3,5-dibromo-4-hydroxyphenylpyruvate oxime | 83030-41-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 3,5-dibromo-4-hydroxyphenylpyruvate oxime
• 英文别名: methyl 3,5-dibromo-4-hydroxyphenylpyruvate；(E)-methyl 3-(3,5-dibromo-4-hydroxyphenyl)-2-(hydroxyimino)propanoate；(E)-methyl 3-(4-hydroxy-3,5-dibromophenyl)-2-(hydroxyimino)propanoate；methyl (2E)-3-(3,5-dibromo-4-hydroxyphenyl)-2-hydroxyiminopropanoate
• CAS: 83030-41-5
• 化学式: C₁₀H₉Br₂NO₄
• 分子量: 366.994
• InChiKey: TXRUGZWXWPMMQX-MDWZMJQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  17
• 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：

  3,5-dibromo-4-hydroxyphenylpyruvate oxime 在 lithium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 以99%的产率得到(E)-3-(3,5-dibromo-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
• 作为产物：
  描述：

  4-羟苯基丙酮酸 在 palladium on activated charcoal N-溴代丁二酰亚胺(NBS) 、 氢气 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 溶剂黄146 为溶剂， 生成 3,5-dibromo-4-hydroxyphenylpyruvate oxime
  参考文献：
  名称：

  全合成的二硫代酪氨酸生物碱抑制剂的硫羟硫醇S-共轭酰胺酶。

  摘要：

  描述了两个互补的合成序列，用于首次完全合成二溴酪氨酸生物碱（1），据报道该生物碱可以抑制关键的分枝杆菌酶，分枝硫醇S-共轭酰胺酶。将4-羟基苯基丙酮酸的O-苄基肟二溴化，并先后连接至3-氨基丙基链，然后至4-氨基丁基胍单元，然后进行选择性脱保护，得到生物碱1。在改进的变体中，将O-四氢吡喃基肟12与4-氨基丁基胍缩合，然后二溴化成苯酚14，其在Mitsunobu偶联至3-氨基丙基链段并脱保护后生成靶标1。

  DOI：

  10.1016/j.tetlet.2003.10.117

文献信息

• SAR of Sponge-Inspired Hemibastadin Congeners Inhibiting Blue Mussel PhenolOxidase
  作者：Hendrik Niemann、Jens Hagenow、Mi-Young Chung、Claire Hellio、Horst Weber、Peter Proksch

  DOI：10.3390/md13053061

  日期：——

  Hemibastadin derivatives, including the synthetically-derived 5,5′-dibromohemibastadin-1 (DBHB), are potent inhibitors of blue mussel phenoloxidase (PO), which is a key enzyme involved in the firm attachment of this invertebrate to substrates and, thus, a promising molecular target for anti-fouling research. For a systematic investigation of the enzyme inhibitory activity of hemibastadin derivatives, we have synthesized nine new congeners, which feature structural variations of the DBHB core structure. These structural modifications include, e.g., different halogen substituents present at the aromatic rings, different amine moieties linked to the (E)-2-(hydroxyimino)-3-(4-hydroxyphenyl)propionic acid, the presence of free vs. substituted aromatic hydroxyl groups and a free vs. methylated oxime group. All compounds were tested for their inhibitory activity towards the target enzyme in vitro, and IC50 values were calculated. Derivatives, which structurally closely resemble sponge-derived hemibastadins, revealed superior enzyme inhibitory properties vs. congeners featuring structural moieties that are absent in the respective natural products. This study suggests that natural selection has yielded structurally-optimized antifouling compounds.

  Hemibastadin衍生物，包括合成衍生的5,5′-二溴海绵生物碱1（DBHB），是蓝贻贝酚氧化酶（PO）的有效抑制剂，PO是该无脊椎动物牢固附着于基材的重要酶，因此，成为了防污研究的有希望的分子靶点。为了系统地研究hemibastadin衍生物的酶抑制活性，我们合成了九种新的同系物，这些同系物在DBHB核心结构上具有结构变化。这些结构修改包括，例如，芳环上存在不同的卤素取代基、不同的胺基部分与（E）-2-（羟亚胺）-3-（4-羟基苯基）丙酸相连、自由与取代的芳香醇羟基以及自由与甲基化的腙基。所有化合物在体外测试了它们对靶酶的抑制活性，并计算了IC50值。与在各自天然产物中缺失的结构部分的同系物相比，结构上与海绵来源的hemibastadins相似的衍生物表现出更优越的酶抑制特性。这项研究表明，自然选择产生了结构优化的防污化合物。
• Syntheses of pseudoceramines A–D and a new synthesis of spermatinamine, bromotyrosine natural products from marine sponges
  作者：J. Mikael Hillgren、Christopher T. Öberg、Mikael Elofsson

  DOI：10.1039/c1ob06722b

  日期：——

  Herein we report the total syntheses of pseudoceramine A-D (2–5) and spermatinamine (1) isolated from the marine sponge Pseudoceratina sp. Direct acyl substitution of α-hydroxyiminoesters with amine nucleophiles was developed as a key transformation. The synthetic compounds confirm the reported structures and importantly gives access to non-symmetrical spermine based natural products carrying two different bromotyrosine building blocks. Our new synthesis of spermatinamine is two steps shorter and more efficient than the previously reported sequence.

  在此，我们报告了从海洋海绵中分离出的假精胺 A-D（2â5）和精胺（1）的全合成。合成的化合物证实了所报道的结构，重要的是提供了含有两种不同溴酪氨酸结构单元的非对称精胺类天然产物。与之前报道的序列相比，我们的精胺新合成方法缩短了两个步骤，效率更高。
• Biomimetic oxidation of methyl 3,5-dibromo-4-hydroxyphenylpyruvate oxime and related phenols
  作者：Hitoshi Noda、Masatake Niwa、Shosuke Yamamura

  DOI：10.1016/s0040-4039(01)81875-x

  日期：1981.1

  Methyl 3,5-dibromo-4-hydroxyphenylpyruvate oxime and related phenols are subjected to oxidation using thallium (III) nitrate as well as to anodic oxidation to afford the corresponding spiro-isoxazols, dimeric compounds, and others.

  使用硝酸al（III）对3,5-二溴-4-羟基苯基丙酮酸甲酯肟和相关的苯酚进行氧化，并进行阳极氧化，得到相应的螺-异恶唑，二聚化合物等。
• Total synthesis of bastadins
  作者：Shigeru Nishiyama、Shosuke Yamamura

  DOI：10.1016/s0040-4039(00)87083-5

  日期：1982.1
• 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.