(3-((((2E,6E)-8-bromo-2,6-dimethylocta-2,6-dien-1-yl)oxy)methyl)phenyl)(phenyl)methanone | 185686-52-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (3-((((2E,6E)-8-bromo-2,6-dimethylocta-2,6-dien-1-yl)oxy)methyl)phenyl)(phenyl)methanone
• 英文别名: (3-(((2E,6E)-8-bromo-2,6-dimethylocta-2,6-dienyloxy)methyl)phenyl)(phenyl)-methanone；(E,E)-8-O-(3-benzoylbenzyl)-3,7-dimethyl-2,6-octadiene-1-bromide；[3-[[(2E,6E)-8-bromo-2,6-dimethylocta-2,6-dienoxy]methyl]phenyl]-phenylmethanone
• CAS: 185686-52-6
• 化学式: C₂₄H₂₇BrO₂
• 分子量: 427.381
• InChiKey: OXEXHQWDUDCIHY-APFDVHGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3-((((2E,6E)-8-bromo-2,6-dimethylocta-2,6-dien-1-yl)oxy)methyl)phenyl)(phenyl)methanone 在 tris(tetra-n-butylammonium) hydrogen pyrophosphate 作用下， 以 乙腈 为溶剂， 以38%的产率得到(2E,6E)-8-[(3-Benzoylbenzyl)oxy]-3,7-dimethylocta-2,6-dienyl trihydrogen diphosphate
  参考文献：
  名称：

  法尼基和香叶基香叶基焦磷酸酯类似物并入苯甲酰基苄基醚：酵母蛋白法尼基转移酶的合成和抑制

  摘要：

  描述了结合了稳定的醚连接二苯甲酮的法呢基焦磷酸的两种光敏类似物（1a和1b）的合成。由香叶醇制备化合物1a和1b，总产率为17％。既1A和1B是相对于酵母蛋白质法尼基转移酶的竞争性抑制剂来法尼基焦磷酸和的K 1个49 45纳米的值纳摩。光解12小时后，1a和1b均使酶失活40％

  DOI：

  10.1016/s0040-4039(96)02066-7
• 作为产物：
  描述：

  (E,E)-8-O-(3-benzoylbenzyl)-3,7-dimethyl-2,6-octadiene-1-ol 在 三苯基膦树脂 、 四溴化碳 作用下， 以 二氯甲烷 为溶剂， 生成 (3-((((2E,6E)-8-bromo-2,6-dimethylocta-2,6-dien-1-yl)oxy)methyl)phenyl)(phenyl)methanone
  参考文献：
  名称：

  Synthesis of high specific activity 35S-labelled N-methanesulfonyl farnesylcysteine and a photoactive analog

  摘要：

  前烯丙基化半胱氨酸类似物模拟前烯丙基化 GTP 结合蛋白（G 蛋白）的前烯丙基化半胱氨酸残基，已被广泛用于研究前烯丙基化 G 蛋白的行为。在这一领域的早期研究中，我们制备了光活性类似物 [35S]4，并证明它能在光解时标记 RhoGDI；这些结果与 GDI 包含异肾上腺素结合位点的观点一致。在此，我们介绍了 N-乙酰法尼基半胱氨酸及其甲酯的[35S]N-甲磺酰基标记类似物（1a 和 2a）的制备过程，以及光活性类似物 3 和 4 的改进合成过程；其比活性达到了 1100 Ci/mmol。未标记的化合物 1a 和 2a 被用作光解反应的竞争者，表明甲磺酰胺基是一种合理的乙酰胺取代基。其他实验表明，光活性酯 [35S]3 可以交联纯化形式和粗细菌提取物中的 GDI。然而，使用酯（[35S]3）获得的交联程度明显低于使用游离酸（[35S]4）观察到的交联程度，尽管酯化形式可能更接近于反映前炔化蛋白质 C 端的结构；使用 GDI-Cdc42 共晶体结构，讨论了这些结果的结构基础。Copyright © 2002 John Wiley & Sons, Ltd. All Rights Reserved.

  DOI：

  10.1002/jlcr.638

文献信息

• A Photoactive Isoprenoid Diphosphate Analogue Containing a Stable Phosphonate Linkage:  Synthesis and Biochemical Studies with Prenyltransferases
  作者：Amanda J. DeGraw、Zongbao Zhao、Corey L. Strickland、A. Huma Taban、John Hsieh、Michael Jefferies、Wenshuang Xie、David K. Shintani、Colleen M. McMahan、Katrina Cornish、Mark D. Distefano

  DOI：10.1021/jo0623033

  日期：2007.6.1

  biosynthesis of a wide array of compounds. Photoactivatable analogues have been developed to study isoprenoid utilizing enzymes such as the isoprenoid synthases and prenyltransferases. While these initial analogues proved to be excellent structural analogues with good cross-linking capability, they lack the stability needed when the goals include isolation of cross-linked species, tryptic digestion, and subsequent

