1-formamido-2-methylpropanephosphonic acid diphenyl ester | 901773-68-0

• 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: 1-formamido-2-methylpropanephosphonic acid diphenyl ester
• 英文别名: N-[2-methyl-1-[oxido(diphenoxy)phosphaniumyl]propyl]formamide
• CAS: 901773-68-0
• 化学式: C₁₇H₂₀NO₄P
• 分子量: 333.324
• InChiKey: KRLJHFODDSMWAH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  70.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-formamido-2-methylpropanephosphonic acid diphenyl ester 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 生成 phenyl <1-(1-N-formylamino)-2-methylpropyl>phosphonate
  参考文献：
  名称：

  Remote Binding Energy in Antibody Catalysis:  Studies of a Catalytically Unoptimized Specificity Pocket

  摘要：

  Binding interactions remote from the hydrolytic reaction center have been probed with substrate and phosphonate transition state analogues to understand how these types of interactions are used to promote catalysis in the 17E8 system, We find that the hapten-generated recogniton pocket in 17E8 has properties that are analogous to those of specificity pockets in enzymes, pie have also found that there are specific requirements to form catalytically productive interactions between the side chain and the recognition pocket including conformation, size, and geometry. An additional requirement includes Favorable simultaneous interactions between the side chain and binding packet along with favorable interactions with the oxyanion hole. The 17E8 side chain recognition pocket seems to be less catalytically efficient than analogous pockets in enzymatic systems. The apparent binding energy gained from the methylene-packet interactions in the 17E8 system is significantly smaller than those observed in natural enzymes. Furthermore, 17E8 does not use specific interactions in the recognition pocket to significantly affect catalytic turnover (k(cat)) which is thought to be a trait of an unoptimized catalyst. Analysis of the crystal structure of the 17E8,hapten complex has allowed for the identification of differences between the active sites of 17E8; and several proteases, The identified differences give insight to the sources of the inefficient use of binding energy.

  DOI：

  10.1021/ja983017e
• 作为产物：
  描述：

  亚磷酸三苯酯 在 氢溴酸 、 三乙胺 作用下， 以 二氯甲烷 、 水 、 溶剂黄146 为溶剂， 反应 0.5h， 生成 1-formamido-2-methylpropanephosphonic acid diphenyl ester
  参考文献：
  名称：

  Synthesis of isocyanide derivatives of α-aminoalkylphosphonate diphenyl esters

  摘要：

  This letter describes the first example of the synthesis of isocyanide derivatives of alpha-aminoalkylphosphonate diphenyl esters. This method produces the title compounds in high purity and in very good yields. It also permits the generation of an alpha-aminophosphonate-based library of biologically active phosphonopeptides. Preliminary experiments demonstrate their application as substrates for the Ugi-type multicomponent condensation. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2006.04.058

文献信息

• Phosphonic pseudopeptides as human neutrophil elastase inhibitors—a combinatorial approach
  作者：Marcin Sieńczyk、Dawid Podgórski、Aleksandra Błażejewska、Julita Kulbacka、Jolanta Saczko、Józef Oleksyszyn

  DOI：10.1016/j.bmc.2010.12.008

  日期：2011.2

  Here we present a simple and rapid method for the construction of phosphonic peptide mimetic inhibitor libraries-products of Ugi and Passerini multicomponent condensations leading to the selection of new biologically active phosphonic pseudopeptides. As the starting isonitriles, 1-isocyanoalkylphosphonate diaryl ester derivatives were applied. The structure of the synthesized inhibitors was designed to target human neutrophil elastase, a serine protease whose uncontrolled activity may lead to development of several pathophysiological states such as rheumatoid arthritis, cystic fibrosis or tumor growth and invasion. After screening the inhibitory activity of our constructed libraries, the most active compounds were synthesized as single molecules. One of the obtained inhibitors, Cbz-Met-O-Met-Val(P)(OC6H4-p-Cl)(2), displayed apparent second-order inhibition value at 40,105 M-1 s(-1) as the diastereomers mixture. Inhibition potency and selectivity of action toward other serine proteases as well as the results of initial in vitro experiments regarding inhibitors influence on cancer cell proliferation are presented. (C) 2010 Elsevier Ltd. All rights reserved.
• Remote Binding Energy in Antibody Catalysis:  Studies of a Catalytically Unoptimized Specificity Pocket
  作者：Herschel Wade、Thomas S. Scanlan

  DOI：10.1021/ja983017e

  日期：1999.2.1

  Binding interactions remote from the hydrolytic reaction center have been probed with substrate and phosphonate transition state analogues to understand how these types of interactions are used to promote catalysis in the 17E8 system, We find that the hapten-generated recogniton pocket in 17E8 has properties that are analogous to those of specificity pockets in enzymes, pie have also found that there are specific requirements to form catalytically productive interactions between the side chain and the recognition pocket including conformation, size, and geometry. An additional requirement includes Favorable simultaneous interactions between the side chain and binding packet along with favorable interactions with the oxyanion hole. The 17E8 side chain recognition pocket seems to be less catalytically efficient than analogous pockets in enzymatic systems. The apparent binding energy gained from the methylene-packet interactions in the 17E8 system is significantly smaller than those observed in natural enzymes. Furthermore, 17E8 does not use specific interactions in the recognition pocket to significantly affect catalytic turnover (k(cat)) which is thought to be a trait of an unoptimized catalyst. Analysis of the crystal structure of the 17E8,hapten complex has allowed for the identification of differences between the active sites of 17E8; and several proteases, The identified differences give insight to the sources of the inefficient use of binding energy.
• Synthesis of isocyanide derivatives of α-aminoalkylphosphonate diphenyl esters
  作者：Marcin Sieńczyk、Maciej Kliszczak、Józef Oleksyszyn

  DOI：10.1016/j.tetlet.2006.04.058

  日期：2006.6

  This letter describes the first example of the synthesis of isocyanide derivatives of alpha-aminoalkylphosphonate diphenyl esters. This method produces the title compounds in high purity and in very good yields. It also permits the generation of an alpha-aminophosphonate-based library of biologically active phosphonopeptides. Preliminary experiments demonstrate their application as substrates for the Ugi-type multicomponent condensation. (c) 2006 Elsevier Ltd. All rights reserved.