S-[(E)-4-[(2R,3S)-3-formyloxiran-2-yl]but-3-enyl] octanethioate | 1196806-43-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: S-[(E)-4-[(2R,3S)-3-formyloxiran-2-yl]but-3-enyl] octanethioate
• CAS: 1196806-43-5
• 化学式: C₁₅H₂₄O₃S
• 分子量: 284.42
• InChiKey: FVILNKASGPMGFY-BIYBCCJYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  19
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  72
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  S-[(E)-4-[(2R,3S)-3-formyloxiran-2-yl]but-3-enyl] octanethioate 、 9-芴甲醇 在 3-benzyl-4,5-dimethylthiazol-3-ium chloride 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以77%的产率得到9H-fluoren-9-ylmethyl (E,3S)-3-hydroxy-7-octanoylsulfanylhept-4-enoate
  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：

  S-[(E)-4-[(2R,3R)-3-(hydroxymethyl)oxiran-2-yl]but-3-enyl] octanethioate 在 三氧化硫吡啶 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 1.0h， 以87%的产率得到S-[(E)-4-[(2R,3S)-3-formyloxiran-2-yl]but-3-enyl] octanethioate
  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.