8-methyl-2-[[(2S,5R)-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methoxy]-2-oxo-4H-1,3,2$l^{5}-benzodioxaphosphinine-6-carbaldehyde | 934477-23-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: 8-methyl-2-[[(2S,5R)-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methoxy]-2-oxo-4H-1,3,2$l^{5}-benzodioxaphosphinine-6-carbaldehyde
• 英文别名: 8-methyl-2-[[(2S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methoxy]-2-oxo-4H-1,3,2λ5-benzodioxaphosphinine-6-carbaldehyde
• CAS: 934477-23-3
• 化学式: C₁₉H₁₉N₂O₈P
• 分子量: 434.342
• InChiKey: XZCROKDHIICKSV-HZZXRAHOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  8-methyl-2-[[(2S,5R)-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methoxy]-2-oxo-4H-1,3,2$l^{5}-benzodioxaphosphinine-6-carbaldehyde 、 乙酸酐 在 氯化锆(IV) 作用下， 以 乙腈 为溶剂， 反应 0.75h， 生成 [acetoxy-[8-methyl-2-[[(2S,5R)-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methoxy]-2-oxo-4H-1,3,2$l^{5}-benzodioxaphosphinin-6-yl]methyl] acetate
  参考文献：
  名称：

  Enzymatically Activated cycloSal-d4T-monophosphates:  The Third Generation of cycloSal-Pronucleotides

  摘要：

  The third generation of cycloSal-pronucleotides, 5-diacetoxymethyl-cycloSal-d4T-monophosphates (5-di-AM-cycloSal-d4TMPs), is reported as a new class of "lock-in"-modified cycloSal-pronucleotides. These compounds bear an esterase-cleavable geminal dicarboxylate (acylal) attached to the aromatic ring of the saligenyl unit. The conversion into a strong acceptor group (aldehyde) leads to a strong decrease in hydrolytic stability. As a consequence, a fast release of a nucleoside monophosphate (i.e., d4TMP) follows. The concept of this enzymatic activation is proven by hydrolysis studies in phosphate buffer, cell extracts, and human serum. These investigations showed the conversion of the acylal group into a polar aldehyde by enzymatic cleavage. Besides, antiviral activities against HIV are presented.

  DOI：

  10.1021/jm0613267
• 作为产物：
  描述：

  3-甲基水杨酸 在 吡啶 、 盐酸 、 叔丁基过氧化氢 、 lithium aluminium tetrahydride 、 正丁基锂 、 硫酸 、 溴 、 对甲苯磺酸 、 sodium sulfate 、 N,N-二异丙基乙胺 、 三氯化磷 作用下， 以 四氢呋喃 、 正己烷 、 氯仿 、 丙酮 、 乙腈 为溶剂， 反应 176.5h， 生成 8-methyl-2-[[(2S,5R)-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methoxy]-2-oxo-4H-1,3,2$l^{5}-benzodioxaphosphinine-6-carbaldehyde
  参考文献：
  名称：

  Enzymatically Activated cycloSal-d4T-monophosphates:  The Third Generation of cycloSal-Pronucleotides

  摘要：

  The third generation of cycloSal-pronucleotides, 5-diacetoxymethyl-cycloSal-d4T-monophosphates (5-di-AM-cycloSal-d4TMPs), is reported as a new class of "lock-in"-modified cycloSal-pronucleotides. These compounds bear an esterase-cleavable geminal dicarboxylate (acylal) attached to the aromatic ring of the saligenyl unit. The conversion into a strong acceptor group (aldehyde) leads to a strong decrease in hydrolytic stability. As a consequence, a fast release of a nucleoside monophosphate (i.e., d4TMP) follows. The concept of this enzymatic activation is proven by hydrolysis studies in phosphate buffer, cell extracts, and human serum. These investigations showed the conversion of the acylal group into a polar aldehyde by enzymatic cleavage. Besides, antiviral activities against HIV are presented.

  DOI：

  10.1021/jm0613267

文献信息

• Enzymatically Activated <i>cyclo</i>Sal-d4T-monophosphates:  The Third Generation of <i>cyclo</i>Sal-Pronucleotides
  作者：Nicolas Gisch、Jan Balzarini、Chris Meier

  DOI：10.1021/jm0613267

  日期：2007.4.1

  The third generation of cycloSal-pronucleotides, 5-diacetoxymethyl-cycloSal-d4T-monophosphates (5-di-AM-cycloSal-d4TMPs), is reported as a new class of "lock-in"-modified cycloSal-pronucleotides. These compounds bear an esterase-cleavable geminal dicarboxylate (acylal) attached to the aromatic ring of the saligenyl unit. The conversion into a strong acceptor group (aldehyde) leads to a strong decrease in hydrolytic stability. As a consequence, a fast release of a nucleoside monophosphate (i.e., d4TMP) follows. The concept of this enzymatic activation is proven by hydrolysis studies in phosphate buffer, cell extracts, and human serum. These investigations showed the conversion of the acylal group into a polar aldehyde by enzymatic cleavage. Besides, antiviral activities against HIV are presented.