Total Synthesis of Termicalcicolanone A via Organocatalysis and Regioselective Claisen Rearrangement

A total synthesis of an anticancer xanthone natural product termicalcicolanone A utilizing multiple nucleophilic aromatic substitutions and pericyclic reactions has been developed. The pyrano­[3,2-b]­xanthen-6-one scaffold was constructed via NHC-catalyzed aroylation to produce the benzophenone intermediate, Claisen cyclization to form the pyran ring, and intramolecular 1,4-addition to construct the xanthone framework. The prenyl group was introduced in the final stages of the synthesis through regioselective Claisen rearrangement. The synthesis has been achieved in 19 steps.