First total synthesis of piperodione and analogs

Piperodione (3), a secondary metabolite previously isolated from the Javanese pepper plant Piper retrofractum in 0.0002% isolated yield was synthesized in a convergent strategy utilizing a Mannich and a Stetter reaction. An over-all yield of 76% could be achieved. Several analogs were prepared by this synthetic sequence. None of the compounds showed a significant cytotoxicity for human tumor cells (photometric sulforhodamine B assay).