bis(isopropylidene)-3,3'-bis(hydroxymethyl)biphenyl-2,2'-diol | 91084-80-9

• 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: bis(isopropylidene)-3,3'-bis(hydroxymethyl)biphenyl-2,2'-diol
• 英文别名: 8-(2,2-dimethyl-4H-1,3-benzodioxin-8-yl)-2,2-dimethyl-4H-1,3-benzodioxine
• CAS: 91084-80-9
• 化学式: C₂₀H₂₂O₄
• 分子量: 326.392
• InChiKey: JILKGPWOOKWBTC-UHFFFAOYSA-N

物化性质

• 沸点：
  492.3±45.0 °C(Predicted)
• 密度：
  1.127±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  36.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  bis(isopropylidene)-3,3'-bis(hydroxymethyl)biphenyl-2,2'-diol 在 Dowex 50X₈ 、 三氯化磷 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 70.17h， 生成 8-[2-(diethylamino)-4H-1,3,2-benzodioxaphosphinin-8-yl]-N,N-diethyl-4H-1,3,2-benzodioxaphosphinin-2-amine
  参考文献：
  名称：

  Bis-cycloSal-d4T-monophosphates:  Drugs That Deliver Two Molecules of Bioactive Nucleotides

  摘要：

  Bis-cycloSal-d4T-monophosphates have been synthesized as potentially anti-HIV active "dimeric" prodrugs of 2',3'-dideoxy-2',3'-didehydrothymidine monophosphate (d4TMP). These pronucleotides display a mask-drug ratio of 1:2, a novelty in the field of pronucleotides. Both bis-cycloSal-d4TMP 6 and bis-5-methyl-cycloSal-d4TMP 7 showed increased hydrolytic stability as compared to their "monomeric" counterparts and a completely selective hydrolytic release of d4TMP. The hydrolysis pathway was investigated via P-31 NMR spectroscopy. Moreover, due to the steric bulkiness, compound 6 already displayed strongly reduced inhibitor potency toward human butyrylcholinesterase (BChE), while compound 7 turned out to be devoid of any inhibitory activity against BChE. Partial separation of the diastereomeric mixture of 6 revealed strong dependence of the pronucleotides' properties on the stereochemistry at the phosphorus centers. Both 6and 7 showed good activity against HIV-1 and HIV-2 in wild-type CEM cells in vitro. These compounds were significantly more potent than the parent nucleoside d4T 1in HIV-2-infected TK-deficient CEM cells, indicating an efficient TK-bypass.

  DOI：

  10.1021/jm0611713
• 作为产物：
  描述：

  3-bromosalicyl alcohol isopropylidene acetal 在 正丁基锂 、 iron(III)-acetylacetonate 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 18.0h， 以84%的产率得到bis(isopropylidene)-3,3'-bis(hydroxymethyl)biphenyl-2,2'-diol
  参考文献：
  名称：

  Bis-cycloSal-d4T-monophosphates:  Drugs That Deliver Two Molecules of Bioactive Nucleotides

  摘要：

  Bis-cycloSal-d4T-monophosphates have been synthesized as potentially anti-HIV active "dimeric" prodrugs of 2',3'-dideoxy-2',3'-didehydrothymidine monophosphate (d4TMP). These pronucleotides display a mask-drug ratio of 1:2, a novelty in the field of pronucleotides. Both bis-cycloSal-d4TMP 6 and bis-5-methyl-cycloSal-d4TMP 7 showed increased hydrolytic stability as compared to their "monomeric" counterparts and a completely selective hydrolytic release of d4TMP. The hydrolysis pathway was investigated via P-31 NMR spectroscopy. Moreover, due to the steric bulkiness, compound 6 already displayed strongly reduced inhibitor potency toward human butyrylcholinesterase (BChE), while compound 7 turned out to be devoid of any inhibitory activity against BChE. Partial separation of the diastereomeric mixture of 6 revealed strong dependence of the pronucleotides' properties on the stereochemistry at the phosphorus centers. Both 6and 7 showed good activity against HIV-1 and HIV-2 in wild-type CEM cells in vitro. These compounds were significantly more potent than the parent nucleoside d4T 1in HIV-2-infected TK-deficient CEM cells, indicating an efficient TK-bypass.

  DOI：

  10.1021/jm0611713

文献信息

• KATZ, H. E.;CRAM, D. J., J. AMER. CHEM. SOC., 1984, 106, N 17, 4977-4987
  作者：KATZ, H. E.、CRAM, D. J.

  DOI：——

  日期：——