9-Acetoxy-5,11-dimethyl-2-((3S,4R,5R,6S)-3,4,5-triacetoxy-6-methyl-tetrahydro-pyran-2-yl)-6H-pyrido[4,3-b]carbazol-2-ium; bromide | 114547-05-6

• 分子结构分类: 有机化合物
• 英文名称: 9-Acetoxy-5,11-dimethyl-2-((3S,4R,5R,6S)-3,4,5-triacetoxy-6-methyl-tetrahydro-pyran-2-yl)-6H-pyrido[4,3-b]carbazol-2-ium; bromide
• CAS: 114547-05-6；114547-15-8
• 化学式: Br*C₃₁H₃₃N₂O₉
• 分子量: 657.515
• InChiKey: FHDIKGVGLOEDGR-SONAVWGSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.02
• 重原子数：
  43.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  134.1
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  9-Acetoxy-5,11-dimethyl-2-((3S,4R,5R,6S)-3,4,5-triacetoxy-6-methyl-tetrahydro-pyran-2-yl)-6H-pyrido[4,3-b]carbazol-2-ium; bromide 在 氨 作用下， 以 甲醇 为溶剂， 生成 (2R,3S,4R,5S,6S)-2-(9-hydroxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazol-2-ium-2-yl)-6-methyloxane-3,4,5-triol;bromide 、 (2S,3S,4R,5S,6S)-2-(9-hydroxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazol-2-ium-2-yl)-6-methyloxane-3,4,5-triol;bromide
  参考文献：
  名称：

  立体选择性合成9-羟基玫瑰树碱苷，新型和高活性抗肿瘤药。

  摘要：

  一系列新型且高效的抗肿瘤药物，即9-羟基石蒜碱糖苷，通过改进的缩合反应在良好产率下立体选择性地合成。该反应以碳酸镉为催化剂，将9-乙酸氧基石蒜碱与全酧化的糖基卤化物进行反应，随后用甲醇氨去除醧基。

  DOI：

  10.1248/cpb.35.3975
• 作为产物：
  描述：

  2,3,4-三-O-乙酰基-6-脱氧-alpha-L-溴代半乳糖 、 9-acetyloxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazole 在 无水碳酸镉 作用下， 以 硝基甲烷 为溶剂， 以95%的产率得到9-Acetoxy-5,11-dimethyl-2-((3S,4R,5R,6S)-3,4,5-triacetoxy-6-methyl-tetrahydro-pyran-2-yl)-6H-pyrido[4,3-b]carbazol-2-ium; bromide
  参考文献：
  名称：

  立体选择性合成9-羟基玫瑰树碱苷，新型和高活性抗肿瘤药。

  摘要：

  一系列新型且高效的抗肿瘤药物，即9-羟基石蒜碱糖苷，通过改进的缩合反应在良好产率下立体选择性地合成。该反应以碳酸镉为催化剂，将9-乙酸氧基石蒜碱与全酧化的糖基卤化物进行反应，随后用甲醇氨去除醧基。

  DOI：

  10.1248/cpb.35.3975

文献信息

• Synthesis and antitumor activity of quaternary ellipticine glycosides, a series of novel and highly active antitumor agents
  作者：Tadashi Honda、Mika Kato、Minako Inoue、Tetsuo Shimamoto、Keiyuu Shima、Toshihiro Nakanishi、Takako Yoshida、Teruhisa Noguchi

  DOI：10.1021/jm00402a007

  日期：1988.7

  A series of ellipticine glycosides [2-N-glycosyl quaternary pyridinium salts of three ellipticines: ellipticine (1), 9-methoxyellipticine (2), and 9-hydroxyellipticine (4)] were stereoselectively synthesized in good yields by an improved condensation reaction between ellipticines [1, 2, and 9-acetoxyellipticine (3)] and protected (peracylated and perbenzylated) glycosyl halides with cadmium carbonate, followed by deprotection. These glycosides were preliminarily evaluated for their antitumor activity in the L1210 leukemia system. Twenty-six (53%) of the 49 glycosides tested were curative, and five [9-hydroxyellipticine L-arabinopyranoside (41b), D-lyxofuranoside (43a), L-lyxopyranoside (44b), D-xylofuranoside (49a), and L-rhamnopyranoside (56)] were selected for extended evaluation on the basis of their high levels of activity. The structure-activity relationships are discussed. The selected glycosides showed remarkable activity in six different murine tumor systems with excellent therapeutic ratios; their efficacy surpassed that of doxorubicin against three of these systems. On the basis of these results and ease of formulation, the two glycosides 41b (SUN4599) and 49a (SUN5073) were selected for further preclinical evaluation and possible clinical development.