(4R)-2-[2-[[[(E,3S)-3-[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-methylbutanoyl]oxy-7-tritylsulfanylhept-4-enoyl]amino]methyl]-1,3-thiazol-4-yl]-4-methyl-5H-1,3-thiazole-4-carboxylic acid | 1092363-38-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (4R)-2-[2-[[[(E,3S)-3-[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-methylbutanoyl]oxy-7-tritylsulfanylhept-4-enoyl]amino]methyl]-1,3-thiazol-4-yl]-4-methyl-5H-1,3-thiazole-4-carboxylic acid
• CAS: 1092363-38-6
• 化学式: C₅₅H₅₄N₄O₇S₃
• 分子量: 979.254
• InChiKey: QHIJAUVASCNMBL-PFHNEUNNSA-N

物化性质

• 熔点：
  108-110 °C
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  10.7
• 重原子数：
  69
• 可旋转键数：
  22
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  235
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (4R)-2-[2-[[[(E,3S)-3-[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-methylbutanoyl]oxy-7-tritylsulfanylhept-4-enoyl]amino]methyl]-1,3-thiazol-4-yl]-4-methyl-5H-1,3-thiazole-4-carboxylic acid 在 N-羟基-7-氮杂苯并三氮唑 、 三异丙基硅烷 、 二乙胺 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 36.0h， 生成 (5R,8S,11S)-5-methyl-8-propan-2-yl-11-[(E)-4-(thiophen-2-ylmethylsulfanyl)but-1-enyl]-10-oxa-3,17-dithia-7,14,19,20-tetrazatricyclo[14.2.1.12,5]icosa-1(18),2(20),16(19)-triene-6,9,13-trione
  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
• 作为产物：
  描述：

  (R)-methyl 2-(2-(((3S,4E)-3-hydroxy-7-(tritylthio)hept-4-enamido)methyl)thiazol-4-yl)-4-methyl-4,5-dihydrothiazole-4-carboxylate 在 4-二甲氨基吡啶 、 2,4,6-三氯苯甲酰氯 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.25h， 生成 (4R)-2-[2-[[[(E,3S)-3-[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-methylbutanoyl]oxy-7-tritylsulfanylhept-4-enoyl]amino]methyl]-1,3-thiazol-4-yl]-4-methyl-5H-1,3-thiazole-4-carboxylic acid
  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

• Concise total synthesis of largazole
  作者：Qiong Xiao、Li-Ping Wang、Xiao-Zhen Jiao、Xiao-Yu Liu、Qian Wu、Ping Xie

  DOI：10.1080/10286020.2010.510114

  日期：2010.11

  The concise total synthesis of largazole was accomplished. The key step included the use of the Nagao thiazolidinethione auxiliary for the diastereoselective acetate aldol reaction and it acts as an acylating agent for the peptide formation.