[(3R/S)-3-(tert-butyldiphenylsilyl)oxymethyl-1-(5,6,7-trimethoxyindol-2'-yl-carbonyl)-2,3-dihydro-1H-indol-6-yl]-2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside | 366789-58-4

• 分子结构分类: 有机化合物
• 英文名称: [(3R/S)-3-(tert-butyldiphenylsilyl)oxymethyl-1-(5,6,7-trimethoxyindol-2'-yl-carbonyl)-2,3-dihydro-1H-indol-6-yl]-2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside
• CAS: 366789-58-4
• 化学式: C₅₁H₅₈N₂O₁₅Si
• 分子量: 967.111
• InChiKey: IYYVYFRWWZCIEX-POTCVNKKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.98
• 重原子数：
  69.0
• 可旋转键数：
  16.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  196.68
• 氢给体数：
  1.0
• 氢受体数：
  15.0

反应信息

• 作为反应物：
  描述：

  [(3R/S)-3-(tert-butyldiphenylsilyl)oxymethyl-1-(5,6,7-trimethoxyindol-2'-yl-carbonyl)-2,3-dihydro-1H-indol-6-yl]-2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside 在 四氯化碳 、 四丁基氟化铵 、 sodium methylate 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 30.0h， 生成 [(3R/S)-3-chloromethyl-1-(5,6,7-trimethoxyindol-2'-yl-carbonyl)-2,3-dihydro-1H-indol-6-yl]-β-D-glucopyranoside
  参考文献：
  名称：

  A strategy for tumor-selective chemotherapy by enzymatic liberation of seco-duocarmycin SA-derivatives from nontoxic prodrugs

  摘要：

  Immuno-conjugates obtained by linking enzymes with appropriate monoclonal antibodies, which bind to tumor-associated antigens, can be employed in a tumor-selective antibody directed enzyme prodrug therapy (ADEPT). For this strategy the glycosides 17a-c were prepared as prodrugs of CI-TMI 14 which is a structurally simplified analogue of the highly potent antitumor agent duocarmycin SA 2. Exposure of 17a-c to cultured carcinoma cells of line A549 displayed a very low toxicity; however, after addition of the corresponding enzymes and exposure for 24 h at prodrug concentrations of <0.1 M the proliferation of the carcinoma cells was inhibited almost completely with ED50prodrug/ED50drug of UP to 270 in the presence and in the absence of the enzyme. The synthesis of 17a-c was achieved by transformation of nitroanisidine 6 into 12 which was glycosidated to give 16a-c. Removal of the silyl groups, introduction of a chlorine atom and solvolysis of the acetal groups led to 17a-c, of which 17a and 17c are promising candidates for further elaboration. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00098-0
• 作为产物：
  描述：

  (3R/S)-6-benzyloxy-3-(tert-butyldiphenylsilyl)oxymethyl-1-(5',6',7'-trimethoxyindol-2'-yl-carbonyl)-2,3-dihydro-1H-indole 在 palladium on activated charcoal 4 Angstroem MS 、 三氟化硼乙醚 、 氢气 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 20.0 ℃ 、300.0 kPa 条件下， 反应 32.0h， 生成 [(3R/S)-3-(tert-butyldiphenylsilyl)oxymethyl-1-(5,6,7-trimethoxyindol-2'-yl-carbonyl)-2,3-dihydro-1H-indol-6-yl]-2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside
  参考文献：
  名称：

  A strategy for tumor-selective chemotherapy by enzymatic liberation of seco-duocarmycin SA-derivatives from nontoxic prodrugs

  摘要：

  Immuno-conjugates obtained by linking enzymes with appropriate monoclonal antibodies, which bind to tumor-associated antigens, can be employed in a tumor-selective antibody directed enzyme prodrug therapy (ADEPT). For this strategy the glycosides 17a-c were prepared as prodrugs of CI-TMI 14 which is a structurally simplified analogue of the highly potent antitumor agent duocarmycin SA 2. Exposure of 17a-c to cultured carcinoma cells of line A549 displayed a very low toxicity; however, after addition of the corresponding enzymes and exposure for 24 h at prodrug concentrations of <0.1 M the proliferation of the carcinoma cells was inhibited almost completely with ED50prodrug/ED50drug of UP to 270 in the presence and in the absence of the enzyme. The synthesis of 17a-c was achieved by transformation of nitroanisidine 6 into 12 which was glycosidated to give 16a-c. Removal of the silyl groups, introduction of a chlorine atom and solvolysis of the acetal groups led to 17a-c, of which 17a and 17c are promising candidates for further elaboration. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00098-0