Asymmetric Synthesis of Nidulalin A and Nidulaxanthone A: Selective Carbonyl Desaturation Using an Oxoammonium Salt

Nidulaxanthone A is a dimeric, dihydroxanthone natural product which was isolated in 2020 from Aspergillus sp. Structur-ally, the compound features an unprecedented heptacyclic 6/6/6/6/6/6/6 ring system which is unusual for natural xanthone dimers. Biosynthetically, nidulaxanthone A originates from the monomer nidulalin A via stereoselective Diels-Alder dimeri-zation. To expedite the synthesis of nidulalin A and study the proposed dimerization, we developed methodology involving use of allyl triflate for chromone ester activation followed by vinylogous addition to rapidly forge the nidulalin A scaffold in a four-step sequence which also features ketone desaturation using Bobbitt’s oxoammonium salt. The asymmetric synthesis of nidulalin A was achieved using acylative kinetic resolution (AKR) of chiral, racemic 2H-nidulalin A. Dimerization of en-antioenriched nidulalin A to nidulaxanthone A was achieved using solvent-free, thermolytic conditions. Computational studies have been conducted to probe both the desaturation and (4+2) dimerization events.