(1S)-1-{[(benzyloxy)carbonyl]amino}-2-phenylethylphosphinic acid | 182211-08-1

• 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: (1S)-1-{[(benzyloxy)carbonyl]amino}-2-phenylethylphosphinic acid
• 英文别名: [(1S)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphinic acid
• CAS: 182211-08-1
• 化学式: C₁₆H₁₈NO₄P
• 分子量: 319.297
• InChiKey: JEFFINAXGSNNQU-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 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：

  (1S)-1-{[(benzyloxy)carbonyl]amino}-2-phenylethylphosphinic acid 在 palladium on activated charcoal 、 Lindlar's catalyst 三甲基氯硅烷 、 potassium tert-butylate 、 氢气 、 甲酸铵 、 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 、 N,N'-羰基二咪唑 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  Phe-Arg次膦酸二肽等排物的有用合成

  摘要：

  描述了构建含有Phe-Arg次膦次膦酸等排物的多肽的模块化方法。

  DOI：

  10.1016/s0040-4039(02)00957-7
• 作为产物：
  描述：

  氯甲酸苄酯 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 16.0h， 生成 (1S)-1-{[(benzyloxy)carbonyl]amino}-2-phenylethylphosphinic acid
  参考文献：
  名称：

  Antibody-Catalyzed Hydrolysis of an Unsubstituted Amide

  摘要：

  The generation of antibodies capable of catalyzing the unassisted hydrolysis of unactivated amides has been an enduring goal of research in the field. Antidialkylphosphinate 1 monoclonal antibodies were screened for their ability to catalyze the hydrolysis of four methyl esters and four primary amides at pH 5.0, 7.0, and 9.0. One of 68 antibodies, 13D11, enantiospecifically hydrolyzed the C-terminal carboxamide of a dansyl-alkylated derivative of (R)-phenylalaninamide (2b). At pH 9.0, 13D11 catalyzed amide hydrolysis with a k(cat) of 1.65 X 10(-7) s(-1) and a K-m of 432 mu M and was stereospecifically inhibited by hapten with a K-i of 14.0 mu M. A shorter, acetylated derivative 3b was not hydrolyzed by 13D11, demonstrating that dansyl-alkyl binding interactions are essential for catalysis. Equally active antibody preparations were obtained from two separate batches of ascites. The antibody Fab' fragment was prepared, purified, and found to retain full activity. Amidolytic activity was not abolished by any of nine inhibitors of natural proteolytic enzymes. The rate of uncatalyzed amide hydrolysis was experimentally determined to be 1.25 x 10(-9) s(-1), indicating an antibody catalytic rate enhancement (k(cat)/k(uncat)) of 132.

  DOI：

  10.1021/ja00094a003

文献信息

• Phosphinic Amino Acid Compounds
  申请人：Dive Vincent

  公开号：US20080153890A1

  公开（公告）日：2008-06-26

  Compounds of formula (I): wherein: R 1 represents hydrogen, alkylcarbonyloxyalkyl or alkylcarbonylthioalkyl, R 2 represents hydrogen, alkylcarbonyloxyalkyl, arylcarbonylthioalkyl or optionally substituted arylalkyl, R 3 represents phenyl, which is optionally substituted, or indolyl, their isomers, and addition salts thereof with a pharmaceutically acceptable acid or base. Medicinal products containing the same which are useful in the treatment of arterial hypertension and complications thereof.

  式(I)的化合物：其中：R1代表氢、烷基羰基氧烷基或烷基羰基硫烷基，R2代表氢、烷基羰基氧烷基、芳基羰基硫烷基或可选择取代的芳基烷基，R3代表苯基（可选择取代）或吲哚基，它们的异构体以及与药学上可接受的酸或碱形成的加合物。含有这些化合物的药物，用于治疗动脉高血压及其并发症。
• Active Methylene Phosphinic Peptides:  A New Diversification Approach
  作者：Magdalini Matziari、Magdalini Nasopoulou、Athanasios Yiotakis

