(E)-methyl 2-(hydroxyimino)-3-(4-hydroxyphenyl)propanoate | 50563-23-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (E)-methyl 2-(hydroxyimino)-3-(4-hydroxyphenyl)propanoate
• 英文别名: methyl (2E)-2-(N-hydroxyimino)-3-(4-hydroxyphenyl)propanoate；methyl (2E)-2-hydroxyimino-3-(4-hydroxyphenyl)propanoate
• CAS: 50563-23-0
• 化学式: C₁₀H₁₁NO₄
• 分子量: 209.202
• InChiKey: YPSPDGUMPSSYDS-PKNBQFBNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 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

安全信息

• 海关编码：
  2928000090

反应信息

• 作为反应物：
  描述：

  (E)-methyl 2-(hydroxyimino)-3-(4-hydroxyphenyl)propanoate 在 N-溴代丁二酰亚胺(NBS) 、 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 、 乙腈 为溶剂， 反应 19.25h， 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：

  L-酪氨酸甲酯 在 sodium tungstate (VI) dihydrate 、 双氧水 作用下， 以 乙醇 、 水 为溶剂， 反应 4.5h， 以82%的产率得到(E)-methyl 2-(hydroxyimino)-3-(4-hydroxyphenyl)propanoate
  参考文献：
  名称：

  从斯里兰卡真菌Serpula sp。分离得到的Serpulanines A至C，N氧化酪氨酸衍生物：结构阐明，合成和组蛋白去乙酰化酶抑制。

  摘要：

  Serpulanines A（1），B（2）和C（3）已从罕见的斯里兰卡大型真菌Serpula sp的提取物中分离出来。的结构1，2，和3通过光谱和单晶X射线衍射分析的组合阐明。Serpulanines A（1）和B（2）都包含稀有的（E）-2-羟基亚氨基异羟肟酸官能团阵列。拟议的Serpulanine B（2）的生物发生表明其（E）-2-羟基亚氨基异羟肟酸部分来自二酮哌嗪前体。合成丝氨脂A（1）在小鼠转移性肺癌细胞中抑制I / II类组蛋白脱乙酰基酶，IC 50为7μM。

  DOI：

  10.1021/acs.jnatprod.7b00680

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。
• Enantiopure building blocks for marine natural products via differentiation of enantiotopic groups
  作者：Winfried Beil、Peter G. Jones、Frank Nerenz、Ekkehard Winterfeldt

  DOI：10.1016/s0040-4020(98)00158-6

  日期：1998.6

  The group and face-selective cycloaddition of the enantiopure cyclopentadiene 4 to the tyrosine-related spirocylohexadienone 10 provided a high yield of the enantiomerically pure cyclohexadienone 11. Stereoselective transformations at the remaining double bond followed by a thermal retro-process, finally giving rise to the chromophore of the marine agelorin antibioticcs isolated from the sponge Agelas

  对映体纯的环戊二烯4与酪氨酸相关的螺环己二烯酮10的基团和面选择性环加成反应提供了高纯度的对映体纯的环己二酮11。在剩余的双键处进行立体选择性转化，然后进行热逆过程，最终产生从海绵Agelas oroides Schmidt分离出的海洋苦瓜素抗生素的发色团。
• 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.
• Serpulanines A to C, N-Oxidized Tyrosine Derivatives Isolated from the Sri Lankan Fungus <i>Serpula</i> sp.: Structure Elucidation, Synthesis, and Histone Deacetylase Inhibition
  作者：David E. Williams、Niranjan W. Gunasekara、Pamoda B. Ratnaweera、Zehua Zheng、Samantha Ellis、Sarah Dada、Brian O. Patrick、Ravi L. C. Wijesundera、Chandrika M. Nanayakkara、Wilfred A. Jefferies、E. Dilip de Silva、Raymond J. Andersen

  DOI：10.1021/acs.jnatprod.7b00680

  日期：2018.1.26

  Serpulanines A (1), B (2), and C (3) have been isolated from extracts of the rare Sri Lankan macrofungus Serpula sp. The structures of 1, 2, and 3 were elucidated by a combination of spectroscopic and single-crystal X-ray diffraction analyses. Serpulanines A (1) and B (2) both contain the rare (E)-2-hydroxyimino hydroxamic acid functional group array. A proposed biogenesis for serpulanine B (2) suggests

  Serpulanines A（1），B（2）和C（3）已从罕见的斯里兰卡大型真菌Serpula sp的提取物中分离出来。的结构1，2，和3通过光谱和单晶X射线衍射分析的组合阐明。Serpulanines A（1）和B（2）都包含稀有的（E）-2-羟基亚氨基异羟肟酸官能团阵列。拟议的Serpulanine B（2）的生物发生表明其（E）-2-羟基亚氨基异羟肟酸部分来自二酮哌嗪前体。合成丝氨脂A（1）在小鼠转移性肺癌细胞中抑制I / II类组蛋白脱乙酰基酶，IC 50为7μM。