Iso-Guttiferone J and Structure Revision of Guttiferone J from Garcinia gummi-gutta: A Combined Experimental and Integrated QM/NMR Approach

Abstract

AbstractMany polyprenylated acylphloroglucinols with fascinating chemical structures and intriguing biological activities have been identified as key to phytochemicals isolated from Garcinia, Hypericum, and related genera. In the present work, two chiral, tautomeric, highly-oxygenated polyprenylated acylphloroglucinols tethered with acyl and prenyl moieties on a bicyclo[3.3.1]nonanetrione core were isolated from the 95% ethanolic extract of Garcinia gummi-gutta fruit. The structures of both compounds were elucidated based on the NMR and MS data with ambiguity in the exact position of the enol and keto functions at C-1 and C-3 of the core structure. The structures of both polyprenylated acylphloroglucinols were established as a structurally revised guttiferone J and the new iso-guttiferone J with the aid of gauge-independent atomic orbital NMR calculations, CP3 probability analyses, specific rotation calculations, and electronic circular dichroism calculations in combination with the experimental data. The structures of both compounds resemble hyperforin, a potent activator of the human pregnane X receptor. As expected, both compounds showed strong pregnane X receptor activation at 10 µM [7.1-fold (guttiferone J) and 5.0-fold (iso-guttiferone J)], explained by a molecular docking study, necessitating further in-depth investigation to substantiate the herb-drug interaction potential of G. gummi-gutta upon co-administration with pharmaceutical drugs.