(2R)-1-{[(2R)-1-甲氧基-1-氧代-2-丙基]氨基}-1-氧代-2-丙氯化铵 | 105328-90-3

• 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
• 中文名称: (2R)-1-{[(2R)-1-甲氧基-1-氧代-2-丙基]氨基}-1-氧代-2-丙氯化铵
• 英文名称: D-Ala-D-Ala-OMe hydrochloride
• 英文别名: D-alanyl-D-alanine methyl ester hydrochloride；(R)-Methyl 2-((R)-2-aminopropanamido)propanoate hydrochloride；methyl (2R)-2-[[(2R)-2-aminopropanoyl]amino]propanoate;hydrochloride
• CAS: 105328-90-3
• 化学式: C₇H₁₄N₂O₃*ClH
• 分子量: 210.661
• InChiKey: WVSVBOMWSCRPGM-TYSVMGFPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.7
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  83
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 储存条件：
  -20℃

反应信息

• 作为反应物：
  描述：

  (2R)-1-{[(2R)-1-甲氧基-1-氧代-2-丙基]氨基}-1-氧代-2-丙氯化铵 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 41.15h， 生成
  参考文献：
  名称：

  Asymmetric Catalysis at a Distance: Catalytic, Site-Selective Phosphorylation of Teicoplanin

  摘要：

  We report three distinct, peptide-based catalysts that enable site-selective phosphorylation of three distinct hydroxyl groups within the complex glycopeptide antibiotic teicoplanin A(2)-2. Two of the catalysts are based on a design that capitalizes on a catalyst substrate interaction that mimics the biological mechanism of action for teicoplanin. These catalysts are based on a DXaa-DXaa peptide motif that is known to target the teicoplanin structure in a specific manner. The third was identified through evaluation of a set of catalysts that had been developed for historically distinct projects. Each catalyst contains additional functionality designed to dispose a catalytic moiety (a nudeophilic alkylimidazole) at a different region of the glycopeptide structure. A combination of mass spectrometry and 2D-NMR spectroscopy allowed structural assignment of the distinct phosphorylated teicoplanin derivatives. Mechanistic studies are also reported that support the hypotheses that led to the discovery of the catalysts. In this manner, small molecule catalysts have been achieved that allow rational, catalytic control over reactions at sites that are separated by 11.6, 16.5, and nearly 17.7 angstrom, based on the X-ray crystal structure of teicoplanin A(2)-2. Finally, we report the biological activity of the new phosphorylated teicoplanin analogs and compare the results to the natural product itself.

  DOI：

  10.1021/ja406067v
• 作为产物：
  描述：

  N-Boc-D-alanyl-D-alanine methyl ester 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 (2R)-1-{[(2R)-1-甲氧基-1-氧代-2-丙基]氨基}-1-氧代-2-丙氯化铵
  参考文献：
  名称：

  用于合成脂质 II 类似物的一锅保护糖基化反应

  摘要：

  (2,6-二氯-4-甲氧基苯基)(2,4-二氯苯基)甲基三氯乙酰亚胺酯( 3 )及其聚合物支撑试剂4可成功应用于一锅保护糖基化反应，形成二糖衍生物7d 用于合成脂质 II 类似物。C-6位的临时保护基或连接基和7d的N -Troc保护基可以通过还原条件同时裂解。通过使用所描述的方法，脂质 II ( 1 ) 和橙花基脂质 II N ε -丹磺基硫脲的合成总产率显着提高。 

  DOI：

  10.1002/chem.201400307

文献信息

• [EN] COMPOUNDS FOR AMIDE-FORMING REACTIONS<br/>[FR] COMPOSÉS POUR DES RÉACTIONS DE FORMATION D'AMIDE
  申请人：UNIV TENNESSEE RES FOUNDATION

  公开号：WO2013180815A1

  公开（公告）日：2013-12-05

  Provided herein is a compound of Formula I, that displays remarkable physicochemical properties as a peptide-coupling additive for peptide-forming reactions in water, wherein said coupling reactions proceed without measurable racemization. A method of producing the compound of Formula I comprising reaction of a malononitrile precursor compound with sodium nitrite and glacial acetic acid, is also provided.

