3’,4’,5-trichloro-7-hexyl-6-hydroxy-1’-methyl-1’H-spiro[1-benzofuran-2,2’-pyrrole]-3,5’-dione | 1402209-04-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: 3’,4’,5-trichloro-7-hexyl-6-hydroxy-1’-methyl-1’H-spiro[1-benzofuran-2,2’-pyrrole]-3,5’-dione
• 英文别名: 5-Chloro-Armeniaspirole A；3',4',5-trichloro-7-hexyl-6-hydroxy-1'-methylspiro[1-benzofuran-2,5'-pyrrole]-2',3-dione
• CAS: 1402209-04-4
• 化学式: C₁₈H₁₈Cl₃NO₄
• 分子量: 418.704
• InChiKey: KZMWNWHPQYHFGI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3’,4’,5-trichloro-7-hexyl-6-hydroxy-1’-methyl-1’H-spiro[1-benzofuran-2,2’-pyrrole]-3,5’-dione 在 Chiralpak IC column 作用下， 35.0 ℃ 、20.0 MPa 条件下， 生成 5-Chloro Armeniaspirole A 、 (2S)-3',4',5-trichloro-7-hexyl-6-hydroxy-1'-methylspiro[1-benzofuran-2,5'-pyrrole]-2',3-dione
  参考文献：
  名称：

  Armeniaspiroles, a new class of antibacterials: antibacterial activities and total synthesis of 5-chloro-Armeniaspirole A

  摘要：

  Armeniaspiroles, a novel class of natural products isolated from Streptomyces armeniacus, are characterized by a novel spiro[4.4]non-8-ene scaffold. Various derivatives of Armeniaspiroles could be obtained by halogenation, alkylation, addition/elimination or reductions. A total synthesis of the 5-chloro analog of Armeniaspirole A has been accomplished in a linear six-step sequence. 5-Chloro-Armeniaspirole A exhibits good activity against a range of multidrug-resistant, Gram-positive bacterial pathogens. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.107
• 作为产物：
  描述：

  吡咯-2-羧酸 在 N-氯代丁二酰亚胺 、 草酰氯 、 三溴化硼 、 四氯化锡 、 sodium hydride 、 溶剂黄146 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.25h， 生成 3’,4’,5-trichloro-7-hexyl-6-hydroxy-1’-methyl-1’H-spiro[1-benzofuran-2,2’-pyrrole]-3,5’-dione
  参考文献：
  名称：

  Armeniaspiroles, a new class of antibacterials: antibacterial activities and total synthesis of 5-chloro-Armeniaspirole A

  摘要：

  Armeniaspiroles, a novel class of natural products isolated from Streptomyces armeniacus, are characterized by a novel spiro[4.4]non-8-ene scaffold. Various derivatives of Armeniaspiroles could be obtained by halogenation, alkylation, addition/elimination or reductions. A total synthesis of the 5-chloro analog of Armeniaspirole A has been accomplished in a linear six-step sequence. 5-Chloro-Armeniaspirole A exhibits good activity against a range of multidrug-resistant, Gram-positive bacterial pathogens. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.107

文献信息

• Armeniaspirol analogues with more potent Gram-positive antibiotic activity show enhanced inhibition of the ATP-dependent proteases ClpXP and ClpYQ
  作者：Michael G. Darnowski、Taylor D. Lanosky、Puneet Labana、Jordan T. Brazeau-Henrie、Nicholas D. Calvert、Mark H. Dornan、Claudia Natola、André R. Paquette、Adam J. Shuhendler、Christopher N. Boddy

  DOI：10.1039/d1md00355k

  日期：——

  Antibiotics with fundamentally new mechanisms of action such as the armeniaspirols, which target the ATP-dependent proteases ClpXP and ClpYQ, must be developed to combat antimicrobial resistance.

  必须开发具有根本新机制的抗生素，例如针对ATP依赖性蛋白酶ClpXP和ClpYQ的armeniaspirols，以应对抗微生物耐药性。
• Armeniaspirol analogues disrupt the electrical potential (ΔΨ) of the proton motive force
  作者：Michael G. Darnowski、Taylor D. Lanosky、André R. Paquette、Christopher N. Boddy

  DOI：10.1016/j.bmcl.2023.129210

  日期：2023.3

  kanamycin, an antibiotic that required ΔΨ for penetration. By evaluating the antibiotic activity and disruption of the PMF by sixteen armeniaspirol analogs, we find that disruption of the PMF is necessary but not sufficient for antibiotic activity. Analogs that are potent disruptors of the PMF without possessing the ability to inhibit ClpXP and ClpYQ are not potent antibiotics. Thus we propose that the

  亚美尼亚螺醇天然产物抗生素家族已被证明可抑制 ATP 依赖性蛋白酶 ClpXP 和 ClpYQ，并通过穿梭质子穿过膜破坏膜电位。在这里，我们研究了它们破坏质子动力 (PMF) 的能力。我们显示，使用电压敏感，亚美尼亚醇会破坏 PMF 的电膜电位 (ΔΨ) 分量，而不是跨膜质子梯度 (ΔpH)。使用棋盘分析，我们通过显示拮抗作用证实了这一点，卡那霉素是一种需要 ΔΨ 才能渗透的抗生素。通过评估 16 种亚美尼亚螺醇类似物对 PMF 的抗生素活性和破坏，我们发现 PMF 的破坏是必要的，但对于抗生素活性来说还不够。不具有抑制 ClpXP 和 ClpYQ 能力的 PMF 强效干扰物的类似物不是强效抗生素。因此，我们提出亚美尼亚螺醇利用双重作用机制，即破坏 PMF 并抑制 ATP 依赖性蛋白酶 ClpXP 和 ClpYQ。这种类型的双重机制已在其他基于天然产物的抗生素中观察到，最显着的是 chelocardin。
• Armeniaspirols inhibit the AAA+ proteases ClpXP and ClpYQ leading to cell division arrest in Gram-positive bacteria
  作者：Puneet Labana、Mark H. Dornan、Matthew Lafrenière、Tomasz L. Czarny、Eric D. Brown、John P. Pezacki、Christopher N. Boddy

  DOI：10.1016/j.chembiol.2021.07.001

  日期：2021.12
• Armeniaspiroles, a new class of antibacterials: antibacterial activities and total synthesis of 5-chloro-Armeniaspirole A
  作者：Cédric Couturier、Armin Bauer、Astrid Rey、Cosima Schroif-Dufour、Mark Broenstrup

  DOI：10.1016/j.bmcl.2012.06.107

  日期：2012.10

  Armeniaspiroles, a novel class of natural products isolated from Streptomyces armeniacus, are characterized by a novel spiro[4.4]non-8-ene scaffold. Various derivatives of Armeniaspiroles could be obtained by halogenation, alkylation, addition/elimination or reductions. A total synthesis of the 5-chloro analog of Armeniaspirole A has been accomplished in a linear six-step sequence. 5-Chloro-Armeniaspirole A exhibits good activity against a range of multidrug-resistant, Gram-positive bacterial pathogens. (C) 2012 Elsevier Ltd. All rights reserved.