tert-butyl (1-((2-butyl-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)amino)-4,8,12,16,20,24-hexaoxo-7,15,23-tris((tetrahydro-2H-pyran-2-yl)oxy)-3,7,11,15,19,23-hexaazahexacosan-26-yl)carbamate | 846601-83-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: tert-butyl (1-((2-butyl-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)amino)-4,8,12,16,20,24-hexaoxo-7,15,23-tris((tetrahydro-2H-pyran-2-yl)oxy)-3,7,11,15,19,23-hexaazahexacosan-26-yl)carbamate
• CAS: 846601-83-0
• 化学式: C₅₆H₈₃N₉O₁₆
• 分子量: 1138.33
• InChiKey: GOAYPRGZAPFTSM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.72
• 重原子数：
  81.0
• 可旋转键数：
  31.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.66
• 拓扑面积：
  291.35
• 氢给体数：
  5.0
• 氢受体数：
  17.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (1-((2-butyl-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)amino)-4,8,12,16,20,24-hexaoxo-7,15,23-tris((tetrahydro-2H-pyran-2-yl)oxy)-3,7,11,15,19,23-hexaazahexacosan-26-yl)carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以82%的产率得到3-amino-N-[3-[[3-[[3-[[3-[[3-[2-[(2-butyl-1,3-dioxobenzo[de]isoquinolin-6-yl)amino]ethylamino]-3-oxopropyl]-hydroxyamino]-3-oxopropyl]amino]-3-oxopropyl]-hydroxyamino]-3-oxopropyl]amino]-3-oxopropyl]-N-hydroxypropanamide
  参考文献：
  名称：

  Ferrioxamine B Analogues:  Targeting the FoxA Uptake System in the Pathogenic Yersinia enterocolitica

  摘要：

  A series of ferrioxamine 6 analogues that target the bacterium Yersinia enterocolitica were prepared. These iron carriers are composed of three hydroxamate-containing monomeric units. Two identical monomers consist of N-hydroxy-3-aminopropionic acid coupled with beta-alanine, and a third unit at the amino terminal is composed of N-hydroxy-3-aminopropionic acid and one of the following amino acids: beta-alanine (1a), phenylalanine (1b), cyclohexylalanine (1c), or glycine (1d). Thermodynamic results for representatives of the analogues have shown a strong destabilization (3-4 orders of magnitude) of the ferric complexes with respect to ferrioxamine B, probably due to shorter spacers and a more strained structure around the metal center. No significant effect of the variations at the N-terminal has been observed on the stability of the ferric complexes. By contrast, using in vivo radioactive uptake experiments, we have found that these modifications have a substantial effect on the mechanism of iron(Ill) uptake in the pathogenic bacteria Yersinia enterocolitica. Analogues la and 1d were utilized by the ferrioxamine B uptake system (FoxA), while 1b and 1c either used different uptake systems or were transported to the microbial cell nonspecifically by diffusion via the cell membrane. Transport via the FoxA system was also confirmed by uptake experiments with the FoxA deficient strain of Yersinia enterocolitica. A fluorescent marker, attached to 1a in a way that did not interfere with its biological activity, provided additional means to monitor the uptake mechanism by fluorescence techniques. Of particular interest is the observation that 1a was utilized by the uptake system of ferrioxamine B in Yersinia enterocolitica (FoxA) but failed to use the ferrioxamine uptake route in Pseudomonas putida. Here, we present a case in which biomimetic siderophore analogues deliberately designed for a particular bacterium can distinguish between related uptake systems of different microorganisms.

  DOI：

  10.1021/ja035182m
• 作为产物：
  描述：

  3-[Benzyloxy-(3-{3-[benzyloxy-(3-{3-[benzyloxy-(3-tert-butoxycarbonylamino-propionyl)-amino]-propionylamino}-propionyl)-amino]-propionylamino}-propionyl)-amino]-propionic acid methyl ester 在 palladium on activated charcoal sodium hydroxide 、 氢气 、 1-羟基苯并三唑 、 对甲苯磺酸 、 达卡巴嗪 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 tert-butyl (1-((2-butyl-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)amino)-4,8,12,16,20,24-hexaoxo-7,15,23-tris((tetrahydro-2H-pyran-2-yl)oxy)-3,7,11,15,19,23-hexaazahexacosan-26-yl)carbamate
  参考文献：
  名称：

  Ferrioxamine B Analogues:  Targeting the FoxA Uptake System in the Pathogenic Yersinia enterocolitica

  摘要：

  A series of ferrioxamine 6 analogues that target the bacterium Yersinia enterocolitica were prepared. These iron carriers are composed of three hydroxamate-containing monomeric units. Two identical monomers consist of N-hydroxy-3-aminopropionic acid coupled with beta-alanine, and a third unit at the amino terminal is composed of N-hydroxy-3-aminopropionic acid and one of the following amino acids: beta-alanine (1a), phenylalanine (1b), cyclohexylalanine (1c), or glycine (1d). Thermodynamic results for representatives of the analogues have shown a strong destabilization (3-4 orders of magnitude) of the ferric complexes with respect to ferrioxamine B, probably due to shorter spacers and a more strained structure around the metal center. No significant effect of the variations at the N-terminal has been observed on the stability of the ferric complexes. By contrast, using in vivo radioactive uptake experiments, we have found that these modifications have a substantial effect on the mechanism of iron(Ill) uptake in the pathogenic bacteria Yersinia enterocolitica. Analogues la and 1d were utilized by the ferrioxamine B uptake system (FoxA), while 1b and 1c either used different uptake systems or were transported to the microbial cell nonspecifically by diffusion via the cell membrane. Transport via the FoxA system was also confirmed by uptake experiments with the FoxA deficient strain of Yersinia enterocolitica. A fluorescent marker, attached to 1a in a way that did not interfere with its biological activity, provided additional means to monitor the uptake mechanism by fluorescence techniques. Of particular interest is the observation that 1a was utilized by the uptake system of ferrioxamine B in Yersinia enterocolitica (FoxA) but failed to use the ferrioxamine uptake route in Pseudomonas putida. Here, we present a case in which biomimetic siderophore analogues deliberately designed for a particular bacterium can distinguish between related uptake systems of different microorganisms.

  DOI：

  10.1021/ja035182m