(E)-3-(3-bromo-4-hydroxyphenyl)-2-(hydroxyimino)-N-(2-mercaptoethyl)propanamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (E)-3-(3-bromo-4-hydroxyphenyl)-2-(hydroxyimino)-N-(2-mercaptoethyl)propanamide
• 英文别名: (2E)-3-(3-bromo-4-hydroxyphenyl)-2-hydroxyimino-N-(2-sulfanylethyl)propanamide
• 化学式: C₁₁H₁₃BrN₂O₃S
• 分子量: 333.206
• InChiKey: PCQQFHBCWBFDEF-NTEUORMPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  82.9
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (E)-3-(3-bromo-4-hydroxyphenyl)-2-(hydroxyimino)-N-(2-mercaptoethyl)propanamide 在 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 13.5h， 生成 psammaplin F
  参考文献：
  名称：

  Synthesis of the Marine Bromotyrosine Psammaplin F and Crystal Structure of a Psammaplin A Analogue

  摘要：

  在2003年，从海绵Pseudoceratina purpurea中分离出了不对称二硫化物溴酪氨酸Psammaplin F。我们在这里报告了Psammaplin F的首次总合成，整体产率为12%，关键步骤采用了Cleland试剂还原。从3-溴-4-羟基苯甲醛和氢噻嗪开始的最长线性合成序列为七步。此外，首次提供了Psammaplin A类似物8b的详细X射线晶体结构分析。

  DOI：

  10.3390/molecules15128784
• 作为产物：
  描述：

  帕马普林A 在 1,4-dithio-D,L-threitol 、 水 、 potassium hydroxide 作用下， 以 甲醇 为溶剂， 以93.7%的产率得到(E)-3-(3-bromo-4-hydroxyphenyl)-2-(hydroxyimino)-N-(2-mercaptoethyl)propanamide
  参考文献：
  名称：

  研究硫醇基团修饰的沙门菌素 A 单体对组蛋白去乙酰化酶的抑制和凋亡诱导

  摘要：

  Psammaplin A (PsA) 是一种溴酪氨酸二硫化物二聚体，具有组蛋白脱乙酰酶 (HDAC) 抑制作用，并通过还原的单体 PsA-SH 发挥作用。我们通过缺失 ( 6a ) 或用异羟肟酸 ( 10b ) 或苯甲酰胺 ( 12g )替代修饰 -SH 基团，研究了 HDAC 抑制、细胞生长抑制和 PsA-SH 凋亡诱导之间的联系。PsA-SH 抑制 HDAC1/2/3 和6a失去 HDAC 抑制能力。10b抑制 HDAC1/2/3/6，而12g显示对 HDAC3 的选择性抑制。PsA-SH 和10b，但既不是6a也不是12g，诱导人类白血病 HL-60 细胞凋亡，这与组蛋白 H3 乙酰化增加有关。PsA-SH 和10b在体外抑制几种实体瘤细胞系的生长以及在体内抑制 Lewis 肺癌细胞的生长。PsA-SH 是一种用于开发选择性 HDAC 抑制剂的简单支架，并通过抑制 HDAC1/2 诱导细胞凋亡。

  DOI：

  10.1021/acsmedchemlett.0c00369

文献信息

• New synthetic strategies towards psammaplin A, access to natural product analogues for biological evaluation
  作者：Matthias G. J. Baud、Thomas Leiser、Franz-Josef Meyer-Almes、Matthew J. Fuchter

  DOI：10.1039/c0ob00824a

  日期：——

  New synthetic routes towards the natural product psammaplin A were developed with the particular view to preparing diverse analogues for biological assessment. These routes utilize cheap and commercially available starting materials, and allowed access to psammaplin A analogues not accessible via currently reported methods. Preliminary biological studies revealed these compounds to be the most potent non peptidic inhibitors of the enzyme histone deacetylase 1 (HDAC1, class I) discovered so far. Interestingly, psammaplin A and our synthetic analogues show class I selectivity in vitro, an important feature for the design and synthesis of future isoform selective inhibitors.

  开发了新的合成路线以制备天然产物海绵抑素A（psammaplin A）及其多样化的类似物，这些类似物用于生物学评估。这些路线采用廉价且商业可获得的起始原料，并能合成目前报道方法难以获得的psammaplin A类似物。初步生物学研究表明，这些化合物是目前所发现的最强效的非肽类组蛋白去乙酰化酶1（HDAC1，I类）抑制剂。有趣的是，psammaplin A及其我们的合成类似物在体外显示出I类选择性，这对于设计和合成未来同工型选择性抑制剂具有重要意义。
• Defining the Mechanism of Action and Enzymatic Selectivity of Psammaplin A against Its Epigenetic Targets
  作者：Matthias G. J. Baud、Thomas Leiser、Patricia Haus、Sharon Samlal、Ai Ching Wong、Robert J. Wood、Vanessa Petrucci、Mekala Gunaratnam、Siobhan M. Hughes、Lakjaya Buluwela、Fabrice Turlais、Stephen Neidle、Franz-Josef Meyer-Almes、Andrew J. P. White、Matthew J. Fuchter

