(2S,3R)-2-(((benzyloxy)carbonyl)amino)-4-methoxy-3-methyl-4-oxobutanoic acid | 177472-10-5

• 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: (2S,3R)-2-(((benzyloxy)carbonyl)amino)-4-methoxy-3-methyl-4-oxobutanoic acid
• 英文别名: (2S,3R)-N-benzyloxycarbonyl-3-methylaspartic acid 4-methyl ester；(2S,3R)-4-methoxy-3-methyl-4-oxo-2-(phenylmethoxycarbonylamino)butanoic acid
• CAS: 177472-10-5
• 化学式: C₁₄H₁₇NO₆
• 分子量: 295.292
• InChiKey: MVWRHDVEGRHFPN-KOLCDFICSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,3R)-2-(((benzyloxy)carbonyl)amino)-4-methoxy-3-methyl-4-oxobutanoic acid 在 palladium on activated charcoal lithium hydroxide 、 sodium tetrahydroborate 、 氢气 、 N,N'-二环己基碳二亚胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 水 为溶剂， 反应 27.0h， 生成 Lithium; (R)-(S)-2-aziridin-2-yl-propionate
  参考文献：
  名称：

  Synthesis of Optically Active 2-Alkyl-3,4-iminobutanoic Acids. β-Amino Acids Containing an Aziridine Heterocycle

  摘要：

  All four stereoisomers of 2-alkyl-3,4-iminobutanoic acid, a novel class of beta -amino acids bearing a chemically versatile aziridine ring, were synthesized starting with aspartic acid. The synthetic strategy involves the introduction of an alkyl group at the beta -position of fully protected optically active aspartic acid followed by the construction of an aziridine ring making use of the alpha -carboxylate and alpha -amino groups. The alpha -carboxylate was reduced to the corresponding alcohol, which was then subjected to cyclization to form an aziridine ring with the N-protected amino group. Removal of the protection groups yielded the target compounds.

  DOI：

  10.1021/jo0014055
• 作为产物：
  描述：

  BOC-L-天冬氨酸二甲酯 在 sodium carbonate 、 乙酰氯 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 水 为溶剂， 反应 18.0h， 生成 (2S,3R)-2-(((benzyloxy)carbonyl)amino)-4-methoxy-3-methyl-4-oxobutanoic acid
  参考文献：
  名称：

  Synthesis of Optically Active 2-Alkyl-3,4-iminobutanoic Acids. β-Amino Acids Containing an Aziridine Heterocycle

  摘要：

  All four stereoisomers of 2-alkyl-3,4-iminobutanoic acid, a novel class of beta -amino acids bearing a chemically versatile aziridine ring, were synthesized starting with aspartic acid. The synthetic strategy involves the introduction of an alkyl group at the beta -position of fully protected optically active aspartic acid followed by the construction of an aziridine ring making use of the alpha -carboxylate and alpha -amino groups. The alpha -carboxylate was reduced to the corresponding alcohol, which was then subjected to cyclization to form an aziridine ring with the N-protected amino group. Removal of the protection groups yielded the target compounds.

  DOI：

  10.1021/jo0014055

文献信息

• Mapping the Aspartic Acid Binding Site of <i>Escherichia coli</i> Asparagine Synthetase B Using Substrate Analogs
  作者：Ian B. Parr、Susan K. Boehlein、Anthony B. Dribben、Sheldon M. Schuster、Nigel G. J. Richards

  DOI：10.1021/jm9601009

  日期：1996.1.1

  Novel inhibitors of asparagine synthetase, that will lower circulating levels of blood asparagine, have considerable potential in developing new protocols for the treatment of acute lymphoblastic leukemia. We now report the indirect characterization of the aspartate binding site of Escherichia coli asparagine synthetase B (AS-B) using a number of stereochemically, and conformationally, defined aspartic

