N⁵-acetyl-N⁵-(benzyloxy)-N²-(benzyloxycarbonyl)-L-ornithine | 89969-29-9

• 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: N⁵-acetyl-N⁵-(benzyloxy)-N²-(benzyloxycarbonyl)-L-ornithine
• 英文别名: (2S)-5-[acetyl(phenylmethoxy)amino]-2-(phenylmethoxycarbonylamino)pentanoic acid
• CAS: 89969-29-9
• 化学式: C₂₂H₂₆N₂O₆
• 分子量: 414.458
• InChiKey: JHAPPQJEBYIXGF-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.13
• 重原子数：
  30.0
• 可旋转键数：
  11.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  105.17
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N⁵-acetyl-N⁵-(benzyloxy)-N²-(benzyloxycarbonyl)-L-ornithine 以67%的产率得到
  参考文献：
  名称：

  DOLENCE, E. KURT.;LIN, CHIA-EN;MILLER, MARVIN J.;PAYNE, SHELLEY M., J. MED. CHEM., 34,(1991) N, C. 956-968

  摘要：

  DOI：
• 作为产物：
  描述：

  N⁵-Acetyl-N⁵-benzyloxy-N²-(benzyloxycarbonyl)-L-ornithin-tert-butylester 在 三氟乙酸 作用下， 反应 0.5h， 以100%的产率得到N⁵-acetyl-N⁵-(benzyloxy)-N²-(benzyloxycarbonyl)-L-ornithine
  参考文献：
  名称：

  Synthesis and siderophore activity of albomycin-like peptides derived from N5-acetyl-N5-hydroxy-L-ornithine

  摘要：

  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.

  DOI：

  10.1021/jm00107a013

文献信息

• Constituents of microbial iron chelators. The synthesis of optically active derivatives of δ-N-hydroxy-L-ornithine.
  作者：Byung Hyun Lee、Marvin J. Miller

  DOI：10.1016/s0040-4039(01)80064-2

  日期：1984.1

  δ-N-Hydroxy-L-ornithine derivatives were synthesized from L-glutamic acid by reduction of the γ-acid chloride to the aldehyde, formation of the substituted oxime, and reductive acylation.

  通过将γ-酰氯还原为醛，形成取代的肟和还原性酰化作用，由L-谷氨酸合成δ-N-羟基-L-鸟氨酸衍生物。
• Albomycine, III. Synthese vonN5-Acetyl-N5-hydroxy-L-ornithin ausL-Glutaminsäure
  作者：Günter Benz

  DOI：10.1002/jlac.198419840804

  日期：1984.8.10

  Die Hydroxamsäure N5-Acetyl-N5-hydroxy-L-ornithin (2a) besitzt entscheidende Bedeutung für die biologische Wirkung der Siderochrome. Die preiswerte L-Glutaminsäure (3) kann nach Schutz der α-Aminosäuregruppierung selektiv an der γ-Carbonsäurefunktion derivatisiert werden. Ein orthogonales Schutzgruppenmuster ist Voraussetzung für selektive Spaltungen zu partial geschützten Aminosäuren und zur Hydroxamsäure

  异羟肟酸N 5-乙酰基-N 5-羟基-L-鸟氨酸（2a）对于铁铬染料的生物学作用具有决定性的重要性。在保护了α-氨基酸基团之后，可以在γ-羧酸官能团上选择性地衍生廉价的L-谷氨酸（3）。正交保护基图案是选择性切割为部分受保护的氨基酸和异羟肟酸2a的先决条件。
• 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。
• Desketoneoenactin-Siderophore Conjugates for <i>Candida</i> : Evidence of Iron Transport-Dependent Species Selectivity
  作者：Geneviève Bernier、Vinay Girijavallabhan、Aaron Murray、Noormohamed Niyaz、Pingyu Ding、Marvin J. Miller、François Malouin

  DOI：10.1128/aac.49.1.241-248.2005

  日期：2005.1

  We investigated the inhibitory activity of synthetic isocyanurate-based as well as linear mono- and trihydroxamate siderophore-drug conjugates against Candida spp. The conjugated drug was 13C-desketoneoenactin (DE). The MICs of siderophore-drug conjugates were determined in the absence and presence of 2,2′-dipyridyl to restrict iron availability. The ability of various siderophore types to promote growth in an iron-restricted medium was also assayed. Addition of a siderophore portion to the drug strongly impaired the inhibitory activity of DE. However, the activity of the drug conjugates was increased by up to 16-fold in iron-depleted medium for species having their growth strongly promoted by most hydroxamate-type siderophores ( C. albicans , C. stellatoidea , and C. pseudotropicalis ). The uptake of ⁵⁵ Fe from ferrichrome and from two siderophore-drug conjugates was improved when C. albicans cells were grown in a low-iron medium. In the same assay, unlabeled ferrichrome was able to compete with the uptake of ⁵⁵ Fe from both conjugates, indicating a common mechanism of uptake. A C. albicans strain lacking the siderophore transporter CaSit1/CaArn1 was not able to use ferrichrome or the synthetic ornithine-based trihydroxamate siderophore for growth promotion and was much less susceptible to the siderophore-drug conjugates than its isogenic parent strain. In summary, the ability of some Candida spp. to use ferrichrome-like siderophores for growth promotion explains the selective activity of hydroxamate-drug conjugates, and this activity seems to be related to the presence, in C. albicans , of the siderophore transporter CaSit1/CaArn1. New conjugate designs are necessary to fully restore or improve the initial DE activity.

  摘要 我们研究了合成的异氰脲酸酯以及线性单羟基和三羟基氨基甲酸酯苷酸-药物共轭物对念珠菌的抑制活性。 念珠菌 13C-desketoneoenactin (DE)。在没有和有 2,2′-二吡啶限制铁的情况下，测定了嗜苷酸盐-药物共轭物的 MICs。此外，还测定了各种类型的嗜苷酸盐在铁限制培养基中促进生长的能力。在药物中加入嗜苷酸盐部分会大大削弱 DE 的抑制活性。然而，在缺铁培养基中，对于大多数羟酰胺类嗜苷酸盐能强烈促进生长的菌种（白念珠菌）来说，药物共轭物的活性最多可提高 16 倍。 白僵菌 , 白僵菌 和 C. pseudotropicalis ).吸收 55 铁铬和两种苷元-药物共轭物中铁的吸收率在 白僵菌 细胞在低铁培养基中生长时，其对 55 Fe 的吸收率有所提高。在同一试验中，未标记的亚铁铬能够与白僵菌细胞对 55 Fe 的吸收竞争。 55 铁的吸收，这表明两种共轭物具有共同的吸收机制。A 白僵菌 菌株不能利用亚铁铬或合成的基于鸟氨酸的三羟基氨基甲酸酯苷酸促进生长，而且对苷酸盐-药物共轭物的敏感性比其同源亲本菌株低得多。总之，一些 念珠菌 菌属能利用类似亚铁铬的嗜铁素促进生长，这解释了羟氨酸盐-药物共轭物的选择性活性。 白僵菌 中存在嗜苷酸盐转运体 CaSit1/CaArn1。有必要设计新的共轭物来完全恢复或提高最初的 DE 活性。
• N5-Acetyl-N5-hydroxy-L-ornithine-derived siderophore-carbacephalosporin .beta.-lactam conjugates: iron transport mediated drug delivery
  作者：E. Kurt Dolence、Albert A. Minnick、Marvin J. Miller

  DOI：10.1021/jm00164a001

  日期：1990.2