A54556 factor E

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: A54556 factor E
• 英文别名: sorboyl-Phe-Ser(1)-Pro-N(Me)Ala-Ala-Pro-(1)；(2E,4E)-N-[(2S)-1-oxo-3-phenyl-1-[[(3S,7S,13S,16S,19S)-13,16,17-trimethyl-2,6,12,15,18-pentaoxo-5-oxa-1,11,14,17-tetrazatricyclo[17.3.0.07,11]docosan-3-yl]amino]propan-2-yl]hexa-2,4-dienamide
• 化学式: C₃₅H₄₆N₆O₈
• 分子量: 678.786
• InChiKey: BBLLKVNXEOVWAQ-CLHOJCJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  49
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  175
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  tert-butyl(S)-2-(((S)-1-(((S)-1-((S)-2-(((S)-2-(((benzyloxy)carbonyl)amino)-3-oxo-3-(2-oxo-2-phenylethoxy)propoxy)carbonyl)pyrrolidin-1-yl)-1-oxopropan-2-yl)amino)-1-oxopropan-2-yl)(methyl)carbamoyl)pyrrolidine-1-carboxylate: 在 盐酸 、 五氟苯酚 、 palladium 10% on activated carbon 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 水 、 氢气 、 溶剂黄146 、 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 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， -20.0~20.0 ℃ 、101.33 kPa 条件下， 反应 157.0h， 生成 A54556 factor E
  参考文献：
  名称：

  Total Synthesis and Antibacterial Testing of the A54556 Cyclic Acyldepsipeptides Isolated fromStreptomyces hawaiiensis

  摘要：

  The first total synthesis of all six known A54556 acyldepsipeptide (ADEP) antibiotics from Streptomyces hawaiiensis is reported. This family of compounds has a unique mechanism of antibacterial action, acting as activators of caseinolytic protease (ClpP). Assembly of the 16-membered depsipeptide core was accomplished via a pentafluorophenyl ester-based macrolactamization strategy. Late stage amine deprotection was carried out under neutral conditions by employing a mild hydrogenolysis strategy, which avoids the formation of undesired ring-opened depsipeptide side products encountered during deprotection of acid-labile protecting groups. The free amines were found to be significantly more reactive toward late stage amide bond formation as compared to the corresponding ammonium salts, giving final products in excellent yields. A thorough NMR spectroscopic analysis of these compounds was carried out to formally assign the structures and to aid with the spectroscopic assignment of ADEP analogues. The identity of two of the structures was confirmed by comparison with biologically produced samples from S. hawaiiensis. An X-ray crystallographic analysis of an ADEP analogue reveals a conformation similar to that found in cocrystal structures of ADEPs with ClpP protease. The degree of antibacterial activity of the different compounds was evaluated in vitro using MIC assays employing both Gram-positive and Gram-negative strains and a fluorescence-based biochemical assay.

  DOI：

  10.1021/np500158q

文献信息

• Total Synthesis and Antibacterial Testing of the A54556 Cyclic Acyldepsipeptides Isolated from<i>Streptomyces hawaiiensis</i>
  作者：Jordan D. Goodreid、Keith Wong、Elisa Leung、Shannon E. McCaw、Scott D. Gray-Owen、Alan Lough、Walid A. Houry、Robert A. Batey

  DOI：10.1021/np500158q

  日期：2014.10.24

  The first total synthesis of all six known A54556 acyldepsipeptide (ADEP) antibiotics from Streptomyces hawaiiensis is reported. This family of compounds has a unique mechanism of antibacterial action, acting as activators of caseinolytic protease (ClpP). Assembly of the 16-membered depsipeptide core was accomplished via a pentafluorophenyl ester-based macrolactamization strategy. Late stage amine deprotection was carried out under neutral conditions by employing a mild hydrogenolysis strategy, which avoids the formation of undesired ring-opened depsipeptide side products encountered during deprotection of acid-labile protecting groups. The free amines were found to be significantly more reactive toward late stage amide bond formation as compared to the corresponding ammonium salts, giving final products in excellent yields. A thorough NMR spectroscopic analysis of these compounds was carried out to formally assign the structures and to aid with the spectroscopic assignment of ADEP analogues. The identity of two of the structures was confirmed by comparison with biologically produced samples from S. hawaiiensis. An X-ray crystallographic analysis of an ADEP analogue reveals a conformation similar to that found in cocrystal structures of ADEPs with ClpP protease. The degree of antibacterial activity of the different compounds was evaluated in vitro using MIC assays employing both Gram-positive and Gram-negative strains and a fluorescence-based biochemical assay.