methyl (S)-3-(4-benzoylphenyl)-2-((tert-butoxycarbonyl)amino)propanoate | 300811-75-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (S)-3-(4-benzoylphenyl)-2-((tert-butoxycarbonyl)amino)propanoate
• 英文别名: methyl (S)-3-(4-benzoylphenyl)-2-(tert-butoxycarbonylamino)propanoate；Boc-L-3-(4-benzoylphenyl)alanyl-OMe；methyl (2S)-3-(4-benzoylphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• CAS: 300811-75-0
• 化学式: C₂₂H₂₅NO₅
• 分子量: 383.444
• InChiKey: SYIXVSLPIVNWJQ-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (S)-3-(4-benzoylphenyl)-2-((tert-butoxycarbonyl)amino)propanoate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 methyl (S)-3-(4-benzoylphenyl)-2-(5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido)propanoate
  参考文献：
  名称：

  Native FKBP12 Engineering by Ligand-Directed Tosyl Chemistry: Labeling Properties and Application to Photo-Cross-Linking of Protein Complexes in Vitro and in Living Cells

  摘要：

  The ability to modify target "native" (endogenous) proteins selectively in living cells with synthetic molecules should provide powerful tools for chemical biology. To this end, we recently developed a novel protein labeling technique termed ligand-directed tosyl (LDT) chemistry. This method uses labeling reagents in which a protein ligand and a synthetic probe are connected by a tosylate ester group. We previously demonstrated its applicability to the selective chemical labeling of several native proteins in living cells and mice. However, many fundamental features of this chemistry remain to be studied. In this work, we investigated the relationship between the LDT reagent structure and labeling properties by using native FK506-binding protein 12 (FKBP12) as a target protein. In vitro experiments revealed that the length and rigidity of the spacer structure linking the protein ligand and the tosylate group have significant effects on the overall labeling yield and labeling site. In addition to histidine, which we reported previously, tyrosine and glutamate residues were identified as amino acids that are modified by LDT-mediated labeling. Through the screening of various spacer structures, piperazine was found to be optimal for FKBP12 labeling in terms of labeling efficiency and site specificity. Using a piperazine-based LDT reagent containing a photoreactive probe, we successfully demonstrated the labeling and UV-induced covalent cross-linking of FKBP12 and its interacting proteins in vitro and in living cells. This study not only furthers our understanding of the basic reaction properties of LDT chemistry but also extends the applicability of this method to the investigation of biological processes in mammalian cells.

  DOI：

  10.1021/ja209641t
• 作为产物：
  描述：

  (R)-N-叔丁氧羰基-3-碘代丙氨酸甲酯 在 三甲基氯硅烷 、 氯化镍二甲氧基乙烷 、 [Ir(dF(CF₃)ppy)₂(dtbbpy)](PF₆) 、 2-[(4S)-4-叔丁基-4,5-二氢-2-恶唑基]-5-三氟甲基吡啶 、 锌 作用下， 以 1,2-二溴乙烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 38.0h， 生成 methyl (S)-3-(4-benzoylphenyl)-2-((tert-butoxycarbonyl)amino)propanoate
  参考文献：
  名称：

  光氧化还原镍催化 Stille 交叉偶联反应

  摘要：

  首次设计了一种新型光氧化还原/镍催化立体收敛Stille反应，可以构建丰富的C( sp 3 )−C( sp 3 )、C( sp 3 )−C( sp 2 )、 C( sp 3 )−C( sp ) 在极其温和的条件下以良好至高的产率以优异的立体选择性键合。协同光氧化还原/镍催化的创新应用实现了锡烷试剂的新型单电子金属转移过程，为 Stille 反应领域提供了新的研究范式。

  DOI：

  10.1002/anie.202314832

文献信息

• Ketone Synthesis by a Nickel-Catalyzed Dehydrogenative Cross-Coupling of Primary Alcohols
  作者：Thomas Verheyen、Lars van Turnhout、Jaya Kishore Vandavasi、Eric S. Isbrandt、Wim M. De Borggraeve、Stephen G. Newman

  DOI：10.1021/jacs.9b03280

  日期：2019.5.1

  intermolecular coupling of primary alcohols and organotriflates has been developed to provide ketones by the action of a Ni(0) catalyst. This oxidative transformation is proposed to occur by the union of three distinct catalytic cycles. Two competitive oxidation processes generate aldehyde in situ via hydrogen transfer oxidation or (pseudo)dehalogenation pathways. As aldehyde forms, a Ni-catalyzed carbonyl-Heck

  伯醇和有机三氟甲磺酸酯的分子间偶联已被开发出来，通过 Ni(0) 催化剂的作用提供酮。这种氧化转化被认为是通过三个不同的催化循环的结合而发生的。两种竞争性氧化过程通过氢转移氧化或（伪）脱卤途径原位生成醛。随着醛的形成，Ni催化的羰基-Heck过程能够形成关键的碳-碳键。通过合成多种复杂的生物活性分子，证明了这种稀有醇转化为酮的效用。
• Room-Temperature Decarboxylative Couplings of α-Oxocarboxylates with Aryl Halides by Merging Photoredox with Palladium Catalysis
  作者：Wan-Min Cheng、Rui Shang、Hai-Zhu Yu、Yao Fu

