Annamiacids A and B: Two dissymmetric bis-diterpenes containing a rare ketal-γ-lactone motif from Podocarpus annamiensis and their inhibitory effects on ATP-citrate lyase

Abstract

Two undescribed dissymmetric bis-diterpenes, annamiacids A (1) and B (2), were isolated from the renewable twigs and leaves of Podocarpus annamiensis, a ‘vulnerable’ conifer endemic to China. Their structures and absolute configurations were determined by spectroscopic and computational methods. The homodimeric (abietane-O-abietane, 1) and heterodimeric (abietane-O-totarane, 2) dimers were constructed from an identical phenolic abietane unit through an ether linkage with a phenolic abietane acid and a phenolic totarane acid, respectively. Both comprise a rare intramolecular 6-ketal-19,6-γ-lactone motif. Compound 2 could significantly inhibit ATP-citrate lyase with an IC50 value of 5.92 μM. A molecular docking study disclosed alternative H-bonds/interacting amino acid residues and binding pockets between 2 and the ACL enzyme when compared with those of compound 1, which supports their in vitro data.