benzyl (2S)-2-[3-[(2R)-2-tert-butoxycarbonylamino-3-(phenyl)propionylamino]propionyloxy]-4-methylpentanoate | 654068-57-2

• 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: benzyl (2S)-2-[3-[(2R)-2-tert-butoxycarbonylamino-3-(phenyl)propionylamino]propionyloxy]-4-methylpentanoate
• CAS: 654068-57-2
• 化学式: C₃₀H₄₀N₂O₇
• 分子量: 540.657
• InChiKey: YSXNQAMFJMYYEQ-RPBOFIJWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.33
• 重原子数：
  39.0
• 可旋转键数：
  13.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  120.03
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  benzyl (2S)-2-[3-[(2R)-2-tert-butoxycarbonylamino-3-(phenyl)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 、 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 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 、 丙酮 、 乙腈 为溶剂， 反应 16.0h， 生成 demethoxycryptophycin-24
  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：

  Boc-D-苯丙氨酸 、 在 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 16.5h， 以2.70 g的产率得到benzyl (2S)-2-[3-[(2R)-2-tert-butoxycarbonylamino-3-(phenyl)propionylamino]propionyloxy]-4-methylpentanoate
  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