tetra-O-benzyl danoxamine | 284666-59-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tetra-O-benzyl danoxamine
• 英文别名: tetra-O-benzyldanoxamine；4-Oxo-4-[5-[[4-oxo-4-[5-[[4-oxo-4-[phenylmethoxy(5-phenylmethoxypentyl)amino]butanoyl]amino]pentyl-phenylmethoxyamino]butanoyl]amino]pentyl-phenylmethoxyamino]butanoic acid
• CAS: 284666-59-7
• 化学式: C₅₅H₇₃N₅O₁₁
• 分子量: 980.212
• InChiKey: JUSBUZBMYWLBGU-UHFFFAOYSA-N

物化性质

• 熔点：
  63-64.5 °C
• 密度：
  1.183±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  71
• 可旋转键数：
  38
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  193
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  tetra-O-benzyl danoxamine 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 11.0h， 以97%的产率得到Desferri-danoxamin
  参考文献：
  名称：

  Trihydroxamate Siderophore–Fluoroquinolone Conjugates Are Selective Sideromycin Antibiotics that Target Staphylococcus aureus

  摘要：

  Siderophores are multidentate iron(III) chelators used by bacteria for iron assimilation. Sideromycins, also called siderophore-antibiotic conjugates, are a unique subset of siderophores that enter bacterial cells via siderophore uptake pathways and deliver the toxic antibiotic in a "Trojan horse" fashion. Sideromycins represent a novel antibiotic delivery technology with untapped potential for developing sophisticated microbe-selective antibacterial agents that limit the emergence of bacterial resistance. The chemical synthesis of a series of mono-, bis-, and trihydroxamate sideromycins are described here along with their biological evaluation in antibacterial susceptibility assays. The linear hydroxamate siderophores used for the sideromycins in this study were derived from the ferrioxamine family and inspired by the naturally occurring salmycin sideromycins. The antibacterial agents used were a beta-lactam carbacepholosporin, Lorabid, and a fluoroquinolone, ciprofloxacin, chosen for the different locations of their biological targets, the periplasm (extracellular) and the cytoplasm (intracellular). The linear hydroxamate-based sideromycins were selectively toxic toward Gram-positive bacteria, especially Staphylococcus aureus SG511 (MIC = 1.0 mu M for the trihydroxamate-fluoroquinolone sideromycin). Siderophore-sideromycin competition assays demonstrated that only the fluoroquinolone sideromycins required membrane transport to reach their cytoplasmic biological target and that a trihydroxamate siderophore backbone was required for protein-mediated active transport of the sideromycins into S. aureus cells via siderophore uptake pathways. This work represents a comprehensive study of linear hydroxamate sideromycins and teaches how to build effective hydroxamate-based sideromycins as Gram-positive selective antibiotic agents.

  DOI：

  10.1021/bc300610f
• 作为产物：
  描述：

  5-氯戊腈 在 镍 4-二甲氨基吡啶 、 二苯基磷酸 、 氨 、 氢气 、 sodium hydride 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 、 sodium iodide 作用下， 以 吡啶 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 35.25h， 生成 tetra-O-benzyl danoxamine
  参考文献：
  名称：

  Total Synthesis of the Siderophore Danoxamine

  摘要：

  The total synthesis of the linear trihydroxamate siderophore, Danoxamine, is described. Danoxamine is a siderophore component of the naturally occurring siderophore-drug conjugates Salmycin A-D. The synthesis of Danoxamine features a series of coupling reactions involving N-(5-benzyloxypentyl)-O-benzylhydroxylamine being linked by a succinoyl linker to N-(benzyloxy)-1,5-pentanediamine. Two more succinoyl linkers and another N-(benzyloxy)-1,5-pentanediamine were used in coupling reactions to afford the fully protected siderophore. The linear tetrabenzyl-protected trihydroxamate was deprotected to afford the natural product Danoxamine.

  DOI：

  10.1021/jo000050m

文献信息

• Iron(III)-Templated Macrolactonization of Trihydroxamate Siderophores
  作者：Timothy A. Wencewicz、Allen G. Oliver、Marvin J. Miller

  DOI：10.1021/ol301869x

  日期：2012.9.7

  A method was developed to synthesize macrocyclic trihydroxamate siderophores using optimized Yamaguchi macrolactonization conditions. The natural ability of siderophores to bind iron(III) was exploited to template the reactions and allowed for rapid reaction rates, high product conversions, and the formation of large macrolactone rings up to 35 atoms. An X-ray structure of a 33-membered macrolactone siderophore-Fe(III) complex is presented.
• Trihydroxamate Siderophore–Fluoroquinolone Conjugates Are Selective Sideromycin Antibiotics that Target Staphylococcus aureus
  作者：Timothy A. Wencewicz、Timothy E. Long、Ute Möllmann、Marvin J. Miller

  DOI：10.1021/bc300610f

  日期：2013.3.20

  Siderophores are multidentate iron(III) chelators used by bacteria for iron assimilation. Sideromycins, also called siderophore-antibiotic conjugates, are a unique subset of siderophores that enter bacterial cells via siderophore uptake pathways and deliver the toxic antibiotic in a "Trojan horse" fashion. Sideromycins represent a novel antibiotic delivery technology with untapped potential for developing sophisticated microbe-selective antibacterial agents that limit the emergence of bacterial resistance. The chemical synthesis of a series of mono-, bis-, and trihydroxamate sideromycins are described here along with their biological evaluation in antibacterial susceptibility assays. The linear hydroxamate siderophores used for the sideromycins in this study were derived from the ferrioxamine family and inspired by the naturally occurring salmycin sideromycins. The antibacterial agents used were a beta-lactam carbacepholosporin, Lorabid, and a fluoroquinolone, ciprofloxacin, chosen for the different locations of their biological targets, the periplasm (extracellular) and the cytoplasm (intracellular). The linear hydroxamate-based sideromycins were selectively toxic toward Gram-positive bacteria, especially Staphylococcus aureus SG511 (MIC = 1.0 mu M for the trihydroxamate-fluoroquinolone sideromycin). Siderophore-sideromycin competition assays demonstrated that only the fluoroquinolone sideromycins required membrane transport to reach their cytoplasmic biological target and that a trihydroxamate siderophore backbone was required for protein-mediated active transport of the sideromycins into S. aureus cells via siderophore uptake pathways. This work represents a comprehensive study of linear hydroxamate sideromycins and teaches how to build effective hydroxamate-based sideromycins as Gram-positive selective antibiotic agents.
• Total Synthesis of the Siderophore Danoxamine
  作者：John M. Roosenberg、Marvin J. Miller

  DOI：10.1021/jo000050m

  日期：2000.8.1

  The total synthesis of the linear trihydroxamate siderophore, Danoxamine, is described. Danoxamine is a siderophore component of the naturally occurring siderophore-drug conjugates Salmycin A-D. The synthesis of Danoxamine features a series of coupling reactions involving N-(5-benzyloxypentyl)-O-benzylhydroxylamine being linked by a succinoyl linker to N-(benzyloxy)-1,5-pentanediamine. Two more succinoyl linkers and another N-(benzyloxy)-1,5-pentanediamine were used in coupling reactions to afford the fully protected siderophore. The linear tetrabenzyl-protected trihydroxamate was deprotected to afford the natural product Danoxamine.