methyl 4-(dimethoxyphosphinyl)-4-oxobutanoate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: methyl 4-(dimethoxyphosphinyl)-4-oxobutanoate
• 英文别名: Methyl 4-dimethoxyphosphoryl-4-oxobutanoate
• 化学式: C₇H₁₃O₆P
• 分子量: 224.15
• InChiKey: KBKKUQDERVQGOR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  14
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  78.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 4-(dimethoxyphosphinyl)-4-oxobutanoate 在 lithium bromide 作用下， 以 乙腈 为溶剂， 生成 lithium methyl (4-methoxy-4-oxobutanoyl)phosphonate
  参考文献：
  名称：

  Succinylphosphonate Esters Are Competitive Inhibitors of MenD That Show Active-Site Discrimination between Homologous α-Ketoglutarate-Decarboxylating Enzymes

  摘要：

  MenD is a thiamin diphosphate-dependent enzyme catalyzing the First unique step in menaquinone biosynthesis in bacteria. We have synthesized acylphosphonate ester analogues of alpha-ketoglutarate, a substrate of MenD. These compounds are competitive inhibitors of MenD, with K-i values its low its 700 nM. Observed structure-activity relationships are in notable contrast to those reported previously for succinylphosphonate inhibition of the alpha-ketoglutarate dehydrogenase complex, despite the apparent homology of these enzymes, and the identical decarboxylation reactions catalyzed. Inhibiting menaquinone biosynthesis is it proposed approach to inhibiting Mycobacterium tuberculosis growth. These inhibitors showed no significant. inhibition of M. tuberculosis growth in vitro under aerobic and hypoxic conditions but give new information about the binding characteristics of the MenD active site. Site-directed Mutation of Ser391 to alanine had only it minor effect on catalysis, but even the conservative mutation of Arg395 to lysine had it significant effect on the catalytic processing of isochorismate.

  DOI：

  10.1021/bi901432d
• 作为产物：
  描述：

  丁二酸单甲酯 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 生成 methyl 4-(dimethoxyphosphinyl)-4-oxobutanoate
  参考文献：
  名称：

  Succinylphosphonate Esters Are Competitive Inhibitors of MenD That Show Active-Site Discrimination between Homologous α-Ketoglutarate-Decarboxylating Enzymes

  摘要：

  MenD is a thiamin diphosphate-dependent enzyme catalyzing the First unique step in menaquinone biosynthesis in bacteria. We have synthesized acylphosphonate ester analogues of alpha-ketoglutarate, a substrate of MenD. These compounds are competitive inhibitors of MenD, with K-i values its low its 700 nM. Observed structure-activity relationships are in notable contrast to those reported previously for succinylphosphonate inhibition of the alpha-ketoglutarate dehydrogenase complex, despite the apparent homology of these enzymes, and the identical decarboxylation reactions catalyzed. Inhibiting menaquinone biosynthesis is it proposed approach to inhibiting Mycobacterium tuberculosis growth. These inhibitors showed no significant. inhibition of M. tuberculosis growth in vitro under aerobic and hypoxic conditions but give new information about the binding characteristics of the MenD active site. Site-directed Mutation of Ser391 to alanine had only it minor effect on catalysis, but even the conservative mutation of Arg395 to lysine had it significant effect on the catalytic processing of isochorismate.

  DOI：

  10.1021/bi901432d

文献信息

• Compounds and compositions
  申请人：FBC Limited

  公开号：US04339443A1

  公开（公告）日：1982-07-13

  There are described pesticidal compositions comprising one or more compounds of the formula I, ##STR1## in which Ra is a group R.sup.2 or --OR.sup.2, E is oxygen or sulphur, Rm is --O.sup..crclbar. M.sup..sym. or --NRyRz, M.sup..sym. is one equivalent of an agriculturally acceptable cation, R.sup.1 and R.sup.2, which may be the same or different, each represent hydrogen, alkyl, alkenyl, alkynyl or aryl; the alkyl, alkenyl, alkynyl or aryl optionally being substituted by one or more halogen, alkoxy, nitro, alkyl, --CF.sub.3, nitrile, or carboxylic acid or a salt, ester, or amide thereof, and Ry and Rz, which may be the same or different, each represent hydrogen or alkyl, or an agriculturally acceptable derivative thereof. There are also described methods for making and using compounds of formula I.

