NMR Fingerprints of Formyl Phloroglucinol Meroterpenoids and Their Application to the Investigation of Eucalyptus gittinsii subsp. gittinsii.

ABSTRACT

NMR fingerprints provide powerful tools to identify natural products in complex mixtures. Principal component analysis and machine learning using 1H and 13C NMR data, alongside structural information from 180 published formyl phloroglucinols, have generated diagnostic NMR fingerprints to categorize subclasses within this group. This resulted in the reassignment of 167 NMR chemical shifts ascribed to 44 compounds. Three pyrano-diformyl phloroglucinols, euglobal In-1 and psiguadiols E and G, contained 1H and 13C NMR data inconsistent with their predicted phloroglucinol subclass. Subsequent reinterpretation of their 2D NMR data combined with DFT 13C NMR chemical shift and ECD calculations led to their structure revisions. Direct covariance processing of HMBC data permitted 1H resonances for individual compounds in mixtures to be associated, and analysis of their 1H/13C HMBC correlations using the fingerprint tool further classified components into phloroglucinol subclasses. NMR fingerprinting HMBC data obtained for six eucalypt flower extracts identified three subclasses of pyrano-acyl-formyl phloroglucinols from Eucalyptus gittinsii subsp. gittinsii. New, eucalteretial F and (+)-eucalteretial B, and known, (-)-euglobal VII and eucalrobusone C, compounds, each belonging to predicted subclasses, were isolated and characterized. Staphylococcus aureus and Plasmodium falciparum screening revealed eucalrobusone C as the most potent antiplasmodial formyl phloroglucinol to date.