O-cyclohexyl-O'-(2',3'-didehydro-2',3'-dideoxythymidin-5'-yl) phosphonate | 376357-17-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: O-cyclohexyl-O'-(2',3'-didehydro-2',3'-dideoxythymidin-5'-yl) phosphonate
• 英文别名: 1-[(2R,5S)-5-(cyclohexyloxyphosphonoyloxymethyl)-2,5-dihydrofuran-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 376357-17-4
• 化学式: C₁₆H₂₃N₂O₆P
• 分子量: 370.342
• InChiKey: QFSJMPQOKIKITC-UONOGXRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  94.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  O-cyclohexyl-O'-(2',3'-didehydro-2',3'-dideoxythymidin-5'-yl) phosphonate 在 ammonium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 2.0h， 生成 O-cyclohexyl-O'-(2',3'-didehydro-2',3'-dideoxythymidin-5'-yl) boranophosphate
  参考文献：
  名称：

  Synthesis of AZT/d4T Boranophosphates as Anti-HIV Prodrug Candidates

  摘要：

  AZT/d4T膦酸盐是通过在异戊酰氯存在下，依次将AZT/d4T与相应的醇或5′-DMT胸苷缩合合成的。这些膦酸盐依次进行硅烷化、硼化及在氨水中水解，得到抗HIV前药候选物AZT/d4T硼膦酸盐。

  DOI：

  10.1055/s-2004-815939
• 作为产物：
  描述：

  司他夫定 在 三氯化磷 作用下， 以 二氯甲烷 为溶剂， 反应 7.5h， 生成 O-cyclohexyl-O'-(2',3'-didehydro-2',3'-dideoxythymidin-5'-yl) phosphonate
  参考文献：
  名称：

  Novel benzyl rearrangements in electrospray ionization multistage tandem mass spectra of benzyl 2′,3′- didehydro-2′,3′-dideoxythymidin-5′-yl H-phosphonate

  摘要：

  通过电喷雾电离多级串联质谱（ESI-MSn）对几种烷基2′,3′-二脱氢-2′,3′-二脱氧胸苷-5′-基H-磷酸酯进行了合成和分析。在ESI-MS2的[M + H]+、[M + Na]+和[M + K]+中，观察到两种新的苄基重排反应。苄基2′,3′-二脱氢-2′,3′-二脱氧胸苷-5′-基H-磷酸酯的ESI-MS2。串联质谱、高分辨质谱和控制实验的结果表明，苄基迁移可以发生四元环状重排反应，并且苄基在该过程中是必不可少的。版权所有©2004约翰·威利父子有限公司。

  DOI：

  10.1002/jms.643

文献信息

• Sun, Xiao Bin; Kang, Jian Xun; Zhao, Yu Fen, Chemical Communications, 2002, # 20, p. 2414 - 2415
  作者：Sun, Xiao Bin、Kang, Jian Xun、Zhao, Yu Fen

  DOI：——

  日期：——
• Design and synthesis of novel distamycin-modified nucleoside analogues as HIV-1 reverse transcriptase inhibitors
  作者：Chao Li、Chunying Ma、Jin Zhang、Ning Qian、Jingjing Ding、Renzhong Qiao、Yufen Zhao

  DOI：10.1016/j.antiviral.2013.12.002

  日期：2014.2

  Design and synthesis of nucleoside analogues have persistently attracted extensive interest because of their potential application in the field of antiviral therapy, and its study also receives additional impetus for improvement in the ProTide technology. Previous studies have made great strides in the design and discovery of monophosphorylated nucleoside analogues as potential kinase-independent antiretrovirals. In this work, a series of nucleoside phosphoramidates modified by distamycin analogues was synthesized and evaluated as nucleoside reverse transcriptase inhibitors (NRTIs) in HIV-1-infected MT-4 and CEM cells, including variations in nucleoside, alkyl moiety, and the structure of distamycin analogues. These compounds exhibited modest potency with the EC50 value in the range of 1.3- to 6.5-fold lower than their corresponding parent drugs in MT-4 cells, which may be attributed to increasing intracellular availability due to the existence of distamycin analogue with favorable hydrophilic-lipophilic equilibrium. Meanwhile, the length of distamycin analogue was considered and assessed as an important factor that could affect antiviral activity and cytotoxicity. Enzymatic and metabolic stability studies have been performed in order to better understand the antiviral behavior of these compounds. The present work revealed the compounds to have a favorable and selective anti-HIV-1 activity in MT-4 and CEM cells, and helped to develop strategies for design and synthesis of effective monophosphorylated nucleoside analogues, which may be applied to antiretroviral research as NRTIs. (C) 2013 Elsevier B.V. All rights reserved.
• Synthesis of AZT/d4T Boranophosphates as Anti-HIV Prodrug Candidates
  作者：Hua Fu、Yufen Zhao、Changxue Lin、Guangzhong Tu

  DOI：10.1055/s-2004-815939

  日期：——

  AZT/d4T phosphonates were synthesized by sequential condensation of AZT/d4T with the corresponding alcohols or 5′-DMT-thymidine in the presence of pivaloyl chloride. Sequential silylation, boronation, and hydrolysis in ammonium hydroxide of these phosphonates led to anti-HIV prodrug candidates AZT/d4T boranophosphates.

  AZT/d4T膦酸盐是通过在异戊酰氯存在下，依次将AZT/d4T与相应的醇或5′-DMT胸苷缩合合成的。这些膦酸盐依次进行硅烷化、硼化及在氨水中水解，得到抗HIV前药候选物AZT/d4T硼膦酸盐。
• Novel benzyl rearrangements in electrospray ionization multistage tandem mass spectra of benzyl 2′,3′- didehydro-2′,3′-dideoxythymidin-5′-yl H-phosphonate
  作者：Yi Chen、Xiaobin Sun、Hua Fu、Xiaohong Liu、Yufen Zhao

  DOI：10.1002/jms.643

  日期：2004.7

  Several alkyl 2′,3′-didehydro-2′,3′-dideoxythymidin-5′-yl H-phosphonates were synthesized and analyzed by electrospray ionization multistage tandem mass spectrometry (ESI − MSn). Two kinds of novel benzyl rearrangement reactions were observed in ESI − MS2 of [M + H]+, [M + Na]+ and [M + K]+ of benzyl 2′,3′-didehydro-2′,3′-dideoxythymidin-5′-yl H-phosphonate. Results from tandem mass spectrometry, high-resolution mass spectrometry and control experiments showed that the benzyl migration could undergo a four-membered cyclic rearrangement reaction, and benzyl was essential in the process. Copyright © 2004 John Wiley & Sons, Ltd.

  通过电喷雾电离多级串联质谱（ESI-MSn）对几种烷基2′,3′-二脱氢-2′,3′-二脱氧胸苷-5′-基H-磷酸酯进行了合成和分析。在ESI-MS2的[M + H]+、[M + Na]+和[M + K]+中，观察到两种新的苄基重排反应。苄基2′,3′-二脱氢-2′,3′-二脱氧胸苷-5′-基H-磷酸酯的ESI-MS2。串联质谱、高分辨质谱和控制实验的结果表明，苄基迁移可以发生四元环状重排反应，并且苄基在该过程中是必不可少的。版权所有©2004约翰·威利父子有限公司。