tert-butyldimethylsilyl 3-azido-4,6-di-O-chloroacetyl-2,3-dideoxy-β-D-ribo-hexopyranoside | 215935-10-7

• 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-4,6-di-O-chloroacetyl-2,3-dideoxy-β-D-ribo-hexopyranoside
• 英文别名: [(2R,3S,4S,6S)-4-azido-6-[tert-butyl(dimethyl)silyl]oxy-3-(2-chloroacetyl)oxyoxan-2-yl]methyl 2-chloroacetate
• CAS: 215935-10-7
• 化学式: C₁₆H₂₇Cl₂N₃O₆Si
• 分子量: 456.398
• InChiKey: PEMRVQHYQKHQHN-JLUCKKNBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.73
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  85.4
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyldimethylsilyl 3-azido-4,6-di-O-chloroacetyl-2,3-dideoxy-β-D-ribo-hexopyranoside 在 palladium on activated charcoal 三氟甲磺酸三甲基硅酯 、 4 A molecular sieve 、 Amberlite IRA 410 ion-exchange (OH^-) resin 、 氢气 、 对甲苯磺酸 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 148.0h， 生成 4-O-(3"-amino-N-(ethylamino)-2",3"-dideoxy-4",6"-O-ethylidene-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：

  4,6-di-O-acetyl-3-azido-2,3-dideoxy-D-erythro-hexopyranose 在 吡啶 、 咪唑 、 sodium methylate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 tert-butyldimethylsilyl 3-azido-4,6-di-O-chloroacetyl-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.