TFA*ProIleAsp(OBzl)2 | 1097833-45-8

• 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: TFA*ProIleAsp(OBzl)2
• 英文别名: H-L-ProIleAsp(OBzl)2*CF3COOH
• CAS: 1097833-45-8
• 化学式: C₂HF₃O₂*C₂₉H₃₇N₃O₆
• 分子量: 637.653
• InChiKey: IKTUPPAGJXJXOF-QVROWXSHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.26
• 重原子数：
  45.0
• 可旋转键数：
  13.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  160.13
• 氢给体数：
  4.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  TFA*ProIleAsp(OBzl)2 、 溴乙酸 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以83%的产率得到BrCH2ProlIleAsp(OBzI)
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Vinca Alkaloids and Phomopsin Hybrids

  摘要：

  Ten hybrids of vinca alkaloids and phomopsin A have been synthesized by linking the octahydrophomopsin lateral chain to the tertiary amine of the cleavamine moiety of anhydrovinblastine (AVLB) and vinorelbine. These compounds have been elaborated in order to obtain original products that may interfere with both binding sites of vinblastine (VLB) and phomopsin in tubulin. Although NMR and molecular modeling studies have shown that the orientation of the added peptide chains of these hybrids is not the same as those of phomopsin A, most of them are very potent inhibitors of microtubules assembly and they present good cytotoxicity against KB cell line. These interesting biological activities may eventually be explained by the fact that their lateral chain resides in a pocket distinct from that of the phomopsin A peptide, at the interface of tubulins beta and alpha.

  DOI：

  10.1021/jm801064y
• 作为产物：
  描述：

  Boc-ProIleAsp-(OBzl)2 、 三氟乙酸 以 二氯甲烷 为溶剂， 以100%的产率得到TFA*ProIleAsp(OBzl)2
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Vinca Alkaloids and Phomopsin Hybrids

  摘要：

  Ten hybrids of vinca alkaloids and phomopsin A have been synthesized by linking the octahydrophomopsin lateral chain to the tertiary amine of the cleavamine moiety of anhydrovinblastine (AVLB) and vinorelbine. These compounds have been elaborated in order to obtain original products that may interfere with both binding sites of vinblastine (VLB) and phomopsin in tubulin. Although NMR and molecular modeling studies have shown that the orientation of the added peptide chains of these hybrids is not the same as those of phomopsin A, most of them are very potent inhibitors of microtubules assembly and they present good cytotoxicity against KB cell line. These interesting biological activities may eventually be explained by the fact that their lateral chain resides in a pocket distinct from that of the phomopsin A peptide, at the interface of tubulins beta and alpha.

  DOI：

  10.1021/jm801064y

文献信息

• Elaboration of vinblastine hybrids using a reactive in situ generated N-carboxyanhydride
  作者：Claire Rannoux、Fanny Roussi、Marie-Thérèse Martin、Françoise Guéritte

  DOI：10.1039/c0ob01065k

  日期：——

  Hybrids of vinblastine and phomopsin, designed by a molecular modelling study, were elaborated in order to target tubulin. The key step of the synthesis (fragmentation and insertion of vindoline) was mediated by an internal N-carboxyanhydride (or O-acylcarbamate). This reaction was diastereospecific and addition of silver salts could reverse the diastereoselectivity. Even if the synthesized compounds are inactive, this synthesis represents an original example of a C–N fragmentation mediated by a N-carboxyanhydride.

  通过分子建模研究，我们设计出了针对微管蛋白的长春新碱和磷霉素混合物。合成的关键步骤（吲哚啉的破碎和插入）由内部的 N-羧基酸酐（或 O-酰基氨基甲酸酯）介导。该反应具有非对映选择性，加入银盐可逆转非对映选择性。即使合成的化合物没有活性，这一合成也代表了由 N-羧基酸酐介导的 C-N 断裂反应的一个原始实例。