N-benzyloxycarbonylaminomethyl-H-phosphinic acid | 131066-43-8

• 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: N-benzyloxycarbonylaminomethyl-H-phosphinic acid
• 英文别名: N-benzyloxycarbonylaminomethylphosphinic acid；Benzyloxycarbonyl aminomethylphosphinic acid；Cbz-aminomethylphosphinic acid；Phenylmethoxycarbonylaminomethylphosphinic acid
• CAS: 131066-43-8
• 化学式: C₉H₁₂NO₄P
• 分子量: 229.172
• InChiKey: MFOWJUVWRYJUER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-benzyloxycarbonylaminomethyl-H-phosphinic acid 在 N,O-双三甲硅基乙酰胺 、 sulfur 、 甲醇 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以90%的产率得到N-benzyloxycarbonylaminomethylthiophosphonic acid
  参考文献：
  名称：

  Vassiliou, Stamatia, ARKIVOC, 2012, vol. 2012, # 4, p. 7 - 14

  摘要：

  DOI：
• 作为产物：
  描述：

  aminomethylphosphinate hydrochloride 、 氯甲酸苄酯 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 生成 N-benzyloxycarbonylaminomethyl-H-phosphinic acid
  参考文献：
  名称：

  作为谷氨酰胺合成酶抑制剂的膦丝菌素类似物的设计，合成和活性。

  摘要：

  设计并合成了一组新的有效的谷氨酰胺合成酶抑制剂。细菌谷氨酰胺合成酶与膦丝菌素复合的X射线结构用于基于计算机辅助结构的抑制剂设计，其中以膦丝菌素的甲基作为修饰位点。将氨基和羟基部分引入到先导分子的次膦酸部分中，以与酶的活性裂口中的铵结合位点相互作用。设计的化合物以类似于1-谷氨酸的对映体纯形式合成。大肠杆菌谷氨酰胺合成酶的体外动力学研究证实了所设计抑制剂的生物活性，其K（i）值在微摩尔范围内（K（i）= 0。

  DOI：

  10.1021/jm050474e

文献信息

• Novel organophosphorus scaffolds of urease inhibitors obtained by substitution of Morita-Baylis-Hillman adducts with phosphorus nucleophiles
  作者：Vassilis Ntatsopoulos、Stamatia Vassiliou、Katarzyna Macegoniuk、Łukasz Berlicki、Artur Mucha

  DOI：10.1016/j.ejmech.2017.03.070

  日期：2017.6

  The reactivity of Morita-Baylis-Hillman allyl acetates was employed to introduce phosphorus-containing functionalities to the side chain of the cinnamic acid conjugated system by nucleophilic displacement. The proximity of two acidic groups, the carboxylate and phosphonate/phosphinate groups, was necessary to form interactions in the active site of urease by recently described inhibitor frameworks

  利用Morita-Baylis-Hillman乙酸烯丙酯的反应性，通过亲核取代将含磷官能团引入肉桂酸共轭体系的侧链。通过最近描述的抑制剂框架，两个酸性基团（羧酸根和膦酸酯/次膦酸酯基）的接近对于在脲酶的活性位点形成相互作用是必需的。获得了几种有机磷支架，并筛选了抑制细菌尿素酶的方法，尿素酶是尿液和胃肠道病原体存活所必需的一种酶。α-取代的膦酰基甲基-肉桂酸酯和2-膦酰基乙基-肉桂酸酯似乎是最有效的并且已被进一步优化。结果，确定了脲酶最有效的有机磷抑制剂之一，α-膦酰基甲基-对甲基肉桂酸，Ki = 0。6μM的巴氏芽孢杆菌尿素酶。通过这种结构可以实现与酶活性位点的高度互补，因为任何进一步的修饰都会大大降低其亲和力。最后，这项工作描述了开发脲酶配体所面临的挑战。
• Bis(aminomethyl)phosphinic Acid, a Highly Promising Scaffold for the Development of Bacterial Urease Inhibitors
  作者：Katarzyna Macegoniuk、Anna Dziełak、Artur Mucha、Łukasz Berlicki

