Synthesis of (−)-callicarpenal, a potent arthropod repellent

Callicarpenal (1), a natural terpenoid isolated from American beautyberry (Callicarpa americana), has shown significant repellent activities against mosquitoes, ticks, and imported fire ants. Here we report our efficient synthetic approach to this natural product, and preliminary results of the mosquito biting-deterrent effects of callicarpenal as well as its synthetic precursors and related C8-epimers. The synthetic strategy allows rapid access to various epimers and analogues of the natural product that can be used to explore its structure–activity relationship and optimize its biological properties.

Callicarpenal (1), a natural terpenoid isolated from American beautyberry (Callicarpa americana), has shown significant repellent activities against mosquitoes, ticks, and imported fire ants. Here we report an efficient synthetic approach to this natural product, and preliminary results of the mosquito biting-deterrent effects of callicarpenal as well as its synthetic precursors and related C8-epimers. The synthesis is enantioselective, amenable to rapid functionalization of the bicyclic core, and suitable for scale-up.Figure optionsDownload as PowerPoint slide