  DOI：10.1021/jm2016182

  日期：2012.2.23

  Psammaplin A (11c) is a marine metabolite previously reported to be a potent inhibitor of two classes of epigenetic enzymes: histone deacetylases and DNA methyltransferases. The design and synthesis of a focused library based on the psammaplin A core has been carried out to probe the molecular features of this molecule responsible for its activity. By direct in vitro assay of the free thiol generated upon reduction of the dimeric psammaplin scaffold, we have unambiguously demonstrated that 11c functions as a natural prodrug, with the reduced form being highly potent against HDAC1 in vitro (IC50 0.9 nM). Furthermore, we have shown it to have high isoform selectivity, being 360-fold selective for HDAC1 over HDAC6 and more than 1000-fold less potent against HDAC7 and HDAC8. SAR around our focused library revealed a number of features, most notably the oxime functionality to be important to this selectivity. Many of the compounds show significant cytotoxicity in A549, MCF7, and W138 cells, with the SAR of cytotcodcity correlating to HDAC inhibition. Furthermore, compound treatment causes upregulation of histone acetylation but little effect on tubulin acetylation. Finally, we have found no evidence for 11c functioning as a DNMT inhibitor.
• Brominated tyrosine metabolites from an unidentified sponge
  作者：Lili Arabshahi、Francis J. Schmitz

  DOI：10.1021/jo00392a016

  日期：1987.8
• Studying Histone Deacetylase Inhibition and Apoptosis Induction of Psammaplin A Monomers with Modified Thiol Group
  作者：Yu Bao、Qihao Xu、Lin Wang、Yunfei Wei、Baichun Hu、Jian Wang、Dan Liu、Linxiang Zhao、Yongkui Jing

  DOI：10.1021/acsmedchemlett.0c00369

  日期：2021.1.14

  histone deacetylase (HDAC) inhibition and acts through reduced monomer PsA-SH. We studied the connection of HDAC inhibition, cell growth inhibition, and apoptosis induction of PsA-SH by modifying the −SH group with deletion (6a) or replacement with hydroxamic acid (10b) or benzamide (12g). PsA-SH inhibits HDAC1/2/3 and 6a loses the HDAC inhibition ability. 10b inhibits HDAC1/2/3/6 while 12g shows selective

  Psammaplin A (PsA) 是一种溴酪氨酸二硫化物二聚体，具有组蛋白脱乙酰酶 (HDAC) 抑制作用，并通过还原的单体 PsA-SH 发挥作用。我们通过缺失 ( 6a ) 或用异羟肟酸 ( 10b ) 或苯甲酰胺 ( 12g )替代修饰 -SH 基团，研究了 HDAC 抑制、细胞生长抑制和 PsA-SH 凋亡诱导之间的联系。PsA-SH 抑制 HDAC1/2/3 和6a失去 HDAC 抑制能力。10b抑制 HDAC1/2/3/6，而12g显示对 HDAC3 的选择性抑制。PsA-SH 和10b，但既不是6a也不是12g，诱导人类白血病 HL-60 细胞凋亡，这与组蛋白 H3 乙酰化增加有关。PsA-SH 和10b在体外抑制几种实体瘤细胞系的生长以及在体内抑制 Lewis 肺癌细胞的生长。PsA-SH 是一种用于开发选择性 HDAC 抑制剂的简单支架，并通过抑制 HDAC1/2 诱导细胞凋亡。
• Synthesis of the Marine Bromotyrosine Psammaplin F and Crystal Structure of a Psammaplin A Analogue
  作者：Qianjiao Yang、Dan Liu、Deyang Sun、Sen Yang、Guodong Hu、Zuti Wu、Linxiang Zhao

  DOI：10.3390/molecules15128784

  日期：——

  Psammaplin F, an unsymmetrical disulfide bromotyrosine, was isolated from the sponge Pseudoceratina purpurea in 2003. We reported here the first total synthesis of psammaplin F in 12% overall yield by employing Cleland’s reagent reduction as key step. The longest linear synthetic sequence starting from 3-bromo-4-hydroxybenzaldehyde and hydantoin was seven steps. In addition, a detailed X-ray crystal structure analysis of psammaplin A analogue 8b is given for the first time.

  在2003年，从海绵Pseudoceratina purpurea中分离出了不对称二硫化物溴酪氨酸Psammaplin F。我们在这里报告了Psammaplin F的首次总合成，整体产率为12%，关键步骤采用了Cleland试剂还原。从3-溴-4-羟基苯甲醛和氢噻嗪开始的最长线性合成序列为七步。此外，首次提供了Psammaplin A类似物8b的详细X射线晶体结构分析。