6-bromo-4-tert-butylsalicyl alcohol isopropylidene acetal | 1072917-24-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: 6-bromo-4-tert-butylsalicyl alcohol isopropylidene acetal
• 英文别名: 3-bromo-5-tert-butylsalicyl alcohol isopropylidene acetal；8-bromo-6-tert-butyl-2,2-dimethyl-4H-1,3-benzodioxine
• CAS: 1072917-24-8
• 化学式: C₁₄H₁₉BrO₂
• 分子量: 299.208
• InChiKey: XDCWOLFECDEVFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-bromo-4-tert-butylsalicyl alcohol isopropylidene acetal 、 N,N-二甲基甲酰胺 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 0.75h， 以76%的产率得到6-tert-butyl-2,2-dimethyl-4H-benzo[1,3]dioxine-8-carbaldehyde
  参考文献：
  名称：

  Studies on Enzyme-Cleavable Dialkoxymethyl-cycloSaligenyl-2′,3′-dideoxy-2′,3′-didehydrothymidine Monophosphates

  摘要：

  Recently we reported on conceptually new enzymatically activated cycloSal-pronucleotides. Now, we developed this concept further with new compounds of this type. The basic idea is fast intracellular cleavage of a functionalized group at the cycloSal residue that results in a rapid delivery of the nucleotide and thus an intracellular enrichment of the nucleotide. The introduction of a higher alkylated acylal group, the di-iso-butyryloxymethyl group, to the aromatic ring led to the expected higher stability of these prodrugs against enzymatic cleavage but also entailed surprisingly a decrease in hydrolysis stabilities and solubility problems. For some compounds, a separation of the two diastereomeric forms (R-P, or S-P) was achieved. By X-ray structure analysis, the absolute configuration at the P-atom was assigned. For all separated diastereomers the (S-P) form showed better antiviral activity than the (R-P) form.

  DOI：

  10.1021/jm800853p
• 作为产物：
  描述：

  2-bromo-4-tert-butyl-6-(hydroxymethyl)phenol 、 2,2-二甲氧基丙烷 在 对甲苯磺酸 、 sodium sulfate 作用下， 以 丙酮 为溶剂， 反应 72.0h， 以86%的产率得到6-bromo-4-tert-butylsalicyl alcohol isopropylidene acetal
  参考文献：
  名称：

  Studies on Enzyme-Cleavable Dialkoxymethyl-cycloSaligenyl-2′,3′-dideoxy-2′,3′-didehydrothymidine Monophosphates

  摘要：

  Recently we reported on conceptually new enzymatically activated cycloSal-pronucleotides. Now, we developed this concept further with new compounds of this type. The basic idea is fast intracellular cleavage of a functionalized group at the cycloSal residue that results in a rapid delivery of the nucleotide and thus an intracellular enrichment of the nucleotide. The introduction of a higher alkylated acylal group, the di-iso-butyryloxymethyl group, to the aromatic ring led to the expected higher stability of these prodrugs against enzymatic cleavage but also entailed surprisingly a decrease in hydrolysis stabilities and solubility problems. For some compounds, a separation of the two diastereomeric forms (R-P, or S-P) was achieved. By X-ray structure analysis, the absolute configuration at the P-atom was assigned. For all separated diastereomers the (S-P) form showed better antiviral activity than the (R-P) form.

  DOI：

  10.1021/jm800853p

文献信息

• Studies on Enzyme-Cleavable Dialkoxymethyl-<i>cyclo</i>Saligenyl-2′,3′-dideoxy-2′,3′-didehydrothymidine Monophosphates
  作者：Nicolas Gisch、Jan Balzarini、Chris Meier

  DOI：10.1021/jm800853p

  日期：2008.11.13

  Recently we reported on conceptually new enzymatically activated cycloSal-pronucleotides. Now, we developed this concept further with new compounds of this type. The basic idea is fast intracellular cleavage of a functionalized group at the cycloSal residue that results in a rapid delivery of the nucleotide and thus an intracellular enrichment of the nucleotide. The introduction of a higher alkylated acylal group, the di-iso-butyryloxymethyl group, to the aromatic ring led to the expected higher stability of these prodrugs against enzymatic cleavage but also entailed surprisingly a decrease in hydrolysis stabilities and solubility problems. For some compounds, a separation of the two diastereomeric forms (R-P, or S-P) was achieved. By X-ray structure analysis, the absolute configuration at the P-atom was assigned. For all separated diastereomers the (S-P) form showed better antiviral activity than the (R-P) form.