3,4-bis(benzyloxy)-5-(((3S,7S,11S)-7,11-bis(2,3-bis(benzyloxy)benzamido)-2,6,10-trioxo-1,5,9-trioxacyclododecan-3-yl)carbamoyl)benzoic acid | 1407510-70-6

• 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: 3,4-bis(benzyloxy)-5-(((3S,7S,11S)-7,11-bis(2,3-bis(benzyloxy)benzamido)-2,6,10-trioxo-1,5,9-trioxacyclododecan-3-yl)carbamoyl)benzoic acid
• 英文别名: 3-[[(3S,7S,11S)-7,11-bis[[2,3-bis(phenylmethoxy)benzoyl]amino]-2,6,10-trioxo-1,5,9-trioxacyclododec-3-yl]carbamoyl]-4,5-bis(phenylmethoxy)benzoic acid
• CAS: 1407510-70-6
• 化学式: C₇₃H₆₃N₃O₁₇
• 分子量: 1254.31
• InChiKey: LFHORORBWPYAGJ-RATTXREYSA-N

物化性质

• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  11.1
• 重原子数：
  93
• 可旋转键数：
  25
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  259
• 氢给体数：
  4
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  3,4-bis(benzyloxy)-5-(((3S,7S,11S)-7,11-bis(2,3-bis(benzyloxy)benzamido)-2,6,10-trioxo-1,5,9-trioxacyclododecan-3-yl)carbamoyl)benzoic acid 、 1-氨基-11-叠氮-3,6,9-三氧杂十一烷 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以68%的产率得到N1-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethyl)-4,5-bis-(benzyloxy)-N3-((3S,7S,11S)-7,11-bis(2,3-bis(benzyloxy)benzamido)-2,6,10-trioxo-1,5,9-trioxacyclododecan-3-yl)isophthalamide
  参考文献：
  名称：

  ENTEROBACTIN CONJUGATES AND USES THEREOF

  摘要：

  本发明提供了新型肠杆菌铁胞内载体共轭物，如式(I)化合物及其盐，其中X是载体，可以是抗生素、荧光素或生物素。本发明还提供了涉及式(I)化合物的络合物、组合物、试剂盒和方法，用于将载体传递给细菌，治疗受试者的细菌感染、囊性纤维化和/或炎症性肠病，预防受试者的细菌感染、囊性纤维化和/或炎症性肠病，抑制或杀死细菌的生长，或确定生物样品中细菌的浓度。在某些实施例中，细菌是革兰氏阴性细菌。

  公开号：

  US20150105337A1
• 作为产物：
  描述：

  N,N′-((3S,7S,11S)-11-(2,3-bis(benzyloxy)-5-formylbenzamido)-2,6,10-trioxo-1,5,9-trioxacyclododecane-3,7-diyl)bis(2,3-bis(benzyloxy)benzamide) 在 sodium chlorite 、 氨基磺酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 0.66h， 以76%的产率得到3,4-bis(benzyloxy)-5-(((3S,7S,11S)-7,11-bis(2,3-bis(benzyloxy)benzamido)-2,6,10-trioxo-1,5,9-trioxacyclododecan-3-yl)carbamoyl)benzoic acid
  参考文献：
  名称：

  ENTEROBACTIN CONJUGATES AND USES THEREOF

  摘要：

  本发明提供了新型肠杆菌铁胞内载体共轭物，如式(I)化合物及其盐，其中X是载体，可以是抗生素、荧光素或生物素。本发明还提供了涉及式(I)化合物的络合物、组合物、试剂盒和方法，用于将载体传递给细菌，治疗受试者的细菌感染、囊性纤维化和/或炎症性肠病，预防受试者的细菌感染、囊性纤维化和/或炎症性肠病，抑制或杀死细菌的生长，或确定生物样品中细菌的浓度。在某些实施例中，细菌是革兰氏阴性细菌。

  公开号：

  US20150105337A1

文献信息

• Evaluation of a reducible disulfide linker for siderophore-mediated delivery of antibiotics
  作者：Wilma Neumann、Elizabeth M. Nolan

