N-(benzyloxy)-N-(5-benzyloxypentyl)succinamic acid | 284666-50-8

• 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: N-(benzyloxy)-N-(5-benzyloxypentyl)succinamic acid
• 英文别名: 4-Oxo-4-[phenylmethoxy(5-phenylmethoxypentyl)amino]butanoic acid
• CAS: 284666-50-8
• 化学式: C₂₃H₂₉NO₅
• 分子量: 399.487
• InChiKey: QXOFWZYWZBMRPW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  29
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(benzyloxy)-N-(5-benzyloxypentyl)succinamic acid 在 palladium on activated charcoal 4-二甲氨基吡啶 、 二苯基磷酸 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 吡啶 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 38.25h， 生成 Desferri-danoxamin
  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
• 作为产物：
  描述：

  5-苄氧基-1-戊醇 在 4-二甲氨基吡啶 、 sodium hydride 、 三乙胺 、 三氟乙酸 作用下， 以 吡啶 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 28.17h， 生成 N-(benzyloxy)-N-(5-benzyloxypentyl)succinamic acid
  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

• Chemical Approach for Investigation of the Structure‐Activity Relationship of Salmycin and Identification of a Glycan‐based Analogue for Drug Resistant <i>Staphylococcus aureus</i>
  作者：Cheng‐Hsin Chiu、De‐Yi Huang、Wei‐Hsiang Ma、Yu‐Xun Chen、Sih‐Yu Yang、Yu‐Chie Chen、Kwok‐Kong Tony Mong

  DOI：10.1002/adsc.202300969

  日期：2024.1.9

  New synthetic routes were devised for total synthesis of Fe3+-bound (ferri−) salmycin B (Sal B) (1), glycan-based Sal analogues 2–5 and their Fe3+-unbound (desferri−) counterparts 1′–5′ for the structure to activity relationship (SAR) study. The results of SAR study reveal the effective structure of 1 and its desferri-counterpart 1′ that are responsible for the observed inhibitory activity against

  设计了新的合成路线，用于全合成 Fe 3+结合 ( ferri −) 沙霉素 B (Sal B) ( 1 )、基于聚糖的 Sal 类似物2 – 5及其 Fe 3+未结合 ( desferri −) 对应物1′ – 5'用于结构与活性关系（SAR）研究。SAR 研究结果揭示了1及其去铁蛋白对应物1'的有效结构，它们负责观察到的对金黄色葡萄球菌( S. aureus ) 的抑制活性。在类似物2 – 5和2′ – 5′中，基于葡萄糖的类似物2及其去铁对应物2′表现出与1和1′相当的抑制效力。通过对2′进行化学修饰，进一步进行抗菌研究，我们发现了desferri -Sal类似物7′，它具有更简单的药效团结构，但对甲氧西林敏感和耐药的金黄色葡萄球菌的抗菌效力明显高于天然产物1′，甚至临床上也有显着提高。万古霉素。类似物7'具有更好的水解稳定性和更短的合成路线，是一种值得进一步探索的有吸引力的抗生素先导化合物。
• 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.