[1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-(methyl)thymine]-3'-spiro-5''-(4''-methoxalylamino-1'',2''-oxathiole-2'',2''-dioxide) | 378748-02-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-(methyl)thymine]-3'-spiro-5''-(4''-methoxalylamino-1'',2''-oxathiole-2'',2''-dioxide)
• 英文别名: methyl 2-[[(5R,6R,8R,9R)-9-[tert-butyl(dimethyl)silyl]oxy-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-8-(3,5-dimethyl-2,4-dioxopyrimidin-1-yl)-2,2-dioxo-1,7-dioxa-2lambda6-thiaspiro[4.4]non-3-en-4-yl]amino]-2-oxoacetate；methyl 2-[[(5R,6R,8R,9R)-9-[tert-butyl(dimethyl)silyl]oxy-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-8-(3,5-dimethyl-2,4-dioxopyrimidin-1-yl)-2,2-dioxo-1,7-dioxa-2λ6-thiaspiro[4.4]non-3-en-4-yl]amino]-2-oxoacetate
• CAS: 378748-02-8
• 化学式: C₂₈H₄₇N₃O₁₁SSi₂
• 分子量: 689.932
• InChiKey: IHSFHWYSYUNOGQ-GESRNHSJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.39
• 重原子数：
  45
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  176
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-(methyl)thymine]-3'-spiro-5''-(4''-methoxalylamino-1'',2''-oxathiole-2'',2''-dioxide) 在 水 作用下， 以 二甲基亚砜 为溶剂， 反应 2.0h， 以80%的产率得到methyl 2-[[(5R,6R,8R,9R)-9-[tert-butyl(dimethyl)silyl]oxy-8-(3,5-dimethyl-2,4-dioxopyrimidin-1-yl)-6-(hydroxymethyl)-2,2-dioxo-1,7-dioxa-2lambda6-thiaspiro[4.4]non-3-en-4-yl]amino]-2-oxoacetate
  参考文献：
  名称：

  5'-的前所未有的不稳定性ø -叔从3'-螺-5'丁基二甲硅烷基组' - （4' ' -酰基-1' '2' '-oxathiole-2''，2' “二氧化物）通过4''-酰氨基残基的邻近基团参与的核苷衍生物

  摘要：

  叔胺的温和去甲硅烷基化的稀有例子先前已经描述了丁基二甲基甲硅烷基（TBDMS）醚基团通过相邻基团的参与。在这里，我们将详细研究在DMSO溶液中5'-TBDMS基团对4''-酰基氨基TSAO衍生物的不寻常不稳定性的发现。报道了具有不同羰基官能度的各种4''-取代的TSAO衍生物在不同溶剂中的合成和比较化学稳定性研究。还已在TSAO分子的5'-位进行了修饰，以深入了解发生脱甲硅烷基化的结构要求。还研究了溶剂的作用。此外，已经进行了NMR和理论研究，以进一步了解构象，几何，和/或可能在5'-TBDMS组的“自发”释放中起作用的电子参数。提出了涉及4''-酰基氨基的相邻基团参与的甲硅烷基水解机理。

  DOI：

  10.1021/jo0520588
• 作为产物：
  描述：

  甲基戊酰氯 、 1-[(5R,6R,7R,9R)-4-氨基-6-(叔丁基-二甲基硅烷基)氧基-9-[(叔丁基-二甲基硅烷基)氧基甲基]-2,2-二氧代-1,8-二氧杂-2lambda6-硫杂螺[4.4]壬-3-烯-7-基]-3,5-二甲基嘧啶-2,4-二酮 在 三乙胺 作用下， 生成 [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-(methyl)thymine]-3'-spiro-5''-(4''-methoxalylamino-1'',2''-oxathiole-2'',2''-dioxide)
  参考文献：
  名称：

  Novel TSAO Derivatives Modified at Positions 3′ and 4′ Of the Spiro Moiety

  摘要：

  We have explored the introduction of different functional groups at positions 3 " and 4 " of the spiro moiety of TSAO-T. Alkylation of this spiro moiety afforded mixtures of N and/or C-alkylated derivatives, while acylation occurs, exclusively, on the amino group. Position 3 " has been selectively functionalized by halogenation followed by Stille-cross coupling reaction with organostannanes under a variety of experimental conditions.

  DOI：

  10.1080/15257779908041536

文献信息

• Unusual Lability of 5′-<i>O</i>-<i>tert</i>-Butyldimethylsilyl Group On 4″-Acyl TSAO Derivatives
  作者：Sonia de Castro、María-Jesús Pérez-Pérez、Esther Lobatón、Erik De Clercq、Jan Balzarini、María-José Camarasa、Sonsoles Velázquez

