6-chloro-9-[2,3,5-tri-O-(4-methylbenzoyl)-β-D-ribofuranosyl]purine | 756494-14-1

• 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-chloro-9-[2,3,5-tri-O-(4-methylbenzoyl)-β-D-ribofuranosyl]purine
• 英文别名: [(2R,3R,4R,5R)-5-(6-chloropurin-9-yl)-3,4-bis[(4-methylbenzoyl)oxy]oxolan-2-yl]methyl 4-methylbenzoate
• CAS: 756494-14-1
• 化学式: C₃₄H₂₉ClN₄O₇
• 分子量: 641.08
• InChiKey: CRCWHGSWLUWZIH-QWOIFIOOSA-N

物化性质

• 熔点：
  149-151 °C(Solvent: Ethanol)
• 沸点：
  789.7±70.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  46
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  132
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  6-chloro-9-[2,3,5-tri-O-(4-methylbenzoyl)-β-D-ribofuranosyl]purine 在 4-二甲氨基吡啶 、 ammonium hydroxide 、 三甲基氯硅烷 、 三乙胺 、 zinc(II) chloride 、 锌 、 二溴甲烷 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 11.0h， 生成 6-(methanesulfonyloxymethyl)-9-(2,3,5-tri-O-(p-toluoyl)-β-D-ribofuranosyl)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：

  2',3',5'-tri-O-(4-methylbenzoyl)inosine 在 苄基三乙基氯化铵 、 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 0.17h， 以85%的产率得到6-chloro-9-[2,3,5-tri-O-(4-methylbenzoyl)-β-D-ribofuranosyl]purine
  参考文献：
  名称：

  S_NAr Iodination of 6-Chloropurine Nucleosides:  Aromatic Finkelstein Reactions at Temperatures Below −40 °C¹

  摘要：

  Mesitoyl or toluoyl esters of inosine and 2'-deoxyinosine were deoxychlorinated at C6 to give the crystalline 6-chloropurine nucleoside derivatives, which underwent quantitative conversion to the 6-iodo analogues with Nal/TFA/butanone at -50 to -40 degreesC. The 6-iodo compounds were efficient substrates for SNAr, Sonogashira, and Suzuki-Miyaura reactions, in contrast with the 6-chloro analogues, and gave good to high yields of C-N and C-C coupled products.

  DOI：

  10.1021/ol048987n

文献信息

• Synthesis, cytostatic, and antiviral activity of novel 6-[2-(dialkylamino)ethyl]-, 6-(2-alkoxyethyl)-, 6-[2-(alkylsulfanyl)ethyl]-, and 6-[2-(dialkylamino)vinyl]purine nucleosides
  作者：Martin Kuchař、Michal Hocek、Radek Pohl、Ivan Votruba、I-hung Shih、Eric Mabery、Richard Mackman

  DOI：10.1016/j.bmc.2007.10.063

  日期：2008.2.1

  An efficient and facile synthesis of a large series of diverse 6-[2-(dialkylamino)vinyl]-, 6-[2-(dialkylamino)ethyl]-, 6-(2-alkoxyethyl)-, and 6-[2-(alkylsulfanyl)ethyl]purine nucleosides (35 examples of both ribo- and 2'-deoxyribonucleosides) was developed. The key transformations involved conjugate nucleophilic additions of amines, alcoholates, or thiolates to Tol-protected 6-alkylylpurine or 6-vinylpurine

  一种高效且简便的合成方法，可合成多种多样的6- [2-（二烷基氨基）乙烯基]-，6- [2-（二烷基氨基）乙基]-，6-（2-烷氧基乙基）-和6- [2- （烷基硫烷基）乙基]嘌呤核苷（核糖-和2'-脱氧核糖核苷均有35个实例）。关键转化涉及将胺，醇化物或硫醇化物共轭亲核加成到Tol保护的6-烷基烷基嘌呤或6-乙烯基嘌呤核苷上。6-[（2-二烷基氨基）乙烯基]-和一些6-[（2-二烷基氨基）乙基]嘌呤核糖核苷以低选择性发挥了显着的细胞抑制作用和一些抗HCV活性。
• Synthesis of substituted 6-cyclopropylpurine bases and nucleosides by cross-coupling reactions or cyclopropanations
  作者：Martin Kuchař、Radek Pohl、Blanka Klepetářová、Ivan Votruba、Michal Hocek