  新的天冬酰胺合成酶抑制剂将降低血液中天冬酰胺的循环水平，在开发治疗急性淋巴细胞白血病的新方案方面具有巨大潜力。我们现在报告使用许多立体化学和构象确定的天冬氨酸类似物对大肠杆菌天冬酰胺合成酶B（AS-B）的天冬氨酸结合位点进行间接表征。在针对AS-B的动力学研究中，已发现使用天冬氨酸二酯的立体特异性β-官能化的新反应条件制备的两种化合物是相对于天冬氨酸的竞争性抑制剂。使用[（氟磺酰基）苯甲酰基]腺苷（​​FSBA）（一种ATP类似物）的化学修饰实验表明，两种抑制剂均与AS-B的天冬氨酸结合位点结合。
• Structure-Guided Design of a “Bump-and-Hole” Bromodomain-Based Degradation Tag
  作者：Radosław P. Nowak、Yuan Xiong、Nadia Kirmani、Joann Kalabathula、Katherine A. Donovan、Nicholas A. Eleuteri、J. Christine Yuan、Eric S. Fischer

  DOI：10.1021/acs.jmedchem.1c00958

  日期：2021.8.12

  Chemical biology tools to modulate protein levels in cells are critical to decipher complex biology. Targeted protein degradation offers the potential for rapid and dose-dependent protein depletion through the use of protein fusion tags toward which protein degraders have been established. Here, we present a newly developed protein degradation tag BRD4BD1L94V along with the corresponding cereblon (CRBN)-based

  调节细胞中蛋白质水平的化学生物学工具对于破译复杂的生物学至关重要。通过使用蛋白质融合标签，靶向蛋白质降解提供了快速和剂量依赖性蛋白质消耗的潜力，蛋白质降解剂已经建立。在这里，我们提出了一种新开发的蛋白质降解标签 BRD4 BD1 L94V 以及基于“凹凸洞”方法的相应基于 cereblon (CRBN) 的异质双功能降解剂。所得到的化合物XY-06-007示出了半降解浓度（DC 50，6小时对BRD4为10nM）BD1 L94V无的脱靶降解，如由整个蛋白质组质谱评估，并演示了合适的药代动力学在体内学习。我们证明 BRD4 BD1 L94V 可以与 dTAG 方法相结合，以同时实现降解剂介导的各自蛋白质融合的消耗。这种正交系统补充了当前可用的蛋白质降解标签，并能够调查先前不可治疗的疾病相关性的快速降解所导致的后果。
• [EN] PROTEIN TAG TO INDUCE LIGAND DEPENDENT DEGRADATION OF PROTEIN/PROTEIN-FUSIONS<br/>[FR] ÉTIQUETTE PROTÉIQUE POUR INDUIRE UNE DÉGRADATION DÉPENDANTE D'UN LIGAND DE FUSIONS PROTÉINE/PROTÉINE
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2021262591A1

  公开（公告）日：2021-12-30

  Disclosed is a dTAG system comprising small molecule degraders of mutant BET family protein-tagged proteins via recruitment of an E3 ubiquitin ligase and uses thereof.

  本文披露了一种dTAG系统，通过招募E3泛素连接酶，利用小分子降解剂对突变的BET家族蛋白标记蛋白进行处理，并其应用。
• Synthesis of Optically Active 2-Alkyl-3,4-iminobutanoic Acids. β-Amino Acids Containing an Aziridine Heterocycle
  作者：Jeong-il Park、Guan Rong Tian、Dong H. Kim

  DOI：10.1021/jo0014055

  日期：2001.6.1

  All four stereoisomers of 2-alkyl-3,4-iminobutanoic acid, a novel class of beta -amino acids bearing a chemically versatile aziridine ring, were synthesized starting with aspartic acid. The synthetic strategy involves the introduction of an alkyl group at the beta -position of fully protected optically active aspartic acid followed by the construction of an aziridine ring making use of the alpha -carboxylate and alpha -amino groups. The alpha -carboxylate was reduced to the corresponding alcohol, which was then subjected to cyclization to form an aziridine ring with the N-protected amino group. Removal of the protection groups yielded the target compounds.