(diisopropoxyphosphorylmethanesulfonylmethanesulfonylmethyl)phosphonic acid diisopropyl ester | 312512-49-5

• 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: (diisopropoxyphosphorylmethanesulfonylmethanesulfonylmethyl)phosphonic acid diisopropyl ester
• 英文别名: diisopropyl (diisopropoxyphosphorylmethylsulfonylmethylsulfonylmethyl)phosphonate；(diisopropoxyphosphorylmethanesulfonylmethyl)-phosphonic acid diisopropyl ester；2-[Di(propan-2-yloxy)phosphorylmethylsulfonylmethylsulfonylmethyl-propan-2-yloxyphosphoryl]oxypropane
• CAS: 312512-49-5
• 化学式: C₁₅H₃₄O₁₀P₂S₂
• 分子量: 500.508
• InChiKey: IVKSPTSDVMFZEX-UHFFFAOYSA-N

物化性质

• 沸点：
  647.3±50.0 °C(Predicted)
• 密度：
  1.272±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  29
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  156
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  6-溴藜芦醛 、 (diisopropoxyphosphorylmethanesulfonylmethanesulfonylmethyl)phosphonic acid diisopropyl ester 在 N,N-二异丙基乙胺 、 lithium bromide 作用下， 以 四氢呋喃 为溶剂， 以75%的产率得到bis(trans-β-6-bromo-3,4-dimethoxy-styrenesulfonyl)methane
  参考文献：
  名称：

  环取代基对作为HIV-1抑制剂的乙烯基砜的生物活性的影响。

  摘要：

  在先前的研究中，我们准备了一个小型的菊苣酸类似物文库，该文库具有强大的抗整合酶和抗病毒活性。还显示出活性化合物分为两类之一：抑制病毒复制早期的化合物和抑制病毒复制的化合物。在这项研究中，已合成了一系列具有一系列环取代基的含乙烯基双膦二砜的化合物，以探讨结构对抑制机理的影响。使用HIV药物敏感性测定法鉴定了四种活性化合物。芳香环上没有取代基或没有吸电子取代基的三种抑制剂导致高水平的细胞毒性和抗病毒活性。迷恋电子效应对活动的潜在影响，我们研究了活性化合物是否可以通过1,4-加成发生非特异性反应。为了研究该假设，将化合物与谷胱甘肽一起孵育，并通过LC / MS分析，鉴定了与单加成和双加成加合物相对应的分子离子峰。其次，我们合成了缺乏参与1，4-加成能力的类似物，并测试了它们的抗病毒活性和细胞毒性，发现该化合物对这两种活性均无活性。综上所述，本文报道的研究表明，在芳环上缺乏供电子取代基的化合物是生

  DOI：

  10.1016/j.bmc.2006.10.017
• 作为产物：
  描述：

  diisopropyl (mercaptomethyl) phosphonate 在 Oxone 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 生成 (diisopropoxyphosphorylmethanesulfonylmethanesulfonylmethyl)phosphonic acid diisopropyl ester
  参考文献：
  名称：

  A novel reagent for the synthesis of geminal di-sulfones

  摘要：

  A novel reagent (diisopropoxyphosphorylmethanesulfonylmethyl)-phosphonic acid diisopropyl ester (8) capable of forming symmetrical and non-symmetrical alpha,beta unsaturated gem-disulfones is reported. Both aromatic and aliphatic aldehydes react in good yields to give exclusively the trans isomer. Selectivity for the mono-olefin can be achieved by varying the stoichiometry of reagents. (C) 2001 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4039(01)01004-8

文献信息

• Synthesis of sulfone-based nucleotide isosteres: identification of CMP-sialic acid synthetase inhibitors
  作者：Jessica H. Wong、Urvashi Sahni、Yanhong Li、Xi Chen、Jacquelyn Gervay-Hague

  DOI：10.1039/b819155g

  日期：——

  A modular replacement approach to the synthesis of sulfo-nucleotide analogs prepared from condensation of nucleoside aldehydes with bis phosphonate Horner-Wadsworth-Emmons reagents is disclosed. These analogs were shown to be inhibitors of Neisseria meningitidis CSS (NmCSS), which is a key enzyme in the biosynthesis of the capsular polysaccharides required for bacterial infection.

