6-(fluoromethyl)-9-(tetrahydropyran-2-yl)purine | 667420-78-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 6-(fluoromethyl)-9-(tetrahydropyran-2-yl)purine
• 英文别名: 6-fluoromethyl-9-(tetrahydro-2H-pyran-2-yl)purine；6-(Fluoromethyl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine；6-(fluoromethyl)-9-(oxan-2-yl)purine
• CAS: 667420-78-2
• 化学式: C₁₁H₁₃FN₄O
• 分子量: 236.249
• InChiKey: MQUPMZHGCNSSTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  52.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(fluoromethyl)-9-(tetrahydropyran-2-yl)purine 在 Dowex 50 WX₈ (H(+) form) 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以70%的产率得到6-fluoro-9H-purine
  参考文献：
  名称：

  The first synthesis and cytostatic activity of novel 6-(fluoromethyl)purine bases and nucleosides

  摘要：

  本文描述了两种合成新型6-（氟甲基）嘌呤碱和核苷的方法，即直接脱氧氟化或从6-（羟甲基）嘌呤开始的多步官能团转化。6-（氟甲基）嘌呤核糖核苷显示出显著的细胞抑制作用。

  DOI：

  10.1039/b508122j
• 作为产物：
  描述：

  6-methyl-9-(tetrahydro-2-pyranyl)purine 在 双(三甲基硅烷基)氨基钾 、 N-氟苯磺酰胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.58h， 以57.8%的产率得到6-(fluoromethyl)-9-(tetrahydropyran-2-yl)purine
  参考文献：
  名称：

  Regioselective Metalation of 6-Methylpurines: Synthesis of Fluoromethyl Purines and Related Nucleosides for Suicide Gene Therapy of Cancer

  摘要：

  Metalation of 6-methyl-9-(tetrahydro-2H-pyran-2-yl)purine (10) with lithiating agents of varying basicities such as n-BuLi and LiHMDS in THF at - 78 degrees C resulted in metalation at both of the 6-CH3 moiety and the 8-CH position, irrespective of the molar equivalence of the base. On the other hand, a regioselective metalation at the 6-CH3 moiety of 10 was observed with NaHMDS or KHMDS, under similar conditions. Treatment of the potassium salts of 10 and of the protected riboside derivative 6-methyl-9-(beta-D-2,3,5-tri-O-tert-butyldimethylsilylribofuranosyl)purine (22) with N-fluorobenzenesulfonamide (NFSI) at - 78 degrees C gave the corresponding 6-fluoromethylpurine derivatives 11 and 23, respectively, in good yields. Deprotection of 11 and 23 under standard conditions gave 6-fluoromethylpurine (6-FMeP, 3) and 6-fluoromethyl-9-(beta-D-ribofuranosyl)purine (6-FMePR, 4), respectively, in high yield. Both 3 and 4 demonstrated cytotoxic activity against CCRF-CEM cells in culture. 6-FMePR is a good substrate for E. coli purine nucleoside phosphorylase (E. coli PNP) with a comparable substrate activity to that of the parent nucleoside, 6-methyl-9-(beta-D-ribofuranosyl)purine (&MePA 21). The cytotoxic activity of 6-FMeP along with the substrate activity of 6-FMePR with E. coli PNP meet the fundamental requirements for using 6-FMeP as a Potential toxin in PAT/prodrug based cancer gene therapy.

  DOI：

  10.1080/15257770903091938

文献信息

• The first synthesis and cytostatic activity of novel 6-(fluoromethyl)purine bases and nucleosides
  作者：Peter Šilhár、Radek Pohl、Ivan Votruba、Michal Hocek

  DOI：10.1039/b508122j

  日期：——

  Two alternative approaches to the synthesis of novel 6-(fluoromethyl)purine bases and nucleosides are described either by direct deoxyfluorination or by multistep functional group transformations starting from 6-(hydroxymethyl)purines. 6-(Fluoromethyl)purine ribonucleoside displayed significant cytostatic effects.

  本文描述了两种合成新型6-（氟甲基）嘌呤碱和核苷的方法，即直接脱氧氟化或从6-（羟甲基）嘌呤开始的多步官能团转化。6-（氟甲基）嘌呤核糖核苷显示出显著的细胞抑制作用。
• Selective Metalation of 6-Methylpurines: Synthesis of 6-Fluoromethylpurines and Related Nucleosides
  作者：Abdalla E. A. Hassan、William B. Parker、Paula W. Allan、John A. Montgomery、John A. Secrist

  DOI：10.1081/ncn-120022625

  日期：2003.10

  A selective metalation at the 6-CH3 over C-8 of 6-methylpurine derivative 6 was observed with softer counter cation (Na+ or K+) of the base, while the harder Li+ showed no selectivity. In the presence of N-fluorobenzenesulfonamide (NFSI), this property was utilized for the synthesis of 6-fluoromethylpurine derivatives 4 and 5 as potential toxins for suicide gene therapy.
• Regioselective Metalation of 6-Methylpurines: Synthesis of Fluoromethyl Purines and Related Nucleosides for Suicide Gene Therapy of Cancer
  作者：Abdalla E. A. Hassan、William B. Parker、Paula W. Allan、John A. Secrist

  DOI：10.1080/15257770903091938

  日期：2009.8.11

  Metalation of 6-methyl-9-(tetrahydro-2H-pyran-2-yl)purine (10) with lithiating agents of varying basicities such as n-BuLi and LiHMDS in THF at - 78 degrees C resulted in metalation at both of the 6-CH3 moiety and the 8-CH position, irrespective of the molar equivalence of the base. On the other hand, a regioselective metalation at the 6-CH3 moiety of 10 was observed with NaHMDS or KHMDS, under similar conditions. Treatment of the potassium salts of 10 and of the protected riboside derivative 6-methyl-9-(beta-D-2,3,5-tri-O-tert-butyldimethylsilylribofuranosyl)purine (22) with N-fluorobenzenesulfonamide (NFSI) at - 78 degrees C gave the corresponding 6-fluoromethylpurine derivatives 11 and 23, respectively, in good yields. Deprotection of 11 and 23 under standard conditions gave 6-fluoromethylpurine (6-FMeP, 3) and 6-fluoromethyl-9-(beta-D-ribofuranosyl)purine (6-FMePR, 4), respectively, in high yield. Both 3 and 4 demonstrated cytotoxic activity against CCRF-CEM cells in culture. 6-FMePR is a good substrate for E. coli purine nucleoside phosphorylase (E. coli PNP) with a comparable substrate activity to that of the parent nucleoside, 6-methyl-9-(beta-D-ribofuranosyl)purine (&MePA 21). The cytotoxic activity of 6-FMeP along with the substrate activity of 6-FMePR with E. coli PNP meet the fundamental requirements for using 6-FMeP as a Potential toxin in PAT/prodrug based cancer gene therapy.