Ferrocene-modified imidazoles: One-pot oxalyl chloride-assisted synthesis, HPLC enantiomeric resolution, and in vivo antitumor effects

Highlights on the development of ferrocene biochemistry in Russia since the 1950s are given. Here, avoiding high-toxic precursors, ferrocene-based imidazoles and benzimidazoles (16 compounds) were synthesized in good to high yields via the reaction of the alpha-(hydroxy)alkyl ferrocenes with modified heterocycles using oxalyl chloride to activate imidazole system. Mild conditions (room temperature, chloroform, stirring for up to 1.5 h) allowed preparing a number of various ferrocene-containing imidazoles, which are promising as antitumor agents. The analytical HPLC method was successfully applied to enantioseparation of the resulting ferrocene enantiomers (Chiralcel OD column). Antitumor activities of the preparing compounds against murine solid tumours such as Acatol adenocarcinoma and Ca755 carcinoma have been studied in vivo. Some of the tested compounds have been strong effective against Acatol adenocarcinoma. The value of the tumour growth inhibition coefficient was about 90% versus control in this strain.