4-((tert-butyldimethylsilyl)oxy)-2-hydroxybenzaldehyde | 129742-35-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-((tert-butyldimethylsilyl)oxy)-2-hydroxybenzaldehyde
• 英文别名: 4-[Tert-butyl(dimethyl)silyl]oxy-2-hydroxybenzaldehyde
• CAS: 129742-35-4
• 化学式: C₁₃H₂₀O₃Si
• 分子量: 252.386
• InChiKey: DDJNUUOEMABUGY-UHFFFAOYSA-N

物化性质

• 沸点：
  295.2±30.0 °C(Predicted)
• 密度：
  1.043±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.59
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-((tert-butyldimethylsilyl)oxy)-2-hydroxybenzaldehyde 在 N-甲基吗啉 、 三聚氯氰 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 7-hydroxy-3-(4-iodophenyl)-2H-chromen-2-one
  参考文献：
  名称：

  7-Hydroxycoumarins Are Affinity-Based Fluorescent Probes for Competitive Binding Studies of Macrophage Migration Inhibitory Factor

  摘要：

  Macrophage migration inhibitory factor (MIF) is a cytokine with key roles in inflammation and cancer, which qualifies it as a potential drug target. Apart from its cytokine activity, MIF also harbors enzyme activity for keto-enol tautomerization. MIF enzymatic activity has been used for identification of MIF binding molecules that also interfere with its biological activity. However, MIF tautomerase activity assays are troubled by irregularities, thus creating a need for alternative methods. In this study, we identified a 7-hydroxycoumarin fluorophore with high affinity for the MIF tautomerase active site (Ki = 18 ± 1 nM) that binds with concomitant quenching of its fluorescence. This property enabled development of a novel competition-based assay format to quantify MIF binding. We also demonstrated that the 7-hydroxycoumarin fluorophore interfered with the MIF-CD74 interaction and inhibited proliferation of A549 cells. Thus, we provide a high-affinity MIF binder as a novel tool to advance MIF-oriented research.

  DOI：

  10.1021/acs.jmedchem.0c01160
• 作为产物：
  描述：

  2,4-di-O-tert-butyldimethylsiloxybenzaldehyde 在 zinc(II) chloride 作用下， 以 1,2-二氯乙烷 为溶剂， 以91%的产率得到4-((tert-butyldimethylsilyl)oxy)-2-hydroxybenzaldehyde
  参考文献：
  名称：

  Positional chemoselectivity in the Zn(II)-mediated removal of phenol protecting groups

  摘要：

  A protocol was developed for the chemoselective ortho-deprotection of polyphenolic substrates using readily available (ZnX2)-X-II salts. This procedure provides exceptional positional selectivity for the deprotection of phenols that reside adjacent to directing carbonyl functionality in the presence of similar protecting groups at the meta and para positions. Good to excellent yields of the desired free phenols were obtained (<= 96%), and a wide assortment of protecting groups was readily removed under the reaction conditions. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2012.07.103
• 作为试剂：
  描述：

  4-((tert-butyldimethylsilyl)oxy)-2-hydroxybenzaldehyde 、 2-(4-((tert-butyldimethylsilyl)-oxy)phenyl)acetaldehyde 在 4-((tert-butyldimethylsilyl)oxy)-2-hydroxybenzaldehyde 作用下， 以30的产率得到4',7-di-tert-butyldimethylsilyloxy-2-morpholinoisoflav-3-ene
  参考文献：
  名称：

  Bioorg. Med. Chem. 2012, 20, 2353-2361

  摘要：

  DOI：

文献信息

• [EN] TARGETED BIFUNCTIONAL DEGRADERS<br/>[FR] AGENTS DE DÉGRADATION BIFONCTIONNELS CIBLÉS
  申请人：UNIV YALE

  公开号：WO2021072269A1

  公开（公告）日：2021-04-15

  The present invention provides, in one aspect, bifunctional compounds that can be used to promote or enhance degradation of certain circulating proteins. In another aspect, the present invention provides bifunctional compounds that can be used to promote or enhance degradation of certain autoantibodies. In certain embodiments, treatment or management of a disease and/or disorder requires degradation, removal, or reduction in concentration of the circulating protein or the autoantibody in the subject. Thus, in certain embodiments, administration of a compound of the invention to the subject removes or reduces the circulation concentration of the circulating protein or the autoantibody, thus treating, ameliorating, or preventing the disease and/or disorder. In certain embodiments, the circulating protein is TNF.

  本发明在一个方面提供了可以用来促进或增强降解某些循环蛋白的双功能化合物。在另一个方面，本发明提供了可以用来促进或增强降解某些自身抗体的双功能化合物。在某些实施方式中，治疗或管理疾病和/或疾病需要降解、去除或减少受试者体内循环蛋白或自身抗体的浓度。因此，在某些实施方式中，将本发明的化合物给予受试者可去除或减少循环蛋白或自身抗体的循环浓度，从而治疗、改善或预防疾病和/或疾病。在某些实施方式中，循环蛋白是TNF。
• Proteolysis Targeting Chimera (PROTAC) for Macrophage Migration Inhibitory Factor (MIF) Has Anti‐Proliferative Activity in Lung Cancer Cells
  作者：Zhangping Xiao、Shanshan Song、Deng Chen、Ronald Merkerk、Petra E. Wouden、Robbert H. Cool、Wim J. Quax、Gerrit J. Poelarends、Barbro N. Melgert、Frank J. Dekker

  DOI：10.1002/anie.202101864

  日期：2021.8.2

  Macrophage migration inhibitory factor (MIF) is involved in protein-protein interactions that play key roles in inflammation and cancer. Current strategies to develop small molecule modulators of MIF functions are mainly restricted to the MIF tautomerase active site. Here, we use this site to develop proteolysis targeting chimera (PROTAC) in order to eliminate MIF from its protein-protein interaction

