di(butyryloxymethyl) 4-[benzyloxy(methyl)amino]-4-oxobutylphosphonate | 1376377-49-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: di(butyryloxymethyl) 4-[benzyloxy(methyl)amino]-4-oxobutylphosphonate
• 英文别名: [Butanoyloxymethoxy-[4-[methyl(phenylmethoxy)amino]-4-oxobutyl]phosphoryl]oxymethyl butanoate
• CAS: 1376377-49-9
• 化学式: C₂₂H₃₄NO₉P
• 分子量: 487.487
• InChiKey: ZNJCMLZRVKUOBM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  33
• 可旋转键数：
  19
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 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(butyryloxymethyl) 4-[benzyloxy(methyl)amino]-4-oxobutylphosphonate 在 palladium 10% on activated carbon 、 氢气 作用下， 反应 1.0h， 以94%的产率得到di(butyryloxymethyl) 4-[hydroxy(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
• 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(butyryloxymethyl) 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.