Wheldone is a fungal metabolite isolated from the coculture of Aspergillus fischeri and Xylaria flabelliformis, displaying cytotoxic activity against breast, melanoma, and ovarian cancer cell lines. Initially, its structure was characterized as an unusual 5-methyl-bicyclo[5.4.0]undeca-3,5-diene scaffold with a 2-hydroxy-1-propanone side chain and a 3-(2-(1-hydroxyethyl)-2-methyl-2,5-dihydrofuran-3-yl)acrylic acid moiety. Upon further examination, minor inconsistencies in the data suggested the need for the structure to be revisited. Thus, the structure of wheldone has been revised using an orthogonal experimental-computational approach, which combines 1,1-HD-ADEQUATE NMR experiments, DFT-GIAO chemical shift calculations, and single-crystal X-ray diffraction (SCXRD) analysis of a semisynthetic p-bromobenzylamide derivative, formed via a Steglich-type reaction. The summation of these data now permits the unequivocal assignment of both the structure and absolute configuration of the natural product.

Chemistry School of Natural and Environmental Sciences Newcastle University Newcastle NE1 7RU U K

Department of Chemistry and Biochemistry University of North Carolina at Greensboro Greensboro North Carolina 27402 United States

Department of Chemistry and Biochemistry University of North Carolina Wilmington Wilmington North Carolina 28409 United States

Department of Chemistry Universitas Indonesia Depok Jawa Barat 16424 Indonesia

Department of Structure Analysis Institute of Physics of the Czech Academy of Sciences Na Slovance 2 Prague 18221 Czech Republic

Indicatrix Crystallography Ltd Newcastle University Newcastle NE1 7RU U K

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