N-<(2S,4R)-2-<amino>-4-methylheptanoyl>-N-methyl-L-leucinyl>-L-leucinyl>-N1'-methoxy-N-methyl-L-tryptophanyl>amino>-4-methylheptanoyl>-N-methyl-L-alanine | 237431-35-5

• 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-<(2S,4R)-2-<amino>-4-methylheptanoyl>-N-methyl-L-leucinyl>-L-leucinyl>-N1'-methoxy-N-methyl-L-tryptophanyl>amino>-4-methylheptanoyl>-N-methyl-L-alanine
• 英文别名: N-<(2S,4R)-2-<amino>-4-methylheptanoyl>-N-methyl-L-leucinyl>-L-leucinyl>-N^1'-methoxy-N-methyl-L-tryptophanyl>amino>-4-methylheptanoyl>-N-methyl-L-alanine
• CAS: 237431-35-5
• 化学式: C₅₃H₈₆N₈O₁₀
• 分子量: 995.313
• InChiKey: XNTQNWZPWCGMAH-DOXSKGAYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.47
• 重原子数：
  71.0
• 可旋转键数：
  32.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  243.71
• 氢给体数：
  5.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  N-<(2S,4R)-2-<amino>-4-methylheptanoyl>-N-methyl-L-leucinyl>-L-leucinyl>-N1'-methoxy-N-methyl-L-tryptophanyl>amino>-4-methylheptanoyl>-N-methyl-L-alanine 在 N-甲基吗啉 、 乙基硫脲 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 生成 (2R)-N-[N-[(2S,4R)-2-[[N-[N-[N-[(2S,4R)-2-amino-4-methylheptanoyl]-N-methyl-L-leucinyl]-L-leucinyl]-N¹'-methoxy-N-methyl-L-tryptophanyl]amino]-4-methylheptanoyl]-N-methyl-L-alaninyl]amino-4-cyanobutanoic acid methyl ester
  参考文献：
  名称：

  A Convenient Protocol for Selective Cleavage of 2-Hydroxy Acid Amides. Application to Semisynthesis of the Cyclic Heptapeptide Aza HUN-7293

  摘要：

  A two-step protocol for the first chemoselective cleavage of 2-hydroxy acid amides has been developed. Mesylation of the model substrate 2-(hydroxypropionylamino)-4-methylpentanoic acid methyl ester (11) followed by treatment with N-ethylthiourea (13) allows cleavage of 2-hydroxy acid amides under smooth conditions. Successful application of this methodology to the open-chain transesterification product 15 (methylester) of the cyclic heptadepsipeptide HUN-7293, a potent inhibitor of inducible cell adhesion molecule expression, delivered the corresponding hexapeptide 18 with unprotected N-terminus in 70-75% yield. This result demonstrates that the protocol developed even works in the presence of an ester and several methylated and unmethylated amide bonds. Finally, a sequence of ligation of methyl D-dehydroglutaminate (20) to the C-terminus of the saponification product 21, followed by the degradation protocol and ring closure, allowed chemical "point mutation" at the DGCN site affording the aza analogue of HUN-7293 (24) in 15% overall yield. To the best of our knowledge this is the first report on chemoselective cleavage of 2-hydroxy acid amides.

  DOI：

  10.1021/jo025979g
• 作为产物：
  描述：

  N-<(2S,4R)-2-<amino>-4-methylheptanoyl>-N-methyl-L-leucinyl>-L-leucinyl>-N^1'-methoxy-N-methyl-L-tryptophanyl>amino>-4-methylheptanoyl>-N-methyl-L-alanine methyl ester 在 lithium hydroxide 作用下， 以 叔丁醇 为溶剂， 反应 1.0h， 以100%的产率得到N-<(2S,4R)-2-<amino>-4-methylheptanoyl>-N-methyl-L-leucinyl>-L-leucinyl>-N1'-methoxy-N-methyl-L-tryptophanyl>amino>-4-methylheptanoyl>-N-methyl-L-alanine
  参考文献：
  名称：

  HUN-7293 的全合成

  摘要：

  详细介绍了环状七肽 HUN-7293 (1) 的首次全合成，这是一种具有抗炎特性的细胞粘附分子表达的强效抑制剂。最有效的方法依赖于异常有效的大环化，形成 MLEU3-LEU4 仲酰胺，这可能受益于无环底物的分子内 H 键预组织。必需的线性缩酚肽与后期引入的连接酯聚合组装，该酯化作用发生在 DGCN α-中心的反转中，允许利用容易获得的 l-氨基酸前体生成 d α-羟基羧酸残留物。一种替代且类似有吸引力的直接大环内酯化方法，必须结合 d-DGCN 亚基，证明是可行的，尽管效果较差。血管粘附分子表达的细胞测定中的生物学评估证实合成 HUN-7923 (1...

  DOI：

  10.1021/ja990918u