2-((1S,2R,3R,5R)-3-ethynyl-2-(3-hydroxypropyl)-3-(benzylamino)-5-methylcyclohexyl)acetonitrile | 1225377-69-4

• 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: 2-((1S,2R,3R,5R)-3-ethynyl-2-(3-hydroxypropyl)-3-(benzylamino)-5-methylcyclohexyl)acetonitrile
• 英文别名: 2-[(1S,2R,3R,5R)-3-(benzylamino)-3-ethynyl-2-(3-hydroxypropyl)-5-methylcyclohexyl]acetonitrile
• CAS: 1225377-69-4
• 化学式: C₂₁H₂₈N₂O
• 分子量: 324.466
• InChiKey: LGFFRHOKAMQEGZ-CWJKEVGVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  56
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-((1S,2R,3R,5R)-3-ethynyl-2-(3-hydroxypropyl)-3-(benzylamino)-5-methylcyclohexyl)acetonitrile 在 咪唑 、 carbon monoxide,cobalt,cyclopenta-1,3-diene 、 四丁基氟化铵 、 三苯基膦 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 四氯化碳 、 甲苯 为溶剂， 反应 61.0h， 生成 (5R,5′R,6S,6′S,14R,14′R,16R,16′R)-1,1′-dibenzyl-11-(tert-butyldimethylsilyl)-16,16′-dimethyl-1,1′,2,2′,3,3′,4,4′,5,5′,6,6′,7,7′,-15,15′,16,16′,17,17′-icosahydro-10,10′-bi(5,10b-propano1,7-phenanthroline)
  参考文献：
  名称：

  Syntheses of (+)-Complanadine A and Lycodine Derivatives by Regioselective [2 + 2 + 2] Cycloadditions

  摘要：

  The dimeric alkaloid complanadine A has shown promise in regenerative science, promoting neuronal growth by inducing the secretion of growth factors from glial cells. Through the use of tandem, cobalt-mediated [2 + 2 + 2] cycloaddition reactions, two synthetic routes have been developed with different sequences for the formation of the unsymmetric bipyridyl core. The regioselective formation of each of the pyridines was achieved based on the inherent selectivity of the molecules or by reversing the regioselectivity through the addition of Lewis bases. This strategy has been successfully employed to provide laboratory access to complanadine A as well as structurally related compounds possessing the lycocline core.

  DOI：

  10.1021/jo400695c
• 作为产物：
  描述：

  3-((1R,2R,4R,6S)-2-(benzylamino)-6-(cyanomethyl)-2-ethynyl-4-methylcyclohexyl)propyl acetate 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 7.0h， 以99%的产率得到2-((1S,2R,3R,5R)-3-ethynyl-2-(3-hydroxypropyl)-3-(benzylamino)-5-methylcyclohexyl)acetonitrile
  参考文献：
  名称：

  Syntheses of (+)-Complanadine A and Lycodine Derivatives by Regioselective [2 + 2 + 2] Cycloadditions

  摘要：

  The dimeric alkaloid complanadine A has shown promise in regenerative science, promoting neuronal growth by inducing the secretion of growth factors from glial cells. Through the use of tandem, cobalt-mediated [2 + 2 + 2] cycloaddition reactions, two synthetic routes have been developed with different sequences for the formation of the unsymmetric bipyridyl core. The regioselective formation of each of the pyridines was achieved based on the inherent selectivity of the molecules or by reversing the regioselectivity through the addition of Lewis bases. This strategy has been successfully employed to provide laboratory access to complanadine A as well as structurally related compounds possessing the lycocline core.

  DOI：

  10.1021/jo400695c

文献信息

• Complanadine A, a selective agonist for the Mas-related G protein-coupled receptor X2
  作者：Trevor Johnson、Dionicio Siegel

  DOI：10.1016/j.bmcl.2014.05.060

  日期：2014.8

  The first biological target for the natural product complanadine A has been determined. The pseudosymmetric alkaloid functions as a selective agonist for the Mas-related G protein-coupled receptor X2 (MrgprX2), a G protein-coupled receptor that is highly expressed in neurons. Given the potential of MrgprX2 to function as a modulator of pain, complanadine A represents a new chemical probe to selectively interrogate the physiological function of MrgprX2 as well as a potential lead for the development of antihyperalgesics for the treatment of persistent pain. While complanadine A possess agonistic activity the related natural product lycodine, representing half of complanadine A, lacks activity providing a cursory description of the structural requirements for agonistic activity. (C) 2014 Elsevier Ltd. All rights reserved.
• Synthesis of (+)-Complanadine A, an Inducer of Neurotrophic Factor Excretion
  作者：Changxia Yuan、Chih-Tsung Chang、Abram Axelrod、Dionicio Siegel

  DOI：10.1021/ja101956x

  日期：2010.5.5

  A total synthesis of the Lycopodium alkaloid (+)-complanadine A is described. Complanadine A has been shown to induce the secretion of neurotrophic factors from 1321N1 cells, promoting the differentiation of PC-12 cells. The use of a simplifying metal mediated [2+2+2] + [2+2+2] sequence using a silyl-substituted diyne and 2 equiv of the corresponding alkyne-nitrile has provided rapid access to the natural product.