(S)-6-[Hexadecanoyl-(2-trimethylsilanyl-ethoxymethoxy)-amino]-2-{[(S)-2-(2-hydroxy-phenyl)-4,5-dihydro-oxazole-4-carbonyl]-amino}-hexanoic acid | 188743-88-6

• 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: (S)-6-[Hexadecanoyl-(2-trimethylsilanyl-ethoxymethoxy)-amino]-2-{[(S)-2-(2-hydroxy-phenyl)-4,5-dihydro-oxazole-4-carbonyl]-amino}-hexanoic acid
• 英文别名: (2S)-6-[hexadecanoyl(2-trimethylsilylethoxymethoxy)amino]-2-[[(4S)-2-(2-hydroxyphenyl)-4,5-dihydro-1,3-oxazole-4-carbonyl]amino]hexanoic acid
• CAS: 188743-88-6
• 化学式: C₃₈H₆₅N₃O₈Si
• 分子量: 720.035
• InChiKey: QCPCXOIFWJQSFD-LQJZCPKCSA-N

物化性质

• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.83
• 重原子数：
  50
• 可旋转键数：
  29
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  147
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (S)-6-[Hexadecanoyl-(2-trimethylsilanyl-ethoxymethoxy)-amino]-2-{[(S)-2-(2-hydroxy-phenyl)-4,5-dihydro-oxazole-4-carbonyl]-amino}-hexanoic acid 、 {(S)-1-[(S)-1-(tert-Butyl-diphenyl-silanyloxy)-2-oxo-azepan-3-ylcarbamoyl]-2-hydroxy-ethyl}-carbamic acid benzyl ester 在 4-二甲氨基吡啶 、 N-羟基-7-氮杂苯并三氮唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以91%的产率得到[(2S)-3-[[(3S)-1-hydroxy-2-oxoazepan-3-yl]amino]-3-oxo-2-(phenylmethoxycarbonylamino)propyl] (2S)-6-[hexadecanoyl(2-trimethylsilylethoxymethoxy)amino]-2-[[(4S)-2-(2-hydroxyphenyl)-4,5-dihydro-1,3-oxazole-4-carbonyl]amino]hexanoate
  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 4-二甲氨基吡啶 、 lithium hydroxide 、 氢气 、 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 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 49.5h， 生成 (S)-6-[Hexadecanoyl-(2-trimethylsilanyl-ethoxymethoxy)-amino]-2-{[(S)-2-(2-hydroxy-phenyl)-4,5-dihydro-oxazole-4-carbonyl]-amino}-hexanoic acid
  参考文献：
  名称：

  分枝杆菌素 S、耻垢分枝杆菌的铁载体和生长促进剂的全合成及其对结核分枝杆菌的生长抑制活性的测定

  摘要：

  以分枝杆菌素 S 为代表的分枝杆菌素的一般全合成是通过收敛方法实现的。两种异羟肟酸残基 28 和 40b 是通过二甲基二环氧乙烷氧化从市售的 Nα-Cbz-l-赖氨酸制备的。羟胺 34 环化为七元异羟肟酸 35 是由 DCC、DMAP 和 DMAP·HCl 介导的。使用 [2-(三甲基甲硅烷基) 乙氧基] 甲基作为 Nα-Cbz-Ne-羟基-Ne-棕榈酰基-l-赖氨酸甲酯 (28) 的羟基保护基团对于该合成至关重要。生物学测试表明，合成的分枝杆菌素 S 是一种有效的结核分枝杆菌 H37Rv 生长抑制剂，尽管它与结核分枝杆菌的铁载体生长促进剂分枝杆菌素 T 仅在一个立体中心不同。

  DOI：

  10.1021/ja963968x