[1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-(methyl)thymine]-3'-spiro-5''-(4''-benzyloxycarbonylethylamino-1'',2''-oxathiole-2'',2''-dioxide) | 848417-26-5

• 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''-benzyloxycarbonylethylamino-1'',2''-oxathiole-2'',2''-dioxide)
• 英文别名: benzyl 3-[[(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]propanoate；benzyl 3-[[(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]propanoate
• CAS: 848417-26-5
• 化学式: C₃₅H₅₅N₃O₁₀SSi₂
• 分子量: 766.073
• InChiKey: PZBOXGPUGKTJHD-PLAIFVNNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.83
• 重原子数：
  51
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  158
• 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''-benzyloxycarbonylethylamino-1'',2''-oxathiole-2'',2''-dioxide) 在 palladium on activated charcoal 氨 、 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， -20.0~30.0 ℃ 、206.84 kPa 条件下， 反应 1.0h， 生成 [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-(methyl)thymine]-3'-spiro-5''-(4''-carbamoylethylamino-1'',2''-oxathiole-2'',2''-dioxide)
  参考文献：
  名称：

  Novel [2‘,5‘-Bis-O-(tert-butyldimethylsilyl)-β-d-ribofuranosyl]- 3‘-spiro-5‘ ‘-(4‘ ‘-amino-1‘ ‘,2‘ ‘-oxathiole-2‘ ‘,2‘ ‘-dioxide) Derivatives with Anti-HIV-1 and Anti-Human-Cytomegalovirus Activity

  摘要：

  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.

  DOI：

  10.1021/jm040868q
• 作为产物：
  描述：

  <1-(β-D-ribofuranosyl)thymine>-3'-spiro-5''-<4''-amino-1'',2''-oxathiole 2'',2''-dioxide> 在 4-二甲氨基吡啶 、 potassium carbonate 、 1-chloro-3-hydroxy-1,1,3,3-tetrabutyldistannoxane 作用下， 以 甲醇 、 丙酮 、 甲苯 、 乙腈 为溶剂， 反应 269.0h， 生成 [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-(methyl)thymine]-3'-spiro-5''-(4''-benzyloxycarbonylethylamino-1'',2''-oxathiole-2'',2''-dioxide)
  参考文献：
  名称：

  Novel [2‘,5‘-Bis-O-(tert-butyldimethylsilyl)-β-d-ribofuranosyl]- 3‘-spiro-5‘ ‘-(4‘ ‘-amino-1‘ ‘,2‘ ‘-oxathiole-2‘ ‘,2‘ ‘-dioxide) Derivatives with Anti-HIV-1 and Anti-Human-Cytomegalovirus Activity

  摘要：

  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.

  DOI：

  10.1021/jm040868q

文献信息

• 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.