  巨噬细胞迁移抑制因子 (MIF) 参与蛋白质-蛋白质相互作用，在炎症和癌症中发挥关键作用。目前开发 MIF 功能小分子调节剂的策略主要局限于 MIF 互变异构酶活性位点。在这里，我们利用该位点开发蛋白水解靶向嵌合体 (PROTAC)，以从其蛋白质-蛋白质相互作用网络中消除 MIF。我们报道了第一个有效的 MIF 导向的 PROTAC，表示为MD13，它在低微摩尔浓度下诱导几乎完全的 MIF 降解，在 A549 细胞中DC 50约为 100 nM。MD13抑制 A549 细胞的增殖，这可以通过 MAPK 途径失活以及随后诱导细胞周期停滞在 G2/M 期来解释。MD13在 3D 肿瘤球体模型中也表现出抗增殖作用。总之，我们描述了第一个MIF导向的PROTAC（MD13）作为研究工具，这也证明了PROTAC在癌症治疗中的潜力。
• Total Synthesis of Two Glycosylated Stilbenes, Oxyresveratrol 2-<i>O</i>-β-<scp>d</scp>-Glucopyranoside and 2,3,5,4′-Tetrahydroxystilbene 2-<i>O</i>-β-<scp>d</scp>-Glucopyranoside
  作者：Sunil Kumar、Hsueh-Yun Lee、Jing-Ping Liou

  DOI：10.1021/acs.jnatprod.6b00861

  日期：2017.5.26

  multiflorum, respectively. A facile four-step synthesis of 1 involved selective protection of the hydroxy groups and Wittig olefination to generate the compound in 8% overall yield. For compound 1′, a 10-step synthesis utilized selective protection of the hydroxy groups, Baeyer–Villiger oxidation, modified Duff formylation, and Wittig olefination to generate the compound in 6.9% overall yield.

  糖基化的对苯二酚是植物的生物活性次生代谢产物，具有缓解广泛人类疾病的潜力。然而，这些化合物中的一些不是天然丰富的，因此期望合成此类分子。本文报道了氧白藜芦醇2- O- β- d-吡喃葡萄糖苷（1）和2,3,5,4'-四羟基sti -2- （2 - O - β - d-吡喃葡萄糖苷（1'）的首次合成，这是一种二苯乙烯苷分别来自Schoenocaulon officinale和何首乌的根茎。轻松的四步合成1涉及羟基的选择性保护和Wittig烯化反应以8％的总收率生成该化合物。对于化合物1'，分十步进行的合成利用了羟基的选择性保护，Baeyer-Villiger氧化，改良的Duff甲酰化和Wittig烯烃化，以6.9％的总收率生成该化合物。
• Biomimetic Synthesis of Santalin A,B and Santarubin A,B, the Major Colorants of Red Sandalwood
  作者：Sebastian Strych、Dirk Trauner

  DOI：10.1002/anie.201302317

  日期：2013.9.2

  Better late than never! Almost 200 years after Pelletier's pioneering studies on the chemical constituents of red sandalwood, the major santalins and santarubins have been synthesized. This efficient approach integrates a Knochel isoflavonoid synthesis with Friedel–Crafts allylations or olefin metatheses, and a final biomimetic reaction cascade that furnishes the venerable benzoxanthenone dyes in a

  迟到总比不到好！在Pelletier对红檀香的化学成分进行开创性研究后近200年，已经合成了主要的檀香木和檀香木素。这种有效的方法将Knochel异黄酮合成与Friedel-Crafts烯丙基化或烯烃复分解反应结合在一起，以及最终的仿生反应级联反应，可在一次操作中提供古老的苯并氧杂蒽酮染料（参见方案）。
• A Fluorescence Polarization Assay for Binding to Macrophage Migration Inhibitory Factor and Crystal Structures for Complexes of Two Potent Inhibitors
  作者：José A. Cisneros、Michael J. Robertson、Margarita Valhondo、William L Jorgensen

  DOI：10.1021/jacs.6b04910

  日期：2016.7.13

  on monitoring the tautomerase activity using l-dopachrome methyl ester or 4-hydroxyphenyl pyruvic acid as substrates. The accuracy of these assays is compromised by several issues including substrate instability, spectral interference, and short linear periods for product formation. In this work, we report the syntheses of fluorescently labeled MIF inhibitors and their use in the first fluorescence polarization-based

  人类巨噬细胞迁移抑制因子 (MIF) 既是一种酮-烯醇互变异构酶，又是一种与多种炎症疾病和癌症相关的细胞因子。与观察到的酶活性和生物活性抑制之间的相关性一致，MIF 抑制剂的发现集中在使用 l-多巴色素甲酯或 4-羟基苯基丙酮酸作为底物监测互变异构酶活性。这些测定的准确性受到若干问题的影响，包括底物不稳定性、光谱干扰和产物形成的短线性周期。在这项工作中，我们报告了荧光标记的 MIF 抑制剂的合成及其在第一个基于荧光偏振的测定中的应用，以测量抑制剂与活性位点的直接结合。该测定允许以可扩展用于高通量筛选的方式准确有效地识别 MIF 的竞争性、非竞争性和共价抑制剂。22 种化合物的结果表明，最有效的 MIF 抑制剂结合的 Kd 值为约。50纳米；两个来自我们的实验室，另一个是专利文献中的化合物。此处还报告了与 MIF 结合的两种最有效化合物的 X 射线晶体结构。蛋白质-配体氢键、芳基-芳基和阳离