3-[(5R,6R,8R,9R)-9-(tert-Butyl-dimethyl-silanyloxy)-6-(tert-butyl-dimethyl-silanyloxymethyl)-8-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-2,2-dioxo-1,7-dioxa-2λ⁶-thia-spiro[4.4]non-3-en-4-ylamino]-propionic acid methyl ester | 1054662-17-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-[(5R,6R,8R,9R)-9-(tert-Butyl-dimethyl-silanyloxy)-6-(tert-butyl-dimethyl-silanyloxymethyl)-8-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-2,2-dioxo-1,7-dioxa-2λ⁶-thia-spiro[4.4]non-3-en-4-ylamino]-propionic acid methyl ester
• 英文别名: methyl 3-[[(5R,6R,8R,9R)-9-[tert-butyl(dimethyl)silyl]oxy-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-8-(5-methyl-2,4-dioxopyrimidin-1-yl)-2,2-dioxo-1,7-dioxa-2lambda6-thiaspiro[4.4]non-3-en-4-yl]amino]propanoate；methyl 3-[[(5R,6R,8R,9R)-9-[tert-butyl(dimethyl)silyl]oxy-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-8-(5-methyl-2,4-dioxopyrimidin-1-yl)-2,2-dioxo-1,7-dioxa-2λ6-thiaspiro[4.4]non-3-en-4-yl]amino]propanoate
• CAS: 1054662-17-7
• 化学式: C₂₈H₄₉N₃O₁₀SSi₂
• 分子量: 675.948
• InChiKey: MIVITPNIHGFBRS-ZXAUVLDCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.25
• 重原子数：
  44
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  167
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  3-[(5R,6R,8R,9R)-9-(tert-Butyl-dimethyl-silanyloxy)-6-(tert-butyl-dimethyl-silanyloxymethyl)-8-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-2,2-dioxo-1,7-dioxa-2λ⁶-thia-spiro[4.4]non-3-en-4-ylamino]-propionic acid methyl ester 在 potassium carbonate 、 1-chloro-3-hydroxy-1,1,3,3-tetrabutyldistannoxane 作用下， 以 丙酮 、 甲苯 为溶剂， 反应 24.0h， 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
• 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 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 245.0h， 生成 3-[(5R,6R,8R,9R)-9-(tert-Butyl-dimethyl-silanyloxy)-6-(tert-butyl-dimethyl-silanyloxymethyl)-8-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-2,2-dioxo-1,7-dioxa-2λ⁶-thia-spiro[4.4]non-3-en-4-ylamino]-propionic acid methyl ester
  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