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

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.