Asymmetric synthesis of nidulalin A and nidulaxanthone A: selective carbonyl desaturation using an oxoammonium salt
Date
2024-02-21
Authors
Ji, Kaijie
Johnson, Richard P.
McNeely, James
Al Faruk, Md
Porco, John A.
Version
Accepted manuscript
OA Version
Citation
K. Ji, R.P. Johnson, J. McNeely, M. Al Faruk, J.A. Porco. 2024. "Asymmetric Synthesis of Nidulalin A and Nidulaxanthone A: Selective Carbonyl Desaturation Using an Oxoammonium Salt." Journal of the American Chemical Society, Volume 146, Issue 7, pp.4892-4902. https://doi.org/10.1021/jacs.3c13864
Abstract
Nidulaxanthone A is a dimeric, dihydroxanthone natural product that was isolated in 2020 from Aspergillus sp. Structurally, 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 dimerization. To expedite the synthesis of nidulalin A and study the proposed dimerization, we developed methodology involving the 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. An asymmetric synthesis of nidulalin A was achieved using acylative kinetic resolution (AKR) of chiral, racemic 2H-nidulalin A. Dimerization of enantioenriched nidulalin A to nidulaxanthone A was achieved using solvent-free, thermolytic conditions. Computational studies have been conducted to probe both the oxoammonium-mediated desaturation and (4 + 2) dimerization events.