  DOI：10.1007/s00775-018-1588-y

  日期：2018.10

  be hijacked for the targeted delivery of antibiotics into pathogens by attaching antibiotics to siderophores, iron chelators that are employed by bacteria to obtain this essential nutrient. We synthesized and evaluated Ent-SS-Cipro, a siderophore-antibiotic conjugate comprised of the triscatecholate siderophore enterobactin and the fluoroquinolone antibiotic ciprofloxacin that contains a self-immolative

  通过将抗生素附着到铁载体上，细菌可以利用铁吸收剂将细菌的铁吸收机制有针对性地释放到病原体中，铁螯合剂被细菌用来获得这种基本营养。我们合成并评估了Ent-SS-Cipro，这是一种铁载体-抗生素共轭物，由三儿茶酚铁载体肠杆菌素和氟喹诺酮类抗生素环丙沙星组成，后者含有自消灭性二硫键。该接头被设计成在摄入细菌细胞质的还原环境后被切割。我们显示Ent-SS-Cipro的二硫键被还原剂裂解，包括细胞还原剂谷胱甘肽，导致释放未修饰的氟喹诺酮抗生素。对一组大肠杆菌的抗菌活性分析表明，Ent-SS-Cipro对某些（而非全部）大肠杆菌表现出活性。这项工作为铁载体-抗生素结合物的设计提供了依据，特别是那些携带了具有胞质靶标的抗生素的结合物，这些结合物需要被摄入细菌细胞后释放，并表明二硫键可能通常不适用于抗生素的结合策略。
• Evaluation of (acyloxy)alkyl ester linkers for antibiotic release from siderophore–antibiotic conjugates
  作者：Tengfei Zheng、Elizabeth M. Nolan

  DOI：10.1016/j.bmcl.2015.02.034

  日期：2015.11

  The syntheses of five ciprofloxacin-modified (acyloxyl) alkyl esters and two siderophore-ciprofloxacin conjugates based on enterobactin that harbor such hydrolyzable linkages are reported. The hydrolytic stabilities of ciprofloxacin-modified (acyloxy) alkyl esters, evaluated at pH 7.5 and 30 degrees C, vary by >370-fold depending on the substituents in the vicinity of the ester linkage. (C) 2015 Elsevier Ltd. All rights reserved.
• Siderophore-Mediated Cargo Delivery to the Cytoplasm of <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i>: Syntheses of Monofunctionalized Enterobactin Scaffolds and Evaluation of Enterobactin–Cargo Conjugate Uptake
  作者：Tengfei Zheng、Justin L. Bullock、Elizabeth M. Nolan

  DOI：10.1021/ja3077268

  日期：2012.11.7

  The design and syntheses of monofunctionalized enterobactin (Ent, L- and D-isomers) scaffolds where one catecholate moiety of enterobactin houses an alkene, aldehyde, or carboxylic acid at the C5 position are described. These molecules are key precursors to a family of 10 enterobactin-cargo conjugates presented in this work, which were designed to probe the extent to which the Gram-negative ferric enterobactin uptake and processing machinery recognizes, transports, and utilizes derivatized enterobactin scaffolds. A series of growth recovery assays employing enterobactin-deficient E. coli ATCC 33475 (ent-) revealed that six conjugates based on L-Ent having relatively small cargos promoted E. coli growth under iron limiting conditions whereas negligible-to-no growth recovery was observed for four conjugates with relatively large cargos. No growth recovery was observed for the enterobactin receptor deficient strain of E. coli H1187 (fepA-) or the enterobactin esterase deficient derivative of E. coli K-12 JW0576 (fes-), or when the D-isomer of enterobactin was employed These results demonstrate that the E. coli ferric enterobactin transport machinery identifies and delivers select cargo-modified scaffolds to the E. coli cytoplasm. Pseudomonas aeruginosa PAO1 K648 (pvd-, pch-) exhibited greater promiscuity than that of E. coli for the uptake and utilization of the enterobactin-cargo conjugates, and growth promotion was observed for eight conjugates under iron-limiting conditions. Enterobactin may be utilized for delivering molecular cargos via its transport machinery to the cytoplasm of E. coli and P. aeruginosa thereby providing a means to overcome the Gram-negative outer membrane permeability barrier.
• US9902986B2
  申请人：——

  公开号：US9902986B2

  公开（公告）日：2018-02-27