(3S,6R,10R,13E,16S)-6-(3-azidopropyl)-10-[(3-chloro-4-methoxyphenyl)methyl]-3-(2-methylpropyl)-16-[(1S)-1-[(2R,3R)-3-phenyloxiran-2-yl]ethyl]-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone | 1424402-66-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (3S,6R,10R,13E,16S)-6-(3-azidopropyl)-10-[(3-chloro-4-methoxyphenyl)methyl]-3-(2-methylpropyl)-16-[(1S)-1-[(2R,3R)-3-phenyloxiran-2-yl]ethyl]-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone
• CAS: 1424402-66-3
• 化学式: C₃₇H₄₆ClN₅O₈
• 分子量: 724.254
• InChiKey: LWUAIQMSAVOWGP-ACQAAUEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  51
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  147
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (3S,6R,10R,13E,16S)-6-(3-azidopropyl)-10-[(3-chloro-4-methoxyphenyl)methyl]-3-(2-methylpropyl)-16-[(1S)-1-[(2R,3R)-3-phenyloxiran-2-yl]ethyl]-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone 、 2-甲基-3-丁炔-2-醇 在 copper(l) iodide 、 N,N-二异丙基乙胺 作用下， 以 甲苯 为溶剂， 反应 20.0h， 以90%的产率得到(3S,6R,10R,13E,16S)-10-[(3-chloro-4-methoxyphenyl)methyl]-6-[3-[4-(2-hydroxypropan-2-yl)triazol-1-yl]propyl]-3-(2-methylpropyl)-16-[(1S)-1-[(2R,3R)-3-phenyloxiran-2-yl]ethyl]-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone
  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
• 作为产物：
  描述：

  L-alpha-羟基异己酸 在 哌啶 、 咪唑 、 4-二甲氨基吡啶 、 ammonium cerium (IV) nitrate 、 草酰氯 、 乙酰溴 、 4-甲基苯磺酸吡啶 、 potassium carbonate 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 水 、 乙二醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 46.55h， 生成 (3S,6R,10R,13E,16S)-6-(3-azidopropyl)-10-[(3-chloro-4-methoxyphenyl)methyl]-3-(2-methylpropyl)-16-[(1S)-1-[(2R,3R)-3-phenyloxiran-2-yl]ethyl]-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone
  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.