4,18-dimethoxy-2-oxa-tricyclo[13.3.1.13,7]icosa-1(18),3(20),4,6,15(19),16-hexaen-10-ol | 1354834-25-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4,18-dimethoxy-2-oxa-tricyclo[13.3.1.13,7]icosa-1(18),3(20),4,6,15(19),16-hexaen-10-ol
• 英文别名: 4,18-Dimethoxy-2-oxatricyclo[13.3.1.13,7]icosa-1(18),3,5,7(20),15(19),16-hexaen-10-ol；4,18-dimethoxy-2-oxatricyclo[13.3.1.13,7]icosa-1(18),3,5,7(20),15(19),16-hexaen-10-ol
• CAS: 1354834-25-5
• 化学式: C₂₁H₂₆O₄
• 分子量: 342.435
• InChiKey: GRXKIUYDENCFMC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  47.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4,18-dimethoxy-2-oxa-tricyclo[13.3.1.13,7]icosa-1(18),3(20),4,6,15(19),16-hexaen-10-ol 、 苯乙酰氯 在 吡啶 、 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 以95%的产率得到(4,18-Dimethoxy-2-oxatricyclo[13.3.1.13,7]icosa-1(18),3,5,7(20),15(19),16-hexaen-10-yl) 2-phenylacetate
  参考文献：
  名称：

  大环二芳基庚烷衍生物的合成和抗菌评价。

  摘要：

  由结核分枝杆菌和其他有问题的细菌病原体引起的细菌感染继续对全球公共卫生构成重大威胁。因此，迫切需要新的化学型抗菌剂来补充和增强抗菌药物的发现和开发渠道。作为开发天然药物启发的新型抗菌剂的抗菌研究计划的一部分，我们在此报告对具有多种胺，酰胺，尿素和磺酰胺官能团的大环二芳基庚烷类化合物的扩展化学文库进行合成，抗菌评估和构效关系研究。这项研究的结果产生了大环香叶胺和4-氟苯乙胺取代的衍生物，对M的活性中等至良好。

  DOI：

  10.1016/j.bmcl.2016.06.075
• 作为产物：
  描述：

  methyl 3-(3-bromo-4-methoxyphenyl)propanoate 在 N-甲基吗啉 、 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 甲醇 、 sodium tetrahydroborate 、 2-氯-4,6-二甲氧基-1,3,5-三嗪 、 palladium on activated charcoal 、 氢气 、 potassium carbonate 、 copper(II) oxide 、 sodium hydroxide 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 乙醚 、 二氯甲烷 、 甲苯 为溶剂， 反应 51.42h， 生成 4,18-dimethoxy-2-oxa-tricyclo[13.3.1.13,7]icosa-1(18),3(20),4,6,15(19),16-hexaen-10-ol
  参考文献：
  名称：

  Synthesis and evaluation of macrocyclic diarylether heptanoid natural products and their analogs

  摘要：

  The macrocyclic diarylether heptanoid (MDEH) natural products have been used in folk medicine for centuries. MDEHs are reported to exert anti-tumor properties by inhibiting the activation of NF-kappa B. Here we report the synthesis of a small MDEH library (first reported synthesis of racemic platycarynol) using a Grubbs cross metathesis/Ullmann cyclization strategy. Evaluation of the library led to the identification of MDEH 9b which sensitizes pancreatic cancer cells to gemcitabine mediated growth inhibition and apoptosis. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.025

文献信息

• Syntheses and evaluation of macrocyclic engelhardione analogs as antitubercular and antibacterial agents
  作者：Li Shen、Marcus M Maddox、Sudip Adhikari、David F Bruhn、Manish Kumar、Robin E Lee、Julian G Hurdle、Richard E Lee、Dianqing Sun

  DOI：10.1038/ja.2013.21

  日期：2013.6

  The natural product engelhardione is an underexplored chemotype for developing novel treatments for bacterial infections; we therefore explored this natural product scaffold for chemical diversification and structure–activity relationship studies. Macrocyclic engelhardione and structural regioisomers were synthesized using a series of aldol condensations and selective hydrogenations to generate the 1,7-diarylheptan-3-one derivatives, followed by microwave-assisted intramolecular Ullmann coupling to afford a series of macrocyclic diaryl ether analogs. An extended macrocyclic chemical library was then produced by oxime formation, reductive amination and O-alkylation. Antibacterial evaluation revealed that the reductive amination derivatives 7b and 7d showed moderate activities (minimum inhibitory concentrations: 12.5–25 μg ml−1) against Mycobacterium tuberculosis and Gram-positive pathogens, as well as anti-Gram-negative activity against an efflux impaired Escherichia coli strain. These results provide validated leads for further optimization and development.

  天然产物恩格尔哈酮是一种尚未充分开发的化学类型，可用于开发细菌感染的新疗法；因此，我们探索了这种天然产物的化学多样性，并对其结构-活性关系进行了研究。通过一系列醛缩合和选择性氢化反应，我们合成了大环恩格尔哈酮和结构区域异构体，生成1,7-二芳基庚烷-3-酮衍生物，然后通过微波辅助分子内乌尔曼偶联反应，得到一系列大环二芳基醚类似物。通过肟形成、还原胺化和O-烷基化反应，我们构建了一个扩展的大环化学库。抗菌评估显示，还原胺化衍生物7b和7d对结核分枝杆菌和革兰氏阳性病原体具有中等活性（最低抑菌浓度：12.5-25µg·ml-1），对一种外排受损的大肠杆菌菌株具有抗革兰氏阴性活性。这些结果为进一步优化和开发提供了有效的线索。
• Synthesis and evaluation of macrocyclic diarylether heptanoid natural products and their analogs
  作者：Vashti C. Bryant、G.D. Kishore Kumar、Abijah M. Nyong、Amarnath Natarajan

  DOI：10.1016/j.bmcl.2011.11.025

  日期：2012.1

  The macrocyclic diarylether heptanoid (MDEH) natural products have been used in folk medicine for centuries. MDEHs are reported to exert anti-tumor properties by inhibiting the activation of NF-kappa B. Here we report the synthesis of a small MDEH library (first reported synthesis of racemic platycarynol) using a Grubbs cross metathesis/Ullmann cyclization strategy. Evaluation of the library led to the identification of MDEH 9b which sensitizes pancreatic cancer cells to gemcitabine mediated growth inhibition and apoptosis. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis and antibacterial evaluation of macrocyclic diarylheptanoid derivatives
  作者：Hao Lin、David F. Bruhn、Marcus M. Maddox、Aman P. Singh、Richard E. Lee、Dianqing Sun

  DOI：10.1016/j.bmcl.2016.06.075

  日期：2016.8

  public health. As such, new chemotype antibacterial agents are desperately needed to fuel and strengthen the antibacterial drug discovery and development pipeline. As part of our antibacterial research program to develop natural product-inspired new antibacterial agents, here we report synthesis, antibacterial evaluation, and structure-activity relationship studies of an extended chemical library of macrocyclic

  由结核分枝杆菌和其他有问题的细菌病原体引起的细菌感染继续对全球公共卫生构成重大威胁。因此，迫切需要新的化学型抗菌剂来补充和增强抗菌药物的发现和开发渠道。作为开发天然药物启发的新型抗菌剂的抗菌研究计划的一部分，我们在此报告对具有多种胺，酰胺，尿素和磺酰胺官能团的大环二芳基庚烷类化合物的扩展化学文库进行合成，抗菌评估和构效关系研究。这项研究的结果产生了大环香叶胺和4-氟苯乙胺取代的衍生物，对M的活性中等至良好。