Synthesis and cytotoxicity of some new eriocalyxin B derivatives

Eriocalyxin B (1) was regarded as the promising candidate for new anticancer agent because of its potent activity and novel mechanism of action. Systematic modifications of 1 were done, and nineteen derivatives were synthesized and their cytotoxicities against five tumor cell lines were evaluated. The structure–activity relationship (SAR) of 1 confirmed that the α,β-unsaturated ketone moieties in ring A and D are the leading active sites; the 7,20-epoxy moiety, OH-6 and OH-7 play an important role in keeping the cytotoxicity. The 6,7-seco derivative 19 had remarkable activity while derivative 20 oxidized from 19 was completely inactive, which suggested that the carboxyl group could destroy the cytoxicity of 20 despite the presence of α,β-unsaturated ketone moiety.