6-bromo-4'-N-demethylaplysinopsin | 97480-15-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 6-bromo-4'-N-demethylaplysinopsin
• 英文别名: (E)-2-amino-5-((6-bromo-1H-indol-3-yl)methylene)-1-methyl-1H-imidazol-4(5H)-one；(E)-2-amino-5-[(6-bromo-1H-indol-3-yl)methylidenyl]-1-methyl-1H-imidazol-4(5H)-one；6-bromo-12-nor-(E)-aplysinopsin；(5E)-2-amino-5-[(6-bromo-1H-indol-3-yl)methylidene]-1-methylimidazol-4-one
• CAS: 97480-15-4
• 化学式: C₁₃H₁₁BrN₄O
• 分子量: 319.161
• InChiKey: DLMWCHNLJCOUQC-NYYWCZLTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.06
• 重原子数：
  19.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  74.48
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  6-bromo-(E)-aplysinopsin 、 6-bromo-4'-N-demethylaplysinopsin 在 bismuth(lll) trifluoromethanesulfonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 以3.4%的产率得到(±)-dictazole B
  参考文献：
  名称：

  利用Aplysinopsin系列中的内在反应性来合成复杂的二聚体：从头到尾都是天然的

  摘要：

  摘要 Apssinopsin单体被认为是更广泛的海洋生物碱Apssinopsin家族的合理的生物合成前体。从这种状态来看，利用它们的内在反应性进行二恶唑或环皂素的合成的想法是逻辑上出现的。这些生物合成方面的考虑使我们首次合成了咔唑B和其他有价值的环丁烷。当进一步利用预编码的反应性时，我们的第一个总合成的tubastrindole B源自其dictazole型前体的扩环级联。此外，瞬态生物合成中间体的分离与含乙内酰脲的单体的二聚化结果相结合，使我们能够解释环皂素A和B的形成。 1引言 2轻松获得Dictazole Cyclobutanes 3扩环合成环皂甙 4结论与未来展望 Apssinopsin单体被认为是更广泛的海洋生物碱Apssinopsin家族的合理的生物合成前体。从这种状态来看，利用它们的内在反应性进行二恶唑或环皂素的合成的想法是逻辑上出现的。这些生物合成方面的考虑使我们首次合成了

  DOI：

  10.1055/s-0034-1381032
• 作为产物：
  描述：

  肌酸酐 、 6-溴吲哚-3-甲醛 以 neat (no solvent) 为溶剂， 以59%的产率得到6-bromo-4'-N-demethylaplysinopsin
  参考文献：
  名称：

  人工日光照射下（±）-二唑B的自发仿生形成

  摘要：

  出于生物合成方面的考虑，首次报道了dictazole B的总合成。提供了容易获得具有海洋挑战性的环丁烷生物碱的实验证据，这些生物碱通常被认为是结构更复杂的生物合成前体。

  DOI：

  10.1002/anie.201403454

文献信息

• Constituents of morphologically similar sponges
  作者：Adrienne A. Tymiak、Kenneth L. Rinehart、Gerald J. Bakus

  DOI：10.1016/s0040-4020(01)96471-3

  日期：1985.1

  the marine sponge Smenospongia aurea have been isolated and characterized as 5-bromo- and 5,6-dibromo-N,N-dimethyltryptamines (1 and 2), aureol (3), and two new aplysinopsin derivatives (6-bromoaplysinopsin and 6-bromo-4'-N-demethylaplysinopsin, 4 and 5, respectively). Morphologically similar species from the Caribbean have been surveyed and found to contain either mixtures of these metabolites or

  已从海洋海绵金黄色葡萄球菌中分离出化合物，并将其表征为5-溴和5,6-二溴-N，N-二甲基色胺（1和2），金黄色酚（3）和两种新的皂素衍生物（6-溴皂素和6-溴-4'-N-去甲基aplysinopsin ，分别为4和5）。已经对加勒比地区形态相似的物种进行了调查，发现它们既包含这些代谢物的混合物，也包含溴酪氨酸衍生的化合物。讨论了含溴吲哚的代谢物的1 H NMR光谱。
• Synthesis and evaluation of aplysinopsin analogs as inhibitors of human monoamine oxidase A and B
  作者：Kevin Lewellyn、Dobroslawa Bialonska、Narayan D. Chaurasiya、Babu L. Tekwani、Jordan K. Zjawiony

