H-Hyo(N⁵-Ac)-Hyo(N⁵-Ac)-Hyo(N⁵-Ac)-OH | 92412-99-2

• 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: H-Hyo(N⁵-Ac)-Hyo(N⁵-Ac)-Hyo(N⁵-Ac)-OH
• 英文别名: N⁵-acetyl-N⁵-hydroxy-L-ornithyl-N⁵-acetyl-N⁵-hydroxy-L-ornithyl-N⁵-acetyl-N⁵-hydroxy-L-ornithine；(N⁵-Acetyl-N⁵-hydroxy-L-ornithyl)-(N⁵-acetyl-N⁵-hydroxy-L-ornithyl)-N⁵-acetyl-N⁵-hydroxy-L-ornithin；(S)-2-((S)-2-((S)-2-amino-5-(N-hydroxyacetamido)pentanamido)-5-(N-hydroxyacetamido)pentanamido)-5-(N-hydroxyacetamido)pentanoic acid；5-[N-acetyl(hydroxyamino)]-2-{5-[N-acetyl(hydroxyamino)]-2-{5-[N-acetyl(hydroxyamino)]-2-aminovalerylamino}valerylamino}valeric acid；linear desferrichrome；LDFC；(2S)-5-[acetyl(hydroxy)amino]-2-[[(2S)-5-[acetyl(hydroxy)amino]-2-[[(2S)-5-[acetyl(hydroxy)amino]-2-aminopentanoyl]amino]pentanoyl]amino]pentanoic acid
• CAS: 92412-99-2
• 化学式: C₂₁H₃₈N₆O₁₀
• 分子量: 534.567
• InChiKey: URZSBXLQDOXBNC-BZSNNMDCSA-N

物化性质

• 熔点：
  73-75 °C
• 密度：
  1.363±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -5.4
• 重原子数：
  37
• 可旋转键数：
  17
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  243
• 氢给体数：
  7
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  H-Hyo(N⁵-Ac)-Hyo(N⁵-Ac)-Hyo(N⁵-Ac)-OH 、 digoxigenin-3-O-methylcarbonyl-ε-aminocaproic acid N-hydroxysuccinimide ester 在 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以85%的产率得到
  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
• 作为产物：
  描述：

  N-苄氧羰基-N’-叔丁氧羰基-L-鸟氨酸 在 N-羟基丁二酰亚胺 、 palladium on activated charcoal 、 氢气 、 碳酸氢钠 、 potassium hydrogencarbonate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 82.0h， 生成 H-Hyo(N⁵-Ac)-Hyo(N⁵-Ac)-Hyo(N⁵-Ac)-OH
  参考文献：
  名称：

  直接测量气相配位配合物水合状态的一般方法：变温质谱法

  摘要：

  基于金属的诊断和治疗的三元水复合物的形成与其体内功效密切相关，但量化配位水配体存在的方法是有限的。我们介绍了一种通用的高通量方法，用于基于变温离子阱串联质谱法表征气相中顺磁性和反磁性配位配合物的水合状态。三元水复合物可直接在质谱中观察到，并作为离子阱温度的函数进行量化。我们恢复了镧系元素水合的预期周期性趋势，并通过检查温度相关的物种形成曲线来区分具有几种内球水配体的配合物。我们推导出可辨别的内球和第二球水合事件的气相热力学参数，并讨论它们在预测溶液相行为方面的应用。水在内部和外部球体中结合的温度差异主要来自熵效应。这种方法的广泛适用性使我们能够在活跃的临床前和临床研究中估计 Ga、Sc 和 Zr 配合物的水合状态，但水合数尚未确定。变温质谱仪作为表征和量化元素周期表内球体水合作用趋势的通用工具而出现。Sc 和 Zr 配合物正在进行积极的临床前和临床研究，水合值尚未确定。变温质谱仪作为表征和

  DOI：

  10.1021/jacs.9b05874

文献信息

• Albomycine, IV. Isolierung und Totalsynthese von (N5-Acetyl-N5-hydroxy-L-ornithyl)-(N5-acetyl-N5-hydroxy-L-ornithyl)-N5-acetyl-N5-hydroxy-L-ornithin
  作者：Günter Benz、Delf Schmidt

  DOI：10.1002/jlac.198419840805

  日期：1984.8.10

  Die Isolierung, Charakterisierung und Synthese von (N5-Acetyl-N5-hydroxy-L-ornithyl)-(N5-acetyl-N5-hydroxy-L-ornithyl)-N5-hydroxy-L-ornithin (2), der Hydroxamsäureseitenkette der Albomycine wird beschrieben.

