Structure Revision of Formyl Phloroglucinol Meroterpenoids: A Unified Approach Using NMR Fingerprinting and DFT NMR and ECD Analyses

NMR fingerprints are valuable tools for analyzing complex natural product mixtures and identifying incorrectly assigned structures in the literature. Our diagnostic NMR fingerprints for formyl phloroglucinol meroterpenoids revealed discrepancies in the structures reported for eucalyprobusal C (1a) and eucalypcamal K (2a). NMR fingerprinting PCA analyses identified 1a as an oxepine-diformyl phloroglucinol and 2a as an oxepine 3-acyl-1-formyl phloroglucinol, contrary to their initial assignments as pyrano-diformyl and pyrano 3-acyl-1-formyl phloroglucinols, respectively. Extensive reinterpretation of their reported one- and two-dimensional NMR data, coupled with GIAO DFT-calculated 1H and 13C NMR chemical shift and DP4+ analyses, supported the unequivocal reassignment of eucalyprobusal C to 1b and eucalypcamal K to 2b. The absolute configurations of the revised oxepine-containing phloroglucinol meroterpenoids were confirmed via the reinterpretation of their reported ROESY and NOESY NMR data, along with comparative TDDFT-calculated and experimental ECD spectra.