S-[(E)-4-[(2R,3R)-3-(hydroxymethyl)oxiran-2-yl]but-3-enyl] octanethioate | 1196806-28-6

• 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,3R)-3-(hydroxymethyl)oxiran-2-yl]but-3-enyl] octanethioate
• CAS: 1196806-28-6
• 化学式: C₁₅H₂₆O₃S
• 分子量: 286.436
• InChiKey: QHPKEKPCDKOSJK-BIYBCCJYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  75.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  在 四丁基氟化铵 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 0.5h， 以35%的产率得到S-[(E)-4-[(2R,3R)-3-(hydroxymethyl)oxiran-2-yl]but-3-enyl] octanethioate
  参考文献：
  名称：

  Largazole的全合成-一种新的合成策略的转移

  摘要：

  蓝细菌分离物拉格唑体现了相对简单而独特的环状双缩肽结构的令人信服的组合，该结构具有显着水平的针对癌细胞系和未转化细胞的选择性细胞毒性。largazole的独特结构激发了一种战略上新颖且具有侵略性的方法来实现方便的全合成。这涉及到初始分解为环氧醛和未保护的四肽，分别代表拉格唑的聚酮和多肽结构域。这些片段使用NHC介导的酰胺化成功连接，但随后通过内酯化的环状二肽的组装受到阻碍。关键联轴器的重新排序导致了largazole的成功组装。 全合成-杂环-十肽-N-杂环卡宾-噻唑啉

  DOI：

  10.1055/s-0029-1216931

文献信息

• Total Synthesis of Largazole - Devolution of a Novel Synthetic Strategy
  作者：Craig Forsyth、Bo Wang

  DOI：10.1055/s-0029-1216931

  日期：2009.9

  largazole embodies a compelling combination of a relatively simple, yet unique cyclic depsipeptide structure with remarkable levels of selective cytotoxicity against cancer cell lines versus nontransformed cells. The unique structure of largazole inspired a strategically novel and aggressive approach towards its expedient total synthesis. This involved an initial dissection into an epoxy aldehyde and an unprotected

  蓝细菌分离物拉格唑体现了相对简单而独特的环状双缩肽结构的令人信服的组合，该结构具有显着水平的针对癌细胞系和未转化细胞的选择性细胞毒性。largazole的独特结构激发了一种战略上新颖且具有侵略性的方法来实现方便的全合成。这涉及到初始分解为环氧醛和未保护的四肽，分别代表拉格唑的聚酮和多肽结构域。这些片段使用NHC介导的酰胺化成功连接，但随后通过内酯化的环状二肽的组装受到阻碍。关键联轴器的重新排序导致了largazole的成功组装。 全合成-杂环-十肽-N-杂环卡宾-噻唑啉
• 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.