(3R,7aR)-3-(trichloromethyl)-7a-((3,6,7-trimethoxyphenanthren-9-yl)methyl)tetrahydropyrrolo[1,2-c]oxazol-1(3H)-one | 1397943-62-2

• 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: (3R,7aR)-3-(trichloromethyl)-7a-((3,6,7-trimethoxyphenanthren-9-yl)methyl)tetrahydropyrrolo[1,2-c]oxazol-1(3H)-one
• 英文别名: (3R,7aR)-3-trichloromethyl-7a-(3,6,7-trimethoxy-phenanthren-9-ylmethyl)-tetrahydro-pyrrolo[1,2-c]oxazol-1-one；(3R,7aR)-3-(trichloromethyl)-7a-[(3,6,7-trimethoxyphenanthren-9-yl)methyl]-3,5,6,7-tetrahydropyrrolo[1,2-c][1,3]oxazol-1-one
• CAS: 1397943-62-2
• 化学式: C₂₅H₂₄Cl₃NO₅
• 分子量: 524.828
• InChiKey: URTUYRFKAJKHTK-ISKFKSNPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  57.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3R,7aR)-3-(trichloromethyl)-7a-((3,6,7-trimethoxyphenanthren-9-yl)methyl)tetrahydropyrrolo[1,2-c]oxazol-1(3H)-one 在 乙酰氯 作用下， 以 甲醇 为溶剂， 反应 48.0h， 以72%的产率得到(R)-2-(3,6,7-trimethoxy-phenanthren-9-ylmethyl)-pyrrolidine-2-carboxylic acid methyl ester
  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
• 作为产物：
  描述：

  (3,6,7-trimethoxyphenanthren-9-yl)methanol 在 正丁基锂 、 三溴化磷 、 二异丙胺 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 7.5h， 生成 (3R,7aR)-3-(trichloromethyl)-7a-((3,6,7-trimethoxyphenanthren-9-yl)methyl)tetrahydropyrrolo[1,2-c]oxazol-1(3H)-one
  参考文献：
  名称：

  Enantioselective Approach to 13a-Methylphenanthroindolizidine Alkaloids

  摘要：

  The first enantioselective approach to 13a-methylphenanthroindolizidine alkaloids is reported, featuring an efficient stereoselective Seebach's alkylation and Pictet-Spengler cyclization. The proposed and other three most probable structures were ruled out, indicating hypoestestatin 1 needs further assignment.

  DOI：

  10.1021/jo3012122

文献信息

• Enantioselective Approach to 13a-Methylphenanthroindolizidine Alkaloids
  作者：Bo Su、Chunlong Cai、Qingmin Wang

  DOI：10.1021/jo3012122

  日期：2012.9.21

  The first enantioselective approach to 13a-methylphenanthroindolizidine alkaloids is reported, featuring an efficient stereoselective Seebach's alkylation and Pictet-Spengler cyclization. The proposed and other three most probable structures were ruled out, indicating hypoestestatin 1 needs further assignment.
• Design, synthesis, and evaluation of a water-soluble antofine analogue with high antiproliferative and antitumor activity
  作者：Yongseok Kwon、Jayoung Song、Boeun Lee、Jinkyung In、Hohyun Song、Hwa-Jin Chung、Sang Kook Lee、Sanghee Kim

  DOI：10.1016/j.bmc.2012.11.039

  日期：2013.2

  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.