  本文提供的是一种具有显著物理化学性质的化合物，作为肽偶联添加剂用于水中的肽形成反应，其中所述的偶联反应在没有可测量的旋光异构化的情况下进行。还提供了一种制备公式I化合物的方法，包括将丙二腈前体化合物与亚硝酸钠和冰乙酸反应。
• [EN] INHIBITORS OF METALLO-BETA-LACTAMASE (MBL) COMPRISING A ZINC CHELATING MOIETY<br/>[FR] INHIBITEURS DE MÉTALLO-BÊTA-LACTAMASE (MBL) COMPRENANT UNE FRACTION DE CHÉLATION DU ZINC
  申请人：UNI I OSLO

  公开号：WO2015049546A1

  公开（公告）日：2015-04-09

  The invention provides compounds according to formula I: A - L - B wherein A represents a lipophilic chelating moiety which is selective for Zn2+ ions; L is a covalent bond or a linker; and B is a vector which is either a moiety capable of interacting with one or more biological structures found in a bacterium (preferably in a bacterial cell wall), for example a penicillin-binding protein such as a metallo-β- lactamase or DD-transferase, or a moiety capable of enhancing transport of the compound across a bacterial cell membrane. Such compounds find use in a method of treating and/or preventing a bacterial infection in a human or non-human mammal. In such a method, the compound of formula I may be administered in combination with (either simultaneously, separately, or sequentially) a β-lactam antibiotic.

  该发明提供了符合以下公式I的化合物：A - L - B，其中A代表选择性对Zn2+离子的亲脂螯合基团；L是共价键或连接物；B是矢量，可以是能与细菌中的一个或多个生物结构相互作用的基团（最好是在细菌细胞壁中找到的），例如金黄色葡萄球菌结合蛋白（例如金属β-内酰胺酶或DD-转移酶），或者是能增强化合物穿过细菌细胞膜的基团。这种化合物可用于治疗和/或预防人类或非人哺乳动物的细菌感染的方法。在这种方法中，公式I的化合物可以与（同时、分开或顺序地）β-内酰胺类抗生素一起给予。
• Synthesis and biological evaluation of zinc chelating compounds as metallo-β-lactamase inhibitors
  作者：Geir Kildahl-Andersen、Christian Schnaars、Anthony Prandina、Sylvie Radix、Marc Le Borgne、Lars Petter Jordheim、Tor Gjøen、Adriana Magalhães Santos Andresen、Silje Lauksund、Christopher Fröhlich、Ørjan Samuelsen、Pål Rongved、Ove Alexander Høgmoen Åstrand

  DOI：10.1039/c8md00578h

  日期：——

  pentadentate). The chosen peptides were mainly based on the known sequence of the C-terminus of the bacterial peptidoglycan precursors. Biological evaluation on clinical bacterial isolates, harbouring either the NDM-1 or VIM-2 metallo-β-lactamase, showed a clear relationship between the zinc chelator strength and restoration of meropenem activity. However, evaluation of toxicity on different cancer cell lines