  DOI：10.1016/j.bmcl.2012.06.058

  日期：2012.8

  Aplysinopsins are tryptophan-derived natural products that have been isolated from a variety of marine organisms. Previous studies have shown aplysinopsin analogs to possess a variety of biological activities, including modulation of neurotransmissions. A series of fifty aplysinopsin analogs was synthesized and assayed for monoamine oxidase A and B inhibitory activity. Three compounds displayed significant MAO inhibitory activity and selectivity. The compound (E)-5-[(6-bromo-1H-indol-3-yl) methylene]-2-imino-1,3-dimethylimidazolidin-4-one (3x) possessed an IC50 of 5.6 nM at MAO-A and had a selectivity index of 80.24. An SAR study revealed that multiple N-methylations, one of which should be at position N-2', and bromination at C-5 or C-6 are important factors for MAO-A potency and selectivity. (c) 2012 Elsevier Ltd. All rights reserved.
• In vitro structure–activity relationships of aplysinopsin analogs and their in vivo evaluation in the chick anxiety–depression model
  作者：Kevin Lewellyn、Dobroslawa Bialonska、Melissa J. Loria、Stephen W. White、Kenneth J. Sufka、Jordan K. Zjawiony

  DOI：10.1016/j.bmc.2013.09.011

  日期：2013.11

  Aplysinopsins are tryptophan-derived natural products that have been isolated from a variety of marine organisms and have been shown to possess a range of biological activities. In vitro receptor binding assays showed that of the 12 serotonin receptor subtypes, analogues showed a high affinity for the 5-HT2B and 5-HT2C receptor subtypes, with selectivity for 5-HT2B over 5-HT2C. While no conclusions could be drawn about the number and position of N-methylations, bromination at C-4 and C-5 of the indole ring resulted in greater binding affinities, with K-i's as low as 35 nM. This data, combined with previous knowledge of the CNS activity of aplysinopsin analogs, suggested that these compounds may have potential as leads for antidepressant drugs. Compounds 3c, 3u, and 3x were evaluated in the chick anxiety-depression model to assess their in vivo efficacy. Compound 3c showed a modest antidepressant effect at a dose of 30 nM/kg in the animal model. (C) 2013 Elsevier Ltd. All rights reserved.
• Spontaneous Biomimetic Formation of (±)‐Dictazole B under Irradiation with Artificial Sunlight
  作者：Adam Skiredj、Mehdi A. Beniddir、Delphine Joseph、Karine Leblanc、Guillaume Bernadat、Laurent Evanno、Erwan Poupon

  DOI：10.1002/anie.201403454

  日期：2014.6.16

  Guided by biosynthetic considerations, the total synthesis of dictazole B is reported for the first time. Experimental evidence for an easy access to challenging cyclobutane alkaloids of marine origin, which are often postulated to be biosynthetic precursors of more complex structures, is provided.

  出于生物合成方面的考虑，首次报道了dictazole B的总合成。提供了容易获得具有海洋挑战性的环丁烷生物碱的实验证据，这些生物碱通常被认为是结构更复杂的生物合成前体。
• Harnessing the Intrinsic Reactivity within the Aplysinopsin Series for the Synthesis of Intricate Dimers: Natural from Start to Finish
  作者：Laurent Evanno、Erwan Poupon、Adam Skiredj、Mehdi Beniddir、Delphine Joseph、Guillaume Bernadat

  DOI：10.1055/s-0034-1381032

  日期：——

  exploiting pre-encoded reactivity, our first total synthesis of tubastrindole B originated from the ring-expansion cascade of its dictazole-type precursor. Moreover, the isolation of a transient biosynthetic intermediate combined with dimerization outcomes of a hydantoin-containing monomer allowed us to explain the formation of cycloaplysinopsins A and B. 1 Introduction 2 Easy Access to Dictazole Cyclobutanes

  摘要 Apssinopsin单体被认为是更广泛的海洋生物碱Apssinopsin家族的合理的生物合成前体。从这种状态来看，利用它们的内在反应性进行二恶唑或环皂素的合成的想法是逻辑上出现的。这些生物合成方面的考虑使我们首次合成了咔唑B和其他有价值的环丁烷。当进一步利用预编码的反应性时，我们的第一个总合成的tubastrindole B源自其dictazole型前体的扩环级联。此外，瞬态生物合成中间体的分离与含乙内酰脲的单体的二聚化结果相结合，使我们能够解释环皂素A和B的形成。 1引言 2轻松获得Dictazole Cyclobutanes 3扩环合成环皂甙 4结论与未来展望 Apssinopsin单体被认为是更广泛的海洋生物碱Apssinopsin家族的合理的生物合成前体。从这种状态来看，利用它们的内在反应性进行二恶唑或环皂素的合成的想法是逻辑上出现的。这些生物合成方面的考虑使我们首次合成了