Structural Revision of Wentiquinone C and Related Congeners from Anthraquinones to Xanthones Using Chemical Derivatization and NMR Analysis

Abstract

Wentiquinone C, which was previously isolated from the marine brown alga-derived endophytic fungus Aspergillus wentii EN-48, was found to be a potent antioxidant against α,α-diphenyl-picrylhydrazyl (DPPH) radical. The structure of wentiquinone C was originally assigned as an anthraquinone derivative (1,10-dihydroxy-3-(hydroxymethyl)-8-methoxydibenzo [b,e]oxepine-6,11-dione, 1) by 1D and 2D NMR experiments. However, the minor differences of the chemical shifts between xanthones and anthraquinones were queried, leading to the structure of 1 to be revised as a xanthone analog (8-hydroxy-6-(hydroxymethyl)-3-methoxy-9-oxo-9H-xanthene-1-carboxylic acid, 2) on the basis of a methylation and subsequent NMR measurements, and was confirmed by X-ray crystallographic analysis. The method established in this paper could be applied to the structural re-examination or revision for some of the reported seco-anthraquinone derivatives.

Ominoxanthone—The First Xanthone Linearly Fused to a γ-Lactone from Cortinarius ominosus Bidaud Basidiomata. CASE- and DFT-Based Structure Elucidation

“…A bibliographic survey confirmed the considerable difficulties in distinguishing these two scaffolds, as such pairs of compounds display identical carbon connectivities, and thus similar sets of HMBC correlations [ 9 ]. Interestingly, oxepinedione-containing metabolites were claimed to have been isolated from fungal sources on several occasions, mostly from micromycetes [ 10 , 11 , 12 ].…”

Pitfalls in the structural elucidation of small molecules. A critical analysis of a decade of structural misassignments of marine natural products

“…41 However, given the similarities in NMR spectra of 19 and calyxanthone ( 21 ) (Fig. 6), 42,43 revision to 20 was suspected. Remarkably, a distinction between the two structures based on chemical shifts and HMBC data was difficult, but the issue could be resolved by methylation, which made an unambiguous NMR analysis possible.…”

“…Remarkably, a distinction between the two structures based on chemical shifts and HMBC data was difficult, but the issue could be resolved by methylation, which made an unambiguous NMR analysis possible. 43…”

Recent Achievements in Total Synthesis for Integral Structural Revisions of Marine Natural Products

“…Iriomoteolide-2a Incorrect stereochemistry [30,31 ] Incorrect stereochemistry [26] Anabaenopeptin Incorrect stereochemistry [30,31 ] Incorrect stereochemistry [27] Anabaenopeptin Incorrect constitution [34] Xanthone Chemical derivatization…”

“…Despite these differences, it was not unreasonable to consider that this C-6 epimer was the most plausible structure to date. Thus, after Incorrect constitution [34] Xanthone Chemical derivatization…”