  描述了包含化学式I中一个或多个化合物的杀虫组合物，其中Ra是一个基团R.sup.2或--OR.sup.2，E是氧或硫，Rm是--O.sup..crclbar. M.sup..sym.或--NRyRz，M.sup..sym.是一当量的农业可接受阳离子，R.sup.1和R.sup.2，可能相同也可能不同，分别代表氢、烷基、烯基、炔基或芳基；所述烷基、烯基、炔基或芳基可以选择性地被一个或多个卤素、烷氧基、硝基、烷基、--CF.sub.3、腈基或羧酸或其盐、酯或酰胺取代，Ry和Rz，可能相同也可能不同，分别代表氢或烷基，或其农业可接受的衍生物。还描述了制备和使用化学式I中化合物的方法。
• Pesticidally active salts and compositions containing them and processes for their manufacture and use
  申请人：FBC LIMITED

  公开号：EP0009348A2

  公开（公告）日：1980-04-02

  There are described pesticidal compositions comprising one or more compounds of the formula 1, in which Ra is a group R2 or -OR2, E is oxygen or sulphur, Rm is-O⊖M⊕ or -NRyRz, M⊕ is one equivalent of an agriculturally acceptable cation, R1 and R2, which may be the same or different, each represent hydrogen, alkyl, alkenyl, alkynyl or aryl; the alkyl, alkenyl, alkynyl or aryl optionally being substituted by one or more halogen, alkoxy, nitro, alkyl, -CH3, nitrile, or carboxylic acid or a salt, ester, or amide thereof, and Ry and Rz, which may be the same or different, each represent hydrogen or alkyl, or an agriculturally acceptable derivative thereof. There are also described methods for making and using compounds of formula I.

  所述杀虫剂组合物包含一种或多种式 1、 其中 Ra 是基团 R2 或 -OR2、 E 是氧或硫、 Rm 是-O⊖M⊕或-NRyRz、 M⊕ 是一个等价的农业上可接受的阳离子、 R1 和 R2，可以相同或不同，各自代表氢、烷基、烯基、炔基或芳基；烷基、烯基、炔基或芳基可选择被一个或多个卤素、烷氧基、硝基、烷基、-CH3、腈或羧酸或其盐、酯或酰胺取代，以及 Ry和Rz可以相同或不同，各自代表氢或烷基、 或其农业上可接受的衍生物。 还描述了制造和使用式 I 化合物的方法。
• US4339443A
  申请人：——

  公开号：US4339443A

  公开（公告）日：1982-07-13
• Succinylphosphonate Esters Are Competitive Inhibitors of MenD That Show Active-Site Discrimination between Homologous α-Ketoglutarate-Decarboxylating Enzymes
  作者：Maohai Fang、R. Daniel Toogood、Andrea Macova、Karen Ho、Scott G. Franzblau、Michael R. McNeil、David A. R. Sanders、David R. J. Palmer

  DOI：10.1021/bi901432d

  日期：2010.3.30

  MenD is a thiamin diphosphate-dependent enzyme catalyzing the First unique step in menaquinone biosynthesis in bacteria. We have synthesized acylphosphonate ester analogues of alpha-ketoglutarate, a substrate of MenD. These compounds are competitive inhibitors of MenD, with K-i values its low its 700 nM. Observed structure-activity relationships are in notable contrast to those reported previously for succinylphosphonate inhibition of the alpha-ketoglutarate dehydrogenase complex, despite the apparent homology of these enzymes, and the identical decarboxylation reactions catalyzed. Inhibiting menaquinone biosynthesis is it proposed approach to inhibiting Mycobacterium tuberculosis growth. These inhibitors showed no significant. inhibition of M. tuberculosis growth in vitro under aerobic and hypoxic conditions but give new information about the binding characteristics of the MenD active site. Site-directed Mutation of Ser391 to alanine had only it minor effect on catalysis, but even the conservative mutation of Arg395 to lysine had it significant effect on the catalytic processing of isochorismate.