tert-butyldimethylsilyl 3-azido-4-O-chloroacetyl-2,3,6-trideoxy-6-iodo-β-D-ribo-hexopyranoside | 189454-64-6

• 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-4-O-chloroacetyl-2,3,6-trideoxy-6-iodo-β-D-ribo-hexopyranoside
• 英文别名: [(2S,3S,4S,6S)-4-azido-6-[tert-butyl(dimethyl)silyl]oxy-2-(iodomethyl)oxan-3-yl] 2-chloroacetate
• CAS: 189454-64-6
• 化学式: C₁₄H₂₅ClIN₃O₄Si
• 分子量: 489.813
• InChiKey: KTJDJVHLPKQXPD-LFSVMHDDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.39
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyldimethylsilyl 3-azido-4-O-chloroacetyl-2,3,6-trideoxy-6-iodo-β-D-ribo-hexopyranoside 在 sodium azide 、 Amberlite resin IRA 410 (OH^-) 、 三氟化硼乙醚 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 4-O-(3",6"-diazido-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-2,3-dideoxy-β-D-ribo-hexopyranoside 在 吡啶 、 sodium iodide 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 92.0h， 生成 tert-butyldimethylsilyl 3-azido-4-O-chloroacetyl-2,3,6-trideoxy-6-iodo-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