O-t-Bu-Val-α-methylazidoserine amide | 1196806-38-8

• 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: O-t-Bu-Val-α-methylazidoserine amide
• 英文别名: tert-butyl (2S)-2-[[(2S)-2-azido-3-hydroxy-2-methylpropanoyl]amino]-3-methylbutanoate
• CAS: 1196806-38-8
• 化学式: C₁₃H₂₄N₄O₄
• 分子量: 300.358
• InChiKey: CWAAEPFFBALHGM-ZANVPECISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  90
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  O-t-Bu-Val-α-methylazidoserine amide 在 lithium hydroxide monohydrate 、 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 2.17h， 生成 tert-butyl (2S)-2-[[(2R)-2-azido-2-methyl-3-sulfanylpropanoyl]amino]-3-methylbutanoate
  参考文献：
  名称：

  Total Syntheses of the Histone Deacetylase Inhibitors Largazole and 2-epi-Largazole: Application of N-Heterocyclic Carbene Mediated Acylations in Complex Molecule Synthesis

  摘要：

  Details of the evolution of strategies toward convergent assembly of the histone deacetylase inhibiting natural product largazole exploiting gamma,delta-unsaturated-alpha,beta-epoxy-aldehydes and a thiazole-thiazoline containing omega-amino-acid are described. The initial N-heterocyclic carbene mediated redox amidation exploying these two types of building blocks representing largazole's structural domains of distinct biosynthetic origin directly afforded the seco-acid of largazole. This was accomplished without any protecting groups resident upon either thioester bearing epoxy-aldehyde or the tetrapeptide. However, the ineffective production of largazole via the final macrolactonization led to an alternative intramolecular esterification/macrolactamization strategy employing the established two building blocks. This provided largazole along with its C2-epimer via an unexpected inversion of the alpha-stereocenter at the valine residue. The biological evaluation demonstrated that both largazole and 2-epi-largazole led to dose-dependent increases of acetylation of histone H3, indicating their potencies as class I histone deacetylase selective inhibitiors. Enhanced p21 expression was also induced by largazole and its C2 epimer. In addition, 2-epi-largazole displayed more potent activity than largazole in cell viability assays against PC-3 and LNCaP prostate cancer cell lines.

  DOI：

  10.1021/jo102478x
• 作为产物：
  描述：

  L-缬氨酸叔丁酯盐酸盐 、 (S)-2-叠氮基-3-羟基-2-甲基丙酸 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以94%的产率得到O-t-Bu-Val-α-methylazidoserine amide
  参考文献：
  名称：

  Total Syntheses of the Histone Deacetylase Inhibitors Largazole and 2-epi-Largazole: Application of N-Heterocyclic Carbene Mediated Acylations in Complex Molecule Synthesis

  摘要：

  Details of the evolution of strategies toward convergent assembly of the histone deacetylase inhibiting natural product largazole exploiting gamma,delta-unsaturated-alpha,beta-epoxy-aldehydes and a thiazole-thiazoline containing omega-amino-acid are described. The initial N-heterocyclic carbene mediated redox amidation exploying these two types of building blocks representing largazole's structural domains of distinct biosynthetic origin directly afforded the seco-acid of largazole. This was accomplished without any protecting groups resident upon either thioester bearing epoxy-aldehyde or the tetrapeptide. However, the ineffective production of largazole via the final macrolactonization led to an alternative intramolecular esterification/macrolactamization strategy employing the established two building blocks. This provided largazole along with its C2-epimer via an unexpected inversion of the alpha-stereocenter at the valine residue. The biological evaluation demonstrated that both largazole and 2-epi-largazole led to dose-dependent increases of acetylation of histone H3, indicating their potencies as class I histone deacetylase selective inhibitiors. Enhanced p21 expression was also induced by largazole and its C2 epimer. In addition, 2-epi-largazole displayed more potent activity than largazole in cell viability assays against PC-3 and LNCaP prostate cancer cell lines.

  DOI：

  10.1021/jo102478x

文献信息

• Total Syntheses of the Histone Deacetylase Inhibitors Largazole and 2-<i>epi</i>-Largazole: Application of <i>N</i>-Heterocyclic Carbene Mediated Acylations in Complex Molecule Synthesis
  作者：Bo Wang、Po-Hsien Huang、Ching-Shih Chen、Craig J. Forsyth

  DOI：10.1021/jo102478x

  日期：2011.2.18

  Details of the evolution of strategies toward convergent assembly of the histone deacetylase inhibiting natural product largazole exploiting gamma,delta-unsaturated-alpha,beta-epoxy-aldehydes and a thiazole-thiazoline containing omega-amino-acid are described. The initial N-heterocyclic carbene mediated redox amidation exploying these two types of building blocks representing largazole's structural domains of distinct biosynthetic origin directly afforded the seco-acid of largazole. This was accomplished without any protecting groups resident upon either thioester bearing epoxy-aldehyde or the tetrapeptide. However, the ineffective production of largazole via the final macrolactonization led to an alternative intramolecular esterification/macrolactamization strategy employing the established two building blocks. This provided largazole along with its C2-epimer via an unexpected inversion of the alpha-stereocenter at the valine residue. The biological evaluation demonstrated that both largazole and 2-epi-largazole led to dose-dependent increases of acetylation of histone H3, indicating their potencies as class I histone deacetylase selective inhibitiors. Enhanced p21 expression was also induced by largazole and its C2 epimer. In addition, 2-epi-largazole displayed more potent activity than largazole in cell viability assays against PC-3 and LNCaP prostate cancer cell lines.