(11R)-13-(propargyl amine)-11,13-dihydroludartin | 1449759-40-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (11R)-13-(propargyl amine)-11,13-dihydroludartin
• 英文别名: (1S,2S,5R,6S,12R,14S)-9,14-dimethyl-5-[(prop-2-ynylamino)methyl]-3,13-dioxatetracyclo[8.4.0.02,6.012,14]tetradec-9-en-4-one
• CAS: 1449759-40-3
• 化学式: C₁₈H₂₃NO₃
• 分子量: 301.386
• InChiKey: VOHYXHGFAPKEBP-LQEUCBJPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  50.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-叠氮基萘 、 (11R)-13-(propargyl amine)-11,13-dihydroludartin 在 copper(ll) sulfate pentahydrate 、 L-sodium ascorbate 作用下， 以 水 、 叔丁醇 为溶剂， 以76%的产率得到(1S,2S,5R,6S,12R,14S)-9,14-dimethyl-5-[[(1-naphthalen-1-yltriazol-4-yl)methylamino]methyl]-3,13-dioxatetracyclo[8.4.0.02,6.012,14]tetradec-9-en-4-one
  参考文献：
  名称：

  Click chemistry inspired facile synthesis and bioevaluation of novel triazolyl analogs of Ludartin

  摘要：

  A convenient and modular synthesis involving diastereoselective Michael addition followed by regioselective Huisgen 1,3-dipolar cycloaddition reaction was carried out to furnish 1,4-disubstituted-1,2,3-triazoles of Ludartin. This reaction scheme involving Michael addition followed by regioselective Huisgen 1,3-dipolar cycloaddition reaction leading to the formation of triazolyl analogs is being reported for the first time. All the triazolyl products were characterised using spectral data analysis. Sulphorhodamine B cytotoxicity screening of the resulting products against a panel of five human cancerous cell-lines revealed that few of the analogs display promising broad spectrum cytotoxic effect. Among all the synthesized compounds, only 3q displayed the best cytotoxic effect with IC50 values of 12, 11, 38, 39 and 8.5 mu M but less than the standard Ludartin (1) with IC50 values of 6.3, 7.4, 7.5, 6.9 and 0.5 mu M against human neuroblastoma (T98G), lung (A-549), prostate (PC-3), colon (HCT-116) and breast (MCF-7) cancer cell lines, respectively. The present synthesis was designed based on the previous literature reports of Ludartin as an aromatase inhibitor. Our work provides an initial study on structure-activity relationship of triazolyl analogs of sesquiterpene lactones in general and Ludartin (1) in particular. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.01.018
• 作为产物：
  描述：

  ludartin 、 炔丙胺 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 12.0h， 以80%的产率得到(11R)-13-(propargyl amine)-11,13-dihydroludartin
  参考文献：
  名称：

  Click chemistry inspired facile synthesis and bioevaluation of novel triazolyl analogs of Ludartin

  摘要：

  A convenient and modular synthesis involving diastereoselective Michael addition followed by regioselective Huisgen 1,3-dipolar cycloaddition reaction was carried out to furnish 1,4-disubstituted-1,2,3-triazoles of Ludartin. This reaction scheme involving Michael addition followed by regioselective Huisgen 1,3-dipolar cycloaddition reaction leading to the formation of triazolyl analogs is being reported for the first time. All the triazolyl products were characterised using spectral data analysis. Sulphorhodamine B cytotoxicity screening of the resulting products against a panel of five human cancerous cell-lines revealed that few of the analogs display promising broad spectrum cytotoxic effect. Among all the synthesized compounds, only 3q displayed the best cytotoxic effect with IC50 values of 12, 11, 38, 39 and 8.5 mu M but less than the standard Ludartin (1) with IC50 values of 6.3, 7.4, 7.5, 6.9 and 0.5 mu M against human neuroblastoma (T98G), lung (A-549), prostate (PC-3), colon (HCT-116) and breast (MCF-7) cancer cell lines, respectively. The present synthesis was designed based on the previous literature reports of Ludartin as an aromatase inhibitor. Our work provides an initial study on structure-activity relationship of triazolyl analogs of sesquiterpene lactones in general and Ludartin (1) in particular. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.01.018

