diethyl (1,1-difluoro-3-oxopropyl)phosphonate | 126181-59-7

• 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: diethyl (1,1-difluoro-3-oxopropyl)phosphonate
• 英文别名: Diethyl 1,1-difluoro-3-oxopropylphosphonate；3-diethoxyphosphoryl-3,3-difluoropropanal
• CAS: 126181-59-7
• 化学式: C₇H₁₃F₂O₄P
• 分子量: 230.148
• InChiKey: MTMAEKQJENCPGN-UHFFFAOYSA-N

物化性质

• 沸点：
  254.4±40.0 °C(Predicted)
• 密度：
  1.216±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  14
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  diethyl (1,1-difluoro-3-oxopropyl)phosphonate 在 乙酸酐 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.0h， 生成 diethyl (3‐(N‐(benzyloxy)formamido)‐1,1‐difluoropropyl)phosphonate
  参考文献：
  名称：

  α,α-二氟膦酰异羟肟酸衍生物是最佳抗菌磷霉素类似物之一

  摘要：

  从 1,1-二氟丁-3-烯基膦酸二乙酯合成了 fosmidomycin 的三种 α,α-二氟膦酸酯衍生物，并在大肠杆菌中进行了评估。其中两种是最好的 1-脱氧-d-木酮糖 5-磷酸还原异构酶抑制剂，IC 50在 nM 范围内，远好于参考化合物磷米霉素。与相应的磷酸盐和非氟化膦酸盐相比，它们还显示出对培养皿上大肠杆菌的增强抗菌活性。

  DOI：

  10.3390/molecules26165111
• 作为产物：
  描述：

  溴氟甲基膦酸二乙酯 在 臭氧 、 锌 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 diethyl (1,1-difluoro-3-oxopropyl)phosphonate
  参考文献：
  名称：

  α,α-二氟膦酰异羟肟酸衍生物是最佳抗菌磷霉素类似物之一

  摘要：

  从 1,1-二氟丁-3-烯基膦酸二乙酯合成了 fosmidomycin 的三种 α,α-二氟膦酸酯衍生物，并在大肠杆菌中进行了评估。其中两种是最好的 1-脱氧-d-木酮糖 5-磷酸还原异构酶抑制剂，IC 50在 nM 范围内，远好于参考化合物磷米霉素。与相应的磷酸盐和非氟化膦酸盐相比，它们还显示出对培养皿上大肠杆菌的增强抗菌活性。

  DOI：

  10.3390/molecules26165111

文献信息

• Fluorine in enzyme chemistry part 2 The preparation of difluoromethylenephosphonate analogues of glycolytic phosphates. Approaching an isosteric and isoelectronic phosphate mimic
  作者：R.D. Chambers、R. Jaouhari、D. O'Hagan

  DOI：10.1016/s0040-4020(01)81089-9

  日期：1989.1

  The preparation of difluoromethylenephosphonate analogues of the glycolytic intermediates, glycerol-3-phosphate and 3-phosphoglycerate are described. Attempts to prepare the corresponding analogue of dihydroxyacetone phosphate failed due the facile elimination of hydrogen fluoride from the target molecule. Finally the synthesis of a difluoromethylenephosphonate possessing inhibitory activity against

  描述了糖酵解中间体的二氟亚甲基膦酸酯类似物3-磷酸甘油酯和3-磷酸甘油酸酯的制备。尝试从目标分子中轻松消除氟化氢，尝试制备相应的磷酸二羟基丙酮类似物的尝试失败。最后，描述了对流感病毒的RNA转录酶具有抑制活性的二氟亚甲基膦酸酯的合成。
• Fluorine in enzyme Chemistry: Part 1. Synthesis of difluoromethylenephosphonate derivatives as phosphate mimics
  作者：R.D. Chambers、R. Jaouhari、D. O'Hagan

