(3S,2'S)-((9H-fluoren-9-ylmethoxycarbonylamino)-3-methylbutanoyloxy)-pent-4-enoic acid | 1229877-92-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (3S,2'S)-((9H-fluoren-9-ylmethoxycarbonylamino)-3-methylbutanoyloxy)-pent-4-enoic acid
• 英文别名: (3S)-3-[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-methylbutanoyl]oxypent-4-enoic acid
• CAS: 1229877-92-2
• 化学式: C₂₅H₂₇NO₆
• 分子量: 437.492
• InChiKey: APKYUCCPRVUYTL-MWTRTKDXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  32
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3S,2'S)-((9H-fluoren-9-ylmethoxycarbonylamino)-3-methylbutanoyloxy)-pent-4-enoic acid 、 2-(氨基甲基)-1,3-噻唑-4-甲腈 在 4-二甲氨基吡啶 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 作用下， 以 乙腈 为溶剂， 以93%的产率得到(2S,3'S)-(5-(4-cyanothiazol-2-ylmethylamino)-5-oxopent-1-en-3-yl) 2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-methylbutanoate
  参考文献：
  名称：

  Synthesis and Biological Characterization of the Histone Deacetylase Inhibitor Largazole and C7- Modified Analogues

  摘要：

  Largazole 4a and analogues with modifications at the C7 position, as well as 2,4'-bithiazole 5a, have been synthesized using an acyclic cross-metathesis of the corresponding depsipeptide structures assembled by N-C6(O) or C15(O)-N lactam formation. Similar to the parent system 4a, the series of largazole depsipeptides 4b-d, but not 2,4'-bithiazole 5a, showed a marked inhibition of recombinant HDAC1 and selectivity over HDAC4, as well as strong pro-apoptotic effects on the NB4 leukemia cell line, but they failed to induce differentiation to mature granulocytes. Functional assays of the analogues correlated with the in vitro activities, as shown by increased H3 and a-tubulin acetylation levels and p21(WAF1/C1P1) up-regulation in NB4 cells. The activity of the natural product HDACi largazole 4a is not significantly altered by the presence of groups of different size (H, Et, Ph) at C7 on the dihydrothiazole ring.

  DOI：

  10.1021/jm100244y
• 作为产物：
  描述：

  tert-butyl (3S,2'S)-3-(2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-methylbutanoyloxy)-pent-4-enoate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以99%的产率得到(3S,2'S)-((9H-fluoren-9-ylmethoxycarbonylamino)-3-methylbutanoyloxy)-pent-4-enoic acid
  参考文献：
  名称：

  Synthesis and Biological Characterization of the Histone Deacetylase Inhibitor Largazole and C7- Modified Analogues

  摘要：

  Largazole 4a and analogues with modifications at the C7 position, as well as 2,4'-bithiazole 5a, have been synthesized using an acyclic cross-metathesis of the corresponding depsipeptide structures assembled by N-C6(O) or C15(O)-N lactam formation. Similar to the parent system 4a, the series of largazole depsipeptides 4b-d, but not 2,4'-bithiazole 5a, showed a marked inhibition of recombinant HDAC1 and selectivity over HDAC4, as well as strong pro-apoptotic effects on the NB4 leukemia cell line, but they failed to induce differentiation to mature granulocytes. Functional assays of the analogues correlated with the in vitro activities, as shown by increased H3 and a-tubulin acetylation levels and p21(WAF1/C1P1) up-regulation in NB4 cells. The activity of the natural product HDACi largazole 4a is not significantly altered by the presence of groups of different size (H, Et, Ph) at C7 on the dihydrothiazole ring.

  DOI：

  10.1021/jm100244y