1-(2,3,5-tri-O-acetyl-β-D-arabinofuranosyl)-5-<2-(trimethylsilyl)ethynyl>uracil | 88425-50-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 1-(2,3,5-tri-O-acetyl-β-D-arabinofuranosyl)-5-<2-(trimethylsilyl)ethynyl>uracil
• 英文别名: [(2R,3R,4S,5R)-3,4-diacetyloxy-5-[2,4-dioxo-5-(2-trimethylsilylethynyl)pyrimidin-1-yl]oxolan-2-yl]methyl acetate
• CAS: 88425-50-7
• 化学式: C₂₀H₂₆N₂O₉Si
• 分子量: 466.52
• InChiKey: SYOKKSUNHMPPIH-VXIBKDFQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.09
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  138
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-(2,3,5-tri-O-acetyl-β-D-arabinofuranosyl)-5-<2-(trimethylsilyl)ethynyl>uracil 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以81%的产率得到5-(2-trimethylsilylethynyl)arabinouridine
  参考文献：
  名称：

  5-Alkynyl Analogs of Arabinouridine and 2‘-Deoxyuridine:  Cytostatic Activity against Herpes Simplex Virus and Varicella-Zoster Thymidine Kinase Gene-Transfected Cells

  摘要：

  A group of arabinouridines (TMSEAU, EAU, IEAU-TA) and 2'-deoxyuridines (TMSEDU, EDU, IEDU) having a variety of substituents at the uracil C-5 position (trimethylsilylethynyl, TMSE; ethynyl, E; or iodoethynyl, IE), and the sugar C-2' position (2'-arabino OH in arabinouridine, AU; or 2'-deoxyribo H in 2'-deoxyuridine, DU) were prepared to acquire antiviral structure-activity relationships. A broad-spectrum viral panel screen showed that these 5-alkynylarabino/deoxy-uridines exhibit moderate anti-HSV-1 activity, with no difference in potency between arabinouridines and 2'-deoxyuridines. The 2'-deoxyuridines TMSEDU, EDU, and IEDU, unlike the arabinouridines, exhibited potent antiviral activity against cytomegalovirus, but they were also highly cytostatic. The abilities of the 5-alkynylarabino/deoxy-uridines to inhibit nontransfected (wild-type or thymidine kinase-deficient, tk(-)) and viral gene transfected (HSV-1, HSV-2, or VZV thymidine kinase-positive, tk(+)) FM3A and OST (osteosarcoma) cells were determined. This group of 5-alkynylarabino/deoxy-uridines showed an enhanced ability to inhibit cells transfected with a viral thymidine kinase gene (HSV-1tk(+), HSV-2tk(+), VZVtk(+)) relative to wild-type or thymidine kinase-deficient (tk(-)) cells.

  DOI：

  10.1021/jm0701472
• 作为产物：
  描述：

  1-(2,3,5-tri-O-acetyl-β-D-arabinofuranosyl)uracil 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 一氯化碘 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 23.0h， 生成 1-(2,3,5-tri-O-acetyl-β-D-arabinofuranosyl)-5-<2-(trimethylsilyl)ethynyl>uracil
  参考文献：
  名称：

  乙炔核苷。3.一些5-乙炔基嘧啶核苷的合成和生物活性。

  摘要：

  1-（2,3,5-三-O-乙酰基-β-D-阿拉伯呋喃糖基）尿嘧啶的碘化作用提供了5-碘代衍生物（Ib），该衍生物在催化量的四氢呋喃存在下用（三甲基甲硅烷基）乙炔处理（Ph3P）2PdCl2 / CuI和随后的脱保护，得到1-β-D-阿拉伯呋喃糖基-5-乙炔基尿嘧啶（Ie）。5-（二溴乙烯基）尿嘧啶的三甲基甲硅烷基衍生物与3-O-乙酰基-5-O-苯甲酰基-2-脱氧-2-叠氮基-D-阿拉伯呋喃糖基氯的缩合，然后用苯基锂处理，得到1-（2-脱氧-2-叠氮基-β-D-阿拉伯呋喃糖基）-5-乙炔基尿嘧啶（IIb）。3-O-乙酰基-5-O-苯甲酰基-2-脱氧-2-氟-D-阿拉伯呋喃糖基溴与5-乙炔基胞嘧啶的三甲基甲硅烷基衍生物缩合，随后除去保护基，得到1-（2-脱氧-2 -氟-β-D-阿拉伯呋喃糖基）-5-乙炔基胞嘧啶（IIIb）。通过NMR和ORD光谱确定IIb和IIIb的结构。化合物Ie和IIIb分别在1