  DOI：10.1039/b802833h

  日期：——

  Synthesis of novel purine bases and nucleosides bearing unsubstituted or substituted cyclopropyl rings in position 6 is reported. Unsubstituted 6-cyclopropylpurines were efficiently prepared by cross-coupling reactions of 6-chloropurines with cyclopropylzinc chloride. 6-Vinylpurines underwent Cu-mediated cyclopropanations with ethyl diazoacetate to give 6-[(ethoxycarbonyl)cyclopropyl]purines that were

  报道了在位置6上带有未取代或取代的环丙基环的新型嘌呤碱基和核苷的合成。通过6-氯嘌呤与氯化环丙基锌的交叉偶联反应，可以有效地制备未取代的6-环丙基嘌呤。对6-乙烯基嘌呤用重氮乙酸乙酯进行Cu介导的环丙烷化，得到6-[[（乙氧羰基）环丙基]嘌呤，将其进一步转化为羧酸，酰胺和醇。6-环丙基嘌呤核糖核苷具有显着的细胞抑制作用，而所有取代的衍生物均无活性。
• Synthesis of (purin-6-yl)acetates and their transformations to 6-(2-hydroxyethyl)- and 6-(carbamoylmethyl)purines
  作者：Zbyněk Hasník、Radek Pohl、Blanka Klepetářová、Michal Hocek

  DOI：10.1135/cccc2009042

  日期：——

  A novel approach to the synthesis of (purin-6-yl)acetates was developed based on Pd-catalyzed cross-coupling reactions of 6-chloropurines with a Reformatsky reagent. Their reduction with NaBH₄ and treatment with MnO₂ gave 6-(2-hydroxyethyl)purines, while reactions with amines in presence of NaCN afforded 6-(carbamoylmethyl)purines. Mesylation of the 6-(2-hydroxyethyl)purines followed by nucleophilic substitutions gave rise to several 6-(2-substituted ethyl)purines. This methodology was successfully applied to the synthesis of substituted purine bases and nucleosides for cytostatic and antiviral activity screening. None of the compounds exerted significant activity.

  基于Pd催化的6-氯嘌呤与Reformatsky试剂的交叉偶联反应，开发了一种合成(purin-6-yl)乙酸酯的新方法。它们经过NaBH₄还原和MnO₂处理后，形成6-(2-羟乙基)嘌呤，而与胺在NaCN存在下反应则得到6-(carbamoylmethyl)嘌呤。6-(2-羟乙基)嘌呤的Mesylation后，进行亲核取代反应，可以得到多种6-(2-取代乙基)嘌呤。这种方法成功地应用于合成替代嘌呤碱基和核苷，用于细胞毒和抗病毒活性筛选。但是，这些化合物均未表现出显著的活性。
• Fluoro, Alkylsulfanyl, and Alkylsulfonyl Leaving Groups in Suzuki Cross-Coupling Reactions of Purine 2‘-Deoxynucleosides and Nucleosides
  作者：Jiangqiong Liu、Morris J. Robins

  DOI：10.1021/ol050063s

  日期：2005.3.1

  [GRAPHICS]Protected 2'-deoxynucleoside and nucleoside derivatives of 6-fluoropurine, 6-(3-methylbutyl)sulfanylpurine, and 6-(3-methylbutyl)ylsulfonyipurine undergo nickel- or palladium-mediated C-C cross-coupling with arylboronic acids to give good yields of 6-arylpurine products.
• S_NAr Iodination of 6-Chloropurine Nucleosides:  Aromatic Finkelstein Reactions at Temperatures Below −40 °C¹
  作者：Jiangqiong Liu、Zlatko Janeba、Morris J. Robins

  DOI：10.1021/ol048987n

  日期：2004.8.1

  Mesitoyl or toluoyl esters of inosine and 2'-deoxyinosine were deoxychlorinated at C6 to give the crystalline 6-chloropurine nucleoside derivatives, which underwent quantitative conversion to the 6-iodo analogues with Nal/TFA/butanone at -50 to -40 degreesC. The 6-iodo compounds were efficient substrates for SNAr, Sonogashira, and Suzuki-Miyaura reactions, in contrast with the 6-chloro analogues, and gave good to high yields of C-N and C-C coupled products.