Short synthesis of piperizinohydroisoquinoline ring by selective Pictet-Spengler cyclization and evaluation of antitumor activity

Yu An Chang, Tsung Hsien Sun, Michael Y. Chiang, Pei Jung Lu, Yi Ting Huang, Li Ching Liang, Chi Wi Ong

研究成果: Article同行評審

18 引文 斯高帕斯(Scopus)

摘要

A rapid access to the piperizinohydroisoquinoline motif, which has feature of the saframycins and related pentacyclic antitumor alkaloids is described. The key features of the synthetic strategy include (1) a controlled mono-Pictet-Spengler cyclization of the symmetrical 3,6-bis-[(2,5-dimethoxy-phenyl)methyl]piperizine-2,5-dione (1), with aldehydes to give 2, under a critically controlled ratio of acetic acid and trifluoroacetic acid as solvent and (2) reduction of the activated amide to the hemiaminal, which then undergoes an unexpected dehydrogenation reaction to remove the steric hindrance for the second Pictet-Spengler cyclization to form the pentacyclic piperizinohydroisoquinoline 6. The in vitro antitumor activity of these compounds was tested against five human cancer cell lines (A549 lung, HeLa cervical, SAS oral, SKHep1 hepatoma and PC-3 prostate carcinoma). The pentacyclic saframycin analogues 6, 7 and 9 showed only weak activities. Interestingly, compound 6, having a closer relation to cribrostatin IV, is selective towards oral cancer.

原文English
頁(從 - 到)8781-8787
頁數7
期刊Tetrahedron
63
發行號36
DOIs
出版狀態Published - 2007 9月 3

All Science Journal Classification (ASJC) codes

  • 生物化學
  • 藥物發現
  • 有機化學

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