4-O-(3"-azido-6"-iodo-2",3",6"-trideoxy-β-D-ribo-hexopyranosyl)-4'-benzyloxycarbonyl-epipodophyllotoxin | 189454-68-0

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 木脂素内酯
• 英文名称: 4-O-(3"-azido-6"-iodo-2",3",6"-trideoxy-β-D-ribo-hexopyranosyl)-4'-benzyloxycarbonyl-epipodophyllotoxin
• 英文别名: [4-[(5S,5aR,8aR,9R)-5-[(2R,4S,5S,6S)-4-azido-5-hydroxy-6-(iodomethyl)oxan-2-yl]oxy-8-oxo-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-9-yl]-2,6-dimethoxyphenyl] benzyl carbonate
• CAS: 189454-68-0
• 化学式: C₃₅H₃₄IN₃O₁₂
• 分子量: 815.572
• InChiKey: RHVNHKDZAPLLNJ-QEEXKUPOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  51
• 可旋转键数：
  12
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  152
• 氢给体数：
  1
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  4-O-(3"-azido-6"-iodo-2",3",6"-trideoxy-β-D-ribo-hexopyranosyl)-4'-benzyloxycarbonyl-epipodophyllotoxin 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 乙酸乙酯 为溶剂， 反应 30.0h， 以38%的产率得到4-O-(3"-amino-2",3",6"-trideoxy-β-D-ribo-hexopyranosyl)-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 、 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