(S)-2-[(S)-2-(benzyloxycarbonylamino)-5-(tert-butoxycarbonylamino)valerylamino]-5-(tert-butoxycarbonylamino)valeric acid | 32393-54-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-2-[(S)-2-(benzyloxycarbonylamino)-5-(tert-butoxycarbonylamino)valerylamino]-5-(tert-butoxycarbonylamino)valeric acid
• 英文别名: Cbz-Orn(Boc)(Boc)-Orn(Boc)(Boc)-OH；(2S)-5-[(2-methylpropan-2-yl)oxycarbonylamino]-2-[[(2S)-5-[(2-methylpropan-2-yl)oxycarbonylamino]-2-(phenylmethoxycarbonylamino)pentanoyl]amino]pentanoic acid
• CAS: 32393-54-7
• 化学式: C₂₈H₄₄N₄O₉
• 分子量: 580.679
• InChiKey: YESAMHIYMJZROX-SFTDATJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  41
• 可旋转键数：
  19
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  181
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (S)-2-[(S)-2-(benzyloxycarbonylamino)-5-(tert-butoxycarbonylamino)valerylamino]-5-(tert-butoxycarbonylamino)valeric acid 在 N-羟基丁二酰亚胺 、 palladium 10% on activated carbon 、 氢气 、 sodium acetate 、 potassium hydrogencarbonate 、 苯甲醛 、 溶剂黄146 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 106.0h， 生成 H-Hyo(N⁵-Ac)-Hyo(N⁵-Ac)-Hyo(N⁵-Ac)-OH
  参考文献：
  名称：

  Theranostic Gallium Siderophore Ciprofloxacin Conjugate with Broad Spectrum Antibiotic Potency

  摘要：

  Pathogenic bacteria scavenge ferric iron from the host for survival and proliferation using small-molecular chelators, siderophores. Here, we introduce and assess the gallium(III) complex of ciprofloxacin-functionalized desferrichrome (D2) as a potential therapeutic for bacterial infection using an in vitro assay and radiochemical, tracer-based approach. Ga-D2 exhibits a minimum inhibitory concentration of 0.23 mu M in Escherichia con, in line with the parent fluoroquinolone antibiotic. Competitive and mutant strain assays show that Ga-D2 relies on FhuA-mediated transport for internalization. Ga-D2 is potent against Pseudomonas aeruginosa (3.8 mu M), Staphylococcus aureus (0.94 mu M), and Klebsiella pneumoniae (12.5 mu M), while Fe-D2 is inactive in these strains. Radiochemical experiments with E. coli reveal that Ga-67-D2 is taken up more efficiently than (67)-Ga-citrate. In naive mice, Ga-67-D2 clears renally and is excreted 13% intact in the urine. These pharmacokinetic and bacterial growth inhibitory properties qualify Ga-D2 for future investigations as a diagnosis and treatment tool for infection.

  DOI：

  10.1021/acs.jmedchem.9b01388
• 作为产物：
  描述：

  N-苄氧羰基-N’-叔丁氧羰基-L-鸟氨酸 在 碳酸氢钠 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 16.0h， 生成 (S)-2-[(S)-2-(benzyloxycarbonylamino)-5-(tert-butoxycarbonylamino)valerylamino]-5-(tert-butoxycarbonylamino)valeric acid
  参考文献：
  名称：

  Practical Synthesis of Hydroxamate-Derived Siderophore Components by an Indirect Oxidation Method and Syntheses of a DIG−Siderophore Conjugate and a Biotin−Siderophore Conjugate

  摘要：

  A practical large-scale synthesis of hydroxamate-derived siderophore components (30 and 40) that utilizes an efficient indirect oxidation method is described and applied to the syntheses of nonradioactive labeled siderophores. Oxidation of imines derived from L-ornithine (17) and its tripeptide (19) afforded oxaziridines that were isomerized to stable-nitrones (16 and 18). Acid-catalyzed hydrolysis of nitrones provided hydroxylamines that were converted to the desired hydroxamic acids (30 and 40) suitable for constructing siderophore-drug conjugates (2). The entire synthetic sequence required no chromatographic separation. DIG- and biotin-labeled ferrichrome analogues designed to detect and isolate ferrichrome receptors in various microbes were also synthesized.

  DOI：

  10.1021/jo990769y

文献信息

• Practical Synthesis of Hydroxamate-Derived Siderophore Components by an Indirect Oxidation Method and Syntheses of a DIG−Siderophore Conjugate and a Biotin−Siderophore Conjugate
  作者：Yun-Ming Lin、Marvin J. Miller

  DOI：10.1021/jo990769y

  日期：1999.10.1

  A practical large-scale synthesis of hydroxamate-derived siderophore components (30 and 40) that utilizes an efficient indirect oxidation method is described and applied to the syntheses of nonradioactive labeled siderophores. Oxidation of imines derived from L-ornithine (17) and its tripeptide (19) afforded oxaziridines that were isomerized to stable-nitrones (16 and 18). Acid-catalyzed hydrolysis of nitrones provided hydroxylamines that were converted to the desired hydroxamic acids (30 and 40) suitable for constructing siderophore-drug conjugates (2). The entire synthetic sequence required no chromatographic separation. DIG- and biotin-labeled ferrichrome analogues designed to detect and isolate ferrichrome receptors in various microbes were also synthesized.
• Theranostic Gallium Siderophore Ciprofloxacin Conjugate with Broad Spectrum Antibiotic Potency
  作者：Apurva Pandey、Chloé Savino、Shin Hye Ahn、Zhaoyong Yang、Steven G. Van Lanen、Eszter Boros

  DOI：10.1021/acs.jmedchem.9b01388

  日期：2019.11.14

  Pathogenic bacteria scavenge ferric iron from the host for survival and proliferation using small-molecular chelators, siderophores. Here, we introduce and assess the gallium(III) complex of ciprofloxacin-functionalized desferrichrome (D2) as a potential therapeutic for bacterial infection using an in vitro assay and radiochemical, tracer-based approach. Ga-D2 exhibits a minimum inhibitory concentration of 0.23 mu M in Escherichia con, in line with the parent fluoroquinolone antibiotic. Competitive and mutant strain assays show that Ga-D2 relies on FhuA-mediated transport for internalization. Ga-D2 is potent against Pseudomonas aeruginosa (3.8 mu M), Staphylococcus aureus (0.94 mu M), and Klebsiella pneumoniae (12.5 mu M), while Fe-D2 is inactive in these strains. Radiochemical experiments with E. coli reveal that Ga-67-D2 is taken up more efficiently than (67)-Ga-citrate. In naive mice, Ga-67-D2 clears renally and is excreted 13% intact in the urine. These pharmacokinetic and bacterial growth inhibitory properties qualify Ga-D2 for future investigations as a diagnosis and treatment tool for infection.