  DOI：

  10.1021/jm00369a032

文献信息

• Conversion of vinylsilanes to vinyl halides with xenon difluoride and metal halides. A versatile new route to 5-(2-halovinyl)pyrimidine nucleosides
  作者：Morris J Robins、Stefano Manfredini

  DOI：10.1016/s0040-4039(00)97919-x

  日期：——

  Addition of a protected 5-(2-trimethylsilylvinyl)uracil nucleoside to suspensions of xenon difluoride and alkali metal halides in benzene (or other solvents) resulted in rapid formation of the corresponding 5-(2-halovinyl)uracil products (E-isomer predominating).

  在二氟化氙和碱金属卤化物在苯（或其他溶剂）中的悬浮液中添加受保护的5-（2-三甲基甲硅烷基乙烯基）尿嘧啶核苷可导致快速形成相应的5-（2-卤代乙烯基）尿嘧啶产物（E-异构体占主导地位）。
• Synthesis and Biological Evaluation of 6-(Alkyn-1-yl)furo[2,3<i>-d</i>]pyrimidin-2(3<i>H</i>)-one Base and Nucleoside Derivatives
  作者：Morris J. Robins、Karl Miranda、Vivek K. Rajwanshi、Matt A. Peterson、Graciela Andrei、Robert Snoeck、Erik De Clercq、Jan Balzarini

  DOI：10.1021/jm050867d

  日期：2006.1.1

  6-(alkyn-1-yl)furo[2,3-d]pyrimidin-2(3H)-ones in which the rodlike acetylene spacer replaces the 4-substituted-phenyl ring at C6. Analogues with methyl, beta-d-ribofuranosyl, beta-d-arabinofuranosyl, and 2-deoxy-beta-d-erythro-pentofuranosyl substituents at N3 have been prepared. Long-chain derivatives at C6 in the 2'-deoxynucleoside series showed virus-encoded nucleoside kinase-sensitive anti-VZV activity. Surprisingly

  在C6处带有长链烷基（或4-烷基苯基）取代基的呋喃[2,3-d]嘧啶-2（3H）-one的2'-脱氧核苷衍生物显示出显着的抗VZV（水痘带状疱疹病毒）效力和选择性，以及类似的2'，3'-二脱氧核苷衍生物显示出抗HCMV（人类巨细胞病毒）活性。我们现在报告一种合成方法，该方法能够制备长链6-（炔基-1-基）呋喃并[2,3-d]嘧啶-2（3H）-，其中棒状乙炔间隔基取代了4-取代基-在C6的苯环。已经制备了在N 3处具有甲基，β-d-呋喃呋喃糖基，β-d-阿拉伯呋喃糖基和2-脱氧β-d-赤-戊呋喃糖基取代基的类似物。2'-脱氧核苷系列中C6处的长链衍生物显示病毒编码的核苷激酶敏感的抗VZV活性。令人惊讶的是，3-甲基-6-（辛基-1-基）呋喃[2，
• Nucleic acid related compounds. 65. New syntheses of 1-(.beta.-D-arabinofuranosyl)-5(E)-(2-iodovinyl)uracil (IVAraU) from vinylsilane precursors. Radioiodine uptake as a marker for thymidine kinase herpes viral infections
  作者：Morris J. Robins、Stefano Manfredini、Steven G. Wood、R. James Wanklin、Bruce A. Rennie、Stephen L. Sacks

