(E)-3-(3-chloro-4-hydroxyphenyl)-2-(hydroxyimino)propanoic acid | 1314789-46-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: (E)-3-(3-chloro-4-hydroxyphenyl)-2-(hydroxyimino)propanoic acid
• CAS: 1314789-46-2
• 化学式: C₉H₈ClNO₄
• 分子量: 229.62
• InChiKey: KZRZRHGHTJOCEB-YRNVUSSQSA-N

物化性质

• 熔点：
  117-125 °C(Solv: hexane (110-54-3); dichloromethane (75-09-2))
• 沸点：
  483.3±55.0 °C(Predicted)
• 密度：
  1.50±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  90.12
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  胱胺 、 (E)-3-(3-chloro-4-hydroxyphenyl)-2-(hydroxyimino)propanoic acid 在 N-羟基邻苯二甲酰亚胺 、 N,N'-二环己基碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 14.0h， 以57%的产率得到(2E,2'E)-N,N'-[2,2'-disulfanediylbis(ethane-2,1-diyl)]bis[3-(3-chloro-4-hydroxyphenyl)-2-(hydroxyimino)propanamide]
  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-chloro-L-tyrosine methyl ester 在 sodium tungstate (VI) dihydrate 、 双氧水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 3.0h， 生成 (E)-3-(3-chloro-4-hydroxyphenyl)-2-(hydroxyimino)propanoic acid
  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