  DOI：10.1002/chem.201502286

  日期：2015.9.14

  Enabled by merging iridium photoredox catalysis and palladium catalysis, α‐oxocarboxylate salts can be decarboxylatively coupled with aryl halides to generate aromatic ketones and amides at room temperature. DFT calculations suggest that this reaction proceeds through a Pd0–PdII–PdIII pathway, in which the PdIII intermediate is responsible for reoxidizing IrII to complete the IrIII–*IrIII–IrII photoredox

  通过合并铱的光氧化还原催化和钯催化，α-氧代羧酸盐可以与芳基卤化物脱羧偶联，在室温下生成芳族酮和酰胺。DFT计算表明，该反应通过Pd 0 -Pd II -Pd III途径进行，其中Pd III中间体负责重新氧化Ir II以完成Ir III- * Ir III -Ir II光氧化还原循环。
• Pretubulysin derived probes as novel tools for monitoring the microtubule network via activity-based protein profiling and fluorescence microscopy
  作者：Jürgen Eirich、Jens L. Burkhart、Angelika Ullrich、Georg C. Rudolf、Angelika Vollmar、Stefan Zahler、Uli Kazmaier、Stephan A. Sieber

  DOI：10.1039/c2mb25144b

  日期：——

  Microtubules (mt) are highly dynamic polymers composed of alpha- and beta-tubulin monomers that are present in all dividing and non-dividing cells. A broad variety of natural products exists that are known to interfere with the microtubule network, by either stabilizing or de-stabilizing these rope-like polymers. Among those tubulysins represent a new and potent class of cytostatic tetrapeptides originating from myxobacteria. Early studies suggested that tubulysins interact with the eukaryotic cytoskeleton by inhibition of tubulin polymerization with EC50 values in the picomolar range. Recently, pretubulysins have been described to retain the high tubulin-degradation activity of their more complex tubulysin relatives and represent an easier synthetic target with an efficient synthesis already in place. Although tubulin has been suggested as the dedicated target of tubulysin a comprehensive molecular target analysis of pretubulysin in the context of the whole proteome has not been carried out so far. Here we utilize synthetic chemistry to develop two pretubulysin photoaffinity probes which were applied in cellular activity-based protein profiling and imaging studies in order to unravel and visualize dedicated targets. Our results clearly show a remarkable selectivity of pretubulysin for beta-tubulin which we independently confirmed by a mass-spectrometry based proteomic profiling platform as well as by tubulin antibody based co-staining on intact cells.

  微管（mt）是由α-和β-微管蛋白单体组成的高动态聚合物，存在于所有分裂和非分裂细胞中。已知有多种天然产品可以通过稳定或降低这些绳状聚合物的稳定性来干扰微管网络。其中，管胞素（tubulysins）是一类新型、强效的细胞抑制四肽，源自粘杆菌。早期研究表明，tubulysins 通过抑制微管蛋白聚合与真核细胞骨架相互作用，其 EC50 值在皮摩尔范围内。最近，前管胞素（pretubulysins）被描述为保留了其更复杂的管胞素近亲的高管胞素降解活性，并且是一种更容易合成的目标，其高效合成已经到位。尽管管蛋白被认为是管胞素的专用靶标，但迄今为止还没有在整个蛋白质组的背景下对前管胞素进行过全面的分子靶标分析。在此，我们利用合成化学方法开发了两种pretubulysin光亲和探针，并将其应用于基于细胞活性的蛋白质分析和成像研究，以揭示和观察专用靶标。我们的研究结果清楚地表明，pretubulysin 对 beta-tubulin（β-微管蛋白）具有显著的选择性，这一点我们已通过基于质谱分析的蛋白质组学分析平台以及基于微管蛋白抗体的完整细胞共染色得到了独立证实。
• A concise synthesis of photoactivatable 4-Aroyl-l-phenylalanines
  作者：Enrico Morera、Giorgio Ortar

  DOI：10.1016/s0960-894x(00)00344-9

  日期：2000.8

  An efficient preparation of the title compounds from 4-iodo-L-phenylalanines using a carbonylative Stille cross-coupling reaction as the key-step is described (C) 2000 Elsevier Science Ltd. All rights reserved.
• Stereo-controlled synthesis of novel photoreactive γ-secretase inhibitors
  作者：Guangli Yang、Ye Ingrid Yin、Jiong Chun、Christopher C. Shelton、Ouathek Ouerfelli、Yue-Ming Li

  DOI：10.1016/j.bmcl.2008.11.117

  日期：2009.2

  The stereoselective synthesis of novel photoreactive gamma-secretase inhibitors 2 and 3 has been achieved. Key steps of the strategy involve preparation of alpha-N-Boc-epoxide 8 and formation of lactone 14 in a practical and stereo-controlled fashion. Compounds 2 and 3 are potent gamma-secretase inhibitors and directly interact with presenilin-1, a catalytic subunit of gamma-secretase. (C) 2008 Elsevier Ltd. All rights reserved.