(3S,4E)-7-(tert-butylthio)-3-hydroxy-1-((4R)-4-isopropyl-2-thioxothiazolidin-3-yl)hept-4-en-1-one | 1338230-04-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (3S,4E)-7-(tert-butylthio)-3-hydroxy-1-((4R)-4-isopropyl-2-thioxothiazolidin-3-yl)hept-4-en-1-one
• 英文别名: (E,3S)-7-tert-butylsulfanyl-3-hydroxy-1-[(4R)-4-propan-2-yl-2-sulfanylidene-1,3-thiazolidin-3-yl]hept-4-en-1-one
• CAS: 1338230-04-8
• 化学式: C₁₇H₂₉NO₂S₃
• 分子量: 375.621
• InChiKey: BUWDELGYYYKNPV-RNUUNTDPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  123
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-(2-(tert-butylthio)ethyl)-6H-1,3-diox-4-ene 在 四氯化钛 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 4.83h， 生成 (3S,4E)-7-(tert-butylthio)-3-hydroxy-1-((4R)-4-isopropyl-2-thioxothiazolidin-3-yl)hept-4-en-1-one 、
  参考文献：
  名称：

  Largazole and Analogues with Modified Metal-Binding Motifs Targeting Histone Deacetylases: Synthesis and Biological Evaluation

  摘要：

  The histone deacetylase inhibitor largazole 1 was synthesized by a convergent approach that involved several efficient and high yielding single pot multistep protocols. Initial attempts using tert-butyl as thiol protecting group proved problematic, and synthesis was accomplished by switching to the trityl protecting group. This synthetic protocol provides a convenient approach to many new largazole analogues. Three side chain analogues with multiple heteroatoms for chelation with Zn2+ were synthesized, and their biological activities were evaluated. They were less potent than largazole 1 in growth inhibition of HCT116 colon carcinoma cell line and in inducing increases in global H3 acetylation. Largazole 1 and the three side chain analogues had no effect on HDAC6, as indicated by the lack of increased acetylation of alpha-tubulin.

  DOI：

  10.1021/jm200432a

文献信息

• Largazole and Analogues with Modified Metal-Binding Motifs Targeting Histone Deacetylases: Synthesis and Biological Evaluation
  作者：Pravin Bhansali、Christin L. Hanigan、Robert A. Casero、L. M. Viranga Tillekeratne

  DOI：10.1021/jm200432a

  日期：2011.11.10

  The histone deacetylase inhibitor largazole 1 was synthesized by a convergent approach that involved several efficient and high yielding single pot multistep protocols. Initial attempts using tert-butyl as thiol protecting group proved problematic, and synthesis was accomplished by switching to the trityl protecting group. This synthetic protocol provides a convenient approach to many new largazole analogues. Three side chain analogues with multiple heteroatoms for chelation with Zn2+ were synthesized, and their biological activities were evaluated. They were less potent than largazole 1 in growth inhibition of HCT116 colon carcinoma cell line and in inducing increases in global H3 acetylation. Largazole 1 and the three side chain analogues had no effect on HDAC6, as indicated by the lack of increased acetylation of alpha-tubulin.