4,18-dimethoxy-2-oxa-tricyclo[13.3.1.13,7]icosa-1(18),3(20),4,6,15(19),16-hexaen-10-one | 1330753-37-1

• 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-one
• 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-one
• CAS: 1330753-37-1
• 化学式: C₂₁H₂₄O₄
• 分子量: 340.419
• InChiKey: XCCVGTCYBJSMMG-UHFFFAOYSA-N

物化性质

• 沸点：
  520.8±50.0 °C(Predicted)
• 密度：
  1.105±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 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-one 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 0.33h， 以100%的产率得到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：

  Syntheses and evaluation of macrocyclic engelhardione analogs as antitubercular and antibacterial agents

  摘要：

  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。

  DOI：

  10.1038/ja.2013.21
• 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 、 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 、 乙醚 、 二氯甲烷 、 甲苯 为溶剂， 反应 51.0h， 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-one
  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

• Total synthesis and structural revision of engelhardione
  作者：Li Shen、Dianqing Sun

  DOI：10.1016/j.tetlet.2011.06.112

  日期：2011.8

  The total synthesis of the macrocyclic natural product engelhardione is reported. This effort led to the structural revision of the published structure of engelhardione to that of pterocarine. The revision reflects the change of the substitution pattern of one phenyl ether ring from the meta to the para position. To confirm, pterocarine (2) and its close regioisomer 3 were subsequently synthesized

  报道了大环天然产物恩格尔哈二酮的全合成。这一努力导致已发表的 engelhardione 结构被修改为 pterocarine 的结构。修订反映了一个苯醚环的取代模式从间位到对位的变化。为了证实，随后合成了紫檀香碱 ( 2 ) 及其紧密区域异构体3以进行比较。此外，为了就我们所知，我们的合成1表示具有一个14元的大环二芳基庚的第一个例子的元-元在二苯基醚基团取代模式。
• 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。
• Selective peptide bond hydrolysis of cysteine peptides in the presence of Ni(II) ions
  作者：Anna Maria Protas、Arkadiusz Bonna、Edyta Kopera、Wojciech Bal

  DOI：10.1016/j.jinorgbio.2010.09.003

  日期：2011.1

  this concept by synthesizing three homologous peptides: R1-Ser-Arg-Cys-Trp-R2, R1-Cys-Arg-His-Trp-R2, and R1-Cys-Arg-Cys-Trp-R2, and the R1-Ser-Arg-His-Trp-R2 peptide as comparator (R1 and R2 were CH3CO-Gly-Ala and Lys-Phe-Leu-NH2, respectively). We studied their hydrolysis in the presence of Ni(II) ions, under anaerobic conditions and in the presence of TCEP as a thiol group antioxidant. We measured

  最近，我们描述了在一般序列R1–（Ser / Thr）–Xaa–His–Zaa–R的肽中的序列特异性R1-（Ser / Thr）肽键水解反应，该反应在Ni（II）存在下发生）离子[A. Krężel，E。Kopera，AM Protas，A。Wysłouch-Cieszyńska，J。Poznański，W。Bal，J。Am。化学 Soc。132（2010）3355-3366]。在这项研究中，我们探索了根据Ni（II）辅助的酰基转移反应机理，用Cys残基取代Ser / Thr和His残基的可能性，该残基是反应发生所必需的。我们通过合成三个同源肽（R1-Ser-Arg-Cys-Trp-R2，R1-Cys-Arg-His-Trp-R2和R1-Cys-Arg-Cys-Trp-R2和R1）测试了这一概念-Ser-Arg-His-Trp-R2肽作为比较物（R1和R2分别为CH3CO-Gly-Ala和
• Microwave-assisted synthesis of macrocycles via intramolecular and/or bimolecular Ullmann coupling
  作者：Li Shen、Charles J. Simmons、Dianqing Sun

  DOI：10.1016/j.tetlet.2012.05.142

  日期：2012.8

  Microwave-assisted synthesis of macrocyclic diaryl ethers via intramolecular and/or bimolecular Ullmann coupling is described. Using the optimized conditions, a panel of macrocycles, with different substitution patterns, ring sizes, and linkers, has been successfully synthesized using microwave irradiation. To the best of our knowledge, this work represents the first examples of the microwave-assisted synthesis of macrocyclic diaryl ethers via intramolecular and/or bimolecular Ullmann coupling. (C) 2012 Elsevier Ltd. All rights reserved.
• 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.