  一种模块化替代方法用于合成由核苷醛与双磷酸酯Horner-Wadsworth-Emmons试剂缩合制备的磺酸核苷类似物。研究表明，这些类似物是脑膜炎奈瑟氏菌CSS（NmCSS）的抑制剂，该酶在细菌感染所需的荚膜多糖的生物合成中起关键作用。
• Synthesis and Biological Evaluation of Geminal Disulfones as HIV-1 Integrase Inhibitors
  作者：D. Christopher Meadows、Timothy B. Mathews、Thomas W. North、Michael J. Hadd、Chih Lin Kuo、Nouri Neamati、Jacquelyn Gervay-Hague

  DOI：10.1021/jm049171v

  日期：2005.7.1

  Integration of HIV-1 viral DNA into the host genome is carried out by HIV-integrase (IN) and is a critical step in viral replication. Although several classes of compounds have been reported to inhibit IN in enzymatic assays, inhibition is not always correlated with antiviral activity. Moreover, potent antiviral IN inhibitors such as the chicoric acids do not act upon the intended enzymatic target but behave as entry inhibitors instead. The charged nature of the chicoric acids contributes to poor cellular uptake, and these compounds are further plagued by rapid ester hydrolysis in vivo. To address these critical deficiencies, we designed neutral, nonhydrolyzable analogues of the chicoric acids. Herein, we report the synthesis, enzyme inhibition studies, and cellular antiviral data for a series of geminal disulfones. Of the 10 compounds evaluated, 8 showed moderate to high inhibition of IN in purified enzyme assays. The purified enzyme data correlated with antiviral assays for all but two compounds, suggesting alternative modes of inhibition. Time-of-addition studies were performed on these analogues, and the results indicate that they inhibit an early stage in the replication process, perhaps entry. In contrast, the most potent member of the correlative group shows behavior consistent with IN being the cellular target.
• WO2007/65032
  申请人：——

  公开号：——

  公开（公告）日：——
• Vinyl sulfones
  作者：Jessica H. Wong、Marilyn M. Olmstead、James C. Fettinger、Jacquelyn Gervay-Hague

  DOI：10.1107/s0108270108002692

  日期：2008.3.15

  Four neutral vinyl sulfones, two of which are paired with phosphonate groups, are described. The compounds are diisopropyl (2-phenylethenylsulfonylmethyl) phosphonate, C15H23O5PS, (I), diisopropyl [2-(7-methoxy-1,3-benzodioxol-5-yl) ethenylsulfonyl]methylsulfonylmethyl} phosphonate, C18H27O10PS2, (II), bis(trans-2-phenylethenyl) sulfone, C16H14O2S, (III), and bis(trans-2-phenylethenylsulfonyl) methane, C17H16O4S2, (IV). Their structures can be considered as highly functionalized mimics of mono-, di- and triphosphates. These phosphate isosteres are currently of interest as agents for enzyme inhibition in both cancer and HIV therapy. All except one of the compounds has Z' > 1. The lone exception is (IV), a disulfone with twofold crystallographic symmetry. Geometrically, the sulfone functionality is found to be a good mimic for phosphate. The principal effect of the vinyl group is to shorten the S-C(vinyl) distance relative to the S-CH2 distance by ca 0.05 angstrom. The S-C-S and S-C-P backbones resemble the P-O-P backbone but are not identical because the S - C and P - C distances are longer than the P-O distance and the S-C-S and S-C-P angles are more acute than the P-O-P angle. No prior crystal structures of comparable compounds have been published.