[1-[2',5'-bis-O-tert-butyldimethylsilyl-β-D-ribofuranosyl]-3-N-(tert-butoxyglutaryl)thymine]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide) | 1338582-84-5

• 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-(tert-butoxyglutaryl)thymine]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)
• 英文别名: tert-butyl 5-[3-[(1R,3R,4R,5R)-6-amino-4-[tert-butyl(dimethyl)silyl]oxy-1-[[tert-butyl(dimethyl)silyl]oxymethyl]-8,8-dioxo-2,9-dioxa-8$l^{6}-thiaspiro[4.4]non-6-en-3-yl]-5-methyl-2,6-dioxo-pyrimidin-1-yl]-5-oxo-pentanoate；tert-butyl 5-[3-[(5R,6R,8R,9R)-4-amino-9-[tert-butyl(dimethyl)silyl]oxy-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-2,2-dioxo-1,7-dioxa-2λ6-thiaspiro[4.4]non-3-en-8-yl]-5-methyl-2,6-dioxopyrimidin-1-yl]-5-oxopentanoate
• CAS: 1338582-84-5
• 化学式: C₃₃H₅₇N₃O₁₁SSi₂
• 分子量: 760.066
• InChiKey: NGLMUKCVEBGSSG-RCTKOJHZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.68
• 重原子数：
  50
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  189
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  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-2-硫杂螺[4.4]壬-3-烯-7-基]-5-甲基嘧啶-2,4-二酮 在 四丁基溴化铵 、 sodium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 0.25h， 生成 [1-[2',5'-bis-O-tert-butyldimethylsilyl-β-D-ribofuranosyl]-3-N-(tert-butoxyglutaryl)thymine]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)
  参考文献：
  名称：

  Synthesis and in vitro activity of novel N-3 acylated TSAO-T compounds against HIV-1 and HCV

  摘要：

  Preparation of a small library of derivatives of the potent HIV-1 Reverse Transcriptase inhibitor TSAO-T bearing mono or di-carbonyl substituents (designed after docking analysis) at position N-3 is reported. A one-pot synthetic methodology has been developed that involves: (i) mono-reaction of TSAO-T with glutaryl dichloride under phase transfer conditions and (ii) in situ acyclic substitution of the remaining chloro atom by oxygen or nitrogen nucleophiles. The method is compatible with the polyfunctionality of the TSAO-T molecule, proceeds with high conversion yields and allows introducing molecular diversity. The anti-HIV-1 and -HCV activity was studied in cell culture. The new N-3 acylated TSAO-T derivatives are active against HIV-1 (nanomolar range). Anti-HCV activity was observed in the micromolar range, that is at compound concentrations that were found cytostatic against human T-lymphocytes. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.08.017

文献信息

• Synthesis and in vitro activity of novel N-3 acylated TSAO-T compounds against HIV-1 and HCV
  作者：Marina Moura、Solen Josse、Albert Nguyen Van Nhien、Carole Fournier、Gilles Duverlie、Sandrine Castelain、Elena Soriano、José Marco-Contelles、Jan Balzarini、Denis Postel

  DOI：10.1016/j.ejmech.2011.08.017

  日期：2011.10

  Preparation of a small library of derivatives of the potent HIV-1 Reverse Transcriptase inhibitor TSAO-T bearing mono or di-carbonyl substituents (designed after docking analysis) at position N-3 is reported. A one-pot synthetic methodology has been developed that involves: (i) mono-reaction of TSAO-T with glutaryl dichloride under phase transfer conditions and (ii) in situ acyclic substitution of the remaining chloro atom by oxygen or nitrogen nucleophiles. The method is compatible with the polyfunctionality of the TSAO-T molecule, proceeds with high conversion yields and allows introducing molecular diversity. The anti-HIV-1 and -HCV activity was studied in cell culture. The new N-3 acylated TSAO-T derivatives are active against HIV-1 (nanomolar range). Anti-HCV activity was observed in the micromolar range, that is at compound concentrations that were found cytostatic against human T-lymphocytes. (C) 2011 Elsevier Masson SAS. All rights reserved.