9,11,12,13,13a,14-hexahydro-2,3,6-trimethoxy-13a-methyldibenzo[f,h]pyrrolo[1,2-b]isoquinoline

• 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: 9,11,12,13,13a,14-hexahydro-2,3,6-trimethoxy-13a-methyldibenzo[f,h]pyrrolo[1,2-b]isoquinoline
• 英文别名: 2,3,6-trimethoxy-13a-methyl-9,11,12,13,13a,14-hexahydrodibenzo[f,h]pyrrolo[1,2-b]isoquinoline；(±)-2,3,6-trimethoxy-13a-methyl-9,11,12,13,13a,14-hexahydrodibenzo[f,h]pyrrolo[1,2-b]isoquinoline；2,3,6-trimethoxy-13a-methyl-11,12,13,14-tetrahydro-9H-phenanthro[9,10-f]indolizine
• 化学式: C₂₄H₂₇NO₃
• 分子量: 377.483
• InChiKey: MEDVIHNIGHWCNB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  30.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  Boc-L-脯氨酸甲酯 在 盐酸 、 lithium aluminium tetrahydride 、 正丁基锂 、 三乙基硼氢化锂 、 三乙胺 、 二异丙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 28.33h， 生成 9,11,12,13,13a,14-hexahydro-2,3,6-trimethoxy-13a-methyldibenzo[f,h]pyrrolo[1,2-b]isoquinoline
  参考文献：
  名称：

  Design, synthesis, antiviral activity, and SARs of 13a-substituted phenanthroindolizidine alkaloid derivatives

  摘要：

  On the basis of our previous structure-activity relationship (SAR) and antiviral mechanism studies, a series of 13a-substituted phenanthroindolizidine alkaloid analogues (3a-16a, 3b, 4b, 6b, 7b, 10b, and 14b) were designed targeting tobacco mosaic virus (TMV) RNA, synthesized, and evaluated for their antiviral activity against TMV for the first time. The bioassay results showed that most of the synthesized compounds (such as 4a, 6a, 7a, 11a, 14a, 6b, and 14b) exhibited good to excellent antiviral activity against TMV both in vitro and in vivo. Especially, for inactivation effect and curative effect, compounds 4a, 6a, 7a, 11a, 14a, and 14b showed higher activity at both concentrations (500 mu g mL(-1) and 100 mu g mL(-1)) than commercial Ningnanmycin. Preliminary SARs showed that the substituted groups with hydrogen donor at 13a position were found to be favorable for keeping high antiviral activity. The present work demonstrates that 13a-substituted phenanthroindolizidines can be used as possible lead compounds for developing anti-TMV agents. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.101

文献信息

• Oxazaborolidine-catalyzed reductive parallel kinetic resolution of ketones from β-nitro-azabicycles for the synthesis of chiral hypoestestatins 1, 2
  作者：Wannaporn Disadee、Somsak Ruchirawat

  DOI：10.1039/d1ob01608c

  日期：——

  Finally, the desired product was obtained via a formal reductive removal of the hydroxyl group. This methodology has been applied for the synthesis of 13a-methyl tylophora alkaloids in up to 65% yield over six steps from β-nitro-azabicycles. Both natural and unnatural enantioenriched hypoestestatins 1 and 2, and related compounds were synthesized using parallel kinetic resolution of the CBS-oxazaborolidine-catalyzed

  报道了一种合成 13a-甲基 tylophora 生物碱的新方法。主要特征包括两种不同的合成途径，旨在将 β-硝基氮杂双环转化为菲核心。成功的步骤包括将硝基哌啶部分氧化为相应的α,β-不饱和酮，以及形成菲环的氧化联芳基偶联反应。最后，通过正式还原除去羟基得到所需产物。该方法已应用于从 β-硝基氮杂二环化合物合成 13a-甲基 tylophora 生物碱，六步收率高达 65%。天然和非天然对映体富集的下雌睾酮 1 和 2 以及相关化合物均通过 CBS-恶唑硼烷催化外消旋酮还原的平行动力学拆分合成，以提供两种可分离的非对映醇，总产率高达 91%，并且具有高对映选择性（高达89% ee）。此外，首次报道了催化不对称还原为seco -hypoestestatins 1和2。因此，将外消旋混合物开发为两种对映体富集形式的能力为未来的各种生物测定提供了益处。
• Synthesis of 13a-methylphenanthroindolizidines using radical cascade cyclization: synthetic studies toward (±)-hypoestestatin 1
  作者：Kosuke Takeuchi、Atsuko Ishita、Jun-ichi Matsuo、Hiroyuki Ishibashi

  DOI：10.1016/j.tet.2007.08.030

  日期：2007.11

  A radical cascade involving 6-endo cyclization of aryl radicals generated from N-acryloyl-N-(1-methylethenyl)-9-bromophenanthren-10-ylmethylamines, followed by 5-endo-trig cyclization of the resulting alpha-amidoyl radicals afforded phenanthroindolizidines bearing a methyl substituent at the angular C13a position. 2,3,6-Trimethoxy derivative was synthesized by using this method, but its spectral data were not in accord with those of literature values reported for hypoestestatin 1. Further synthetic study toward hypoestestatin 1 is demonstrated. (c) 2007 Elsevier Ltd. All rights reserved.
• Total Synthesis of Phenanthroindolizidine Alkaloids through an Amidyl Radical Cascade/Rearrangement Reaction
  作者：Guifang Han、Yuxiu Liu、Qingmin Wang

  DOI：10.1021/ol4025925

  日期：2013.10.18

  A short and general synthesis of the phenanthroindolizidine alkaloids is reported, featuring an unusual amidyl radical 5-exo/5-exo/rearrangement cascade of a xanthate precursor. Second, using an amidyl radical 5-exo/6-endo cascade to synthesize a phenanthroindolizidine alkaloid exclusively has been developed through a small structural modification.
• Design, synthesis, antiviral activity, and SARs of 13a-substituted phenanthroindolizidine alkaloid derivatives
  作者：Bo Su、Chunlong Cai、Meng Deng、Demin Liang、Lizhong Wang、Qingmin Wang

  DOI：10.1016/j.bmcl.2014.04.101

  日期：2014.7

  On the basis of our previous structure-activity relationship (SAR) and antiviral mechanism studies, a series of 13a-substituted phenanthroindolizidine alkaloid analogues (3a-16a, 3b, 4b, 6b, 7b, 10b, and 14b) were designed targeting tobacco mosaic virus (TMV) RNA, synthesized, and evaluated for their antiviral activity against TMV for the first time. The bioassay results showed that most of the synthesized compounds (such as 4a, 6a, 7a, 11a, 14a, 6b, and 14b) exhibited good to excellent antiviral activity against TMV both in vitro and in vivo. Especially, for inactivation effect and curative effect, compounds 4a, 6a, 7a, 11a, 14a, and 14b showed higher activity at both concentrations (500 mu g mL(-1) and 100 mu g mL(-1)) than commercial Ningnanmycin. Preliminary SARs showed that the substituted groups with hydrogen donor at 13a position were found to be favorable for keeping high antiviral activity. The present work demonstrates that 13a-substituted phenanthroindolizidines can be used as possible lead compounds for developing anti-TMV agents. (C) 2014 Elsevier Ltd. All rights reserved.