  已经进行了包括具有不同锌亲和力的螯合部分的金属-β-内酰胺酶抑制剂的合成，以及部分受细菌肽序列启发的肽的合成。锌螯合剂的强度使用下列螯合剂来改变，这些螯合剂按结合亲和力的升序排列：二聚烯丙基胺（DPA，三齿），二聚烯丙基-1,2,3-三唑基甲胺（DPTA，四齿）二聚烯丙基乙二胺（DPED，四齿）和三吡啶基乙二胺（TPED，五齿）。选择的肽主要基于细菌肽聚糖前体的C末端的已知序列。对具有NDM-1或VIM-2金属-β-内酰胺酶的临床细菌分离株的生物学评估表明，锌螯合剂的强度与美罗培南活性的恢复之间存在明确的关系。然而，
• Synthesis and Preclinical Evaluation of TPA-Based Zinc Chelators as Metallo-β-lactamase Inhibitors
  作者：Christian Schnaars、Geir Kildahl-Andersen、Anthony Prandina、Roya Popal、Sylvie Radix、Marc Le Borgne、Tor Gjøen、Adriana Magalhães Santos Andresen、Adam Heikal、Ole Andreas Økstad、Christopher Fröhlich、Ørjan Samuelsen、Silje Lauksund、Lars Petter Jordheim、Pål Rongved、Ove Alexander Høgmoen Åstrand

  DOI：10.1021/acsinfecdis.8b00137

  日期：2018.9.14

  development of efficient and clinically available MBL inhibitors. At present, no such inhibitor is available, and research is urgently needed to advance this field. We report herein the development, synthesis, and biological evaluation of chemical compounds based on the selective zinc chelator tris-picolylamine (TPA) that can restore the bactericidal activity of Meropenem (MEM) against Pseudomonas aeruginosa

  全球抗菌素耐药性（AMR）的兴起和表达金属β-内酰胺酶（MBL）的多药耐药生物的日益普及，要求开发有效且临床上可用的MBL抑制剂。目前，尚无此类抑制剂，因此迫切需要研究以促进该领域的发展。我们在此报告了基于选择性锌螯合剂三甲基吡啶胺（TPA）的化合物的开发，合成和生物学评估，该化合物可恢复美罗培南（MEM）对铜绿假单胞菌和肺炎克雷伯菌表达碳青霉烯酶维罗纳整合子编码金属的杀菌活性-β-内酰胺酶（VIM-2）和新德里金属-β-内酰胺酶1（NDM-1）。这些佐剂是通过标准化学方法制备的，并在生物学分析中评估了MEM对细菌的增强作用以及对HepG2人肝癌细胞的毒性（IC50）。最佳化合物之一15在所有测试的表达MBL的临床分离株中以50μM的浓度将MEM的最低抑菌浓度（MIC）降低了32-256倍，并且对表达丝氨酸碳青霉烯酶的分离株无活性。用纯化的VIM-2和NDM-1和15进行生化分析可得出抑制动力学，其kinact
• Inhibitors of Metallo-Beta-Lactamase (MBL) Comprising a Zinc Chelating Moiety
  申请人：UNIVERSITETET I OSLO

  公开号：US20160244431A1

  公开（公告）日：2016-08-25

  Compounds according to formula I are provided: A-L-B wherein A represents a lipophilic chelating moiety which is selective for Zn 2+ ions; L is a covalent bond or a linker; and B is a vector which is either a moiety capable of interacting with one or more biological structures found in a bacterium (preferably in a bacterial cell wall), for example a penicillin-binding protein such as a metallo-β-lactamase or DD-transferase, or a moiety capable of enhancing transport of the compound across a bacterial cell membrane. A method of treating and/or preventing a bacterial infection in a human or non-human mammal employing such compounds are also provided. In such a method, the compound of formula I may be administered in combination with (either simultaneously, separately, or sequentially) a β-lactam antibiotic.

  提供符合公式I的化合物：A-L-B，其中A代表亲脂性螯合基团，该基团选择性地与Zn2+离子结合；L是共价键或连接剂；B是载体，可以是与细菌中的一个或多个生物结构相互作用的基团（优选在细菌细胞壁中），例如与金属β-内酰胺酶或DD转移酶等青霉素结合蛋白相互作用的基团，或者是增强化合物穿过细菌细胞膜的基团。还提供了一种使用这些化合物治疗和/或预防人类或非人哺乳动物细菌感染的方法。在这种方法中，公式I的化合物可以与β-内酰胺类抗生素（同时、分别或顺序）联合使用。