Sesquiterpene lactone cynaropicrin (1) is isolated from artichoke (Cynara scolymus) and has a 5-7-5 guaianolide skeleton with four exo-olefins and six stereocenters. It has been shown to possess various biological activities including inhibitory activity against Trypanosoma brucei which cause human African trypanosomiasis (HAT; sleeping sickness). In this study, we aimed for the first total synthesis of 1. We first tried the synthesis of the five-membered ring segment via a Favorskii rearrangement as a key transformation. Starting from (S)-a-pinene, photo oxidation and ene reaction were performed to afford the precursor of Favorskii rearrangement. Next, conditions of Favorskii reaction were investigated to form five-membered skeleton from six-membered ring. Thus, we achieved the synthesis of the five-membered ring segment with high selectivity in 5.4% overall yield in 18 steps. The Barbier reaction was then carried out to obtain a 5-7 bicyclic compound. Further synthesis of 5-7-5 tricyclic skeleton is currently in progress toward the total synthesis of 1.

Synthetic study of anti-trypanosomal cynaropicrin

255th National Meeting (2018)

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