6-methyl-9-(β-D-2,3,5-tri-O-(tert-butyldimethylsilyl)ribofuranosyl)purine | 667420-77-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 6-methyl-9-(β-D-2,3,5-tri-O-(tert-butyldimethylsilyl)ribofuranosyl)purine
• 英文别名: 2',3',5'-tri-O-(tert-butyldimethylsilyl)-6-methylnebularine；[(2R,3R,4R,5R)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-(6-methylpurin-9-yl)oxolan-2-yl]methoxy-tert-butyl-dimethylsilane
• CAS: 667420-77-1
• 化学式: C₂₉H₅₆N₄O₄Si₃
• 分子量: 609.045
• InChiKey: WHRIABOYCIJIMQ-IGGXFAESSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.83
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  80.5
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-methyl-9-(β-D-2,3,5-tri-O-(tert-butyldimethylsilyl)ribofuranosyl)purine 在 sodium hexamethyldisilazane 、 N-氟苯磺酰胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.08h， 以47.9%的产率得到6-fluoromethyl-9-(2,3,5-tri-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl)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
• 作为产物：
  描述：

  2',3',5'-tri-O-(tert-butyldimethylsilyl)nebularine N1-oxide 在 吡啶 、 乙酸酐 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 6-methyl-9-(β-D-2,3,5-tri-O-(tert-butyldimethylsilyl)ribofuranosyl)purine
  参考文献：
  名称：

  利用 NebularineN1-氧化物对格氏试剂的反应性合成 2,6-二烷基（芳基）嘌呤核苷

  摘要：

  描述了通过将格利雅试剂双加成到 N1-氧化物嘌呤核苷上来合成 2,6-二烷基 (芳基) 嘌呤核苷。合成方案利用了嘌呤碱基的 C6-N1-O- 和 C2-N1-O- 部分的反应性。整个过程包括初始格氏试剂添加到 Nebularine N1-氧化物的 C6 中，然后芳构化得到 C6 取代的核苷。然后在 N1-氧化物再生之后在 C2 处进行第二次格氏加成，导致嘧啶环打开。然后通过系统的芳构化驱动瞬时打开的嘧啶的环化以提供最终的嘌呤系统。

  DOI：

  10.1002/ejoc.201300941

文献信息

• Probing the reactivity of nebularine N1-oxide. A novel approach to C-6 C-substituted purine nucleosides
  作者：Stefano D’Errico、Vincenzo Piccialli、Giorgia Oliviero、Nicola Borbone、Jussara Amato、Valentina D’Atri、Gennaro Piccialli

  DOI：10.1016/j.tet.2011.06.080

  日期：2011.8

  A novel approach to the synthesis of purine nucleoside analogues, featuring the reaction of the C6–N1–O− aldonitrone moiety of 9-ribosyl-purine (nebularine) N1-oxide with some representative dipolarophiles, as well as Grignard reagents, is reported. Addition of Grignard reagents to the electrophilic C-6 carbon of the substrate allows a facile access to C-6 C-substituted purine nucleosides without using

  的新方法，以嘌呤核苷类似物的合成中，特色的C6-的反应Ñ 1-O - aldonitrone 9核糖基嘌呤（水粉蕈素）的结构部分Ñ 1-氧化物与一些代表性dipolarophiles，以及格氏试剂，是报告。向底物的亲电C-6碳中添加格氏试剂可轻松获得C-6 C取代的嘌呤核苷，而无需使用金属催化剂。1,3-偶极环加成过程通过首先形成的异恶唑啉或异恶唑烷环加合物的碱基系统的嘧啶环的打开，降解或扩环，产生新的核苷类似物。
• Synthesis of 2,6-Dialkyl(aryl)purine Nucleosides by Exploiting the Reactivity of Nebularine<i>N</i>1-Oxide towards Grignard Reagents
  作者：Stefano D'Errico、Giorgia Oliviero、Nicola Borbone、Vincenzo Piccialli、Valentina D'Atri、Laura Mayol、Gennaro Piccialli

  DOI：10.1002/ejoc.201300941

  日期：2013.10

  The synthesis of 2,6-dialkyl(aryl)purine nucleosides by application of a double addition of Grignard reagents to N1-oxide purine nucleosides is described. The synthetic protocol exploits the reactivity of both the C6–N1–O– and C2–N1–O– moieties of the purine base. The overall process consists of initial Grignard reagent addition to the C6 of nebularine N1-oxide followed by aromatization to give a C6-substituted

  描述了通过将格利雅试剂双加成到 N1-氧化物嘌呤核苷上来合成 2,6-二烷基 (芳基) 嘌呤核苷。合成方案利用了嘌呤碱基的 C6-N1-O- 和 C2-N1-O- 部分的反应性。整个过程包括初始格氏试剂添加到 Nebularine N1-氧化物的 C6 中，然后芳构化得到 C6 取代的核苷。然后在 N1-氧化物再生之后在 C2 处进行第二次格氏加成，导致嘧啶环打开。然后通过系统的芳构化驱动瞬时打开的嘧啶的环化以提供最终的嘌呤系统。
• 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.