| 1263375-84-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• CAS: 1263375-84-3
• 化学式: C₁₅H₂₄O₃S
• 分子量: 284.42
• InChiKey: FVILNKASGPMGFY-CYUPMTOZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.52
• 重原子数：
  19.0
• 可旋转键数：
  11.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  46.67
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  、 、 3-benzyl-4,5-dimethylthiazol-3-ium chloride 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.54h， 以8.6 mg的产率得到largazole-17-epi-seco acid
  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