1-<2',3'-dideoxy-3'(R)-phenylseleno-β-D-glycero-pentofuranosyl>thymine | 131933-47-6

• 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'-dideoxy-3'(R)-phenylseleno-β-D-glycero-pentofuranosyl>thymine
• 英文别名: 1-(2,3-dideoxy-3-C-selenophenyl-β-D-threo-pentofuranosyl)thymine；3'-β-(phenylselenyl)-3'-deoxythymidine；1-[(2R,4R,5R)-5-(hydroxymethyl)-4-phenylselanyl-tetrahydrofuran-2-yl]-5-methyl-pyrimidine-2,4-dione；1-[(2R,4R,5R)-5-(hydroxymethyl)-4-phenylselanyloxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 131933-47-6
• 化学式: C₁₆H₁₈N₂O₄Se
• 分子量: 381.29
• InChiKey: KQQMAWGZCDIFDY-MGPQQGTHSA-N

物化性质

• 熔点：
  176-178 °C

计算性质

• 辛醇/水分配系数(LogP)：
  -0.06
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-<2',3'-dideoxy-3'(R)-phenylseleno-β-D-glycero-pentofuranosyl>thymine 在 双氧水 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 以99%的产率得到司他夫定
  参考文献：
  名称：

  Selenium nucleophiles for the preparation of antiviral nucleosides

  摘要：

  The reactivity of nucleophilic selenium species toward nucleoside derivatives has been examined. A number of new 2'-deoxyribose nucleosides have been synthesized using this methodology. The cis elimination of the selenoxide obtained from the oxidation of the corresponding phenylselenide has been shown to be an efficient method for the preparation of the 2',3'-unsaturated antiviral nucleoside 1-(2,3-dideoxy-beta-D-glycero-pent-2-enofuranosyl)thymine (DAT).

  DOI：

  10.1021/jo00006a037
• 作为产物：
  描述：

  3'-O-(methylsulfonyl)-5'-O-(4,4'-dimethoxytrityl)-thymidine 在 lithium aluminium tetrahydride 、 水 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 1-<2',3'-dideoxy-3'(R)-phenylseleno-β-D-glycero-pentofuranosyl>thymine
  参考文献：
  名称：

  C3'修饰核苷的合成，用于选择性生成C3'-Deoxy-3'-胸苷基自由基：LEE诱导DNA损伤的拟议中间体

  摘要：

  据信由低能电子（LEE）诱导的DNA损伤途径涉及2-脱氧核糖自由基的形成。这些自由基形成在核苷酸的C3'和C5'位置，是通过将LEEs从核碱基转移至DNA寡聚体的磷酸基团而裂解C–O磷酸二酯键的结果。已经获得了大量信息，以阐明通过该过程形成的未修饰寡核苷酸产物的身份。然而，关于由这些糖基的降解形成的修饰病变的性质的信息很少。确定通过2'，3'-二脱氧-C3'-胸苷基（C3'dephos糖自由基），苯基硒化物和酰基修饰的糖以及核苷衍生物已经合成，并且已经评估了它们作为目标自由基的光化学前体的适用性。在存在氢原子供体三丁基锡氢化物的情况下，对C3'衍生的核苷进行光化学活化后，形成2'，3'-二脱氧胸苷，表明选择性生成了C3'磷酸基团。这些前体将使鉴定和量化由LEEs产生的自由基引起的DNA损伤的产物成为可能。

  DOI：

  10.1021/jo300045m

文献信息

• Synthesis of furo[2,3-c]pyran-β-d-nucleosides by radical-cyclization &amp; their conformational analysis by 500 mhz 1h-nmr spectroscopy
  作者：Zhen Xi、Peter Agback、Anders Sandström、Jyoti Chattopadhyaya

  DOI：10.1016/s0040-4020(01)91032-4

  日期：1991.11

  precursor 10 – 12, under an identical reaction condition, gave [3.4.0]-cis-fused δ-lactones 13 – 15 in 10–53% yields without any trace of reduced products. The synthesis of [3.4.0]-cis-fused furo-pyrans 6 – 9 from 4-oxo-6-heptenyl radical formed from the precursor 2 – 5 and the transformations of 10 – 12 to δ-lactones 13 – 15, respectively, constitute first example of intramolecular 6-exo radical cyclization

