Enantioselective Synthesis of Planar Chiral Ferrocifens that Show Chiral Discrimination in Antiproliferative Activity on Breast Cancer Cells
Résumé
The design and first enantioselective synthesis of a series of chiral ferrocifens and ferrociphenols was realised via enantioselective palladium‐catalysed intramolecular direct C‑H bond activation followed by McMurry coupling. Biological evaluation revealed moderate anticancer activities on breast cancer cells and evidence of chiral discrimination between enantiomers. Treatment of these novel ferrocifens with Ag 2 O revealed that these systems are unable to form a neutral quinone methide, yet still demonstrate marked antiproliferative properties versus both the hormone‐dependent MCF‐7 and hormone‐independent MDA‐MB‐231 cell lines. This bioactivity arises from two mechanisms: Fenton‐type chemistry and the anti‐estrogenic activity associated with the tamoxifen‐like structure.