acetic acid 2-acetoxy-6-methoxy-4-[2-(2-trans-phenylethylenesulfonylmethanesulfonyl)-trans-vinyl]phenyl ester | 366803-88-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: acetic acid 2-acetoxy-6-methoxy-4-[2-(2-trans-phenylethylenesulfonylmethanesulfonyl)-trans-vinyl]phenyl ester
• 英文别名: [2-acetoxy-3-methoxy-5-[(E)-2-[[(E)-styryl]sulfonylmethylsulfonyl]vinyl]phenyl] acetate；[2-acetyloxy-3-methoxy-5-[(E)-2-[[(E)-2-phenylethenyl]sulfonylmethylsulfonyl]ethenyl]phenyl] acetate
• CAS: 366803-88-5
• 化学式: C₂₂H₂₂O₉S₂
• 分子量: 494.543
• InChiKey: UGSQFHIXVYGVOM-WGDLNXRISA-N

物化性质

• 沸点：
  747.4±60.0 °C(Predicted)
• 密度：
  1.384±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  147
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  acetic acid 2-acetoxy-6-methoxy-4-[2-(2-trans-phenylethylenesulfonylmethanesulfonyl)-trans-vinyl]phenyl ester 在 氨 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以29%的产率得到3-methoxy-5-[(E)-2-[[(E)-styryl]sulfonylmethylsulfonyl]vinyl]benzene-1,2-diol
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Geminal Disulfones as HIV-1 Integrase Inhibitors

  摘要：

  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.

  DOI：

  10.1021/jm049171v
• 作为产物：
  描述：

  苯甲醛 、 alkaline earth salt of/the/ methylsulfuric acid 在 N,N-二异丙基乙胺 、 lithium bromide 作用下， 以 四氢呋喃 为溶剂， 生成 acetic acid 2-acetoxy-6-methoxy-4-[2-(2-trans-phenylethylenesulfonylmethanesulfonyl)-trans-vinyl]phenyl ester
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Geminal Disulfones as HIV-1 Integrase Inhibitors

  摘要：

  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.

  DOI：

  10.1021/jm049171v

文献信息

• A novel reagent for the synthesis of geminal di-sulfones
  作者：Michael J Hadd、Mark A Smith、Jacquelyn Gervay-Hague

  DOI：10.1016/s0040-4039(01)01004-8

  日期：2001.7

  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.