Diversity Oriented Synthesis of Allocolchicinoids with Fluoro and/or Oxygen Substituent(s) on the C-Ring from a Single Common Intermediate

Keita Takubo, Kazunori Furutsu, Takafumi Ide, Hiroyuki Nemoto, Yuko Ueda, Kazutake Tsujikawa, Takashi Ikawa, Takehiko Yoshimitsu, Shuji Akai

Research output: Contribution to journalArticle

3 Citations (Scopus)

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. 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.

Original languageEnglish
Pages (from-to)1562-1576
Number of pages15
JournalEuropean Journal of Organic Chemistry
Volume2016
Issue number8
DOIs
Publication statusPublished - Mar 1 2016
Externally publishedYes

Fingerprint

Cells
analogs
Oxygen
rings
oxygen
synthesis
cultured cells
Acids
Poisons
cancer
Cytotoxicity
pancreas
acids
musculoskeletal system
Derivatives
drugs
Pharmaceutical Preparations
N-acetylcolchinol
products

Keywords

  • Allocolchicine
  • Anticancer
  • Domino reactions
  • Drug design
  • Fluorine
  • Synthetic methods

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry

Cite this

Diversity Oriented Synthesis of Allocolchicinoids with Fluoro and/or Oxygen Substituent(s) on the C-Ring from a Single Common Intermediate. / Takubo, Keita; Furutsu, Kazunori; Ide, Takafumi; Nemoto, Hiroyuki; Ueda, Yuko; Tsujikawa, Kazutake; Ikawa, Takashi; Yoshimitsu, Takehiko; Akai, Shuji.

In: European Journal of Organic Chemistry, Vol. 2016, No. 8, 01.03.2016, p. 1562-1576.

Research output: Contribution to journalArticle

Takubo, Keita ; Furutsu, Kazunori ; Ide, Takafumi ; Nemoto, Hiroyuki ; Ueda, Yuko ; Tsujikawa, Kazutake ; Ikawa, Takashi ; Yoshimitsu, Takehiko ; Akai, Shuji. / Diversity Oriented Synthesis of Allocolchicinoids with Fluoro and/or Oxygen Substituent(s) on the C-Ring from a Single Common Intermediate. In: European Journal of Organic Chemistry. 2016 ; Vol. 2016, No. 8. pp. 1562-1576.
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