benzyl (2S,3S)-2-[[(2S)-1-(2-bromoacetyl)pyrrolidine-2-carbonyl]amino]-3-methylpentanoate | 1097833-33-4

• 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: benzyl (2S,3S)-2-[[(2S)-1-(2-bromoacetyl)pyrrolidine-2-carbonyl]amino]-3-methylpentanoate
• CAS: 1097833-33-4
• 化学式: C₂₀H₂₇BrN₂O₄
• 分子量: 439.349
• InChiKey: UMJZDICEAICZKP-ZVZYQTTQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl (2S,3S)-2-[[(2S)-1-(2-bromoacetyl)pyrrolidine-2-carbonyl]amino]-3-methylpentanoate 、 脱水长春碱 以 乙腈 为溶剂， 反应 3.0h， 以65%的产率得到methyl (1R,9R,10S,11R,12R,19R)-11-acetyloxy-12-ethyl-4-[(13S,15R)-17-ethyl-13-methoxycarbonyl-1-[2-[(2S)-2-[[(2S,3S)-3-methyl-1-oxo-1-phenylmethoxypentan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]-11-aza-1-azoniatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9,16-pentaen-13-yl]-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraene-10-carboxylate;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*Pro-Ile-OBzl 、 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85%的产率得到benzyl (2S,3S)-2-[[(2S)-1-(2-bromoacetyl)pyrrolidine-2-carbonyl]amino]-3-methylpentanoate
  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

• Synthesis and Biological Evaluation of Vinca Alkaloids and Phomopsin Hybrids
  作者：Quoc Anh Ngo、Fanny Roussi、Anthony Cormier、Sylviane Thoret、Marcel Knossow、Daniel Guénard、Françoise Guéritte

  DOI：10.1021/jm801064y

  日期：2009.1.8

  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.