ethyl dibenzylphosphonoacetate

• 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: ethyl dibenzylphosphonoacetate
• 英文别名: Dibenzyloxyphosphoryl acetic acid ethyl ester；ethyl 2-bis(phenylmethoxy)phosphorylacetate
• 化学式: C₁₈H₂₁O₅P
• 分子量: 348.336
• InChiKey: VWNNCLKXMXEVOX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl dibenzylphosphonoacetate 在 lithium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 以82%的产率得到dibenzylphosphonoacetic acid
  参考文献：
  名称：

  Development of O–H insertion for the attachment of phosphonates to nucleosides; synthesis of α-carboxy phosphononucleosides

  摘要：

  Development of rhodium catalysed O-H insertion reactions employing alpha-diazophosphonates with appropriately protected adenosine, uridine and thymidine derivatives is described. This synthetic methodology leads, following deprotection, to novel phosphononucleoside derivatives bearing a carboxylic acid moiety adjacent to the phosphonate. Protection strategies are critical to the success of the key O-H insertion. There are two important aspects: avoiding competing insertion pathways or catalyst poisoning, and being able to achieve deprotection without degradation of the phosphononucleosides. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2011.12.077
• 作为产物：
  描述：

  重氮乙酸乙酯 、 亚磷酸二苄酯 在 copper(II) bis(trifluoromethanesulfonate) 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以86%的产率得到ethyl dibenzylphosphonoacetate
  参考文献：
  名称：

  Development of O–H insertion for the attachment of phosphonates to nucleosides; synthesis of α-carboxy phosphononucleosides

  摘要：

  Development of rhodium catalysed O-H insertion reactions employing alpha-diazophosphonates with appropriately protected adenosine, uridine and thymidine derivatives is described. This synthetic methodology leads, following deprotection, to novel phosphononucleoside derivatives bearing a carboxylic acid moiety adjacent to the phosphonate. Protection strategies are critical to the success of the key O-H insertion. There are two important aspects: avoiding competing insertion pathways or catalyst poisoning, and being able to achieve deprotection without degradation of the phosphononucleosides. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2011.12.077

文献信息

• ANTI-BACTERIAL COMPOSITIONS AND METHODS INCLUDING TARGETING VIRULENCE FACTORS OF STAPHYLOCOCCUS AUREUS
  申请人：Oldfield Eric

  公开号：US20120022024A1

  公开（公告）日：2012-01-26

  This disclosure relates to compositions and methods including for the inhibition, prevention, and/or treatment of microbial infections, including infections from such pathogens as Staphylococcus aureus.

  本公开涉及包括用于抑制、预防和/或治疗微生物感染的组合物和方法，包括对金黄色葡萄球菌等病原体引起的感染。
• Mild and efficient Cs2CO3-promoted synthesis of phosphonates
  作者：Richard J Cohen、Daniel L Fox、Jarrod F Eubank、Ralph Nicholas Salvatore

  DOI：10.1016/j.tetlet.2003.09.045

  日期：2003.11

  mild and convenient synthesis for phosphonates using cesium carbonate (Cs2CO3), tetrabutylammonium iodide (TBAI) and DMF was developed at room temperature. Numerous dialkyl phosphites were screened using a diverse array of alkyl halides and these reaction conditions were found to be highly efficient producing various phosphonates exclusively in moderate to high yields. (C) 2003 Elsevier Ltd. All rights reserved.
• Inhibition of Staphyloxanthin Virulence Factor Biosynthesis in <i>Staphylococcus aureus</i>: In Vitro, in Vivo, and Crystallographic Results
  作者：Yongcheng Song、Chia-I Liu、Fu-Yang Lin、Joo Hwan No、Mary Hensler、Yi-Liang Liu、Wen-Yih Jeng、Jennifer Low、George Y. Liu、Victor Nizet、Andrew H.-J. Wang、Eric Oldfield

  DOI：10.1021/jm9001764

  日期：2009.7.9

  The gold color of Staphylococcus aureus is derived from the carotenoid staphyloxanthin, a virulence factor for the organism. Here, we report the synthesis and activity of a broad variety of staphyloxanthin biosynthesis inhibitors that inhibit the first committed step in its biosynthesis, condensation of two farnesyl diphosphate (FPP) molecules to dehydrosqualene, catalyzed by the enzyme dehydrosqualene synthase (CrtM). The most active compounds are phosphonoacetamides that have low nanomolar K-i values for CrtM inhibition and are active in whole bacterial cells and in mice, where they inhibit S. aureus disease progression. We also report the X-ray crystallographic structure of the most active compound, N-3-(3-phenoxyphenyl)propylphosphonoacetamide (IC50 = 8 nM, in cells), bound to CrtM. The structure exhibits a complex network of hydrogen bonds between the polar headgroup and the protein, while the 3-phenoxyphenyl side chain is located in a hydrophobic pocket previously reported to bind farnesyl thiodiphosphate (FsPP), as well as biphenyl phosphonosulfonate inhibitors. Given the good enzymatic, whole cell, and in vivo pharmacologic activities, these results should help guide the further development of novel antivirulence factor-based therapies for S. aureus infections.
• [EN] ANTI-BACTERIAL COMPOSITIONS AND METHODS INCLUDING TARGETING VIRULENCE FACTORS OF STAPHYLOCOCCUS AUREUS<br/>[FR] COMPOSITIONS ANTI-BACTÉRIENNES ET PROCÉDÉS COMPRENANT LE CIBLAGE DE FACTEURS DE VIRULENCE DE STAPHYLOCOCCUS AUREUS
  申请人：UNIV ILLINOIS

  公开号：WO2010123599A9

  公开（公告）日：2011-02-17

  [EN] This disclosure relates to compositions and methods including for the inhibition, prevention, and/or treatment of microbial infections, including infections from such pathogens as Staphylococcus aureus.
  [FR] L'invention se rapporte à des compositions et à des procédés notamment pour l'inhibition, la prévention, et/ou le traitement d'infections microbiennes, y compris des infections par des agents pathogènes tels que Staphylococcus aureus.
• [EN] FC CONJUGATES INCLUDING AN INHIBITOR OF CD73 AND USES THEREOF<br/>[FR] CONJUGUÉS FC COMPRENANT UN INHIBITEUR DE CD73 ET LEURS UTILISATIONS
  申请人：[en]CIDARA THERAPEUTICS, INC.

  公开号：WO2024010810A2

  公开（公告）日：2024-01-11

  The disclosure provides conjugates including an Fc domain monomer or Fc domain covalently linked to a moiety that binds to or inhibits CD73. The disclosure also provides pharmaceutical compositions including such conjugates and uses of such conjugates in the treatment of disorders associated with dysregulation or overexpression of CD73 (e.g., cancer, fibrosis, or a viral infection).