  （N 5-乙酰基-N 5-羟基-L-鸟氨酸）-（N 5-乙酰基-N 5-羟基-L-鸟氨酸）-N 5-羟基-L-鸟氨酸的分离，表征和合成（2） ，描述了阿波霉素的异羟肟酸侧链。
• Synthesis and siderophore activity of albomycin-like peptides derived from N5-acetyl-N5-hydroxy-L-ornithine
  作者：E. Kurt Dolence、Chia En Lin、Marvin J. Miller、Shelley M. Payne

  DOI：10.1021/jm00107a013

  日期：1991.3

  N5-Acetyl-N5-hydroxy-L-ornithine (1), the key constituent of several microbial siderophores, has been synthesized in 23 % yield overall from N-Cbz-L-glutamic acid 1-tert-butyl ester (6) derived from L-glutamic acid. Reduction of 6 to 7 and treatment with N-[(trichloroethoxy)carbonyl]-O-benzylhydroxylamine (8), and diethyl azodicarboxylate and triphenylphosphine followed by deprotection produced the protected N5-acetyl-N5-hydroxy-L-ornithine derivatives 11 and 12 in large quantities (10-20 g). Following alpha-amino and alpha-carboxyl deprotections of 11 and 12, EEDQ [2-ethoxy-N-(ethoxycarbonyl)-1,2-dihydroquinoline] mediated peptide coupling and final deprotection provided amino acid 1 and six albomycin-like peptides (20, 23, 25, 28, 35, and 36). The growth-promoting ability of each was evaluated with the siderophore biosynthesis mutant Shigella flexneri SA240 (SA 100 iucD:Tn5). These results indicate that substantial modification of the framework of peptide-based siderophores can be tolerated by microbial iron-transport systems.
• 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.
• Multifunctional Desferrichrome Analogues as Versatile ⁸⁹Zr(IV) Chelators for ImmunoPET Probe Development
  作者：Casey J. Adams、Justin J. Wilson、Eszter Boros

  DOI：10.1021/acs.molpharmaceut.7b00343

  日期：2017.8.7

  New bifunctional hexa- and octadentate analogues of the hydroxamate-containing siderophore desferri-chrome (DFC) have been synthesized and evaluated as Zr-89-chelating agents for immunoPET applications. The in vitro and in vivo inertness of these new ligands, Orn3-hx (hexadentate) and Orn-4hx derivatives (octadentate), was compared to the gold standard hexadentate, hydroxamate-containing chelator for Zr-89 desferrioxamine (DFO). Density functional theory was employed to model the geometries of the resulting Zr(IV) complexes and to predict their relative stabilities as follows: Zr(Orn4-hx) > Zr(DFC) > Zr(Orn3-hx). Transchelation challenge experiments of the corresponding radiochemical complexes with excess ethylenediaminetetraacetate (EDTA) indicated complex stability in accordance with DFT calculations. Radiolabeling of these ligands with (89)Zt was quantitative (0.25 mu mol of ligand, pH 7.4, room temperature, 20 min). For antibody conjugation, the isothiocyarrate (NOS) functional group was introduced to the N terminus of Orn3-hx and Orn-4hx. An additional trifunctional derivative that bears a silicon-rhodamine fluorophore on the C-terminus and NCS on the N terminus was also furnished. As proof of concept, all NCS derivatives were conjugated to the HER2-targeting antibody, trastuzumab. Radiolabeling of immunoconjngates with Zr-89 was accomplished with radiochemical yields of 16 +/- 2% to 95 +/- 2%. These constructs were administered to naive mice (male, C57BL/6J, n = 4) to assess in vivo inertness, which is inversely correlated with uptake, of Zr-89 in bone, after 96 h circulation time. We found, bone uptake to range from 7.0 +/- 2.2 to 10.7 +/- 1.3% ID/g, values that compare well to the corresponding DFO conjugate (7.1 +/- 0.8% ID/g). In conclusion, we have rationally designed linear, bifunctional and trifunctional desferrichrome analogues suitable for the mild and inert radiolabeling of antibodies with the radionuclide Zr-89.
• Paulsen, Hans; Brieden, Monika; Benz, Guenter, Liebigs Annalen der Chemie, 1987, p. 565 - 576
  作者：Paulsen, Hans、Brieden, Monika、Benz, Guenter

  DOI：——

  日期：——