Diversity Oriented Synthesis of Allocolchicinoids with Fluoro and/or Oxygen Substituent(s) on the C-Ring from a Single Common Intermediate
Diversity Oriented Synthesis of Allocolchicinoids with Fluoro and/or Oxygen Substituent(s) on the C-Ring from a Single Common Intermediate
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从单一常见中间体以多样性为导向合成 C 环上具有氟和/或氧取代基的别秋水仙素类化合物
DOI：
10.1002/ejoc.201501624
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Shuji
中科院分区：
文献类型：
--
作者：
Takubo;Keita; Furutsu;Kazunori; Ide;Takafumi; Nemoto;Hiroyuki; Ueda;Yuko; Tsujikawa;Kazutake; Ikawa;Takashi; Yoshimitsu;Takehiko; Akai; Shuji
异秋水仙素类化合物具有独特的多氧二苯并环庚烷骨架，是一种潜在的抗肿瘤药物。在这项研究中，8个C环氟代类似物allocolchicinoids，7个C环氧取代的类似物，和已知的化合物N-乙酰秋水仙醇和NSC 51046作为外消旋体从一个共同的中间体通过使用脱氧/迁移多米诺反应或酸促进迁移作为关键步骤。在所获得的产物中，一些氟化衍生物强烈抑制前列腺DU 145和胰腺Panc 1癌细胞系的生长，其功效与N-乙酰秋水仙醇和NSC 51046相当或更好。它们对非癌细胞系的毒性也低于已知化合物。
Allocolchicinoids, with a distinct polyoxygenated dibenzocycloheptane skeleton, attract much attention as potential candidate anticancer drugs. In this study, eight C‐ring fluorinated analogues of allocolchicinoids, seven C‐ring oxygen‐substituted analogues, and known compoundsN‐acetylcolchinol and NSC 51046 were synthesized as racemates from a single common intermediate by using either the deoxyfluorination/migration domino reaction or acid‐promoted migration as the key step. Among the products obtained, some of the fluorinated derivatives strongly inhibited the growth of prostate DU145 and pancreas Panc 1 cancer cell lines with efficacy comparable to or better than those ofN‐acetylcolchinol and NSC 51046. They were also less toxic against a non‐cancerous cell line than the known compounds were.