di(pivaloyloxymethyl) 4-[benzyloxy(methyl)amino]-4-oxobutylphosphonate | 1376377-52-4

• 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: di(pivaloyloxymethyl) 4-[benzyloxy(methyl)amino]-4-oxobutylphosphonate
• 英文别名: [2,2-Dimethylpropanoyloxymethoxy-[4-[methyl(phenylmethoxy)amino]-4-oxobutyl]phosphoryl]oxymethyl 2,2-dimethylpropanoate
• CAS: 1376377-52-4
• 化学式: C₂₄H₃₈NO₉P
• 分子量: 515.541
• InChiKey: FLXFRGIQYKDQDY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  35
• 可旋转键数：
  17
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  118
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  di(pivaloyloxymethyl) 4-[benzyloxy(methyl)amino]-4-oxobutylphosphonate 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 为溶剂， 以78 %的产率得到[({4-[hydroxy(methyl)amino]-4-oxobutyl}phosphoryl)bis(oxy)]bis(methylene) bis(2,2-dimethylpropanoate)
  参考文献：
  名称：

  作为抗疟药和抗菌剂的磷霉素替代物的酰氧基甲基和烷氧基羰基氧基甲基前药

  摘要：

  Fosmidomycin 是一种天然抗生素，具有有效的 IspC（DXR，1-脱氧-d-木酮糖-5-磷酸还原异构酶）抑制活性。这种酶催化非甲羟戊酸类异戊二烯生物合成途径的第一个关键步骤，这在大多数细菌（包括鲍曼不动杆菌和结核分枝杆菌）和顶复门寄生虫（包括疟原虫寄生虫）中必不可少。主要由于其高极性，磷米霉素表现出次优的药代动力学特性。此外，fosmidomycin 对鲍曼不动杆菌和结核分枝杆菌无活性由于其无法穿透细菌细胞壁。暂时将膦酸酯部分作为前药进行掩蔽有可能解决这两个问题。我们报告了磷胺霉素替代物的酰氧基甲基和烷氧基羰基氧基甲基膦酸酯前药系列的扩展。前药前体是根据电子、亲脂性和铁载体特性设计的。该研究导致发现了分别具有两位数纳摩尔和亚微摩尔 IC 50值的衍生物，用于对抗恶性疟原虫和鲍曼不动杆菌。

  DOI：

  10.1016/j.ejmech.2022.114924
• 作为产物：
  描述：

  diethyl 4-(benzyloxyamino)-4-oxobutylphosphonate 在 三甲基溴硅烷 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.16h， 生成 di(pivaloyloxymethyl) 4-[benzyloxy(methyl)amino]-4-oxobutylphosphonate
  参考文献：
  名称：

  Growth inhibition of Mycobacterium smegmatis by prodrugs of deoxyxylulose phosphate reducto-isomerase inhibitors, promising anti-mycobacterial agents

  摘要：

  Since Mycobacterium tuberculosis sets up several multiple anti-tuberculosis drug resistance mechanisms, development of new drugs with innovative target is urgent. The methylerythritol phosphate pathway (MEP) involved in the biosynthesis of essential metabolites for the survival of mycobacteria, represents such a target. Fosmidomycin la and FR900098 1b, two inhibitors of DXR, do not affect the viability of M. tuberculosis cells, due to a lack of uptake. To overcome the absence of the mycobacterial cell wall crossing of these compounds, we synthesized and tested the inhibition potency of acyloxymethyl phosphonate esters as prodrugs of fosmidomycin la, FR900098 1b and their analogs 2a and 2b on Mycobacterium smegmatis. Only the prodrugs 4b-6b inhibit the bacterial growth and could be effective antimycobacterial agents. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.02.031

文献信息

• Growth inhibition of Mycobacterium smegmatis by prodrugs of deoxyxylulose phosphate reducto-isomerase inhibitors, promising anti-mycobacterial agents
  作者：Sarah Ponaire、Catherine Zinglé、Denis Tritsch、Catherine Grosdemange-Billiard、Michel Rohmer

  DOI：10.1016/j.ejmech.2012.02.031

  日期：2012.5

  Since Mycobacterium tuberculosis sets up several multiple anti-tuberculosis drug resistance mechanisms, development of new drugs with innovative target is urgent. The methylerythritol phosphate pathway (MEP) involved in the biosynthesis of essential metabolites for the survival of mycobacteria, represents such a target. Fosmidomycin la and FR900098 1b, two inhibitors of DXR, do not affect the viability of M. tuberculosis cells, due to a lack of uptake. To overcome the absence of the mycobacterial cell wall crossing of these compounds, we synthesized and tested the inhibition potency of acyloxymethyl phosphonate esters as prodrugs of fosmidomycin la, FR900098 1b and their analogs 2a and 2b on Mycobacterium smegmatis. Only the prodrugs 4b-6b inhibit the bacterial growth and could be effective antimycobacterial agents. (C) 2012 Elsevier Masson SAS. All rights reserved.