  自由基，从3'- phenylseleno核苷生成作为自由基前体2 - 5，被有效通过烯烃分子内捕获或通过醚函数从5'-末端锚定炔funtion，得到各种[3.4.0] -顺式融合的呋喃[2,3-c]吡喃6 – 9（16–34％），以及一些还原产物（<10％）。用5'-O-α类似的分子内自由基捕获反应，β-酯连接的自由基前体10 - 12中，相同的反应条件下，得到[3.4.0] -顺式稠合δ内酯13 - 15在10-收率53％，没有任何还原的产物。[3.4.0]-顺式呋喃吡喃的合成6- 9从由前体形成的4-氧代-6-庚烯基自由基2 - 5和的变换10 - 12〜δ内酯13 - 15，分别构成的分子内6-外切涉及亲核攻击自由基环化反应第一示例环内自由基对缺电子的环外不饱和链的影响 δ-内酯14和15平滑转化为开环C支链赤型衍生物16（95％）和17（94％）分别用稀氨水处理后，提供了一种通过
• 3′-Modified oligodeoxyribonucleotides for the study of 2-deoxyribose damage in DNA
  作者：Buthina Al-Oudat、Alex Salyer、Kevin Trabbic、Amanda Bryant-Friedrich

  DOI：10.1016/j.bmcl.2012.11.050

  日期：2013.2

  Well-defined substrates for the study of oxidative processes are important for the elucidation of the role of DNA damage in the etiology of diseases such as cancer. We have synthesized 3'-modified oligodeoxyribonucleotides (ODNs) using 5' -> 3' 'reverse' DNA synthesis for the study of 2-deoxyribose oxidative damage to DNA. The modified monomers designed for these studies all share a common feature, they lack the naturally occurring 3'-hydroxyl group found in 2-deoxyribonucleosides. Modified H-phosphonates containing 3'-phenyl selenides as well as saturated and unsaturated sugars were obtained and incorporated in ODNs. These ODNs were used to investigate the fate of C3'-dideoxyribonucleotide radicals in DNA. (c) 2012 Elsevier Ltd. All rights reserved.
• COSFORD, NICHOLAS D. P.;SCHINAZI, RAYMOND F., J. ORG. CHEM., 56,(1991) N, C. 2161-2165
  作者：COSFORD, NICHOLAS D. P.、SCHINAZI, RAYMOND F.

  DOI：——

  日期：——
• Synthesis of C3′ Modified Nucleosides for Selective Generation of the C3′-Deoxy-3′-thymidinyl Radical: A Proposed Intermediate in LEE Induced DNA Damage
  作者：Suaad A. S. Audat、CherylAnn Trzasko Love、Buthina A. S. Al-Oudat、Amanda C. Bryant-Friedrich

  DOI：10.1021/jo300045m

  日期：2012.4.20

  3′-dideoxy-C3′-thymidinyl radical (C3′dephos sugar radical), phenyl selenide and acyl modified sugar and nucleoside derivatives have been synthesized, and their suitability as photochemical precursors of the radical of interest has been evaluated. Upon photochemical activation of C3′-derivatized nucleosides in the presence of the hydrogen atom donor tributyltin hydride, 2′,3′-dideoxythymidine is formed

  据信由低能电子（LEE）诱导的DNA损伤途径涉及2-脱氧核糖自由基的形成。这些自由基形成在核苷酸的C3'和C5'位置，是通过将LEEs从核碱基转移至DNA寡聚体的磷酸基团而裂解C–O磷酸二酯键的结果。已经获得了大量信息，以阐明通过该过程形成的未修饰寡核苷酸产物的身份。然而，关于由这些糖基的降解形成的修饰病变的性质的信息很少。确定通过2'，3'-二脱氧-C3'-胸苷基（C3'dephos糖自由基），苯基硒化物和酰基修饰的糖以及核苷衍生物已经合成，并且已经评估了它们作为目标自由基的光化学前体的适用性。在存在氢原子供体三丁基锡氢化物的情况下，对C3'衍生的核苷进行光化学活化后，形成2'，3'-二脱氧胸苷，表明选择性生成了C3'磷酸基团。这些前体将使鉴定和量化由LEEs产生的自由基引起的DNA损伤的产物成为可能。
• Selenium nucleophiles for the preparation of antiviral nucleosides
  作者：Nicholas D. P. Cosford、Raymond F. Schinazi

  DOI：10.1021/jo00006a037

  日期：1991.3

  The reactivity of nucleophilic selenium species toward nucleoside derivatives has been examined. A number of new 2'-deoxyribose nucleosides have been synthesized using this methodology. The cis elimination of the selenoxide obtained from the oxidation of the corresponding phenylselenide has been shown to be an efficient method for the preparation of the 2',3'-unsaturated antiviral nucleoside 1-(2,3-dideoxy-beta-D-glycero-pent-2-enofuranosyl)thymine (DAT).