tert-butyl (5S,6R)-5-[(2S)-2-[3-[(2R)-2-tert-butoxycarbonylamino-3-(3-chlorophenyl)propionylamino]propionyloxy]-4-methylpentanoyloxy]-6-methyl-8-phenylocta-(2E,7E)-dienoate | 654068-66-3

• 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: tert-butyl (5S,6R)-5-[(2S)-2-[3-[(2R)-2-tert-butoxycarbonylamino-3-(3-chlorophenyl)propionylamino]propionyloxy]-4-methylpentanoyloxy]-6-methyl-8-phenylocta-(2E,7E)-dienoate
• CAS: 654068-66-3
• 化学式: C₄₂H₅₇ClN₂O₉
• 分子量: 769.376
• InChiKey: BBZSQMUPSPYVBB-SSDCLBEOSA-N

物化性质

• 沸点：
  837.2±65.0 °C(predicted)
• 密度：
  1.143±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.79
• 重原子数：
  54.0
• 可旋转键数：
  18.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  146.33
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (5S,6R)-5-[(2S)-2-[3-[(2R)-2-tert-butoxycarbonylamino-3-(3-chlorophenyl)propionylamino]propionyloxy]-4-methylpentanoyloxy]-6-methyl-8-phenylocta-(2E,7E)-dienoate 在 二甲基二环氧乙烷 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 丙酮 、 乙腈 为溶剂， 反应 10.0h， 生成 (E)-(3S,10R,16S)-10-(3-Chloro-benzyl)-3-isobutyl-16-[(S)-1-((2S,3S)-3-phenyl-oxiranyl)-ethyl]-1,4-dioxa-8,11-diaza-cyclohexadec-13-ene-2,5,9,12-tetraone
  参考文献：
  名称：

  Total Synthesis and Antitubulin Activity of C10 Analogues of Cryptophycin-24

  摘要：

  The unsubstituted, 3'-C1, 4'-C1, and 3',4'-diC1 C10 analogues of cryptophycin-24 were prepared via total synthesis and tested in vitro for cytotoxicity against MCF-7 and multi-drug-resistant MCF-7/ADR breast cancer cell lines and in a tubulin assembly assay. The ED50 values ranged from 7.2 to 15.8 muM in the tubulin assay and from 0.05 to 3.4 nM in the cell assays. The presence of a 3'-C1 and/or 4'-C1 substituent on the C10 phenyl ring increased cytotoxicity in the MCF-7 cell line compared to the unsubstituted phenyl ring. The most potent compound in this series possessed a X-Cl substituent on the C10 phenyl ring. The X-Cl analogue had ED50 values of 50 and 580 pM in the MCF-7 and MCF-7/ADR cell lines, respectively. Its activity was very similar to the parent compound cryptophycin-24. Substitution of the 4'-MeO group in cryptophycin-24 with a 4'-C1 moiety did not significantly affect cytotoxicity against MCF-7 and MCF-7/ADR cells compared to the parent compound. These results demonstrated that the 4'-MeO group in cryptophycin-24 is not essential and can be replaced with X-Cl or 4'-C1 substituents.

  DOI：

  10.1021/jm030278c
• 作为产物：
  描述：

  benzyl (2S)-2-[3-[(2R)-2-tert-butoxycarbonylamino-3-(3-chlorophenyl)propionylamino]propionyloxy]-4-methylpentanoate 在 palladium dihydroxide 4-二甲氨基吡啶 、 2,4,6-三氯苯甲酰氯 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 6.0h， 生成 tert-butyl (5S,6R)-5-[(2S)-2-[3-[(2R)-2-tert-butoxycarbonylamino-3-(3-chlorophenyl)propionylamino]propionyloxy]-4-methylpentanoyloxy]-6-methyl-8-phenylocta-(2E,7E)-dienoate
  参考文献：
  名称：

  Total Synthesis and Antitubulin Activity of C10 Analogues of Cryptophycin-24

  摘要：

  The unsubstituted, 3'-C1, 4'-C1, and 3',4'-diC1 C10 analogues of cryptophycin-24 were prepared via total synthesis and tested in vitro for cytotoxicity against MCF-7 and multi-drug-resistant MCF-7/ADR breast cancer cell lines and in a tubulin assembly assay. The ED50 values ranged from 7.2 to 15.8 muM in the tubulin assay and from 0.05 to 3.4 nM in the cell assays. The presence of a 3'-C1 and/or 4'-C1 substituent on the C10 phenyl ring increased cytotoxicity in the MCF-7 cell line compared to the unsubstituted phenyl ring. The most potent compound in this series possessed a X-Cl substituent on the C10 phenyl ring. The X-Cl analogue had ED50 values of 50 and 580 pM in the MCF-7 and MCF-7/ADR cell lines, respectively. Its activity was very similar to the parent compound cryptophycin-24. Substitution of the 4'-MeO group in cryptophycin-24 with a 4'-C1 moiety did not significantly affect cytotoxicity against MCF-7 and MCF-7/ADR cells compared to the parent compound. These results demonstrated that the 4'-MeO group in cryptophycin-24 is not essential and can be replaced with X-Cl or 4'-C1 substituents.

  DOI：

  10.1021/jm030278c