  DOI：10.1016/s0022-1139(00)83944-5

  日期：1989.8

  Diethyl difluoromethylphosphonylcadmium bromide reacts with allyl and benzyl halides in THF to give the corresponding difluoromethylenephosphonate derivatives. The reaction with allyl bromide affords a versatile synthetic intermediate which undergoes a variety of synthetic transformations and therefore becomes a key compound in the preparation of elaborated difluoromethylenephosphonates of biological

  二乙基二氟甲基膦酰基溴化镉与烯丙基和苄基卤化物在THF中反应，生成相应的二氟亚甲基膦酸酯衍生物。与烯丙基溴的反应提供了一种通用的合成中间体，该中间体经历了各种合成转化，因此成为制备具有生物学意义的精制二氟亚甲基膦酸酯的关键化合物。
• Structural-based design and synthesis of novel 9-deazaguanine derivatives having a phosphate mimic as multi-substrate analogue inhibitors for mammalian PNPs
  作者：Sadao Hikishima、Mariko Hashimoto、Lucyna Magnowska、Agnieszka Bzowska、Tsutomu Yokomatsu

  DOI：10.1016/j.bmc.2010.01.062

  日期：2010.3

  9-(5',5'-Difluoro-5'-phosphonopentyl)-9-deazaguanine (DFPP-DG) was designed as a multi-substrate analogue inhibitor against purine nucleoside phosphorylase (PNP) on the basis of X-ray crystallographic data obtained for a binary complex of 9-(5',5'-difluoro-5'-phosphonopentyl)guanine (DFPP-G) with calf-spleen PNP. DFPP-DG and its analogous compounds were synthesized by the Sonogashira coupling reaction between a 9-deaza-9-iodoguanine derivative and omega-alkynyldifluoromethylene phosphonates as a key reaction. The experimental details focused on the synthetic chemistry along with some insights into the physical and biological properties of newly synthesized DFPP-DG derivatives are disclosed. (C) 2010 Elsevier Ltd. All rights reserved.
• Synthesis of a Difluorophosphonate Analog of the Oxathiolanyl Nucleoside (−)-β-L-(2<i>R</i>,5<i>S</i>)-1,3-Oxathianyl-5-fluorocytosine (FTC)
  作者：Richard E. Austin、Darryl G. Cleary

  DOI：10.1080/15257779508009758

  日期：1995.10

  A difluorophosphonate analog of (-)-beta-L-(2R,5S)-1,3-oxathianyl-5-fluorocytosine (FTC) was prepared as part of an effort to probe the possibility of obviating the need for endogenous kinases in the activation of nucleosides as potential therapeutic agents.
• α,α-Difluorophosphonohydroxamic Acid Derivatives among the Best Antibacterial Fosmidomycin Analogues
  作者：Aurore Dreneau、Fanny S. Krebs、Mathilde Munier、Chheng Ngov、Denis Tritsch、Didier Lièvremont、Michel Rohmer、Catherine Grosdemange-Billiard

  DOI：10.3390/molecules26165111

  日期：——

  Three α,α-difluorophosphonate derivatives of fosmidomycin were synthesized from diethyl 1,1-difluorobut-3-enylphosphonate and were evaluated on Escherichia coli. Two of them are among the best 1-deoxy-d-xylulose 5-phosphate reductoisomerase inhibitors, with IC50 in the nM range, much better than fosmidomycin, the reference compound. They also showed an enhanced antimicrobial activity against E. coli

  从 1,1-二氟丁-3-烯基膦酸二乙酯合成了 fosmidomycin 的三种 α,α-二氟膦酸酯衍生物，并在大肠杆菌中进行了评估。其中两种是最好的 1-脱氧-d-木酮糖 5-磷酸还原异构酶抑制剂，IC 50在 nM 范围内，远好于参考化合物磷米霉素。与相应的磷酸盐和非氟化膦酸盐相比，它们还显示出对培养皿上大肠杆菌的增强抗菌活性。