3-(O(-tert-butyldiphenylsilyl)-hydroxymethyl)-3'-(hydroxymethyl)biphenyl-2,2'-diol-2',3'-O-isopropylideneacetal | 935681-46-2

• 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: 3-(O(-tert-butyldiphenylsilyl)-hydroxymethyl)-3'-(hydroxymethyl)biphenyl-2,2'-diol-2',3'-O-isopropylideneacetal
• 英文别名: 2-[[tert-butyl(diphenyl)silyl]oxymethyl]-6-(2,2-dimethyl-4H-1,3-benzodioxin-8-yl)phenol
• CAS: 935681-46-2
• 化学式: C₃₃H₃₆O₄Si
• 分子量: 524.732
• InChiKey: PJOQMTPLJYZZIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.78
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  47.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(O(-tert-butyldiphenylsilyl)-hydroxymethyl)-3'-(hydroxymethyl)biphenyl-2,2'-diol-2',3'-O-isopropylideneacetal 在 氟化铵 、 三氯化磷 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 63.17h， 生成 2-chloro-8-(2,2-dimethyl-4H-1,3-benzodioxin-8-yl)-4H-1,3,2-benzodioxaphosphinine
  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-(O-(tert-butyldiphenylsilyl)hydroxymethyl)-3'-(hydroxymethyl)biphenyl-2,2'-diol 、 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60%的产率得到3-(O(-tert-butyldiphenylsilyl)-hydroxymethyl)-3'-(hydroxymethyl)biphenyl-2,2'-diol-2',3'-O-isopropylideneacetal
  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

• Bis-<i>cyclo</i>Sal-d4T-monophosphates:  Drugs That Deliver Two Molecules of Bioactive Nucleotides
  作者：Christian Ducho、Ulf Görbig、Sönke Jessel、Nicolas Gisch、Jan Balzarini、Chris Meier

  DOI：10.1021/jm0611713

  日期：2007.3.1

  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.