Polycyclic polyprenylated acylphloroglucinol with an unprecedented spirocyclic core from Hypericum patulum

Abstract

Spirohypatone A (1), a spirocyclic PPAP (polycyclic polyprenylated acylphloroglucinol) bearing an unprecedented hexahydro-1′H-spiro[cyclohexane-1,2′-pentalene]-2,4,6-trione core and a new homologue (spirohypatone B, 2) were isolated from Hypericum patulum together with two known biosynthetic precursors. Compound 1 represents the first spirocyclic PPAP possessing a 5/5/6 carbon ring system, biogenetically derived from the intermediate 3 (attack from C-3 to C-12), which was differed from normal spirocyclic PPAPs (attack from C-3 to C-11). In addition, through extensive spectroscopic analysis, an interconversion mechanism of keto-enol of 1 was postulated and confirmed by its methylated reaction. The structures and absolute configurations of 1 and 2 were determined by comprehensive spectroscopic and chemical derivatized methods and X-ray crystallography. Compounds 1, 2, and 4 were tested to exhibit cytotoxic activities against several cancer cell lines.