(4S)-N-[(2S)-1-[[3-[[(3S)-1-[tert-butyl(diphenyl)silyl]oxy-2-oxoazepan-3-yl]amino]-3-oxopropyl]amino]-6-[hexadecanoyl(hydroxy)amino]-1-oxohexan-2-yl]-2-(2-hydroxyphenyl)-4,5-dihydro-1,3-oxazole-4-carboxamide | 370103-06-3

• 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: (4S)-N-[(2S)-1-[[3-[[(3S)-1-[tert-butyl(diphenyl)silyl]oxy-2-oxoazepan-3-yl]amino]-3-oxopropyl]amino]-6-[hexadecanoyl(hydroxy)amino]-1-oxohexan-2-yl]-2-(2-hydroxyphenyl)-4,5-dihydro-1,3-oxazole-4-carboxamide
• CAS: 370103-06-3
• 化学式: C₅₇H₈₄N₆O₉Si
• 分子量: 1025.41
• InChiKey: RMECSPCNDDQOLE-HYGNTPKVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.39
• 重原子数：
  73
• 可旋转键数：
  32
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  199
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (4S)-N-[(2S)-1-[[3-[[(3S)-1-[tert-butyl(diphenyl)silyl]oxy-2-oxoazepan-3-yl]amino]-3-oxopropyl]amino]-6-[hexadecanoyl(hydroxy)amino]-1-oxohexan-2-yl]-2-(2-hydroxyphenyl)-4,5-dihydro-1,3-oxazole-4-carboxamide 在 四丁基氟化铵 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以48.6 mg的产率得到(4S)-N-[(2S)-6-[hexadecanoyl(hydroxy)amino]-1-[[3-[[(3S)-1-hydroxy-2-oxoazepan-3-yl]amino]-3-oxopropyl]amino]-1-oxohexan-2-yl]-2-(2-hydroxyphenyl)-4,5-dihydro-1,3-oxazole-4-carboxamide
  参考文献：
  名称：

  Total Syntheses of Mycobactin Analogues as Potent Antimycobacterial Agents Using a Minimal Protecting Group Strategy

  摘要：

  Mycobactins are a family of iron sequestering agents (siderophores) biosynthesized as growth promoters by mycobacteria including Mycobacterium tuberculosis. They are important siderophores with high affinity and specificity for Fe(III) due to the chemical nature of their component chelating functional groups. The parent compounds and their synthetic analogues can be used for studies of natural iron uptake mechanisms. It was hypothesized by Snow and co-workers that alternate and modified mycobactin analogues might serve as antagonists of mycobacterial growth and be of important therapeutic value. Efficient syntheses of four different analogues are presented. Dramatic improvements on formation of amide and ester bonds were achieved using water soluble carbodiimide (EDC . HCl)-mediated couplings in the presence of 1-hydroxy-7-azabenzotriazole (HOAt) as an additive. Using HOAt over other traditional coupling additives provided significant enhancement of the reaction rate of the desired coupling reactions and minimized side reactions. Further simplifications were made possible by minimizing the use of protecting groups during the syntheses. In fact, coupling components in the presence of free hydroxamic acids and a free phenolic hydroxyl group proceeded in excellent yields. Biological studies indicated that the resulting synthetic analogues effect moderate to high inhibition of the growth of M. tuberculosis H37Rv.

  DOI：

  10.1021/jo980063o
• 作为产物：
  描述：

  methyl (2S)-6-[hexadecanoyl(hydroxy)amino]-2-(phenylmethoxycarbonylamino)hexanoate 在 palladium on activated charcoal lithium hydroxide 、 N-羟基-7-氮杂苯并三氮唑 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、98.06 kPa 条件下， 反应 9.5h， 生成 (4S)-N-[(2S)-1-[[3-[[(3S)-1-[tert-butyl(diphenyl)silyl]oxy-2-oxoazepan-3-yl]amino]-3-oxopropyl]amino]-6-[hexadecanoyl(hydroxy)amino]-1-oxohexan-2-yl]-2-(2-hydroxyphenyl)-4,5-dihydro-1,3-oxazole-4-carboxamide
  参考文献：
  名称：

  Total Syntheses of Mycobactin Analogues as Potent Antimycobacterial Agents Using a Minimal Protecting Group Strategy

  摘要：

  Mycobactins are a family of iron sequestering agents (siderophores) biosynthesized as growth promoters by mycobacteria including Mycobacterium tuberculosis. They are important siderophores with high affinity and specificity for Fe(III) due to the chemical nature of their component chelating functional groups. The parent compounds and their synthetic analogues can be used for studies of natural iron uptake mechanisms. It was hypothesized by Snow and co-workers that alternate and modified mycobactin analogues might serve as antagonists of mycobacterial growth and be of important therapeutic value. Efficient syntheses of four different analogues are presented. Dramatic improvements on formation of amide and ester bonds were achieved using water soluble carbodiimide (EDC . HCl)-mediated couplings in the presence of 1-hydroxy-7-azabenzotriazole (HOAt) as an additive. Using HOAt over other traditional coupling additives provided significant enhancement of the reaction rate of the desired coupling reactions and minimized side reactions. Further simplifications were made possible by minimizing the use of protecting groups during the syntheses. In fact, coupling components in the presence of free hydroxamic acids and a free phenolic hydroxyl group proceeded in excellent yields. Biological studies indicated that the resulting synthetic analogues effect moderate to high inhibition of the growth of M. tuberculosis H37Rv.

  DOI：

  10.1021/jo980063o