(S)-5-azido-2-[(9H-fluorene-9-yl-methoxycarbonylamino)methyl]pentanoic acid | 1424402-17-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (S)-5-azido-2-[(9H-fluorene-9-yl-methoxycarbonylamino)methyl]pentanoic acid
• 英文别名: (2S)-5-azido-2-[(9H-fluoren-9-ylmethoxycarbonylamino)methyl]pentanoic acid
• CAS: 1424402-17-4
• 化学式: C₂₁H₂₂N₄O₄
• 分子量: 394.43
• InChiKey: DCZCILZILIZJKS-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  90
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [(E,2S,3S)-7-[[(2R)-3-(3-chloro-4-methoxyphenyl)-1-oxo-1-(2,2,2-trichloroethoxy)propan-2-yl]amino]-2-[(4R,5R)-2,2-dimethyl-5-phenyl-1,3-dioxolan-4-yl]-7-oxohept-5-en-3-yl] (2S)-2-hydroxy-4-methylpentanoate 、 (S)-5-azido-2-[(9H-fluorene-9-yl-methoxycarbonylamino)methyl]pentanoic acid 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以82%的产率得到[(2S)-1-[(E,2S,3S)-7-[[(2R)-3-(3-chloro-4-methoxyphenyl)-1-oxo-1-(2,2,2-trichloroethoxy)propan-2-yl]amino]-2-[(4R,5R)-2,2-dimethyl-5-phenyl-1,3-dioxolan-4-yl]-7-oxohept-5-en-3-yl]oxy-4-methyl-1-oxopentan-2-yl] (2S)-5-azido-2-[(9H-fluoren-9-ylmethoxycarbonylamino)methyl]pentanoate
  参考文献：
  名称：

  Conjugates of Modified Cryptophycins and RGD-Peptides Enter Target Cells by Endocytosis

  摘要：

  Tumor targeting anticancer drug conjugates that contain a tumor recognition motif (homing device) are of high current relevance. Cryptophycins, naturally occurring cytotoxic cyclo-depsipeptides, have been modified by total synthesis to provide analogues suitable for conjugation to peptide-based homing devices. An array of functionalized beta(2)-amino acids was synthesized and incorporated into cryptophycins. All analogues proved to be highly active in the cytotoxicity assay using the human cervix carcinoma cell line KB-3-1 and its multidrug-resistant subclone KB-V1. Conformational analysis of cryptophycin-52 and two synthetic analogues was performed by NMR and MD methods to obtain information on the influence of the unit C configuration on the overall conformation. An azide-functionalized cryptophycin was connected by CuAAC to an alkyne-containing fluorescently labeled cyclic RGD-peptide as the homing device for internalization studies. Confocal fluorescence microscopy proved integrin-mediated internalization by endocytosis and final lysosomal localization of the cryptophycin prodrug.

  DOI：

  10.1021/jm301346z

文献信息

• Conjugates of Modified Cryptophycins and RGD-Peptides Enter Target Cells by Endocytosis
  作者：Markus Nahrwold、Christine Weiß、Tobias Bogner、Felix Mertink、Jens Conradi、Benedikt Sammet、Ralf Palmisano、Soledad Royo Gracia、Thomas Preuße、Norbert Sewald

  DOI：10.1021/jm301346z

  日期：2013.3.14

  Tumor targeting anticancer drug conjugates that contain a tumor recognition motif (homing device) are of high current relevance. Cryptophycins, naturally occurring cytotoxic cyclo-depsipeptides, have been modified by total synthesis to provide analogues suitable for conjugation to peptide-based homing devices. An array of functionalized beta(2)-amino acids was synthesized and incorporated into cryptophycins. All analogues proved to be highly active in the cytotoxicity assay using the human cervix carcinoma cell line KB-3-1 and its multidrug-resistant subclone KB-V1. Conformational analysis of cryptophycin-52 and two synthetic analogues was performed by NMR and MD methods to obtain information on the influence of the unit C configuration on the overall conformation. An azide-functionalized cryptophycin was connected by CuAAC to an alkyne-containing fluorescently labeled cyclic RGD-peptide as the homing device for internalization studies. Confocal fluorescence microscopy proved integrin-mediated internalization by endocytosis and final lysosomal localization of the cryptophycin prodrug.