  DOI：10.1021/ol060575m

  日期：2006.5.1

  Simple, rapid, and efficient methods for P-1' diversification of phosphinic peptides have been developed, employing alkylation and Knoevenagel-type condensation reactions with active methylene phosphinic scaffolds, thus leading to a wide variety of diversified phosphinic and dehydrophosphinic peptides.
• High-performance liquid chromatographic enantiomer separation and determination of absolute configurations of phosphinic acid analogues of dipeptides and their α-aminophosphinic acid precursors
  作者：Michael Lämmerhofer、Dieter Hebenstreit、Elena Gavioli、Wolfgang Lindner、Artur Mucha、Paweł Kafarski、Piotr Wieczorek

  DOI：10.1016/s0957-4166(03)00537-8

  日期：2003.9

  The enantiomers of N-benzyloxycarbonyl-phospinic pseudodipeptides and their N-benzyloxycarbonyl-alpha-aminophosphinic acid precursors as well as various other structural analogues were separated oil a set of cinchona alkaloid-derived chiral anion-exchangers by HPLC in the reversed-phase mode. Semi-preparative scale chromatography provided single enantiomers in 100 mg quantities. The configurations of the enantiomers were assigned indirectly by enantioselective chromatography on the basis of the elution order and was confirmed by enantiomeric reference compounds. (C) 2003 Elsevier Ltd. All rights reserved.
• Design and synthesis of phosphinic acids that triply inhibit endothelin converting enzyme, angiotensin converting enzyme and neutral endopeptidase 24.11
  作者：Brian A. McKittrick、Andrew W. Stamford、Xiaoyu Weng、Ke Ma、Samuel Chackalamannil、Michael Czarniecki、ReneéM. Cleven、Ahmad B. Fawzi

  DOI：10.1016/0960-894x(96)00297-1

  日期：1996.7

  We have synthesized a series of phosphinic acids as inhibitors of a metalloprotease endothelin converting enzyme (ECE). Potent ECE inhibitors 4g and 4o were identified. These compounds are members of a novel class of ECE inhibitors that are also potent inhibitors of angiotensin converting enzyme and neutral endopeptidase. Copyright (C) 1996 Elsevier Science Ltd
• Conformational and Solvation Studies via Computer Simulation of the Novel Large Scale Diastereoselectively Synthesized Phosphinic MMP Inhibitor RXP03 Diluted in Selected Solvents
  作者：Magdalini Matziari、Dimitris Dellis、Vincent Dive、Athanasios Yiotakis、Jannis Samios

  DOI：10.1021/jp903830v

  日期：2010.1.14

  Structure-activity relationship studies, regarding the influence of side chains of phosphinic pseudotripeptidic inhibitors on matrix metalloproteinases (MMPs), provided potent and selective inhibitors for this family of structurally and functionally related proteases. Among them, phosphinic pseudopeptide CbzPhe psi [P(O)(OH)CH2] phenylpropyl TrpNH(2), known as RXP03, has been extensively used for in vivo and in vitro studies so far. The large quantities of RXP03 required for in vivo studies, as well as the necessity for diastereoisomeric purity, motivated us to further explore and develop an efficient synthetic methodology, which allows separation of the four diastereoisomers of RXP03 based on the astonishing observed differences in solubility of the four isomers In Various solvents. This fact prompted us to examine theoretically the conformational differences of these four isomers via computer simulations in the solvents used experimentally. Given the fact that the four examined diastereoisomeric forms of the phosphinic peptides exhibit different behavior in terms of potency and selectivity profiles toward zinc-metalloproteases, this theoretical study provides valuable information on the conformation of phosphinic inhibitors and therefore improves the design and synthesis of active Structures. The differences ill Solubility of RXP03 diastereoisomers in the used solvents were examined in terms of intra- and intermolecular Structure. It is Found that the different solubility of the RRS and RSS diastereoisomers in EtOH is a result of the different number of hydrogen bonds formed by each isomer with EtOH molecules. In the case of SRS and SSS in Et2O, their different Solubility might be attributed to the different intramolecular hydrogen bonds formed on these diastereoisomers.