Synthesis and cytotoxicity of desmethoxycallipeltin B: lack of a quinone methide for the cytotoxicity of callipeltin B

The desmethoxy analogue of the cytotoxic, cyclic depsipeptide callipeltin B was synthesized to evaluate the role of its beta-MeOTyr residue. The IC(50) of desmethoxycallipeltin B, in which the beta-MeOTyr residue was replaced by d-Tyr, against HeLa cells was found to be 128+/-10 microM in an MTT assay, compared to 98+/-5 microM for the natural product itself. The roughly comparable cytotoxicities suggest that the cytotoxicity of callipeltin B does not arise through the formation of a quinone methide intermediate.