  DOI：10.1021/ml500380f

  日期：2015.2.12

  Inhibitors of bacterial ureases are considered to be promising compounds in the treatment of infections caused by Helicobacter pylori in the gastric tract and/or by urealytic bacteria (e.g., Proteus species) in the urinary tract. A new, extended transition state scaffold, bis(aminomethyl)phosphinic acid, was successfully explored for the construction of effective enzyme inhibitors. A reliable methodology

  细菌脲酶的抑制剂被认为是治疗由胃道中的幽门螺杆菌和/或由尿道中的尿素分解细菌（例如变形杆菌属）引起的感染的有前途的化合物。一个新的扩展的过渡态支架，双（氨基甲基）次膦酸，成功地探索了有效的酶抑制剂的建设。阐述了在三组分曼尼希型反应中合成次膦酸酯类似物的可靠方法。对获得的分子进行了针对从巴氏孢子虫和米氏变形杆菌纯化的脲酶的测定，发现氨基甲基（Nn-己基氨基甲基）次膦酸是最有效的抑制剂，其Ki = 108 nM。
• Design, Synthesis, and Evaluation of Novel Organophosphorus Inhibitors of Bacterial Ureases
  作者：Stamatia Vassiliou、Agnieszka Grabowiecka、Paulina Kosikowska、Athanasios Yiotakis、Paweł Kafarski、Łukasz Berlicki

  DOI：10.1021/jm800570q

  日期：2008.9.25

  A new group of organophosphorus inhibitors of urease, P-methyl phosphinic acids was discovered by using the structure based inhibitor design approach. Several derivatives of the lead compound, aminomethyl(P-methyl)phosphinic acid, were synthesized successfully. Their potency was evaluated in vitro against urease from Bacillus pasteurii and Proteus vulgaris. The studied compounds constitute a group of competitive, reversible inhibitors of bacterial ureases. Obtained thiophosphinic analogues of the most effective structures exhibited kinetic characteristics of potent, slow binding urease inhibitors, with K-i = 170 nM (against B. pasteurii enzyme) for the most active N-(N'-benzyloxycarbonylglycyl)aminomethyl(P-methyl)phosphinothioic acid.
• Berlicki; Mucha; Kafarski, Polish Journal of Chemistry, 2007, vol. 81, # 11, p. 1959 - 1962
  作者：Berlicki、Mucha、Kafarski

  DOI：——

  日期：——
• Phosphinic Peptide Matrix Metalloproteinase-9 Inhibitors by Solid-Phase Synthesis Using a Building Block Approach
  作者：Jens Buchardt、Mercedes Ferreras、Christian Krog-Jensen、Jean-Marie Delaissé、Niels Tækker Foged、Morten Meldal

  DOI：10.1002/(sici)1521-3765(19991001)5:10<2877::aid-chem2877>3.0.co;2-z

  日期：1999.10.1

  The solid-phase synthesis of an array of different pseudopeptides containing a phosphinic glycine-leucine moiety (-G Psi/P(O)OH-CH2}L-)([1]) is described. The resulting pseudopeptides were shown to act as matrix metalloproteinase-9 (MMP-9) inhibitors. Starting from available materials, the protected amino acid isosters benzyloxy-carbonyl aminomethylphosphinic acid (glycine analogue) and ethyl alpha-isobutylacrylate (leucine analogue) were synthesized and coupled with the bis(trimethylsilyl)phosphonite. Protective group interchange yielded a protected phosphinic dipeptide building block 1 ready for use in solid-phase peptide synthesis, Solid-phase peptide synthesis was performed with 9-fluorenylmethyloxycarbonyl (Fmoc) chemistry on a polyethylene glycol polyamide (PEGA) support and the coupling of 1 (1.5 equiv) was carried out with standard activation. The P-4-P-2 and P-2'-P-4' positions of the pseudopeptides were designed by analogy of the cleavage sequences of different natural extracellular matrix protein substrates with a synthetic peptide substrate of MMP-9. The crude peptides were obtained in high yield and purity as determined by RP-HPLC, and were characterized by electrospray mass spectrometry and amino acid analysis after purification. Enzyme kinetic investigations with MMP-9 of the purified peptide inhibitors showed Ki values in the range from mM to nM.