2',3',5'-tri-O-(tert-butyldimethylsilyl)-6-vinylnebularine | 188117-96-6

• 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: 2',3',5'-tri-O-(tert-butyldimethylsilyl)-6-vinylnebularine
• 英文别名: [(2R,3R,4R,5R)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-(6-ethenylpurin-9-yl)oxolan-2-yl]methoxy-tert-butyl-dimethylsilane
• CAS: 188117-96-6
• 化学式: C₃₀H₅₆N₄O₄Si₃
• 分子量: 621.056
• InChiKey: ZBNKVAAXKKKFBP-LYPBTDJXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.17
• 重原子数：
  41
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.77
• 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：

  2',3',5'-tri-O-(tert-butyldimethylsilyl)-6-vinylnebularine 在 四丁基氟化铵 、 palladium diacetate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.0h， 生成 trans-6-styryl-9β-D-ribofuranosyl-9H-purine
  参考文献：
  名称：

  Cytotoxic activity of 6-alkynyl- and 6-alkenylpurines

  摘要：

  6-Alkynyl- and 6-alkenylpurines have been screened for cytotoxic activity against a human chronic myelogenous leukemia cell line; K-562 cells using a [H-3]-thymidine incorporation assay. Most alkynes displayed cytotoxicity comparable to, or better than, the known anticancer drugs 6-mercaptopurine and fludarabine. The 6-alkenylpurines, which are promising plant growth stimulators and 15-lipoxygenase inhibitors, exhibited only low toxicity. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00011-8
• 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 2',3',5'-tri-O-(tert-butyldimethylsilyl)-6-vinylnebularine
  参考文献：
  名称：

  探查Nebularine N 1-oxide的反应性。C-6 C取代嘌呤核苷的新方法

  摘要：

  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。

  DOI：

  10.1016/j.tet.2011.06.080

文献信息

• 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。
• Cytostatic 6-Arylpurine Nucleosides. 6. SAR in Anti-HCV and Cytostatic Activity of Extended Series of 6-Hetarylpurine Ribonucleosides
  作者：Michal Hocek、Petr Nauš、Radek Pohl、Ivan Votruba、Phillip A. Furman、Phillip M. Tharnish、Michael J. Otto

  DOI：10.1021/jm050335x

  日期：2005.9.1

  Significant anti-HCV activity of 6-hetarylpurine ribonucleosides has been discovered and is reported here for the first time and compared with cytostatic effect. An extended series of 6-hetarylpurine ribonucleosides has been prepared by heterocyclizations in position 6 of purine nucleosides or by cross-couplings of 6-chloropurine nucleosides with hetarylboronic acids, -stannanes, or -zinc halides. The most anti-HCV active were purine ribonucleosides bearing pyrrol-3-yl (3k) or 2-furyl (3g) groups exerting EC90 = 0.14 and 0.4 mu M, respectively.
• Synthesis of diverse 6-(1,2-disubstituted ethyl)purine bases and nucleosides via 6-(oxiran-2-yl)purines
  作者：Martin Kuchař、Radek Pohl、Blanka Klepetářová、Michal Hocek

  DOI：10.1016/j.tet.2008.08.074

  日期：2008.11

  Dihydroxylation of 6-vinylpurines with t-BuOOH and OSO4 gave 6-(1,2-dihydroxyethyl)purines 2, while the epoxidation with H2WO4 and t-BuOOH afforded 6-(oxiran-2-yl)purines 3. Oxirane ring-opening reactions of 3 with diverse nucleophiles gave a series of title 6-(1,2-disubstituted ethyl)purine bases and nucleosides, which were tested for cytostatic and antiviral activities. (C) 2008 Published by Elsevier Ltd.
• Lewis acid mediated Diels-Alder reactions of 6-vinylpurines
  作者：Anniken T. Øver»s、Lise-Lotte Gundersen、Frode Rise

  DOI：10.1016/s0040-4020(96)01089-7

  日期：1997.2

  6-Vinylpurines readily undergo Diels-Alder reactions with dienes. Both reactivity and endo selectivity are greatly improved when the cycloadditions are performed in the presence of zinc chloride. Lewis acid mediated Diels-Alder reaction of 6-vinylpurine riboside was employed as a key step in the synthesis of a nucleoside with structural resemblance to potent A(1) adenosine agonists. (C) 1997, Elsevier Science Ltd.