  DOI：10.1021/jm00111a050

  日期：1991.7

  4-tri-O-acetyl-beta-D-arabinofuranosyl)-5(Z)-[2- (trimethylsilyl)vinyl]uracil. Treatment of 5 with iodine monochloride (or sodium iodide/phenyliodine(III) dichloride) in benzene gave 1-(2,3,5-tri-O-acetyl-beta-D-arabinofuranosyl)-5(E)-(2-iodovinyl)uracil (7), whereas polar solvents favored the (Z)-iodovinyl isomer 8. Deacetylation of 7 gave 1-(beta-D-arabinofuranosyl)-5(E)-(2-iodovinyl)uracil (IVAraU, 9). A microscale

  将（三甲基甲硅烷基）乙炔与1-（2,3,5-三-O-乙酰基-β-D-阿拉伯呋喃糖基）-5-碘尿嘧啶偶联，得到1-（2,3,5-三-O-乙酰基-β -D-阿拉伯呋喃糖基）-5- [2-（三甲基甲硅烷基）乙氧基]尿嘧啶。4的Lindlar氢化得到1-（2,3,4-三-O-乙酰基-β-D-阿拉伯呋喃糖基）-5（Z）-[2-（三甲基甲硅烷基）乙烯基]尿嘧啶。用苯中的一氯化碘（或碘化钠/二氯化苯基碘（III））处理5，得到1-（2,3,5-三-O-乙酰基-β-D-阿拉伯呋喃糖基）-5（E）-（2-碘乙烯基）尿嘧啶（7），而极性溶剂偏爱（Z）-碘乙烯基异构体8 。用Na * I进行的微型原位合成得到[* I] IVAraU。用[125I] IVAraU处理被HSV感染的细胞会导致病毒依赖性摄取，与野生型或抗阿昔洛韦的DNA聚合酶突变体（但不包括TK-HSV-1突变体）的核苷磷酸化有关。摄取是病毒-菌落
• Synthesis of (<i>E</i>)-5-(2-Radioiodovinyl)arabinosyl Uridine Analog for Probing HSV-1 Thymidine Kinase Gene
  作者：Chung-Shan Yu、Chien-Hung Wu、Li-Wu Chiang、Ren-Tsong Wang、Heng-Yen Wang、Chien-Hung Yeh、Kun-I Lin

  DOI：10.1246/cl.2005.1390

  日期：2005.10

  genetic probe labeled with positron emitter for monitoring tumor cells transfacted by herpes simplex virus thymidine kinase gene has been intensively studied. A useful synthetic methodology was developed to synthesize(E)-5-[2-(tributyl-stannyl)vinyl]arabinosyl uridine (TSVAU) and to radiolabel (E)-5-2-[ 1 2 5 I]iodovinyl}arabinosyl uridine (IVAU) substrate for herpes simplex virus type-1 thymidine kinase

  正电子发射体标记的基因探针用于监测单纯疱疹病毒胸苷激酶基因转染的肿瘤细胞已得到深入研究。开发了一种有用的合成方法来合成 (E)-5-[2-(三丁基-甲锡烷基) 乙烯基] 阿拉伯糖基尿苷 (TSVAU) 和放射性标记 (E)-5-2-[ 1 2 5 I] 碘乙烯基}阿拉伯糖基单纯疱疹病毒 1 型胸苷激酶基因的尿苷 (IVAU) 底物。合成从阿拉伯糖尿苷开始，经过六个步骤，以 18% 的产率提供 TSVAU。随后在氧化下用 Na-[ 1 2 5 I]I 进行放射性标记以 80% 的放射化学产率提供 [ 1 2 5 I]IVAU。
• ROBINS, MORRIS J.;MANFREDINI, STEFANO, TETRAHEDRON. LETT., 31,(1990) N9, C. 5633-5636
  作者：ROBINS, MORRIS J.、MANFREDINI, STEFANO

  DOI：——

  日期：——