  参考文献：
  名称：

  Essential structure of opioid κ receptor agonist nalfurafine for binding to the κ receptor 2: Synthesis of decahydro(iminoethano)phenanthrene derivatives and their pharmacologies

  摘要：

  To clarify the essential structures of an opioid kappa receptor selective agonist, nalfurafine, for binding to the kappa receptor, we designed and synthesized some nalfurafine derivatives and the decahydro(iminoethano)phenanthrene derivatives with a cyclohexene moiety as a surrogate for the phenol ring. In addition to the 6-amide side chain and the 17-nitrogen substituted by a cyclopropylmethyl group, the 4,5-epoxy ring, phenolic hydroxy group, and angular hydroxy group played important roles in eliciting the binding properties of nalfurafine but these three moieties were not indispensable for binding to the kappa receptor. Moreover, the phenol ring was also not essential for the binding to the kappa receptor, and the cyclohexene moiety would play an important role in fixing the conformation of decahydro(iminoethano) phenanthrene derivatives to effectively raise the amide side chain, rendering a conformation that resembled the active one of nalfurafine. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.122

文献信息

• Stereoselective syntheses of 3-dehydroxynaltrexamines and N-methyl-3-dehydroxynaltrexamines
  作者：Mengchu Li、Celsey M. St. Onge、Yan Zhang

  DOI：10.1016/j.tetlet.2020.152379

  日期：2020.9

  Methodology is presented for the synthesis of 6α/β-3-dehydroxynaltrexamines and 6α/β-N-methyl-3-dehydroxynaltrexamines. A stereoselective route is provided for each target compound while a novel one-pot method for the synthesis of 6α/β-N-methyl-3-dehydroxynaltrexamines is also explored. These results enable the versatile and efficient preparation of key epoxymorphinan intermediates to facilitate future

  介绍了合成 6 α / β -3-脱羟基 naltrexamines 和 6 α / β - N -methyl-3-dehydroxynaltrexamines 的方法。为每个目标化合物提供了立体选择性路线，同时还探索了一种新的一锅法合成 6 α / β - N -甲基-3-脱羟基纳曲胺。这些结果使关键环氧吗啡喃中间体的多功能和高效制备成为可能，以促进未来选择性阿片类配体的发现和开发。