ethyl>phosphonic acid

• 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: ethyl>phosphonic acid
• 英文别名: [(1R)-1-[[(2S)-2-(phenylmethoxycarbonylamino)pentanoyl]amino]ethyl]phosphonic acid
• 化学式: C₁₅H₂₃N₂O₆P
• 分子量: 358.331
• InChiKey: MNWMWFMDAMANCF-YPMHNXCESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  125
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl>phosphonic acid 在 氢溴酸 、 溶剂黄146 作用下， 反应 2.0h， 以44 mg的产率得到(R-(R*,S*))-(1-((2-氨基-1-氧代戊基)氨基)乙基)-膦酸
  参考文献：
  名称：

  脱磷生物合成酶在制备抗alaphosphin的抗菌类似物中的用途。

  摘要：

  脱磷生物合成酶DhpH（DhpH-C）的C末端结构域催化Leu-tRNALeu与（R）-1-氨基乙基膦酸酯（丙氨酸的氨基膦酸酯类似物Ala（P））缩合。该反应的产物Leu-Ala（P）是磷酸二肽，一类化合物，以前已被研究用作临床抗生素。在这项研究中，我们表明DhpH-C具有高度的底物耐受性，并且可以将各种氨基膦酸酯（Gly（P），Ser（P），Val（P），1-氨基-丙基膦酸酯和苯基甘氨酸（P））缩合到Leu。而且，该酶对tRNALeu上连接的氨基酸也具有耐受性。使用缺乏校对能力的亮氨酰tRNA合成酶突变体，可以制备一系列氨酰基-tRNALeu衍生物（Ile，Ala，Val，Met，正缬氨酸和正亮氨酸）。DhpH-C接受这些氨基酰基-tRNA衍生物，并将氨基酸与1-Ala（P）缩合形成相应的磷酸二肽。这些肽的一部分显示出抗微生物活性，表明该酶是制备抗微生物肽的通用生物催化剂。我们还研究了来

  DOI：

  10.1039/c8ob02860e
• 作为产物：
  描述：

  L-正缬氨酸 在 sodium hydroxide 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 乙二醇二甲醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 ethyl>phosphonic acid
  参考文献：
  名称：

  Synthesis and structure-activity relationships of antibacterial phosphonopeptides incorporating (1-aminoethyl)phosphonic acid and (aminomethyl)phosphonic acid

  摘要：

  Phosphonodipeptides and phosphonooligopeptides based on L- and D-(1-aminoethyl)phosphonic acids L-Ala(P) and D-Ala(P) and (aminomethyl)phosphonic acid Gly(P) at the acid terminus have been synthesized and investigated as antibacterial agents, which owe their activity to the inhibition of bacterial cell-wall biosynthesis. A method for large-scale synthesis of the potent antibacterial agent L-Ala-L-Ala(P) (1, Alafosfalin) is described. Structure-activity relationships in the dipeptide series have been studied by systematic variation of structure 1. L stereochemistry is generally required for both components. Changes in the L-Ala(P) moiety mostly lead to loss of antibacterial activity, but the phosphonate analogues of L-phenylalanine, L-Phe(P), and L-serine, L-Ser(P), give rise to weakly active L-Ala-L-Phe(P) and L-Ala-L-Ser(P). Replacement of L-Ala in 1 by common and rare amino acids can give rise to more potent in vitro antibacterials such as L-Nva-L-Ala(P) (45). Synthetic variation of these more potent dipeptides leads to decreased activity. Phosphonooligopeptides such as (L-Ala)2-L-Ala(P) have a broader in vitro antibacterial spectrum than their phosphonodipeptide precursor, but this is not expressed in vivo, presumably due to rapid metabolism to 1. Stabilized compounds such as Sar-L-Nva-L-Nva-L-Ala(P) (46) have been developed that are more potent in vivo and have a broader in vivo antibacterial spectrum than the parent phosphonodipeptide.

