Diversity Oriented Synthesis of Allocolchicinoids with Fluoro and/or Oxygen Substituent(s) on the C‐Ring from a Single Common Intermediate1. Issue 8 (16th February 2016)

• Record Type: Journal Article
• Authors: Takubo, Keita; Furutsu, Kazunori; Ide, Takafumi; Nemoto, Hiroyuki; Ueda, Yuko; Tsujikawa, Kazutake; Ikawa, Takashi; Yoshimitsu, Takehiko; Akai, Shuji
• Is Part Of: European journal of organic chemistry. Issue 8(2016)
• Page Start: 1562
• Page End: 1576
• Publication Date: 2016-02-16
• Subjects: Synthetic methods -- Drug design -- Fluorine -- Allocolchicine -- Anticancer -- Domino reactions; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201501624
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: 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 compounds N ‐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 of N ‐acetylcolchinol and NSC 51046. They were also less toxic against a non‐cancerous cell line than the known compounds were. Abstract : Eight C‐ring fluorinated analogues of allocolchicinoids, seven C‐ring oxygen‐substituted analogues, and known compounds N ‐acetylcolchinol and NSC 51046 were synthesized from a single common intermediate by using either the deoxyfluorination/migration domino reaction or acid‐promoted migration as the key step. Some fluorinated compounds showed high cytotoxicity against prostate cancer cells.