methyl N6-(benzyloxy)-N2-((benzyloxy)carbonyl)-N6-palmitoyl-L-lysinate | 1268337-71-8

• 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: methyl N6-(benzyloxy)-N2-((benzyloxy)carbonyl)-N6-palmitoyl-L-lysinate
• CAS: 1268337-71-8
• 化学式: C₃₈H₅₈N₂O₆
• 分子量: 638.888
• InChiKey: HQSYIRWFQBPORV-DHUJRADRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.07
• 重原子数：
  46.0
• 可旋转键数：
  26.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  94.17
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  methyl N6-(benzyloxy)-N2-((benzyloxy)carbonyl)-N6-palmitoyl-L-lysinate 在 水 、 碳酸氢钠 、 N,N'-二环己基碳二亚胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 53.0h， 生成 (S)-3-((S)-2-(((benzyloxy)carbonyl)amino)-6-(N-(benzyloxy)palmitamido)hexanamido)-2-((tert-butoxycarbonyl)amino)propanoic acid
  参考文献：
  名称：

  Design, Synthesis, and Study of a Mycobactin−Artemisinin Conjugate That Has Selective and Potent Activity against Tuberculosis and Malaria

  摘要：

  Although the antimalarial agent artemisinin itself is not active against tuberculosis, conjugation to a mycobacterial-specific siderophore (microbial iron chelator) analogue induces significant and selective anti-tuberculosis activity, including activity against multi-and extensively drug-resistant strains of Mycobacterium tuberculosis. The conjugate also retains potent antimalarial activity. Physicochemical and whole-cell studies indicated that ferric-to-ferrous reduction of the iron complex of the conjugate initiates the expected bactericidal Fenton-type radical chemistry on the artemisinin component. Thus, this "Trojan horse" approach demonstrates that new pathogen-selective therapeutic agents in which the iron component of the delivery vehicle also participates in triggering the antibiotic activity can be generated. The result is that one appropriate conjugate has potent and selective activity against two of the most deadly diseases in the world.

  DOI：

  10.1021/ja109665t
• 作为产物：
  描述：

  Z-Lys(NOH)-OMe 在 甲醇 、 碳酸氢钠 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 生成 methyl N6-(benzyloxy)-N2-((benzyloxy)carbonyl)-N6-palmitoyl-L-lysinate
  参考文献：
  名称：

  Design, Synthesis, and Study of a Mycobactin−Artemisinin Conjugate That Has Selective and Potent Activity against Tuberculosis and Malaria

  摘要：

  Although the antimalarial agent artemisinin itself is not active against tuberculosis, conjugation to a mycobacterial-specific siderophore (microbial iron chelator) analogue induces significant and selective anti-tuberculosis activity, including activity against multi-and extensively drug-resistant strains of Mycobacterium tuberculosis. The conjugate also retains potent antimalarial activity. Physicochemical and whole-cell studies indicated that ferric-to-ferrous reduction of the iron complex of the conjugate initiates the expected bactericidal Fenton-type radical chemistry on the artemisinin component. Thus, this "Trojan horse" approach demonstrates that new pathogen-selective therapeutic agents in which the iron component of the delivery vehicle also participates in triggering the antibiotic activity can be generated. The result is that one appropriate conjugate has potent and selective activity against two of the most deadly diseases in the world.

  DOI：

  10.1021/ja109665t

文献信息

• Syntheses of mycobactin analogs as potent and selective inhibitors of Mycobacterium tuberculosis
  作者：Raúl E. Juárez-Hernández、Scott G. Franzblau、Marvin J. Miller

  DOI：10.1039/c2ob26077h

  日期：——

  Three analogs of mycobactin T, the siderophore secreted by Mycobacterium tuberculosis (Mtb) were synthesized and screened for their antibiotic activity against Mtb H37Rv and a broad panel of Gram-positive and Gram-negative bacteria. The synthetic mycobactins were potent (MIC90 0.02–0.88 μM in 7H12 media) and selective Mtb inhibitors, with no inhibitory activity observed against any other of the microorganisms tested. The maleimide-containing analog 40 represents a versatile platform for the development of mycobactin-drug conjugates, as well as other applications.

  合成了三种类角菌素 T 结构的类似物，这是结核分枝菌（Mtb）分泌的铁载体，并对其抗菌活性进行了筛选，针对 Mtb H37Rv 及一系列革兰氏阳性和革兰氏阴性细菌。合成的类角菌素具有较强的抑菌活性（在 7H12 培养基中，MIC90 为 0.02–0.88 μM），并且选择性抑制 Mtb，对其他测试的微生物没有抑制活性。含马来酰亚胺的类似物 40 代表了一种多功能平台，可用于类角菌素-药物结合物的开发及其他应用。