Gold-Catalyzed Cycloisomerization of Propargyl Pyruvates Enabling Unified Access to Tricladolides C and D, Chaetomellic Anhydride A, and Tyromycin A.

Gold-catalyzed cycloisomerization of propargyl pyruvates has been developed as a key reaction to prepare maleic anhydride-type natural products. By combining with chemoselective epoxidation of the formed γ-alkylidenebutenolides and oxidative cleavage of epoxides, the first synthesis of tricladolide D and racemic tricladolide C has been achieved in 52 and 16% overall yields with five to seven steps starting from commercially available compounds. Further catalytic hydrogenation of alkenylated maleic anhydrides derived from γ-alkylidenebutenolides produced chaetomellic anhydride A (19% yield for six steps) and tyromycin A (15% yield for six steps), which provides flexible synthetic approaches to these naturally occurring dialkylated maleic anhydrides distinct from the documented ones.