BrCH2ProlIleAsp(OBzI) | 1097833-47-0

• 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: BrCH2ProlIleAsp(OBzI)
• 英文别名: BrAc-Pro-Ile-Asp(OBn)-OBn；dibenzyl (2S)-2-[[(2S,3S)-2-[[(2S)-1-(2-bromoacetyl)pyrrolidine-2-carbonyl]amino]-3-methylpentanoyl]amino]butanedioate
• CAS: 1097833-47-0
• 化学式: C₃₁H₃₈BrN₃O₇
• 分子量: 644.563
• InChiKey: PBAQGTWAWNHNHW-WWZJJOFDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  42
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  131
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  BrCH2ProlIleAsp(OBzI) 、 脱水长春碱 以 乙腈 为溶剂， 反应 3.0h， 以74%的产率得到dibenzyl (2S)-2-[[(2S,3S)-2-[[(2S)-1-[2-[(13S,15R)-13-[(1R,9R,10S,11R,12R,19R)-11-acetyloxy-12-ethyl-10-hydroxy-5-methoxy-10-methoxycarbonyl-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-13-methoxycarbonyl-11-aza-1-azoniatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9,16-pentaen-1-yl]acetyl]pyrrolidine-2-carbonyl]amino]-3-methylpentanoyl]amino]butanedioate;bromide
  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：

  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

文献信息

• Elaboration of Simplified Vinca Alkaloids and Phomopsin Hybrids
  作者：Quoc Anh Ngo、Fanny Roussi、Sylviane Thoret、Françoise Guéritte

  DOI：10.1111/j.1747-0285.2009.00922.x

  日期：2010.3

  Nine simplified vinca alkaloids and phomospin A hybrids, in which vindoline moiety has been replaced by a simpler scaffold, have been elaborated to evaluate their activity on the inhibition of tubulin polymerization. This article deals with the synthesis of various simplified vinca alkaloids, using a stereoselective coupling of catharantine with reactive aromatic compounds and methanol as well as their subsequent condensation with a large peptide chain mimicking those of phomopsin A. Biological evaluation and molecular modeling studies are also reported.