4-O-(3"-amino-2",3"-dideoxy-4",6"-O-ethylidene-β-D-arabino-hexopyranosyl)-epipodophyllotoxin | 189454-48-6

• 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"-amino-2",3"-dideoxy-4",6"-O-ethylidene-β-D-arabino-hexopyranosyl)-epipodophyllotoxin
• 英文别名: (5S,5aR,8aR,9R)-5-[[(2R,4aR,6R,8R,8aS)-8-amino-2-methyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-9-(4-hydroxy-3,5-dimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-8-one
• CAS: 189454-48-6
• 化学式: C₂₉H₃₃NO₁₁
• 分子量: 571.581
• InChiKey: BTKQJXHSDWNDAS-SDKCDZFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  41
• 可旋转键数：
  5
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  146
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 4-O-(3"-amino-2",3"-dideoxy-4",6"-O-ethylidene-β-D-arabino-hexopyranosyl)-epipodophyllotoxin 在 sodium cyanoborohydride 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以51%的产率得到4-O-(3"-dimethylamino-2",3"-dideoxy-4",6"-O-ethylidene-β-D-arabino-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：

  鬼臼毒素 在 palladium on activated charcoal 碘代三甲硅烷 、 三氟化硼乙醚 、 四丁基氟化铵 、 氢气 、 三乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 9.08h， 生成 4-O-(3"-amino-2",3"-dideoxy-4",6"-O-ethylidene-β-D-arabino-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

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.