  许多生化过程都依赖类异戊二烯，包括信号蛋白的翻译后修饰和多种化合物的生物合成。已经开发出了可光活化的类似物以利用诸如类异戊二烯合酶和异戊二烯基转移酶之类的酶研究类异戊二烯。尽管这些最初的类似物被证明是具有良好交联能力的出色结构类似物，但当目标包括分离交联物种，胰蛋白酶消化和随后的肽测序时，它们却缺乏所需的稳定性。在此，描述了含有稳定的膦酰基磷酸酯基的基于二苯甲酮的法呢基二磷酸二磷酸酯类似物的合成。描述了抑制动力学，光标记实验以及蛋白质异戊二烯基转移酶的X射线晶体学分析，验证该化合物为良好的类异戊二烯模拟物。此外，通过使用这种新类似物对从中获得的粗蛋白提取物进行光亲和标记来探索其实用性。巴西橡胶树乳胶。这些实验表明，在橡胶生物合成过程中，一种小的蛋白质，即橡胶伸长因子，与法呢基二磷酸直接相互作用。这些结果表明，这种基于二苯甲酮的类异戊二烯类似物可用于鉴定以法呢基二磷酸为底物的酶。
• A Photoactivatable Prenylated Cysteine Designed to Study Isoprenoid Recognition
  作者：Tamara A. Kale、Conrad Raab、Nathan Yu、Dennis C. Dean、Mark D. Distefano

  DOI：10.1021/ja0012016

  日期：2001.5.1

  Protein prenylation, involving the alkylation of a specific C-terminal cysteine with a C-15 or C-20 isoprenoid unit, is an essential posttranslational modification required by most GTP-binding proteins for normal biological activity. Despite the ubiquitous nature of this modification and numerous efforts aimed at inhibiting prenylating enzymes for therapeutic purposes, the function of prenylation remains unclear. To explore the role the isoprenoid plays in mediating protein-protein recognition, we have synthesized a photoactivatable, isoprenoid-containing cysteine analogue (2) designed to act as a mimic of the C-terminus of prenylated proteins. Photolysis experiments with 2 and RhoCDI (GDI), a protein which interacts with prenylated Rho proteins, suggest that the GDI is in direct contact with the isoprenoid moiety. These results, obtained using purified GDI as well as Escherichia coli (E. coli) crude extract containing GDI, suggest that this analogue will be an effective and versatile tool for the investigation of putative isoprenoid binding sites in a variety of systems. Incorporation of this analogue into peptides or proteins should allow for even more specific interactions between the photoactivatable isoprenoid and any number of isoprenoid binding proteins.
• Synthesis of a-factor peptide from Saccharomyces cerevisiae and photoactive analogues via Fmoc solid phase methodology
  作者：Daniel G. Mullen、Kelly Kyro、Melinda Hauser、Martin Gustavsson、Gianluigi Veglia、Jeffery M. Becker、Fred Naider、Mark D. Distefano

  DOI：10.1016/j.bmc.2010.11.006

  日期：2011.1

  a-Factor from Saccharomyces cerevisiae is a farnesylated dodecapeptide involved in mating. The molecule binds to a G-protein coupled receptor and hence serves as a simple system for studying the interactions between prenylated molecules and their cognate receptors. Here, we describe the preparation of a-factor and two photoactive analogues via Fmoc solid-phase peptide synthesis using hydrazinobenzoyl AM NovaGel (TM) resin; the structure of the synthetic a-factor was confirmed by MS-MS analysis and NMR; the structures of the analogues were confirmed by MS-MS analysis. Using a yeast growth arrest assay, the analogues were found to have activity comparable to a-factor itself. (C) 2010 Elsevier Ltd. All rights reserved.
• Photoaffinity labeling of Ras converting enzyme using peptide substrates that incorporate benzoylphenylalanine (Bpa) residues: Improved labeling and structural implications
  作者：Kelly Kyro、Surya P. Manandhar、Daniel Mullen、Walter K. Schmidt、Mark D. Distefano

  DOI：10.1016/j.bmc.2011.10.027

  日期：2011.12

  Rce1p catalyzes the proteolytic trimming of C-terminal tripeptides from isoprenylated proteins containing CAAX-box sequences. Because Rce1p processing is a necessary component in the Ras pathway of oncogenic signal transduction, Rce1p holds promise as a potential target for therapeutic intervention. However, its mechanism of proteolysis and active site have yet to be defined. Here, we describe synthetic peptide analogues that mimic the natural lipidated Rce1p substrate and incorporate photolabile groups for photo-affinity-labeling applications. These photoactive peptides are designed to crosslink to residues in or near the Rce1p active site. By incorporating the photoactive group via p-benzoyl-L-phenylalanine (Bpa) residues directly into the peptide substrate sequence, the labeling efficiency was substantially increased relative to a previously-synthesized compound. Incorporation of biotin on the N-terminus of the peptides permitted photolabeled Rce1p to be isolated via streptavidin affinity capture. Our findings further suggest that residues outside the CAAX-box sequence are in contact with Rce1p, which has implications for future inhibitor design. (C) 2011 Elsevier Ltd. All rights reserved.
• Farnesyl and geranylgeranyl pyrophosphate analogs incorporating benzoylbenzyl ethers: Synthesis and inhibition of yeast protein farnesyltransferase
  作者：Igor Gaon、Tammy C. Turek、Mark D. Distefano

  DOI：10.1016/s0040-4039(96)02066-7

  日期：1996.12

  The syntheses of two photoactive analogs (1a and 1b) of farnesyl pyrophosphate that incorporate stable ether-linked benzophenones are described. Compounds 1a and 1b were prepared from geraniol in 17% overall yield. Both 1a and 1b are competitive inhibitors of yeast protein famesyltransferase with respect to farnesyl pyrophosphate and have K1 values of 45 nM and 49 nM. Upon photolysis for twelve hours

  描述了结合了稳定的醚连接二苯甲酮的法呢基焦磷酸的两种光敏类似物（1a和1b）的合成。由香叶醇制备化合物1a和1b，总产率为17％。既1A和1B是相对于酵母蛋白质法尼基转移酶的竞争性抑制剂来法尼基焦磷酸和的K 1个49 45纳米的值纳摩。光解12小时后，1a和1b均使酶失活40％