N-benzyloxycarbonyl-L-alanyl-L-(Nδ-tert-butoxycarbonyl)lysine benzyl ester | 725240-04-0

• 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: N-benzyloxycarbonyl-L-alanyl-L-(Nδ-tert-butoxycarbonyl)lysine benzyl ester
• 英文别名: Cbz-Ala-Lys(Boc)-OBn；N-benzyloxycarbonyl-L-alanyl-L-(N^δ-tert-butoxycarbonyl)lysine benzyl ester
• CAS: 725240-04-0
• 化学式: C₂₉H₃₉N₃O₇
• 分子量: 541.645
• InChiKey: JTKLANBQHPXUCW-URXFXBBRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.22
• 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：
  0.45
• 拓扑面积：
  132.06
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  N-benzyloxycarbonyl-L-alanyl-L-(Nδ-tert-butoxycarbonyl)lysine benzyl ester 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-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 生成
  参考文献：
  名称：

  A strategy for dual inhibition of the proteasome and fatty acid synthase with belactosin C-orlistat hybrids

  摘要：

  The proteasome, a validated cellular target for cancer, is central for maintaining cellular homeostasis, while fatty acid synthase (FAS), a novel target for numerous cancers, is responsible for palmitic acid biosynthesis. Perturbation of either enzymatic machine results in decreased proliferation and ultimately cellular apoptosis. Based on structural similarities, we hypothesized that hybrid molecules of belactosin C, a known proteasome inhibitor, and orlistat, a known inhibitor of the thioesterase domain of FAS, could inhibit both enzymes. Herein, we describe proof-of-principle studies leading to the design, synthesis and enzymatic activity of several novel, B-lactone-based, dual inhibitors of these two enzymes. Validation of dual enzyme targeting through activity-based proteome profiling with an alkyne probe modeled after the most potent inhibitor, and preliminary serum stability studies of selected derivatives are also described. These results provide proof of concept for dual targeting of the proteasome and fatty acid synthase-thioesterase (FAS-TE) enabling a new approach for the development of drug-candidates with potential to overcome resistance. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.01.020
• 作为产物：
  描述：

  Fmoc-Lys(Boc)-OBn 在 N-羟基-7-氮杂苯并三氮唑 、 胸苷酸 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 二乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 19.0h， 生成 N-benzyloxycarbonyl-L-alanyl-L-(Nδ-tert-butoxycarbonyl)lysine benzyl ester
  参考文献：
  名称：

  Enantioselective Total Syntheses of Belactosin A, Belactosin C, and Its Homoanalogue

  摘要：

  Enantioselective total syntheses of belactosin A, belactosin C, and its homoanalogue have been accomplished in high overall yields (32% for belactosin A from the amino acid 10, and 35 and 36% for belactosin C and its homoanalogue, respectively). This concise approach comprises a novel sequential acylation/beta-lactonization reaction and allows a facile alteration of the substituents, thus providing a flexible route to a new family of highly active belactosin-based proteasome inhibitors.

  DOI：

  10.1021/ol049409+