4-(3-dodecylamino-2-hydroxypropoxy)chromen-2-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 4-(3-dodecylamino-2-hydroxypropoxy)chromen-2-one
• 英文别名: 4-[3-(Dodecylamino)-2-hydroxypropoxy]chromen-2-one；4-[3-(dodecylamino)-2-hydroxypropoxy]chromen-2-one
• 化学式: C₂₄H₃₇NO₄
• 分子量: 403.562
• InChiKey: VYIPSIYJCNWHGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  29
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(3-dodecylamino-2-hydroxypropoxy)chromen-2-one 在 N,N'-二环己基碳二亚胺 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 (R)-4-(3-dodecylamino-2-hydroxypropoxy)-2H-chromen-2-one
  参考文献：
  名称：

  Resolution, absolute configuration and antifilarial activity of coumarinyl amino alcohols

  摘要：

  The resolution of racemic coumarinyl amino alcohols 5-10 was achieved by using the inexpensive and readily accessible chiral resolving agent N-carbethoxy-L-proline (S)-11. Direct esterification of rac-5-10 with (S)-11 furnished diastereomeric esters, which were easily separated by column chromatography. The obtained diastereomers yielded the desired enantiopure coumarinyl amino alcohols (S)-(+)-5-10 and (R)-(-)-5-10 in good yields with high enantiomeric excess on saponification. The absolute configurations were determined by X-ray crystal analysis and/or by comparison of the specific rotations. Furthermore, in in vitro antifilarial motility inhibition assays, enantiopure coumarins (S)-(+)-9, (R)-(-)-9 and (S)-(+)-10, (R)-(-)-10 were found to be less efficient in affecting the viability of macrofilariae of Brugia malayi than their racemic forms 9 and 10, respectively, indicating the synergistic effect of the enantiomers in evoking antifilarial action. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2017.04.005
• 作为产物：
  描述：

  4-羟基香豆素 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 生成 4-(3-dodecylamino-2-hydroxypropoxy)chromen-2-one
  参考文献：
  名称：

  Resolution, absolute configuration and antifilarial activity of coumarinyl amino alcohols

  摘要：

  The resolution of racemic coumarinyl amino alcohols 5-10 was achieved by using the inexpensive and readily accessible chiral resolving agent N-carbethoxy-L-proline (S)-11. Direct esterification of rac-5-10 with (S)-11 furnished diastereomeric esters, which were easily separated by column chromatography. The obtained diastereomers yielded the desired enantiopure coumarinyl amino alcohols (S)-(+)-5-10 and (R)-(-)-5-10 in good yields with high enantiomeric excess on saponification. The absolute configurations were determined by X-ray crystal analysis and/or by comparison of the specific rotations. Furthermore, in in vitro antifilarial motility inhibition assays, enantiopure coumarins (S)-(+)-9, (R)-(-)-9 and (S)-(+)-10, (R)-(-)-10 were found to be less efficient in affecting the viability of macrofilariae of Brugia malayi than their racemic forms 9 and 10, respectively, indicating the synergistic effect of the enantiomers in evoking antifilarial action. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2017.04.005

文献信息

• Synthesis and biological evaluation of 4-oxycoumarin derivatives as a new class of antifilarial agents
  作者：Sweta Misra、Lav Kumar Singh、Priyanka、Jyoti Gupta、Shailja Misra-Bhattacharya、Diksha Katiyar

  DOI：10.1016/j.ejmech.2015.02.043

  日期：2015.4

  A series of 4-oxycoumarin derivatives was synthesized, characterized and evaluated in vitro and in vivo for antifilarial activity against the human lymphatic filarial parasite, Brugia malayi. A majority of the compounds studied showed potent in vitro activity with low IC50 values in the micro molar (mu M) range (0.014-1.73 and 0.0056-0.43) against adult worms and microfilariae, respectively. Compounds 8 and 9 were identified to be the most promising antifilarial candidate molecules exhibiting activity in the nanomolar (nM) range. The IC50 values for compound 8 were 14 nM and 5.6 nM while for compound 9 were 94 nM and 13 nM, respectively, for adult worm and microfilaria. These two compounds also displayed promising adulticidal activity (74.9 +/- 4.8% and 69.4 +/- 2.8%, respectively) in the primary rodent (jird) screen. This study also serves as a starting point for investigating structure-activity relationship with different amino substituents. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Resolution, absolute configuration and antifilarial activity of coumarinyl amino alcohols
  作者：Priyanka、Sweta Misra、Shailja Misra-Bhattacharya、Ray J. Butcher、Diksha Katiyar

  DOI：10.1016/j.tetasy.2017.04.005

  日期：2017.5

  The resolution of racemic coumarinyl amino alcohols 5-10 was achieved by using the inexpensive and readily accessible chiral resolving agent N-carbethoxy-L-proline (S)-11. Direct esterification of rac-5-10 with (S)-11 furnished diastereomeric esters, which were easily separated by column chromatography. The obtained diastereomers yielded the desired enantiopure coumarinyl amino alcohols (S)-(+)-5-10 and (R)-(-)-5-10 in good yields with high enantiomeric excess on saponification. The absolute configurations were determined by X-ray crystal analysis and/or by comparison of the specific rotations. Furthermore, in in vitro antifilarial motility inhibition assays, enantiopure coumarins (S)-(+)-9, (R)-(-)-9 and (S)-(+)-10, (R)-(-)-10 were found to be less efficient in affecting the viability of macrofilariae of Brugia malayi than their racemic forms 9 and 10, respectively, indicating the synergistic effect of the enantiomers in evoking antifilarial action. (C) 2017 Elsevier Ltd. All rights reserved.