6-trichloromethyl-9-(tetrahydro-2H-pyran-2-yl)purine | 1203479-12-2

• 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-trichloromethyl-9-(tetrahydro-2H-pyran-2-yl)purine
• CAS: 1203479-12-2
• 化学式: C₁₁H₁₁Cl₃N₄O
• 分子量: 321.594
• InChiKey: JKVOCUANUFTVOI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.35
• 重原子数：
  19.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  52.83
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  6-methyl-9-(tetrahydro-2-pyranyl)purine 在 sodium hexamethyldisilazane 、 对甲苯磺酰氯 作用下， 以 四氢呋喃 为溶剂， 反应 0.33h， 以41%的产率得到6-chloromethyl-9-(tetrahydro-2H-pyran-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