Cbz-N(Me)Val-Pro-OtBu | 205498-72-2

• 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: Cbz-N(Me)Val-Pro-OtBu
• 英文别名: tert-butyl (2S)-1-[(2S)-3-methyl-2-[methyl(phenylmethoxycarbonyl)amino]butanoyl]pyrrolidine-2-carboxylate
• CAS: 205498-72-2
• 化学式: C₂₃H₃₄N₂O₅
• 分子量: 418.533
• InChiKey: GZYMRWOUZAMEBZ-OALUTQOASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  76.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Cbz-N(Me)Val-Pro-OtBu 在 palladium on activated charcoal 盐酸 、 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 34.0h， 生成 Cbz-Val-Val-N(Me)Val-Pro-OtBu
  参考文献：
  名称：

  Synthesis and Biological Activity of Chimeric Structures Derived from the Cytotoxic Natural Compounds Dolastatin 10 and Dolastatin 15

  摘要：

  The natural cytotoxic compounds dolastatins 10 and 15 exhibit great similarities in structure and in their biological activity profiles. Two compounds (1 and 2) formed by interchanging the dolaisoleuine residue of dolastatin 10 and the MeVal-Pro dipeptide of dolastatin 15 were synthesized in order to evaluate the possible equivalence of these units. These compounds can be considered as chimeras of dolastatins 10 and 15 formed by the N-terminal part of the former and the C-terminal part of the latter and vice versa. Both analogues exhibited a marked decrease in their cytotoxic activity but showed similar differential cytotoxicity with regard to the cell Lines assayed compared with the parent compounds. HT-29 cell line was the least sensitive one. However, this activity was in the nanomolar level and close to that of vincristine. The differences in their effect on tubulin polymerization were less pronounced. We confirmed the already known crucial role of the Dil residue in this assay. The nonequivalence of the Dil unit and the MeVal-Pro dipeptide probably reflects modification in the relative positions of the N-dimethylamino and the phenyl moieties.

  DOI：

  10.1021/jm970800t
• 作为产物：
  描述：

  N-苄氧羰基-N-甲基-L-缬氨酸 、 L-脯氨酸叔丁酯 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以84%的产率得到Cbz-N(Me)Val-Pro-OtBu
  参考文献：
  名称：

  草皮内酯的全合成。

  摘要：

  从海洋蓝细菌分离出的一种抗癌环二肽多肽草肽内酯的第一个全合成已通过17个步骤完成，总产率为11.3％。

  DOI：

  10.1039/c0cc01200a

文献信息

• Total synthesis of grassypeptolide
  作者：Hui Liu、Yuqing Liu、Xiangyou Xing、Zhengshuang Xu、Tao Ye

  DOI：10.1039/c0cc01200a

  日期：——

  The first total synthesis of grassypeptolide, an anticancer cyclodepsipeptide isolated from marine cyanobacteria, has been achieved in 17 steps and an overall 11.3% yield.

  从海洋蓝细菌分离出的一种抗癌环二肽多肽草肽内酯的第一个全合成已通过17个步骤完成，总产率为11.3％。
• Total Synthesis and Biological Evaluation of Grassypeptolide A
  作者：Hui Liu、Yuqing Liu、Zhuo Wang、Xiangyou Xing、Anita R. Maguire、Hendrik Luesch、Hui Zhang、Zhengshuang Xu、Tao Ye

  DOI：10.1002/chem.201203667

  日期：2013.5.17

  investigations into the synthesis of grassypeptolide A (1) in 17 linear steps with an overall yield of 11.3 %. In particular, this work features the late‐stage introduction of sensitive bis(thiazoline) heterocycles and 31‐membered macrocyclization conducted at the sterically congested secondary amide site in superb conversion (72 % yield). Biological evaluation indicated that grassypeptolide A significantly

  在本文中，我们全面描述了草皮肽A（1）分17线性步长，总收率为11.3％。特别是，这项工作的特点是后期引​​入了敏感的双（噻唑啉）杂环和在空间拥挤的仲酰胺位点进行了出色的转化（72％收率）的31元大环化。生物学评估表明，草肽内酯A以剂量依赖的方式显着抑制癌细胞的增殖。它诱导癌细胞凋亡，这与聚（ADP-核糖）聚合酶（PARP）的切割增加和bcl-2和bcl-xL的表达降低有关。此外，草肽A还通过增加G1期的细胞和减少S期和G2期的细胞而引起细胞周期的重新分布。另外，细胞周期停滞与细胞周期蛋白D的下调以及p27和p21的上调相关。
• Synthesis and Biological Activity of Chimeric Structures Derived from the Cytotoxic Natural Compounds Dolastatin 10 and Dolastatin 15
  作者：Joël Poncet、Magali Busquet、Florence Roux、Alain Pierré、Ghanem Atassi、Patrick Jouin

  DOI：10.1021/jm970800t

  日期：1998.4.1

  The natural cytotoxic compounds dolastatins 10 and 15 exhibit great similarities in structure and in their biological activity profiles. Two compounds (1 and 2) formed by interchanging the dolaisoleuine residue of dolastatin 10 and the MeVal-Pro dipeptide of dolastatin 15 were synthesized in order to evaluate the possible equivalence of these units. These compounds can be considered as chimeras of dolastatins 10 and 15 formed by the N-terminal part of the former and the C-terminal part of the latter and vice versa. Both analogues exhibited a marked decrease in their cytotoxic activity but showed similar differential cytotoxicity with regard to the cell Lines assayed compared with the parent compounds. HT-29 cell line was the least sensitive one. However, this activity was in the nanomolar level and close to that of vincristine. The differences in their effect on tubulin polymerization were less pronounced. We confirmed the already known crucial role of the Dil residue in this assay. The nonequivalence of the Dil unit and the MeVal-Pro dipeptide probably reflects modification in the relative positions of the N-dimethylamino and the phenyl moieties.