Total Synthesis and Structural Confirmation of the Antimalarial Naphthopyrone Lasionectrin

The total synthesis of lasionectrin, a naphthopyrone metabolite of an Acremonium-like fungus collected in Equatorial Guinea, is reported. Divergent access to four stereoisomers confirmed the natural product to be the enantiomer of the originally proposed structure. Highlights of the synthesis include ring opening of a chiral oxetane using a thiol, a highly E-selective Julia-Kocienski olefination, and a modified Sharpless/Upjohn dihydroxylation. Palladium-catalyzed carbonylative lactonization was used to assemble the fused naphthopyrone ring system.