  DOI：

  10.1021/jm00151a005

文献信息

• Aminosäurederivate, Verfahren zu deren Herstellung, Zwischenprodukte bei deren Herstellung und diese enthaltende pharmazeutische Präparate
  申请人：F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft

  公开号：EP0002534B1

  公开（公告）日：1982-01-13
• Synthesis and structure-activity relationships of antibacterial phosphonopeptides incorporating (1-aminoethyl)phosphonic acid and (aminomethyl)phosphonic acid
  作者：Frank R. Atherton、Cedric H. Hassall、Robert W. Lambert

  DOI：10.1021/jm00151a005

  日期：1986.1

  Phosphonodipeptides and phosphonooligopeptides based on L- and D-(1-aminoethyl)phosphonic acids L-Ala(P) and D-Ala(P) and (aminomethyl)phosphonic acid Gly(P) at the acid terminus have been synthesized and investigated as antibacterial agents, which owe their activity to the inhibition of bacterial cell-wall biosynthesis. A method for large-scale synthesis of the potent antibacterial agent L-Ala-L-Ala(P) (1, Alafosfalin) is described. Structure-activity relationships in the dipeptide series have been studied by systematic variation of structure 1. L stereochemistry is generally required for both components. Changes in the L-Ala(P) moiety mostly lead to loss of antibacterial activity, but the phosphonate analogues of L-phenylalanine, L-Phe(P), and L-serine, L-Ser(P), give rise to weakly active L-Ala-L-Phe(P) and L-Ala-L-Ser(P). Replacement of L-Ala in 1 by common and rare amino acids can give rise to more potent in vitro antibacterials such as L-Nva-L-Ala(P) (45). Synthetic variation of these more potent dipeptides leads to decreased activity. Phosphonooligopeptides such as (L-Ala)2-L-Ala(P) have a broader in vitro antibacterial spectrum than their phosphonodipeptide precursor, but this is not expressed in vivo, presumably due to rapid metabolism to 1. Stabilized compounds such as Sar-L-Nva-L-Nva-L-Ala(P) (46) have been developed that are more potent in vivo and have a broader in vivo antibacterial spectrum than the parent phosphonodipeptide.
• Use of the dehydrophos biosynthetic enzymes to prepare antimicrobial analogs of alaphosphin
  作者：Despina J. Bougioukou、Chi P. Ting、Spencer C. Peck、Subha Mukherjee、Wilfred A. van der Donk

  DOI：10.1039/c8ob02860e

  日期：——

  enzyme is also tolerant with respect to the amino acid attached to tRNALeu. Using a mutant of leucyl tRNA synthetase that is deficient in its proofreading ability allowed the preparation of a series of aminoacyl-tRNALeu derivatives (Ile, Ala, Val, Met, norvaline, and norleucine). DhpH-C accepted these aminoacyl-tRNA derivatives and condensed the amino acid with l-Ala(P) to form the corresponding phosphonodipeptides

  脱磷生物合成酶DhpH（DhpH-C）的C末端结构域催化Leu-tRNALeu与（R）-1-氨基乙基膦酸酯（丙氨酸的氨基膦酸酯类似物Ala（P））缩合。该反应的产物Leu-Ala（P）是磷酸二肽，一类化合物，以前已被研究用作临床抗生素。在这项研究中，我们表明DhpH-C具有高度的底物耐受性，并且可以将各种氨基膦酸酯（Gly（P），Ser（P），Val（P），1-氨基-丙基膦酸酯和苯基甘氨酸（P））缩合到Leu。而且，该酶对tRNALeu上连接的氨基酸也具有耐受性。使用缺乏校对能力的亮氨酰tRNA合成酶突变体，可以制备一系列氨酰基-tRNALeu衍生物（Ile，Ala，Val，Met，正缬氨酸和正亮氨酸）。DhpH-C接受这些氨基酰基-tRNA衍生物，并将氨基酸与1-Ala（P）缩合形成相应的磷酸二肽。这些肽的一部分显示出抗微生物活性，表明该酶是制备抗微生物肽的通用生物催化剂。我们还研究了来