tert-butyl 4,5,6a,7-tetrahydro-1,2-dimethoxy-9,11-dioxa-6-azabenzo[fg]cyclopenta[b]anthracene-6-carboxylate | 934355-70-1

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 阿朴菲
• 英文名称: tert-butyl 4,5,6a,7-tetrahydro-1,2-dimethoxy-9,11-dioxa-6-azabenzo[fg]cyclopenta[b]anthracene-6-carboxylate
• 英文别名: Tert-butyl 18,19-dimethoxy-5,7-dioxa-13-azapentacyclo[10.7.1.02,10.04,8.016,20]icosa-1(20),2,4(8),9,16,18-hexaene-13-carboxylate
• CAS: 934355-70-1
• 化学式: C₂₄H₂₇NO₆
• 分子量: 425.481
• InChiKey: VFYDYCGJKWNJMN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  66.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 4,5,6a,7-tetrahydro-1,2-dimethoxy-9,11-dioxa-6-azabenzo[fg]cyclopenta[b]anthracene-6-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以52%的产率得到(+/-)-Nornantenine
  参考文献：
  名称：

  微波辅助直接联芳偶联：首次应用于阿朴啡合成

  摘要：

  我们研究了微波在直接联芳基偶联反应中用于合成阿朴啡生物碱 nantenine 类似物的用途。我们的研究表明，使用这种方法可以从苄基四氢异喹啉底物快速获得阿朴啡核心。这是阿朴啡分子合成中微波辅助直接联芳基偶联反应的首次报道。

  DOI：

  10.1016/j.tetlet.2009.03.029
• 作为产物：
  描述：

  tert-butyl 1-[(5-bromobenzo[d][1,3]dioxol-6-yl)methyl]-3,4-dihydro-6,7-dimethoxyisoquinoline-2(1H)-carboxylate 在 palladium diacetate potassium carbonate 作用下， 以 二甲胺 为溶剂， 以99%的产率得到tert-butyl 4,5,6a,7-tetrahydro-1,2-dimethoxy-9,11-dioxa-6-azabenzo[fg]cyclopenta[b]anthracene-6-carboxylate
  参考文献：
  名称：

  通过直接芳基化合成阿朴啡生物碱并使其多样化

  摘要：

  钯催化的芳基氯化物、溴化物和碘化物的直接芳基化已被应用于通过与苯并二恶唑、吡啶 N-氧化物和吡嗪 N-氧化物反应制备新的阿朴啡类似物，包括 C2 取代的阿朴啡。直接芳基化在这些多样化反应中的成功应用突出了其不仅在收敛合成中而且在发散合成中的效用。我们还描述了 (R)-nornuciferine 和 (R)-nuciferine 的对映选择性合成，采用催化不对称转移氢化以高产率和优异的对映体过量。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

  DOI：

  10.1002/ejoc.200600674

文献信息

• Microwave-assisted direct biaryl coupling: first application to the synthesis of aporphines
  作者：Sandeep Chaudhary、Stevan Pecic、Onica LeGendre、Wayne W. Harding

  DOI：10.1016/j.tetlet.2009.03.029

  日期：2009.5

  microwaves in a direct biaryl coupling reaction for the synthesis of analogs of the aporphine alkaloid nantenine. Our study shows that the aporphine core may be rapidly accessed from benzyl-tetrahydroisoquinoline substrates with this method. This is the first report of a microwave-assisted direct biaryl coupling reaction in the synthesis of aporphine molecules.

  我们研究了微波在直接联芳基偶联反应中用于合成阿朴啡生物碱 nantenine 类似物的用途。我们的研究表明，使用这种方法可以从苄基四氢异喹啉底物快速获得阿朴啡核心。这是阿朴啡分子合成中微波辅助直接联芳基偶联反应的首次报道。
• Aporphine Alkaloid Synthesis and Diversification via Direct Arylation
  作者：Marc Lafrance、Nicole Blaquiere、Keith Fagnou

  DOI：10.1002/ejoc.200600674

  日期：2007.2

  aporphines by reaction with benzodioxole, pyridine N-oxide and pyrazine N-oxide. Successful application of direct arylation in these diversification reactions highlights its utility not only in convergent, but also in divergent synthesis. We also describe enantioselective syntheses of (R)-nornuciferine and (R)-nuciferine employing a catalytic asymmetric transfer hydrogenation in high yield and excellent enantiomeric

  钯催化的芳基氯化物、溴化物和碘化物的直接芳基化已被应用于通过与苯并二恶唑、吡啶 N-氧化物和吡嗪 N-氧化物反应制备新的阿朴啡类似物，包括 C2 取代的阿朴啡。直接芳基化在这些多样化反应中的成功应用突出了其不仅在收敛合成中而且在发散合成中的效用。我们还描述了 (R)-nornuciferine 和 (R)-nuciferine 的对映选择性合成，采用催化不对称转移氢化以高产率和优异的对映体过量。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
• Affinity of aporphines for the human 5-HT2A receptor: Insights from homology modeling and molecular docking studies
  作者：Stevan Pecic、Pooja Makkar、Sandeep Chaudhary、Boojala V. Reddy、Hernan A. Navarro、Wayne W. Harding

  DOI：10.1016/j.bmc.2010.06.043

  日期：2010.8

  Analogs of nantenine were docked into a modeled structure of the human 5-HT2A receptor using ICM Pro, GLIDE, and GOLD docking methods. The resultant docking scores were used to correlate with observed in vitro apparent affinity (K-e) data. The GOLD docking algorithm when used with a homology model of 5-HT2A, based on a bovine rhodopsin template and built by the program MODELLER, gives results which are most in agreement with the in vitro results. Further analysis of the docking poses among members of a C1 alkyl series of nantenine analogs, indicate that they bind to the receptor in a similar orientation, but differently than nantenine. Besides an important interaction between the protonated nitrogen of the C1 alkyl analogs and residue Asp155, we identified Ser242, Phe234, and Gly238 as key residues responsible for the affinity of these compounds for the 5-HT2A receptor. Specifically, the ability of some of these analogs to establish a H-bond with Ser242 and hydrophobic interactions with Phe234 and Gly238 appears to explain their enhanced affinity as compared to nantenine. Published by Elsevier Ltd.