  DOI：10.1081/ncn-120022695

  日期：2003.10
• Novel [2‘,5‘-Bis-<i>O-</i>(<i>tert-</i>butyldimethylsilyl)-β-<scp>d</scp>-ribofuranosyl]- 3‘-spiro-5‘ ‘-(4‘ ‘-amino-1‘ ‘,2‘ ‘-oxathiole-2‘ ‘,2‘ ‘-dioxide) Derivatives with Anti-HIV-1 and Anti-Human-Cytomegalovirus Activity
  作者：Sonia de Castro、Esther Lobatón、María-Jesús Pérez-Pérez、Ana San-Félix、Alessandra Cordeiro、Graciela Andrei、Robert Snoeck、Erik De Clercq、Jan Balzarini、María-José Camarasa、Sonsoles Velázquez

  DOI：10.1021/jm040868q

  日期：2005.2.1

  New [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro-5"-(4"-amino-1",2"-oxathiole-2",2"-dioxide) (TSAO) derivatives substituted at the 4"-amino group of the spiro moiety with different carbonyl functionalities have been designed and synthesized. Various synthetic procedures, on the scarcely studied reactivity of the 3'-spiroaminooxathioledioxide moiety, have been explored. The compounds were evaluated for their inhibitory effect on both wild-type and TSAO-resistant HIV-1 strains, in cell culture. The presence of a methyl ester (10) or amide groups (12) at the 4"-position conferred the highest anti-HIV-1 activity, while the free oxalyl acid derivative (11) was 10- to 20-fold less active against the virus. In contrast, the presence at this position of (un)substituted ureido or acyl groups markedly diminished or annihilated the anti-HIV-1 activity. Surprisingly, some of the target compounds also showed inhibition of human cytomegalovirus (HCMV) replication at subtoxic concentrations. This has never been observed previously for TSAO derivatives. In particular, compound 26 represents the first TSAO derivative with dual anti-HIV-1 and -HCMV activity.
• “SECOND GENERATION” OF TSAO COMPOUNDS DIRECTED AGAINST HIV-1 TSAO-RESISTANT STRAINS
  作者：E. Lobatón、S. Velázquez、M. J. Pérez-Pérez、M. L. Jimeno、A. San-Félix、E. De Clercq、J. Balzarini、M. J. Camarasa

  DOI：10.1081/ncn-100002356

  日期：2001.3.31

  A "second generation" of TSAO molecules directed against TSAO-resistant strains have been prepared. The presence of two neighboring carbonyl groups at the 4 " position of the 3'-spiro moiety seems to be important for the anti-HIV-1 activity against both wild type and TSAO-resistant strains. NMR conformational studies in solution and theoretical calculations of the novel compounds have also been carried out.
• Unprecedented Lability of the 5‘-<i>O</i>-<i>tert</i>-Butyldimethylsilyl Group from 3‘-Spiro-5‘ ‘-(4‘ ‘-acylamino-1‘ ‘,2‘ ‘-oxathiole-2‘ ‘,2‘ ‘-dioxide) Nucleoside Derivatives via Neighboring Group Participation of the 4‘ ‘-Acylamino Residue
  作者：Sonia de Castro、Angel Lozano、María-Luisa Jimeno、María-Jesús Pérez-Pérez、Ana San-Félix、María-José Camarasa、Sonsoles Velázquez

  DOI：10.1021/jo0520588

  日期：2006.2.1

  detail, the discovery of the unusual lability of the 5‘-TBDMS group on 4‘ ‘-acylamino TSAO derivatives in DMSO solution. The synthesis and comparative chemical stability studies in different solvents of a variety of 4‘ ‘-substituted TSAO derivatives bearing different carbonyl functionalities are reported. Modifications have also been performed at the 5‘-position of the TSAO molecule to gain insight into

  叔胺的温和去甲硅烷基化的稀有例子先前已经描述了丁基二甲基甲硅烷基（TBDMS）醚基团通过相邻基团的参与。在这里，我们将详细研究在DMSO溶液中5'-TBDMS基团对4''-酰基氨基TSAO衍生物的不寻常不稳定性的发现。报道了具有不同羰基官能度的各种4''-取代的TSAO衍生物在不同溶剂中的合成和比较化学稳定性研究。还已在TSAO分子的5'-位进行了修饰，以深入了解发生脱甲硅烷基化的结构要求。还研究了溶剂的作用。此外，已经进行了NMR和理论研究，以进一步了解构象，几何，和/或可能在5'-TBDMS组的“自发”释放中起作用的电子参数。提出了涉及4''-酰基氨基的相邻基团参与的甲硅烷基水解机理。
• Novel TSAO Derivatives Modified at Positions 3′ and 4′ Of the Spiro Moiety
  作者：E. Lobatón、S. Velázquez、A. San-Félix、C. Chamorro、V. Tuñón、A. Esteban-gamboa、E. De Clercq、J. Balzarini、M. J. Camarasa、M. J. Pérez-Pérez

  DOI：10.1080/15257779908041536

  日期：1999.4

  We have explored the introduction of different functional groups at positions 3 " and 4 " of the spiro moiety of TSAO-T. Alkylation of this spiro moiety afforded mixtures of N and/or C-alkylated derivatives, while acylation occurs, exclusively, on the amino group. Position 3 " has been selectively functionalized by halogenation followed by Stille-cross coupling reaction with organostannanes under a variety of experimental conditions.