(E)-methyl 3-(3-bromo-4-hydroxyphenyl)-2-(hydroxyimino)-propanoate | 83030-43-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (E)-methyl 3-(3-bromo-4-hydroxyphenyl)-2-(hydroxyimino)-propanoate
• 英文别名: (E)-methyl 3-(3-bromo-4-hydroxyphenyl)-2-(hydroxyimino)propanoate；methyl 3-bromo-4-hydroxyphenylpyruvate oxime；Methyl 3-(3-bromo-4-hydroxyphenyl)-2-(hydroxyimino)-propanoate；methyl (2E)-3-(3-bromo-4-hydroxyphenyl)-2-hydroxyiminopropanoate
• CAS: 83030-43-7
• 化学式: C₁₀H₁₀BrNO₄
• 分子量: 288.098
• InChiKey: AMXHNFGHJPBXSJ-XYOKQWHBSA-N

物化性质

• 沸点：
  425.7±55.0 °C(Predicted)
• 密度：
  1.60±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  79.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (E)-methyl 3-(3-bromo-4-hydroxyphenyl)-2-(hydroxyimino)-propanoate 在 N-羟基邻苯二甲酰亚胺 、 N,N'-二环己基碳二亚胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 14.0h， 生成 帕马普林A
  参考文献：
  名称：

  Epigenetic profiling of the antitumor natural product psammaplin A and its analogues

  摘要：

  A collection of analogues of the dimeric natural product psammaplin A that differ in the substitution on the ( halo) tyrosine aryl ring, the oxime and the diamine connection has been synthesized. The effects on cell cycle, induction of differentiation and apoptosis of the natural-product inspired series were measured on the human leukaemia U937 cell line. Epigenetic profiling included induction of p21(WAF1), effects on global H3 histone and tubulin acetylation levels as well as in vitro enzymatic assays using HDAC1, DNMT1, DNMT3A, SIRT1 and a peptide domain with p300/CBP HAT activity. Whereas the derivatives of psammaplin A with modifications in the length of the connecting chain, the oxime bond and the disulfide unit showed lower potency, the analogues with changes on the bromotyrosine ring exhibited activities comparable to those of the parent compound in the inhibition of HDAC1 and in the induction of apoptosis. The lack of HDAC1 activity of analogues modified on the disulfide bond suggests that its cleavage must occur in cells to produce the monomeric Zn2+-chelating thiol. This assumption is consistent with the molecular modelling of the complex of psammaplin A thiol with h-HDAC8. Only a weak inhibition of DNMT1, DNMT3A and residual activities with SIRT1 and a p300/CBP HAT peptide were measured for these compounds. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.12.026
• 作为产物：
  描述：

  (3-bromo-4-hydroxyphenyl)pyruvic acid 在 盐酸 、 盐酸羟胺 作用下， 以 水 为溶剂， 生成 (E)-methyl 3-(3-bromo-4-hydroxyphenyl)-2-(hydroxyimino)-propanoate
  参考文献：
  名称：

  Total synthesis of bastadins

  摘要：

  DOI：

  10.1016/s0040-4039(00)87083-5

文献信息

• Fluorescent analogs of the marine natural product psammaplin A: synthesis and biological activity
  作者：Fabia Hentschel、Florenz Sasse、Thomas Lindel

  DOI：10.1039/c2ob25909e

  日期：——

  The symmetrical disulfide psammaplin A from the marine sponge Pseudoceratina sp. was synthesized and structurally altered by replacement of one of the α-(hydroxyimino)acyl units by a fluorescent 4-coumarinacetyl moiety. Thus, the first fluorescent analogs of psammaplin A were obtained. Structural variation also covered the substitution pattern of the phenyl ring. Cytotoxicity of psammaplin A against

  来自海洋海绵Pseudoceratina sp。的对称二硫化物psammaplinA 。通过用荧光的4-香豆素乙酰基部分取代α-（羟基亚氨基）酰基单元之一来合成和结构改变。因此，获得了psammaplin A的第一个荧光类似物。结构变化也涵盖了苯环的取代模式。psammaplin A对小鼠成纤维细胞L-929细胞株的细胞毒性（IC 50 0.42μgmL -1）比荧光杂化化合物高约两倍，而含有两个4-香豆素乙酰基的二硫键则没有活性。荧光显微镜检查显示4-香豆素乙酰基-α-（羟基亚氨基）酰基杂化物被吸收到细胞质中，导致核包膜附近发生荧光，这很可能是在高尔基体中发生的。我们没有在细胞核内观察到强烈的荧光，大多数目标组蛋白脱乙酰基酶都位于细胞核内。我们得出的结论是二硫化物的还原可能发生在核外。psammaplin衍生的硫醇在低纳摩尔范围内表现出强大的抗组蛋白脱乙酰基酶活性，但细胞毒性却降低了。还确定了新衍生物的抗菌活性。
• Epigenetic profiling of the antitumor natural product psammaplin A and its analogues
  作者：José García、Gianluigi Franci、Raquel Pereira、Rosaria Benedetti、Angela Nebbioso、Fátima Rodríguez-Barrios、Hinrich Gronemeyer、Lucia Altucci、Angel R. de Lera

  DOI：10.1016/j.bmc.2010.12.026

  日期：2011.6

  A collection of analogues of the dimeric natural product psammaplin A that differ in the substitution on the ( halo) tyrosine aryl ring, the oxime and the diamine connection has been synthesized. The effects on cell cycle, induction of differentiation and apoptosis of the natural-product inspired series were measured on the human leukaemia U937 cell line. Epigenetic profiling included induction of p21(WAF1), effects on global H3 histone and tubulin acetylation levels as well as in vitro enzymatic assays using HDAC1, DNMT1, DNMT3A, SIRT1 and a peptide domain with p300/CBP HAT activity. Whereas the derivatives of psammaplin A with modifications in the length of the connecting chain, the oxime bond and the disulfide unit showed lower potency, the analogues with changes on the bromotyrosine ring exhibited activities comparable to those of the parent compound in the inhibition of HDAC1 and in the induction of apoptosis. The lack of HDAC1 activity of analogues modified on the disulfide bond suggests that its cleavage must occur in cells to produce the monomeric Zn2+-chelating thiol. This assumption is consistent with the molecular modelling of the complex of psammaplin A thiol with h-HDAC8. Only a weak inhibition of DNMT1, DNMT3A and residual activities with SIRT1 and a p300/CBP HAT peptide were measured for these compounds. (C) 2010 Elsevier Ltd. All rights reserved.
• Total synthesis of bastadins
  作者：Shigeru Nishiyama、Shosuke Yamamura

  DOI：10.1016/s0040-4039(00)87083-5

  日期：1982.1