1-tert-butyl 2-methyl 2-((3,6,7-trimethoxyphenanthren-9-yl)methyl)pyrolidi-ne-1,2-dicarboxylate | 1422049-66-8

• 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: 1-tert-butyl 2-methyl 2-((3,6,7-trimethoxyphenanthren-9-yl)methyl)pyrolidi-ne-1,2-dicarboxylate
• 英文别名: 1-tert-butyl 2-methyl 2-((3,6,7-trimethoxyphenanthren-9-yl)methyl)pyrrolidine-1,2-dicarboxylate
• CAS: 1422049-66-8
• 化学式: C₂₉H₃₅NO₇
• 分子量: 509.599
• InChiKey: YPCWJRJVZWOLGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  37.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  83.53
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  1-tert-butyl 2-methyl 2-((3,6,7-trimethoxyphenanthren-9-yl)methyl)pyrolidi-ne-1,2-dicarboxylate 在 盐酸 、 lithium aluminium tetrahydride 、 草酰氯 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 反应 27.0h， 生成 2,3,6-trimethoxy-9,11,12,13,13a,14-hexahydrodibenzo[f,h]pyrrolo[1,2-b]isoquinoline-13a-carbaldehyde
  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
• 作为产物：
  描述：

  Boc-L-脯氨酸甲酯 、 10-(bromomethyl)-2,3,6-trimethoxyphenanthrene 在 六甲基磷酰三胺 、 正丁基锂 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 2.0h， 以71%的产率得到1-tert-butyl 2-methyl 2-((3,6,7-trimethoxyphenanthren-9-yl)methyl)pyrolidi-ne-1,2-dicarboxylate
  参考文献：
  名称：

  Design, synthesis, and evaluation of a water-soluble antofine analogue with high antiproliferative and antitumor activity

  摘要：

  New water soluble antofine C-13a analogues were designed, synthesized, and evaluated for antiproliferative activity against cancer cells. Particularly, (-)-(R)-13a-hydroxymethylantofine ((-)-(R)-4b) demonstrated notable growth inhibition against a panel of human cancer cell lines. This growth inhibition was associated with the arrest of the cell cycle in the G0/G1 phases and suppression of mTOR signaling in human lung A549 cancer cells. Compound (-)-(R)-4b also overcame paclitaxel-resistance in human lung cancer cells (A549-Pa) by suppressing P-glycoprotein expression. Furthermore, compound (-)-(R)-4b significantly inhibited the tumor growth of A549 and A549-Pa xenografts in a nude mouse model, which suggests it is a promising novel antitumor agent with sufficient aqueous solubility. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.11.039

文献信息

• Spatial Configuration and Three-Dimensional Conformation Directed Design, Synthesis, Antiviral Activity, and Structure–Activity Relationships of Phenanthroindolizidine Analogues
  作者：Bo Su、Chunlong Cai、Meng Deng、Qingmin Wang

  DOI：10.1021/acs.jafc.5b06112

  日期：2016.3.16

  conformation of the molecules on their anti-TMV activities and related structure–activity relationship (SAR), a series of D-ring opened derivatives 3, 4, 5a–5j, 6, and 7, chiral 13a- and/or 14-substituted phenanthroindolizidine analogues 10–12 and 18–20, and their enantiomers ent-10–ent-12 and ent-18–ent-20 were synthesized and evaluated for their anti-TMV activities. Bioassay results showed that most of the

  我们最近对菲咯啉吲哚啶生物碱类似物的抗烟草花叶病毒（TMV）活性的研究初步表明，与分子的空间排列密切相关的分子C13a位置的基本骨架和取代模式具有很大的作用。对生物活性的影响。为了进一步研究的空间配置和其抗TMV活动分子和相关的结构-活性关系（SAR）的三维（3D）构象的深入影响，一系列d形环的开衍生物3，4，5a – 5j，6和7，手性13a和/或14取代的菲咯啉吲哚并烷类似物合成了10 – 12和18 – 20以及它们的对映体ent-10 – ent-12和ent-18 – ent-20，并评估了它们的抗TMV活性。生物测定结果显示，大多数手性菲咯啉吲哚并咪唑具有良好的体内抗TMV活性。在这些化合物中，ent-11与宁南霉素（最成功的商业抗病毒药物之一）相比，它具有更强的活性，因此逐渐成为植物病毒的潜在抑制剂。在手性情况下，还首次讨论了其他SAR，这表明分子的空间构型和3D构象对于保持高抗TMV活性至关重要。