文献信息

• Synthesis and biological evaluation of amino analogs of Ludartin: Potent and selective cytotoxic agents
  作者：Shabir H. Lone、Khursheed A. Bhat、Shakeel-u-Rehman、Rabiya Majeed、Abid Hamid、Mohd A. Khuroo

  DOI：10.1016/j.bmcl.2013.06.068

  日期：2013.9

  Diverse amino analogs of Ludartin, a cytotoxic guaianolide and a position isomer of an anticancer drug, Arglabin were prepared through Michael type addition at its highly active alpha-methylene-gamma-lactone motif. The semisynthetic derivatives were subjected to sulphorhodamine B cytotoxicity assay against a panel of four different human cancer cell lines viz. lung (A-549), leukemia (THP-1), prostate (PC-3) and colon (HCT-116) to look into structure-activity relationship. Few of the analogs displayed potent selective cytotoxicity compared to the parent molecule-Ludartin (1). (11R)-13-(Diethyl amine)-11,13-dihydroludartin (6) and (11R)-13-(piperidine)-11,13-dihydroludartin (10) showed almost same cytotoxicity against leukemia cell lines (THP-1) as that of parent molecule-Ludartin, but were More active against colon (HCT-116) cancer cells. (11R)-13-(Morpholine)-11,13-dihydroludartin (11) displayed selectively better cytotoxicity against Leukemia cancer cells (THP-1) exhibiting IC50 of 2.8 mu M. (11R)-13-(6-Nitroindazole)-11,13-dihydroludartin (17) was four times more potent than Ludartin with selective cytotoxic effects against prostate cancer cells (2.2 mu M) while as (11R)-13-(6-nitroindazole)-11,13-dihydroludartin (18) exhibited three-fold selective cytotoxicity for Lung (A-549) cancer cell lines exhibiting IC50 of 2.6 mu M. (C) 2013 Elsevier Ltd. All rights reserved.
• Click chemistry inspired facile synthesis and bioevaluation of novel triazolyl analogs of Ludartin
  作者：Shabir H. Lone、Khursheed A. Bhat、Rabiya Majeed、Abid Hamid、Mohd A. Khuroo

  DOI：10.1016/j.bmcl.2014.01.018

  日期：2014.2

  A convenient and modular synthesis involving diastereoselective Michael addition followed by regioselective Huisgen 1,3-dipolar cycloaddition reaction was carried out to furnish 1,4-disubstituted-1,2,3-triazoles of Ludartin. This reaction scheme involving Michael addition followed by regioselective Huisgen 1,3-dipolar cycloaddition reaction leading to the formation of triazolyl analogs is being reported for the first time. All the triazolyl products were characterised using spectral data analysis. Sulphorhodamine B cytotoxicity screening of the resulting products against a panel of five human cancerous cell-lines revealed that few of the analogs display promising broad spectrum cytotoxic effect. Among all the synthesized compounds, only 3q displayed the best cytotoxic effect with IC50 values of 12, 11, 38, 39 and 8.5 mu M but less than the standard Ludartin (1) with IC50 values of 6.3, 7.4, 7.5, 6.9 and 0.5 mu M against human neuroblastoma (T98G), lung (A-549), prostate (PC-3), colon (HCT-116) and breast (MCF-7) cancer cell lines, respectively. The present synthesis was designed based on the previous literature reports of Ludartin as an aromatase inhibitor. Our work provides an initial study on structure-activity relationship of triazolyl analogs of sesquiterpene lactones in general and Ludartin (1) in particular. (C) 2014 Elsevier Ltd. All rights reserved.