tert-butyldimethylsilyl 3-azido-2,3-dideoxy-β-D-ribo-hexopyranoside | 189454-50-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: tert-butyldimethylsilyl 3-azido-2,3-dideoxy-β-D-ribo-hexopyranoside
• 英文别名: (2R,3S,4S,6S)-4-azido-6-[tert-butyl(dimethyl)silyl]oxy-2-(hydroxymethyl)oxan-3-ol
• CAS: 189454-50-0
• 化学式: C₁₂H₂₅N₃O₄Si
• 分子量: 303.434
• InChiKey: CHVQAMOISPQQTA-VLEAKVRGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.16
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  73.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyldimethylsilyl 3-azido-2,3-dideoxy-β-D-ribo-hexopyranoside 在 吡啶 、 Amberlite resin IRA 410 (OH^-) 、 三氟化硼乙醚 、 sodium iodide 作用下， 以 甲醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 100.0h， 生成 4-O-(3"-azido-6"-iodo-2",3",6"-trideoxy-β-D-ribo-hexopyranosyl)-4'-benzyloxycarbonyl-epipodophyllotoxin
  参考文献：
  名称：

  Synthesis and Antitumor Activity of New Glycosides of Epipodophyllotoxin, Analogues of Etoposide, and NK 611

  摘要：

  A series of 3-amino- and 3-alkylamino-2-deoxy-beta-D-ribo- and beta-D-arabino-glycosides of 4'-demethylepipodophyllotaxin have been synthesized by means of an improved trimethylsilyl-iodide procedure for the podophyllotoxin-4'-demethylepipodophyllotoxin conversion, an efficient and high yielding synthesis of silyl glycoside donors of 3-azido-2, 3-dideoxy-beta-D-ribo- and beta-D-arabino-hexopyranoside's and stereoselective glycosylations. In vitro evaluation of cytotoxic effects against murine L1210 leukemia critically demonstrates the essential role played by a 4,6-acetal for biological activity. Among the most cytotoxic compounds, 3-amino-2,3-dideoxy- and 3-N,N-(dimethylamino)-2,3-dideoxy etoposide analogues, 17 and 27-29 are at least as potent as etoposide on the in vivo P388 (iv/ip) murine leukemia models. However, surprisingly enough, none of these compounds inhibits the human DNA topoisomerases I or II or binds to tubulin to prevent its polymerization and microtubule assembly. Therefore, their mechanism of action remains to be cleared up.

  DOI：

  10.1021/jm9800752
• 作为产物：
  描述：

  tert-butyldimethylsilyl 3-azido-4,6-di-O-acetyl-2,3-dideoxy-β-D-ribo-hexopyranoside 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 1.5h， 以99%的产率得到tert-butyldimethylsilyl 3-azido-2,3-dideoxy-β-D-ribo-hexopyranoside
  参考文献：
  名称：

  Synthesis and Antitumor Activity of New Glycosides of Epipodophyllotoxin, Analogues of Etoposide, and NK 611

  摘要：

  A series of 3-amino- and 3-alkylamino-2-deoxy-beta-D-ribo- and beta-D-arabino-glycosides of 4'-demethylepipodophyllotaxin have been synthesized by means of an improved trimethylsilyl-iodide procedure for the podophyllotoxin-4'-demethylepipodophyllotoxin conversion, an efficient and high yielding synthesis of silyl glycoside donors of 3-azido-2, 3-dideoxy-beta-D-ribo- and beta-D-arabino-hexopyranoside's and stereoselective glycosylations. In vitro evaluation of cytotoxic effects against murine L1210 leukemia critically demonstrates the essential role played by a 4,6-acetal for biological activity. Among the most cytotoxic compounds, 3-amino-2,3-dideoxy- and 3-N,N-(dimethylamino)-2,3-dideoxy etoposide analogues, 17 and 27-29 are at least as potent as etoposide on the in vivo P388 (iv/ip) murine leukemia models. However, surprisingly enough, none of these compounds inhibits the human DNA topoisomerases I or II or binds to tubulin to prevent its polymerization and microtubule assembly. Therefore, their mechanism of action remains to be cleared up.

  DOI：

  10.1021/jm9800752

文献信息

• Synthesis and Antitumor Activity of New Glycosides of Epipodophyllotoxin, Analogues of Etoposide, and NK 611
  作者：Laurent Daley、Yves Guminski、Pierre Demerseman、Anna Kruczynski、Chantal Etiévant、Thierry Imbert、Bridget T. Hill、Claude Monneret

  DOI：10.1021/jm9800752

  日期：1998.11.1

  A series of 3-amino- and 3-alkylamino-2-deoxy-beta-D-ribo- and beta-D-arabino-glycosides of 4'-demethylepipodophyllotaxin have been synthesized by means of an improved trimethylsilyl-iodide procedure for the podophyllotoxin-4'-demethylepipodophyllotoxin conversion, an efficient and high yielding synthesis of silyl glycoside donors of 3-azido-2, 3-dideoxy-beta-D-ribo- and beta-D-arabino-hexopyranoside's and stereoselective glycosylations. In vitro evaluation of cytotoxic effects against murine L1210 leukemia critically demonstrates the essential role played by a 4,6-acetal for biological activity. Among the most cytotoxic compounds, 3-amino-2,3-dideoxy- and 3-N,N-(dimethylamino)-2,3-dideoxy etoposide analogues, 17 and 27-29 are at least as potent as etoposide on the in vivo P388 (iv/ip) murine leukemia models. However, surprisingly enough, none of these compounds inhibits the human DNA topoisomerases I or II or binds to tubulin to prevent its polymerization and microtubule assembly. Therefore, their mechanism of action remains to be cleared up.