6-demethylmitomycin D

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 6-demethylmitomycin D
• 英文别名: [(4S,6S,7R,8R)-11-amino-7-hydroxy-5-methyl-10,13-dioxo-2,5-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),11-dien-8-yl]methyl carbamate
• 化学式: C₁₄H₁₆N₄O₅
• 分子量: 320.305
• InChiKey: BERDCXFVILOZHD-NVTIQEIFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  139
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  7-demethoxy-6-demethyl-7,7-(ethylenedioxy)-6-(phenylseleno)-6,7-dihydromitomycin B 在 氨 、 5,5-二甲基-1,3-环己二酮 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 41.0h， 生成 6-demethylmitomycin D
  参考文献：
  名称：

  Synthesis and Antitumor Activity of Various 6-Demethylmitomycins and 6-Demethyl-6-halomitomycins

  摘要：

  A series of 6-demethylmitomycins and 6-demethyl-6-halomitomycins having various mitomycin skeletons were synthesized, taking into account the electronic effect toward the quinone moiety and the partition coefficients. Treatment of enones 15 and 16 with selenenamide or N-halosuccinimide-Et(2)NH afforded the 6-demethyl intermediates 17, 18, and 21-24 via the tandem Michael addition/retro-Mannich reaction sequence. Subsequent conversions into the mitomycin skeletons resulted in the formation of the desired derivatives 7a-c, 8a-c, 11a-c, and 12a,b. These mitomycin derivatives including 3a-c and 4a-c were evaluated for their anticellular activity against HeLa S-3 cells and antitumor activity against Sarcoma 180 in mice. The anticellular activity of 1 and 3a-c depends on the substituent at the C-6 position and the order of increasing activity is H < CH3 < Br < Cl. A similar tendency was observed in their antitumor potency (ED(50)) The activities of 9 and 11a-c also follow a pattern similar to that of 1 and 3a-c. Compounds 4b,c, 8b,c, and 12b having both a halogen at the C-6 position and a methoxy group at the C-7 position did not show the activities because of the instability of the compounds. Interestingly, a correlation between the anticellular activity (IC50) and the partition coefficients (log k') determined by HPLC was observed within the compounds studied except the unstable compounds, while their antitumor activity (ED(50) or T/C) did not correlate with the quinone reduction potential (E(1/2)). These results would indicate the importance of the C-6 substituents and the mitomycin skeletons for exhibiting both anticellular and antitumor activities.

  DOI：

  10.1021/jm00016a005

文献信息

• Synthesis and Antitumor Activity of Various 6-Demethylmitomycins and 6-Demethyl-6-halomitomycins
  作者：Hitoshi Arai、Tadashi Ashizawa、Katsushige Gomi、Motomichi Kono、Hiromitsu Saito、Masaji Kasai

  DOI：10.1021/jm00016a005

  日期：1995.8

  A series of 6-demethylmitomycins and 6-demethyl-6-halomitomycins having various mitomycin skeletons were synthesized, taking into account the electronic effect toward the quinone moiety and the partition coefficients. Treatment of enones 15 and 16 with selenenamide or N-halosuccinimide-Et(2)NH afforded the 6-demethyl intermediates 17, 18, and 21-24 via the tandem Michael addition/retro-Mannich reaction sequence. Subsequent conversions into the mitomycin skeletons resulted in the formation of the desired derivatives 7a-c, 8a-c, 11a-c, and 12a,b. These mitomycin derivatives including 3a-c and 4a-c were evaluated for their anticellular activity against HeLa S-3 cells and antitumor activity against Sarcoma 180 in mice. The anticellular activity of 1 and 3a-c depends on the substituent at the C-6 position and the order of increasing activity is H < CH3 < Br < Cl. A similar tendency was observed in their antitumor potency (ED(50)) The activities of 9 and 11a-c also follow a pattern similar to that of 1 and 3a-c. Compounds 4b,c, 8b,c, and 12b having both a halogen at the C-6 position and a methoxy group at the C-7 position did not show the activities because of the instability of the compounds. Interestingly, a correlation between the anticellular activity (IC50) and the partition coefficients (log k') determined by HPLC was observed within the compounds studied except the unstable compounds, while their antitumor activity (ED(50) or T/C) did not correlate with the quinone reduction potential (E(1/2)). These results would indicate the importance of the C-6 substituents and the mitomycin skeletons for exhibiting both anticellular and antitumor activities.